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■ Proton pump inhibitors ■ Vitamin D supplements ■ Antibiotics for skin abscess CLINICAL CHALLENGE

Increased heart rate and numbness: is it a heart attack? LEGAL ADVISOR

A contraceptive device leads to a blood clot.

■ Dermatology Clinic




■ Feature






HEART FAILURE Improving control of symptom exacerbation is key for managing heart failure patients.

Editor Colby Stong Senior editor Sandhya George Associate editor Lauren Grygotis

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If a patient has you stumped, write us and we’ll forward your query to one of our consultants and publish the response in Advisor Forum.You can also use this space to contribute a clinical pearl of your own or comment on another letter.

Advisor Forum These are letters from practitioners around the country who want to share their clinical problems and successes, observations, and pearls with their colleagues. Responding consultants are identified below. We invite you to participate.


It cannot be beat.—TERRI JORDAN, ARNP, Daytona Beach, Fla. (202-2)

NEUTROPHILS AND LYMPHOCYTES In interpreting a complete blood count with differential, anytime the neutrophils and lymphocytes are numerically close, it is a viral cause; when the neutrophils and lymphocytes are numerically distant, it is a bacterial cause. This is very helpful in determining treatment.—DONNA CARTER, FNP-C, Scottsburg, Ind. (202-1) GENERIC “CAINE” IS EFFECTIVE FOR WOUND CARE For pain relief, most pharmacies offer a “caine” at 2-510%, and basically nothing higher, for between $5 and $30 per tube. I work in wound care and use Walmart’s

INTRA-ARTICULAR INJECTIONS FOR SEVERE OSTEOARTHRITIS Patients with severe osteoarthritis in the knees seem to do better with intra-articular injections if you have them sit up and dangle their legs off the examination table and distract the knee slightly when administering the injection.—ROSEMARY LEDBETTER, PhD, PA, Troy, Ill. (202-3)

YOUR COMMENTS SLIPPED CAPITAL FEMORAL EPIPHYSIS IN OBESE ADOLESCENTS I just read the CME/CE article by Marilou Shreve, DNP, APRN, entitled, “Assessing and treating pediatric obesity” [ June 2015]. I was concerned regarding the oversight of a critical issue in obese adolescents: the increased risk of slipped capital femoral epiphysis (SCFE). This was not addressed in the article. The case study (p. 55) gave incomplete advice regarding the evaluation of an obese adolescent male with knee pain. The most common etiology of the insidious onset of knee pain in children is the hip, due to referred pain from the

Equate brand—vagicaine 20% benzocaine. When using this before debriding a wound, give it three minutes to sedate the nerves, then perform the procedure. I get good results, as patients say. It relieves pain and burning for $1.88.

Advisor F

Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 114 West 26th Street, 4th Floor, New York, NY 10001. You may contact us by e-mail at editor@ If you are writing in response to a published letter, please indicate so by including the number in parentheses at the end of each item. Letters are edited for length and clarity. The Clinical Advisor’s policy is to print the author’s name with the letter. No anonymous contributions will be accepted.


These are lette and successe rs from practitioners s, observat around the below. We ions, and country who OUR CONSULTANTS pearls with invite you want to shar to participa their colle e their clinic agues. Resp te. al problems onding cons ultants are identified CON SULTAT IONS

TREATM ENT FOR INFECT URINAR ION SGLT2 REC MALE CHI S IN THE UNC Y TRACT IRCUMCI LD FOR DIA EPTOR BLOCKE If a male SED child conti Deborah L. Cross, MPH, CRNP, Laura A.BET Foster,ES CRNP, FNP, Abby A. Jacobson, PA-C, RS Abimbola Farinde, PhD, PharmD, With the nues toassociate ANP-BC, is practices family medicine is a physician assistant is a professor redevprogram adven t ofPrimary circu SGLT2 recep at Delaware Valley urinaryattract director, Gerontology NP elop Program, mcisi Columbia Southern moda litywith Palmetto on be perfo for type tor infecPhysicians Dermatology University of Pennsylvania School blockersGroup University 2 diabe rmed? regarding inCare as a treatm in Wilmington, Del. in Orange Beach, Ala. useCharleston, S.C. tes, is there ent urology is of Nursing, Philadelphia. any evide NATHAN in patients with to protect the is well advise nce or data type 1 diabe GARDNE d tes mellitus?— R, PA-C, continues to to recommend a circum upper tracts, the kidne CPAAPA, ys. develo cision It p recurr•ent 44 THE ADVISOR AUGUST 2015 •on Castleton, severaCLINICAL l consideration urinary tract the male child who As it currently stands N.Y. , SGLT2 s that infections. for glycemic impede the receptor blocke There are control in ability to cleansenter into this decisio rs are FDA adults with n. Poor hygien should the e and quell -approved child have e may appro diet and exercise, but with type 2 diabetes phimosis, simpl infection potential. appropriate the in ved conjun FDA for use in patien Moreover, AdvisorForum_CA0815.indd urine 44 9/29/15ction 2:38 PM e cathet culture can ts with type has stated that they ketoacidosi steroid cream be a challenge. erization to obtain s, or those are not may tempo an FAR with severe 1 diabetes, patients with Having a short tion of the rarily solve renal functi diabetic steroid the trial of informINDE, PhD, Pharm these issues tenden , though after for infection D (See bottom on.—ABIMBOL ation about once again.—C cy redevelops, placin cessaA Dr. Farinde.) of this page Milwaukee g (203-2) for more , Wis. (203- OLEEN ROSEN, the child at risk 1) DNP, FNP -C, CLI Philip R. Cohen, MD,

is clinicaltions associate professor , shou ld of dermatology, University a of Texas Medical Center, The focus of Houston.


Send us your letter Advisor Forum, The s with questions New York, and comm Clinical Advisor ents to: , 114 clinicaladvisoNY 10001. You may contacWest 26th Street , please If you are writing in t us by e-mail at 4th Floor, each item. e so by including response editor@ to a the Letters are policy is edited for number in parent published letter, to heses at length and contribution print the author ’s name with clarity. The Clinicathe end of s will be accepted. l Advisor the letter. No anonym ’s ous

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VAGINA L RESULT DISCHARGE AND ING FRO If a female M TAMPON ODOR patient has USE a ask if she uses tamp history of vaginal disch ons. If she the pelvic arge with says “yes,” exam when cond odor, that you woul , do not enter ucting the rotating of d to take a pap smea vagina in the same the specu way r. Instead, the cervix. lum Most retain from side to side start shallow until reach ed tampons ing are lodge d in the fold

Philip R.

Cohen, MD, is clinical associa te profess of dermat or ology, of Texas MedicaUniversity l Center, Houston.

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Deborah L. Cross, MPH, ANP-B

CRNP, C, is associa te program director, Geronto logy NP Program University of Pennsyl vania School , of Nursing , Philadelphia.



MBER 2015

Abimbo la Farinde

, PhD,

is a profess PharmD, or at Columb ia Souther n Univers in Orange ity Beach, Ala.

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Laura A.


practices familyCRNP, FNP, with Palmett medicine o Primary Care Physicia ns in Charles ton, S.C.

Abby A.


is a physicia n, PA-C, n at Delawa assistant re Dermatology Valley in Wilmington,Group Del.

.indd 62


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Dermatology Clinic n A worsening rash with a malodor n Hyperpigmented macules in the interscapular region


Dermatologic Look-Alikes An erythematous plaque


Clinical Challenge A faster heart rate and numbness: Is the patient having a heart attack? A 30-year-old woman presents with an increased heart rate, shortness of breath, and tingling in her right arm. She also reported radiating pain to her right shoulder but denied having a fever, coughing, arrhythmia, or edema.


Legal Advisor Hormonal birth control leads to a blood clot. A patient presents with chest pain 6 weeks after beginning use of a contraceptive device.

Newsline ■■Proton pump inhibitor use is

associated with an excess risk of death. ■■Antibiotics may improve short-term outcomes in small skin abscesses. ■■Increasing use of high-dose vitamin D supplements may lead to a higher rate of adverse events. ■■Coffee consumption is associated with a lower mortality risk. ■■USPSTF recommends screening for obesity in children aged 6 years and older. ■■A DASH dietary pattern is associated with a lower risk of gout. ■■CDC: Opioid prescription rate remains high and varies by county.

How safe are proton pump inhibitors? 10

FEATURES 3 Managing patients with systolic 1 heart failure Primary care providers can help significantly reduce heart failure exacerbations and improve their patients’ overall quality of life. 24

CME/CE Impact of HFrEF vs


CME/CE Feature posttest

Clinical Challenge: An increased heart rate 43

Continues on page 6

HFpEF: How do we measure up? Considering MOGE(S) nosology along with ACCF/AHA stages and NYHA classifications can enhance heart failure prevention and detection.


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CONTENTS DEPARTMENTS cont’d Alternative Meds Update Boron. One of the best-studied functions of boron is in the metabolism of human bone. Boron also appears to play a significant role in wound healing. In addition, there is a high level of interest in boron’s potential role in cancer prevention and treatment.

Top: © Harley Schwadron, 2017. Bottom: © The New Yorker Collection 2017 from All Rights Reserved.


“Today’s numbers: sea shells up 2, mussels down 1, clams up 1, lobsters up 4 …”


Your Comments ■ Epilepsy and the ketogenic diet. Diet is a key component for managing seizure control in children.


My Most Memorable Patient ■ Fulfi lling a dying patient’s request. A nurse practitioner accompanies a man on a memorable 2-hour drive to attend the Renaissance Festival.



■ Proton pum ■ Vitamin D p inhibitors supplements ■ Antibiotics for skin absc ess CLINICAL



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ILURE Improving control of symptom exacerba tion for managin is key g heart failure pati ents.

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Multimedia CDC: US opioid prescription rates remain high A report from the CDC found that the number of opioids prescribed in the US decreased between 2010 and 2015, but the overall rate remains high. Watch the video here:

Higher childhood intelligence linked to lower mortality risk Childhood intelligence scores are associated with a lower risk of mortality caused by coronary heart disease, stroke, cancers related to smoking, respiratory diseases, digestive diseases, injury, and dementia.


Antibody screenings could detect celiac disease in asymptomatic children Serum TG2A screening has a positive predictive value of 61% for celiac disease.

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Cardiometabolic comorbidity rates high in psoriasis patients The most common comorbidities found in patients with psoriasis are hyperlipidemia, hypertension, depression, type 2 diabetes mellitus, and obesity. Aspirin is effective in preventing preterm preeclampsia in women who are at high risk Preterm preeclampsia occurred in 13 women (1.6%) in the aspirin group, compared with 35 (4.3%) in the placebo group. Majority of opioid prescriptions are written for patients with mental disorders Among the nearly 40 million Americans who have a mental health condition, about 19% use prescription opioids.

The Waiting Room

Jim Anderson, MPAS, PA-C, DFAAPA A look back at the AAPA 2017 House of Delegates The House of Delegates discussed the recertification process for PAs and the future of the PA profession at the 2017 Annual Meeting of the American Academy of Physician Assistants. Sharon O’Brien, MPAS, PA-C Sleep disturbances after traumatic brain injury The House of Delegates discussed the recertification process for PAs and the future of the PA profession at the 2017 Annual Meeting of the American Academy of Physician Assistants. Jillian Knowles, MMS, PA-C Small procedures, lasting impact The Mitrofanoff procedure is a simple yet ingenious concept that creates a passageway for the easy removal of urine in patients who self-catheterize.

WHO updates Essential Medicines List, recommendations for antibiotics The update includes 30 new medicines for adults and 25 for children and groups antibiotics into 3 distinct categories.


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INTERACT WITH YOUR PEERS by viewing the images and offering your diagnosis and comments. To post your answer, obtain more clues, or view similar cases, visit Learn more about diagnosing and treating these conditions, and see how you compare with your fellow colleagues.

Ortho Dx

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Journal of Orthopedics for Physician Assistants

Ankle stabilization A 19-year-old female presents with chronic instability of the left ankle. She is an avid soccer player and has had multiple sprains. On exam, the patient has an increased anterior drawer test and slight talar tilt of the left ankle compared with the right ankle. Radiographs of the left ankle show no abnormalities. She was seen recently by a foot and ankle specialist, who recommended a surgical procedure called a modified Brostrom procedure. WHICH LIGAMENTS WILL BE REPAIRED?

• • • •

Posterior and anterior talofibular ligament Anterior talofibular ligament and deltoid ligament Deltoid ligament and tibiofibular syndesmosis Anterior talofibular and calcaneofibular ligaments

● See the full case at

Derm Dx Simultaneous appearance of multiple indurated plaques A 70-year-old man presents with skin lesions located on his back, left thigh, and scalp. These arose simultaneously approximately 4 weeks previously. He is in good health and is a nonsmoker. He takes omeprazole for gastric reflux. He denies fatigue, weight loss, or swollen glands. Examination reveals several dusky red indurated plaques. CAN YOU DIAGNOSE THIS CONDITION?

• Kaposi sarcoma • B-cell lymphoma

• Angiosarcoma • T-cell lymphoma

● See the full case at • THE CLINICAL ADVISOR • AUGUST 2017 9

Newsline A U G U S T 2 017

Vitamin D supplements and adverse events page 11

DASH diet is linked to a lower risk for gout page 12

CDC: opioid prescriptions remain high page 12

PROTON pump inhibitor (PPI) use is associated with excess risk of death, according to data published in the BMJ Open. The risk of death is increased among those without gastrointestinal conditions and with prolonged use. Researchers conducted a longitudinal observational cohort study to determine the association between PPI use and risk of all-cause mortality in a cohort of new users of a PPI or histamine H2 receptor agonists from the US Department of Veteran Affairs (n = 349,312). The study included an additional

cohort of PPI use vs no PPI use (n = 3,288,092) and a cohort of PPI use vs no PPI and no H 2 blockers (n = 2,887,030). The results showed that PPI use was linked to increased mortality risk compared with H 2 blocker use (hazard ratio [HR], 1.25) after a median follow-up period of 5.71 years. Mortality risk associated with PPI use was higher in analyses adjusted for high-dimensional propensity score (HR, 1.16). The risk was also higher in two-stage residual inclusion estimation (HR, 1.21) and in 1:1 time-dependent propensity score-matched cohort (HR, 1.34).


Proton pump inhibitor use associated with excess risk of death PPIs are used to relieve the symptoms of gastroesophageal reflux disease, which is caused when the lower esophageal sphincter does not close properly, and stomach contents leak back into the esophagus.

The investigators also found that mortality risk was higher for PPI use vs no PPI use (HR, 1.15) and for PPI use vs no PPI and H 2 blockers (HR, 1.23). In addition, mortality risk associated with PPI use was higher in participants without gastrointestinal conditions in the PPI vs H 2 blocker cohort (HR, 1.24), the PPI use vs no PPI use cohort (HR, 1.19), and the PPI use vs no PPI and H 2 blockers cohort (HR, 1.22).

Antibiotics improve short-term outcomes in small skin abscesses PATIENTS WITH A SIMPLE abscess who received clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) in addition to incision and drainage had improved short-term outcomes compared with those who received incision and drainage alone, according to data published in the New England Journal of Medicine. Robert S. Daum, MD, CM, from the University of Chicago Hospitals, and colleagues conducted a multicenter, prospective, double-blind trial that included 786 outpatient adults and children who had a skin abscess smaller than 5 cm in diameter. The participants were stratified according to the presence of a surgically drainable abscess, abscess size, number of sites of skin infection, and the presence of nonpurulent cellulitis. They were randomly assigned to receive clindamycin, TMP-SMX, or placebo for 10 days after abscess incision and drainage.

S. aureus was isolated from 67.0% of participants, and methicillinresistant Staphylococcus aureus (MRSA) was isolated from 49.4% of participants. After 10 days of therapy, the cure rate among participants receiving clindamycin was 83.1% compared with 81.7% among those receiving TMP-SMX. The cure rate in both groups was higher than that in the placebo group (68.9%). Among the participants who were initially cured, 6.8% of participants in the clindamycin group had a new infection at the 1-month follow-up, compared with 13.5% of participants in the TMP-SMX group and 12.4% of participants in the placebo group. The investigators note that adverse events were more common in the clindamycin group (21.9%) than in the TMP-SMX group (11.1%) or in the placebo group (12.5%). All adverse events resolved with sequelae, and one participant who received TMP-SMX had a hypersensitivity reaction.


