First name
Joseph
Last name
Rossano

Title

MYH7 variants cause complex congenital heart disease.

Year of Publication

2022

Number of Pages

2772-2776

Date Published

05/2022

ISSN Number

1552-4833

Abstract

MYH7, encoding the myosin heavy chain sarcomeric β-myosin heavy chain, is a common cause of both hypertrophic and dilated cardiomyopathy. Additionally, families with left ventricular noncompaction cardiomyopathy (LVNC) and congenital heart disease (CHD), typically septal defects or Ebstein anomaly, have been identified to have heterozygous pathogenic variants in MHY7. One previous case of single ventricle CHD with heart failure due to a MYH7 variant has been identified. Herein, we present a single center's experience of complex CHD due to MYH7 variants. Three probands with a history of CHD, LVNC, and/or arrhythmias were identified to have MYH7 variants through multigene panel testing or exome sequencing. These three patients collectively had 12 affected family members, four with a history of Ebstein anomaly and seven with a history of LVNC. These findings suggest a wider phenotypic spectrum in MYH7-related CHD than previously understood. Further investigation into the possible role of MYH7 in CHD and mechanism of disease is necessary to fully delineate the phenotypic spectrum of MYH7-related cardiac disease. MYH7 should be considered for families with multiple individuals with complex CHD in the setting of a family history of LVNC or arrhythmias.

DOI

10.1002/ajmg.a.62766

Alternate Title

Am J Med Genet A

PMID

35491958

Title

Burden of Pediatric Heart Failure in the United States.

Year of Publication

2022

Number of Pages

1917-1928

Date Published

05/2022

ISSN Number

1558-3597

Abstract

BACKGROUND: There are currently limited accurate national estimates for pediatric heart failure (HF).

OBJECTIVES: This study aims to describe the current burden of primary and comorbid pediatric HF in the United States.

METHODS: International Classification of Diseases, Clinical Modification codes were used to identify HF cases and comorbidities from the Kids' Inpatient Database, National Inpatient Sample, National Emergency Department (ED) Sample, and National Vital Statistics System for 2012 and 2016. To describe HF events, all visits/events among pediatric and adult subjects were included in the analysis. HF events were classified into 1 of 3 groups: 1) no HF; 2) primary HF; or 3) comorbid HF. We compared patients with and without HF and calculated unique event rates with age and sex standardization.

RESULTS: Congenital heart disease, conduction disorders/arrhythmias, and cardiomyopathy were responsible for the majority of pediatric HF-related ED visits and hospitalizations. Compared to 2012, in 2016, there was an increase in comorbid HF ED visits (rate ratio: 1.93; P < 0.001) and primary HF hospitalizations (rate ratio: 1.14; P = 0.002). Pediatric HF burden was lower compared to adult HF; however, deaths in the ED and in-hospital were significantly more likely in children presenting with HF than adults.

CONCLUSIONS: The burden of pediatric HF continues to increase. Compared to adults with HF presenting to the ED and in-hospital, outcomes are inferior and per patient resource use is higher for children hospitalized with HF. National initiatives to understand risk factors for morbidity and mortality in pediatric HF and continued surveillance and mitigation of preventable risk factors may attenuate this uptrend.

DOI

10.1016/j.jacc.2022.03.336

Alternate Title

J Am Coll Cardiol

PMID

35550689

Title

Successful merging of data from the United Network for Organ Sharing and the Pediatric Health Information System databases.

Year of Publication

2018

Number of Pages

e13168

Date Published

2018 Aug

ISSN Number

1399-3046

Abstract

Data routinely collected through United Network for Organ Sharing (UNOS) lack the detailed information on medical resource utilization and treatment costs required to accomplish for center-level comparisons of quality of care and cost for pediatric heart transplantation. We aimed to overcome this limitation by merging UNOS with the Pediatric Health Information System (PHIS) database, an administrative database containing inpatient, emergency department, ambulatory surgery, and observation unit information from over 40 not-for-profit, tertiary care pediatric hospitals. Utilizing a probabilistic match based on center, date of birth, recipient gender, and transplant date within ±2 days, more than 90% of eligible UNOS patients (N = 2264) were successfully merged to their corresponding PHIS records. Thirty-day and 1-year mortality rates observed for the merged cohort (3.2% and 9.0%, respectively) were compared with those previously reported for pediatric heart transplants, as were the significant predictors of increased mortality. These results demonstrate that the established UNOS-PHIS cohort will provide a valid platform for subsequent research aimed at identifying center-level differences that could be exploited to optimize quality of care while minimizing cost across institutions.

DOI

10.1111/petr.13168

Alternate Title

Pediatr Transplant

PMID

29635813

Title

Technology Landscape of Pediatric Mechanical Circulatory Support Devices- A Systematic Review 2010-2021.

