ACMS February 2024 Bulletin - Renewed

BULLETIN Allegheny County Medical Society

February 2024 / Vol. 114 No. 02

BULLETIN Allegheny County Medical Society

February 2024 / Vol. 114 No. 02

Opinion Editorial

• Winter Nourishment Deval (Reshma) Paranjpe, MD, MBA, FACS

Editorial

• The Dancing Earring Sign And Other Ear Signs of Heart Disease Michael Lamb, MD

Editorial

• The Last Time I Saw Yina: The Mother With The Heart of Steel Anthony L. Kovatch, MD

Editorial

• Top 5 Lessons From Our Residency Clinic's Journey to Enhance Hypertension Care Alexandra Johnston, DO; Lauren Mathos, DO; Kyle Kapcin, DO; Asisha Shah, MD; Mrudula Gadani, MD

Society News ACMS News

Articles Medical News

• ACMS in Action January 2024

ACMS News

• An Update From The Corcoran Collective The Importance of Public Relations Jordan Corcoran

• Reportable Diseases 2023: Q1-Q4 Allegheny County Health Department Selected Reportable Diseases/Conditions Kristen Mertz, MD — Allegheny County Health Department

Materia Medica

• Aspruzyo Sprinkle™ (ranolazine) A Sprinkle is All It Takes ACMS News Taylor Thompson, PharmD, MBA, • Specialty Group Updates BCPS; Joseph Rizkalla, PharmD, ACMS Staff: Nadine Popovich, BCPS; Heather Sakely, PharmD, Eileen Taylor, and Melanie Mayer BCPS, BCGP

ACMS News

• ACMS Foundation 2024 Grant Awardee Networking Reception

Editorial

• The Call Andrea G. Witlin, DO, PhD Cover Photo by John Hyland, MD John Hyland, MD specializes in Radiation Oncology 2

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Bulletin Managing Editor Sara C. Hussey, MBA, CAE ACMS Executive Director shussey@acms.org Medical Editor Deval (Reshma) Paranjpe, MD reshma_paranjpe@hotmail.com

2024 Executive Committee and Board of Directors

PAMED District Trustee G. Alan Yeasted, MD, FACP

President Raymond E. Pontzer, MD

2024 Board Committees

President-elect Keith T. Kanel, MD

Bylaws Kirsten D. Lin, MD

Secretary Kirsten D. Lin, MD

Finance William Coppula, MD

Treasurer William F. Coppula, MD

Nominating Keith T. Kanel, MD

Board Chair Matthew B. Straka, MD

Women’s Committee Anu Anand, MD & Tiffany DuMont, DO

Bulletin Designer Victoria Gricks

victoria@thecorcorancollective.com

Term Ending 2024 Richard Daffer, MD; Anthony Kovatch, MD; Andrea Witlin, MD Term Ending 2025 Robert Howland, MD; John Williams, MD; Alexandra Johnston, DO; Charles Mount, MD

Directors Term Expires 2024 Douglas F. Clough, MD David J. Deitrick, DO Jan B. Madison, MD Raymond J. Pan, MD G. Alan Yeasted, MD, FACP Term Expires 2025 Anuradha Anand, MD Amber Elway, DO Mark A. Goodman, MD Elizabeth Ungerman, MD, MS Alexander Yu, MD

Administrative Staff Executive Director Sara Hussey shussey@acms.org Vice President - Member and Association Services Nadine M. Popovich npopovich@acms.org

Term Expires 2026 Michael M. Aziz, MD, MPH, FACOG Michael W. Best, MD Richard B. Hoffmaster, MD Micah A. Jacobs, MD, FIDSA Jody Leonardo, MD

Manager - Member and Association Services Eileen Taylor etaylor@acms.org

Operations Coordinator ACMS & ACMS Foundation Melanie Mayer mmayer@acms.org Part-Time Controller Elizabeth Yurkovich eyurkovich@acms.org Bulletin Designer Victoria Gricks victoria@thecorcorancollective.com

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Improving Healthcare through Education, Service, and Physician Well-Being ACMS Bulletin / February 2024

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ISSN: 0098-3772

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Opinion

Winter Nourishment By: Deval (Reshma) Paranjpe, MD, MBA, FACS Ah, February. A mix of arctic cold and soring-like weather in Pittsburgh leads to alternating yearnings for hygge versus al fresco dining (with many, many heat lamos). One yearns for hot comforting stew in front of the fireplace, snuggled under a blanket on the sofa watching a great movie. One also yearns to travel to sunnier climes and explore exciting and adventurous cuisine in places where the drinks are cold, but not one’s nose.

For your dining, takeout and delivery pleasure, may I suggest the following dreamy new restaurants which have appeared on the Greater Pittsburgh culinary scene: Sankalp 1187 Freedom Rd C-105 Cranberry Twp, PA 16066 (724) 591-8888 Run, don’t walk to Sankalp. This is my favorite Indian restaurant in the area, and I only discovered it by accident a year after they opened, because they do not advertise.

Located in an unassuming Cranberry strip mall, Sankalp is a franchise of an international chain originating in India with locations in India, the US, and Australia among other countries. The recipes and menu are standardized and not modified to suit local tastes, ensuring an authentic experience.

The menu is endless, which at first made me concerned—how could any place do a hundred dishes quickly and well?! When the maître d’ explained that Sankalp boasted South Indian cook for the South Indian station, North Indian cooks for the North Indian station, and

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Mumbai cooks for the Mumbai station--all imported from the culinary capital of Mumbai….my worries evaporated. Of note, Sankalp features authentic and beloved Indo-Chinese dishes difficult to find outside of major metropolitan areas in the US. Every dish, whether North Indian, South Indian, Indo-Chinese, Mumbai snack food or Gujarati Thali transported me straight back to India. Even the classics you’d find in a standard Indian restaurant in the US shine---the butter chicken and chicken tikka masala are sublime. The food is served in authentic ornate metal dishes you wouldn’t normally find outside nice restaurants in India. I nearly cried with joy when I had the Rajbhog Falooda--a heavenly rose and saffron milkshake with ice cream, rose syrup, basil seeds (think bubble tea but better), glass vermicelli noodles and pistachios--that transported me straight back to childhood summers in Mumbai.

Cranberry is a great location for this restaurant as it is a mecca for recent Indian expats working in the area in engineering and software development.

Sankalp is truly a taste of the old country—the place is always packed with Indian clientele, always a great sign for an Indian restaurant.

I have never had a meal short of spectacular here, and could eat here every night of the week. This amazes me, because before Sankalp I would never go out for Indian food on my own—no place fully lived up to my expectations.

Things you must try: Garlic Naan, Chicken Manchow or Chicken Lemon Coriander Soup, Seekh Kabab (served

sizzling on cast iron), the Chicken 65 appetizer, any of the Indo Chinese dishes, Chicken Kali Mirch, Goan Shrimp Curry, Butter Chicken, all the Bombay snacks, Paper Dosa, and the Falooda.

Indians typically do not drink alcohol with the main meal—perhaps with appetizers. This place is BYOB; if you must drink, skip the wine and bring some Kingfisher beer (a light lager which would complement the food well).

Barcelona Wine Bar 922 Penn Avenue Cultural District 412-525-7722 This is THE hottest new spot downtown—from the exciting ambiance to the mile long list of exquisite tapas to the range of paellas and whole branzino, this place brings sparkle and elegance to Pittsburgh. Come for the tasty food, come for the scene, come for the well curated wine list and cocktails—including a special section for regional Spanish gin-tonics (who knew the Spanish loved gin and tonics so much?!). Bring your love for date night or stop by for drinks and snacks after work with friends. This is quickly becoming a go-to spot for cocktails and dinner before and after the symphony and theater downtown. It’s a national chain, but a welcome and unusual and wildly successful one.

