Prognostic implications of genotype findings in non-ischaemic dilated cardiomyopathy: A network meta-analysis.

AIMS: Evidence on the relative impact of diverse genetic backgrounds associated with non-ischaemic dilated cardiomyopathy (DCM) remains contradictory. This study sought to synthesize the available data regarding long-term outcomes of different gene groups in DCM. METHODS AND RESULTS: Electronic databases were systematically screened to identify studies reporting prognostic data on pre-specified gene groups. Those included pathogenic/likely pathogenic (P/LP) variants, truncating titin variants (TTNtv), lamin A/C variants (LMNA), and desmosomal proteins. Outcomes were divided into composite adverse events (CAEs), malignant ventricular arrhythmic events (MVAEs) and heart failure events (HFEs). A total of 26 studies (n = 7255) were included in the meta-analysis and 6791 patients with genotyped DCM were analysed. Patients with P/LP variants had a higher risk for CAEs (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.67-2.65), MVAEs (OR 1.86, 95% CI 1.52-2.26), and HFEs (OR 2.01, 95% CI 1.08-3.73) than genotype-negative patients. The presence of TTNtv was linked to a higher risk for CAEs (OR 1.78, 95% CI 1.20-2.63), but not MVAEs or HFEs. LMNA and desmosomal groups suffered a higher risk for CAEs, MVAEs, and HFEs compared to non-LMNA and non-desmosomal groups, respectively. When genes were indirectly compared, the presence of LMNA resulted in a more detrimental effect that TTNtv, with respect to all composite outcomes but no significant difference was found between LMNA and desmosomal genes. Desmosomal genes harboured a higher risk for MVAEs compared to TTNtv. CONCLUSIONS: Different genetic substrates associated with DCM result in divergent natural histories. Routine utilization of genetic testing should be employed to refine risk stratification and inform therapeutic strategies in DCM.

Apical Hypertrophic Cardiomyopathy: Diagnosis, Natural History, and Management.

Apical hypertrophic cardiomyopathy (ApHCM) represents a rare variant of hypertrophic cardiomyopathy (HCM) with distinct phenotypic characteristics. The prevalence of this variant varies according to each study's geographic region. The leading imaging modality for the diagnosis of ApHCM is echocardiography. Cardiac magnetic resonance, however, is the gold standard for ApHCM diagnosis in case of poor acoustic windows or equivocal echocardiographic findings but also in cases of suspected apical aneurysms. The prognosis of ApHCM was reported to be relatively benign, although more recent studies seem to contradict this, demonstrating similar incidence of adverse events compared with the general HCM population. The aim of this review is to summarize the available evidence for the diagnosis of ApHCM, highlight distinctions in comparison to more frequent forms of HCM with regards to its natural history, prognosis, and management strategies.

Mitral regurgitation impact on left atrial myopathy in hypertrophic cardiomyopathy.

BACKGROUND: Recent studies have shown that mitral regurgitation (MR) represents a major determinant of left atrial (LA) function in patients with heart failure with preserved ejection fraction. The role of MR in determining LA myopathy in hypertrophic cardiomyopathy (HCM) is unknown. The aim of this study was to examine the association of MR with LA myopathy, assessed by LA strain values in HCM patients. METHODS: In total 250 consecutive patients (mean age 51 ± 16 years, 67.2% male) with an established diagnosis of HCM and with sinus rhythm at index echocardiography evaluation were included. LA reservoir, conduit and booster strain were analyzed, besides LA size, left ventricular (LV) systolic and diastolic function. The predictors of LA strain values were identified with linear regression analysis. RESULTS: Significant (more than mild) MR was a significant univariate predictor of all the three LA strain values. In multivariate linear regression analysis, independent predictors of LA reservoir strain were more than mild MR (r = -.23), LV global longitudinal strain (r = -.49), LA volume index (r = -.27) and patient age (r = -.23). Significant MR was also an independent determinant of LA conduit (r = -.17) and booster strain (r = -.12). In patients with LA volume index < 34 ml/m2 more than mild MR was an independent predictor of LA reservoir (r = -.32) and conduit strain (r = -.27), but not LA booster strain. CONCLUSION: Significant MR is associated with LA myopathy independently of the LV diastolic and systolic function and LA size.

Validation of the new American College of Cardiology/American Heart Association Guidelines for the risk stratification of sudden cardiac death in a large Mediterranean cohort with Hypertrophic Cardiomyopathy.

