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The purpose of this work is to revisit the history of surgical treatment for obstructive hypertrophic cardiomyopathy (oHCM) over the last 60 years, in the light of advancing knowledge of the pathophysiology of obstruction.In this narrative review the contribution of the different surgical approaches to the field will be assessed in our personal experience in Florence.Septal myectomy is the treatment of choice in patients with obstructive hypertrophic cardiomyopathy who remain symptomatic despite optimal medical treatment. Over the decades, numerous "theme variations" of the Morrow operation have been proposed, each of them targeting a specific pathophysiological determinant of left ventricular outflow tract obstruction.Precision surgery in oHCM patients today depends on the ability of the surgeon to combine and master these variations, with the bird's eye view allowed by climbing on the shoulders of giants.

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.

We assessed the efficacy and safety of ranolazine in real-world patients with hypertrophic cardiomyopathy (HCM).Ranolazine is an anti-anginal drug that inhibits the late phase of the inward sodium current. In a small prospective trial, ranolazine reduced the arrhythmic burden and improved biomarker profile in HCM patients. However, systematic reports reflecting real-world use in this setting are lacking.Changes in clinical and instrumental features, symptoms and arrhythmic burden were evaluated in 119 patients with HCM before and during treatment with ranolazine at a national referral centre for HCM.Patients were treated with ranolazine for 2 [1-4] years; 83 (70%) achieved a dosage ≥1000 mg per day. Treatment interruption was necessary in 24 patients (20%) due to side effects (n = 10, 8%) or disopyramide initiation (n = 8, 7%). Seventy patients (59%) were treated with ranolazine for relief of angina. Among them, 51 (73%) had total symptomatic relief and 47 patients (67%) showed ≥2 Canadian Cardiovascular society (CCS) angina grade improvement. Sixteen patients (13%) were treated for recurrent ventricular arrhythmias, including 4 with a clear ischemic trigger, who experienced no further arrhythmic episodes while on ranolazine. Finally, 33 patients (28%) were treated for heart failure associated with severe diastolic dysfunction: no symptomatic benefit could be observed in this group.Ranolazine was safe and well tolerated in patients with HCM. The use of ranolazine may be considered in patients with HCM and microvascular angina.

Little is known about prevalence and predictors of myocardial infarction with non-obstructive coronary arteries (MINOCA) in Fabry disease (FD) and hypertrophic cardiomyopathy (HCM). We assessed and compared the prevalence and predictors of MINOCA in a large cohort of HCM and FD patients.In this multicenter, retrospective study we enrolled 2870 adult patients with HCM and 267 with FD. The only exclusion criterion was documented obstructive coronary artery disease. MINOCA was defined according to guidelines. For each patient we collected clinical, ECG and echocardiographic data recorded at initial evaluation.Overall, 36 patients had MINOCA during a follow-up period of 4.5 ± 11.2 years. MINOCA occurred in 16 patients with HCM (0.5%) and 20 patients with FD (7.5%; p lt; 0.001). The difference between the 2 groups was highly significant, also after adjustment for the main clinical, ECG and echocardiographic variables (OR 6.12; 95%CI 2.80-13.3; p lt; 0.001). In the FD population MINOCA occurred in 17 out of 96 patients with left ventricle hypertrophy (LVH, 17.7%) and in 3 out of 171 patients without LVH (1.7%; OR 12.0; 95%CI 3.43-42.3; p lt; 0.001). At multivariable analysis, voltage criteria for LVH at ECG (OR 7.3; 95%CI 1.93-27.7; p = 0.003) and maximal LV wall thickness at echocardiography (OR 1.15; 95%CI 1.05-1.27; p = 0.002) maintained an independent association with MINOCA. No major significant differences were found in clinical, ECG and echocardiographic findings between HCM patients with or without MINOCA.MINOCA was rare in HCM patients, and 6-fold more frequent in FD patients. MINOCA may be considered a red flag for FD and aid in the differential diagnosis from HCM.

