Clinical course of hypertrophic cardiomyopathy patients implanted with a transvenous or subcutaneous defibrillator.

AIMS: The implantable cardioverter-defibrillator (ICD) is a life-saving therapy in patients with hypertrophic cardiomyopathy (HCM) at risk of sudden cardiac death. Implantable cardioverter-defibrillator complications are of concern. The subcutaneous ICD (S-ICD) does not use transvenous leads and is expected to reduce complications. However, it does not provide bradycardia and anti-tachycardia pacing (ATP). The aim of this study was to compare appropriate and inappropriate ICD interventions, complications, disease-related adverse events and mortality between HCM patients implanted with a S- or transvenous (TV)-ICD. METHODS AND RESULTS: Consecutive HCM patients implanted with a S- (n = 216) or TV-ICD (n = 211) were enrolled. Propensity-adjusted cumulative Kaplan-Meier curves and multivariate Cox proportional hazard ratios were used to compare 5-year event-free survival and the risk of events. The S-ICD patients had lower 5-year risk of appropriate (HR: 0.32; 95%CI: 0.15-0.65; P = 0.002) and inappropriate (HR: 0.44; 95%CI: 0.20-0.95; P = 0.038) ICD interventions, driven by a high incidence of ATP therapy in the TV-ICD group. The S- and TV-ICD patients experienced similar 5-year rate of device-related complications, albeit the risk of major lead-related complications was lower in S-ICD patients (HR: 0.17; 95%CI: 0.038-0.79; P = 0.023). The TV- and S-ICD patients displayed similar risk of disease-related complications (HR: 0.64; 95%CI: 0.27-1.52; P = 0.309) and mortality (HR: 0.74; 95%CI: 0.29-1.87; P = 0.521). CONCLUSION: Hypertrophic cardiomyopathy patients implanted with a S-ICD had lower 5-year risk of appropriate and inappropriate ICD therapies as well as of major lead-related complications as compared to those implanted with a TV-ICD. Long-term comparative follow-up studies will clarify whether the lower incidence of major lead-related complications will translate into a morbidity or survival benefit.

Diagnostic and prognostic electrocardiographic features in patients with hypertrophic cardiomyopathy.

The standard 12-lead electrocardiogram (ECG) represents a cornerstone for the diagnosis and evaluation of hypertrophic cardiomyopathy (HCM), the most common genetically determined heart muscle disease, due to its cost-effectiveness and wide availability. The ECG may surprisingly look normal in 4-6% of adult patients, and in less than 3% of paediatric patients, but it is abnormal in the vast majority of the remaining patients. 'Specific' features comprise pathological Q-waves, deep S-waves in V1-V3, or high R-waves in V4-V6 due to left ventricular hypertrophy with T-wave (TW) depression or negative TWs. Negative giant TWs are often found in apical HCM. However, in many patients, the ECG may only show non-specific ST-T changes with diphasic or flat TWs. An isolated inverted TW in lateral leads (usually aVL) may be the only marker for HCM in some patients. Electrocardiogram helps to diagnose sarcomeric HCM and distinguish it from different phenocopies, such as cardiac amyloidosis, glycogen storage, or Fabry disease. Electrocardiogram may also have a prognostic role, identifying high-risk features that could impact the clinical outcome.

Stage-specific therapy for hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disease and is defined by otherwise unexplained left ventricular hypertrophy. The main complications include heart failure and arrhythmias such as atrial fibrillation and ventricular arrhythmias. Current treatment rests on septal reduction therapies, prevention of sudden cardiac death through implantable cardioverter defibrillator, and use of drugs such as beta-blockers, calcium antagonists, or amiodarone. In the last years, new pharmacological agents specifically targeting the pathophysiology of the disease have been developed with encouraging results in terms of functional capacity and symptoms improvement from clinical trials. In this review, we summarize the possible treatment approaches for each phase of the natural history of the disease: pre-phenotype expression, classic phenotype, adverse remodelling, and overt dysfunction.

Genetic Testing and Counselling in Hypertrophic Cardiomyopathy: Frequently Asked Questions.