Year of Publication

2022

Date Published

2022 Mar 31

ISSN Number

1525-1594

Abstract

<p><strong>BACKGROUND: </strong>Mechanical circulatory support (MCS) devices, such as ventricular assist devices (VADs) and total artificial hearts (TAHs), have become a vital therapeutic option in the treatment of end-stage heart failure for adult patients. Such therapeutic options continue to be limited for pediatric patients. Clinicians initially adapted or scaled existing adult devices for pediatric patients; however, these adult devices are not designed to support the anatomical structure and varying flow capacities required for this population and are generally operated "off-design", which risks complications such as hemolysis and thrombosis. Devices designed specifically for the pediatric population that seek to address these shortcomings are now emerging and gaining FDA approval.</p>

<p><strong>METHODS: </strong>To analyze the competitive landscape of pediatric MCS devices, we conducted a systematic literature review. Approximately 27 devices were studied in detail: 8 were established or previously approved designs, and 19 were under development (11 VADs, 5 Fontan assist devices, and 3 TAHs).</p>

<p><strong>RESULTS: </strong>Despite significant progress, there is still no pediatric pump technology that satisfies the unique and distinct design constraints and requirements to support pediatric patients, including the wide range of patient sizes, increased cardiovascular demand with growth, and anatomic and physiologic heterogeneity of congenital heart disease.</p>

<p><strong>CONCLUSIONS: </strong>Forward-thinking design solutions are required to overcome these challenges and to ensure the translation of new therapeutic MCS devices for pediatric patients.</p>

DOI

10.1111/aor.14242

Alternate Title

Artif Organs

PMID

35357020

Title

Association of low center performance evaluations and pediatric heart transplant center behavior in the United States.

Year of Publication

2021

Date Published

2021 Apr 22

ISSN Number

1557-3117

Abstract

<p><strong>BACKGROUND: </strong>To date, no study has evaluated the effects of low center performance evaluations (CPE) on pediatric heart transplant center behavior. We sought to assess the impact of low CPE flags on pediatric heart transplant center listing and transplant volumes and center recipient and donor characteristics.</p>

<p><strong>METHODS: </strong>We included centers performing at least 10 pediatric (age &lt;18 years) transplants during the Scientific Registry of Transplant Recipients reporting period January 2009-June 2011 and evaluated consecutive biannual program specific reports until the last reporting period January 2016-June 2018. We evaluated changes in center behavior at following time points: a year before flagging, a year and two years after the flag; and at last reporting period.</p>

<p><strong>RESULTS: </strong>During our study period, 24 pediatric centers were non-flagged and 6 were flagged. Compared to non-flagged centers, there was a decline in candidate listings in flagged centers at the last reporting period (mean increase of 5.5 ± 12.4 listings vs"?&gt; mean decrease of 14.0 ± 14.9 listings; p&nbsp;=&nbsp;.003). Similarly, the number of transplants declined in flagged centers (mean increase of 2.6 ± 9.6 transplants vs"?&gt; mean decrease of 10.0 ± 12.8 transplants; p&nbsp;=&nbsp;.012). Flagged centers had declines in listings for patients with restrictive cardiomyopathy, re-transplant, renal dysfunction, those on mechanical ventilation and extracorporeal membrane oxygenation. There was no significant change in donor characteristics between flagged and non-flagged centers.</p>

<p><strong>CONCLUSIONS: </strong>Low CPE may have unintended negative consequences on center behavior leading to declines in listing and transplant volumes and potentially leading to decreased listing for higher risk recipients.</p>

DOI

10.1016/j.healun.2021.04.008

Alternate Title

J Heart Lung Transplant

PMID

34078559

Title

Early Detection of SARS-CoV-2 and other Infections in Solid Organ Transplant Recipients and Household Members using Wearable Devices.

Year of Publication

2021

Date Published

2021 Mar 18

ISSN Number

1432-2277

Abstract

<p>The increasing global prevalence of SARS-CoV-2 and the resulting COVID-19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns and blood oxygen saturation, show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS-CoV-2 is detectable before clinical symptoms in &gt;80% of adults. Early detection of SARS-CoV-2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self-isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS-CoV-2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS-CoV-2 and other infections are also reviewed.</p>

DOI

10.1111/tri.13860

Alternate Title

Transpl Int

PMID

33735480

Title

Integrated Long-term Multifunctional Pediatric Mechanical Circulatory Assist Device.