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 12‑lead ECG by layman with no medical background.We enrolled 728 (364, 52% males) individuals, aged 12-13 years who underwent ECG screening with a smartphone 12‑lead 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.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%.Layman 12‑lead Smartphone-ECG population screening proved feasible and effective, with a rate of non-interpretable ECG of5%. Potential cost-saving in ECG screening and recording was 19%, providing an appealing opportunity when large campaigns should be addressed also in developing countries.

Over the past decade, the constant progress in science and technologies has provided innovative drug molecules that address specific disease mechanisms thus opening the era of drugs targeting the underlying pathophysiology of the disease. In this scenario, a new paradigm of modulation has emerged, following the development of small molecules capable of interfering with sarcomere contractile proteins. Potential applications include heart muscle disease and various forms of heart failure, although promising targets also include conditions affecting the skeletal muscle, such as degenerative neuromuscular diseases. In cardiac patients, a cardiac myosin stimulator, omecamtiv mecarbil, has shown efficacy in heart failure with reduced systolic function, lowering heart failure related events or cardiovascular death, while two inhibitors, mavacamten and aficamten, in randomized trials targeting hypertrophic cardiomyopathy, have been shown to reduce hypercontractility and left ventricular outflow obstruction improving functional capacity. Based on years of intensive basic and translational research, these agents are the prototypes of active pipelines promising to deliver an array of molecules in the near future. We here review the available evidence and future perspectives of myosin modulation in cardiovascular medicine.

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).

The valine-to-isoleucine substitution (Val122Ile) is the most common variant of transthyretin (TTR) amyloidosis in the United States, affecting primarily individuals of African descent. This variant has been identified recently in a cluster of white individuals in Italy.Clinical phenotype and chamber performance of Black and white individuals with Val122Ile TTR cardiac amyloidosis (ATTR-CA) were compared. Compared to white patients (n = 17), Black individuals (n = 53) had lower systolic blood pressures (110 vs 131 mmHg,0.001), reduced pulse pressures (41 vs 58 mmHg; P0.001), and impaired renal function (eGFR 46 vs 67 mL/min/1.73mDespite presenting at ages similar to those of white patients, Black individuals with Val122Ile-associated ATTR-CA had a greater degree of cardiac chamber dysfunction at the time of diagnosis due to impaired ventricular capacitance. Whether these differences are attributable to amyloidosis or other cardiovascular disease requires further study.

The implantable cardioverter defibrillator(ICD) has revolutionized the management of patients with hypertrophic cardiomyopathy (HCM) at risk of sudden cardiac death (SCD). However, the identification of ideal candidates remains challenging. We aimed to describe the long-term impact of the ICD for primary prevention in patients with HCM based on stringent (high SCD risk) vs lenient indications (need for pacing/personal choice).Data from two Italian HCM Cardiomyopathy Units were retrospectively analyzed. Only patients1 follow-up visits were divided into two groups according to ICD candidacy:stringent (high SCD risk) and lenient (need for pacing, patients' choice, physician advice despite lack of high SCD risk). Major cardiac events (composite of appropriate shock/intervention and SCD) was the primary endpoint. A safety endpoint was defined as a composite of inappropriate shocks and device-related complications.Of 2009 patients, 252(12.5%) received an ICD, including 27(1.3%) in secondary prevention and 225(11.2%) in primary prevention (age at implantation 49 ± 16 years; men 65.3%). Among those in primary prevention, 167(74.2%) had stringent, while 58(25.8%) had lenient indications. At 5 ± 4 years, only stringent ICD patients experienced major cardiac events (2.84%/year, 5-year cumulative incidence: 8.1%, 95%CI [3.5-14.1%]). ICD-related complications were similar across stringent and lenient subgroups. However, patients implanted60 years had a significantly higher risk of adverse events.One third of ICD recipients with HCM in primary prevention received a lenient implantation and had no appropriate intervention. ICD implantation due to systematic upgrade in patients requiring pacing and increased risk perception may offer little advantage and increase complication rates.