High-dose vitamin D supplements and adverse events

Increasing use of vitamin D poses risk for adverse effects.

with the risk of toxic effects increasing above this level. A total of 39,243 participants were included in the analysis; the mean age was 46.6 years, 51.1% were women, and 69.7% selfreported as non-Hispanic white. The prevalence of daily supplemental vitamin D use of 1000 IU or more in 2013 – 2014 was 18.2%,

compared with a rate of 0.3% in 1999 – 2000. In 2013 – 2014, the prevalence of daily supplemental intake of 4000 IU or more was 3.2%. Prior to 2005 – 2006, the prevalence of daily intake of 4000 IU or more was less than 0.1%. The researchers found trends of increasing supplemental vitamin D use in most age groups, race/ethnicities, and men and women. In 2013 – 2014, an intake of 4000 IU or more per day was highest among women (4.2%), non-Hispanic white individuals (3.9%), and those who were 70 years or older (6.6%). Overall, 3% of participants exceeded the tolerable upper limit of 4000 IU daily and may be at risk of adverse effects; 18% exceeded 1000 IU daily, which may be an indicator of intentional use of supplemental vitamin D.

Coffee consumption associated with lower mortality risk COFFEE consumption is associated with lower total mortality, specifically in African Americans, Japanese Americans, Latinos, and whites, according to a study published in the Annals of Internal Medicine. Researchers included 185,855 African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites aged 45 to 75 years in the study. They found that 58,397 participants died during 3,195,484 person-years of followup. Compared with drinking no coffee, coffee consumption was associated with lower total mortality after adjustment for smoking and other potential confounders

(1 cup per day: HR, 0.88; 2 to 3 cups per day: HR, 0.82; 4 or more cups per day: HR, 0.82). Trends were similar between caffeinated and decaffeinated coffee. Significant inverse associations were observed in 4 ethnic groups; however, the association in Native Hawaiians did not reach statistical significance. Inverse associations were also seen in never-smokers, younger participants (younger than age 55 years), and those who had not previously reported a chronic disease. Inverse associations were observed for deaths due to heart disease, cancer, respiratory disease, stroke, diabetes, and kidney disease.

Trends are similar between caffeinated and decaf coffee.

A second study, also published in the Annals of Internal Medicine, was conducted in 10 European countries and included participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 521,330 persons were enrolled. During a mean followup of 16.4 years, 41,693 deaths occurred. Compared with noncoffee consumers, participants in the highest quartile of coffee consumption had lower all-cause mortality (men: hazard ratio [HR], 0.88; women: HR, 0.93). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41) and women (HR, 0.60). • THE CLINICAL ADVISOR • AUGUST 2017 11


THE NUMBER OF US adults taking daily vitamin D supplements of 1000 IU or more and 4000 IU or more increased from 1999 through 2014, which may increase the risk of adverse effects, researchers reported in JAMA. Mary R. Rooney, MPH, from the Division of Epidemiology and Community Health, University of Minnesota in Minneapolis, and colleagues assessed trends in daily supplemental vitamin D intake of 1000 IU or more and 4000 IU or more between 1999 and 2014 using data from the National Health and Nutrition Examination Survey. The recommended dietary allowance for vitamin D is 600 IU/d for adults aged 70 years or younger and 800 IU/d for those who are older than 70 years. The tolerable upper limit is 4000 IU/d,

Newsline Screening for DASH diet linked to lower risk of gout [86.7%] with podagra, 1226 obesity advised THE DIETARY Approaches to [70.8%] with hyperuricemia, 605 Stop Hypertension (DASH) diet is in children [35.0%] with tarsal joint involveassociated with a lower risk of gout, according to a study published in the BMJ. A total of 44,444 men with no history of gout at baseline were included in the study. Participant were assigned a DASH dietary pattern score (based on high intake of fruits, vegetables, nuts and legumes, low-fat dairy products, and whole grains, and low intake of sodium, sweetened beverages, and red and processed meats) and a Western dietary pattern score (based on high intake of red and processed meats, French fries, refined grains, sweets, and desserts). Over 26 years of follow-up, the authors documented 1731 newly diagnosed gout cases meeting the American College of Rheumatology criteria (1500

ment, and 167 [9.6%] with tophi). Men in the highest fifth of DASH dietary pattern score tended to be older and had a lower BMI compared with participants in the lowest fifth. Men in the highest fifth of DASH dietary pattern score also had lower intakes of alcohol A DASH diet is and coffee than participants in the associated with lowest fifth. Comparatively, men a lower risk for gout. In contrast, in the highest fifth of Western pata Western dietary tern score tended to be younger, pattern is linked had a higher BMI, and had higher to a higher risk intakes of alcohol and coffee. for gout. A higher DASH dietary pattern score was associated with a lower risk for gout (adjusted relative risk [RR] 0.68). In contrast, a higher Western dietary pattern score was associated with an increased risk for gout (RR 1.42).

CDC: Opioid prescription rate remains high THE NUMBER of opioid prescriptions remains high in the United States and varies from county to county, according to a report from the CDC. However, the number of prescriptions decreased between 2010 and 2015. Between 2006 and 2015, the number of opioids prescribed peaked in 2010 at 782 morphine milligram equivalents (MME) per person and decreased to 650 MME in 2015. In 2015, the CDC found that 6 times more opioids per resident were dispensed in the highest-prescribing counties compared with the lowest-prescribing counties. The agency also found that daily MME per prescription was stable from 2006 and 2010 and then decreased 17% between 2010 and


2015. The CDC notes that the average days’ supply per prescription increased 33% from 13 days in 2006 to about 18 days in 2015. The report included an analysis of retail prescription data that assessed opioid prescribing in the United States between 2006 and 2015, including rates, amounts, dosages, and durations of the prescriptions. The agency also examined prescribing patterns at the county level between 2010 and 2015. The CDC identified county-level factors associated with higher amounts of opioids prescribed, including a greater percentage of non-Hispanic white residents, a greater prevalence of diabetes or arthritis, nonmetro small cities and small towns, and a higher unemployment rate. n


THE US Preventive Services Task Force (USPSTF) has issued updated recommendations on obesity screening in children and adolescents aged 6 years and older, emphasizing the importance of screenings and referrals to comprehensive, intensive behavioral interventions for patients with obesity. The recommendation statement was published online in JAMA. At present, despite the stabilization of child and adolescent obesity rates during the past decade, certain populations, including African-American girls and Hispanic boys, have experienced an increase in obesity. “These racial/ethnic differences in obesity prevalence are likely a result of both genetic and nongenetic factors,” the authors wrote, noting that socioeconomic status, intake of sugar-sweetened beverages and fast food, and having a television in the bedroom are among the contributing factors. The investigators examined 42 trials with multicomponent behavioral interventions, of which 8 were deemed “good quality” and 34 “fair quality.” The total number of participants in the trials was 6956, and half of the trials were conducted in the United States. According to the findings, comprehensive, intensive behavioral intervention of at least 26 contact hours in children and adolescents with obesity aged 6 years and older can result in improvements in weight status for up to 12 months.


Managing patients with systolic heart failure Primary care providers can help significantly reduce heart failure exacerbations and improve their patients’ overall quality of life. More than 8 million people are expected to have heart failure by the year 2030.


he American Heart Association has identified heart failure (HF) as the No. 1 reason why patients are readmitted to an acute-care facility within 30 days.1 Preventing the exacerbation of HF is expected to improve overall quality of life and survival rates, and to decrease significantly the healthcare costs related to acute-care treatments. HF is a complex condition that develops from a combination of health and environmental factors; management requires a multidisciplinary approach. Aggressive and appropriate outpatient management may be time-consuming and labor-intensive but can result in improved survival and a better quality of life for patients. On the frontline of this effort are primary care providers, who can contribute significantly to reducing HF exacerbations and improving their patients’ overall quality of life.


Disease burden

In 2013, HF was mentioned as the underlying cause of death in more than 65,000 patients in the United States. It is projected that the prevalence of HF will increase by 46%, affecting more than 8 million people, by the year 2030.2 HF accounts for nearly 1 million emergency room visits and is the No. 1 reason for the readmission of patients on Medicare.1 Projections show that by 2030, the costs to treat HF will increase almost 127%, from $30.7 billion in 2012 to $69.7 billion in 2030.2 The prevalence and incidence of HF are expected to continue to increase, in part because Continues on page 17 • THE CLINICAL ADVISOR • AUGUST 2017 13


Systolic heart failure is caused by a progressive deterioration of heart function, and it sometimes can take years before symptoms manifest. strategy to prevent functional decline. Additionally, patients with a family history of coronary artery disease or idiopathic cardiomyopathies and those with a history of rheumatic fever should be monitored more closely as they age.

of the aging population and in part because of an increasing need for earlier and more aggressive outpatient management. Patients with HF have multiple comorbidities; therefore, treatment decisions require balancing risks and benefits. Additionally, these patients require more frequent monitoring.

Clinical presentation

Patients with either systolic (HFrEF) or diastolic (HFpEF) HF usually present in the same way. Common signs and symptoms include the following: worsening fatigue; dyspnea on exertion, which may progress to dyspnea at rest; orthopnea; jugular venous distention; pedal edema; presence of a third or fourth heart sound; loss of appetite; and tachycardia. In some patients, hepatomegaly may also develop as the disease advances. Although dyspnea can be a manifestation of other clinical diagnoses, it is a very sensitive clinical feature of HF. Distinguishing between systolic and diastolic HF is difficult if the distinction is based solely on the clinical presentation. Although the initial treatment for symptomatic heart failure is the same for either HFrEF or HFpEF, it is important to identify the underlying type because treatment approaches and maintenance therapy will vary based on the cause and type.


Although HF is not clearly defined in the literature, the general consensus is that systolic heart failure (SHF) is an ejection fraction (EF) of 40% or lower and can be identified as heart failure with reduced ejection fraction (HFrEF). Diastolic heart failure (DHF), or heart failure with preserved ejection fraction (HFpEF), is a combination of the signs and symptoms of heart failure, a preserved EF, and evidence of diastolic dysfunction involving both ventricles or only one. The American College of Cardiology (ACC) and the American Heart Association (AHA) have staged heart failure on the basis of symptoms. Because of the complexities of HF, only the management of SHF is discussed in this article. Table 1 describes the ACC/AHA stages of heart failure and provides examples. Table 2 compares stages and class. Systolic heart failure is caused by a progressive deterioration of heart function and sometimes can take years before symptoms manifest. Early diagnosis and the aggressive management of known risk factors, such as hypertension, diabetes, obesity, alcohol abuse, and tobacco use, are the best

Diagnostic workup

The diagnostic workup for HF is based largely on the clinical presentation and evidence of volume overload. A comprehensive health history and a thorough physical

TABLE 1. The ACC/AHA stages of heart failure3 Stage




Patients at high risk for HF because of the presence of conditions that are strongly associated with the development of HF; such patients have no identified structural or functional abnormalities of the pericardium, myocardium, or cardiac valves, and they have never shown signs or symptoms of HF

Patients with systemic hypertension, coronary artery disease, diabetes mellitus, history of cardiotoxic drug therapy or alcohol abuse, personal history of rheumatic fever, or family history of cardiomyopathy


Patients with structural heart disease that is strongly associated with the development of HF but who have never shown signs or symptoms of HF

Patients with left ventricular hypertrophy or fibrosis, left ventricular dilatation or hypocontractility, asymptomatic valvular heart disease, or previous myocardial infarction


Patients who have current or prior symptoms of HF associated with underlying structural heart disease

Patients with dyspnea or fatigue due to left ventricular systolic dysfunction, asymptomatic patients who are undergoing treatment for prior symptoms of HF


Patients who have advanced structural heart disease and marked symptoms of HF at rest despite maximal medical therapy and those who require specialized interventions.

Patients who are frequently hospitalized for HF or cannot be safely discharged from the hospital; in the hospital awaiting heart transplant; at home receiving continuous intravenous support for symptom relief or being supported with a m ­ echanical circulatory assist device; or in a hospice setting for the management of HF

ACC = American College of Cardiology; AHA = American Heart Association; HF = heart failure. • THE CLINICAL ADVISOR • AUGUST 2017 17


The goals of treatment for HFrEF are to prevent hospitalization, preserve heart function, and improve the patient’s quality of life and survival. examination will help to rule out other causes of dyspnea. Diagnostic testing should include a basic metabolic panel, a complete blood cell count with differential, two-view chest radiography (posteroanterior and lateral), baseline electrocardiography, and transthoracic echocardiography (TTE). The echocardiogram is the gold standard for diagnosing HF and identifying the type. Additional testing includes transesophageal echocardiography (TEE) and a blood test for B-type natriuretic peptide (BNP). BNP is a protein that is released by the ventricles when they are stretched during volume overload6 and is a reliable indicator of volume overload. Because the test is relatively inexpensive and readily available, BNP is an easy marker to obtain, and its presence can contribute significantly to the diagnosis of HF. Other specialized testing Other tests include coronary stress testing to rule out and/ or correct ischemic causes that may be contributing to HF symptoms. Left heart catheterization (LHC) coronary angiography can be performed to study the coronary anatomy and provides the most accurate evaluation of ischemic vessels. Right heart catheterization (RHC) can also be performed to measure the internal pressures of the heart chambers. Treatment goals and options

The goals of treatment for HFrEF are to prevent hospitalization, preserve heart function, and improve the patient’s

quality of life and survival. Strategies to achieve these goals are geared toward addressing patients’ self-care needs and medication adherence; early open discussion about implantable devices and initial discussions regarding advance directives are also included. Self-care Self-care is the most important (although difficult) strategy to implement and maintain. Having patients maintain a healthful lifestyle is highly effective but requires close monitoring and acceptance on their part. Addressing issues such as access, schedules, and work and family obligations can help to increase patient adherence. For exercise programs to be optimally effective, the duration of activity should range from 20 to 30 minutes on 5 days each week. Recent research has demonstrated that short bouts of moderately intense physical activity throughout the day are just as effective as a full 30 minutes of continuous exercise once daily.7 Maintaining a low-sodium or no-added-salt diet is essential to reduce water retention. A moderate to high dietary intake of sodium is an independent risk factor for HF.8 Ideally, the total recommended daily sodium intake for a patient with HF is 1500 mg; however, because this is usually hard to achieve, the interim achievable goal is up to 2300 mg/d.9 Every effort to support smoking cessation should be discussed, and alternatives must be offered at each encounter.

TABLE 2. Comparison of the NYHA classes and ACC/AHA stages of heart failure4,5 NYHA functional classification


ACC/AHA stage of heart failure Stage A


Class I

No limitation of physical activity; ordinary physical activity does not cause undue fatigue, palpitation, dyspnea

Class II

Slight limitation of physical activity; comfortable at rest; Stage B ordinary physical activity results in fatigue, palpitation, dyspnea

Class III

Marked limitation of physical activity; comfortable at rest; less than ordinary activity results in fatigue, palpitation, or dyspnea

Stage C

Symptomatic HF associated with underlying structural heart disease

Class IV

Unable to carry on any physical activity without discomfort; symptoms of HF at rest; if any physical activity is undertaken, discomfort increases

Stage D

Advanced structural heart disease and marked symptoms of HF at rest despite maximal medical therapy

At high risk for the development of HF; no identified structural or functional abnormality; no signs or symptoms Developed structural heart disease that is strongly associated with the development of HF, but without signs or symptoms

ACC = American College of Cardiology; AHA = American Heart Association; HF = heart failure; NYHA = New York Heart Association.


