Death In Hypertrophic Cardiomyopathy Patients Research Articles

Additional factors associated with sudden cardiac death in HCM patients

Abstract Background Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by an increase in the thickness of the left ventricular (LV) wall, which is not explained only by abnormal loading conditions. Sudden cardiac death (SCD) is the most devastating complication of HCM occurring in asymptomatic or younger patients without warning. Purpose To evaluate additional SCD risk factors in Ukrainian population of HCM patients. Materials and methods We retrospectively evaluated 350 consecutive HCM patients that were followed from 2006 to 2021 in our Cardiological Department. General clinical examination, standard 12-lead ECG, transthoracic echocardiography and 24 hours Holter ECG monitoring data were estimated. The 5-year SCD risk was calculated according to the HCM Risk-SCD score. The endpoint of the study was SCD and its surrogates, including adequate performance of the implantable cardioverter-defibrillator and successful resuscitation. Results Follow-up time was 5.0 (1.5-9.5) years. During this time, 16 patients (4.6%) reached the end point, which was 0.9%/year. According to the HCM Risk-SCD score, 5 (31.3%) of this group had a high risk of SCD (≥ 6%) and 3 (18.8%) had an intermediate risk (≥ 4% and < 6%). In multivariable Cox regression analysis adjusted for conventional SCD risk factors it was found that independent predictors of SCD were unexplained syncope (HR 3.81, 95% CI 1.11-13.12, p=0.034), systolic blood pressure (SBP) (HR 0.97 , 95% CI 0.94- 0.99, p=0.026), "infarct-like" ST elevation on ECG (HR 6.81, 95% CI 2.09-22.16, p=0.001) and PQ interval duration (HR 1.03, 95% CI 1.01-1.05, p=0.002), Harrell's C-index 0.84, 95% CI 0.73-0.95, p < 0.0001). Conclusions In our study HCM Risk-SCD score predicted SCD or surrogates only in 50% of cases. In order to improve the risk stratification some additional independent predictors of SCD can be proposed. ECG parameters ("infarct-like" ST elevation and PQ interval duration) and level of SBP were found to have SCD predictive value.

ECG changes and their prognostic value for the development of sudden cardiac death in HCM patients

Background. Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease characterized by an increase in the left ventricular (LV) wall thickness, which is not explained only by abnormal loading conditions. The development of sudden cardiac death (SCD) is one of the most dangerous complications of HCM. The aim of our study was to evaluate the prognostic value of electrocardiography (ECG) changes for the development of SCD in the Ukrainian population of patients with HCM. Materials and methods. We evaluated 350 patients with HCM who were examined in the City Clinical Hospital 8 (Kharkiv, Ukraine) from 2006 to 2021. The diagnosis of HCM was made in accordance with the current guidelines of the European Society of Cardiology. Clinical and instrumental data of patients with HCM were analyzed retrospectively, including general clinical data, 12-lead ECG, echocardiography, Holter monitoring, calculation of the 5-year risk of SCD according to the HCM Risk-SCD tool. The endpoint of the study was SCD and its surrogates, including adequate performance of the implantable cardioverter-defibrillator and the state after a successful resuscitation. Results. Follow-up was 5.0 (1.5–9.5) years. During this time, 16 patients (4.6 %) reached the endpoint, which was 0.9 %/year. According to the HCM Risk-SCD, 5 (31.3 %) patients in this group were at a high (≥ 6 %) and 3 (18.8 %) were at an intermediate risk of SCD (≥ 4 and < 6 %). A multivariable Cox regression analysis has shown that independent predictors of SCD are syncope (hazard ratio (HR) 3.81, 95% confidence interval (CI) 1.11–13.12, p = 0.034), systolic blood pressure (HR 0.97, 95% CI 0.94–0.99, p = 0.026), ECG with “infarction-like” ST elevation (HR 6.81, 95% CI 2.09–22.16, p = 0.001) and PQ interval value (HR 1.03, 95% CI 1.01–1.05, p = 0.002), Harrell’s C-index (HR 0.84, 95% CI 0.73–0.95, p < 0.0001). Conclusions. The proposed HCM Risk-SCD tool was not effective enough in predicting SCD in our study. In order to improve the risk stratification, ECG changes (“infarction-like” ST elevation and PQ interval prolongation) and systolic blood pressure lowering can be used, which were found to be independent predictors of SCD risk.

The China Hypertrophic Cardiomyopathy Project (CHCMP): The Rationale and Design of a Multicenter, Prospective, Registry Cohort Study.

