Nationwide Children's Heart Center Striving for Optimal Outcomes for Patients with CHD

The Heart Center

Striving for Optimal Outcomes for Patients With Congenital Heart Disease

The Heart Center

Committed to Quality, Safety and Transparency At The Heart Center at Nationwide Children’s Hospital, we are committed to quality, safety and transparency at every level.

Our program is actively involved in quality assurance and improvement on a national, state and local level.

Nationally, we participate in several databases (STS Congenital Heart Surgery Database, NACHRI, UNOS) from which we receive annual reports that are reviewed for areas of improvement. Additionally, we participate in the Optum Health’s Centers of Excellence advisory panel for congenital heart surgery where issues of value (outcomes/ cost) are reviewed and incorporated into our quality improvement programs. The Cardiothoracic Surgical program is also part of a statewide database and participates on the Cardiac Standards Subcommittee of the Bureau for Children with Medical Handicaps. The Heart Center also actively participates in multiple national multi-center quality collaboratives designed at improving outcomes, including CPO3, PC4/PAC3, CNOC, NPC-QIC and ACTION.

Committed to QUALITY AND SAFETY Nationwide Children’s Zero Hero program has made our institution a national leader in quality and safety. Our goal for every patient, every department, is zero preventable harm. We achieve this goal through many quality-improvement measures and persistent tracking of preventable harm data.

Reduction

QUALITY IMPROVEMENT

PROJECTS

2 ONLY

in Radiation

exposure for catheterization & electrophysiology

procedure from

2015 TO 2019

CLABSIs

*

in the

50 %

REDUCTION

In Preventable Harm

2015 TO 2019

>450 Days (and counting!) without

a CLABSI on our acute care

Cardiothoracic ICU

in 507 days

cardiology floor

* Central Line Associated Blood Stream Infection

| 1 |

APPROXI

>35 50 Ongoing %

MATELY

| 2 |

The Heart Center

Committed to Quality, Safety and Transparency At The Heart Center at Nationwide Children’s Hospital, we are committed to quality, safety and transparency at every level.

Our program is actively involved in quality assurance and improvement on a national, state and local level.

Nationally, we participate in several databases (STS Congenital Heart Surgery Database, NACHRI, UNOS) from which we receive annual reports that are reviewed for areas of improvement. Additionally, we participate in the Optum Health’s Centers of Excellence advisory panel for congenital heart surgery where issues of value (outcomes/ cost) are reviewed and incorporated into our quality improvement programs. The Cardiothoracic Surgical program is also part of a statewide database and participates on the Cardiac Standards Subcommittee of the Bureau for Children with Medical Handicaps. The Heart Center also actively participates in multiple national multi-center quality collaboratives designed at improving outcomes, including CPO3, PC4/PAC3, CNOC, NPC-QIC and ACTION.

Committed to QUALITY AND SAFETY Nationwide Children’s Zero Hero program has made our institution a national leader in quality and safety. Our goal for every patient, every department, is zero preventable harm. We achieve this goal through many quality-improvement measures and persistent tracking of preventable harm data.

Reduction

QUALITY IMPROVEMENT

PROJECTS

2 ONLY

in Radiation

exposure for catheterization & electrophysiology

procedure from

2015 TO 2019

CLABSIs

*

in the

50 %

REDUCTION

In Preventable Harm

2015 TO 2019

>450 Days (and counting!) without

a CLABSI on our acute care

Cardiothoracic ICU

in 507 days

cardiology floor

* Central Line Associated Blood Stream Infection

| 1 |

APPROXI

>35 50 Ongoing %

MATELY

| 2 |

Committed to Transparency: Sharing Surgical Outcomes

Heart Center Volumes

Congenital heart surgeons perform more than 200 different types of procedures on fewer than 1 million patients each year in the United States. This makes comparing survival outcomes difficult.

The Heart Center at Nationwide Children’s is a high-volume, comprehensive center focused on delivering best outcomes to children living with congenital heart conditions. From our fetal interventions to our adult congenital heart disease (ACHD) clinics, we are here to provide a lifetime of care. The table below shows our volumes for specialty services other than surgery and interventional cardiology.

The Heart Center at Nationwide Children’s participates in public reporting through the Society of Thoracic Surgeons (STS).

The STS groups different types of pediatric cardiothoracic surgeries and procedures based on complexity, called STAT categories, with 1 the lowest complexity procedures and 5 the highest complexity.

Comprehensive Volumes at the Heart Center

2017 AT THE 2018 COMPREHENSIVE VOLUMES HEART 2019 CENTER

Our expert surgeons are known for their treatment of complex, high-risk patients. By comparing data from previous years, we can track annual improvement in the quality of our program and patient outcomes.

30000

Average surgical mortality among pediatric heart programs remains around 2.8%, with most centers between 2.5 and 4%.

Nationwide Children’s has remained committed to improving outcomes and, through various targeted initiatives, has successfully lowered surgical mortality, with rates better than the national average for the last 3 years.

25000

SURGICAL MORTALITY 20000

VOLUMES

7 6

PERCENT

5 4

15000

10000

3 2

5000

1 0

0

2017

2018

2019

Patient Days

2020

Echocardiograms

Other Diagnostics

2017

STAT OUTCOMES 2020

2019

Surgeries Deaths

Mortality Surgeries Deaths Rate

Mortality Surgeries Rate

2018

2017

Deaths

Mortality Surgeries Deaths Rate

Mortality Rate

Adult Congenital

Noninvasive Disease Comprehensive Volumes at the Heart Heart Center

2018

Outpatient Visits

2019

30000

A Decade of Remarkable Transformation THE HEART CENTER

25000 STAT Level 1

71

0

0.00%

65

0

0.00%

64

0

0.00%

78

0

0.00%

STAT Level 2

95

1

1.05%

119

0

0.00%

114

1

0.88%

109

1

0.92%

STAT Level 3

38

0

0.00%

30

0

0.00%

20

0

0.00%

42

0

0.00%

STAT Level 4

52

4

7.69%

63

3

4.76%

78

4

5.13%

62

5

8.06%

STAT Level 5

17

0

0.00%

21

3

14.29%

16

0

0.00%

33

6

18.18%

20000

World's First Hybrid Catheterization Suite and Operating Room

15000

2010

2010

Six-year-old 10000 Receives First Bloodless Heart Transplant

Congenital Heart Collaborative Launches

2012

2014

Preeminent Tissue-Engineering Program First in the World to Tissue Engineer Blood Vessels and Implant Them in Human Infants for Repair of Congenital Heart Defects