An ACE-1 inhibitor should be introduced at the lowest dose and titrated upward per the patient’s blood chemistries and tolerance of the drug. Methods to increase compliance include constant encouragement in addition to open and frequent discussions. Praising the patient for every effort and including the family in medical visits are successful methods of increasing compliance. Medications Angiotensin-converting enzyme 1 (ACE-1) inhibitors. ACE-1 inhibitors are the first-line drug treatments for HF. In two large randomized controlled trials, CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study) and SOLVD (Studies of Left Ventricular Dysfunction), ACE-1 inhibitor therapy was shown to improve survival rates significantly, reduce hospitalization rates, and improve the quality of life of all patients with symptomatic HF.10 An ACE-1 inhibitor should be introduced at the lowest dose and titrated upward on the basis of the patient’s blood chemistries and tolerance of the drug (Table 3). Beta-blockers. In the COPERNICUS (Carvedilol Prospective Randomized Cumulative Survival) trial and in MERIT-HF (Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure), the addition of a betablocker also improved survival, decreased symptoms, and improved quality of life in patients with mild, moderate, or moderately severe but stable HF.10 Beta-blockers are not appropriate for and should be avoided in patients who have class IV HF or are experiencing an acute exacerbation. The drug should be initiated at the lowest dose and titrated to the target dose as tolerated. Of note, in COMET (Carvedilol or Metoprolol European Trial), carvedilol was substantially more beneficial than the short-acting metoprolol.11 Table 4 describes dosages for these drugs. Angiotensin receptor blockers (ARBs). ARBs are used as an alternative treatment option for patients who cannot tolerate an ACE-1 inhibitor as a first-line modality. For patients who continue to experience symptoms after being optimized on ACE and beta-blocker therapy, an ARB can be added as a second-line treatment to relieve symptoms (Table 5).10 Aldosterone antagonists (AAs). AAs may offer some additional benefit for patients with moderately severe or severe (NYHA class III/IV) HF; however, there is no evidence to suggest that adding an AA to the therapy of a patient who does not have NYHA class III/IV HF will result in any further benefit.10 Dosages are listed in Table 6.

Other medical therapy options. The use of digoxin has not been shown to improve survival rates.10 In the presence of atrial fibrillation, digoxin can be added after the betablocker dose has been maximized and has failed to control the heart rate adequately. Diuretics are commonly used for the management of HF; however, they are given solely for symptom relief and improvement in quality of life. Diuretics have not been shown to have any benefit in improving the survival rates of patients. TABLE 3. Angiotensin-converting enzyme 1 (ACE-1) inhibitors ACE-1 inhibitor

Starting dose, mg

Target dose, mg


2.5, twice daily

10-20, twice daily


2.5 to 5, daily

20-35, daily


2.5, daily

5, twice daily or 10, daily


6.26, three times daily

50, three times daily

TABLE 4. Beta-blockers Beta-blocker

Starting dose, mg

Target dose, mg

Metoprolol CR/XL

12.5-25, daily

200, daily


3.125, twice daily

25-50, twice daily


1.25, daily

10, daily

TABLE 5. Angiotensin receptor blockers (ARB) ARB

Starting dose, mg

Target dose, mg


4 or 8, daily

32, daily


40, twice daily

160, twice daily

TABLE 6. Aldosterone antagonists Aldosterone antagonist

Starting dose, mg

Target dose, mg


25, daily or on alternating days

25–50, daily


25, daily

50, daily • THE CLINICAL ADVISOR • AUGUST 2017 19

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Significant improvements in survival rates and reductions in hospitalization rates can be achieved with close and aggressive outpatient management. The combination of hydralazine and isosorbide dinitrate has proved beneficial when added to ACE/ARB therapy in African American patients with NYHA class III or IV HF.12 The recommended starting dose of hydralazine is 37.5 mg, which is titrated upward to 75 mg three times daily. The starting dose of isosorbide dinitrate is 20 mg and is titrated to a target dose of 40 mg three times daily. The Food and Drug Administration (FDA) recently approved two new agents for use in patients with HF. Entresto is an angiotensin receptor–neprilysin inhibitor (ARNi). This combination agent consists of a neprilysin inhibitor (sacubitril) and an angiotensin 2 receptor blocker (valsartan). Entresto was shown to reduce cardiovascular or HF hospitalization by 20% in comparison with enalapril alone.13,14 The PARADIGM-HF (Prospective Comparison of ARNi with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial was stopped early because of evidence of significant benefit in the treatment arm, in which patients received the combination of an ARB and ARNi therapy. Suitable candidates are those identified as having NYHA class II to IV heart failure.13 Before initiating treatment with Entresto, the clinician must have the patient stop any use of an ACE inhibitor or ARB for a minimum of 36 hours as a washout period to minimize the possibility of angioedema, hypotension, or hyperkalemia.14 Entresto is contraindicated for concomitant use in those who are taking aliskiren for diabetes.15 The second agent is ivabradine, which works by selectively inhibiting the funny channel current of the sinoatrial node. The recommended indication is to reduce hospitalization for HF in patients with NYHA class II or III HF. Clinicians must first maximize beta-blocker treatment, and the patient’s resting heart rate must be faster than 70 beats per minute.13 Advanced therapeutic options: implantable devices Cardiac resynchronization therapy. Cardiac resynchronization therapy with biventricular pacemakers has been shown to improve the quality of life and functional status of those with NYHA class III or IV HF who have a wide QRS complex on their electrocardiogram and lifethreatening arrhythmias.16 CardioMEMSTM HF system. This is an implantable device for monitoring pulmonary artery pressure. It is the first and only FDA-approved HF monitoring system proven to reduce hospitalization significantly and improve quality of

life in patients with NYHA class III HF regardless of their ejection fraction status.17 Prevention

Preventing an exacerbation of HF is a high priority for clinicians and patients alike. Significant improvements in quality of life and survival rates and reductions in hospitalization rates can be achieved with close and aggressive outpatient management. Encouraging and supporting a patient’s efforts to maintain a healthful lifestyle and follow a daily exercise routine, and ensuring preventive care such as up-to-date immunizations, will contribute to the achievement of this goal. Social and emotional support are essential to help patients maintain constructive lifestyle changes and remain compliant with medication regimens. Using social network and community outreach programs to keep patients engaged and involved in their own care can be a highly effective strategy. Cardiac rehabilitation Patients with HF are often unable to perform the activities of daily living without experiencing some degree of dyspnea. Cardiac rehabilitation is a critical component of the management of HF to improve patient quality of life. Until recently, cardiac rehabilitation was approved only for patients with coronary artery disease. The decision by the US Centers for Medicare and Medicaid Services to include HFrEF as a reimbursable diagnosis for cardiac rehabilitation is expected to increase its utilization by providers and patients alike.18 Continues on page 22


Which of the following self-care measures is the most effective for patients with heart failure? n=1,037

3.38% 21.22%

■ Physical exercise ■ Quitting smoking ■ Eating a heart-healthy diet

22.95% 52.46%

■ Managing stress


For more polls, visit


Psychosocial components Because HF is a chronic condition that is incurable, it can cause significant impairment in patient quality of life. Social isolation, lack of social support, and a diminishing ability to carry out the activities of daily living independently all negatively affect the patient’s psychological well-being. The incidence of depression in this population is four- to fivefold higher than that in the general population.19 Depression contributes to medication nonadherence, reduces patient compliance with any lifestyle modification strategy, increases the utilization of healthcare services, increases healthcare costs, and further reduces patient quality of life.20-22 The need to screen and treat depression in the community setting is of paramount importance if HF is to be managed adequately. Patients who have a diagnosis of HF or who are identified as at high risk for the development of HF should be screened and treated early for depression.

2. Mozaffarian D, Benjamin EJ, Go AS, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015;131: e29-e322. 3. Hunt SA, Baker DW, Chin MH, et al; American College of Cardiology/ American Heart Association. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol. 2001;38:2101-2113. 4. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston, MA: Little Brown & Co; 1994:253-256. 5. Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart

Patient education and follow-up

Association Task Force on Practice Guidelines (Writing Committee

To increase compliance with therapy, it is important to educate patients and reinforce teaching points at each encounter. Discussing the benefits of prescribed treatments will increase patient compliance with the regimen. Emphasis should be placed on symptom control and quality-of-life issues. Patients should understand that treatment with medication alone is not optimal. It is important to stress proper diet and daily exercise and to manage depression. The clinician should always reinforce the fact that medications will decrease the symptoms of heart failure, prevent hospitalization, improve the quality of life, and prolong survival.

to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation. 2005;112:e154-e235. 6. Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet. 2000;355:1126-1130. 7. King AC, Rejeski WJ, Buchner DM. Physical activity interventions targeting older adults: a critical review and recommendations. Am J Prev Med. 1998;15:316-333.


8. He J, Ogden LG, Bazzano LA, Vupputuri S, Loria C, Whelton PK.

Although death rates from heart disease have declined, the effects of cardiovascular disease remain high, and the burden of treating it continues to grow. The primary care provider can significantly improve the control of symptom exacerbation. Guided by the evidence, the busy practitioner can effectively and confidently manage patients with HF and prevent rehospitalization.1 n

Dietary sodium intake and incidence of congestive heart failure in

Shenaz Georgilis, MSN, FNP-BC, is an assistant professor at Queensborough Community College of the City University of New York in Bayside, Queens, New York.

10. McMurray J, Cohen‐Solal A, Dietz R, et al. Practical recommendations

overweight US men and women: first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Arch Intern Med. 2002;162:1619-1624. 9. American Heart Association Nutrition Committee, Lichtenstein AH, Appel LJ, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006;114:82-96. for the use of ACE inhibitors, beta‐blockers, aldosterone antagonists, and angiotensin receptor blockers in heart failure: putting guidelines into practice. Eur J Heart Fail. 2005;7:710-721.


11. Poole-Wilson PA, Swedberg K, Cleland JG, et al; Carvedilol Or

1. Roger VL, Go AS, Lloyd-Jones DM, et al; American Heart Association

Metoprolol European Trial Investigators. Comparison of carvedilol and

Statistics Committee and Stroke Statistics Subcommittee. Executive sum-

metoprolol on clinical outcomes in patients with chronic heart failure in

mary: heart disease and stroke statistics—2012 update: a report from the

the Carvedilol Or Metoprolol European Trial (COMET): randomised con-

American Heart Association. Circulation. 2012;125:188-197.

trolled trial. Lancet. 2003;362:7-13.


12. Taylor AL, Ziesche S, Yancy C, et al; African-American Heart Failure Trial Investigators. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351:2049-2057. 13. McMurray JJ, Packer M, Desai AS, et al; PARADIGM-HF Committees and Investigators. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin‐converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM‐HF). Eur J Heart Fail. 2013;15:1062-1073. 14. Yancy CW, Jessup M, Bozkurt B, et al. 2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2016;134:e282-e293.

“The high price is due to the great view of the beach.”

15. Fala L. Entresto (sacubitril/valsartan): first-in-class angiotensin receptor neprilysin inhibitor FDA approved for patients with heart failure. Am Health Drug Benefits. 2015;8:330-334. 16. Young JB, Abraham WT, Smith AL, et al; Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators. Combined cardiac resynchronization and implantable cardioversion defi2003;289:2685-2694. 17. Abraham WT, Adamson PB, Bourge RC, et al; CHAMPION Trial Study Group. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomized controlled trial. Lancet. 2011;377:658-666. 18. Jacques L, Syrek Jensen T, Schafer J, Chin J, Issa M. Decision memo for cardiac rehabilitation (CR) programs—chronic heart failure (CAG00437N). Centers for Medicare & Medicaid Services website. https:// aspx?NCAId=270. Published February 18, 2014. Accessed June 27, 2017.

“You know what I really hate about going back to school? Everybody’s doing it.”

19. Adelborg K, Schmidt M, Sundboll J, et al. Mortality risk among heart failure patients with depression: a nationwide population-based cohort study. J Am Heart Assoc. 2016;5:e004137. 20. Lett HS, Blumenthal JA, Babyak MA, et al. Depression as a risk factor for coronary artery disease: evidence, mechanisms, and treatment. Psychosom Med. 2004;66:305-315. 21. Lichtman JH, Bigger JT Jr, Blumenthal JA, et al. Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association. Circulation. 2008;118:1768-1775. 22. Rutledge T, Reis VA, Linke SE, Greenberg BH, Mills PJ. Depression in heart failure: a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes. J Am Coll Cardiol. 2006;48:1527-1537.

“It was love at first sight. She married him without even googling him!” • THE CLINICAL ADVISOR • AUGUST 2017 23

Top, bottom: © Harley Schwadron, 2017. Center: © The New Yorker Collection 2017 from All Rights Reserved.

brillation in advanced chronic heart failure: the MIRACLE ICD Trial. JAMA.


n EDUCATIONAL OBJECTIVES At the conclusion of this activity, participants should be better able to: • Differentiate pathophysiologies between heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), including multiple abnormalities • Identify consistent diagnostic criteria to differentiate HFrEF and HFpEF • Describe the category of HF with midrange ejection fraction (HFmrEF) and the MOGE(S) classification system n COMPLETE THE POSTTEST: Page 29

Release Date: May 5, 2017 Expiration Date: May 5, 2018 Estimated Time to Complete: 30 minutes Accredited Provider: This program is provided by the American College of Cardiology Foundation in collaboration with Haymarket Medical Education. Commercial Supporter: This activity is supported by an educational grant from Novartis Pharmaceuticals Corporation. Program Description: The American College of Cardiology Foundation/American Heart Association (ACCF/ AHA) guidelines categorize heart failure (HF) according to patients with HF with reduced ejection fraction (HFrEF), defined as a left ventricular ejection fraction (LVEF) less than or equal to 40%, and those with HF with preserved ejection fraction (HFpEF). Nevertheless, HF comprises a wide array of patient types. For one, there is a group of patients—those with an LVEF ranging from 40% to 49%— who can be considered to belong to a “borderline” or “intermediate” category. In addition, while the ACCF/AHA guidelines remain the gold standard for patient management, we have become increasingly aware of the importance of genetic factors in the development of HF. In this “Viewpoint” article, Dr. Marc Silver reviews HF phenotypes, with a particular emphasis on patients with midrange LVEF (HFmrEF) as well as a proposed classification system that incorporates the genetics of HF. Intended Audience: Cardiologists, internists, primary care physicians, nurses, nurse practitioners (NPs), physician assistants (PAs), and other clinicians who manage patients with chronic heart failure Educational Objectives: At the conclusion of this activity, participants should be better able to:  ifferentiate pathophysiologies between heart failure •D (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), including multiple abnormalities • Identify consistent diagnostic criteria to differentiate HFrEF and HFpEF  escribe the category of HF with midrange ejection frac•D tion (HFmrEF) and the MOGE(S) classification system Accredited Provider Disclosure of Conflicts of Interest Statement and Disclosure Policy: As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME) and the American Nurses Credentialing Center (ANCC), the American College of Cardiology Foundation (ACCF) must ensure balance, independence, objectivity, and scientific rigor in all of its directly provided or jointly provided/co-provided educational activities. Planners, presenters, and other contributors in a position to control the content are required to disclose to the audience all relevant financial relationships he/she and/ or his/her spouse or domestic partner may have, occurring within the past 12 months, with any entity producing, marketing, reselling, or distributing healthcare goods or services consumed by, or used on, patients. When an unlabeled use of a commercial product or an investigational use not yet approved for any purpose is discussed during an educational activity, the contributor should disclose that the product is not labeled for the use under discussion or that the product is still investigational. ACCF is committed to providing its learners with high-quality activities and materials that promote improvements and quality in healthcare and not a specific proprietary business or commercial interest. The intent of this disclosure is not to prevent participation in certified educational activities by persons with a financial or other relationship, but rather

to provide learners with information on which they can make their own determination whether financial interests or relationships may influence the certified activity. ACCF assesses conflict of interest (COI) with its faculty, planners, managers, staff, and other individuals who are in a position to control the content of cer tified CME/ CNE activities. All relevant potential conflicts of interest that are identified are thoroughly vetted by course directors, ACCF education staff, and members of the Accreditation Compliance Workgroup through a process that includes appropriate peer review for fair balance, scientific objectivity and validity, and patient care and safety recommendations. Faculty OVERSIGHT COMMITTEE Margaret Bowers, DNP, RN, FNP-BC, CHFN, AACC, FAANP Associate Professor Faculty Coordinator, Adult Nurse Practitioner Programs Lead Faculty, Cardiovascular Specialty Duke University School of Nursing Durham, NC Margaret Bowers, DNP, RN, FNP-BC, CHFN, AACC, FAANP, has received speakers’ bureau fees from Amgen. Akshay Desai, MD, MPH, FACC Director, Heart Failure Disease Management Cardiovascular Division Brigham and Women’s Hospital Associate Professor of Medicine Harvard Medical School Boston, MA Akshay Desai, MD, MPH, FACC, reports receiving research grants from Novartis and consulting fees from AstraZeneca, Cheetah Medical, Janssen, Merck, Novartis, Relypsa, Sanofi, and St. Jude Medical. Alan Wasserman, MD, MACP, FACC Chairman, Department of Medicine Eugene Meyer Professor of Medicine George Washington School of Medicine & Health Sciences George Washington University Medical Center Washington, DC Alan Wasserman, MD, MACP, FACC, has no relevant financial relationships to disclose. Cathleen Biga, RN, MSN President and CEO Cardiovascular Management of Illinois Woodridge, IL Cathleen Biga, RN, MSN, has no relevant financial relationships to disclose Kimberly V. Cheramie, MSN, RN-BC Nurse Planner American College of Cardiology Washington, DC Kimberly V. Cheramie, MSN, RN-BC, has no relevant financial relationships to disclose. FACULTY AUTHOR Marc A. Silver, MD, FACP, FACC, FAHA, FHFSA Chief, Division of Medical Services Chairman, Department of Medicine Founder, Heart Failure Institute Advocate Christ Medical Center Clinical Professor of Medicine University of Illinois at Chicago Chicago, IL Marc A. Silver, MD, FACP, FACC, FAHA, FHFSA, receives a salary from Legacy Heart.