BACKGROUND: The aim of our study was to assess the performance of the new American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines, with respect to sudden cardiac death (SCD) prevention, in comparison with the established risk score of the European Society of Cardiology (hypertrophic cardiomyopathy [HCM] Risk-SCD), in a large Mediterranean cohort of HCM patients. METHODS: The clinical and imaging characteristics of 784 HCM patients (mean age at first evaluation 52 ± 16 years, 67.2% males) were analyzed retrospectively. The sensitivity, specificity, and negative predictive value for SCD events of the presence of ≥1 risk factor for SCD according to the ACC/AHA Guidelines 2020 and of the HCM Risk-SCD≥6% and HCM Risk-SCD≥4% were estimated during follow-up. RESULTS: During follow-up, 47 (6%) patients suffered an SCD event. The presence of ≥1 major risk factor for SCD according to the new ACC/AHA Guidelines had 96% sensitivity (95% CI 85.5-99.5%) with modest specificity of 59% (95% CI 55-62.2%) and negative predictive value of 99.5% (95% CI 98.2-99.9%). On the contrary, HCM- Risk-SCD≥6% had a relatively low sensitivity (32%, 95% CI 19.1-47.1%) and high specificity of 95% (95% CI 93.1-96.4%), whereas, HCM-Risk-SCD≥4% had sensitivity of 60% (95% CI 44-74%) and specificity of 83.9% (95% CI 80-85.6%). Both the HCM Risk-SCD cut-off values demonstrated lower negative predictive value but higher accuracy than the ACC/AHA algorithm for SCD prediction. CONCLUSION: The novel ACC/AHA proposed algorithm identifies most of the patients with an SCD event with the cost of numerous defibrillator implantations. HCM-Risk-SCD demonstrated higher specificity, whereas its sensitivity and negative predictive value are modest.

The predictive value of left ventricular and left atrial mechanics for atrial fibrillation and heart failure in hypertrophic cardiomyopathy: a prospective cohort study.

Atrial fibrillation (AF) and heart failure (HF) represent clinical turning points, altering the natural history of HCM and influencing long-term outcome of the disease. The aim of this study was to evaluate the ability of left ventricular (LV) and left atrial (LA) myocardial deformation parameters to predict new-onset AF and HF outcomes in patients with HCM. This was a prospective study that included HCM patients without severe valvular heart disease, prior myocardial infarction or history of AF. The study sample consisted of 250 patients (mean age 50.8 ± 15.8, 67.2% male). Two-dimensional (2D) speckle tracking deformation parameters including global longitudinal strain (GLS), radial strain, circumferential strain, LA reservoir strain (LAεres), LA conduit strain (LAεcon) and LA booster strain(LAεboost) were examined. During a mean follow-up of 2.5 ± 1.2 years, 44 patients developed new-onset AF. All the LV and LA deformation parameters were significant univariate predictors of AF. GLS and LAεres had the highest C statistic among the LV and LA functional indices. In multivariable analysis, only LAεres remained an independent predictor of the arrhythmia (HR 0.91, 95% CI 0.85-0.98, p: 0.008). Similarly, GLS and LAεres had the highest predictive value among the 2D speckle tracking parameters for HF outcomes. LAεres remained an independent predictor after adjusting for significant covariates. GLS and LAεres demonstrated high predictive value for the development of AF and HF in HCM. LAεres was the only independent predictor of both outcomes.Clinical trial registration: ClinicalTrials.gov identifier: NCT04112511.

The natural history of hypertrophic cardiomyopathy in a large Mediterranean cohort.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) represents the most common inherited cardiomyopathy and it is characterized by phenotypic and genetic heterogeneity. The purpose of our study was to investigate the natural history of HCM in a large Mediterranean cohort and to identify predictors of outcomes. METHODS: The clinical and echocardiographic characteristics of 690 patients with HCM were examined. The predictors of mortality and sudden cardiac events were examined during a mean follow-up of 8.5 years. RESULTS: Asymmetrical hypertrophy was the most common among our cohort (82.9%) followed by apical hypertrophy pattern (13.6%). Atrial fibrillation was present in 22.3%, whereas nonsustained ventricular tachycardia occurred in 10.4% of the patients. During follow-up, a total of 7.4% of patients died. Specifically, 5.5% HCM patients died from cardiovascular causes, including 2.8% from heart failure and 2% from sudden death. Obstructive phenotype did not have any effect on mortality. Atrial fibrillation, ejection fraction and right ventricular systolic pressure (RVSP) were common independent predictors for overall and cardiovascular mortality. A total of 6.1% of HCM patients suffered sudden arrhythmic events and maximal wall thickness, ejection fraction, nonsustained ventricular tachycardia, syncopal episodes and, more importantly, the presence of an apical aneurysm were all independent risk factors. CONCLUSION: HCM is a relatively benign cardiomyopathy in Greece, similarly to other countries. Apical hypertrophy pattern is more common in Greece than in the other European countries, whereas the presence of apical aneurysm is the most important risk factor for arrhythmic events on top of the established risk factors for sudden death.