Fetal Intervention Program Launches

2013 2016

2017 2020 2017 2018

Whole Exome Sequencing Used to Identify Causes of Congenital Heart Disease

5000

Total

273

5

1.83%

298

6

2.01%

292

5

1.71%

324

12

3.70%

The Heart Center at Nationwide Children’s is one of the nation’s top programs for diagnosis and treatment of congenital and acquired heart conditions in children. From fetal diagnosis and intervention, to long-term adult congenital care, our program has remained dedicated to providing the highest quality of comprehensive care.

0 | 3 |

Patient Days

Echocardiograms

| 4 | Other Diagnostics Noninvasive

Adult Congenital Heart Disease

Outpatient Visits

Committed to Transparency: Sharing Surgical Outcomes

Heart Center Volumes

Congenital heart surgeons perform more than 200 different types of procedures on fewer than 1 million patients each year in the United States. This makes comparing survival outcomes difficult.

The Heart Center at Nationwide Children’s is a high-volume, comprehensive center focused on delivering best outcomes to children living with congenital heart conditions. From our fetal interventions to our adult congenital heart disease (ACHD) clinics, we are here to provide a lifetime of care. The table below shows our volumes for specialty services other than surgery and interventional cardiology.

The Heart Center at Nationwide Children’s participates in public reporting through the Society of Thoracic Surgeons (STS).

The STS groups different types of pediatric cardiothoracic surgeries and procedures based on complexity, called STAT categories, with 1 the lowest complexity procedures and 5 the highest complexity.

Comprehensive Volumes at the Heart Center

2017 AT THE 2018 COMPREHENSIVE VOLUMES HEART 2019 CENTER

Our expert surgeons are known for their treatment of complex, high-risk patients. By comparing data from previous years, we can track annual improvement in the quality of our program and patient outcomes.

30000

Average surgical mortality among pediatric heart programs remains around 2.8%, with most centers between 2.5 and 4%.

Nationwide Children’s has remained committed to improving outcomes and, through various targeted initiatives, has successfully lowered surgical mortality, with rates better than the national average for the last 3 years.

25000

SURGICAL MORTALITY 20000

VOLUMES

7 6

PERCENT

5 4

15000

10000

3 2

5000

1 0

0

2017

2018

2019

Patient Days

2020

Echocardiograms

Other Diagnostics

2017

STAT OUTCOMES 2020

2019

Surgeries Deaths

Mortality Surgeries Deaths Rate

Mortality Surgeries Rate

2018

2017

Deaths

Mortality Surgeries Deaths Rate

Mortality Rate

Adult Congenital

Noninvasive Disease Comprehensive Volumes at the Heart Heart Center

2018

Outpatient Visits

2019

30000

A Decade of Remarkable Transformation THE HEART CENTER

25000 STAT Level 1

71

0

0.00%

65

0

0.00%

64

0

0.00%

78

0

0.00%

STAT Level 2

95

1

1.05%

119

0

0.00%

114

1

0.88%

109

1

0.92%

STAT Level 3

38

0

0.00%

30

0

0.00%

20

0

0.00%

42

0

0.00%

STAT Level 4

52

4

7.69%

63

3

4.76%

78

4

5.13%

62

5

8.06%

STAT Level 5

17

0

0.00%

21

3

14.29%

16

0

0.00%

33

6

18.18%

20000

World's First Hybrid Catheterization Suite and Operating Room

15000

2010

2010

Six-year-old 10000 Receives First Bloodless Heart Transplant

Congenital Heart Collaborative Launches

2012

2014

Preeminent Tissue-Engineering Program First in the World to Tissue Engineer Blood Vessels and Implant Them in Human Infants for Repair of Congenital Heart Defects

Fetal Intervention Program Launches

2013 2016

2017 2020 2017 2018

Whole Exome Sequencing Used to Identify Causes of Congenital Heart Disease

5000

Total

273

5

1.83%

298

6

2.01%

292

5

1.71%

324

12

3.70%

The Heart Center at Nationwide Children’s is one of the nation’s top programs for diagnosis and treatment of congenital and acquired heart conditions in children. From fetal diagnosis and intervention, to long-term adult congenital care, our program has remained dedicated to providing the highest quality of comprehensive care.

0 | 3 |

Patient Days

Echocardiograms

| 4 | Other Diagnostics Noninvasive

Adult Congenital Heart Disease

Outpatient Visits

Mila’s Quest for the Best Possible Hybrid Stage 2 Surgery Mila was born with hypoplastic left heart syndrome (HLHS) and experienced complications that resulted in a prolonged initial hospital stay of 96 days near the family’s Iowa home. There, she underwent the Hybrid Stage 1 palliation.

Most infants with HLHS undergo the Norwood operation as the first of three operations in this care path. The alternative “hybrid” approach also has three expected operations, but the hybrid approach begins with stage 1 palliation, which offers a lower risk initial surgery and puts off the more complex operation until the patient is 4 to 6 months old.

In The Heart Center at Nationwide Children’s, the hybrid procedure is the preferred approach to treating HLHS. This means that surgeons at Nationwide Children’s do far more Comprehensive Stage 2 procedures than surgeons in other centers.