Hypertrophic cardiomyopathy (HCM) is associated with adverse outcomes, such as heart failure, arrhythmia, and mortality. Sudden cardiac death (SCD) is a common cause of death in HCM patients, and identification of patients at a high risk of SCD is crucial in clinical practice.The China Hypertrophic Cardiomyopathy Project is a hospital-based, multicenter, prospective, registry cohort study of HCM patients, covering a total of 3000 participants and with a 5-year follow-up plan. A large number of demographic characteristics and clinical data will be fully collected to identify prognostic factors in Chinese HCM patients. Furthermore, the main purpose of this study is to integrate demographic and clinical characteristics to establish new 5-year SCD risk predictive equations for Chinese HCM patients by the use of machine learning technologies.The project has crucial clinical significance for risk stratification and determination of HCM patients with high risk of adverse outcomes. CLINICAL TRIALS REGISTRATION: ChiCTR2300070909.

Reversed Septal Curvature Is Associated With Nonsustained Ventricular Tachycardia in Hypertrophic Cardiomyopathy

Sudden cardiac death (SCD) is associated with nonsustained ventricular tachycardia (NSVT) in patients with hypertrophic cardiomyopathy (HCM). Recently, differences regarding septal morphology have been reported, with an increased probability of sudden death in HCM patients who had reverse septal curvature (RSC). The aim of this study was to examine the relationship between RSC and NSVT in HCM. A total of 138 patients with HCM were enrolled. Of 138 patients, 47 (34.1%) were diagnosed with RSC and 42 patients (30.4%) had NSVT. Compared with the non-RSC group, those with RSC were much younger and had an increased incidence of NSVT, thicker septal thickness, larger mass, and a higher proportion of HCM or SCD family history. Furthermore, patients with RSC had a higher risk of SCD according to the European Society of Cardiology calculator (2.5 (1.6, 4.6) vs. 1.6(1.1, 2.3)(%/5 year), p <0.001). Multivariate analysis showed that RSC was a strong and independent risk factor for NSVT (odds ratio = 2.756, 95% confidence interval: 1.164-6.525, p = 0.021). In conclusion, the presence of RSC in HCM patients is independently associated with NSVT. Further studies are needed to evaluate the role of RSC as a risk factor for SCD in this population.

Risk factors, clinical features, and outcomes of patients with hypertrophic cardiomyopathy complicated by ischemic stroke: A single-center retrospective study.

This study aimed to explore risk factors, clinical features, and prognosis of patients with hypertrophic cardiomyopathy (HCM) complicated by ischemic stroke (IS). We conducted a retrospective analysis of all HCM patient data and a 1-year follow-up study. Totally, 506 patients with HCM, including 71 with IS, were enrolled. Older age (≥63 years) was associated with an increased risk of IS in HCM patients (OR = 1.045, 95% CI: 1.018-1.072, p = 0.001). Among 37 patients complicated by IS, 22 (59.5%, 22/37) manifested as cardioembolism (CE) subtype, and 13 (35.1%, 3/37) small artery occlusion (SAO) subtype, according to TOAST classification. In the acute phase, the IS patients presented with NIHSS 4 (interquartile range: 1, 10). Multi-infarction was more common than single infarction (72.7 vs. 27.3%), while cortical + subcortical infarction (CE group: 50%) or subcortical infarction (SAO group: 53.8%) constituted most IS cases. Additionally, the blood supply areas of anterior circulation (CE group: 45.5%; SAO group: 92.3%) or anterior + posterior circulation (CE group: 50%) were mainly involved. The 1-year survival rate of HCM patients with concomitant IS was 81.8%, and IS was associated with 1-year all-cause death in HCM patients (HR = 5.689, 95% CI: 1.784-18.144, p = 0.003). Older age is a risk factor for IS occurrence in HCM patients. Patients with HCM complicated by IS had mild or moderate neurologic deficits at disease onset. CE and SAO subtypes predominate in patients with concomitant IS, especially the former. Multiple cortical and subcortical infarctions are their neuroimaging characteristics, mainly involving the anterior circulation or anterior + posterior circulation. Is is a risk factor for all-cause death in HCM patients within 1 year.

Updated risk assessments for sudden cardiac death in hypertrophic cardiomyopathy patients with implantable cardioverter-defibrillator.