Accredited Provider Disclosures: ACCF staff involved in this activity have no relevant financial relationships to disclose. Haymarket Medical Education staff involved in this activity have no relevant financial relationships to disclose. Accreditation Statement: The American College of Cardiology Foundation (ACCF) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Designation Statement: The ACCF designates this enduring material for a maximum of 0.50 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physician Assistants The American Academy of Physician Assistants (AAPA) accepts certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by ACCME. Accreditation Statement: The American College of Cardiology Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. Designation Statement: The ACCF designates this educational activity for a maximum of 0.50 continuing nursing education contact hour. Requirements for successful completion are viewing of module in its entirety and completing the evaluation tool. While offering credits noted above, the module is not intended to provide extensive training or certification in the field. Disclosure of Unlabeled Use: This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options for a specific patient’s medical condition. Disclaimer: The American College of Cardiology Foundation (ACCF) is not responsible for statements made by any contributor. Statements or opinions expressed in this program reflect the views of the contributors and do not reflect the official policy of the ACCF. Instructions: There are no fees for participating in and receiving CME/CNE credit for this activity. During the period May 5, 2017, through May 5, 2018, participants must: 1) read the learning objectives and faculty disclosures; 2) complete the pre-assessment test; 3) study the educational activity; and 4) complete the post-test and submit it online. If you have an American College of Cardiology (ACC) account, you can choose to have your credit information sent to your ACC Transcript upon completion of the course. You will be prompted to log in to your ACC account, which will automatically trigger your credit submission. If you do not have an ACC account, you will have the opportunity to create one. A statement of credit will be issued only upon receipt of the above elements and a post-test score of 70% or higher. All components must be completed and submitted online at Provided by

In collaboration with


The impact of HFrEF vs HFpEF: How do we measure up? Considering MOGE(S) nosology along with ACCF/AHA stages and NYHA classifications can enhance heart failure prevention and detection.


Doppler echocardiographic assessment of left ventricular ejection fraction


he American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines for classification of heart failure (HF) are the gold standard for patient management. Nevertheless, new information is constantly emerging, including greater information about various HF phenotypes and a better understanding of the importance of genetic factors in the development of HF. In this article, Dr. Marc Silver reviews HF phenotypes, with a particular emphasis on the group of patients with left ventricular ejection fraction (LVEF) who fall into the midrange (40%-49%) between HF with reduced ejection fraction (HFrEF), defined as LVEF equal to or less than 40%, and those with HF with preserved ejection fraction (HFpEF), defined as equal to or greater than 50%. Dr. Silver also discusses the potential clinical application of a proposed classification system that incorporates the genetics of HF. About this article: This article is part of RightSTEPS: Optimizing Medical Therapy for Chronic Heart Failure, a comprehensive curriculum on chronic heart failure provided by the American College of Cardiology (ACC) in collaboration with Haymarket Medical Education (HME).The program blends print, online, and live activities to enhance understanding of how specified optimal medical therapy guidelines improve heart failure outcomes. To learn more about this ACC curriculum, please visit • THE CLINICAL ADVISOR • AUGUST 2017 25



Taking the measure of ejection fraction

Perhaps one of the longest-enduring and still-potent measures of heart failure (HF) is that of the left ventricular ejection fraction (LVEF). Since the EF implies diagnostic and prognostic information, it remains a key diagnostic measure; fortunately, our understanding of how and why it provides such import has grown, and a better understanding of its subtleties is worth a brief review. The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines categorize patient management according to whether the patient has HF with preserved EF (HFpEF) or HF with reduced EF (HFrEF).1 Compared with HFrEF, diagnosing HFpEF continues to be a challenging endeavor. One major limitation is the lack of a consistent definition and the variable terminology used to describe the condition. Previously, the term “diastolic HF” was commonly used; however, because of the lack of specificity with this terminology, HFpEF is now the preferred term. Another limitation within the HF literature is the variability in LVEF cutoff points that are used to define HFpEF—ie, 40%, 45%, 50%, or 55%.2 HFpEF diagnosis is based on patient history, signs and symptoms, absence of LV systolic dysfunction, and exclusion of other conditions that may resemble HF, such as valvular or pericardial disease. Dyspnea on exertion is a key clinical finding. Brain (aka B-type) natriuretic peptide (BNP) or pro-BNP plasma levels are often elevated in HFpEF, albeit to a lesser extent than in HFrEF. Elevated levels of these biomarkers help to confirm diagnosis and generally predict a worse outcome; however, the absence of their elevation does not rule out the diagnosis of HFpEF.3-5 A common finding in HFpEF is an exaggerated increase in pulmonary capillary wedge pressure and pulmonary artery pressure during exercise, with an attenuated increase in cardiac output. Electrocardiogram (ECG) findings may indicate LV hypertrophy or atrial enlargement. Doppler echocardiography is useful for identifying diastolic abnormalities. Other procedures that may be helpful in some patients include exercise testing, stress echocardiography, and cardiac catheterization to directly measure LV diastolic pressure.3 Pathophysiology The pathophysiology of HFpEF is multifactorial and not fully clear. Diastolic dysfunction is thought to be a major contributor in most cases, although factors other than diastolic dysfunction are also thought to play a role. The ability of the ventricle to relax and fill during diastole is affected by a multitude of factors, such as plasma volume, structural characteristics of the LV wall, active energy-driven

processes involved in LV relaxation, atrial contraction, and mitral valve integrity. Focal or diffuse scarring secondary to myocardial infarction or chronic inflammation is often seen.3 Over time, these changes lead to increased collagen deposition and fibrosis that may further impair diastolic function. In patients with HFpEF, a common finding is LV hypertrophy and increasing stiffness secondary to hypertension. Concentric remodeling or an increased LV wall thickness relative to the cavity size may also occur. Neurohormones—eg, angiotensin II, aldosterone, and norepinephrine—are thought to play a role in remodeling, similar to what occurs in HFrEF.3 Depending on etiology, the left ventricle typically is dilated in HFrEF, with eccentric remodeling; furthermore, LV systolic elastance is reduced and arterial elastance is elevated, thereby impairing ventricular–vascular coupling.3,6 A new category is born: HF with midrange EF (HFmrEF)

The European Society of Cardiology (ESC) HF guidelines, published in 2016, recognize people with HFmrEF as a distinct group of patients.3 Akin to HFpEF, the ESC diagnostic criteria for HFmrEF include elevated natriuretic peptides and relevant structural heart disease (LV hypertrophy and/or left atrial enlargement) or diastolic dysfunction; it is thought that patients with HFmrEF likely have mostly mild systolic dysfunction that is accompanied by features of diastolic dysfunction. Current ESC guidelines define HFmrEF as an LVEF ranging from 40% to 49%—although, as seen in the literature, the upper limit of LVEF is up to 55%.7 The actual value of this new category as well as its distinct therapeutic approaches should become clearer in the years ahead. Medications deemed effective in randomized controlled trials in patients with HFrEF have generally failed to show benefit for patients with HFpEF; consequently, treatment of HFpEF remains focused on controlling symptoms, comorbidities, and cardiovascular (CV) risk factors.1 There are limited data on the HFmrEF phenotype and outcomes, and the impact of recovered systolic function on the clinical features, functional capacity, and outcomes of this population are not clear. Some older studies that evaluated patients with HFmrEF have shown clinical features and mortality rates that are intermediate between those of HFrEF and HFpEF.8-10 Data on HFmrEF There is substantial heterogeneity in patients with HF with midrange LVEF. This group includes patients with de novo HF as well as patients with HF with previously reduced LVEF who have recovered their systolic function.7


Notably, this latter group of patients has been shown to have a more favorable prognosis among patients with HF.11 A study by Nadruz and colleagues evaluated 944 patients with HF and the impact of recovered systolic function on the clinical features, functional capacity, and outcomes in this population. Patients with HF were categorized into the following groups: HFrEF (LVEF <40%; n=620); HFmrEF and no recovered EF (LVEF consistent between 40% and 55%; n=107); HF with recovered midrange EF (LVEF 40%-55% but previous LVEF <40%; n=170); and HFpEF (LVEF >55%; n=47). What this study showed was that patients with HFmrEF have a distinct clinical profile apart from HFpEF and HFrEF. Other key findings from this study included the following7: • Among patients with HFmrEF, those with HF with recovered midrange EF had similar clinical characteristics

and measures of exercise tolerance but a better prognosis as compared with HFmrEF and no recovered EF • Although their clinical characteristics were distinct from HFpEF and HFrEF, patients with HFmrEF and no recovered EF and those with HF with recovered midrange EF had ventilatory responses to exercise that were better than HFrEF and similar to HFpEF • Patients with HF with recovered midrange EF had event rates that were lower than HFrEF and similar to HFpEF, whereas those with HFmrEF and no recovered EF had an intermediate risk of outcomes in comparison with HFpEF and HFrEF These findings suggest that among patients with HF with midrange LVEF, recovered systolic function may be a marker of a more favorable prognosis despite similar clinical characteristics and cardiopulmonary response to exercise.7

Heart failure resources JOURNALS AND GUIDELINES • Journal of the American College of Cardiology (JACC): • JACC-Heart Failure (JACC-HF): • 2013 ACCF/AHA Guideline for the Management of Heart Failure: • 2016 Focused Update on New Pharmacological Therapy for Heart Failure: CIR.0000000000000435 • Heart Failure Focused Update on Pharmacological Therapy (summary of 10 points to remember): • 2017 Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: jacc.2017.04.025 • Get With the Guidelines—Heart Failure: GetWithTheGuidelines/GetWithTheGuidelines-HF/Get-WithThe-Guidelines-Heart-Failure-Home-Page_UCM_306087_ SubHomePage.jsp

GROUPS/ASSOCIATIONS WEBSITES • American College of Cardiology (ACC): • ACC Accreditation Services: • American Heart Association (AHA): • American Association of Heart Failure Nurses (AAHFN): • European Society of Cardiology (ESC): • Heart Failure Society of America (HFSA): ACC/CARDIOSMART RESOURCES • ACC CardioSmart—Heart Failure: • Heart Failure Practice Solutions: heart-failure-practice-solutions • Practice Solutions (Heart Failure Toolkit): • Succeed in Managing Heart Failure Initiative: succeed-in-managing-heart-failure-initiative • ACC Clinical Topics—Heart Failure and Cardiomyopathies: re86069%20descending • THE CLINICAL ADVISOR • AUGUST 2017 27



Results from a large study of hospitalized Medicare patients (N=40,239) with HF showed that patients with HFpEF and borderline LVEF (defined as 40% to <50%) had slightly lower mortality and higher all-cause readmission risk than patients with HFrEF, although the mortality differences did not persist after risk adjustment. Moreover, patients with borderline LVEF had a distinct risk profile for readmission, with a larger proportion of admissions related to cardiovascular disease (CVD).12 It is hoped that further research concentrated on this “gray area” of HF will help to elucidate the characteristics, pathophysiology, outcomes, and optimal treatment interventions for patients with HFmrEF.3 The MOGE(S) classification system

The terminology we use to define and categorize HF describes a phenotype: it doesn’t account for genetic factors or causes. Yet most cardiomyopathies, we are learning, are familial diseases. For half a century, cardiomyopathy classifications have been based on the morphofunctional phenotypes, allowing cardiologists to group patients into rather broad descriptive categories. However, phenotyping may not always conform to genetic characteristics or allow for risk stratification, and it may not suggest preclinical diagnosis among family members.13,14 In addition, all current treatment protocols are based on the phenotype along with signs and symptoms. Phenotype-based classification describes the major forms of cardiomyopathy (eg, hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/arrhythmogenic ventricular cardiomyopathy, and left ventricular noncompaction), but not their etiologies. However, cardiomyopathies are clinically heterogeneous diseases, and within each subtype of cardiomyopathy there are differences in sex, age of onset, rate of progression, risk of development of overt HF, and risk of sudden death.14 Given the genetic heterogeneity of HF and our current era of genomic testing, new strategies are needed to describe cardiomyopathies associated with different genetic mutations. The recently proposed MOGE(S) nosology, which has been endorsed by the World Heart Federation, originated from the desire to integrate a morphofunctional phenotype-based description with information regarding extracardiac organ involvement and clinical (pattern of inheritance) and molecular (disease gene and mutation) genetics in familial disease. The MOGE(S) classification system aims to describe sporadic cardiomyopathies and their etiology. The system, which has been likened to oncology’s tumor-node-metastases staging system, addresses 5 key characteristics13:

• • • •

Morphofunctional phenotype (M) Organ involvement (O) Genetic or familial inheritance pattern (G) Etiological description (E) of genetic defect or nongenetic underlying cause • Functional status (S) using the ACC/AHA (A to D) stage and New York Heart Association (NYHA; I to IV) functional class Note that the “S” component is particularly useful when mutation carriers are healthy or if they demonstrate imagingverified early abnormalities suggestive of cardiomyopathy.13 At first glance, implementation of the MOGE(S) classification system might seem daunting; however, it is flexible, bedsidefriendly, and relatively simple to integrate into practice. Genetic testing isn’t mandatory with MOGE(S); however, clinicians should try to obtain a family history and document familial patterns. Overall, MOGE(S) requires a description of the results obtained in the diagnosis of HF, including clinical cardiologic evaluation, extracardiac evaluation, clinical genetics, family screening, molecular genetics, and functional status, to provide a uniform terminology and easily captured identical information. A companion application, which is available free for various platforms, allows for stepwise data compilation, which can optionally be submitted to data repositories. Conclusion

Although the ACC HF guidelines define only 2 categories of HF based on EF (HFpEF and HFrEF), many patients have EFs that fall into a midrange, defined by the ESC as HFmrEF. Although no evidence-based treatment recommendations exist for this group of patients, this additional construct can add nuance to our thinking about the clinical management of these patients. Similarly, the MOGE(S) nosology can add a valuable dimension to other established classifications and categorizations of HF, notably the ACCF/AHA stages and NYHA functional classifications of HF. The combined use of these different terminologies and definitions may allow for enhanced prevention and improved detection and management of HF in our patient populations. ■ References 1. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147-e239. 2. Howard PA. Treating heart failure with preserved ejection fraction: a challenge for clinicians. Hosp Pharm. 2015;50(6):454-459. 3. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the


diagnosis and treatment of acute and chronic heart failure. Eur J Heart Fail.