As Mila’s parents, Jacob and Kayla, started to research the stage 2 procedure, they noticed that the mortality rates at Nationwide Children’s Hospital were better than average. They also discovered that many of the publications about this procedure came from Mark Galantowicz, MD, chief of Cardiothoracic Surgery, co-director of The Heart Center at Nationwide Children’s and co-inventor of the hybrid procedure.

“Our research and analysis show that it takes doing the procedure about 10 to 12 times for a surgical team to become competent across the board,” explains Dr. Galantowicz. “In centers that only do hybrids as a back-up plan, it’s hard to achieve those volumes.”

Dr. Galantowicz and his team have performed almost 200 Comprehensive Stage 2 procedures — and that now includes Mila’s.

“It became really important for us to have Mila’s surgery done by the most experienced team we could find — Nationwide Children’s,” says Jacob. “We are incredibly thankful for Dr. Galantowicz and the team’s expertise and compassion.”

Mila’s surgery at Nationwide Children’s went well, and after just an eight day inpatient stay, she is now home with her family.

| 5 |

Abigail Wexner Research Institute at Nationwide Children’s Hospital Joins Four Other Top Research Institutions in Joint Initiative Focused on Single Ventricle Heart Defects $5.7 million was awarded across the group as they set out with the goal of accelerating scientific discoveries and development of treatments for single ventricle heart defects In January, the Abigail Wexner Research Institute at Nationwide Children’s Hospital announced that it was the recipient of a $1 million Innovation Fund, endowed by the nonprofit foundation: Additional Ventures. In receiving this funding, AWRI joined four other research institutions in a large-scale coordinated research effort centered on identifying new avenues to functionally cure patients with single ventricle heart defects (SVDs).

“Our goal is to provide a platform for scientists and clinicians to test bold, transformative ideas, and then the space to come together and share their learnings. By attracting these world-class experts and incentivizing risk-taking, we believe we can make a significant impact for these kids in a short amount of time,” said Kirstie Keller, PhD, director of Scientific Programs at Additional Ventures.

In June 2020, Nationwide Children’s awarded funding to the following three projects under the Additional Ventures Innovation Fund: • Elucidating Mechanisms of • Developing a protocol to risk stratify • Unlocking our regenerative capacity: ventricular hypoplasia in PA-IVS individuals with singe ventricle Elucidating the role of LYST on using patient-derived iPSCs. CHD using deep phenotyping and neo-tissue formation in tissue Co-principal investigators for the genome sequencing. Co-principal engineered constructs. Co-principal project are: Vidu Garg, MD, PhD, investigators for the project are: Kim investigators for the project are: director of the Center for CardioMcBride, MD, MS, division chief Christopher Breuer, MD, direcvascular Research and Director of of Genetic and Genomic Medicine, tor of the Center for Regenerative Translational Research in The Heart and Peter White, PhD, senior direcMedicine, and Rick Wilson, PhD, Center, and Mingtao Zhao, DVM, tor of Computational Genomics. co-executive director of the Institute PhD, principal investigator in the for Genomic Center for Cardiovascular Research.

Medicine. | 6 |

Mila’s Quest for the Best Possible Hybrid Stage 2 Surgery Mila was born with hypoplastic left heart syndrome (HLHS) and experienced complications that resulted in a prolonged initial hospital stay of 96 days near the family’s Iowa home. There, she underwent the Hybrid Stage 1 palliation.

Most infants with HLHS undergo the Norwood operation as the first of three operations in this care path. The alternative “hybrid” approach also has three expected operations, but the hybrid approach begins with stage 1 palliation, which offers a lower risk initial surgery and puts off the more complex operation until the patient is 4 to 6 months old.

In The Heart Center at Nationwide Children’s, the hybrid procedure is the preferred approach to treating HLHS. This means that surgeons at Nationwide Children’s do far more Comprehensive Stage 2 procedures than surgeons in other centers.

As Mila’s parents, Jacob and Kayla, started to research the stage 2 procedure, they noticed that the mortality rates at Nationwide Children’s Hospital were better than average. They also discovered that many of the publications about this procedure came from Mark Galantowicz, MD, chief of Cardiothoracic Surgery, co-director of The Heart Center at Nationwide Children’s and co-inventor of the hybrid procedure.

“Our research and analysis show that it takes doing the procedure about 10 to 12 times for a surgical team to become competent across the board,” explains Dr. Galantowicz. “In centers that only do hybrids as a back-up plan, it’s hard to achieve those volumes.”

Dr. Galantowicz and his team have performed almost 200 Comprehensive Stage 2 procedures — and that now includes Mila’s.

“It became really important for us to have Mila’s surgery done by the most experienced team we could find — Nationwide Children’s,” says Jacob. “We are incredibly thankful for Dr. Galantowicz and the team’s expertise and compassion.”

Mila’s surgery at Nationwide Children’s went well, and after just an eight day inpatient stay, she is now home with her family.

| 5 |

Abigail Wexner Research Institute at Nationwide Children’s Hospital Joins Four Other Top Research Institutions in Joint Initiative Focused on Single Ventricle Heart Defects $5.7 million was awarded across the group as they set out with the goal of accelerating scientific discoveries and development of treatments for single ventricle heart defects In January, the Abigail Wexner Research Institute at Nationwide Children’s Hospital announced that it was the recipient of a $1 million Innovation Fund, endowed by the nonprofit foundation: Additional Ventures. In receiving this funding, AWRI joined four other research institutions in a large-scale coordinated research effort centered on identifying new avenues to functionally cure patients with single ventricle heart defects (SVDs).

“Our goal is to provide a platform for scientists and clinicians to test bold, transformative ideas, and then the space to come together and share their learnings. By attracting these world-class experts and incentivizing risk-taking, we believe we can make a significant impact for these kids in a short amount of time,” said Kirstie Keller, PhD, director of Scientific Programs at Additional Ventures.