Genetic counselling and genetic testing in hypertrophic cardiomyopathy (HCM) represent an integral part of the diagnostic algorithm to confirm the diagnosis, distinguish it from phenocopies, and suggest tailored therapeutic intervention strategies. Additionally, they enable cascade genetic testing in the family. With the implementation of Next Generation Sequencing technologies (NGS), the interpretation of genetic data has become more complex. In this regard, cardiologists play a central role, aiding geneticists to correctly evaluate the pathogenicity of the identified genetic alterations. In the ideal setting, geneticists and cardiologists must work side by side to diagnose HCM as well as convey the correct information to patients in response to their many questions and concerns. After a brief overview of the role of genetics in the diagnosis of HCM, we present and discuss the frequently asked questions by HCM patients throughout our 20-year genetic counselling experience. Appropriate communication between the team and the families is key to the goal of delivering the full potential of genetic testing to our patients.

Real-World Use and Predictors of Response to Disopyramide in Patients with Obstructive Hypertrophic Cardiomyopathy.

Background: Although disopyramide has been widely used to reduce left ventricular outflow obstruction (LVOTO) and to improve symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM), its use in real world as well as patient characteristics associated with a positive treatment response are still unclear. Methods: From 1980 to 2021, 1527 patients with HCM were evaluated and 372 (23%) had a LVOTO with active follow-up. The efficacy and safety of disopyramide were assessed systematically during 12 months (2-, 6-, and 12-month visits). Responders were patients with a final NYHA = I and a LVOTO < 30 mmHg; incomplete responders were those patients with NYHA > I and a LVOTO < 30 mmHg; and non-responders were symptomatic patients with no change in functional class NYHA and a LVOT gradient > 30 mmHg. Results: Two-hundred-fifty-four (66%) patients were in functional class NYHA I/II and 118 (34%) in NYHA III/IV. A total of 118/372 (32%, 55 ± 16 years) underwent disopyramide therapy. Twenty-eight (24%) patients responded to therapy, 39 (33%) were incomplete responders, and 51 (43%) did not respond. Responder were mainly patients in functional NYHA class I/II (24/28, 86%), whereas incomplete responders and non-responders were more often in functional NYHA class III/IV (50/54 (93%)). An independent predictor of response to disopyramide treatment was the presence of NYHA I/II at the initiation of therapy (HR 1.5 (95% CI 1.1-4.5), p = 0.03). No major life-threatening arrhythmic events or syncope occurred, despite 19 (16%) patients showing reduced QTc from baseline, 19 (16%) having no difference, while 80 (69%) patients had prolonged QTc interval. Thirty-one (26%) patients experienced side effects, in particular, 29 of the anticholinergic type. Conclusions: Disopyramide was underused in oHCM but effective in reducing LVOTO gradients and symptoms in slightly symptomatic patients with less severe disease phenotype with a safe pro-arrhythmic profile.

Validation of a multiple­lead smartphone-based electrocardiograph with automated lead placement for layman use in patients with hypertrophic cardiomyopathy.

BACKGROUND: A smartphone 12-Lead ECG that enables layman ECG screening is still lacking. We aimed to validate D-Heart ECG device, a smartphone 8/12 Lead electrocardiograph with an image processing algorithm to guide secure electrode placement by non-professional users. METHODS: One-hundred-fourty-five patients with HCM were enrolled. Two uncovered chest images were acquired using the smartphone camera. An image with virtual electrodes placement by imaging processing algorithm software was compared to the 'gold standard' electrode placement by a doctor. D-Heart 8 and 12-Lead ECG were obtained, immediately followed by 12­lead ECGs and were assessed by 2 independent observers. Burden of ECG abnormalities was defined by a score based on the sum of 9 criteria, identifying four classes of increasing severity. RESULTS: A total of 87(60%) patients presented a normal/mildly abnormal ECG, whereas 58(40%) had moderate or severe ECG alteration. Eight(6%) patients had ≥1 misplaced electrode. D-Heart 8-Lead and 12­lead ECGs concordance according to Cohen's weighted kappa test was 0,948 (p < 0,001, agreement of 97.93%). Concordance was high for the Romhilt-Estes score (kw = 0,912; p < 0.01). Concordance between D-Heart 12-Lead ECG and standard 12-Lead ECG was perfect (kw = 1). PR and QRS intervals measurements comparison with Bland-Altman method showed good accuracy (95% limit of agreement ±18 ms for PR and ± 9 ms for QRS). CONCLUSIONS: D-Heart 8/12-Lead ECGs proved accurate, allowing an assessment of ECG abnormalities comparable to the standard 12­lead ECG in patients with HCM. The image processing algorithm provided accurate electrode placement, standardizing exam quality, potentially opening perspectives for layman ECG screening campaigns.