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Medical News

Reportable Diseases 2023: Q1-Q4

Allegheny County Health Department Selected Reportable Diseases/Conditions

*Case classifications reflect definitions utilized by CDC Morbidity and Mortality Weekly Report. **These counts do not reflect official case counts, as current year numbers are not yet finalized. Inaccuracies in working case counts may be due to reporting/investigation lag. ***Newly reportable in 2022.

NOTE: Disease reports may be filed electronically via PA-NEDSS. To register for PA-NEDSS, go to https://www.nedss. state.pa.us/NEDSS. To report outbreaks or diseases reportable within 24 hours, please call the Health Department’s 24-hour telephone line at 412-687-2243. For more complete surveillance information, see ACHD’s 10-year summary of reportable diseases: https://www.alleghenycounty.us/Health-Department/Resources/Data-and-Reporting/Infectious-Disease-Epidemiology/Epidemiology-Reports-and-Resources.aspx.

ACMS Bulletin / February 2024

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Society News

ACMS in Action January 2024

January was a busy month for the ACMS! We kicked off the new year with a Virtual Town Hall, our new Board Member Orientation, a staff Volunteer Day at Beverly’s Birthdays, and our 2024 Leadership Social at Cadence Cellers + Speakeasy!

1. The ACMS Team spent their quarterly volunteer day at Beverly’s Birthdays, and ACMS Foundation Grant Awardee for 2023-24.

2. ACMS Leadership Social (L-R) – Maria Baker (Foundation), Larry John, MD (Foundation), Michael Aziz, MD (Board/Delegate), Kevin Miko (Foundation), Alma Lucas (Foundation), Laura Caravello (Foundation).

3. 2024 ACMS President Raymond Pontzer, MD and Pitt Medical Student Marissa TremogliBarkowski 4. Vint Blackburn, MD (Delegate), William Coppula, MD (ACMS Treasurer), Michael McDowell, MD (Delegate).

5. State Rep. Arvind Venkat, MD and ACMS Staff Member, Melanie Mayer 6. Kirsten Lin, MD (ACMS Secretary) and ACMS Executive Director, Sara Hussey 7. ACMS Past Presidents and Current Board Members: Doug Clough, MD and Dave Deitrick, DO

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Society News

An Update From The Corcoran Collective

The Importance of Public Relations By: Jordan Corcoran — Owner and CEO of The Corcoran Collective The Corcoran Collective is lucky enough to have incredible clients on our diverse roster and we love working with them all. Now, that being said, ACMS has such a special place in our hearts.

Getting the opportunity to highlight some of the extraordinary things being accomplished by its members in the press has been so rewarding. We are consistently blown away by everyone’s dedication, talent, and sense of community.

Through our time working with ACMS, we have highlighted social media campaigns that prioritize the mental health of healthcare workers, had members used as experts in local and national media stories involving healthcare, and supported philanthropic efforts ACMS has made to impact the community.

Recently, our team was volunteering at Dress for Success Pittsburgh. During our time there, we found out that scrubs were on the top of the list of items Dress for Success needed more of for their inventory. We immediately reached out to Sara Hussey who instantly agreed to jump to action and the strategy fell right into place.

Through the next four weeks, we put marketing materials together, launched the social media campaign, and conducted outreach to the media to help spread the word. The scrub drive was featured on Rick Dayton’s radio show on KDKA and the social media posts helped get the attention of so many. The ACMS members pulled together close to 300 sets of scrubs, securing 100 women multiple sets for their professional needs. This major contribution left Dress for Success

ACMS Bulletin / February 2024

beaming with appreciation and gratitude as Sara Hussey’s team pulled up with three full cars of donations. It was truly remarkable.

Public relations, social media, and marketing in general are all long games.

The focus of our strategy is always consistency over time. The more frequently we can pitch something special going on within the association and secure coverage, that snowball of visibility continues to grow and grow.

For this to continue down the road of progress, we need your support.

So many of you and so many of your colleagues are doing exceptional things every single day, things that our media connections would love to cover and that could help continue to build ACMS’ reputation in Pittsburgh. In order to secure coverage, we need to know these things are happening.

We are fully aware of how uncomfortable it can feel to be pitching your work to us – please know that we get it. We can absolutely relate. We urge you to challenge that discomfort and forge ahead for the greater good of ACMS. It will help visibility. It will help with membership. It will help continue the longevity of the success and impact of this association.

Please reach out to Sarah Arbogast (sarah@thecorcorancollective.com) or myself (jordan@thecorcorancollective. com) with human-interest stories, important events taking place, rare educational information you are allowed to share or are working on, or anything you think may be of interest to the media. Please send it all our way and give us the opportunity to shine some well-deserved light on the essential

work you all are doing every single day.

One last little piece of good news?

The Corcoran Collective recently moved into the Babb Building on Ridge Avenue on the fourth floor. If you are stopping by the ACMS office, please feel free to make a quick stop upstairs and introduce yourself. We would love to connect and learn more about all you have going on.

Working with ACMS continues to be such a pleasure. We look forward to uncovering more extraordinary stories as we continue to collaborate with this association.

The ACMS Team + Corcorcan Collective Team delivered Scrubs collected from the Scrub Drive to Dress for Success Pittsburgh.

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Society News

Specialty Group Updates February 2024

By: Nadine Popovich, Eileen Taylor and Melanie Mayer Allegheny County Immunization Coalition (ACIC) — 2024 Chair - Ashley Ayers, MBA, BS, CIC: Members and potential members are encouraged to save the dates for the upcoming quarterly meetings at the AIU Building's Dewey room. The dates are March 21, June 20, September 19, and December 5. The meetings will be held from 9:00 am to 11:00 am. These meetings will be conducted in a hybrid format, allowing for both in-person attendance and virtual participation through a Zoom link provided upon online registration.

Additionally, ACMS members interested in vaccines can engage with the ACIC through volunteer opportunities focusing on vaccine education. Upcoming opportunities in February and March include:

May 29, and "Surgical Jeopardy" will be held on October 2. The ACS is excited to increase member engagement with a quarterly newsletter for members, as well as hosting additional membersonly events. Please visit acs-swpa.org for updates and more information on 2024 programming.

Pennsylvania Geriatric Society Western Division (PAGS-WD) — 2024 President - Heather Sakely, PharmD, BCPS, BCGP: The PAGS-WD is hosting the 32nd Annual Virtual Clinical Update in Geriatric Medicine on April 25-26, 2024. The goal of this conference is to help provide superb care to older adults by ensuring that each session provides evidence-based “pearls” that you can immediately incorporate into your practice. Conference registration is now open. You will receive a discounted rate if you register by March 11. The PAGS-WD Teacher of the Year Award is also accepting nominations for the 2024 season. Please visit www.pagswd. org for other society news and updates.

Most Interesting Cases 2023 - In photo left to right: Richard Fortunato, DO, FACS, Chapter President; Michael Paolini, MD, 1st Place Winner; Sarah Burki, MD, 2nd Place; Sowmya Narayanan, MD, PhD, 3rd Place; and Ari Reichstein, MD, FACS, Program Chair

The Pittsburgh Ophthalmology Society (POS) — 2024 President Pamela P. Rath, MD: Thomas Gardner, MD, MS, was the featured Guest Faculty at the January 11 Pittsburgh Ophthalmology Society Meeting. The event drew an enthusiastic crowd, with Dr. Gardner, a prominent figure in Ophthalmology and Visual Sciences, being welcomed by attendees. Raven Diacou, MD, a resident at UPMC Vision Institute, presented an intriguing case

• The Beverly's Birthdays Monroeville Community Baby Shower on February 28, 2024, from 11:00 AM to 1:00 PM at 4370 Northern Pike, Monroeville, PA 15146.