Reduction in Mortality (CHARM) Investigators. Influence of ejection


fraction on cardiovascular outcomes in a broad spectrum of heart failure

4. Abbate A, Arena R, Abouzaki N, et al. Heart failure with preserved

patients. Circulation. 2005;112:3738-3744.

ejection fraction: refocusing on diastole. Int J Cardiol. 2015;179:430-440.

10. He KL, Burkhoff D, Leng WX, et al. Comparison of ventricular structure

5. van Veldhuisen DJ, Linssen GC, Jaarsma T, et al. B-type natriuretic

and function in Chinese patients with heart failure and ejection fractions

peptide and prognosis in heart failure patients with preserved and

>55% versus 40% to 55% versus <40%. Am J Cardiol. 2009;103:845-851.

reduced ejection fraction. J Am Coll Cardiol. 2013;6(14):1498-1506.

11. Basuray A, French B, Ky B, et al. Heart failure with recovered ejec-

6. Iwano H, Little WC. Heart failure: what does ejection fraction have to

tion fraction: clinical description, biomarkers, and outcomes. Circulation.

do with it? J Cardiol. 2013;62:1-3.


7. Nadruz W Jr, West E, Santos M, et al. Heart failure and midrange

12. Cheng RK, Cox M, Neely ML, et al. Outcomes in patients with heart

ejection fraction: implications of recovered ejection fraction for exercise

failure with preserved, borderline, and reduced ejection fraction in the

tolerance and outcomes. Circ Heart Fail. 2016;9(4):e002826.

Medicare population. Am Heart J. 2014;168(5):721-730.

8. Gottdiener JS, McClelland RL, Marshall R, et al. Outcome of congestive

13. Arbustini E, Narula N, Tavazzi L, et al. The MOGE(S) classification of

heart failure in elderly persons: influence of left ventricular systolic function:

cardiomyopathy for clinicians. J Am Coll Cardiol. 2014;64(3):304-318.

the Cardiovascular Health Study. Ann Intern Med. 2002;137:631-639.

14. Berezin A. Epigenetics in heart failure phenotypes. BBA Clin.

9. Solomon SD, Anavekar N, Skali H, et al; Candesartan in Heart Failure



POST-TEST Expiration date: May 5, 2018

Credit Designation: The ACCF designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. The ACCF designates this educational activity for a maximum of 0.50 continuing nursing education contact hour. Requirements for successful completion are viewing of module in its entirety and completing the evaluation tool. A statement of credit will be issued only upon receipt of a completed pre-assessment test, polling questions, activity evaluation form, and post-test with a score of 70% or higher. All components must be completed and submitted online at CREDITS: 0.50 | The impact of HFrEF vs HFpEF: How do we measure up?

1. Which of the following is a common finding in heart failure with preserved ejection fraction (HFpEF)? a. A decrease in brain natriuretic peptide (BNP) or proBNP plasma levels b. An exaggerated increase in pulmonary capillary wedge pressure c. Left ventricular (LV) dilation with eccentric remodeling d. A reduction in LV systolic elastance 2. Heart failure with reduced ejection fraction (HFrEF) is associated with: a. Elevated BNP or pro-BNP levels b. Dyspnea c. Elevated arterial elastance d. LV hypertrophy

3. The European Society of Cardiology (ESC) guidelines define HF with midrange ejection fraction (HFmrEF) as: a. Patients with de novo HF and LVEF 40-49% b. Patients with LVEF 40%-49% and previously reduced LVEF c. Patients with LVEF ≤40%-49% regardless of previous systolic function d. Patients with LVEF ≥50% and mild diastolic dysfunction 4. Which of the following is a characteristic of morphofunctional phenotype under the MOGE(S) classification system? a. Hypertrophic cardiomyopathy b. Involvement of extracardiac organs c. Familial HF d. American College of Cardiology/American Heart Association Stage C HF


Advisor Forum These are letters from practitioners around the country who want to share their clinical problems and successes, observations, and pearls with their colleagues. Responding consultants are identified below. We invite you to participate.

YOUR COMMENTS EPILEPSY AND THE KETOGENIC DIET I have been a devoted reader since I first became a nurse practitioner in 2004. I felt compelled to write about the epilepsy CME article (“Paving the way to better epilepsy outcomes,” page 24) in the June 2017 issue. Although Drs Joseph Sirven and Sheryl Haut covered the topic of improving seizure control, improving patient adherence (likely due to the difficulty to tolerate medications), and minimizing side effects, I was terribly disappointed to see nothing about diet covered in this comprehensive article. Your readers quite likely use the material you publish to enhance their practice, and we nurse practitioners are a rather holistic bunch. It is well-documented in the literature that those with epilepsy benefit greatly from a ketogenic diet, especially children. Often, medications are not even needed in a lot of cases. The ketogenic diet is—and remains—the only treatment with the Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 275 7th Avenue, 10th Floor, New York, NY 10001.You may contact us by e-mail at If you are writing in response to a published letter, please indicate so by including the number in parentheses at the end of each item. Letters are edited for length and clarity. The Clinical Advisor’s policy is to print the author’s name with the letter. No anonymous contributions will be accepted.

consistent ability to prevent seizures, as ketogenic diets just work! The diet increases the conversion of glutamate into glutamine into GABA, reducing neuronal excitability. It increases antioxidant status in the neuronal mitochondria, improving their function. It also reduces free radical formation in neurons, a likely cause of seizures. The following are links to recent studies on the subject: • CD001903.pub2/full • S0920121112000502 • S1059131110001202 • • • I am sure that Drs Sirven and Haut are great doctors, but they seem to focus only on conventional medicine and heavy use of pharmaceuticals, which only treats the symptoms of the disease. I practice functional medicine, which tries to get to the cause of the disease, treating the actual disease itself. Although I practice in diabetes, I am an expert in the Paleo diet, which can often be ketogenic. —CHRYSTYNE OLIVIERI, DNP, FNP-BC, CDE, Greenlawn, N.Y. (226-1)


Philip R. Cohen, MD,

is clinical associate professor of dermatology, University of Texas Medical Center, Houston.

Deborah L. Cross, MPH, CRNP, ANP-BC, is associate program

director, Gerontology NP Program, University of Pennsylvania School of Nursing, Philadelphia.

Abimbola Farinde, PhD, PharmD,

is a professor at Columbia Southern University in Orange Beach, Ala.


Laura A. Foster, CRNP, FNP,

Abby A. Jacobson, MS, PA-C,

practices family medicine with Palmetto Primary Care Physicians in Charleston, S.C.

is an assistant professor at Thomas Jefferson University and a dermatology PA at Family Dermatology of Reading, Pa.

MY MOST MEMORABLE PATIENT FULFILLING A DYING PATIENT’S REQUEST: A TRIP TO THE RENAISSANCE FESTIVAL As a palliative care nurse practitioner, I have the opportunity to have many memorable patient experiences, but one stands out above many others. Dealing with patients who have serious life-threatening illnesses allows me to have conversations with them about their quality of life and their last wishes, their “bucket list” in a condensed time frame, so to speak. Several years ago, I met a patient, Mr G. He was diagnosed with stage 4 lung cancer and was given a 2-month life expectancy. His life was complicated by drugs, alcohol, mental illness, and familial estrangement for approximately 20 years. While assisting him to complete his living will, I asked him the question that I have asked many of my patients previously: “If there was only one thing you could do before you die, what would it be?” Mr G thought for a moment and then responded, “I would like to attend a Renaissance Festival.” Now realize, I have had many patients request many things, including malts from a specialty ice cream shop, a visit with their new grandchild, a bag of Oreos, or a fried oyster po-boy. But this was a request that put me on a mission. Ironically (I believe everything happens for a reason), I found a private Renaissance Festival that occurred 2 weeks after our conversation and fell within the 2-month time frame that Mr G had been given to live. I immediately jumped into action making phone calls and requests for donations to assist with fulfilling a dying man’s last wish. Four hours after his request, I entered Mr G’s hospital room to offer him the adventure of a lifetime if he could stay healthy enough to attend and be out of the hospital. His

Debra August King, PhD, PA,

is senior physician assistant at New York-Presbyterian Hospital, New York City.

Mary Newberry, CNM, MSN,

provides well-woman gynecologic care as a midwife with Prima Medical Group, Greenbrae, Calif.

face said it all. Mr G improved dramatically over the next few days and was discharged home. A week after discharge, Mr G and I embarked on an adventure 2 hours away from home that would change both of our lives forever. The Renaissance organization made it its mission to provide an unforgettable experience to a man with a simple request. Mr G was greeted with a costume, a horse-drawn chariot, and numerous gifts, and he was invited to sit with the nobility, an honor reserved for hierarchy at these types of events. He was brought to the battlefield during a battle to be granted the title of honorary “Lord” for the day and was given a beautiful medieval knife as a memorial gift. Although Mr G was highly debilitated by his disease and required continuous oxygen and extensive medical care, for one day he was alive, energetic, happy, and fulfilled. Mr G expressed feeling overwhelmed by the welcoming that he received and the experience that was created “for a simple man like me with a dying request.” As I watched an organization come together to make the wish of a simple man a reality, I was filled with emotion. It was in that moment and due to that experience that I realized that often in life we miss the opportunities to address the things that really matter in the end. He did not wish for better health or pray to win the lottery. He did not wish to have a big house or a fancy car. What mattered was an experience that would be his most treasured memory until the day of his death 3 months after our adventure. Mr G’s memory lives on in my heart, and the lessons learned are offered to many of my patients—be present and listen with an open heart, as sometimes it’s not the medicine, the treatment, or the new advances in medicine that really matter, but the simplicities that make life memorable to each and every one of us.—MICHELE LANDRY, MSN, APRN, ANP-BC, CHPN, Lafayette, La. (226-2) n

Claire O’Connell, MPH, PA-C,

an associate professor at the Rutgers University Physician Assistant Program, Piscataway, N.J.


Katherine Pereira, DNP, FNP,

is assistant professor, Duke University School of Nursing, Durham, N.C.

Sherril Sego, FNP-C, DNP,

is an independent consultant in Kansas City, Mo. • THE CLINICAL ADVISOR • AUGUST 2017 31

Writers’ Guidelines The Clinical Advisor welcomes submissions from its readers. Writing for us is an opportunity to share your knowledge and experience with your colleagues — and to collect a fee in the bargain! We pay an honorarium for every submission we accept. We’ll be glad to work with you to develop your ideas into compelling articles. As for length, that depends on which kind of article you submit. CLINICAL FEATURES update our readers on the latest information about conditions seen in everyday practice. Running approximately 2,500 to 5,000 words, including the references, features can be written either as regular narratives or as a series of questions and answers. Topics should be selected with the busy primary-care clinician in mind; specialists should review specialty topics from the primary-care point of view. If at all possible, articles should be accompanied by clinical photos. Charts, tables, and algorithms are also encouraged. Please include your title and affiliation. CLINICAL CHALLENGE is our popular department comprising histories of difficult cases. Each case is presented as a step-by-step, chronological account, revealing the author’s thought processes along the way. It is divided into sections in this order: the patient presentation; the patient history; the twists and turns eventually leading to a diagnosis; the treatment and outcome; and a discussion of the lessons learned or of the condition in general. The length should be about 1,500 words, and accompanying images are encouraged. Please include your title and affiliation. DERMATOLOGY CLINIC is a department that presents photos of actual cases and asks readers to identify the condition. Each case opens with one or two color photos and a 75-to-100-word description of the patient presentation, without giving away the diagnosis. This is followed by a 750-to-1,000-word summary that includes a fuller description of the ailment, an explanation of how the correct diagnosis was reached, a general review of the condition along with a differential diagnosis, and a description of the patient’s treatment and outcome. Topics must be approved by the editor prior to submission. Please include your title and affiliation. COMMENTARY is our guest editorial page. It gives you the opportunity to sound off on an issue of importance to your colleagues nationwide. A typical Commentary runs about 600 words in length. Please include your title and affiliation. To discuss your editorial ideas, contact us by phone at 646.638.6078; by e-mail to; or by mail to The Clinical Advisor, 275 7th Avenue, 10th Floor, New York, NY 10001. 32 THE CLINICAL ADVISOR • AUGUST 2017 •

Dermatology Clinic CASE #1

A worsening rash with a malodor JIATING JIANG, BS, DAVID RIZK, BS, ANDREW FISCHER, MD

The patient is a 19-year-old woman who presents to her primary care provider after having a worsening rash over several years. The rash appears as erythematous, hyperkeratotic thin plaques that have been occurring in a seborrheic distribution. The patient states that the rash is very irritating, and it is sometimes pruritic. The woman’s main complaint is that the rash exudes a malodor. Furthermore, the patient states that her father has had a similar rash that he chooses not to treat. What is your diagnosis? Turn to page 34


Hyperpigmented macules in the interscapular region ALEX KOLKIN, BS, CHRISTOPHER RIZK, MD

The patient is a 38-year-old Hispanic woman who presents with a 1-year history of having a very pruritic rash throughout her interscapular area. On examination, she has a circular area of slightly hyperpigmented macules in the interscapular region. The patient complains of pruritus, but she has no pain in the area of the rash. She has no other medical problems and has no systemic symptoms. In addition, the patient has no relevant social or family history and does not take any medications. What is your diagnosis? Turn to page 36 • THE CLINICAL ADVISOR • AUGUST 2017 33

Dermatology Clinic CASE #1

Darier disease

Darier disease, also known as keratosis follicularis or Darier-White disease, is a rare genodermatosis due to abnormal intracellular Ca 2+ signaling, leading to acantholytic dyskeratosis. It is characterized by keratotic papules in a seborrheic distribution with characteristic nail findings.1,2 Studies have estimated its prevalence at approximately 1 in 30,000 to 100,000 people.1 Darier disease is inherited in an autosomal dominant manner; however, sporadic mutations may account for as many as 40% to 50% of cases.3 The primary pathologic process is that of a mutated ATP2A2 gene long arm of chromosome 12 at 12q2324.1.3 The ATP2A2 gene encodes SERCA2 (sarcoplasmic/ endoplasmic reticulum Ca2+-ATPase), a calcium adenosine triphosphatase (ATPase) that is responsible for transporting Ca 2+ from the cytosol into the endoplasmic reticulum.2 When this calcium ATPase is dysfunctional, Ca 2+ accumulates in the cytosol, leading to the characteristic acantholysis and apoptosis seen in the disease. It is not exactly understood how this occurs, but it may be due to inhibited processing and trafficking of desmosomal proteins, such as desmoplakin, from the endoplasmic reticulum to the cell surface, or stress-induced apoptosis of keratinocytes secondary to calcium depletion.1,3 Clinical features typically appear in patients between 6 and 20 years of age (often around puberty), and may be varied. The predominant clinical finding is keratotic papules distributed symmetrically in a seborrheic distribution over the neck, shoulders, face, extremities, front of the chest, and midline of the back; it can also progress to include the buttocks and genitals.2 The papules are often initially skin colored, but mature into dark, crusted, greasy, vegetating plaques.2 Patients characteristically have notched (V-shaped knicks), subungual keratotic nails that contain longitudinal, alternating white and red streaks.1,2 Other clinical features include punctate palmoplantar keratosis, hypopigmented macules (especially in dark-skinned individuals), flat papules resembling flat warts, and small, white, mucosal papules.1,2 Exacerbating factors include heat, high humidity, sweat, ultraviolet light, pregnancy, surgery, bacterial colonization, and, in some cases, lithium carbonate.1 Itching and malodor are common complaints, especially if secondary infection

is present. In certain cases, the disease and symptoms may lead to social isolation. Neuropsychiatric disorders such as major depression, intellectual disability, epilepsy, and bipolar disorders have been associated with the disease.1 It is not known whether the ATP2A2 gene is primarily implicated in these disorders as well, if there are closely linked susceptibility genes, or if the relationship is not genetic. Social isolation may contribute to the social morbidity often observed in patients with Darier disease. Darier disease is characterized histologically by acantholytic dyskeratosis.5 Acantholysis presents as suprabasilar clefting and is due to a loss of cell-to-cell adhesions. Dyskeratosis takes the form of corps ronds and grains, and is secondary to keratinocyte apoptosis. Corps ronds are round, pale to eosinophilic, dyskeratotic cells in the spinous or granular layer, which typically contain a perinuclear halo.5 Corps grains are flat, basophilic, dyskeratotic cells in the granular layer and stratum corneum.5 Hyperkeratosis and parakeratosis is also observed in the overlying stratum corneum. The differential diagnosis includes Hailey-Hailey disease, acrokeratosis verruciformis of Hopf, Grover disease, seborrheic dermatitis, pemphigus vegetans, blastomycosis-like pyoderma, flat warts, acanthosis nigricans, and epidermodysplasia verruciformis.1,3 A personal and family history, in conjunction with results of a physical examination, is often highly suggestive of the diagnosis. A biopsy demonstrating acantholytic dyskeratosis further helps to make the correct diagnosis. Hailey-Hailey disease, also caused by a defect in calcium signaling, may share similar features with Darier disease.1 However, its predominant feature of flaccid vesicles on erythematous skin with a predilection for the intertriginous areas, along with a histologically distinct pattern of acantholysis, can be used to make the distinction. Darier disease and acrokeratosis verruciformis of Hopf both feature flat-topped papules on the dorsal surface of the extensors.2 If the other features of Darier disease are absent, differentiation from acrokeratosis verruciformis of Hopf on clinical grounds may be impossible. Results of a biopsy readily distinguish the two, because acrokeratosis verruciformis of Hopf lacks acantholysis and dyskeratosis.1,2 Both entities share the same mutated gene, and some consider them to be related.1 Grover disease and seborrheic dermatitis are other considerations based on clinical features (Grover disease may even feature similar histology); however, there is no involvement of acral skin, the nails, or the oral mucosa in either of these diseases. Treatment for Darier disease is symptomatic. Patients should be instructed to protect themselves from sun exposure