In June 2020, Nationwide Children’s awarded funding to the following three projects under the Additional Ventures Innovation Fund: • Elucidating Mechanisms of • Developing a protocol to risk stratify • Unlocking our regenerative capacity: ventricular hypoplasia in PA-IVS individuals with singe ventricle Elucidating the role of LYST on using patient-derived iPSCs. CHD using deep phenotyping and neo-tissue formation in tissue Co-principal investigators for the genome sequencing. Co-principal engineered constructs. Co-principal project are: Vidu Garg, MD, PhD, investigators for the project are: Kim investigators for the project are: director of the Center for CardioMcBride, MD, MS, division chief Christopher Breuer, MD, direcvascular Research and Director of of Genetic and Genomic Medicine, tor of the Center for Regenerative Translational Research in The Heart and Peter White, PhD, senior direcMedicine, and Rick Wilson, PhD, Center, and Mingtao Zhao, DVM, tor of Computational Genomics. co-executive director of the Institute PhD, principal investigator in the for Genomic Center for Cardiovascular Research.

Medicine. | 6 |

Technical Aspects of Fetal Aortic Valvuloplasty Predict Success of the Procedure The procedure is often successful but comes with significant risks to fetal health and life.

Fetal aortic valvuloplasty (FAV) is performed mid-gestation in fetuses with aortic stenosis who who, without intervention, would likely develop hypoplastic left heart syndrome. Although often technically successful, it is a high-risk procedure that is associated with significant rates of complications and fetal mortality.

In a recent study, researchers from institutions including Nationwide Children’s Hospital evaluated how technical aspects of FAV impacted procedural risks and pregnancy outcomes using the International Fetal Cardiac Intervention Registry.

“We found that technical success was the strongest predictor of live birth,” says Aimee Armstrong, MD, director of Cardiac Catheterization & Interventional Therapies at Nationwide Children’s and one of the study’s authors. “Success is really dependent on getting the proper trajectory. You need that needle to come in the apex of the left ventricle and be pointed right at the aortic valve.”

Mortality within the first 48 hours was 16.7%, relatively higher than what has been reported in other studies – potentially due to differing amounts of experience or varying procedural technique among centers.

Dr. Armstrong and her colleagues found that complications occurred in nearly half of attempted interventions. Multiple cardiac punctures were associated with increased rates of complications and fetal mortality and lower rates of technical success.

The researchers also found that larger needle size was associated with higher rates of pericardial effusion.

“We learned that we want to use as small a catheter as possible,” says Dr. Armstrong, who is also a professor of Pediatrics at The Ohio State University College of Medicine. “But some people choose larger needles because they want to use a larger balloon for improved opening of the aortic valve.”

Dr. Armstrong says the study shows that clinicians should use as small a needle as they can for the balloon size they think will be effective.

“Plus, if we aren’t successful on the first cardiac puncture, we need to really weigh the risks and benefits of a second cardiac puncture because with each puncture, the chances of success go down and the complications go up,” she says.

Reference: Patel ND, Nageotte S, Ing FF, Armstrong AK, Chmait R, Detterich JA, Galindo A, Gardiner H, Grineco S, Herberg U, Jaeggi E, Morris SA, Oepkes D, Simpson JM, Moon-Grady A, and Pruetz JD. Procedural, pregnancy, and short-term outcomes after fetal aortic valvuloplasty [published online ahead of print, 2020 Mar 26]. Catheter Cardiovasc Interv. 2020;10.1002/ccd.28846. doi:10.1002/ccd.28846.

| 7 |

| 8 |

CMS Approves New Code for Adult Congenital Heart Disease Subspecialty The official billing code will enable growth of the subspecialty and is expected to result in improved patient care.

A unique code approved in March by the Centers for Medicare and Medicaid Services (CMS) will allow boardcertified adult congenital heart disease (ACHD) specialists to bill as such, rather than as general cardiologists, for the care they provide to the more than 1.5 million U.S. adults with ACHD. “More importantly, we’ll be able to track quality metrics and outcomes for patients followed by board-certified ACHD cardiologists,” says Curt Daniels, MD, director of the Adolescent and Adult Congenital Heart Disease Program at The Heart Center at Nationwide Children’s Hospital, and a leader of the American College of Cardiology’s application for the new code. “It should be easier for hospitals to build formal ACHD programs due to the billing and financial implications, which can have a great impact on patient care.”

Adults with congenital heart disease make up two-thirds of the total congenital heart disease population in the United States. There are more than 3,000 pediatric cardiology specialists, but only about 450 board-certified ACHD clinicians. Dr. Daniels believes that the CMS code will make it more appealing for cardiologists to consider pursuing ACHD credentials, since hospitals can now more easily hire and charge for these specialists appropriately.

Dr. Daniels has co-authored an analysis of the importance of board-certified ACHD cardiologists and specialty teams for clinical care. The study, published in August in Cardiology Clinics, includes a count of specialists per state; 14% of states (7) have no board-certified ACHD cardiologists, and another 24% (12) states have three or fewer.

Dr. Daniels and other cardiologists started petitioning in 2012 to launch fellowship programs and a board certification for ACHD. The formal training for ACHD cardiologists is now the longest of any cardiology subspecialty, and the board granted its first batch of ACHD certifications in 2015.

“We’re finally on track to see the product of all of our work,” says Dr. Daniels. “It will help centers like ours at Nationwide Children’s grow to keep up with patient demand.

Many places around the country are suffering from a shortage of appropriate ACHD providers, which of course ultimately emphasizes the importance of this change for patient care.”

Reference: Fernandes SM, Marelli A, Hile DM, Daniels CJ. Access and delivery of adult congenital heart disease care in the United States: Quality-driven team-based care.

Cardiology Clinics. 2020;38(3):295-304.

