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Aim: To develop a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET).

Methods: We retrospectively pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n = 197) were performed with three different PET devices. A low-end scanner (66 scans) was used for method development, and remaining scans with newer devices for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall and calculation of LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n = 47) and WT to 2D-echocardiography (2DE, n = 36). PET accuracy was tested using linear regression, Bland–Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients.

Results: High correlations were found in the blinded analyses (r ≥ 0.87, P < 0.0001 for all). AUC for detecting increased LVM and WT (> 12 mm and > 15 mm) was ≥ 0.95 (P < 0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P < 0.0001).

Conclusion: 15O-water PET might detect LV hypertrophy with high accuracy and precision.

Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.

Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.

Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.

Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.

Background Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease associated with arrhythmias. Non-sustained ventricular tachycardia (NSVT) is a risk factor for sudden cardiac death and part of the current risk stratification. Furthermore, atrial fibrillation (AF), which increases the risk of stroke, is believed to be common in HCM patients. Routine ambulatory monitoring captures the rhythm only periodically over 24-48 h; thus, the true burden of arrhythmia is unknown. The insertable cardiac monitor (ICM) should help determine a more realistic arrhythmia assessment in HCM patients. Objective The purpose of this study was to ascertain the incidence of NSVT, AF, and bradycardia in unselected HCM patients by the use of an ICM. Methods Thirty adults, mean age 49.9 +/- 12.3 years, 25 (83.3%) males were implanted with a Confirm Rx ICM. The monitoring application was installed on the patient's smartphone, which allowed for patient activation in case of symptoms. The ICM was programmed as follows: ventricular tachycardia (VT) >= 160 beats per minute (bpm) for >= 8 intervals, AF >= 2 min of duration, and bradycardia <= 40 bpm or pause >= 3.0 s. Results The mean calculated 5-year risk was 2.3%, and 29/30 of the patients had a risk <4%. During follow-up, AF was found in nine patients (30.0%). At least one episode of NSVT was detected in seven patients (23.3%). In 13 patients (43.3%), sinoatrial block/sinus arrest/sinus bradycardia were seen. No arrhythmia was detected in nine patients (30.0%). Conclusion In this first prospective study using an ICM, the arrhythmia burden in HCM patients yielded 30.0% AF and 23.3% NSVT.

Surgical myectomy (SM) and alcohol septal ablation (ASA) are two invasive therapies for symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM), despite medical therapy. This meta-analysis aims to compare the efficacy of the two procedures. We searched all electronic databases until February 2020 for clinical trials and cohorts comparing clinical outcomes of ASA and SM treatment of patients with HOCM. The primary endpoint was all-cause mortality, cardiovascular (CV) mortality, sudden cardiac death (SCD), re-intervention, and complications. Secondary endpoints included relief of clinical symptoms and drop of left ventricular outflow tract (LVOT) gradient. Twenty studies (4547 patients; 2 CTs and 18 cohorts) comparing ASA vs. SM with a mean follow-up of 47 ± 28.7 months were included. Long term (8.72 vs. 7.84%, p = 0.42) and short term (1.12 vs. 1.27%, p = 0.93) all-cause mortality, CV mortality (2.48 vs. 3.66%, p = 0.26), SCD (1.78 vs. 0.76%, p = 0.20) and stroke (0.36 vs. 1.01%, p = 0.64) were not different between procedures. ASA was associated with lower peri-procedural complications (5.57 vs. 10.5%, p = 0.04) but higher rate of re-interventions (10.1 vs. 0.27%; p < 0.001) and pacemaker dependency (12.4 vs. 4.31%, p = 0.0004) compared to SM. ASA resulted in less reduction in LVOT gradient (−47.8 vs. −58.4 mmHg, p = 0.01) and less improvement of clinical symptoms compared to SM (New York Heart Association (NYHA) class III/IV, 82.4 vs. 94.5%, p < 0.001, angina 53.2 vs. 84.2%, p = 0.02). Thus, ASA and SM treatment of HOCM carry a similar risk of mortality. Peri-procedural complications are less in alcohol ablation but re-intervention and pacemaker implantations are more common. These results might impact the procedure choice in individual patients, for the best clinical outcome.