• The Greater Pittsburgh Community Food Bank Southside on March 27, 2024, from 5:00 PM to 7:30 PM at the Southside Market House.

Membership to the ACIC is free. Visit www.immunizeallegheny.org to become a member and stay informed about upcoming opportunities.

American College of Surgeons Southwestern Pennsylvania Chapter (ACS-SWPA) — 2024 President – Richard Fortunato, DO, FACS: The ACS-SWPA plans to host their annual meetings again in 2024. "Debates & Dilemmas" will be held on March 27, "Most Interesting Cases" will be held on

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Greater Pittsburgh Diabetes Club (GPDC): The GPDC is currently planning for programming and membership for 2024. Stay tuned for updates.

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Society News for discussion by Dr. Gardner. The meeting was made possible with the support of Thierry Verstraeten, MD, who invited Dr. Gardner, and sponsorship from Apellis Pharmaceuticals, Genentech, and Zeiss.

Following the business meeting, members of the Society had the opportunity to welcome Senator Devlin J. Robinson, representing the 37th Pennsylvania State Senatorial District.

The district includes parts of Allegheny County. The photo below features Leanne Labriola, DO; Pamela Rath, MD; Senator Robinson; David Baker, MD, and Sharon Taylor, MD.

Ophthalmic Personnel. Both events are scheduled for March 8, 2024, at the Omni William Penn Hotel in Pittsburgh, PA. Contributing to the enriching conference experience is Dr. Daniel F. Martin, 43rd Harvey E. Thorpe Lecturer, and distinguished guest faculty, Dr. Jane C. Edmond, Dr. Mark A. Rolain, and Dr. Joshua D. Stein. The program will highlight recent developments regarding diagnosis and medical and surgical therapy of common eye diseases.

The 44th Annual Meeting for Ophthalmic Personnel, presented by the Pittsburgh Ophthalmology Society, will run concurrently with the POS Annual Meeting. The course has been awarded 13.0 IJCAHPO credits, with attendees able to claim up to 7.0 credits. Course directors have prepared an exceptional educational offering, covering topics

such as Cataract, Retina, Ophthalmic Jeopardy!, Back-to-Basics Bootcamp, Pupil Workshop, Triage (and Workup), Myopia, OCT, and Low Vision.

The conference aims to provide exceptional educational opportunities for ophthalmic personnel in the region, attracting well-respected local faculty for relevant and quality instruction.

Registration details for physicians and office personnel are available.

Questions can be directed to Nadine Popovich, administrator, at npopovich@ acms.org or 412.321.5030 x110. To register, visit https://pghoph.org/.

Attending the meeting were Raven Diacou, MD (Resident Presenter); Pamela Rath, MD (President, POS); Thomas Gardner, MD, MS (Guest Speaker); Albert Biglan, MD (Society Member) and Jose Alain Sahel, MD, (Society member and Distinguished Professor and Chairman Department of Ophthalmology University of Pittsburgh School of Medicine)

The Pittsburgh Ophthalmology Society (POS) continued: Registration is now open for the 59th Annual Meeting of the Pittsburgh Ophthalmology Society and the 44th Meeting for

ACMS Bulletin / February 2024

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Society News

ACMS Foundation

2024 Grant Awardee Networking Reception The ACMS Foundation recently awarded over $250,000 in grants to 26 local non-profit organizations who meet the mission of the ACMS Foundation: Advancing wellness by confronting social determinants and health disparities. On February 1, the ACMS Foundation welcomed the 2023-24 Grant Recipients to the Babb Building in the North Side for a Grant Awardee Reception. We were thrilled to have so many of the organizations attend this event to network with each other, foster collaboration, and continue to create a network of change-makers. Thank you to Babb, Inc. for opening up their beautiful and historic building to the Foundation for this event.

ACMS & ACMS Foundation Executive Director Sara Hussey and Babb, Inc. President and CEO, Russell Livingston

Kareliz Ramos Aponte and Angela Garcia from Global Links

Phil Spina and Jerell Gilliam from Light of Life Rescue Mission

Judi Costanza and Jordan Corcoran from New Sun Rising/Listen Lucy

George Sebolt and Jerry Gaughan from the Laughlin Children’s Center

Megan Lang and Christy Pietryga from HEARTH – North Hills Affordable Housing

ACMS Foundation Featured Organizations

Scan the QR codes to learn more about these organization at ACMS Insights.

ACMS Bulletin / February 2024

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Opinion

The Dancing Earring Sign And Other Ear Signs of Heart Disease By: Michael Lamb, MD A woman in her late sixties wearing pendulous earrings was relaying her history of dyspnea to me. As she spoke, I noted her right earring dancing up and down. A diagnosis of tricuspid insufficiency was immediately suspected and subsequently confirmed by auscultation and echocardiography.

I call this the “dancing earring sign”, a dramatic corollary of “Woods Winking Ear Lobe sign” (originally attributed to master cardiologist Paul Wood). The sign most prominently involves the right ear and consists of a bobbing pulsation of the right ear lobe with each systole.

This is uniformly associated with giant CV waves especially in the right jugular venous pulse and moderate to severe tricuspid valve insufficiency. This sign is very important to recognize in patients with a massive pulmonary embolism causing extreme pressure elevation in the right heart chambers.

Giant CV waves in the neck were claimed by noted cardiologist James Shaver of UPMC as the best sign of tricuspid insufficiency (even in the absence of an audible murmur). In his classic textbook of medicine, William Osler commented on the fact that in tricuspid valve insufficiency the pulsation in the right jugular vein “is more forcible than in the left”. In his popular textbook on the examination of the heart, Joseph Perloff noted that “in pure tricuspid regurgitation in sinus rhythm the ascent of the V wave is earlier in systole and its crest is higher, and disproportionate systolic filling of the right internal jugular vein which is in a direct line with the right atrium, right ventricle, right innominate vein and the superior vena cava results in a right to

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left head bob.” Not surprisingly, one can also find in significant chronic tricuspid insufficiency, a venous purplish/ erythematous suffusion of the right ear lobe compared to the left. This sign has not been described previously and is most evident when comparing the lower aspect of both ear lobes. Observation of the ear can thus be very useful in the diagnosis of moderate to severe tricuspid insufficiency.

Small ear lobes (microtia) have been associated with various types of congenital heart disease especially in microdeletion of chromosome 22q11.

These children often have a right sided aortic arch with or without Tetralogy of Fallot plus isolated patent ductus arteriosus or septal defects. The upper contour of the ear lobe is often squared off in this condition which is one of the most common chromosomal anomalies. Low set ear lobes are characteristic of Noonan Syndrome and Cardiofacio-cutaneous Syndrome both of which are often associated with pulmonic stenosis. Turner’s Syndrome is also associated with low set ears.

Those patients often have coarctation of the aorta. Children with CHARGE Syndrome can have large floppy ear lobes and often have congenital heart defects, especially Tetralogy of Fallot.

Hearing loss is commonly associated with hereditary forms of heart disease including a variant of Long QT Syndrome and mitochondrial cardiomyopathies.

There is also a general association between hearing loss in the elderly and atherosclerotic cardiovascular disease that has recently been reported in several studies.

