Hypertrophic Cardiomyopathy: Pathophysiology, Genetics and Invasive Treatment

Hypertrophic cardiomyopathy (HCM) is the most common inheritable cardiac disorder with a phenotypic prevalence of 1:500. It is defined by the presence of left ventricular hypertrophy (LVH) in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality. Hundreds of mutations scattered among at least 25 putative HCM susceptibility genes encoding various sarcomere, Z-disk, calciumhandling, and mitochondrial proteins are known to cause HCM and are found in up to 60% of cases. Besides the genetic heterogeneity, HCM is also characterized by phenotypic heterogeneity; ranging from negligible to extreme hypertrophy, absent or severe left ventricular outflow tract obstruction, normal longevity or premature sudden cardiac death (SCD), even in patients carrying the same pathogenic HCM mutation. Since the introduction of HCM as a clinical entity in 1958, extensive research has been performed regarding diagnosis, prognosis, therapy and genetics. However, correct diagnosis and optimal management of HCM patients and their asymptomatic affected family members still offers difficulties to the physician. This thesis describes the findings of HCM patients followed at the ErasmusMC in Rotterdam for years. It is directed towards the different pheno- and genotypical aspects of this disease. Furthermore results of basic sarcomere investigations, pathophysiologic characteristics to explain clinical findings, therapeutic measures both with and without surgery and natural history are described

Quality of life and societal costs in hypertrophic cardiomyopathy:protocol of the AFFECT-HCM study

Background: Ever since the first description of hypertrophic cardiomyopathy (HCM), the most common genetic cardiac disease, tremendous progress has been made in the evaluation and management of HCM patients, but little attention has been focused on the impact of HCM on societal costs and quality of life (QoL). Aims: This paper describes the study protocol for the AFFECT-HCM study into burden of disease (BoD), which aims to estimate health-related QoL and societal costs in HCM patients and genotype-positive phenotype-negative (G+/P−) relatives during a one-year follow-up study, and relate this to the phenotypical HCM expression. Methods: A total of 400 Dutch HCM patients and 100 G+/P− subjects will be followed for one year in a prospective, multi-centre, prevalence-based BoD study. Societal costs will be measured via a bottom-up approach using the cost questionnaires iMCQ and iPCQ. For QoL, the generic EQ-5D-5L and disease-specific Kansas City Cardiomyopathy Questionnaire will be used. QoL and societal costs will be compared with phenotype-specific HCM characteristics and other determinants to identify factors that influence BoD. Accelerometry will test the correlation between BoD and physical activity. Conclusion: The AFFECT-HCM study will evaluate the BoD in HCM patients and G+/P− subjects to improve the understanding of the societal and economic impact of HCM.</p

FIRST RESULTS OF MICROSPHERE EMBOLIZATION AS AN ALTERNATIVE FOR ALCOHOL IN PERCUTANEOUS TRANSLUMINAL SEPTAL MYOCARDIAL ABLATION

Farrando Sicilia, Jordi; Fuente Fuente, Carlo

Left-ventricular outflow tract acceleration time is associated with symptoms in patients with obstructive hypertrophic cardiomyopathy

AIMS: Not all obstructive hypertrophic cardiomyopathy (HCM) patients are symptomatic. The relation between obstructive HCM and symptoms is not well understood. The hypothesis of this study is that left-ventricular outflow tract (LVOT) acceleration time (AT) is associated with symptoms. METHODS: We included 187 patients (61% men, mean age 55 ± 14 years) with obstructive HCM, defined as a maximal wall thickness ≥ 15 mm and a resting or provoked LVOT peak gradient ≥ 30 mmHg. Peak velocity (PV), left-ventricular (LV) ejection time (ET), and AT (the time between LVOT flow onset and the moment of PV) were measured on continuous-wave (CW) Doppler tracings. Logistic and Cox proportional hazard regression analyses were used to evaluate the relation between symptoms [New York Heart Association (NYHA) class ≥ II] and echocardiographic measurements, including AT. Reproducibility was assessed using the intraclass correlation coefficient (ICC). RESULTS: Symptomatic patients were more often female and had higher mean AT values. Logistic regression demonstrated a significant association between AT and symptomatic status (odds ratio 1.31 per 10 ms, p < 0.01) after adjustment for sex, negative inotropes, PV, LVOT diameter, and diastolic dysfunction. AT was independently associated with symptoms and septal reduction during follow-up (hazard ratio 1.09 per 10 ms, p < 0.05). The ICC was 0.98 with a mean difference of 0.28 ± 8.4 ms. CONCLUSION: In obstructive HCM patients, increased AT is significantly related to symptoms after adjustment for sex, negative inotropes, PV, LVOT diameter, and diastolic dysfunction, and is associated with the symptomatic status during follow-up. AT represents an easily measured echocardiographic variable with excellent inter-reader reproducibility. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40477-020-00513-3) contains supplementary material, which is available to authorized users