34 THE CLINICAL ADVISOR â&#x20AC;˘ AUGUST 2017 â&#x20AC;˘

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Dermatology Clinic and wear lightweight clothing to prevent exacerbations. Antimicrobial agents are used for bacterial colonization and keratolytic moisturizers for scaling.1,2 Topical retinoids and topical steroids can be used with some benefit in localized disease. Oral retinoids are effective, but often limited by side effects, and patients have a relapse after cessation.1,3 Surgical procedures, including dermabrasion, laser ablation, and excision and split-thickness grafting, can lead to long-term remission for recalcitrant hypertrophic lesions.1 The patient in this case was disturbed by her disease and was started on an oral retinoid for treatment. On follow-up the patient had significantly improved and was happy with the outcome of her treatment. Jiating Jiang, BS, is a medical student at the Baylor College of Medicine, David Rizk, BS, is a medical student at the University of South Alabama, and Andrew Fischer MD, is a dermatology resident at Colorado University. References 1. Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012. 2. James WD, Berger TG, Elston DM, Neuhaus IM. Andrews’ Diseases of the Skin: Clinical Dermatology. 12th ed. Philadelphia, PA: Elsevier; 2016. 3. Takagi A, Kamijo M, Ikeda S. Darier disease. J Dermatol. 2016;43:275-279. 4. Wang Y, Bruce AT, Tu C, et al. Protein aggregation of SERCA2 mutants associated with Darier disease elicits ER stress and apoptosis in keratinocytes. J Cell Sci. 2011;124:3568-3580. 5. Elston D, Ferringer T, Ko CJ, Peckham S, High WA, DiCaudo DJ. Dermatopathology. Philadelphia, PA: Elsevier Saunders; 2014.


Macular amyloidosis

Macular amyloidosis is a chronic pigmentary disorder of the skin; it is found with the highest prevalence in Asia, the Middle East, and South America.1-4 Along with lichen amyloidosis and nodular amyloidosis, it comprises one of three major subtypes of primary localized cutaneous amyloidosis, a condition in which amyloid deposition occurs in otherwise normal skin without associated amyloid deposits in systemic organs.4 Macular amyloidosis most

commonly presents between the ages of 21 and 50 years in patients with Fitzpatrick skin phenotype III or IV.2-4 It is predominantly seen in women, with an estimated femaleto-male ratio approximating 5:1.1-3 Macular amyloidosis is characterized by a rippled pattern of hyperpigmented brown macules characteristically found in the interscapular area of the back.1-5 It is also commonly found on the extensor surfaces of the extremities, and less commonly on the face, breasts, axilla, and buttocks.1-4 Pruritus is the most common symptom that is associated with macular amyloidosis, though some cases are asymptomatic.2,4 The exact cause of macular amyloidosis remains unknown, though factors such as sunlight exposure, friction, sex, race, genetic factors, Epstein-Barr virus infection, and autoimmune reactions have been proposed.2,4 Classically, frictional rubbing and sunlight exposure are considered the major etiologic drivers of the disease process,1,4 though both of these factors have been challenged by recent studies.2,3 Macular amyloidosis is associated with autoimmune disorders such as systemic lupus erythematosus, dermatomyositis, primary biliary cirrhosis, and atopic dermatitis.1,3,4 The amyloid deposits found in macular amyloidosis are believed to originate from keratin derived from damaged basal keratinocytes; staining of these deposits with monoclonal antibodies such as EKH4 or EAB-903 against the keratin of basal keratinocytes has demonstrated positive reactions.1,4,5 Apolipoprotein E4, as well as type IV collagen and laminin, are also associated with the formation of the amyloid deposits specific to macular amyloidosis.4 The pathogenesis of macular amyloidosis is currently attributed to two major theories—the fibrillary body theory and the secretory theory.2,4 The fibrillary body theory proposes that damaged basal keratinocytes pass into the papillary dermis after undergoing filamentous degeneration, where they are subsequently modified into amyloid material by histiocytes and dermal fibroblasts.2,4 The secretory theory proposes that damaged basal keratinocytes directly secrete amyloid precursor proteins at the epidermo-dermal interface, which then pass through the damaged lamina densa into the papillary dermis.2,4 Macular amyloidosis is typically diagnosed clinically by its rippled pattern of hyperpigmented brown macules. Results of skin biopsies sent for routine histologic analysis can commonly appear normal and may fail to demonstrate the amyloid deposits characteristic of the condition.1,2 If present, characteristic macular amyloidosis biopsy specimens show amorphous amyloid deposits within the dermal


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Dermatology Clinic papillae, located directly below the epidermis.1 When stained with Congo red, the deposits demonstrate characteristic apple green birefringence under polarized light.2,4 Like the amyloid found in systemic amyloidosis, deposits in macular amyloidosis can be identified with electron microscopy as nonbranching fibrils within biopsy specimens.4 The differential diagnosis for macular amyloidosis should include lichen amyloidosis, notalgia paresthetica, prurigo nodularis, and lichen simplex chronicus.4 The differential diagnosis should also include other skin disorders with pigmentary skin changes, including porphyria, Waldenström macroglobulinemia, colloid milium, and lipoid proteinosis.5

The patient in this case was treated with clobetasol ointment (a high-potency topical steroid). Use of clobetasol twice daily, along with education on avoiding scratching and friction, led to the resolution of the rash and her symptoms of pruritus. n Alex Kolkin, BS, is a medical student, and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine. References 1. James WD, Berger TG, Elston DM, Neuhaus IM. Errors in metabolism. In: James WD, Berger TG, Elston DM, Neuhaus IM, eds. Andrews’ Diseases of the Skin: Clinical Dermatology. 12th ed. Philadelphia, PA: Elsevier; 2016:509-513. 2. Bandhlish A, Aggarwal A, Koranne RV. A clinico-epidemiological

Reducing friction and rubbing of the affected skin area is a high priority, given that friction is a possible cause.

study of macular amyloidosis from North India. Indian J Dermatol. 2012;57:269-274. 3. Rasi A, Khatami A, Javaheri SM. Macular amyloidosis: an assessment of prevalence, sex, and age. Int J Dermatol. 2004;43:898-899. 4. Groves RW, Black MM. Amyloidosis. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012:699-708. 5. Rapini RP. Deposition and metabolic diseases. In: Rapini RP, ed. Practical Dermatopathology. 2nd ed. Philadelphia, PA: Elsevier Saunders; 2012:122-124.

“Early retirement is an OK long-term goal, Kevin, but most folks need to get a job first.”


© Harley Schwadron 2017

Macular amyloidosis is histologically similar to lichen amyloidosis but can be differentiated by clinical presentation. Lichen amyloidosis presents as hyperpigmented lichenified plaques with a rippled appearance, typically presenting on the shins.4,5 When both macular amyloidosis and lichen amyloidosis appear in the same skin region, biphasic amyloidosis is diagnosed.4 Macular amyloidosis can be difficult to treat.1 Highpotency topical steroids applied once or twice daily, along with education on the itch-scratch cycle, are the mainstays of treatment. Reducing friction and rubbing of the affected skin area is a high priority, given the evidence identifying friction as a possible etiologic factor.1 Additionally, intralesional corticosteroids, topical tacrolimus 0.1% ointment, 10% dimethyl sulfoxide topical ointment, psoralen plus ultraviolet A light, tar, and calcipotriol have all been used in trials with varying levels of efficacy.1,2 Etretinate and acitretin therapy have been associated with modest success in reducing symptoms, but relapse after treatment cessation is commonly reported.2 Oral retinoids, amitriptyline, thalidomide, and systemic immunosuppressive agents have also failed to provide unequivocal control of symptoms.1 Recent discoveries regarding the role of interleukin-31 in causing pruritus has prompted research into therapies targeting this cytokine pathway in order to control the itching associated with macular amyloidosis.2

Dermatologic Look-Alikes An erythematous plaque EVAN A. SCHAUER, BS, ARIELLE GRAY, BS, CHRISTOPHER RIZK, MD



The patient is a 44-year-old woman who presents with a 2-month history of a pruritic rash on her arm. The patient states that she noticed the rash when her arm began to itch. On examination, the rash appears to be an annular, erythematous plaque with overlying scale. Over the past 2 months, the rash has grown in size and become more pruritic. She has tried over-the-counter lotions with no relief. The patient has a past medical history of type 2 ­diabetes. The patient has no relevant family or social history.

The patient is a 33-year-old healthy man who presents with a quickly spreading rash on his right thigh. The patient says the rash is asymptomatic but is cosmetically troublesome. He states that he has had similar rashes in the past that resolved on their own. He is worried because his rash recurs. On examination, the patient has an erythematous, figurate plaque with a trailing scale. The patient is otherwise healthy and has no medical problems, or relevant family or social history. • THE CLINICAL ADVISOR • AUGUST 2017 39

Dermatologic Look-Alikes CASE #1

Tinea corporis

Tinea corporis is a cutaneous fungal infection colloquially called ringworm; it is especially common in warm, humid climates, and shows no predilection for any sex or age group. After acne, tinea infections are the most frequently reported skin disease.1-3 Tinea corporis occurs on the trunk and limbs, and is distinguished from other tinea infections based on location. Other specific varieties are tinea capitis (scalp), tinea cruris (groin), onychomycosis (nails), tinea manuum (hands), tinea pedis (feet), and tinea barbae (beard).2 Although tinea infections occur in all demographics, tinea corporis and tinea capitis are more common in prepubescent children, whereas tinea cruris, onychomycosis, and tinea pedis are more common in adolescents and adults.4 Wrestlers are particularly susceptible to ringworm; it is called tinea corporis gladiatorum in these cases.2,5 Tinea corporis is seen in healthy individuals, but is more prevalent in people with chronic conditions such as diabetes, immunodeficiency, and leukemia.2

Most localized tinea corporis infections respond well to topical antifungal agents such as butenafine and terbinafine. The causative organisms are aerobic fungi from the Trichophyton, Microsporum, or Epidermophyton genera, which are collectively called dermatophytes.6 Every species in these genera is a pathogen and is anthropophilic, zoophilic, or geophilic; Trichophyton rubrum, T mentagrophytes, and Microsporum canis are the most common agents responsible for cases worldwide; other species, such as T violaceum, are more common in India and Africa.1,3,7,8 Cases result from direct contact with infected individuals, as well as from contaminated soil, animals, spores known as arthroconidia, or other fomites; carriers are often asymptomatic.3,7 Dermatophytes are capable of producing enzymes such as keratinase that allow them to survive in the stratum corneum of the epidermis, nails, and hair. Hair follicles can act as reservoirs, making the infection more resistant to treatment.4,8 The incubation period for a new infection

is approximately 1 to 3 weeks, and targets exposed skin; the degree of inflammation is determined by the host’s immune response and the specific pathogen (zoophilic species stimulate more inflammation).3,8 Tinea corporis is characterized by annular, scaly, erythematous patches and plaques that occur in cyclical patterns due to the pathogen’s hyphae extending centrifugally once in the host.9 The peripheral border of the lesion is more pronounced and sometimes pustular. The annular border usually surrounds a pale, erythematous resolving center.8,9 Multiple lesions can coalesce together to create intricate, polycyclic designs with papular borders; the lesions are distributed asymetrically.1,6 The lesions are commonly pruritic and can cause a burning sensation; however, they can also be asymptomatic.6,8 Individual lesions are approximately 1 to 5 cm.4 It should be noted that topical corticosteroids can alter the appearance of tinea corporis by reducing scale and allowing expansion of the lesions.1,2,8 The majority of tinea corporis cases are diagnosed clinically.10 If clinicians want to diagnose tinea corporis in the office, they may perform a potassium hydroxide (KOH) preparation to look for fungal hyphae. This is performed by scraping the active border of the lesion, then treating the scrapings with 10% KOH and observing them under a light microscope. In many cases of tinea corporis, translucent fungal hyphae are visible under light microscopy.2,6 Alternatively, clinicians may perform a biopsy (for routine histologic examination) or fungal culture of the lesion to confirm the diagnosis.7 The differential diagnosis for tinea corporis often includes erythema annulare centrifugum (EAC), eczema, seborrheic dermatitis, psoriasis, granuloma annulare, impetigo, and pityriasis.7 Most localized tinea corporis infections respond well to topical antifungal agents such as butenafine and terbinafine; these are preferred over older medications such as miconazole and clotrimazole.4,7 The topical cream should be applied to the entire lesion, and 2 cm around the active border; treatment should be continued for at least 2 weeks, or until the lesions have completely resolved.1,7 If the lesions are widespread or severe, oral antifungal treatment with medications such as terbinafine can be used (usually a 30-day course for cutaneous involvement). If the patient has nail involvement (onychomycosis), he or she may require up to 3 months of terbinafine daily. Common side effects of oral terbinafine include liver enzyme elevations and interactions with β-blockers. Thus, clinicians should confirm that patients do not have a history of elevated liver function enzymes and are not taking β-blockers before prescribing oral terbinafine. Some recommendations also suggest


checking liver function enzymes at 6 weeks in patients taking a 3-month course of terbinafine for onychomycosis. In this case, due to the localized nature of the patient’s rash, the patient was treated with topical butenafine. The patient applied topical butenafine twice daily for 1 month, which led to the resolution of the rash.