Background: EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy) demonstrated that mavacamten, a cardiac myosin inhibitor, improves symptoms, exercise capacity, and left ventricular outflow tract (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM). Objectives: The purpose of this study was to evaluate mavacamten's effect on measures of cardiac structure and function and its association with changes in other clinical measures. Methods: Key echocardiographic parameters from serial echocardiograms over 30 weeks from 251 symptomatic oHCM patients (mavacamten [n = 123], placebo [n = 128]) were assessed in a core laboratory. Results: More patients on mavacamten (80.9%; n = 76 of 94) vs placebo (34.0%; n = 33 of 97) showed complete resolution of mitral valve systolic anterior motion after 30 weeks (difference, 46.8%; P < 0.0001). Mavacamten also improved measures of diastolic function vs placebo, including left atrial volume index (LAVI) (mean ± SD baseline: 40 ± 12 mL/m2 vs 41 ± 14 mL/m2; mean change from baseline of –7.5 mL/m2 [95% CI: –9.0 to –6.1 mL/m2] vs –0.09 mL/m2 [95% CI: –1.6 to 1.5 mL/m2]; P < 0.0001) and lateral E/e’ (baseline, 15 ± 6 vs 15 ± 8; change of –3.8 [95% CI: –4.7 to –2.8] vs 0.04 [95% CI: –0.9 to 1.0]; P < 0.0001). Among mavacamten-treated patients, improvement in resting, Valsalva, and post-exercise LVOT gradients, LAVI, and lateral E/e’ was associated with reduction in N-terminal pro–B-type natriuretic peptide (P ≤ 0.03 for all). Reduction in LAVI was associated with improved peak exercise oxygen consumption (P = 0.04). Conclusions: Mavacamten significantly improved measures of left ventricular diastolic function and systolic anterior motion. Improvement in LVOT obstruction, LAVI, and E/e’ was associated with reduction in a biomarker of myocardial wall stress (N-terminal pro–B-type natriuretic peptide). These findings demonstrate improvement in important markers of the pathophysiology of oHCM with mavacamten. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545)

Objectives\udThe aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM).\ud\udBackground\udLeft ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD).\ud\udMethods\udA 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death.\ud\udResults\udMWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years’ experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range –59% to 117% [SD ±20%] and –61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk).\ud\udConclusions\udUsing the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM.

Purpose: To characterize the genetic architecture of left ventricular noncompaction (LVNC) and investigate the extent to which it may represent a distinct pathology or a secondary phenotype associated with other cardiac diseases. Methods: We performed rare variant association analysis with 840 LVNC cases and 125,748 gnomAD population controls, and compared results to similar analyses on dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Results: We observed substantial genetic overlap indicating that LVNC often represents a phenotypic variation of DCM or HCM. In contrast, truncating variants in MYH7, ACTN2, and PRDM16 were uniquely associated with LVNC and may reflect a distinct LVNC etiology. In particular, MYH7 truncating variants (MYH7tv), generally considered nonpathogenic for cardiomyopathies, were 20-fold enriched in LVNC cases over controls. MYH7tv heterozygotes identified in the UK Biobank and healthy volunteer cohorts also displayed significantly greater noncompaction compared with matched controls. RYR2 exon deletions and HCN4 transmembrane variants were also enriched in LVNC, supporting prior reports of association with arrhythmogenic LVNC phenotypes. Conclusion: LVNC is characterized by substantial genetic overlap with DCM/HCM but is also associated with distinct noncompaction and arrhythmia etiologies. These results will enable enhanced application of LVNC genetic testing and help to distinguish pathological from physiological noncompaction.