Perhaps the most important ear

Frank's diagonal ear crease

abnormality associated with heart disease is the 45 degree diagonal ear crease in the lower lobe as described

by Sanders T. Frank in the New England Journal of Medicine in 1973. The significance of the sign is influenced by the age of the patient and whether it is unilateral or bilateral. In patients under the age of 65 with bilateral ear lobe creases, there is clearly an associated increased risk of coronary artery disease reported in multiple studies. In the more elderly, this can be associated with normal aging due to elastin degradation in the ear lobe.

Elastin related genes have also been implicated in early coronary artery disease. Elastin chemistry may very well be the link between the diagonal ear crease (Frank’s sign) and early coronary disease.

Because of a lack of a definitive pathological mechanism connecting these ear creases and cardiovascular disease, there has been for 50 years some dispute regarding the significance of the crease. Today, the bulk of the data supports this crease being a predictor of cardiovascular disease risk. In some studies, it was

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Opinion more predictive than hyperlipidemia or family history. At the very least the presence of this sign should add a little more evidence towards a diagnosis of cardiovascular disease. Frank’s sign has also been shown to correlate with intimal arterial thickness as well as the complexity of coronary lesions.

Additionally, it has been shown to be associated with cerebrovascular disease and stroke. Although it seems to have greater significance under the age of 65, it also seems to have predictive value in the more aged. Paired ear creases at the top of the helix (PECH) may have a similar significance. Diagonal ear creases are also seen in Beckwith Syndrome, but in that situation, they are not associated with coronary artery disease. However, congenital cardiac malformations of various types as well as cardiomyopathy are commonly reported with Beckwith Syndrome. In his classic cardiology text, Paul White, the premier cardiologist of the mid-20th century, stated that in the evaluation of heart disease patients “the ears rarely require study”. He seems to have been mistaken in that regard. Today’s doctors would be wise to be more attentive to the examination of the ears.

References Sappira M.D., Joseph D., “The Art and Science of Bedside Diagnosis”, Urban and Schwarzenberg, Inc., 1990, pages 322-323. \ Perloff, Joseph K, “Physical Examination of the Heart and Circulation”, Second Edition, W.B.Saunders Company, pages 122-123.

Osler M.D., William, “The Principles and Practice of Medicine”, D. Appleton and Company, New York, 1892, pages 618-619.

Byrd MD., “Lateral systolic pulsation of the earlobe: a sign of tricuspid regurgitation”, Am J Cardiol. 1984; 54:244. – PubMed Shikino K, Ikusaka M., “Earlobe pulsation: a sign of tricuspid regurgitation”, BMJ Case Rep. 2018,11(1):e227861. – PMC – PubMed Ono, Ryohei et al, “Winking Earlobe Sign”, Clin Case Rep. 2022 Jan 11;10(1):e05280. Doi: 10.1002/ ccr3.5280.eCollection 2022 Jan. Brown, SC et al, “Cardiac abnormalities and facial anthropometric measurements in Children from the Free State and Northern Cape provinces of South Africa with Chromosome 22q11.2 microdeletion”, Cardiovascular Journal of Africa, Vol 21\No 1, Jan/Feb 2010.

Pacei, F et al, “Diagonal earlobe crease (Frank’s sign) and increased risk of cerebro-Vascular diseases: review of the literature and implications for clinical practice”, Neurol. Sci. 2020 Feb; 41(2):257-262.

Nazzal, S. et al, “Diagonal earlobe crease (Frank’s sign): A predictor of Cerebral Vascular Events”, Am J Med. 2017 Nov; 130(11):1324.e1-1324. e5.

Wattamwar, Kapil et al, “Association of Cardiovascular Comorbidities with Hearing Loss In the Older Old”, JAMA Otolaryngol Head Neck Surg 2018 Jul;144(7).

Left ear lobe (tricuspid insufficiency patient)

Relative cyanosis and erythema of the lower right ear lobe (tricuspid insufficiency patient)

ACMS Bulletin / February 2024

Gasga, Arturo et al, “Familial Frank’s Sign: Diagonal Ear Lobe Creases and Premature Coronary Artery Disease”. J Gen Intern Med 2021 Apr;36(4):1106-1107.

Curtis, Jon et al, “Why we should be looking for ear lobe creases in ENT. Systematic Review and meta-analysis of diagonal ear lobe crease and coronary artery disease”, J Laryngol Otol 2021 Dec 20:1-24.

Sasaki et al, “Earlobe creases as a Marker of the Risk for Coronary Atherosclerosis Before Angiography in Elderly and Non-elderly Patients”.

Cureus 2023 Mar 23; 15(3): E36609.

Elliott, WJ, “Ear lobe crease and coronary artery disease. 1,000 patients and review of the Literature”, Am J Med 1983 Dec;75(6):1024-32.

Stoyanov, George S et al, “The Histological Basis of Frank’s Sign”, Head Neck Pathol 2021 Jun; 15(2):402-407.

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Opinion

The Last Time I Saw Yina: The Mother With The Heart of Steel By: Anthony L. Kovatch, MD “It breaks your heart. It is designed to break your heart. The game begins in the spring when everything else begins again, and it blossoms in the summer, filling the afternoons and evenings, and then as soon as the chill rains come, it stops and leaves you to face the fall alone—just when you need it the most.”

—A. Bartlett Giamatti, former commissioner of baseball, renowned for his insatiable love of the game. He died of a myocardial infarction at the age of only 51 while still in office.

When the doe started making repeated visits early in the spring of 2015 to the thickets at the distant perimeter of our backyard, my wife and I knew that we were soon to become foster parents to her offspring. Two fawns were born in April, sometime around baseball season’s opening day, out of sight behind the thick shield of giant weeds (some the size of Christmas trees). Sporadically and unpredictably, one or both of the babies would venture plaintively out of their hidden abode to investigate the grassy part of our yard; I suspected they were merely looking for their mother.

Every morning that spring and summer, I hoped that this would be the lucky day that they would wander closer to the bay window of the family room facing the backyard, allowing me to smile upon them like a grandparent as I sat on the sofa sipping my morning cup of coffee! As I watched them grow from toddlers to lanky-legged teenagers as they roamed closer and closer to the window, I even gave them names to fit their personalities and dedicated the Robert Frost poem “Tree at my Window”

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to these “grandchildren”: Tree at my window, window tree, My sash is lowered when night comes on; But let there never be curtain drawn Between you and me One fall day, I had to confront the bitter reality that, like my own children, they had grown up enough to abandon the thickets and would never return— just when I needed them the most!

Over the years, when I was running at

Deer at my window, window deer

North Park, I convinced myself that any deer staring intently at me as I ran near it was a sign that it recognized and remembered me; however, as I approached and smiled and called out the names I had given them, they always turned away and ran into the woods. It always struck a painful chord in my own heart when I drove past the motionless carcass of one of their brethren lying on the roadside.

The last time I saw Yina I had absolutely no premonition that it would be our final professional encounter.

It was one of those cool days in early September which harbingers the arrival of autumn and the boys of October who bring us the World Series. She was very uncharacteristically 20 minutes late because of heavy midday traffic on the Parkway West—I wonder now if she might have been preoccupied.

When asked by the office staff if I could still see her two scheduled children, I paused before remembering that I was the “poster child” of all doctors late and behind. “Bring them right in” I exclaimed, to the chagrin of the nurses—never suspecting that something might be remiss.

I was actually quite sanguine that day having started it off by sipping my coffee while smiling at the baby deer.

Additionally, I knew that Yina always had every detail of her children’s paperwork impeccably and thoroughly completed, so that all I ever had to do was add my signature. Please don’t get me wrong!