Reference: Patel ND, Nageotte S, Ing FF, Armstrong AK, Chmait R, Detterich JA, Galindo A, Gardiner H, Grineco S, Herberg U, Jaeggi E, Morris SA, Oepkes D, Simpson JM, Moon-Grady A, and Pruetz JD. Procedural, pregnancy, and short-term outcomes after fetal aortic valvuloplasty [published online ahead of print, 2020 Mar 26]. Catheter Cardiovasc Interv. 2020;10.1002/ccd.28846. doi:10.1002/ccd.28846.

| 13 |

| 14 |

Tissue Engineering • Tissue engineering is an exciting new surgical technique using a child’s own cells. The cells are “seeded” on a three-dimensional biodegradable scaffold.

Findings Show ...

TEVG Stenosis Spontaneously Resolves The complication that halted a clinical trial for tissue-engineered vascular grafts for children with congenital heart disease may reverse spontaneously.

TISSUE ENGINEERING Three Dimensional Biodegradable Scaffold

Based on promising modeling of a biodegradable scaffold seeded with a patient’s own cells, a clinician-scientist research team now based at Nationwide Children’s Hospital initiated a pediatric tissue engineered vascular graft (TEVG) trial in Japan for children requiring the Fontan procedure for univentricular hearts. After its high success rate — with only 1 in 25 patients developing serious stenosis, which was successfully treated — the group launched a similar study in the United States.

Unfortunately, when 3 of the first 4 patients developed postoperative stenosis requiring balloon angioplasty, the study was terminated. All patients were safely treated and remain well several years after the trial.

To find out why the U.S. trial’s results differed, the investigators initiated robust computer modeling and found a surprising suggested explanation: early stenosis may reverse on its own. Tests on sheep confirmed that stenosis reversed spontaneously in time, without clinical complications.

Three Dimensional Biodegradable Scaffold

According to the research, when the TEVG is implanted, stenosis develops due to inflammation, as the body recruits cells and builds new tissue on the scaffold. When the immune reaction calms, stenosis resolves, and the graft is replaced with a new, natural blood vessel that is virtually indistinguishable from native tissue.

“It’s possible that this exact phenomenon occurred in the Japanese trial, but was largely missed due to post-surgical imaging timing and different criteria for angioplasty,” says Christopher Breuer, MD, director of the Center for Regenerative Medicine and Endowed Chair in Surgical Research at Nationwide Children’s and director of Tissue Engineering at The Ohio State University Wexner Medical Center.

| 9 |

Smooth muscle cells attach to the scaffold.

The scaffold biodegrades leaving a natural vessel.

• The scaffold provides a site for cell attachment and growth. Over time, the scaffold is absorbed within the body, leaving a natural vessel composed of the child’s own cells.

Smooth Muscle cells attach The scaffold biodegrades Dr.to Breuer Toshiharu Shinoka, MD, PhD, co-director of the Tissue Engineering Program at Nationwide theandscaffold leaving a natural vessel Children’s lead the team that designed the TEVG, ran the trials and published the latest results. When the team reexamined imaging from the Japanese trial, they found a few cases where narrowing was observed but monitored via imaging only.

The team has launched a new TEVG trial, with different stenosis monitoring and intervention criteria designed to accommodate the likely scenario of temporary, asymptomatic narrowing with spontaneous resolution.

Reference: 1. Drews JD, Pepper VK, Best CA, Szafron JM, Cheatham JP, Yates AR, Hor KN, Zbinden JC, Chang YC, Mirhaidari GJM, Ramachandra AB, Miyamoto S, Blum KM, Onwuka EA, Zakko J, Kelly J, Cheatham SL, King N, Reinhardt JW, Sugiura T, Miyachi H, Matsuzaki Y, Breuer J, Heuer ED, West TA, Shoji T, Berman D, Boe BA, Asnes J Galantowicz M, Matsumura G, Hibino N, Marsden AL, Pober JS, Humphrey JD, Shinoka T, Breuer CK. Spontaneous reversal of stenosis in tissue-engineered vascular grafts.

Science Translational Medicine. 2020 Apr 1;12(537):eaax6919.

2. Hibino N, McGillicuddy E, Matsumura G, Ichihara Y, Naito Y, Breuer C, Shinoka T. Late-term results of tissue-engineered vascular grafts in humans. Journal of Thoracic and Cardiovascular Surgery. 2010;139:431–436.e2.

| 10 |

Tissue Engineering • Tissue engineering is an exciting new surgical technique using a child’s own cells. The cells are “seeded” on a three-dimensional biodegradable scaffold.

Findings Show ...

TEVG Stenosis Spontaneously Resolves The complication that halted a clinical trial for tissue-engineered vascular grafts for children with congenital heart disease may reverse spontaneously.

TISSUE ENGINEERING Three Dimensional Biodegradable Scaffold

Based on promising modeling of a biodegradable scaffold seeded with a patient’s own cells, a clinician-scientist research team now based at Nationwide Children’s Hospital initiated a pediatric tissue engineered vascular graft (TEVG) trial in Japan for children requiring the Fontan procedure for univentricular hearts. After its high success rate — with only 1 in 25 patients developing serious stenosis, which was successfully treated — the group launched a similar study in the United States.

Unfortunately, when 3 of the first 4 patients developed postoperative stenosis requiring balloon angioplasty, the study was terminated. All patients were safely treated and remain well several years after the trial.

To find out why the U.S. trial’s results differed, the investigators initiated robust computer modeling and found a surprising suggested explanation: early stenosis may reverse on its own. Tests on sheep confirmed that stenosis reversed spontaneously in time, without clinical complications.

Three Dimensional Biodegradable Scaffold

According to the research, when the TEVG is implanted, stenosis develops due to inflammation, as the body recruits cells and builds new tissue on the scaffold. When the immune reaction calms, stenosis resolves, and the graft is replaced with a new, natural blood vessel that is virtually indistinguishable from native tissue.