Erythema annulare centrifugum

EAC (also known as palpable migrating erythema or erythema perstans) is characterized by red, annular patches or plaques that can grow 2 to 3 mm per day, and can reach 6 cm in diameter in less than 2 weeks. Individual lesions can reach approximately 10 cm in diameter, with areas of pale, central clearance and slightly raised, scaling edges.8,11-13 These lesions originate as pinkish, firm papules and occur primarily on the trunk and limbs/extremities (especially the

thighs and hips). Although they are typically asymptomatic, some lesions can develop pruritis.11,8 One of the main distinguishing features of EAC is the presence of a “trailing scale.” The term refers to the fact that the scaling border of EAC is located on the interior edge of the erythematous ring, as opposed to the exterior edge of the lesion.8,11 The surface of the lesions do not typically have crusts or vesicles. EAC is more prevalent in adults.8 Individual lesions can last from a few days to several months, and often disappear and reappear in monthly or yearly cycles (in a cyclical fashion).8,11,14 Diagnosis of EAC can be difficult because of the vagueness of symptoms and the wide variety of associated risk factors; therefore, histologic examination (hematoxylin and eosin stain) can be helpful for diagnosis. The three major histologic characteristics of EAC are parakeratosis, spongiosis, and a distinctive arrangement of lymphocytes around cutaneous vasculature (colloquially referred to as a “coat sleeve”).8,11,13 Due to the vagueness of EAC’s characteristics, the differential diagnosis includes many other cutaneous, annular ailments, including tinea infections, granuloma annulare, Hansen disease, annular urticaria, and secondary syphilis.11 Most cases are idiopathic and spontaneously resolve.11 The majority of patients with EAC do not have an underlying condition; however, EAC is has been associated with

TABLE 1. Tinea corporis versus erythema annulare centrifugum Tinea corporis

Erythema annulare centrifugum

Dermatologic presentation

• Erythematous, annular, scaly lesions with pale central clearing • Cyclical/oval/circinate lesions can coalesce together • Asymmetrically distributed • Can have pustular border

• Begin as firm papules • Erythematous, annular lesions with pale, central clearing and slightly raised borders • White “trailing scale” on inner margin


• Affects all age groups and both sexes • More abundant in hot, humid areas • Lesions can be pruritic, burning, or asymptomatic

• Can be associated with cutaneous infections, neoplasms, pregnancy, foods, pharmaceuticals • Lesions usually asymptomatic


• Dermatophyte infection: most often Trichophyton rubrum, T mentagrophytes, Microsporum canis

• Commonly idiopathic

Characteristic location

• Trunk of body and limbs

• Trunk of body and limbs


• H&E stain shows fungal hyphae

• H&E stain shows spongiosis, parakeratosis, “coat sleeve” of lymphocytes around blood vessels


• Clinically • 10% potassium hydroxide scraping • Fungal culture • Biopsy for histology

• Clinically (trailing scale) • Biopsy for histology


• Topical antifungal agents including butenafine and terbinafine • Oral antifungal agents for severe cases

• Usually spontaneously resolving • Calcipotriol, topical steroids, topical tacrolimus, and oral metronidazole

H&E: hematoxylin and eosin. • THE CLINICAL ADVISOR • AUGUST 2017 41

Dermatologic Look-Alikes underlying infection, neoplasms, pregnancy, pharmaceutical use, and specific foods.8 Some clinicians consider EAC to be a hypersensitivity reaction to a number of different antigens.8,15 If a patient’s EAC is secondary to an underlying condition, treating the underlying condition results in the resolution of the rash.8 EAC is commonly associated with cutaneous infections; 48% of these are caused by dermatophytes (the fungal organisms responsible for tinea infections).16 However, it should be noted that underlying infection occurs in a separate location than the associated EAC. Other specific pathogens associated with EAC include

3. Shy R. Tinea corporis and tinea capitis. Pediatr Rev. 2007;28:164-174. 4. Ely JW, Rosenfeld S, Seabury Stone M. Diagnosis and management of tinea infections. Am Fam Physician. 2014;90:702-710. 5. Habif TP. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 6th ed. Philadelphia, PA: Elsevier, 2016. 6. Frankel DH. Field Guide to Clinical Dermatology. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006. 7. Andrews MD, Burns M. Common tinea infections in children. Am Fam Physician. 2008;77:1415-1420. 8. Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012. 9. Zaidi Z, Lanigan SW. Dermatology in Clinical Practice. New York, NY:

Diagnosis of EAC can be difficult because of the vagueness of symptoms and the wide variety of associated risk factors.

Springer-Verlag; 2010. 10. Pariser RJ, Pariser DM. Primary care physicians’ errors in handling cutaneous disorders. A prospective survey. J Am Acad Dermatol. 1987;17 (2 Pt 1):239-245. 11. James WD, Berger TG, Elston DM, Neuhaus IM. Andrews’ Diseases of the Skin: Clinical Dermatology. 12th ed. Philadelphia, PA: Elsevier; 2016. 12. White JW Jr. Gyrate erythema. Dermatol Clin. 1985;3:129-139.

Epstein-Barr virus, human immunodeficiency virus, and chronic viral hepatitis.14,16 Less frequently, EAC has been associated with benign or malignant hematologic or solid neoplasms.16 Some pharmaceuticals associated with EAC include antimalarial drugs, gold, nonsteroidal anti-inflammatory drugs, and diuretics.8 Two notable foods linked to EAC are tomatoes and bleu cheese; bleu cheese contains a mold organism (Penicillium genus), which may cause this phenomenon.8,11 If EAC is not associated with an underlying condition, the outbreaks are usually self-limited. However, treatment with calcipotriol, topical steroids, topical tacrolimus, and oral metronidazole may be considered for nonspontaneously resolving cases.8,11,14 In this case presentation, the patient had no signs or symptoms indicating a secondary or underlying cause for his EAC. The patient was given topical triamcinolone (a topical steroid), which assisted in the resolution of his rash. n

13. Weyers W, Diaz-Cascajo C, Weyers I. Erythema annulare centrifugum: results of a clinicopathologic study of 73 patients. Am J Dermatopathol. 2003;25:451-462. 14. Mir A, Terushkin V, Fischer M, Meehan S. Erythema annulare centrifugum. Dermatol Online J. 2012;18:21. 15. Ziemer M, Eisendle K, Zelger B. New concepts on erythema annulare centrifugum: a clinical reaction pattern that does not represent a specific clinicopathological entity. Br J Dermatol. 2009;160:119-126. 16. Regula CG, Anderson BE. Erythema annulare centrifugum. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I, eds. Treatment of Skin Disease: Comprehensive Therapeutic Strategies. 4th ed. Philadelphia, PA: Elsevier Saunder; 2014:219-221.

References 1. Ferri FF. Ferri’s Clinical Advisor 2017. Philadelphia, PA: Elsevier; 2017. 2. Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 5th ed. Philadelphia, PA: Elsevier, 2016.


© Harley Schwadron, 2017

Evan A. Schauer, BS, is a medical student at the Baylor College of Medicine; Arielle Gray, BS, is a medical student at Loyola University Chicago; and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston.

Clinical Challenge A faster heart rate and numbness: Is the patient having a heart attack? DINEL EALY, MHS-CLS, PA-S, ALICIA ELAM, PHARMD

A 30-year-old woman presents with an increased heart rate, shortness of breath, and tingling in her right arm.

Ms J, a 30-year-old African American woman, presented to her school’s infirmary with an increased heart rate that skipped a beat, shortness of breath, and tingling and numbness down her right arm. The increased heart rate and skipping heartbeat began earlier that day during class. The shortness of breath also began earlier that day while walking from the parking lot to class and was relieved with less exertion. Ms J had no history of injury, strenuous activity, or trauma. She had not ingested any medication or caffeine that morning to trigger an increased heart rate or skipping heartbeat. All symptoms appeared abruptly and caused immediate discomfort. Decreasing activity improved the shortness of breath, but Ms J found no relief from the racing and skipping heartbeat or tingling sensation in the arm. She felt slight chest pain on deep inhalation after strenuous exercise. Ms J also reported radiating pain to her right shoulder but denied having a fever, coughing, arrhythmia, edema, orthopnea, and paroxysmal nocturnal dyspnea.



HISTORY AND EXAMINATION Ms J was a moderately active student with a history of childhood asthma and seasonal allergies. She reported regular consumption of a healthy diet, including adequate fruits and vegetables, but admitted a periodic overindulgence in sweets. Ms J consumed alcohol socially and a moderate amount of caffeine, but she denied tobacco and illicit drug use. Ms J denied any past surgeries or hospitalizations. Though sexually active, she denied any past pregnancies and was not taking oral contraceptives. Ms J’s family history was positive for hypertension, diabetes, cancer, anemia, and cardiac abnormalities. Her mother died at 52 years of age from a heart arrhythmia associated with mitral valve prolapse. Her father’s comorbidities included hypertension, diabetes, and prostate • THE CLINICAL ADVISOR • AUGUST 2017 43

Clinical Challenge cancer. The family history was negative for hyperlipidemia and stroke. Ms J was alert and responsive to all questions, but she appeared worried and mildly uncomfortable. She also appeared younger than her stated age. Her blood pressure was 126/69 mg/dL, heart rate was 180 beats per minute, temperature was 36.6° C, respiratory rate was 16 breaths per minute, weight was 84 kg, and O2 saturation was at 98%. An electrocardiograph (EKG) recording revealed tachycardia with premature ventricular contractions (PVCs). The cardiac examination revealed a rapid rate, irregular rhythm, and an inconsistent regularity. No lifts, thrills, heaves, murmurs, rubs, or clicks were found. No jugular venous distention or edema was found. No crackles or rhonchi were present, but wheezing was found on expiration. All skin was of good color, with adequate turgor and texture. No visible rashes, exudates, lesions, ulcers, indurations, nevi, petechial, spider angioma, telangiectasia, ecchymosis, or hemangiomas were present. All lymph nodes were nontender and non-palpable. Extraocular movements were intact with pupils equal, round, and reactive to light. No nystagmus, icterus, or rhinorrhea was present upon evaluation. The neck was supple without lymphadenopathy, and there were no bruits or thyromegaly. Oral mucosa was found to be pink and of good quality, with all teeth intact. No masses or lesions were seen in the mouth. Postnasal drip tracts were visible down the palpate. There was no pain in any joints during active and passive movement, and there was no pain in the bones of extremities. No edema was present in the pretibial area, and the patient had difficulty with right side shoulder shrug only.

discussed pharmacologic intervention or cardiac ablation as available treatment options with the patient. Dependent on Ms J’s age, academic obligations, and the desire to pursue pregnancy in the next few years, cardiac ablation was pursued for treatment. The cardiac ablation required a greater area of focus than expected, but was successful in eliminating the PVCs. Post-procedure patient expectations included gradual resumption of exercise, embracing a heart-healthy lifestyle, monitoring caffeine intake, and limiting the consumption of salt and sugar.

Supraventricular tachycardia (SVT) is a term that describes a group of heart arrhythmias with a rate greater than 100 beats per minute caused by an electrical impulse originating above the bundle of His.1 The incidence of SVT is 35 per 100,000 person-years with a prevalence of 2.29 per 1,000 persons excluding atrial fibrillation or atrial flutter and multifocal atrial tachycardia (AT).2 There are 3 main types of SVT that occur: atrioventricular nodal reentrant tachycardia (AVNRT), AT, and atrioventricular reciprocating tachycardia (AVRT).3,4 In adults, AVNRT is the most common type of SVT, and AVRT is the most common in children.1 AVNRT commonly affects young, healthy women without structural heart disease.5 Common tachycardic risk factors include drug induction, caffeine, prior history of heart disease, alcohol use, stress, anxiety, and other factors that potentially cause stress.



Ms J’s differential included anxiety and mild heart attack. The most likely diagnosis was heart arrhythmia, due to a positive family history, racing heart rate, and skipping heartbeats. Cardiac enzyme testing and EKG ruled out a mild heart attack. At a subsequent visit with a cardiologist, an echocardiogram was performed, with caffeine, exercise, and strenuous activity restrictions. A 48-hour Holter monitor and stress test were ordered, and the latter was found to be negative. The echocardiogram revealed no abnormal heart findings. The Holter monitor recorded over 20,000 premature ventricular contractions in 2 days, which supported a patient referral to an electrophysiologist. The cardiologist and electrophysiologist determined a diagnosis of supraventricular tachycardia. The electrophysiologist

Triggers for SVT and increased heart rate must be differentiated from other similar conditions. Symptoms associated with SVT include chest discomfort or pressure, shortness of breath, fatigue, lightheadedness or dizziness, and palpitations.1 A positive previous history of heart disease (especially mitral valve prolapse, previous myocardial infarction, or pericarditis), young age, and female gender increase the risk for a diagnosis of SVT.1 Other risk factors of AVNRT include heavy caffeine intake, heavy alcohol use, illicit drug use, family history of tachycardia, medication induced, and extreme stress and anxiety. The patient needs to be queried regarding any potential risk factors and any past or present symptoms. This disease process has a tendency to be misdiagnosed as anxiety or panic disorder among patients with a psychiatric history.6



Physical examination in the diagnosis of SVT may or may not be helpful in determining the etiology of the presenting symptoms. Younger, presumably healthy individuals usually have normal findings during physical examination with a single abnormal finding of tachycardia.1

WORKUP OF SVT The focused exam should include the cardiovascular, respiratory, and endocrine systems. During the cardiovascular exam, a practitioner should auscultate carefully for murmur(s), friction rub, third heart sound, and cannon waves. These findings are significant in the diagnosis of valvular heart disease, pericarditis, heart failure, and specific types of tachycardia, which is the culprit for arrhythmias and other symptoms. A respiratory exam could reveal crackles that would lead to the diagnosis of heart failure as the precipitant of tachycardia. An endocrine exam will pinpoint or rule out hyperthyroidism or thyroiditis as the cause of tachycardia.1 The diagnostic workup office visit should include vitals, orthostatic blood pressure, blood work (complete blood count, thyroid stimulating hormone, basic metabolic panel, brain natriuretic peptide, and cardiac enzymes), and diagnostics (chest X-ray, Holter monitor or event recorder, graded exercise testing, and echocardiography [12 lead]).1 The EKG will determine if pre-excitation is present to differentiate AVRT from other causes of and types of tachycardia. Figure 1 shows how the diagnostic workup of a patient with suspected SVT should be performed.

synchronized cardioversion is the treatment of choice.13 Long-term management distinguishes the SVT type, frequency and intensity, risk of therapy, and overall impact on the life of the patient.9 Options for long-term management include cardiac ablation and pharmacologic treatments.1 The most common method of cardiac ablation is radiofrequency (RF) in which an electrode is threaded through a vein or artery into the heart where it coagulates the abnormal tissue. This procedure forms a scar to prevent the targeted area of the heart from preexcitation, permanently in most situations.10 Pharmacologic treatments for long-term management include beta blockers, diltiazem or verapamil, flecainide or propafenone, amiodarone/ dofetilide or sotalol, and digoxin.13 Some practitioners have adopted a “pill-in-the-pocket” method of long-term management. “Pill-in-the-pocket” methodology has been adopted for patients with infrequent episodes or for those in need of intermittent treatment.11 This patient demographic is advised to keep prescribed medication in her pocket at all times reserved for an episodic occurrence.


SVT treatment focuses on the cessation of active episodes. In individuals with frequent episodes and serious symptoms (pre-syncope and syncope), cessation is critical. Treatment is divided into short-term and long-term management.1 Short-term or urgent treatment may include the use of oral or intravenous antiarrhythmic drug therapy, vagal maneuvers, and electrical cardioversion for SVT.8 According to JAMA Cardiology and the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia, initial treatment should begin with vagal maneuvers and/or adenosine.13 If the patient is hemodynamically stable, pharmacologic treatment (beta blockers, diltiazem, or verapamil) should be administered intravenously for immediate relief.13 If a patient is found to be hemodynamically unstable or pharmacologic intervention is not feasible,

Presenting Symptoms


Irregular Rate

Regular Rate

Adapted from Page et al.13

FIGURE 1. Diagnostic workup of a patient with possible supraventricular tachycardia • THE CLINICAL ADVISOR • AUGUST 2017 45

Clinical Challenge DISCUSSION

cardiac-friendly diet and lifestyle (low sodium, little to no caffeine or alcohol, and minimal stress).