Hypertrophic cardiomyopathy (HCM) is a genetic disease associated with a risk of malignant ventricular tachyarrhythmias and sudden cardiac death (SCD). Assessment of the SCD risk is crucial for its clinical management, and there has been considerable interest in developing risk stratification strategies. An implantable cardioverter-defibrillator (ICD) is a life-saving treatment for patients with HCM who are at a high-risk of ventricular tachyarrhythmias and SCD. However, a substantial number of ICD recipients experience adverse effects arising from inappropriate device therapy and implant-related complications. This has led to numerous investigations of the risk of SCD and the indications for ICD implantation. American guidelines were recently updated to include new risk markers, including left ventricular systolic dysfunction, apical aneurysm, and extensive late gadolinium enhancement, while European guidelines recommend individualized estimated 5-year SCD risk assessment models. Studies evaluating other risk factors for SCD in patients with HCM have also been published. Drawing on recent guidelines and publications on clinical risk factors, we focus this review on updated risk assessments for SCD with ICD therapy in patients with HCM.

Implications of structural right ventricular involvement in patients with hypertrophic cardiomyopathy.

In the clinical practice, the right ventricular (RV) manifestations have received less attention in hypertrophic cardiomyopathy (HCM). This paper aimed to evaluate the risk prediction value and genetic characteristics of RV involvement in HCM patients. A total of 893 patients with HCM were recruited. RV hypertrophy, RV obstruction, and RV late gadolinium enhancement were evaluated by echocardiography and/or cardiac magnetic resonance. Patients with any of the above structural abnormalities were identified as having RV involvement. All patients were followed with a median follow-up time of 3.0 years. The primary endpoint was cardiovascular death; the secondary endpoints were all-cause death and heart failure (HF)-related death. Survival analyses were conducted to evaluate the associations between RV involvement and the endpoints. Genetic testing was performed on 669 patients. RV involvement was recognized in 114 of 893 patients (12.8%). Survival analyses demonstrated that RV involvement was an independent risk factor for cardiovascular death (P = 0.002), all-cause death (P = 0.011), and HF-related death (P = 0.004). These outcome results were then confirmed by a sensitivity analysis. Genetic testing revealed a higher frequency of genotype-positive in patients with RV involvement (57.0% vs. 31.0%, P < 0.001), and the P/LP variants of MYBPC3 were more frequently identified in patients with RV involvement (30.4% vs. 12.0%, P < 0.001). Logistic analyses indicated the independent correlation between RV involvement and these genetic factors. RV involvement was an independent risk factor for cardiovascular death, all-cause death and HF-related death in HCM patients. Genetic factors might contribute to RV involvement in HCM.

Prognostic value of cardiovascular magnetic resonance imaging for life-threatening arrhythmia detected by implantable cardioverter-defibrillator in Japanese patients with hypertrophic cardiomyopathy.

Implantable cardioverter-defibrillator (ICD) is effective to prevent sudden death in HCM patients. We reviewed ICD records to analyze the relation between life-threatening arrhythmia and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) in Japanese hypertrophic cardiomyopathy (HCM) patients. In 102 consecutive patients (median age 63years, 63 males) implanted with an ICD after CMR with gadolinium enhancement (median follow-up 2.8years), the outcome of life-threatening arrhythmic events (appropriate ICD interventions for ventricular tachycardia or ventricular fibrillation) was examined. Appropriate interventions rate were 10.3% per year for secondary prevention and 7.4% per year for primary prevention. The annualized ICD-related complication rate was 3.7%. 43/91 patients (47%) implanted ICD for primary prevention had maximum wall thickness ≥20mm plus LGE in ≥4 of 17 left ventricular segments (cut-off value obtained from ROC curve); the appropriate ICD intervention rate was significantly higher in this group than in other patients group (annualized event rate, 11.1 vs. 4.6%; log-rank P=0.038). A combination of myocardial hypertrophy and LGE is a useful outcome predictive factor for life-threatening ventricular arrhythmia in Japanese HCM patients.

P947Proposed risk factors of sudden cardiac death in hypertrophic cardiomyopathy patients

P947Proposed risk factors of sudden cardiac death in hypertrophic cardiomyopathy patients

The clinical features, outcomes and genetic characteristics of hypertrophic cardiomyopathy patients with severe right ventricular hypertrophy.