“It’s possible that this exact phenomenon occurred in the Japanese trial, but was largely missed due to post-surgical imaging timing and different criteria for angioplasty,” says Christopher Breuer, MD, director of the Center for Regenerative Medicine and Endowed Chair in Surgical Research at Nationwide Children’s and director of Tissue Engineering at The Ohio State University Wexner Medical Center.

| 9 |

Smooth muscle cells attach to the scaffold.

The scaffold biodegrades leaving a natural vessel.

• The scaffold provides a site for cell attachment and growth. Over time, the scaffold is absorbed within the body, leaving a natural vessel composed of the child’s own cells.

Smooth Muscle cells attach The scaffold biodegrades Dr.to Breuer Toshiharu Shinoka, MD, PhD, co-director of the Tissue Engineering Program at Nationwide theandscaffold leaving a natural vessel Children’s lead the team that designed the TEVG, ran the trials and published the latest results. When the team reexamined imaging from the Japanese trial, they found a few cases where narrowing was observed but monitored via imaging only.

The team has launched a new TEVG trial, with different stenosis monitoring and intervention criteria designed to accommodate the likely scenario of temporary, asymptomatic narrowing with spontaneous resolution.

Reference: 1. Drews JD, Pepper VK, Best CA, Szafron JM, Cheatham JP, Yates AR, Hor KN, Zbinden JC, Chang YC, Mirhaidari GJM, Ramachandra AB, Miyamoto S, Blum KM, Onwuka EA, Zakko J, Kelly J, Cheatham SL, King N, Reinhardt JW, Sugiura T, Miyachi H, Matsuzaki Y, Breuer J, Heuer ED, West TA, Shoji T, Berman D, Boe BA, Asnes J Galantowicz M, Matsumura G, Hibino N, Marsden AL, Pober JS, Humphrey JD, Shinoka T, Breuer CK. Spontaneous reversal of stenosis in tissue-engineered vascular grafts.

Science Translational Medicine. 2020 Apr 1;12(537):eaax6919.

2. Hibino N, McGillicuddy E, Matsumura G, Ichihara Y, Naito Y, Breuer C, Shinoka T. Late-term results of tissue-engineered vascular grafts in humans. Journal of Thoracic and Cardiovascular Surgery. 2010;139:431–436.e2.

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COVID-19 in Children With Congenital Heart Disease

Cardiomyopathy in Mothers of Boys With Muscular Dystrophy

Data are still emerging, but COVID-19 – and the subsequent inflammatory syndrome sometimes seen in children – could have serious cardiac impacts

Female carriers of the genetic defect that causes muscular dystrophy in boys show evidence of cardiac fibrosis.

An interdisciplinary team from Nationwide Children’s Hospital found that about half of women who carry the genetic defect responsible for muscular dystrophy show evidence of cardiac fibrosis. The study, published in the International Journal of Cardiology, suggests that cardiac muscle, and not skeletal muscle, is predominantly affected in this population.

In a recent Journal of the American Heart Association article, researchers from institutions including Nationwide Children’s Hospital outlined the impact of COVID-19 in pediatric patients with heart disease.

Given that adults with underlying cardiac conditions are at increased risk for severe COVID-19, doctors were particularly concerned that pediatric patients with congenital heart disease may also be at increased risk.

Duchenne and Becker muscular dystrophy are caused by mutations in the DMD gene. About two-thirds of affected boys inherit the mutation in an X-linked recessive pattern from their mothers.

“Fortunately, our early experience with COVID-19 did not suggest that they were more vulnerable to COVID-19 and that children, generally, fared better than adults with this illness,” says Timothy Feltes, MD, FACC, recently retired pediatric cardiologist at The Heart Center at Nationwide Children’s and one of the article’s authors. “However, it will take time for us to fully appreciate the impact of COVID-19 on our congenital heart disease patients and in children in general.”

Simon Lee, MD, Pediatric Cardiologist at The Heart Center at Nationwide Children’s

For instance, COVID-19 at first appeared to affect children less severely than adults but reports of multisystem inflammatory syndrome in children (MIS-C) following COVID-19 infection spurred renewed interest in the disease’s effects in the pediatric population. Children with MIS-C can develop profound myocarditis, with abnormal ventricular function, or Kawasaki disease-like symptoms, with coronary artery dilation and aneurysm formation.

“The good news is that MIS-C tends to be self-resolving,” says Simon Lee, MD, a pediatric cardiologist at The Heart Center and director of both the Coronary Anomaly Program and the Kawasaki Disease Program at Nationwide Children’s. “We are beginning to see follow-up data from places that were hit with COVID-19 earlier, like New York and New Jersey, that show ventricular function improving and coronary artery abnormalities diminishing in patients recovered from MIS-C.” “However, this syndrome can significantly impact the heart and we do not know if it can cause long-lasting damage,” he says.

New information on COVID-19 is emerging daily. Ongoing research is focused on the significance of the infection in patients with congenital heart disease, as well as the long-term cardiac outcomes for patients with MIS-C. Reference: Alsaied T, Aboulhosn JA, Cotts TB, Daniels CJ, Etheridge SP, Feltes TF, Gurvitz MZ, Lewin MB, Oster ME, Saidi A. Coronavirus Disease 2019 (COVID-19) Pandemic Implications in Pediatric and Adult Congenital Heart Disease. Journal of the American Heart Association. 2020;9(12):e017224.

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It was thought that female carriers of this mutation would be protected from expressing the disease due to the normal copy of the DMD gene on their second X chromosome. However, some mothers of boys with muscular dystrophy have reported symptoms of muscle weakness and cardiac issues.

May Ling Mah, MD Adult Congenital and Pediatric Cardiologist at The Heart Center at Nationwide Children’s

In the study, researchers from the departments of Cardiology, Neurology and Psychology collaborated to test three groups of women: mothers of sons with muscular dystrophy who were genetically confirmed to carry the mutation, mothers of sons with muscular dystrophy who did not have the mutation, and healthy women.

Cardiac MRI revealed that 49% of the genetic carriers had cardiac fibrosis, as opposed to 5% of the noncarriers and none of the healthy controls.