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis. Cardiac specific involvement (CSI) is caused by coronary artery vasculitis, but also by myocardial eosinophilic infiltration. To date, the prevalence of CSI associated with EGPA is unresolved. Aim of this study was to systematically assess the prevalence and clinical impact of CSI in a consecutive outpatient EGPA population. Methods Between October 2018 and July 2019, we prospectively enrolled 52 consecutive EGPA patients. All underwent comprehensive evaluation including a standardized questionnaire, physical examination, 12-lead-ECG, echocardiography. Cardiac magnetic resonance and 24 h-Holter were performed as deemed clinically appropriate. Cardiac abnormalities were defined as CSI based on the likelihood of their relation to EGPA vasculitis, after exclusion of alternative diagnoses. Results 52 enrolled patients, mean age 59±1 years. Thirteen of the 52 patients (25%) were classified as CSI+. CSI was characterized by myocarditis in four patients, non-scar-related regional wall motions abnormalities (RWMA) in three, apical thrombosis in two (one also had RWMA), pericarditis in three and non-atherosclerotic coronary disease (Prinzmetal angina and coronaritis) in 2. Five (38%) of the 13 CSI+ patients, presented an apical aneurysm. Peak eosinophil count at diagnosis was higher in CSI+: 8000 /μl vs CSI-: 3000 /μl, p = 0.017. Overall, 2 patients had severe LV dysfunction, 5 required urgent hospitalization and 8 required long-term cardioactive therapy. Conclusions CSI was present in one-quarter of patients, often associated with high peak eosinophils. Myocarditis, RWMA and apical aneurysms were the most common manifestations. Although rarely severe and life-threatening, CSI often required long-term cardioactive treatment.

A patient with known obstructive hypertrophic cardiomyopathy developed worsening left ventricular outflow tract obstruction, severe mitral regurgitation, and apical ballooning leading to cardiogenic shock, a combination in which treatment of each component could worsen the others. Emergency veno-arterial extracorporeal membrane oxygenation, levosimendan, and noradrenaline transiently restored adequate systemic perfusion and gas exchange. Surgical myectomy offered a more definitive solution. (Level of Difficulty: Intermediate.), Graphical abstract

Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient α-galactosidase A activity that leads to an accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy, myocardial fibrosis, heart failure, and arrhythmias, which limit quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications. Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. Progress in imaging techniques have improved diagnosis and staging of FD-related cardiac disease, suggesting a central role for myocardial inflammation and setting the stage for further research. In addition, with the recent approval of oral chaperone therapy and new treatment developments, the FD-specific treatment landscape is rapidly evolving.

Despite numerous studies assessing the natural history of patients with hypertrophic cardiomyopathy (HCM), there is lack of data regarding the burden of hospitalization. Aim of this study was to describe prevalence, causes and predictors of cardiovascular hospitalization in patients with HCM.We retrospectively included 253 patients with HCM undergoing first evaluation at our center. Enrolment criteria included cardiac magnetic resonance imaging (CMRI) at baseline and 1-year follow-up. All hospital admissions were recorded during follow-up and adjudicated as acute vs elective and cardiovascular (CV) vs non-cardiovascular (non-CV).During 6.4 ± 4.0 years there were 187 hospitalizations in 92 patients (36%, at a rate of 5.7%/year). Most were CV-related (158/187,84.5%; 4.8%/year) while non-CV admissions were 29/187 (15.5%, 0.88%/year). There was a slight predominance of elective (n = 96, 58%, 2.8%/year) vs acute (n = 62, 41.8%, 2.0%/year) CV hospitalizations. Independent predictors of CV hospitalization were baseline symptoms (NYHA class II vs I: HR 2.06; 95% CI 1.24-3.43, NYHA III-IV vs I: HR 3.05; 95% CI 1.40-6.65, p = .004), indexed left atrial (LA) volume (HR 1.03; 95% CI 1.01-1.04, p .001), and lower indexed right ventricular end-diastolic volume iRVEDV) at cardiac magnetic resonance (HR 0.99; 95% CI 0.97-0.99, p = .03).In little over 6 years, CV hospitalization was required in over one-in-three of our HCM patients, often unplanned and due to acute disease-related complications. Symptomatic status, larger LA volume and reduced iRVEDV at baseline were independently associated with CV admissions. Strategies aimed at preventing hospitalizations are an important target to reduce the burden of disease in HCM patients.