Layman electrocardiographic screening using smartphone-based multiple­lead ECG device in school children.

BACKGROUND: Pre-partecipation ECG screening of large populations has a significant socioeconomic impact. Technological progress now allows for high-tech-low-cost ECG screening using validated smartphone-based devices capable of guiding to the correct performance of a 12­lead ECG by layman with no medical background. METHODS: We enrolled 728 (364, 52% males) individuals, aged 12-13 years who underwent ECG screening with a smartphone 12­lead ECG during school hours by layman volunteers. Correct electrodes placement was provided by a validated image-processing algorithm by the smartphone camera in the App. ECG interpretation was via a telecardiology platform and alterations classified following current standards. RESULTS: A total of 741 ECGs were recorded, of which 13(2%) were technically not interpretable. Mean PR, QRS and QTc were: 145 ± 22, 85 ± 19 and 387 ± 57 msec. No QTc prolongation was observed. Mean QRS axis was 15°; 26 (4%) patients presented an iRBB. T-wave inversion from V1-V3 was present in 145 (21%) subjects. Twenty-one(3%) patients were referred to second level examination: deep Q-waves in inferior leads in 12(1.6%), ventricular ectopics in 5(0.7%), anterior T-waves inversions V1-V4 in 3(0.4%); extreme right axis deviation in 1(0.3%). Second line investigations did not provide any definitive diagnosis. Total project costs (material equipment and human cost) was 14.460€, 19.51€ per individual. The potential net saving with respect to current pre-participation screening cost was 19%. CONCLUSIONS: Layman 12­lead Smartphone-ECG population screening proved feasible and effective, with a rate of non-interpretable ECG of <5%. Potential cost-saving in ECG screening and recording was 19%, providing an appealing opportunity when large campaigns should be addressed also in developing countries.

Syncope in hypertrophic cardiomyopathy (part II): An expert consensus statement on the diagnosis and management.

Syncopal events in patients with hypertrophic cardiomyopathy (HCM) are of concern as they are a vital consideration in algorithms for risk stratification for sudden cardiac death (SCD) and ICD implantation. However, the cause of syncope is often under-investigated and/or unexplained. Current syncope guidelines do not provide a detailed definition of unexplained syncope. To address this important gap, an international panel of experts in the field of both syncope and HCM wrote a consensus document with the aim of providing practical guidance for the diagnosis and management of syncope in patients with HCM.

Microvascular Dysfunction in Hypertrophic Cardiomyopathy.

Myocardial ischemia is an established pathophysiological feature of hypertrophic cardiomyopathy (HCM) that impacts various clinical features, including heart failure (HF) and sudden cardiac death (SCD). The major determinant of myocardial ischemia in HCM is coronary microvascular dysfunction (CMD) in the absence of epicardial coronary artery abnormalities. Despite the impossibility to directly visualize microcirculation in vivo, a multimodality approach can allow a detailed assessment of microvascular dysfunction and ischemia. Accordingly, the non-invasive assessment of CMD using transthoracic Doppler echocardiography, positron emission tomography, and cardiac magnetic resonance should now be considered mandatory in any HCM patient. Noteworthy, a complete diagnostic work-up for myocardial ischemia plays a major role in the approach of the patients with HCM and their risk stratification. Chronic and recurrent episodes of ischemia can contribute to fibrosis, culminating in LV remodeling and HF. Ischemia can potentially constitute an arrhythmic substrate and might prove to have an added value in risk stratification for SCD. Accordingly, strategies for the early diagnosis of CMD should now be considered an important challenge for the scientific community.

Syncope in hypertrophic cardiomyopathy (part I): An updated systematic review and meta-analysis.

AIMS: To describe the proportion of patients with syncope among those affected by hypertrophic cardiomyopathy (HCM) and the relevance of syncope as risk factor for sudden cardiac death and life-threatening arrhythmic events. METHOD AND RESULTS: Systematic review of original articles that assessed syncope in HCM patients. Literature search of PubMed including all English publications from 1973 to 2021.We found 57 articles for a total of 21.791 patients; of these, 14 studies reported on arrhythmic events in the follow-up. Syncope was reported in 15.8% (3.452 of 21.791) patients. It was considered unexplained in 91% of cases. Life-threatening arrhythmic events occurred in 3.6% of non-syncopal patients and in 7.7% of syncopal patients during a mean follow-up of 5.6 years. A relative risk of 1.99 (95%CI 1.39 to 2.86) was estimated for syncope patients by the random effect model using Haldane continuity correction for 0 events. CONCLUSIONS: In the current practice, the cause of syncope remained unexplained in most patients affected by HCM. The management of patients seems mainly driven by risk stratification rather than identification of the aetiology of syncope. There is a need of precise instructions how to apply the recommendations of current guidelines to this disease, which tests are indicated and how to interpret their findings. The protocol was registered in Prospero (ID: 275963).

