First name
Anjali
Middle name
T
Last name
Owens

Title

Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry (Sarcomeric Human Cardiomyopathy).

Year of Publication

2023

Number of Pages

Date Published

05/2023

ISSN Number

1524-4539

Abstract

BACKGROUND: The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children.

METHODS: Data from patients with HCM in the international, multicenter SHaRe Registry (Sarcomeric Human Cardiomyopathy) were analyzed. LVSD was defined as left ventricular ejection fraction <50% on echocardiographic reports. Prognosis was assessed by a composite of death, cardiac transplantation, and left ventricular assist device implantation. Predictors of developing incident LVSD and subsequent prognosis with LVSD were assessed using Cox proportional hazards models.

RESULTS: We studied 1010 patients diagnosed with HCM during childhood (<18 years of age) and compared them with 6741 patients with HCM diagnosed as adults. In the pediatric HCM cohort, median age at HCM diagnosis was 12.7 years (interquartile range, 8.0-15.3), and 393 (36%) patients were female. At initial SHaRe Registry site evaluation, 56 (5.5%) patients with childhood-diagnosed HCM had prevalent LVSD, and 92 (9.1%) developed incident LVSD during a median follow-up of 5.5 years. Overall LVSD prevalence was 14.7% compared with 8.7% in patients with adult-diagnosed HCM. Median age at incident LVSD was 32.6 years (interquartile range, 21.3-41.6) for the pediatric cohort and 57.2 years (interquartile range, 47.3-66.5) for the adult cohort. Predictors of developing incident LVSD in childhood-diagnosed HCM included age <12 years at HCM diagnosis (hazard ratio [HR], 1.72 [CI, 1.13-2.62), male sex (HR, 3.1 [CI, 1.88-5.2), carrying a pathogenic sarcomere variant (HR, 2.19 [CI, 1.08-4.4]), previous septal reduction therapy (HR, 2.34 [CI, 1.42-3.9]), and lower initial left ventricular ejection fraction (HR, 1.53 [CI, 1.38-1.69] per 5% decrease). Forty percent of patients with LVSD and HCM diagnosed during childhood met the composite outcome, with higher rates in female participants (HR, 2.60 [CI, 1.41-4.78]) and patients with a left ventricular ejection fraction <35% (HR, 3.76 [2.16-6.52]).

CONCLUSIONS: Patients with childhood-diagnosed HCM have a significantly higher lifetime risk of developing LVSD, and LVSD emerges earlier than for patients with adult-diagnosed HCM. Regardless of age at diagnosis with HCM or LVSD, the prognosis with LVSD is poor, warranting careful surveillance for LVSD, especially as children with HCM transition to adult care.

DOI

10.1161/CIRCULATIONAHA.122.062517

Alternate Title

Circulation

PMID

37226762
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No
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Title

Transforming Growth Factor-β Analysis of the VANISH Trial Cohort.

Year of Publication

2023

Number of Pages

e010314

Date Published

04/2023

ISSN Number

1941-3297

DOI

10.1161/CIRCHEARTFAILURE.122.010314

Alternate Title

Circ Heart Fail

PMID

36999957
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No
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Title

Transforming Growth Factor-β Analysis of the VANISH Trial Cohort.

Year of Publication

2023

Number of Pages

e010314

Date Published

04/2023

ISSN Number

1941-3297

DOI

10.1161/CIRCHEARTFAILURE.122.010314

Alternate Title

Circ Heart Fail

PMID

36999957
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Featured Publication
No
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Title

Transforming Growth Factor-β Analysis of the VANISH Trial Cohort.

Year of Publication

2023

Number of Pages

e010314

Date Published

03/2023

ISSN Number

1941-3297

DOI

10.1161/CIRCHEARTFAILURE.122.010314

Alternate Title

Circ Heart Fail

PMID

36999957
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No
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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
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Title

Sex Differences in Left Ventricular Assist Device-related Emergency Department Encounters in the United States.

Year of Publication

2022

Number of Pages

1445-1455

Date Published

05/2022

ISSN Number

1532-8414

Abstract

BACKGROUND: There is a paucity of data regarding sex differences in the profiles and outcomes of ambulatory patients on left ventricular assist device (LVAD) support who present to the emergency department (ED).