Yina’s three young children all had very complicated medical histories: severe allergies, eosinophilic esophagitis, intractable eczema (more prominent

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Opinion than the cases highlighted in today’s Dupixent commercials). One son had a gastrostomy tube in place; in spite of this, he was a track star like his older brother and younger sister!

Because of Yina’ s superior organizational inclination, we always had time to reminisce. We were like “fraternity brothers,” having both attended the University of Pennsylvania, just in different eras—by the time she was an undergraduate, the kegs of beer at Saturday night parties were history. We were both involved in sports at Penn: I was a reticent sportswriter for the campus newspaper; Yina was a highly—recruited track star—an elite sprinter who paved the way for female athletes in the Ivy League! I became a practicing community pediatrician; she earned a degree in the fledgling field of biomedical engineering. By necessity, she ultimately became one of those uber-devoted mothers who selflessly puts her career on hold to give her offspring with overwhelming medical needs a normal childhood. However, this “full professor of motherhood” remained a fierce advocate for the sciences in the Steel City’s educational system.

I learned that visit that Yina had devised a “protocol” on her own to keep her son properly hydrated via his gastrostomy tube while he sprinted in a series of track events. My only contribution to the stratagem was to sign off on it! In fact, as the years passed, I had begun to sign off on all of the kids’ paperwork without even reading it, well aware that somebody smarter than a doctor had personally completed it and organized every visit to a specialist for all three children.

I have always been fascinated by what a pediatrician can learn about the “past lives” of the mothers of the patients he follows; most rarely talk about their pre-parenting exploits, accomplishments, and honors. I knew more about Yina simply because I felt comfortable pulling it out of her. She had a luminous broad smile when she spoke that opened the door to her

ACMS Bulletin / February 2024

heart.

Of course, when we learned of her untimely death one week later, it sent shock waves through my blood of red and blue (Penn’s colors). It was stated that she succumbed from a heart “rupture,” but I still suspect that that diagnosis was a fabrication! The heart and soul of this “mother of steel” were plainly too powerful to falter. Certainly, neither the chill rains of autumn nor our Pirates demise in the payoffs could break the heart of steel of this woman of such stamina and dignity!

What are the usual medical causes of a rare unanticipated fatal cardiac event in a young healthy mother? I reckoned to myself that it must have been an arrhythmia due to a silent myocarditis complicating a summertime enteroviral infection she contracted from her children.

Or was the culprit a sudden rupture or dissection of a silent congenital coronary artery aneurysm? I was certain it was not a consequence of intravenous drug use nor undisclosed melancholy stemming from the weight of life’s considerations.

As outrageous as it might sound, I would like to think that Yina was untimely grabbed from this sphere by powers beyond our control—that “The One” brokered a trade in the offseason: this world is awarded three young track phenoms to challenge Hussain Bolt (Jamaican Olympic gold medalist who was at that time labelled the “World Fastest Human”) in return for a divine administrative assistant extraordinaire—assigned to organize the paperwork of a world too complex even for the Almighty Powers Themselves.

All of this just when WE here needed her the most.

Yes, those of us who so direly depended on Yina will just have to endure in her absence. I sometimes imagine that I hear thunder from above: “Fill out the paperwork yourself, Kovatch, you lazy, neurotic, good-fornothing…!”

I never truly saw the baby deer again.

I did indeed see Yina in the fall of the years that followed when her 3 legacies came to the office for their annual check-ups. Track stars don’t stop running just because they have crossed the finish line!

Frost’s poem ends: That day she put our heads together, Fate had her imagination about her, Your head so much concerned with outer, Mine with inner, weather.

PS: Without a doubt, I thought it highly ironic when my car struck a deer staring at me in the evening darkness while I was pensively driving home after running at the park just last week. The fur of the large doe covered areas of the smashed-in radiator, the passenger headlight, and the front hood of the old vehicle, but the damage would be reparable. Unable to find the body of the victim anywhere after the accident, I peacefully concluded that the chest of the doe had simply bounced off the front of the vehicle that could not evade it, and then immediately rejoined her family and friends striding back into the woods surrounding the busy road.

Indeed, another mother with a heart of steel!

Dr. Kovatch is a retired community pediatrician who worked in the North Hills of Pittsburgh; he still works parttime as a consulting pediatrician for Southwood Psychiatric Hospital. He has served as an Associate Clinical Professor of Pediatrics at the University of Pittsburgh Medical School and as an Associate Editor for the ACMS Bulletin.

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Opinion

Top Five Lessons

From Our Residency Clinic's Journey to Enhance Hypertension Care By: Alexandra Johnston DO, Lauren Mathos DO, Kyle Kapcin DO, Aaisha Shah MD, Mrudula Gadani MD Hypertension affects millions worldwide and managing it effectively requires a holistic approach. ACC/ AHA guidelines have shown that approximately 46% of adults in the United States have hypertension.

In our clinic by incorporating the AMA MAP framework we’ve learned valuable lessons that have significantly improved our hypertension care. MAP framework has three pillars which include measuring accurately, acting rapidly and partnering with patients.

Out of 6030 clinic patients followed over an 8-month period, 1175 had a BP above goal, and at the end of the study, 717 showed improvement in their BP readings. Out of these 717 patients, 320 patients reached their goal BP and 397 showed improvement in their BP readings. Five themes emerged that were critical to the success of this project: staff education on proper BP measurement, integration of social determinations of health (SDOH) and multidisciplinary teams, medication management and utilizing EMR to work for you.

Proper BP Measurement: A Clinic’s Strategic Shift Ensuring accurate BP readings is fundamental to effective hypertension management, which led us to enhance staff education on proper BP measurement techniques. One significant change was moving away from conventional practice of measuring BP with patients on exam tables. We invested in mobile automated BP cuffs for each medical assistant. This allowed us to take the cuffs directly to patients while they were comfortably seated in chairs.

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Proper seating, back support, and avoiding clothing interference were a few components that became integral to our technique.

We recognized the importance of patient involvement in hypertension management and encouraged patients to participate in Self Measured BP Program (SMBP). Naik et al showed that a collaborative approach to decision making with patients led to improved patient engagement and communication. We directed patients to validatebp.org to guide them in choosing reliable and accurate BP cuffs that they can utilize at home. For those facing financial constraints, we were able to provide loaner devices via an American Heart Association (AHA) grant. We introduced the teach-back technique for providers. The teachback approach ensured that providers not only understood the correct BP measurement but could also effectively communicate this knowledge to patients to allow for accurate readings for our SMBP. Addressing Social Determinants of Health Recognizing that hypertension care extends beyond medications, we delved into addressing SDOH. We identified three critical areas: medication affordability, transportation, and food insecurity. To enhance medication adherence and affordability, we advocated for utilization of combination antihypertensive pills. By prescribing fewer medications that can be taken together, we reduced financial burden on patients with fewer copays.

Ensuring a 90-day fill of medications helped avoid gaps in refills, prompting

continuous treatment.

Addressing transportation challenges and food insecurity became pivotal aspects of our patient care. Screening patients for these barriers allowed us to provide targeted support. AHA Food Bucks Grant empowered patients facing food insecurity with vouchers to purchase fresh produce at participating local grocery stores and farmers’ markets. In addition, AHN Healthy Food Center further expanded our resources by giving us the ability to offer additional food support to patients.

Integration of Multidisciplinary Teams The team-based approach to management of hypertension is invaluable. Harnessing each person’s skillset leads to improved patient engagement and outcomes. Health coaches met with patients at the time of diagnosis and performed patient outreach in between physician visits.