Patients diagnosed with SVT enjoy excellent prognoses. Reducing the risk of occurring episodes is the primary goal and encompasses lifestyle changes, pharmacologic intervention, or surgery. The goal of treating this demographic is to improve quality of life.7 Studies have shown that pharmacologic intervention and cardiac ablation improve quality of life and decrease symptoms, but ablation is superior in eliminating symptoms (74%) vs medication (33%).12 Table 1 illustrates post-ablation SVT episodes decreasing drastically, increasing physical function, less bothersome symptoms, and decreased impact on routine activities of daily living. Table 2 illustrates abatement of the most common symptoms post-ablation. Recent studies have shown that ablation is not only more effective than pharmacologic interventions in the treatment of certain SVT rhythms, but it is also less expensive.13 Untreated or unmanaged, SVT can lead to other possibly fatal heart abnormalities. Patients are advised to practice a

CONCLUSION Ms. J recovered well from the cardiac ablation. She was placed on limited activity until her follow-up appointment scheduled 1 month post-procedure. She experienced chest pain periodically post-procedure that diminished over time. The cardiologist attributed the chest pain to the extent of ablation on the affected areas of her heart. Months later, Ms J returned to normal daily activity, symptom free. Providers should be aware that SVT is an often-misdiagnosed condition commonly mistaken as anxiety attacks, heartburn, or even ischemia. Provider education is vital and can aid in the prevention of cardiomyopathies, or even death, depending on the severity and type of SVT. The ultimate treatment goal for SVT patients is to increase and improve quality of life. This further confirms the importance of provider education,

TABLE 1. Quality of life scores before and after ablation Mean before ablation Mean after ablation No SVT episodes

Change in scores

95% CI

P value




Symptoms bothersomeness




(−.31, −1.0)


Impact of SVT on routine activities






Physical function




(22.1, 6.4)


Health distress




(26.6, 10.3)






(25.8, 9.2)


Adapted from Wood et al.14

TABLE 2. Symptoms prevalence before and after ablation Symptoms

Before ablation

Bothersomeness score

After ablation

Bothersomeness score


Heart racing


















Heart skipping












Adapted from Wood et al.14


appropriate diagnoses, proper follow-up, patient awareness of triggers, and avoidance of modifiable risk factors. n Dinel Ealy, MHS-CLS, PA-S, is a student at Augusta University in Georgia, and Alicia Elam, PharmD, is associate admissions director, Physician Assistant Department, Augusta University. REFERENCES 1. Colucci RA, Silver MJ, Shubrook J. Common types of supraventricular tachycardia: diagnosis and management. Am Fam Physician. 2010;82:942-952. 2. Orejarena LA, Vidaillet H, DeStefano F, et al. Paroxysmal supraventricular tachycardia in the general population. J Am Coll Card. 1998;31:150-157. 3. Porter MJ, Morton JB, Denman R, et al. Influence of age and gender on the mechanism of supraventricular tachycardia. Heart Rhythm. 2004;1:393-396. 4. Ko JK, Deal BJ, Strasburger JF, Benson DW. Supraventricular tachycardia mechanisms and their age distribution in pediatric patients. Am J Card.

“Back to Square One!”

1992;69(12):1028-1032. 5. Rodriguez LM, de Chillou C, Schläpfer J, et al. Age at onset and gender of patients with different types of supraventricular tachycardia. Am J Card. 1992;70(13):1213-1215. 6. Lessmeier TJ, Gamperling D, Johnson-Liddon V, et al. Unrecognized paroxysmal supraventricular tachycardia: potential for misdiagnosis as panic disorder. Arch Intern Med. 1997;157(5):537-543. 7. Blomström-Lundqvist C, Scheinman MM, Aliot EM, et al. ACC/AHA/ ESC guidelines for the management of patients with supraventricular arrhythmias—executive summary. Circulation. 2003;108(15):1871-1909. 8. Wasmer K, Eckardt L. Management of supraventricular arrhythmias in adults with congenital heart disease. Heart. 2016;102:1614-1619. 9. Delacrétaz E. Clinical practice. Supraventricular tachycardia. N Engl J Med. 2006;354(10):1039-1051. 10. Miller JM, Zipes DP. Cardiology patient page. Catheter ablation of arrhythmias. Circulation. 2002;106:e203-e205. pital self-administered single-dose oral drug treatment in the management of infrequent, well-tolerated paroxysmal supraventricular tachycardia. J Am Coll Card. 2001;37(2):548-553. 12. Bathina M, Mickelsen S, Brooks C, et al. Radiofrequency catheter ablation versus medical therapy for initial treatment of supraventricular tachycardia and its impact on quality of life and healthcare costs. Am J Coll Card. 1998;82(5):589-593. 13. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2016;133(14):e506-e574. 14. Wood KA, Stewart AL, Drew BJ, Scheinman MM, Froëlicher ES. Patient perception of symptoms and quality of life following ablation in patients with supraventricular tachycardia. Heart Lung. 2010;39:12-20.

“It’s Sunday, and I’m Brunch!” • THE CLINICAL ADVISOR • AUGUST 2017 47

© The New Yorker Collection 2017 from All Rights Reserved.

11. Alboni P, Tomasi C, Menozzi C, et al. Efficacy and safety of out-of-hos-


Birth control leads to a blood clot


Ms P, aged 37, was a nurse practitioner working in a college clinic that was run by a hospital. She greatly enjoyed the variety of her work and had been there for 5 years. One day in early April, one of Ms P’s patients, Miss K, came in asking about contraception. The young woman, an 18-year old freshman, was in a relationship and wanted to be sure that she did not accidentally become pregnant. Contraception was a common request from students, and Ms P frequently provided contraceptive counseling. As she normally did, she explained all the choices to her patient, and the patient decided on the NuvaRing contraceptive device, a ring containing hormones that is inserted by the patient each month. Ms P discussed the benefits and risks of the device, including the risk of blood clots, with Miss K. She also went over the NuvaRing fact sheet with Miss K, but she did not bother to write this in the patient’s record. After making sure that Miss K understood everything, the clinician dispensed the NuvaRing and ensured that the patient could insert it properly. The patient thanked Ms P and left the clinic.


A patient presents with chest pain 6 weeks after beginning use of a contraceptive device.

A clinician discusses the risks of a hormonal contraceptive device with her patient, but she never notes this in the patient’s record.


On June 1, Miss K returned to the clinic with complaints of shortness of breath and chest pain. She told Ms P that she was feeling tired and had been active on the weekend and had not consumed any water. Ms P noted that the patient also complained of dry mouth and had a family history of heart disease and a chronic heart murmur. The patient’s vital signs were a temperature of 97.9° F, heart rate of 76 beats per minute, blood pressure of 90/60 mm Hg, and a respiration rate of 16 breaths per minute. Her oxygen saturation was 99%. Ms P diagnosed the student with dehydration and did not consider the NuvaRing a precipitating factor for the patient’s symptoms. She advised Miss K to be sure to drink water when she was active and to avoid alcohol intake because that could cause dehydration. Later that day, Miss K went to her pediatrician’s office with the same complaints. The Cases presented are based on actual occurrences. Names of participants and details have been changed. Cases are informational only; no specific legal advice is intended. Persons pictured are not the actual individuals mentioned in the article.

pediatrician diagnosed her with exercise-induced asthma and prescribed an inhaler, despite the fact that Miss K was not wheezing and had no previous history of asthma. The next day, June 2, Miss K presented to the emergency department of another hospital with complaints of chest pain, shortness of breath, and heart palpitations. The hospital noted that Miss K was using the NuvaRing. Her EKG and vital signs were declared to be normal, and she was discharged without undergoing assessment for possible thromboembolism. On June 3, Miss K returned to her pediatrician’s office continuing to complain of chest pain. The pediatrician noted that the pain was persistent without relation to exertion, and it might be related to costochondral pain. He instructed her to return in 2 to 3 days if she did not improve. On June 4, a Friday, a doctor from the June 2 emergency department visit called and reported abnormalities he had seen on the EKG taken during that visit and suggested that she be seen by her pediatric cardiologist. An appointment was made for the following week. Two days before the cardiology appointment, Miss K complained of chest pain and collapsed at home. Her mother began CPR and called emergency services. Miss K was shocked 3 times and administered epinephrine and vasopressin—the total cardiac arrest time was noted to be 8 minutes. At the hospital, Miss K was unresponsive. A CT scan was positive for bilateral pulmonary emboli. An MRI of the brain showed damage and changes. An echocardiogram showed severely diminished right ventricular function. As a consequence of the embolism and cardiac arrest, Miss K had significant and permanent brain damage and required constant, around-the-clock care. Miss K’s mother hired a plaintiff’s attorney and on behalf of her daughter sued the hospital that employed Ms P, the pediatrician, and the hospital whose emergency department Miss K had gone to on June 2. Ms P was notified that her employer was being sued based on her failure to meet the standard of care for her patient. She met with the hospital’s attorney who had retained a medical expert to go over the records. Based on the expert’s opinion, the hospital made a motion for summary judgment, asking the court to dismiss the complaint against it. The court refused. Legal background

A summary judgment motion resolves a lawsuit prior to a trial. It can only be granted when there are no “triable issues of fact”—in other words, when the question is one of law, rather than a factual dispute. In moving for summary judgment in a medical malpractice case, the defendant must establish either

that there was no departure from good and accepted medical practice, or that any departure was not a proximate cause of the plaintiff’s injuries. In this case, Ms P’s employer moved for summary judgment, asserting that she did not depart from accepted standards of medical care, and that even if she had, any failure to properly assess and respond to the patient’s forming a pulmonary embolism was not the proximate cause of her injuries. The expert opined that the plaintiff was properly evaluated at the June 1 visit with Ms P, and that there was no indication that she should be evaluated for thrombophilia at that time. The expert explained that any failure to refer Miss K

When prescribing hormonal birth control, it is important to always keep in mind the danger of blood clots. for more intervention was inconsequential because in the days following her visit to Ms P, the patient saw her pediatrician and several emergency room physicians who observed her symptoms and were aware she was using the NuvaRing. The plaintiff’s attorneys brought in their own medical expert, who said that Ms P should have removed the NuvaRing on June 1, which may have prevented the pulmonary embolism. The two experts disagreed on whether removing the NuvaRing on June 1 would have reduced the risk for Miss K. Because there was an issue of fact as to Ms P’s liability, the court refused to dismiss the case against Ms P’s employer and sent it back for a trial, which is currently pending. Protecting yourself

Although Ms P always discussed the fact sheets and consent forms for NuvaRing with her patients, and claimed to have done so with Miss K, she did not note this in the patient’s records, nor did she include the consent form. Keeping diligent and complete records is always a good idea and will serve to protect you. When prescribing hormonal birth control, it is important to always keep in mind the danger of blood clots. If a patient on a hormonal form of birth control presents with chest pain, difficulty breathing, or anything that could indicate thrombosis, it is essential to consider this. n Ms Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y. • THE CLINICAL ADVISOR • AUGUST 2017 49


What you should know about the herbs and supplements patients use By Sherril Sego, FNP-C, DNP Ms. Sego is an independent consultant in Kansas City, Mo.



Even though it is listed in the periodic table,1 the metallic element boron is not a naturally occurring element. It is found in small amounts in the earth’s surface, and it is thought to be produced solely by the collection of particulate matter of meteorites; in this form, it is water-soluble. The largest known deposit of this mineral is in Turkey, which produces more than 47% of the world’s supply.2

Background Borax (the common name for the mineral salt of boron) was used in China as long ago as 300 AD and Persian alchemists used it in their process of glazing pottery. Other records discuss its use as a flux in metal work. Then, in 1777, the soluble boric acid was found in hot springs near Florence, Italy. This is the first mention of boron’s medicinal use. Boron was not classified as an element until 1809. Many Americans are familiar with the product ‘Twenty-Mule Team Borax,’ a brand name of a soap called ‘Boraxo.’ Borax was first found in the United States in the arid desert Southwest in the late 1800s. It became popular as a soap during this mining era when it was found to emulsify heavy dirt and oil on wet hands.

Science In humans, the role of boron was discovered only recently, and the information continues to accumulate. One of the

best-studied functions of boron is in the metabolism of human bone. Laboratory research discovered boron to be an essential trace element in the survival, proliferation, and mineralization of osteoblasts and required for messenger RNA production of the proteins associated with this process.2 Further studies have demonstrated the osteogenic effects of boron on bone marrow stromal cells.3 Researchers found that treatment of laboratory cell cultures with supplemental boron led to increased calcium depositions when compared to untreated cells.3 These findings suggest a significant step in the prevention of osteoporosis and its related sequelae. Boron also appears to play a significant role in wound healing. Wound healing involves the epithelial cell type known as keratinocyte. The actual process requires both migration and proliferation of new cells.4 One in-vitro study of human keratinocyte cultures studied the effect of varied strengths of boron solution on culture media on which an intentional 2-mm gap had been formed. After 24 hours, the cell culture treated with boron showed ‘gap closure’ to be 20% greater


than the control culture.4 Boron has also been found to be essential for the production of vascular endothelial growth factor (VEGF).5 There is also a high level of interest in boron’s potential role in cancer prevention and treatment. To date, the best studied cancers are prostate and cervical. One study followed more than 1,000 women to monitor for abnormal cervical cytology.6 The women were categorized as having a high- or low-intake of dietary boron; there was an approximate difference of nearly 7 mg/d of dietary intake between the two groups. Women in the high-intake group had no abnormal cytological findings, whereas 15 women in the low intake group were found to have abnormal findings. Boron in the plasma form of boric acid also has been found to inhibit the growth of human prostate cancer cells.7 In laboratory research using cultured lines of human prostate cancer cells, the application of boric acid showed an increase in cell death and an inhibitory effect on new cell growth.7

Safety, interactions Large amounts of boron in either a single dose or chronically can cause poisoning. Signs of poisoning include skin inflammation, tremors, seizures, diarrhea, vomiting.8 Boron also has been found to increase estrogen levels in the body when taken in large amounts.9

How supplied, cost

vegetable intake. Considering an estimated 85% of Americans do not meet the recommended daily intake of these foods, boron deficiency may be a frequent issue.12 As with all supplements and other alternative therapies, the goal is to achieve a healthy body in the most natural way possible. Since we know the impact of fruits and vegetables on many other aspects of our health, the need for boron adds yet another incentive to improve our dietary habits. n Foods rich in boron include fruits, vegetables, and nuts.

Large amounts of boron can cause poisoning. Signs of poisoning include skin inflammation, tremors, seizures, and vomiting.

References 1. Meija J, Coplen T, Berglund M, et al. Atomic weights of the elements 2013 (IUPAC Technical Report). Pure and Applied Chemistry. 2016;88:265-291. doi:10.1515/pac-2015-0305. 2. Hakki SS, Bozkurt BS, Hakki EE. Boron regulates mineralized tissue-associated proteins in osteoblasts (MC3T3-E1). J Trace Elem Med Biol. 2010. 24:243-250. 3. Ying X, Cheng S, Wang W, et al. Effect of boron on osteogenic differentiation of human bone marrow stromal cells. Biol Trace Elem Res. 2011;144:306-315. 4. Chebassier N, Ouijja EH, Viegas I, Dreno B. Stimulatory effect of boron and manganese salts on keratinocyte migration. Acta Derm Venereol. 2004;84:191-194. 5. Dzondo-Gadet M, Mayap-Nzietchueng R, Hess K, Nabet F, Belleville F, Dousset B. Action of boron at the molecular level: Effects on transcription and translation in an acellular system. Bio Trace Elem Res. 2002;85:23-33. 6. Korkmaz M, Uzgören E, Bakirdere S, Aydin F, Ataman OY. Effects of dietary boron on cervical cytopathology and on micronucleus frequency in exfoliated buccal cells. Environ Toxicol. 2007;22:17-25. 7. Barranco WT, Eckhert CD. Boric acid inhibits human pros-


tate cancer cell proliferation. Cancer Lett. 2004;216:21-29. 8. Nielsen FH. Boron in human and animal nutrition. Plant and Soil. 1997;193:199-208. 9. Naghii MR, Mofid M, Asgari AR, Hedayati M, Daneshpour MS. Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and pro-inflammatory cytokines. J Trace Elem Med Biol. 2011;25:54-58. 10. Nielsen FH. Is boron nutritionally relevant? Nutr Rev. 2008;66:183-191. 11. Boron. Acu-Cell Nutrition website. 12. Moore LV, Thompson FE. Adults meeting fruit and

Boron appears to be yet another reason for the nutritional recommendations for high fruit and

vegetable intake recommendations—United States, 2013. MMWR Morb Mortal Wkly Rep. 2015;64:709-713. • THE CLINICAL ADVISOR • AUGUST 2017 51


Foods rich in boron include fruits, vegetables, and nuts.10 Supplemental boron is available in tablet and capsule form, but there are questions as to its solubility and bioavailability compared to natural boron in foods. The maximum recommended intake for adults is 20mg/d, but there is no established minimum amount.13 Nutritionists agree that a habitual intake of 1 to 3 mg/d would prevent deficiency.

August 2017 Clinical Advisor  
August 2017 Clinical Advisor