Results from the 18-month randomized treatment period of the phase 3 ATTRACT study demonstrated the efficacy and safety of oral migalastat compared with enzyme replacement therapy (ERT) in patients with Fabry disease who previously received ERT. Here, we report data from the subsequent 12-month, migalastat-only, open-label extension (OLE) period. ATTRACT (Study AT1001–012; NCT01218659) was a randomized, open-label, active-controlled study in patients aged 16–74 years with Fabry disease, an amenable GLA variant, and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. During the OLE, patients who received migalastat 150 mg every other day (QOD) during the randomized period continued receiving migalastat (Group 1 [MM]); patients who received ERT every other week discontinued ERT and started migalastat treatment (Group 2 [EM]). Outcome measures included eGFR, left ventricular mass index (LVMi), composite clinical outcome (renal, cardiac or cerebrovascular events), and safety. Forty-six patients who completed the randomized treatment period continued into the OLE (Group 1 [MM], n = 31; Group 2 [EM], n = 15). eGFR remained stable in both treatment groups. LVMi decreased from baseline at month 30 in Group 1 (MM) in patients with left ventricular hypertrophy at baseline. Only 10% of patients experienced a new composite clinical event with migalastat treatment during the OLE. No new safety concerns were reported. In conclusion, in patients with Fabry disease and amenable GLA variants, migalastat 150 mg QOD was well tolerated and demonstrated durable, long-term stability of renal function and reduction in LVMi.

Background: In patients with left-sided infective endocarditis (IE) and heart failure associated with large vegetations, early surgery prevents embolic events. However, optimal timing of surgery for other indications is still unresolved particularly when the presence of large vegetations represents the sole indication. Methods: We retrospectively analyzed 308 consecutive patients admitted to our department with definite left-sided IE. Of these patients, 243 (79%) underwent cardiac surgery (complicated IE), 34 patients with uncomplicated IE received medical treatment, 24 were not operated due to prohibitive general conditions and 7 refused surgery. Long-term follow-up was obtained by structured telephone interviews. Results: During the 6-year follow-up (average 121.8 weeks ± 76), patients not operated because of general conditions or refusal had the worst prognosis, while outcome in operated patients for complicated IE was comparable to that of uncomplicated IE treated medically. Early (

Background Subcutaneous implantable cardioverter-defibrillators (S-ICDs) are attractive for preventing sudden cardiac death in hypertrophic cardiomyopathy (HCM) as they mitigate risks of transvenous leads in young patients. However, S-ICDs may be associated with increased inappropriate shock (IAS) in HCM patients. Objective The purpose of this study was to assess the incidence and predictors of appropriate shock and IAS in a contemporary HCM S-ICD cohort. Methods We collected electrocardiographic and clinical data from HCM patients who underwent S-ICD implantation at 4 centers. Etiologies of all S-ICD shocks were adjudicated. We used Firth penalized logistic regression to derive adjusted odds ratios (aORs) for predictors of IAS. Results Eighty-eight HCM patients received S-ICDs (81 for primary and 7 for secondary prevention) with a mean follow-up of 2.7 years. Five patients (5.7%) had 9 IAS episodes (3.8 IAS per 100 patient-years) most often because of sinus tachycardia and/or T-wave oversensing. Independent predictors of IAS were higher 12-lead electrocardiographic R-wave amplitude (aOR 2.55 per 1 mV; 95% confidence interval 1.15–6.38) and abnormal T-wave inversions (aOR 0.16; 95% confidence interval 0.02–0.97). There were 2 appropriate shocks in 7 secondary prevention patients and none in 81 primary prevention patients, despite 96% meeting Enhanced American College of Cardiology/American Heart Association criteria and the mean European HCM Risk-SCD score predicting 5.7% 5-year risk. No patients had sudden death or untreated sustained ventricular arrhythmias. Conclusion In this multicenter HCM S-ICD study, IAS were rare and appropriate shocks confined to secondary prevention patients. The R-wave amplitude increased IAS risk, whereas T-wave inversions were protective. HCM primary prevention implantable cardioverter-defibrillator guidelines overestimated the risk of appropriate shocks in our cohort.