After visit phone calls were conducted to verify that medications were obtained and started, reeducated on home BP monitoring techniques, and identified barriers to successful management. If underlying mental health issues were identified as barriers, behavioral health consultants were available to address these concerns. Patients were also scheduled for BP checks with nurses. Patients who had obtained their own home BP monitoring device were asked to bring it to the nurse appointment so that their machine could be tested for accuracy using a validated strategy from the AHA. Clinical pharmacists were available to provide suggestions for complex cases where comorbid disease

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Opinion or cost impacted available treatment options. Social workers were available to assist with cost issues. The patients were also offered referral registered dietician for helpful tips and tricks to execute dietary changes to improve BP. Medication Management: Tips for Optimizing BP Control Despite the prevalence of hypertension and guidelines backed by adequate data, medication management can be complex due to factors such as therapeutic inertia, cost of medications, medication monitoring, and adverse effects.

• The 2017 ACC/AHA guidelines recommend that for patients with hypertension and an average BP greater than 20 systolic or 10 diastolic above the patient’s BP goal, that two agents be initially initiated unless there is concern for side effects. This can reduce the time and resources necessary to achieve adequate control.

• Mineralocorticoid receptor antagonists (MRAs) should be considered as a fourth line agent for hypertension. If aldosterone and renin levels have not been assessed, be sure to collect them prior to initiation of MRA. • In patients with advanced CKD IV, chlorthalidone has is effective for hypertension control. Chlorthalidone is 2-3 times more potent than hydrochlorothiazide and dosing starts at 25mg. It can be dosed every other day due to its long half-life, allowing patients to avoid splitting pills. There is an increased tendency towards hypokalemia, so laboratory monitoring is essential. If a loop diuretic is being utilized, such as furosemide for volume control, it will require an increased dosing frequency of at least twice daily for effectiveness in treating hypertension.

• Although SLGT2 inhibitors are not indicated for hypertension treatment, they do provide minimal BP reduction and are indicated for many comorbidities such as heart failure, diabetes, and CKD. Delaying progression of CKD with a SGLT2

ACMS Bulletin / February 2024

inhibitors allows patients to remain on optimal medical therapy for hypertension and CKD. Do not miss secondary causes of hypertension Secondary hypertension is elevated BP that results from an identifiable, and sometimes correctable, underlying cause. It is especially important to consider in individuals with high BP who are less than 30 years old devoid of other risk factors, those with resistant hypertension, suddenly worsening BP control, hypertensive urgency or emergency, and when there is strong clinical suspicion. Review all medications, herbal supplements, recreational supplements, and alcohol with your patients as offending agents are commonly used. Consider alternative primary conditions such as hyperaldosteronism and hypercortisolism.

Use your EMR to Work for You Electronic medical records have revolutionized the way we practice medicine and deliver health care. Note templates were created specifically for hypertension initial treatment and follow up. Creation of smart phrases made it quite simple to include resources to patients in the after-visit summary. This technology allowed providers to give patients a list of validated BP cuffs for purchase, review proper techniques for monitoring home BP, and diet tips to stop hypertension with a simple click of a button. Patients were able to send in BP logs through the patient portal for providers to review. Notes could be added to these logs allowing patients to comment on symptoms that they may have been experiencing that day.

This practice allowed us to notice if medication doses needed adjusted or potential medication side effects that could be addressed before a patient’s next appointment. Reminders could be added to patient charts that would notify staff to call patients when they were due for labs or office appointments.

Our clinic’s journey towards improving

hypertension management has been marked by these invaluable lessons.

From staff education, to involving patients in SMBP, addressing SDOH, incorporating multidisciplinary team approach, overcoming therapeutic inertia, and leveraging EMR contributed to a more patient-centered hypertension care model.

Resources: Patient training checklist: SMBP Patient Training Checklist – Target:BP (targetBP.org) How to measure BP at home: SMBP Infographic – Target:BP (targetBP.org) SMBP Device accuracy: SMBP Device Accuracy Test – Target:BP (targetBP.org)

References: Agarwal R, et al. Chlorthalidone for hypertension in advanced chronic kidney disease. New England Journal of Medicine. 2021;385(27):2507-2519. doi:10.1056/nejmoa2110730 Hanlin RB, et al. Measure Accurately, Act Rapidly, and Partner with Patients (MAP) improves hypertension control in medically underserved patientsThe Journal of Clinical Hypertension.

2018;20(1):79-87. doi:hhtps://doi.org/10.1111/ jcg.13141 Naik AD, et al. Improving hypertension control in diabetes mellitus: the effects of collaborative and proactive health communication. Circulation. 2008 Mar 18;117(11):1361-8. PMID: 18316489.

Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. Hypertension. 2018;71(6). doi:10.1161/hyp.0000000000000065 Hypertension.

2018;71(6). doi:10.1161/hyp.0000000000000065

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Opinion

The Call By: Andrea G. Witlin, DO, PhD I was barely a teenager and had no inkling of a future medical career.

My mother’s brother was a novice orthopedic surgeon and my father’s niece had recently started medical school. Personally, I visited our GP for my numerous URIs and ear infections. Little did anyone suspect that those pesky infections were the harbinger of my future diagnosis of primary immunodeficiency. Medical issues involving my parents were either concealed or nonexistent. I recall my mother’s reference that her father (my beloved grandfather and “primary parent” until age 8) had a heart condition that required him to swallow pills emergently. I never witnessed these presumed cardiac events and to be real, my grandfather never appeared like anyone I imagined with heart disease.

That was the background for the first of many similar calls. Well actually, I never personally received that first call. It was an era long before cell phones, texts, emails, and just about any communication convenience we depend upon. So, I was blindsided and silently anguished when my mother awakened me early one morning to inform me that her father (my grandfather) had been taken to the hospital critically ill. My parents were leaving emergently for the hospital and my sister and I were to go to school as usual. I was further devastated when my mother later told me that her father died from heart failure prior to their arrival. It was near impossible to process as an 11 year old. I recall my mother’s brief expression of anger towards her brother, the physician

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who had delayed in notifying her. My mother’s grief was suppressed and there never seemed to be any time for mine.

A year or so later, my father’s father was admitted to the hospital emergently and died suddenly from heart failure. This time, my cousin, the medical student was the interlocutor.

The rest of the story was similar except by then, I was devoid of further grief.

Neither grandparent had a typical phenotype associated with heart disease. Neither smoked, neither was overweight. The surgeon general’s report on the risks of smoking had recently been published. (1) As a young teenager, I had no idea what it all meant other than heart disease lurked in my family -- a fate I hoped to escape.

I worried about my father. My father always overate and bragged about his excessive weight. He hid candy, imbibed half gallons of ice cream in one sitting, and smoked heavily. He was proud that he didn’t exercise. Dinner became a competitive sport as it was a fight to get my share of anything carb or dessert related before the entire family portion was devoured.

By college and early med school, I started pondering about when I would get that dreaded call. By then, I recognized that my father matched the typical phenotype for coronary artery disease and was at high risk for MI. I noted labored breathing suggestive of dyspnea on exertion.

But similar to my experience with my respective grandfathers, any discussion of potential medical issues was whitewashed. Each year my fears escalated. As a daughter and a fledgling

physician in training, I was helpless to do anything. My father did eventually stop smoking. But, as I vaguely recall, his dietary excesses suffered as a result.