Age-dependent diagnostic yield of echocardiography as a second-line diagnostic investigation in athletes with abnormalities at preparticipation screening.

AIMS: Systematic pre-participation screening of subjects practicing sports activity has the potential to identify athletes at risk of sudden cardiac death. However, limited evidence are present concerning the yield of echocardiography as a second-line exam in athletes with abnormal pre-participation screening. METHODS: Consecutive athletes were screened (2011-2017) in a community-based sports medicine center in Tuscany, with familial history, physical examination and ECG. Patients with abnormal/>1 borderline ECG findings, symptoms/signs of cardiovascular diseases, cardiovascular risk factors or family history of juvenile/genetic cardiac disease underwent echocardiography. RESULTS: A total of 30109 athletes (age 21 [15;31]) were evaluated. Of these, 6234 (21%) were aged 8-11 years, 18309 (61%) 12-18 years, 4442 (15%) 19-35 years, 1124 (4%) >35 years. A total of 2569 (9%) athletes were addressed to echocardiography. Referral rates increased significantly with age (5% in preadolescents to 38% in master athletes, P< 0.01). Subclinical heart diseases were found in 290/30109 (0.8%) and were common >35 years (135/1124, 11%), but rare at 19-35 years (91/4442, 2%), very rare <18 years (64/24 543, 0.2%; P< 0.01). Seventy-four (0.3%) athletes were disqualified because of the structural alterations identified, 29 (0.1%) with cardiac structural diseases at risk for sudden death. CONCLUSIONS: Italian community-based pre-participation screening showed an age-dependent yield, with a three-fold increase in referral in athletes >35 years. Subclinical structural abnormalities potentially predisposing to sudden death were rare (0.01%), mostly in post-pubertal and senior athletes. Age-specific pre-participation screening protocols may help optimize resources and improve specificity.

Italian Cardiological Guidelines (COCIS) for Competitive Sport Eligibility in athletes with heart disease: update 2020.

Since 1989, SIC Sport and a FMSI, in partnership with leading Italian Cardiological Scientific Associations (ANCE, ANMCO and SIC) have produced Cardiological Guidelines for Completive Sports Eligibility for athletes with heart disease (COCIS -- 1989, 1995, 2003, 2009 and 2017). The English version of the Italian Cardiological Guidelines for Competitive Sports Eligibility for athletes with heart disease was published in 2013 in this Journal. This publication is an update with respect to the document previously published in English in 2013. It includes the principal innovations that have emerged over recent years, and is divided into five main chapters: arrhythmias, ion channel disorders, congenital heart diseases, acquired valve diseases, cardiomyopathies, myocarditis and pericarditis and ischemic heart disease. Wherever no new data have been introduced with respect to the 2013 publication, please refer to the previous version. This document is intended to complement recent European and American guidelines but an important difference should be noted. The European and American guidelines indicate good practice for people engaging in physical activity at various levels, not only at the competitive level. In contrast, the COCIS guidelines refer specifically to competitive athletes in various sports including those with high cardiovascular stress. This explains why Italian guidelines are more restrictive than European and USA ones. COCIS guidelines address 'sports doctors' who, in Italy, must certify fitness to participate in competitive sports. In Italy, this certificate is essential for participating in any competition.

Transcatheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy: Long-term results and clinical outcomes.