IntroductionSevere right ventricular hypertrophy (SRVH) is a rare phenotype in hypertrophic cardiomyopathy (HCM) for which limited information is available. This study was undertaken to investigate the clinical, prognostic and genetic characteristics of HCM patients with SRVH.MethodsHCM with SRVH was defined as HCM with a maximum right ventricular wall thickness ≥10 mm. Whole-genome sequencing (WGS) was performed in HCM patients with SRVH. Multivariate Cox proportional hazards regression models were used to identify risk factors for cardiac death and events in HCM with SRVH. Patients with apical hypertrophic cardiomyopathy (ApHCM) were selected as a comparison group. The clinical features and outcomes of 34 HCM patients with SRVH and 273 ApHCM patients were compared.ResultsCompared with the ApHCM group, the HCM with SRVH group included younger patients and a higher proportion of female patients and also displayed higher cardiovascular morbidity and mortality. The multivariate Cox proportional hazards regression models identified 2 independent predictors of cardiovascular death in HCM patients with SRVH, a New York Heart Association class ≥III (hazard ratio [HR] = 8.7, 95% confidence interval (CI): 1.43-52.87, p = 0.019) and an age at the time of HCM diagnosis ≤18 (HR = 5.5, 95% CI: 1.24-28.36, p = 0.026). Among the 11 HCM patients with SRVH who underwent WGS, 10 (90.9%) were identified as carriers of at least one specific sarcomere gene mutation. MYH7 and TTN mutations were the most common sarcomere mutations noted in this study. Two or more HCM-related gene mutations were observed in 9 (82%) patients, and mutations in either other cardiomyopathy-related genes or ion-channel disease-related genes were found in 8 (73%) patients.ConclusionsHCM patients with SRVH were characterized by poor clinical outcomes and the presentation of multiple gene mutations.

Spectrum of MYBPC3 Gene Mutations in Patients with Hypertrophic Cardiomyopathy, Reporting Two Novel Mutations from North-West of Iran

Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death (SCD) in children and young adults and is the most frequent genetically determined cardiovascular disease following autosomal dominant pattern of inheritance. A number of genes have been shown to be responsible for HCM including MYBPC3. Cmybc, the protein encoded by MYBPC3 is a sarcomeric thick filament protein that interacts with titin, myosin, and actin to control sarcomeric gathering. Mutations in the MYBPC3 gene have been found to be associated with a history of sudden cardiac death in HCM patients. The main objective of the present study was to investigate the type and frequency of mutations in the MYBPC3 gene in HCM patients from the North-West of Iran. All the exons and exon-intron flanking regions of the MYBPC3 gene were assessed by PCR-SSCP, and the PCR products with divergent pattern of bands on polyacrylamide gel were sent for bi-directional sequencing. Mutational screening of a cohort of 42 HCM cases led to the identification of 14 MYBPC3 variations. Three cases out of those variations were frameshift, 1 case was splice site, 3 cases were missense, 2 cases were synonymous, and 5 cases were intronic variants. MYBPC3 mutations (28.5%) represent the most prevalent cause of inherited HCM. The age of onset was 39.3 in MYBPC3 carrier patients. Multiple gene mutations were recognized in 1 case (2.3%). The results obtained from the present study indicate a significant role of MYBPC3 gene mutations in HCM disease and can be used for pre-symptomatic diagnosis of at risk family members of affected individuals.

The Case Files

The Case Files

Has late gadolinium enhancement an incremental value for management of patients with hypertrophic cardiomyopathy?

Purpose: Some authors suggest the presence of fibrosis, identified with Late Gadolinium Enhancement (LGE) in Cardiac Magnetic Resonance (CMR), can be related to the subject arrhythmogenic risk in patients (P) with Hypertrophic Cardiomyopathy (HCM). We aim to examine the association between clinical-morphological variables, risk factors for sudden cardiac death and LGE findings in a population with HCM. Methods: From a population of 74 HCM P, we studied 55 P (51% male; age 63±18 years) who performed CMR. They were divided in 2 groups: LGE+ (with LGE; n=25; 45.5%) and LGE- (without LGE; n=30; 54.5%). Follow-Up (FU) regarding ventricular arrhythmias and Mortality (M) was done. Results: HCM diagnosis was done at a younger age (53±17 vs 61±17; p=0.051) in LGE+. No differences were found regarding gender, cardiovascular risk factors, previous syncope, NYHA class, ambulatory medication, identification of HCM mutation, electrocardiographic criteria for left ventricular hypertrophy or atrial fibrillation. LGE+ more often had family history of sudden death (32% vs 3.4%; p=0.008) and known coronary artery disease (12.0% vs 0%; p=0.088). They also presented a trend towards higher NTproBNP values (5151±7882 vs 1489±2422, p=0.089). Blood pressure response during exercise test was similar. Regarding echocardiogram LGE+ had higher interventricular septum (IVS) thickness (18.8±5.1 vs 15.9±3.09; p=0.017) and left atrium (LA) volume (102.1±33.7 vs 85.4±32.9, p=0.078); more often presented a restrictive pattern of diastolic dysfunction (8.7% vs 4.2%; p=0.021) with a higher E/E' relation (16.5±7.6 vs 12.0±5.9; p=0.022); and left ventricular systolic impairment (24.0% vs 3.3%; p=0.039). No differences were found concerning HCM phenotype, presence of obstruction or mitral regurgitation severity. CMR reinforced the association between LGE+ and previously echocardiographic findings: higher LA volume (32.88±3.6 vs 29.3±5.2; p=0.034); IVS thickness (21.3±4.1 vs 17.9±2.8; p=0.001) and left ventricle ejection fraction (64.1±8.9 vs 68.0±8.6; p=0.064). LGE+ more often had an implantable cardioverter defibrillator (ICD) (36.0% vs 6.7%, p=0.006). At FU (32.0±74.4 months), no differences were found regarding the frequency of ventricular arrhythmias, appropriated ICD therapies or mortality. Conclusions: In this population the presence of LGE emerges as a risk marker, associated with the classical predictors of sudden cardiac death in HCM patients. However its independent association to clinical events requires the study of larger populations, so it can be interpreted as having an incremental value for risk stratification of these P.