There were no differences between the genetic carriers and the other two groups on treadmill testing, suggesting the genetic defect predominantly affects cardiac muscle and not skeletal muscle in this population.

The researchers also found that, despite cardiomyopathy, the functional capacity of genetic carriers’ heart muscles was maintained.

May Ling Mah, MD, and Kan Hor, MD, cardiologists and investigators at The Heart Center at Nationwide Children’s, recommend genetic testing for mothers of boys with Duchenne and Becker muscular dystrophies and, for genetically confirmed carriers of the DMD gene, cardiac MRI by their third decade.

This study is part of a larger longitudinal project funded by a grant from Parent Project Muscular Dystrophy. Dr. Mah says that, together, findings from neuromuscular, cognitive and cardiac tests will provide a detailed picture of this disease, as well as its trajectory.

Reference: Mah ML, Cripe L, Slawinski MK, Al-Zaidy SA, Camino E, Lehman KJ, Jackson JL, Iammarino M, Miller N, Mendell JR, Hor KN. Duchenne and Becker muscular dystrophy carriers: Evidence of cardiomyopathy by exercise and cardiac MRI testing. International Journal of Cardiology. 27 May 2020. [Epub ahead of print]

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COVID-19 in Children With Congenital Heart Disease

Cardiomyopathy in Mothers of Boys With Muscular Dystrophy

Data are still emerging, but COVID-19 – and the subsequent inflammatory syndrome sometimes seen in children – could have serious cardiac impacts

Female carriers of the genetic defect that causes muscular dystrophy in boys show evidence of cardiac fibrosis.

An interdisciplinary team from Nationwide Children’s Hospital found that about half of women who carry the genetic defect responsible for muscular dystrophy show evidence of cardiac fibrosis. The study, published in the International Journal of Cardiology, suggests that cardiac muscle, and not skeletal muscle, is predominantly affected in this population.

In a recent Journal of the American Heart Association article, researchers from institutions including Nationwide Children’s Hospital outlined the impact of COVID-19 in pediatric patients with heart disease.

Given that adults with underlying cardiac conditions are at increased risk for severe COVID-19, doctors were particularly concerned that pediatric patients with congenital heart disease may also be at increased risk.

Duchenne and Becker muscular dystrophy are caused by mutations in the DMD gene. About two-thirds of affected boys inherit the mutation in an X-linked recessive pattern from their mothers.

“Fortunately, our early experience with COVID-19 did not suggest that they were more vulnerable to COVID-19 and that children, generally, fared better than adults with this illness,” says Timothy Feltes, MD, FACC, recently retired pediatric cardiologist at The Heart Center at Nationwide Children’s and one of the article’s authors. “However, it will take time for us to fully appreciate the impact of COVID-19 on our congenital heart disease patients and in children in general.”

Simon Lee, MD, Pediatric Cardiologist at The Heart Center at Nationwide Children’s

For instance, COVID-19 at first appeared to affect children less severely than adults but reports of multisystem inflammatory syndrome in children (MIS-C) following COVID-19 infection spurred renewed interest in the disease’s effects in the pediatric population. Children with MIS-C can develop profound myocarditis, with abnormal ventricular function, or Kawasaki disease-like symptoms, with coronary artery dilation and aneurysm formation.

“The good news is that MIS-C tends to be self-resolving,” says Simon Lee, MD, a pediatric cardiologist at The Heart Center and director of both the Coronary Anomaly Program and the Kawasaki Disease Program at Nationwide Children’s. “We are beginning to see follow-up data from places that were hit with COVID-19 earlier, like New York and New Jersey, that show ventricular function improving and coronary artery abnormalities diminishing in patients recovered from MIS-C.” “However, this syndrome can significantly impact the heart and we do not know if it can cause long-lasting damage,” he says.

New information on COVID-19 is emerging daily. Ongoing research is focused on the significance of the infection in patients with congenital heart disease, as well as the long-term cardiac outcomes for patients with MIS-C. Reference: Alsaied T, Aboulhosn JA, Cotts TB, Daniels CJ, Etheridge SP, Feltes TF, Gurvitz MZ, Lewin MB, Oster ME, Saidi A. Coronavirus Disease 2019 (COVID-19) Pandemic Implications in Pediatric and Adult Congenital Heart Disease. Journal of the American Heart Association. 2020;9(12):e017224.

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It was thought that female carriers of this mutation would be protected from expressing the disease due to the normal copy of the DMD gene on their second X chromosome. However, some mothers of boys with muscular dystrophy have reported symptoms of muscle weakness and cardiac issues.

May Ling Mah, MD Adult Congenital and Pediatric Cardiologist at The Heart Center at Nationwide Children’s

In the study, researchers from the departments of Cardiology, Neurology and Psychology collaborated to test three groups of women: mothers of sons with muscular dystrophy who were genetically confirmed to carry the mutation, mothers of sons with muscular dystrophy who did not have the mutation, and healthy women.

Cardiac MRI revealed that 49% of the genetic carriers had cardiac fibrosis, as opposed to 5% of the noncarriers and none of the healthy controls.

There were no differences between the genetic carriers and the other two groups on treadmill testing, suggesting the genetic defect predominantly affects cardiac muscle and not skeletal muscle in this population.

The researchers also found that, despite cardiomyopathy, the functional capacity of genetic carriers’ heart muscles was maintained.

May Ling Mah, MD, and Kan Hor, MD, cardiologists and investigators at The Heart Center at Nationwide Children’s, recommend genetic testing for mothers of boys with Duchenne and Becker muscular dystrophies and, for genetically confirmed carriers of the DMD gene, cardiac MRI by their third decade.

This study is part of a larger longitudinal project funded by a grant from Parent Project Muscular Dystrophy. Dr. Mah says that, together, findings from neuromuscular, cognitive and cardiac tests will provide a detailed picture of this disease, as well as its trajectory.

