Significance of Sarcomere Gene Mutations Analysis in the End-Stage Phase of Hypertrophic Cardiomyopathy

Biagini, Elena; Olivotto, Iacopo; Iascone, Maria; Parodi, Maria Isola; Girolami, Francesca; Frisso, Giulia; Autore, Camillo; Limongelli, Giuseppe; Cecconi, Massimiliano; Maron, Barry J.; Maron, Martin S.; Rosmini, Stefania; Formisano, Francesco; Musumeci, Beatrice; Cecchi, Francesca; Iacovoni, Attilio; Haas, Tammy S.; Reggiani, Maria Letizia Bacchi; Ferrazzi, Paolo; Salvatore, Francesco; Spirito, Paolo; Rapezzi, Claudio

doi:10.1016/j.amjcard.2014.05.065

Cited by 81 publications

(67 citation statements)

References 27 publications

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“…They found 3 patients from 2 families who were homozygotes for a P/LP variant. Biagini et al 9 found that 13 out of 156 patients (13%) with end-stage HCM had >1 pathogenic variant; however, the details of variants were not available for evaluation.…”

Section: Case Reports and Seriesmentioning

confidence: 99%

“…7,8 Specifically, an earlier disease onset, more severe left ventricular hypertrophy, higher prevalence of advanced heart failure, 9 and increased risk of sudden cardiac death (SCD) 10 have all been reported in patients with double mutations. These associations, however, are based on relatively small series and case reports and in most cases rely on genetic variant classification before the age of large exome databases.…”

Section: See Editorial By Fatkin and Johnson See Clinical Perspectivementioning

confidence: 99%

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Prevalence and Clinical Implication of Double Mutations in Hypertrophic Cardiomyopathy

Fourey

Care

Siminovitch

et al. 2017

Circ Cardiovasc Genet

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Background-Available data suggests that double mutations in patients with hypertrophic cardiomyopathy are not rare and are associated with a more severe phenotype. Most of this data, however, is based on noncontemporary variant classification. Methods and Results-Clinical data of all hypertrophic cardiomyopathy patients with 2 rare genetic variants were retrospectively reviewed and compared with a group of patients with a single disease-causing variant. Furthermore, a literature search was performed for all studies with information on prevalence and outcome of patients with double mutations. Classification of genetic variants was reanalyzed according to current guidelines. In our cohort (n=1411), 9% of gene-positive patients had 2 rare variants in sarcomeric genes but only in 1 case (0.4%) were both variants classified as pathogenic. Patients with 2 rare variants had a trend toward younger age at presentation when compared with patients with a single mutation. All other clinical variables were similar. In data pooled from cohort studies in the literature, 8% of gene-positive patients were published to have double mutations. However, after reanalysis of reported variants, this prevalence diminished to 0.4%. All patients with 2 radical mutations in MYBPC3 in the literature had severe disease with death or heart transplant during the first year of life. Data on other specific genotype-phenotype correlations were scarce. Conclusions-Double mutations in patients with hypertrophic cardiomyopathy are much less common than previously estimated. With the exception of double radical MYBPC3 mutations, there is little data to guide clinical decision making in cases with double mutations. (Circ Cardiovasc

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Section: Case Reports and Seriesmentioning

confidence: 99%

Section: See Editorial By Fatkin and Johnson See Clinical Perspectivementioning

confidence: 99%

Prevalence and Clinical Implication of Double Mutations in Hypertrophic Cardiomyopathy

Fourey

Care

Siminovitch

et al. 2017

Circ Cardiovasc Genet

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“…3 These patients may never become candidates for aggressive therapeutic options such as heart transplantation (HT). [12][13][14][15][16] Conversely, young HCM patients with restrictive evolution may develop severe HF requiring aggressive management despite LVEF values well above 50%. 13 Therefore, the overall burden of advanced HF related to HCM progression, defined by clinical rather than instrumental indices of cardiac dysfunction, remains unresolved.…”

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confidence: 99%

Clinical Spectrum, Therapeutic Options, and Outcome of Advanced Heart Failure in Hypertrophic Cardiomyopathy

Pasqualucci

Fornaro

Castelli

et al. 2015

Circ: Heart Failure

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Background-The clinical course of patients with hypertrophic cardiomyopathy and advanced heart failure (HF) subtended by progressive left ventricular dysfunction has received limited attention. Our aim was to assess the outcome of HF and impact of treatment options including the implantable cardioverter-defibrillator and heart transplantation (HT) in patients with hypertrophic cardiomyopathy evaluated at 2 Italian referral centers >3 decades. Methods and Results-All-cause mortality and a combined end point including death, HT, or appropriate implantable cardioverter-defibrillator shock were assessed in 71 consecutive patients with HF not related to outflow obstruction (7% of the entire hypertrophic cardiomyopathy cohort) followed up for 6.1±6.9 years after development of New York Heart Association class III to IV symptoms. At enrollment, left ventricular ejection fraction was <50% in 55 patients and >50% in 16; all had restrictive left ventricular filling. During follow-up, 35 patients died (49%%; 5-year rate, 49%) and 53 met the combined end point (75%; 5-year rate, 62%). Most events occurred in the 3 years after HF onset (17% per year compared with only 3% per year subsequently). Appropriate implantable cardioverter-defibrillator shocks occurred in 11 of 34 implanted patients. Of 37 patients evaluated for HT, 14 were transplanted, 10 listed, and 13 excluded; 2 early post-HT deaths occurred in patients with elevated pulmonary vascular resistance. Eleven of the 14 HT patients were alive at 10±8 years. Conclusions-In hypertrophic cardiomyopathy, advanced HF not associated with outflow obstruction portends a severely unfavorable prognosis, particularly in the first 3 years after onset of symptoms, despite frequently preserved systolic function in about one quarter of the patients. Outcome of HT is favorable but requires early consideration, as the window of opportunity may be short. (Circ Heart

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“…На самом деле пациенты с ФВ ЛЖ менее 50 % могут иметь невыраженные симпто-мы ХСН с медленным их прогрессированием до пожи-лого возраста. Эти пациенты могут никогда не попадать на трансплантацию сердца (ТС) [7,8]. И наоборот, моло-дые пациенты с замедленным прогрессированием ХСН могут иметь симптомы выраженной ХСН, требующей агрессивного лечения, несмотря на ФВ ЛЖ более 50 % [9].…”

Section: Discussionunclassified

Clinical variants and outcomes of progressive chronic heart failure in individuals with hypertrphic cardiomyopathy

Комиссарова¹,

Zakharova²,

Iljina³

et al. 2017

RHFJ

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Significance of Sarcomere Gene Mutations Analysis in the End-Stage Phase of Hypertrophic Cardiomyopathy

Cited by 81 publications

References 27 publications

Prevalence and Clinical Implication of Double Mutations in Hypertrophic Cardiomyopathy

Prevalence and Clinical Implication of Double Mutations in Hypertrophic Cardiomyopathy

Clinical Spectrum, Therapeutic Options, and Outcome of Advanced Heart Failure in Hypertrophic Cardiomyopathy

Clinical variants and outcomes of progressive chronic heart failure in individuals with hypertrphic cardiomyopathy

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