A systematic review for sudden cardiac death in hypertrophic cardiomyopathy patients with myocardial fibrosis: a CMR LGE study

To our knowledge this represent the first attempt at a formal meta-analysis to demonstrate that SCD is predicted by LGE, not just VT/VF.

Features of 12-Lead ECG Are the Predictor of Sudden Death in Hypertrophic Cardiomyopathy Patients

Background: Sudden death is often seen in hypertrophic cardiomyopathy (HCM) patients. Some risk factors for sudden death in adult HCM patients are known, but these factors individually have a low positive accuracy. Recently, a scoring system based only on 12-lead ECG features to assess the risk of sudden death in HCM patients was proposed by Ostman-Smith I et al. (Eur Heart J 2010). Objectives: To verify whether the scoring system is proper or not in Japanese adult HCM patients. Methods and Results: Consecutive 22 HCM patients who underwent coronary angiography at our hospital in 2008–2010 were enrolled. We checked the ECGs and case histories of the patients. It was found that three of the 22 patients had histories of cardiac arrest. According to the report by Ostman-Smith I et al., the separation of HCM patients who suffered from cardiac arrest from HCM-cohort is obtained by risk score ≥6 (sensitivity 84%, specificity 85%). In our study, the scores of all three patients were ≥6, whereas the average risk score in the other 19 patients was 4.11. The risk score ≥6 has high sensitivity (100%) and high specificity (79%). Conclusion: It is suggested that features of 12-lead ECG are powerful predictor of sudden death in Japanese HCM patients.

Implantable Cardioverter Defibrillator and Hypertrophic Cardiomyopathy. Experience at Three Centers

Although implantable cardioverter-defibrillators (ICDs) are recommended for high-risk patients with hypertrophic cardiomyopathy (HCM), there is no agreement on their general use. Moreover, little information is available on ICD use in this setting in Spain. Our aims were to describe the characteristics of HCM patients who received ICDs at three hospitals in Spain, and to study indications for device implantation and the results of follow-up in device users. We evaluated risk factors for sudden death in HCM patients with ICDs, including family history of sudden death, recurrent syncope, maximum wall thickness > or =30 mm, left ventricular outflow pressure gradient >30 mmHg, abnormal blood pressure response to exercise, and nonsustained ventricular tachycardia. During regular follow-up, appropriate and inappropriate administration of ICD therapy was recorded. Of 726 HCM patients, 45 (6.2%) had an ICD (mean age 43 [20] years). The proportion of patients with ICDs at the three centers studied was highly variable despite patients' clinical characteristics being similar. The indication for implantation was primary prevention in 27 patients and secondary prevention in 18. During follow-up (median 32 months), ICD therapy was administered appropriately in 10 (22.0%) patients (in nine, as secondary prevention and, in one, as primary prevention). The annual appropriate ICD therapy rate was 11.1% for secondary prevention and 1.6% for primary prevention. Two patients received an ICD to treat ventricular fibrillation and eight, to treat sustained ventricular tachycardia. The only significant predictor of appropriate ICD therapy was a history of sustained ventricular tachycardia or ventricular fibrillation (hazard ratio =13.3, P=.014). The percentage of HCM patients undergoing ICD implantation at Spanish hospitals was highly variable, possibly due to different selection criteria. When used as secondary prevention, ICD therapy was administered appropriately in a high proportion of cases (50% in 3 years).