INTRODUCTION: Radiofrequency transcatheter ablation (RFCA) for atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) has been proven feasible. However, the long-term results of RFCA and its impact on clinical course of HCM are unknown. The aim of this study was to analyse clinical outcomes and long-term efficacy of RFCA in a multicentre cohort of patients with HCM and concomitant AF. METHODS: Patients with HCM and AF consecutively undergoing RFCA were included. Ablation failure was defined as recurrence of AF, atrial tachycardia, or flutter lasting more than 3 min and occurring after the blanking period. RESULTS: Overall, 116 patients with symptomatic AF refractory to antiarrhythmic drugs were included. Over a median follow-up of 6.0 years (interquartile range: 3.0-8.9 years) recurrence rate after a single RFCA was 32.3 per 100 patient/years with 26% of patients free from AF relapses at 6-year follow-up. Among patients experiencing AF recurrence, 51 (66%) underwent at least one redo-procedure. The overall recurrence rate considering redo-procedures was 12.6 per 100 patients/years with 53% of patients free from AF relapses at 6 years. At last follow-up, with an average of 1.6 procedures, 67 (61%) patients were in sinus rhythm (SR). Patients remaining in SR showed better functional status compared with those experiencing arrhythmic recurrences (NYHA Class 1.6 ± 0.1 vs. 2.0 ± 0.1, p = .009). CONCLUSIONS: RFCA of AF in HCM patients is an effective and safe strategy favoring long-term SR maintenance, reduction of atrial arrhythmic events, and improved functional status. However, most patients need repeat procedures and continuation of antiarrhythmic drugs.

An expert consensus document on the management of cardiovascular manifestations of Fabry disease.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the α-galactosidase A (GLA) gene that leads to reduced or undetectable α-galactosidase A enzyme activity and progressive accumulation of globotriaosylceramide and its deacylated form globotriaosylsphingosine in cells throughout the body. FD can be multisystemic with neurological, renal, cutaneous and cardiac involvement or be limited to the heart. Cardiac involvement is characterized by progressive cardiac hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death. The cardiac management of FD requires specific measures including enzyme replacement therapy or small pharmacological chaperones in patients carrying amenable pathogenic GLA gene variants and more general management of cardiac symptoms and complications. In this paper, we summarize current knowledge of FD-related heart disease and expert consensus recommendations for its management.

Multidisciplinary evaluation and management of obstructive hypertrophic cardiomyopathy in 2020: Towards the HCM Heart Team.

Patients with hypertrophic cardiomyopathy (HCM) exhibit a variable phenotype with ventricular hypertrophy as the cardinal manifestation and left ventricular (LV) outflow tract obstruction (LVOTO) as a key pathophysiologic determinant. Patients with severe LVOTO usually present with exertional dyspnea, exertional syncope, and heart failure symptoms, while successful relief of LVOTO by pharmacological or invasive interventions leads to a dramatic improvement in clinical status. Proper management of obstructive HCM remains challenging and poses numerous clinical dilemmas. Since the development of surgical myectomy over half a century ago, progress in the management of LVOTO in HCM has paralleled technological advances in genetic testing, cardiac imaging, arrhythmic prophylaxis, cardiac surgery and interventional cardiology. These changes have been incorporated in dedicated scientific guidelines on both sides of the Atlantic. However, either the 2011 American guidelines or the 2014 European guidelines remain largely based on expert consensus for lack of recommendations with level of evidence A regarding any of the treatment options commonly employed in HCM. Consequently, management of obstructive HCM patients remains largely subjective and dependent on clinical judgment, local expertise, and patient preference. Following the trend that has emerged for other cardiac diseases amenable to invasive interventions, adequate evaluation and management of obstruction in HCM today requires a multidisciplinary team capable of optimizing referral, choosing the best available options, minimizing complications and ensuring state-of-the-art results. The concept of an HCM Heart Team is coming of age. This review aims to provide an update of available pharmacologic and invasive options for the management of LVOTO in HCM, either in adulthood or in childhood, highlighting areas for multidisciplinary integration and future development.

Partial Pericardial Agenesis Mimicking Arrhythmogenic Right Ventricular Cardiomyopathy.

Absence of the pericardium is a rare congenital disease in which the fibroserum membrane covering the heart is partially or totally absent. It is characterized by few echocardiography (ECG) and imaging features that can mislead the diagnosis to an inherited cardiac disease, such as arrhythmogenic right ventricular cardiomyopathy. Although it has often a benign course, this congenital defect should be identified as in some cases herniation and strangulation can be life-threatening and cause sudden cardiac death. Red flags on ECG (sinus bradycardia, variable T-wave inversion), chest x-ray (Snoopy sign, absence of tracheal deviation, and esophagus impression), and transthoracic echocardiogram (unusual windows, teardrop left ventricle, and elongated atria) should rise the suspicion of pericardium absence. The correct diagnosis, confirmed by cardiac magnetic resonance, is mandatory as the consequences on the sport activity certification, the management, and the treatment are extremely different.