That dreaded call came out of nowhere, just like those calls from childhood. The timing was lousy. I had recently started a locum tenens position approximately 1500 miles away. My mother called with what became a familiar narrative, I wasn’t to worry, it wasn’t necessary for me to rush home. My father was in ICU at a local community hospital with a “mild heart attack”. Everything was under control. He was to have a heart cath the following day. My father later called with his cath report - there were significant blockages and evidence of prior “silent” MI (not a surprise to me). He was started on a beta blocker, advised to modify his diet, and it was back to business as usual for my parents.

But my trepidations increased. I was helpless as a physician child to effect any change in his behavior. Instead, I compensated by improving my diet and exercise. I knew this wasn’t to be the last call.

The next call came as I was leaving for an overdue, long awaited vacation.

This time, my father had been admitted to the local community hospital 2 days prior. He experienced diaphoresis and shortness of breath shortly after beginning his morning walk. My mother was initially in denial and didn’t want to bother me. But she did manage to relay the following: no MI, but he was being transferred across town to the cardiac center for emergent bypass surgery.

The following day, the cardiologist

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Opinion shared that the cath revealed virtually complete blockages of 4 coronary arteries; IV nitroglycerin was the only thing keeping him alive. Fortunately, after multiple delays, my father survived his quadruple bypass and flourished.

His breathing sounded normal for the first time in many years. My trepidations diminished. Sort of…

After years of practice, I was well versed in the family game of denial and stoicism. I visited my father about six-weeks post op and accompanied him on his morning walk. I marveled at how well he was doing all the while that I was tacitly struggling to breathe and could barely keep up. In reality, this wasn’t new for me. But the juxtaposition of my 68 year-old father with advanced cardiac disease to me as a presumably healthy mid 30s, active physician was striking. I didn’t have time for this.

My current symptoms were similar to my previous experiences as a young resident ten years earlier running to emergent deliveries. I would arrive huffing and puffing and unable to function for several minutes. Somehow, the rest of my resident colleagues and attendings never noticed.

I finally shared my issues with my PCP and was diagnosed with exercise induced asthma. Inhalers never really helped and nothing made sense. I was slim, exercised regularly, never smoked, and followed a reasonable diet (considering my insane schedule).

The diagnosis of cardiac disease was always discounted by my physicians.

I was young, female, and didn’t look the phenotype. The prevailing wisdom those days was that women developed heart disease later in life than men, if at all. So, mostly, I hid my symptoms. I was embarrassed to bother my colleagues and was too invested in my practice.

As time passed, our mutual complacency grew…until another quiet day was shattered by another delayed call at an inopportune time. Suddenly during an annual, routine treadmill stress test a large plaque/clot broke off and totally obstructed the bifurcation of my father’s aorta. Fortunately, my

ACMS Bulletin / February 2024

father survived a successful axillary bifemoral bypass.

Our medical stories began to coalesce. My father appeared frail. My lupus symptoms were intensifying. I was gobsmacked when my pre-op EKG showed a MI of undetermined age. Déjà vu. I could no longer hide my symptoms.

I compared notes daily with my father as I had stress test after imaging study without a diagnosis. Cardiology punted me to pulmonary, pulmonary back to cardiology, and both suggested neurology. Then the last call came. My father was being wheeled to the OR for a presumed ruptured triple abdominal aortic aneurysm. The most difficult “call” ever was to persuade my mother to sign the DNR papers. My father survived the surgery but died of septic shock and ARDS. There would be no more calls or so I thought.

A year later I was awakened with intense, non-radiating left sided chest pain. Following my learned behavior, I delayed notifying my husband and calling my PCP. MI and pulmonary embolus were eventually ruled out.

This was the first of many episodes of lupus pericarditis. Unfortunately, “just pericarditis” didn’t explain my worsening shortness of breath and occasional episodes of chest pain.

Years of cardiology consults, advanced imaging, and innumerable variations of stress tests followed without diagnosis or treatment. I was on the verge of giving up when an astute NP convinced me to undergo my third exercise right heart cath. Finally, I was diagnosed with pulmonary hypertension and received appropriate treatment. Unfortunately, the years of my personal denial along with dismissiveness from my treating physicians took a toll.

My final call was to 911 two months ago. I was two days post-op ankle surgery and totally immobile. I had the worst palpitations ever accompanied by some sort of tachyarrythmia. My trusty iWatch diagnosed a fib – a new glitch in my complicated cardiac history! I reverted to physician mode and uttered my “textbook” rendition to the skeptical

911 operator. Ultimately cardiology attributed the incident as a one off secondary to my abnormal peri/post operative fluid shifts and medication issues. Regrettably, the emotional baggage from my almost 60 year history of “calls” add to my trepidations for the future and suggest that this won’t be the “last call”.

And so it is for many patients and their families. Years of learned behaviors and varied presentations influence responses. Unfortunately, delay can be deadly.

Dr. Witlin, DO, PhD, associate editor of the ACMS Bulletin, is a retired maternal/fetal medicine physician and researcher. She can be reached at agwmfm@gmail.com.

References: 1. https://www.cdc.gov>tobacco>sgr

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Materia Medica

Aspruzyo Sprinkle™ (ranolazine) A Sprinkle is All It Takes!

By: Taylor Thompson, PharmD, MBA, BCPS; Joseph Rizkalla, PharmD, BCPS Background: Aspruzyo Sprinkle™ is a new dosage form of ranolazine, supplied as extended-release (ER) granules for oral administration. The new dosage form was approved in February 2022. Ranolazine, traditionally available as ER tablets marketed under the brand name Ranexa®, is indicated for the treatment of chronic angina.

This medication has anti-anginal and anti-ischemic effects on the heart, without reductions in blood pressure (BP) or heart rate (HR).1 Both Ranexa® and Aspruzyo Sprinkle™ share the same FDA-approved indications and dosing recommendations. The benefit of the new ER granule dosage form is the ability to sprinkle on soft foods or administer via a gastric (G) or nasogastric (NG) tube. The traditional ranolazine ER tablets cannot be crushed or chewed, which may be problematic for patients with difficulty swallowing or using feeding tubes.2 Ranolazine has been studied in patients with chronic angina, as well as patients following non-ST elevation acute coronary syndrome (NSTEACS).3-5 Aspruzyo Sprinkle™ may be used concomitantly with beta blockers, dihydropyridine or non-dihydropyridine calcium channel blockers, nitrates, angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs).1 Recommended doses of Aspruzyo Sprinkle™ range from 500 mg orally twice daily to 1000 mg orally twice daily.1 Ranolazine is recommended by The American College of Cardiology Foundation and the American Heart Association in the 2012 Guideline for the Diagnosis and Management of Patients

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with Stable Ischemic Heart Disease (SIHD). Ranolazine is recommended as an alternative to beta blockers in patients with SIHD if the patient cannot tolerate or has a contraindication to beta blockers. Ranolazine can also be used as an alternative or as an add-on therapy if beta blockers are ineffective for reducing angina.6 Ranolazine should not be used for acute angina.

Safety: Evidence shows that ranolazine does not have a significant effect on systolic BP and HR, having ~3 mmHg reduction in systolic BP and ~2-3 beats per minute reduction in HR.3 A more recent study in 2016 showed lower peak HR during pharmacological stress in patients treated with ranolazine compared to placebo (peak HR −3.55 beats per minute, p < 0.001) (treatment change in beats per minute 95% CI: −4.99 to −2.12, p <0.001).7 Ranolazine has been shown to increase the QTc interval by 3-12 milliseconds (ms), but did not result in any episodes of torsades de pointes during clinical studies. QTc prolongation was found to be dose-related, with a greater effect seen with higher doses.3 It is recommended to monitor serum creatinine (SCr) and blood urea nitrogen (BUN) in patients with a creatinine clearance (CrCl) less than 60 mL/ minute when administering ranolazine.