Inhibition of pancreatic lipase by grape seed and tea extracts and their primary catechins in vitro

Inhibiting pancreatic lipase activity is an effective means of reducing fat absorption, which may have a role in combating obesity by limiting energy intake. The use of pharmaceutical lipase inhibitors has been limited due to the prevalence of undesirable side effects. Polyphenols represent an alternative strategy to inhibit digestive enzymes using safe, gentle, and cost-effective extracts derived from plant sources. Thus, this study evaluated alternative options by testing various polyphenol-rich plant extracts (grape seed, green tea, TeaVigo®, and white tea) for their ability to inhibit pancreatic lipase activity. Using an in vitro fluorescence assay, the relative potency of extracts tested was determined in comparison to the pharmaceutical orlistat. In addition, the most abundant catechins found in these extracts, epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG), were also tested for the ability to inhibit pancreatic lipase. Results showed the most effective plant-based lipase inhibitors were the concentrated green tea product, TeaVigo® and green tea. Results with the individual catechin trials showed EGCG and EGC were the most potent lipase inhibitors in the plant extracts

Extreme interatrial conduction delay and regularization of atrial arrhythmias in a subgroup of patients with hypertrophic cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) patients may develop interatrial activation delay, indicated by a complete separation of the right and left atrial activation on the ECG. This study aimed to determine the prevalence of interatrial activation delay and the relation to atrial tachycardia (AT) cycle length (CL) in HCM patients. Methods: 159 HCM patients were included (mean age 52±14y). In group I (n=15, 9%) patients had atrial arrhythmias and progressive ATCL. In group II (n=22, 14%) patients had a stable ATCL. In group III (n=122, 77%) HCM patients without AT were included. P wave morphology and change in P wave duration (δP and Pmax) and changes in ATCL (δATCL) were analyzed. Mean follow-up was 8.7±4.7years. Results: In group I 33% (n=5) had separated P waves. In group II no P wave separation was identified (OR 1.50 [1.05-2.15], p=0.007). In group I patients were older compared to group III (62.6±15.1 vs. 50.2±14.0y, p=0.002) and had longer follow-up (13.4±2.2 vs. 7.8±4.6y, p<0.001). In group III Pmax and δP were significantly lower (105.1±22.0ms and 8.9±13.2ms, both p<0.0001). Group I patients had an increased LA size compared to group II (61.1±11.6 vs. 53.7±7.5mm, p=0.028) and higher E/A and E/E prime ratios (p=0.007; p=0.037, respectively). In group I 93.3% of the identified mutations were typical Dutch founder mutations of the MYBPC3 gene. Conclusion: In HCM patients a unique combination of separated P waves and regularization of ATs is associated with larger atria, higher LA pressures and myosin binding protein mutations

Impact of sex on timing and clinical outcome of septal myectomy for obstructive hypertrophic cardiomyopathy

Background: Sex disparities are common in hypertrophic cardiomyopathy (HCM). Previous research has shown that at time of myectomy, women are older, have greater impairment of diastolic function and more advanced cardiac remodeling. The clinical impact of these differences is unknown. Method: This study included 162 HCM patients (61% m