METHODS AND RESULTS: We performed a retrospective analysis of 57,200 LVAD-related ED patient encounters from the 2010 to 2018 Nationwide Emergency Department Sample. International Classification of Diseases Clinical Modification, Ninth Revision and Tenth Revision, codes identified patients aged 18 years or older with LVADs and associated primary and comorbidity diagnoses. Clinical characteristics and outcomes were stratified by sex and compared. Multivariable logistic regression was used to evaluate predictors of hospital admission and death. Female patient encounters comprised 27.2% of ED visits and occurred at younger ages and more frequently with obesity and depression (all P < .01). There were no sex differences in presentation for device complication, stroke, infection, or heart failure (all P > .05); however, female patient encounters were more often respiratory- and genitourinary or gynecological related (both P < .01). After adjustment for age group, diabetes, depression, and hypertension, male patient encounters had a 38% increased odds of hospital admission (95% confidence interval 1.20-1.58), but there was no sex difference in the adjusted odds of death (odds ratio 1.11, 95% confidence interval 0.86-1.45).

CONCLUSIONS: Patient encounters of females on LVAD support have significantly different comorbidities and outcomes compared with males. Further inquiry into these sex differences is imperative to improve long-term outcomes.

DOI

10.1016/j.cardfail.2022.05.005

Alternate Title

J Card Fail

PMID

35644307
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Title

Valsartan in early-stage hypertrophic cardiomyopathy: a randomized phase 2 trial.

Year of Publication

2021

Number of Pages

Date Published

2021 Sep 23

ISSN Number

1546-170X

Abstract

<p>Hypertrophic cardiomyopathy (HCM) is often caused by pathogenic variants in sarcomeric genes and characterized by left ventricular (LV) hypertrophy, myocardial fibrosis and increased risk of heart failure and arrhythmias. There are no existing therapies to modify disease progression. In this study, we conducted a multi-center, double-blind, placebo-controlled phase 2 clinical trial to assess the safety and efficacy of the angiotensin II receptor blocker valsartan in attenuating disease evolution in early HCM. In total, 178 participants with early-stage sarcomeric HCM were randomized (1:1) to receive valsartan (320 mg daily in adults; 80-160 mg daily in children) or placebo for 2 years ( NCT01912534 ). Standardized changes from baseline to year 2 in LV wall thickness, mass and volumes; left atrial volume; tissue Doppler diastolic and systolic velocities; and serum levels of high-sensitivity troponin T and N-terminal pro-B-type natriuretic protein were integrated into a single composite z-score as the primary outcome. Valsartan (n = 88) improved cardiac structure and function compared to placebo (n = 90), as reflected by an increase in the composite z-score (between-group difference +0.231, 95% confidence interval (+0.098, +0.364); P = 0.001), which met the primary endpoint of the study. Treatment was well-tolerated. These results indicate a key opportunity to attenuate disease progression in early-stage sarcomeric HCM with an accessible and safe medication.</p>

DOI

10.1038/s41591-021-01505-4

Alternate Title

Nat Med

PMID

34556856
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Title

Mental Health Disorders and Emergency Resource Use and Outcomes in Ventricular Assist Device Supported Patients.

Year of Publication

2021

Number of Pages

Date Published

2021 Jun 02

ISSN Number

1097-6744

Abstract

<p>There are limited data describing the prevalence of mental health disorders (MHDOs) in patients with ventricular assist devices (VADs), or associations between MHDOs and resource use or outcomes. We used the Nationwide Emergency Department Sample administrative database to analyze 44,041 ED encounters for VAD-supported adults from 2010 to 2017, to assess the relationship between MHDOs and outcomes in this population. MHDO diagnoses were present for 23% of encounters, and were associated with higher charges and rates of admission, but lower mortality.</p>

DOI

10.1016/j.ahj.2021.05.018

Alternate Title

Am Heart J

PMID

34089695
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Title

An Increasing Burden of Disease: Emergency Department Visits Among Patients With Ventricular Assist Devices From 2010 to 2017.