Background Thrill-seeking activities are a favorite pastime for people of all ages. Patients with hypertrophic cardiomyopathy (HCM) are often barred from participation on the basis of danger for arrhythmias. Our aim was to collect information regarding the safety of thrill-seeking activities for HCM patients. Methods An anonymous online survey invited adult HCM patients to report participation in 11 activities (rollercoaster riding, jet skiing, rafting, bungee jumping, rappelling, paragliding, kayaking/canoeing, motor racing, snowboarding, BASE jumping and skydiving) before and after HCM diagnosis, along with major (ICD shock, syncope) or minor (nausea, dizziness, palpitations, chest pain) adverse events related to participation, and relevant physician advice. Results Six hundred forty-seven HCM patients completed the survey, with 571 (88.2%) reporting participation in ≥1 TSAs (participant age 50.85 ± 14.21, 56.6% female, 8143 post-diagnosis participations). At time of survey, 457 participants (70.6%) were ICD-carriers or had ≥1 risk factor for sudden cardiac death. Nine (1.5%) participants reported a major event during or immediately after (60 minutes) of surveyed activity. Minor adverse events were reported by 181 participants (31.6%). In addition, 8 participants reported a major adverse event >60 minutes later but within the same day. Regarding physician advice, of the 213 responders (32.9%) receiving specific advice, 56 (26.2%) were told safety data is absent with no definitive recommendation, while 24 (11.2%) and 93 (43.6%) were told TSAs were respectively safe or dangerous. Conclusions In this cohort, participation in thrill-seeking activities rarely caused major adverse events. This information can be used for shared-decision making between providers and patients.

Whether early vs. delayed referral to septal reduction therapies (SRT, alcohol septal ablation or surgical myectomy) bears prognostic relevance in hypertrophic obstructive cardiomyopathy (HOCM) is unresolved. We analyzed the impact of SRT timing on the outcome of HOCM patients.We followed 126 patients for 5 ± 4 years after SRT (mean age 53 ± 15 years; 55 post-ASA and 71 post-SM). Based on time-to-treatment (TTT; from HOCM diagnosis to SRT), patients were divided into three groups: "3" years, N = 50; "3-5" years, N = 25; "5" years, N = 51.Patients with TTT 5 years were younger at diagnosis and more often had atrial fibrillation (AF). Left ventricular outflow tract (LVOT) gradients were comparable in the 3 TTT groups. Two patients died peri-operatively, all with TTT 5. Long-term, 8 patients died (3 suddenly and 5 due to heart failure). Mortality increased progressively with TTT (2% vs. 4% vs. 12% for TTT "3", "3-5", and "5" years, p for trend = 0.039). Independent predictors of disease progression (new-onset AF, worsening to NYHA III/IV symptoms, re-intervention or death) were TTT ("3-5" vs. "3" years: HR: 4.988, 95%CI: 1.394-17.843; "5" vs. "3" years: HR: 3.420, 95%CI: 1.258-9.293, overall p-value = 0.025), AF at baseline (HR: 1.896, 95%CI: 1.002-3.589, p = 0.036) and LVOT gradient (HR per mm Hg increase: 1.022, 95%CI: 1.007-1.024, p = 0.023).Delay in SRT referral has significant impact on long-term outcome of patients with HOCM, particularly when5 years from first detection of gradient, even when successful relief of symptoms and gradient is achieved. Earlier interventions are associated with lower complication rates and better prognosis, suggesting the importance of timely SRT to maximize treatment benefit and prevent late HOCM-related complications.

