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Objective: Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in HCM remains undefined.Methods: The study prospectively enrolled 977 unrelated patients with HCM with available NT-proBNP results who were prospectively enrolled and followed for 3.0±2.1 years. The Harrell's C-statistic under the receiver operating characteristic curve was calculated to evaluate discrimination performance. A combination model was constructed by adding NT-proBNP tertiles to the HCM Risk-SCD model. The correlation between log NT-proBNP level and cardiac fibrosis as measured by late gadolinium enhancement (LGE) or Masson's staining was analysed.Results: During follow-up, 29 patients had SCD. Increased log NT-proBNP levels were associated with an increased risk of SCD events (adjusted HR 22.27, 95% CI 10.93 to 65.63, p<0.001). The C-statistic of NT-proBNP in predicting SCD events was 0.80 (p<0.001). The combined model significantly improved the predictive efficiency of the HCM Risk-SCD model from 0.72 to 0.81 (p<0.05), with a relative integrated discrimination improvement of 0.002 (p<0.001) and net reclassification improvement of 0.67 (p<0.001). Furthermore, log NT-proBNP levels were significantly correlated with cardiac fibrosis as detected either by LGE (r=0.257, p<0.001) or by Masson's trichrome staining in the myocardium (r=0.198, p<0.05).Conclusion: NT-proBNP is an independent predictor of SCD in patients with HCM and may help with risk stratification of this disease. [ABSTRACT FROM AUTHOR]

Keywords: Asians; cardiomyopathy, hypertrophic; genetic testing; hypertrophy EN Asians cardiomyopathy, hypertrophic genetic testing hypertrophy 2086 2089 4 11/25/20 20201124 NES 201124 Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder characterized by unexplained left ventricular hypertrophy.[1] Although considered as a dominant Mendelian disease mainly caused by rare pathogenic variants in sarcomere genes, the genetic underpinnings of nearly half of patients remain unsolved.[2] Increasing evidence implies that HCM has a more complex genetic architecture.[3] We identified an East Asian-specific common missense variant in I TNNI3 i (rs3729712) associated with HCM in an exome-wide case-control association study of Chinese origin and replicated the finding in 3 independent studies ( I P i =5.80×10 SP -22 sp ). The association was confirmed in each of the 3 replication studies, among which the Beijing replication samples and Xi'an-1 cases were genotyped by a panel sequencing of cardiomyopathy candidate genes, and the Xi'an-1 controls and Xi'an-2 samples by Sanger sequencing. Patients with HCM were classified into SARC+ (pathogenic or likely pathogenic variant identified in a sarcomere gene) and SARC- (no potentially pathogenic variant identified in a sarcomere gene) groups by the presence of any variant of pathogenic, likely pathogenic, or unknown significance in the 8 sarcomere genes (MYH7, MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, and ACTC1) in the discovery study (495 vs 491), Beijing replication study (226 vs 303), and Xi'an-1 study (342 vs 304). [Extracted from the article]

Background: The lack of validated and effective sudden cardiac death (SCD) risk prediction methods is the biggest barrier to perform the lifesaving treatment with a prophylactic implantable cardioverter-defibrillator in Chinese patients with hypertrophic cardiomyopathy (HCM).Objective: This study aimed to evaluate the efficacy of 3 existing SCD risk prediction methods recommended by the 2011 American College of Cardiology Foundation and American Heart Association (ACCF/AHA) guideline, the 2014 European Society of Cardiology (ESC) guideline, and the 2019 enhanced American College of Cardiology (ACC)/AHA strategy in Chinese patients with HCM.Methods: The present study consisted of 1369 consecutive adult patients with HCM without a history of SCD events. The primary end point was a composite of SCD and equivalent events, namely, resuscitation from cardiac arrest and appropriate implantable cardioverter-defibrillator shock therapy for ventricular tachycardia or fibrillation.Results: During follow-up of 3.2 ± 2.4 years, 39 patients reached SCD end points, of whom 26 (66.7%) were correctly predicted as those at a high risk of SCD by using methods recommended by the 2019 enhanced ACC/AHA strategy, 20 (51.3%) by the 2011 ACCF/AHA guideline, but only 5 (12.8%) by the 2014 ESC guideline. The 2019 enhanced ACC/AHA strategy showed a higher C-statistic (0.647) for SCD prediction than did the 2011 ACCF/AHA guideline (0.598) and 2014 ESC guideline (0.605) and resulted in the correct reclassification of SCD risk when compared with the 2011 ACCF/AHA guideline (net reclassification index 0.113; P = .074) and 2014 ESC guideline (net reclassification index 0.245; P = .038).Conclusion: The 2019 enhanced ACC/AHA strategy showed better predictive performance for SCD risk stratification in Chinese patients with HCM, with a notably high sensitivity. [ABSTRACT FROM AUTHOR]

Background: Filamin C (FLNC) mutation was reported as a cause of HCM, with a high probability of sudden cardiac death. However, the mutation profile of FLNC, and its relationship with phenotypic expression in HCM, remains to be elucidated. Methods: In this study, FLNC gene was sequenced in 540 HCM patients and 307 healthy controls. Results: We found that 39 (7.2%) patients carried FLNC mutations, with a similar frequency to that of controls (4.2%, p = 0.101). Pedigree analysis showed that mutations were not well segregated with HCM. The baseline characteristics between HCM patients, with and without mutations, were comparable. FLNC mutations did not increase the risk for either all‐cause mortality (HR 0.746, 95% CI 0.222–2.295, p = 0.575) or cardiac mortality (HR 0.615, 95% CI 0.153–1.947, p = 0.354) in HCM patients during a follow‐up of 4.7 ± 3.2 years. Moreover, there was no significant difference in survival free from sudden cardiac arrest (HR 0.721, 95% CI 0.128–3.667, p = 0.660) and heart failure (HR 0.757, 95% CI 0.318–1.642, p = 0.447). Conclusions: FLNC mutations were common in both HCM patients and healthy population. The pathogenicity of FLNC mutations detected in HCM patients and its association with the clinical outcomes should be cautiously interpreted. As a previously reported cause of HCM, FLNC mutation is found to be very common in the healthy population and HCM patients in this study. Generally, FLNC mutation does not cause HCM, and it does not increase later mortality and morbidity in HCM patients. [ABSTRACT FROM AUTHOR]