Year of Publication

2021

Number of Pages

e018035

Date Published

2021 Feb 05

ISSN Number

2047-9980

Abstract

<p>Background With a growing population of patients supported by ventricular assist devices (VADs) and the improvement in survival of this patient population, understanding the healthcare system burden is critical to improving outcomes. Thus, we sought to examine national estimates of VAD-related emergency department (ED) visits and characterize their demographic, clinical, and outcomes profile. Additionally, we tested the hypotheses that resource use increased and mortality improved over time. Methods and Results This retrospective database analysis uses encounter-level data from the 2010 to 2017 Nationwide Emergency Department Sample. The primary outcome was mortality. From 2010 to 2017, &gt;880&nbsp;million ED visits were evaluated, with 44&nbsp;042 VAD-related ED visits identified. The annual mean visits were 5505 (SD 4258), but increased 16-fold from 2010 to 2017 (824 versus 13&nbsp;155). VAD-related ED visits frequently resulted in admission (72%) and/or death (3.0%). Median inflation-adjusted charges were $25&nbsp;679 (interquartile range, $7450, $63&nbsp;119) per encounter. The most common primary diagnoses were cardiac (22%), and almost 30% of encounters were because of bleeding, stroke, or device complications. From 2010 to 2017, admission and mortality decreased from 82% to 71% and 3.4% to 2.4%, respectively ( for trends &lt;0.001, both). Conclusions We present the first study using national-level data to characterize the growing ED resource use and financial burden of patients supported by VAD. During the past decade, admission and mortality rates decreased but remain substantial; in 2017 ≈1 in every 40 VAD ED encounters resulted in death, making it critical that clinical decision-making be optimized for patients with VAD to maximize good outcomes.</p>

DOI

10.1161/JAHA.120.018035

Alternate Title

J Am Heart Assoc

PMID

33543642
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Title

Baseline Characteristics of the VANISH Cohort.

Year of Publication

2019

Number of Pages

e006231

Date Published

2019 Dec

ISSN Number

1941-3297

Abstract

<p><strong>BACKGROUND: </strong>The VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) targeted young sarcomeric gene mutation carriers with early-stage hypertrophic cardiomyopathy (HCM) to test whether valsartan can modify disease progression. We describe the baseline characteristics of the VANISH cohort and compare to previous trials evaluating angiotensin receptor blockers.</p>

<p><strong>METHODS: </strong>Applying a randomized, double-blinded, placebo-controlled design, 178 participants with nonobstructive HCM (age, 23.3±10.1 years; 61% men) were randomized in the primary cohort and 34 (age, 16.5±4.9 years; 50% men) in the exploratory cohort of sarcomeric mutation carriers without left ventricular hypertrophy.</p>

<p><strong>RESULTS: </strong>In the primary cohort, maximal left ventricular wall thickness was 17±4 mm for adults and score 7.0±4.5 for children. Nineteen percent had late gadolinium enhancement on cardiac magnetic resonance. Mean peak oxygen consumption was 33 mL/kg per minute, and 92% of participants were New York Heart Association functional class I. New York Heart Association class II was associated with older age, variants, and more prominent imaging abnormalities. Six previous trials of angiotensin receptor blockers in HCM enrolled a median of 24 patients (range, 19-133) with mean age of 51.2 years; 42% of patients were in New York Heart Association class ≥II, and sarcomeric mutations were not required.</p>

<p><strong>CONCLUSIONS: </strong>The VANISH cohort is much larger, younger, less heterogeneous, and has less advanced disease than prior angiotensin receptor blocker trials in HCM. Participants had relatively normal functional capacity and mild HCM features. New York Heart Association functional class II symptoms were associated with older age, more prominent imaging abnormalities, and variants, suggesting both phenotype and genotype contribute to disease manifestations.</p>

<p><strong>CLINICAL TRIAL REGISTRATION: </strong>URL: https://www.clinicaltrials.gov. Unique identifier: NCT01912534.</p>

DOI

10.1161/CIRCHEARTFAILURE.119.006231

Alternate Title

Circ Heart Fail

PMID

31813281
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