Ranolazine resulted in acute renal failure in patients with CrCl less than 30 mL/minute. Aspruzyo Sprinkle™ should not be used in patients with liver cirrhosis due to increased drug concentrations and QTc prolongation.1 Drug concentrations increase with worsening hepatic impairment.

Ranolazine drug concentrations may

be increased when co-administered with P-glycoprotein 1 (P-gp) inhibitors.

Dose adjustment is required when ranolazine is co-administered with moderate CYP3A inhibitors. The medication is contraindicated with strong CYP3A inhibitors and CYP3A inducers.1 There is insufficient data to recommend use in pediatric patients.

Controlled studies support the use of Aspruzyo Sprinkle™ in patients 65 years and older. Yet, patients 75 years and older may be more likely to experience adverse events (see tolerability below).

The manufacturer recommends starting at low doses for geriatric patients. Data for use in pregnancy and lactation is limited to animal studies, and use should be a risk versus (vs.) benefit discussion.1 Tolerability: The most common adverse effects seen in clinical trials were dizziness, headache, constipation, and nausea.1 Adverse events resulted in 6% of angina patients discontinuing treatment with ranolazine, while only about 3% discontinued treatment with placebo. The most common cause of discontinuation was dizziness, which may be dose-related.1 Efficacy: Efficacy data for the Aspruzyo Sprinkle™ was extrapolated from clinical trials with the ER tablets.

The CARISA (Combination Assessment of Ranolazine In Stable Angina) study was a 12-week, doubleblind, parallel, placebo-controlled trial, including 823 patients. These patients had chronic angina in the previous three months or coronary artery disease. The patients were also treated with amlodipine, atenolol, or

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Materia Medica diltiazem CD, with sublingual nitrates as needed. Results showed statistically significant improvement in modified Bruce treadmill exercise duration (increase in trough exercise duration from baseline: 115.6 seconds (s) in both ranolazine groups (pooled) vs.

91.7 s with placebo (p = .01)) and time to angina (mean change from baseline in time to onset of angina: 144 s with ranolazine 750 mg twice daily vs. 140.3 s with ranolazine 1000 mg twice daily vs. 114.3 with placebo (p = 0.01, p=0.03)) in patients treated with ranolazine compared to placebo.3 Ranolazine resulted in one less angina attack per week compared to placebo ((mean (standard error) [SE])) angina attacks per week: 3.3 (0.3) for placebo, 2.5 (0.2) for ranolazine 750 mg (p = .006), 2.1 (0.2) for ranolazine 1000 mg (p<0.001)). The effect of ranolazine was maintained, as improved duration of exercise was shown over 12 weeks of therapy. Of note, there was no increase in effect on exercise when increasing the dose from 750 mg to 1000 mg.3 The MERLIN–TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes) trial was a randomized, double-blind, placebocontrolled trial that evaluated use of ranolazine as acute and chronic therapy within 48 hours following NSTE-ACS. This study included 6560 patients. Over 50% of patients included presented with Non-ST elevation myocardial infarction (NSTEMI). There was no significant difference in the composite outcome of cardiovascular death, myocardial infarction, or recurrent ischemia compared to placebo.4 However, ranolazine did result in a significant reduction in recurrent ischemia (13.9% vs. 16.1%; hazard ratio [HR] 0.87; 95% CI: 0.76 to 0.99; p = 0.030), need for increased antianginal therapy (10.6% vs. 13.0%; HR 0.80; 95% CI: 0.69 to 0.93; p = 0.003), and worsening angina (4.2% vs. 5.9%; HR 0.77; 95% CI: 0.62 to 0.97; p = 0.023).

All-cause mortality was not significantly different between groups.4 Of note,

ACMS Bulletin / February 2024

clinically significant arrhythmias were less common with ranolazine (73.7% vs.

83.1%; p < 0.001). Specifically, episodes of ventricular tachycardia were reduced in patients treated with ranolazine.4 The efficacy of Ranolazine In Patients with Chronic Angina trial evaluated a subgroup of patients included in the MERLIN-TIMI trial. The subgroup of 3,565 patients had previous chronic stable angina, which was prior and unrelated to the ACS event.

Patients received aspirin, statins, beta-blockers, and antianginal agents.

There was significant reduction in the composite outcome (cardiovascular death, myocardial infarction, recurrent ischemia) with ranolazine compared to placebo (25.2% vs. 29.4%; HR: 0.86; 95% CI: 0.75 to 0.97; p = 0.017), only due to a significant reduction in the recurrent ischemia component of the composite outcome (HR: 0.78; 95% CI: 0.67 to 0.91; p = 0.002).5 There was no difference in cardiovascular death or myocardial infarction.

Administration: Instruct patients to avoid crushing or chewing the granules.

Sprinkle the granules in water or on one tablespoon of soft food, and use the medication immediately. There are specific directions for NG and G tube administration. The granules should not be taken with grapefruit juice or grapefruit products, as this may increase concentrations of ranolazine.

Patients should avoid alcohol, as alcohol may affect the release and absorption of the granules. While the ER tablets are unaffected by food, the ER granules have slightly increased systemic exposure and higher peak concentrations when given after a meal.1 Price: Aspruzyo Sprinkle™ is supplied in packets of oral granules, with available dosage strengths of 500 mg and 1000 mg. The price of brand Aspruzyo Sprinkle™ in the United States for a thirty-day supply of 60 packets of granules is over $300 at most pharmacies.8 The average wholesale price is $6.07 per each 500 mg pack, and $9.96 per each 1000 mg pack.9 The

medication is dosed twice daily. Thus, the cost is $12.14 and $19.92 per day, respectively. The manufacturer of the medication does not provide a medication assistance program.

Bottom Line: Aspruzyo Sprinkle™ is a new dosage form of ranolazine that is indicated for chronic angina. The medication reduces episodes of angina and recurrent ischemia, but does not reduce cardiovascular death, myocardial infarction, or all-cause mortality.

Ranolazine has little effect on BP and HR, making it a viable option for patients with bradycardia at baseline. Dosing recommendations for the new dosage form are identical to the ER tablets.

When switching between dosage forms, the dose conversion between ranolazine ER tablets and ER granules is 1:1. The ER granules are useful for patients with swallowing difficulty and/or feeding tubes, but use may be limited by cost.

Taylor Thompson, PharmD, MBA, BCPS is a PGY2 Ambulatory Care Pharmacy resident at UPMC St. Margaret and can be reached at thompsontc2@upmc.edu.

Joseph Rizkalla, PharmD, BCPS is a former resident at UPMC St. Margaret and can be reached at rizkallajs@upmc.edu. Heather Sakely, PharmD, BCPS, BCGP, the director of Geriatric Pharmacotherapy and PGY2 Geriatric Pharmacy Residency, served as editor and mentor for this work and can be reached at sakelyh@upmc.edu.

References: 1. Aspruzyo SprinkleTM [package insert].

Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2022.

2. Echaiz, T. A. (Ed.). Oral Dosage Forms That Should Not Be Crushed 2020 [wall chart]. St. Louis, MO: Thomas Land Publishers, Inc. Copyright (C) 2020 Thomas Land Publishers, Inc. 3. JAMA. 2004 Jan 21;291(3):309-16.

4. Expert Rev Cardiovasc Ther. 2008 Jan;6(1):9-16.

5. J Am Coll Cardiol. 2009 Apr 28;53(17):1510-6.

6. J Am Coll Cardiol. 2012 Dec 18;60(24):e44-e164.

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