Year of Publication

2020

Date Published

2020 Nov 15

ISSN Number

1525-1594

Abstract

<p>There continues to be limited, viable VAD technology options to support the dysfunctional states of pediatric heart failure. To address this need, we are developing a magnetically suspended, versatile pumping technology that uniquely integrates two blood pumps in a series configuration within a single device housing. This device enables operational switching from the usage of one pump to another as needed for clinical management or to support growth and development of the pediatric patient. Here we present the initial design where we conducted a virtual fit study, the Taguchi Design Optimization Method, iterative design to develop pump geometries. Computational tools were used to estimate the pressure generation, capacity delivery, hydraulic efficiency, fluid stress levels, exposure time to stresses, blood damage index, and fluid forces on the impellers. Prototypes of the pumps were tested in a hydraulic flow loop using a blood analog water-glycerin solution. Both designs demonstrated the capability to generate target pressures and flows. Blood damage estimations were below threshold levels and achieved design requirements; however, maximum scalar stress levels were above the target limit. Radial and axial forces were less than 1 N and 10 N, respectively. The performance data trends for physical prototypes correlated with theoretical expectations. The centrifugal prototype was able to generate slightly higher pressure rises than numerical predictions. In contrast, the axial prototype outperformed the computational studies. Experimental data were both repeatable and reproducible. The findings from this research are promising, and development will continue.</p>

DOI

10.1111/aor.13863

Alternate Title

Artif Organs

PMID

33191508

Title

Utilization and Outcomes of Children Treated with Direct Thrombin Inhibitors on Paracorporeal Ventricular Assist Device Support.

Year of Publication

2020

Number of Pages

939-945

Date Published

2020 Aug

ISSN Number

1538-943X

Abstract

Thrombotic and bleeding complications have historically been major causes of morbidity and mortality in pediatric ventricular assist device (VAD) support. Standard anticoagulation with unfractionated heparin is fraught with problems related to its heterogeneous biochemical composition and unpredictable pharmacokinetics. We sought to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with direct thrombin inhibitors (DTIs) antithrombosis therapy. Retrospective multicenter review of all pediatric patients (aged <19 years) treated with a DTI (bivalirudin or argatroban) on paracorporeal VAD support, examining bleeding and thrombotic adverse events. From May 2012 to 2018, 43 children (21 females) at 10 centers in North America, median age 9.5 months (0.1-215 months) weighing 8.6 kg (2.8-150 kg), were implanted with paracorporeal VADs and treated with a DTI. Diagnoses included cardiomyopathy 40% (n = 17), congenital heart disease 37% (n = 16; single ventricle n = 5), graft vasculopathy 9% (n = 4), and other 14% (n = 6). First device implanted included Berlin Heart EXCOR 49% (n = 21), paracorporeal continuous flow device 44% (n = 19), and combination of devices in 7% (n = 3). Adverse events on DTI therapy included; major bleeding in 16% (n = 7) (2.6 events per 1,000 patient days of support on DTI), and stroke 12% (n = 5) (1.7 events per 1,000 patient days of support on DTI). Overall survival to transplantation (n = 30) or explantation (n = 8) was 88%. This is the largest multicenter experience of DTI use for anticoagulation therapy in pediatric VAD support. Outcomes are encouraging with lower major bleeding and stroke event rate than that reported in literature using other anticoagulation agents in pediatric VAD support.

DOI

10.1097/MAT.0000000000001093

Alternate Title

ASAIO J.

PMID

32740356

Title

Utilization and Outcomes of Children Treated with Direct Thrombin Inhibitors on Paracorporeal Ventricular Assist Device Support.

Year of Publication

2019

Date Published

2019 Nov 20

ISSN Number

1538-943X

Abstract

<p>Thrombotic and bleeding complications have historically been major causes of morbidity and mortality in pediatric ventricular assist device (VAD) support. Standard anticoagulation with unfractionated heparin is fraught with problems related to its heterogeneous biochemical composition and unpredictable pharmacokinetics. We sought to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with direct thrombin inhibitors (DTIs) antithrombosis therapy. Retrospective multicenter review of all pediatric patients (aged &lt;19 years) treated with a DTI (bivalirudin or argatroban) on paracorporeal VAD support, examining bleeding and thrombotic adverse events. From May 2012 to 2018, 43 children (21 females) at 10 centers in North America, median age 9.5 months (0.1-215 months) weighing 8.6 kg (2.8-150 kg), were implanted with paracorporeal VADs and treated with a DTI. Diagnoses included cardiomyopathy 40% (n = 17), congenital heart disease 37% (n = 16; single ventricle n = 5), graft vasculopathy 9% (n = 4), and other 14% (n = 6). First device implanted included Berlin Heart EXCOR 49% (n = 21), paracorporeal continuous flow device 44% (n = 19), and combination of devices in 7% (n = 3). Adverse events on DTI therapy included; major bleeding in 16% (n = 7) (2.6 events per 1,000 patient days of support on DTI), and stroke 12% (n = 5) (1.7 events per 1,000 patient days of support on DTI). Overall survival to transplantation (n = 30) or explantation (n = 8) was 88%. This is the largest multicenter experience of DTI use for anticoagulation therapy in pediatric VAD support. Outcomes are encouraging with lower major bleeding and stroke event rate than that reported in literature using other anticoagulation agents in pediatric VAD support.</p>

DOI

10.1097/MAT.0000000000001093

Alternate Title

ASAIO J.

PMID

31789654

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