Reference: Mah ML, Cripe L, Slawinski MK, Al-Zaidy SA, Camino E, Lehman KJ, Jackson JL, Iammarino M, Miller N, Mendell JR, Hor KN. Duchenne and Becker muscular dystrophy carriers: Evidence of cardiomyopathy by exercise and cardiac MRI testing. International Journal of Cardiology. 27 May 2020. [Epub ahead of print]

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Technical Aspects of Fetal Aortic Valvuloplasty Predict Success of the Procedure The procedure is often successful but comes with significant risks to fetal health and life.

Fetal aortic valvuloplasty (FAV) is performed mid-gestation in fetuses with aortic stenosis who who, without intervention, would likely develop hypoplastic left heart syndrome. Although often technically successful, it is a high-risk procedure that is associated with significant rates of complications and fetal mortality.

In a recent study, researchers from institutions including Nationwide Children’s Hospital evaluated how technical aspects of FAV impacted procedural risks and pregnancy outcomes using the International Fetal Cardiac Intervention Registry.

“We found that technical success was the strongest predictor of live birth,” says Aimee Armstrong, MD, director of Cardiac Catheterization & Interventional Therapies at Nationwide Children’s and one of the study’s authors. “Success is really dependent on getting the proper trajectory. You need that needle to come in the apex of the left ventricle and be pointed right at the aortic valve.”

Mortality within the first 48 hours was 16.7%, relatively higher than what has been reported in other studies – potentially due to differing amounts of experience or varying procedural technique among centers.

Dr. Armstrong and her colleagues found that complications occurred in nearly half of attempted interventions. Multiple cardiac punctures were associated with increased rates of complications and fetal mortality and lower rates of technical success.

The researchers also found that larger needle size was associated with higher rates of pericardial effusion.

“We learned that we want to use as small a catheter as possible,” says Dr. Armstrong, who is also a professor of Pediatrics at The Ohio State University College of Medicine. “But some people choose larger needles because they want to use a larger balloon for improved opening of the aortic valve.”

Dr. Armstrong says the study shows that clinicians should use as small a needle as they can for the balloon size they think will be effective.

“Plus, if we aren’t successful on the first cardiac puncture, we need to really weigh the risks and benefits of a second cardiac puncture because with each puncture, the chances of success go down and the complications go up,” she says.

Reference: Patel ND, Nageotte S, Ing FF, Armstrong AK, Chmait R, Detterich JA, Galindo A, Gardiner H, Grineco S, Herberg U, Jaeggi E, Morris SA, Oepkes D, Simpson JM, Moon-Grady A, and Pruetz JD. Procedural, pregnancy, and short-term outcomes after fetal aortic valvuloplasty [published online ahead of print, 2020 Mar 26]. Catheter Cardiovasc Interv. 2020;10.1002/ccd.28846. doi:10.1002/ccd.28846.

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CMS Approves New Code for Adult Congenital Heart Disease Subspecialty The official billing code will enable growth of the subspecialty and is expected to result in improved patient care.

A unique code approved in March by the Centers for Medicare and Medicaid Services (CMS) will allow boardcertified adult congenital heart disease (ACHD) specialists to bill as such, rather than as general cardiologists, for the care they provide to the more than 1.5 million U.S. adults with ACHD. “More importantly, we’ll be able to track quality metrics and outcomes for patients followed by board-certified ACHD cardiologists,” says Curt Daniels, MD, director of the Adolescent and Adult Congenital Heart Disease Program at The Heart Center at Nationwide Children’s Hospital, and a leader of the American College of Cardiology’s application for the new code. “It should be easier for hospitals to build formal ACHD programs due to the billing and financial implications, which can have a great impact on patient care.”

Adults with congenital heart disease make up two-thirds of the total congenital heart disease population in the United States. There are more than 3,000 pediatric cardiology specialists, but only about 450 board-certified ACHD clinicians. Dr. Daniels believes that the CMS code will make it more appealing for cardiologists to consider pursuing ACHD credentials, since hospitals can now more easily hire and charge for these specialists appropriately.

Dr. Daniels has co-authored an analysis of the importance of board-certified ACHD cardiologists and specialty teams for clinical care. The study, published in August in Cardiology Clinics, includes a count of specialists per state; 14% of states (7) have no board-certified ACHD cardiologists, and another 24% (12) states have three or fewer.

Dr. Daniels and other cardiologists started petitioning in 2012 to launch fellowship programs and a board certification for ACHD. The formal training for ACHD cardiologists is now the longest of any cardiology subspecialty, and the board granted its first batch of ACHD certifications in 2015.

“We’re finally on track to see the product of all of our work,” says Dr. Daniels. “It will help centers like ours at Nationwide Children’s grow to keep up with patient demand.

Many places around the country are suffering from a shortage of appropriate ACHD providers, which of course ultimately emphasizes the importance of this change for patient care.”

Reference: Fernandes SM, Marelli A, Hile DM, Daniels CJ. Access and delivery of adult congenital heart disease care in the United States: Quality-driven team-based care.

Cardiology Clinics. 2020;38(3):295-304.

Reference: Patel ND, Nageotte S, Ing FF, Armstrong AK, Chmait R, Detterich JA, Galindo A, Gardiner H, Grineco S, Herberg U, Jaeggi E, Morris SA, Oepkes D, Simpson JM, Moon-Grady A, and Pruetz JD. Procedural, pregnancy, and short-term outcomes after fetal aortic valvuloplasty [published online ahead of print, 2020 Mar 26]. Catheter Cardiovasc Interv. 2020;10.1002/ccd.28846. doi:10.1002/ccd.28846.

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Referrals and Consultations Online: NationwideChildrens.org/Heart Phone: (614) 722-6200 | Fax: (614) 722-4000 Physician Direct Connect Line for 24-hour urgent physician consultations: (614) 355-0221 or (877) 355-0221

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1/2021