Introduction: Hypertrophic cardiomyopathy (HCM) is a common disorder with various manifestations, including sudden cardiac death. Patients with suspected or confirmed HCM may be encountered throughout the healthcare system, especially in internal medicine and cardiology. Thus, thorough knowledge of HCM is essential among healthcare providers.

Methods: A web-based questionnaire was developed to assess the cross-sectional evaluation of HCM knowledge. It covered aspects such as epidemiology and diagnosis, treatment, lifestyle, risk stratification of sudden cardiac death, and implantable cardioverter-defibrillator knowledge.

Results: In total, 123 subjects completed the survey. The mean age was 38.5 +/- 10.7 years and two-thirds (n=82) were females; 43.1% were physicians (non-specialist 24.4%, cardiologists 8.9%, specialist, other than cardiology 9.8%); and the remaining were nurses (nurses within cardiology 37.4%, nurses outside cardiology 19.5%). Almost all subjects had heard about the disease (95.9%) and the vast majority (77.2%) had taken part in the management of a patient with HCM. The total mean score was 15.9 +/- 3.9 credits and the 25th, 50th, and 75th percentiles were 14, 15, and 18 credits, respectively. The predefined arbitrary pass score of )60% was reached by 61.8%, and 20.3% were considered to pass with distinction. Physicians scored higher than nurses (70.7 +/- 17.0% vs 58.1 +/- 11.8; p<0.001). Within each professional category, there was a similar score with regard to gender.

Conclusions: There is a considerable lack of knowledge of HCM among healthcare professionals working within the field of internal medicine/cardiology. This insufficient knowledge may contribute to less implementation of evidence-based medicine and current guidelines, although further studies are needed to confirm this.

Objectives N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM. Methods We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion. Results Of 357 patients enrolled, the median age was 52 (IQR: 36-65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10(-4)) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1-2 vs 3-4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001). Conclusions MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM.

Background: The objectives of the study were to describe positron emission tomography (PET) parameters, using the tracers 15O-water at rest/stress, 11C-acetate, and 11C-HED, with regard to nonsustained ventricular tachycardia (NSVT) in hypertrophic cardiomyopathy (HCM). PET offers quantitative assessment of pathophysiology throughout the left ventricular segments, including the endocardium/epicardium. The potential use PET in risk stratification remains to be elucidated. NSVT provides a marker for sudden cardiac death.

Methods: Patients with a validated diagnosis of HCM who had an implantable cardioverter-defibrillator were interrogated at 12 months and independently of PET-examinations.

Results: In total, 25 patients (mean age 56.8 ± 12.9 years, 76% males) were included and 10 reported NSVT. Mean myocardial blood flow (MBF) at rest was 0.91 ml/g/min and decreased at stress, 1.59 ml/g/min. The mean gradient (endocardium/epicardium quotient) at rest was 1.14 ± 0.09, while inverse at stress (mean 0.92 ± 0.16). Notably, MBF gradient at stress was significantly lower in patients with NSVT (p = 0.022) and borderline at rest (p = 0.059) while global MBF at rest and stress were not. Mean myocardial oxygen consumption (MVO2) was 0.088 ml/g/min (higher in NSVT, p = 0.023) and myocardial external efficiency 18.5%. Using 11C-HED, the mean retention index was 0.11 min−1 and a higher volume of distribution (p = 0.089) or transmural gradient of clearance rate (p = 0.061) or lower clearance rate (p = 0.052) showed a tendency of association of NSVT.

Conclusions: The endocardium/epicardium MBF gradient at stress is significantly lower in HCM patients with NSVT. This provides a novel approach to further refine risk stratification of sudden cardiac death.