Pediatric cardiomyopathies of genetic origin directly involving the heart muscle – i.e. not related to metabolic causes - are rare, yet serious diseases of the heart with an annual incidence of 1.1 to 1.5 per 100,000 children. Cardiomyopathies are a prevalent cause of heart failure and the most common cause of heart transplantation in children older than 1 year of age. Dilated and hypertrophic cardiomyopathy (HCM) have the largest prevalence, whereas restrictive cardiomyopathy and left ventricular non-compaction are very rare. The epidemiology, natural history and prognostic indicators of pediatric cardiomyopathies were poorly understood before the 1990s, and many gaps in knowledge remain to this day. Advances in cardiac imaging and genomic characterization, including genome-wide analysis, are providing fresh insights into the etiology and outcome of children with cardiomyopathy. While morphological and clinical manifestations are similar to those of adult patients, pediatric cardiomyopathies tend to have more severe outcomes and may respond less well to pharmacological treatment. The present review aims to examine familial cardiomyopathies in children, focusing particularly on the risk predictors and outcome of HCM, probably the field with the most impressive advances in recent years.

Cardiomyopathies are diseases of the myocardium, often genetically determined, associated with heterogeneous phenotypes and clinical manifestations. Despite significant progress in the understanding of these conditions, available treatments mostly target late complications, whereas approaches that promise to interfere with the primary mechanisms and natural history are just beginning to surface. The last decade has witnessed the establishment of large international cardiomyopathy registries, paralleled by advances in cardiac imaging and genetic testing, deeper understanding of the pathophysiology and growing involvement by the pharmaceutical industry. As a result, the number of molecular interventions under scrutiny is increasing sharply.

Ventricular or supraventricular ectopic beats or atrial fibrillation may be the first presentation of uncommon cardiac disease, both acquired and genetically determined. In some patients, these manifestations can be the first sign of the underlying cardiac disorder. In others, however, they are also important as prognostic indicators, reflecting electrical instability and risk. Most cardiology clinics are busy environments where the implementation of complex diagnostic algorithms is not feasible. However, it is equally impossible to reach a final diagnosis, among the thousands of rare diseases that involve the heart, moving from a first line clinical and instrumental examination. Cardiac and extra-cardiac red flags, an accurate family and clinical history and ECG interpretation may be of help in identifying a rare disease. Advanced imaging and laboratory testing at experienced referral centers is then necessary to reach a final diagnosis, but the first step in the right direction, based on these simple elements, is the most important. We here review arrhythmic presentations of rare or relatively rare diseases, and suggest a simple "rule out-rule in" approach to help direct clinical suspicion and minimize risk of neglect.

Virtual population generation is an emerging field in data science with numerous applications in healthcare towards the augmentation of clinical research databases with significant lack of population size. However, the impact of data augmentation on the development of AI (artificial intelligence) models to address clinical unmet needs has not yet been investigated. In this work, we assess whether the aggregation of real with virtual patient data can improve the performance of the existing risk stratification and disease classification models in two rare clinical domains, namely the primary Sjögren's Syndrome (pSS) and the hypertrophic cardiomyopathy (HCM), for the first time in the literature. To do so, multivariate approaches, such as, the multivariate normal distribution (MVND), and straightforward ones, such as, the Bayesian networks, the artificial neural networks (ANNs), and the tree ensembles are compared against their performance towards the generation of high-quality virtual data. Both boosting and bagging algorithms, such as, the Gradient boosting trees (XGBoost), the AdaBoost and the Random Forests (RFs) were trained on the augmented data to evaluate the performance improvement for lymphoma classification and HCM risk stratification. Our results revealed the favorable performance of the tree ensemble generators, in both domains, yielding virtual data with goodness-of-fit 0.021 and KL-divergence 0.029 in pSS and 0.029, 0.027 in HCM, respectively. The application of the XGBoost on the augmented data revealed an increase by 10.9% in accuracy, 10.7% in sensitivity, 11.5% in specificity for lymphoma classification and 16.1% in accuracy, 16.9% in sensitivity, 13.7% in specificity in HCM risk stratification.