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.

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.

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.

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.

Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe).

Background: A better understanding of the factors that contribute to heterogeneous outcomes and lifetime disease burden in hypertrophic cardiomyopathy (HCM) is critically needed to improve patient management and outcomes. The Sarcomeric Human Cardiomyopathy Registry (SHaRe) was established to provide the scale of data required to address these issues, aggregating longitudinal datasets curated by eight international HCM specialty centers. Methods: Data on 4591 HCM patients (2763 genotyped), followed for a mean of 5.4±6.9 years (24,791 patient-years; median [interquartile range] 2.9 [0.3-7.9] years) were analyzed regarding cardiac arrest, cardiac transplantation, appropriate implantable cardioverter-defibrillator (ICD) therapy, all-cause death, atrial fibrillation, stroke, New York Heart Association Functional Class III/IV symptoms (all comprising the overall composite endpoint), and left ventricular ejection fraction (LVEF)<35%. Outcomes were analyzed individually and as composite endpoints. Results: Median age of diagnosis was 45.8 [30.9-58.1] years and 37% of patients were female. Age of diagnosis and sarcomere mutation status were predictive of outcomes. Patients <40 years old at diagnosis had a 77% [95% confidence interval: 72%, 80%] cumulative incidence of the overall composite outcome by age 60, compared to 32% [29%, 36%] by age 70 for patients diagnosed >60 years. Young HCM patients (20-29 years) had 4-fold higher mortality than the general United States population at a similar age. Patients with pathogenic/likely pathogenic sarcomere mutations had two-fold greater risk for adverse outcomes compared to patients without mutations; sarcomere variants of uncertain significance were associated with intermediate risk. Heart failure and atrial fibrillation were the most prevalent adverse events, although typically not emerging for several years after diagnosis. Ventricular arrhythmias occurred in 32% [23%, 40%] of patients <40 years at diagnosis, but in 1% [1%, 2%] >60 years. Conclusions: The cumulative burden of HCM is substantial and dominated by heart failure and atrial fibrillation occurring many years following diagnosis. Young age of diagnosis and the presence of a sarcomere mutation are powerful predictors of adverse outcomes. These findings highlight the need for close surveillance throughout life, and the need to develop disease-modifying therapies.

International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (EVIDENCE-HCM).

BACKGROUND: Identification of people with hypertrophic cardiomyopathy (HCM) who are at risk of sudden cardiac death (SCD) and require a prophylactic implantable cardioverter defibrillator is challenging. In 2014, the European Society of Cardiology proposed a new risk stratification method based on a risk prediction model (HCM Risk-SCD) that estimates the 5-year risk of SCD. The aim was to externally validate the 2014 European Society of Cardiology recommendations in a geographically diverse cohort of patients recruited from the United States, Europe, the Middle East, and Asia. METHODS: This was an observational, retrospective, longitudinal cohort study. RESULTS: The cohort consisted of 3703 patients. Seventy three (2%) patients reached the SCD end point within 5 years of follow-up (5-year incidence, 2.4% [95% confidence interval {CI}, 1.9-3.0]). The validation study revealed a calibration slope of 1.02 (95% CI, 0.93-1.12), C-index of 0.70 (95% CI, 0.68-0.72), and D-statistic of 1.17 (95% CI, 1.05-1.29). In a complete case analysis (n= 2147; 44 SCD end points at 5 years), patients with a predicted 5-year risk of <4% (n=1524; 71%) had an observed 5-year SCD incidence of 1.4% (95% CI, 0.8-2.2); patients with a predicted risk of ≥6% (n=297; 14%) had an observed SCD incidence of 8.9% (95% CI, 5.96-13.1) at 5 years. For every 13 (297/23) implantable cardioverter defibrillator implantations in patients with an estimated 5-year SCD risk ≥6%, 1 patient can potentially be saved from SCD. CONCLUSIONS: This study confirms that the HCM Risk-SCD model provides accurate prognostic information that can be used to target implantable cardioverter defibrillator therapy in patients at the highest risk of SCD.

Defining the diagnostic effectiveness of genes for inclusion in panels: the experience of two decades of genetic testing for hypertrophic cardiomyopathy at a single center.

PURPOSE: Genetic testing in hypertrophic cardiomyopathy (HCM) has long relied on Sanger sequencing of sarcomeric genes. The advent of next-generation sequencing (NGS) has catalyzed routine testing of additional genes of dubious HCM-causing potential. We used 19 years of genetic testing results to define a reliable set of genes implicated in Mendelian HCM and assess the value of expanded NGS panels. METHODS: We dissected genetic testing results from 1,198 single-center HCM probands and devised a widely applicable score to identify which genes yield effective results in the diagnostic setting. RESULTS: Compared with early panels targeting only fully validated sarcomeric HCM genes, expanded NGS panels allow the prompt recognition of probands with HCM-mimicking diseases. Scoring by "diagnostic effectiveness" highlighted that PLN should also be routinely screened besides historically validated genes for HCM and its mimics. CONCLUSION: The additive value of expanded panels in HCM genetic testing lies in the systematic screening of genes associated with HCM mimics, requiring different patient management. Only variants in a limited set of genes are highly actionable and interpretable in the clinic, suggesting that larger panels offer limited additional sensitivity. A score estimating the relative effectiveness of a given gene's inclusion in diagnostic panels is proposed.

Myocardial blood flow and left ventricular functional reserve in hypertrophic cardiomyopathy: a 13NH3 gated PET study.

INTRODUCTION: Ischemia in hypertrophic cardiomyopathy (HCM) is caused by coronary microvascular dysfunction (CMD), which is detected by measuring myocardial blood flow (MBF) with PET. Whether CMD may be associated with ischemic left ventricular (LV) dysfunction is unclear. We therefore assessed LV ejection fraction (EF) reserve in HCM patients undergoing dipyridamole (Dip) PET. METHODS: Resting and stress 13NH3 dynamic as well as gated PET were performed in 34 HCM patients. Segmental MBF and transmural perfusion gradient (TPG = subendocardial / subepicardial MBF) were assessed. LVEF reserve was considered abnormal if Dip LVEF decreased more than 5 units as compared to rest. RESULTS: Eighteen patients had preserved (group A) and 16 abnormal LVEF reserve (group B; range -7 to -32). Group B patients had greater wall thickness than group A, but resting volumes, LVEF, resting and Dip MBF, and myocardial flow reserve were similar. Group B had slightly higher summed stress score and summed difference score in visual analysis than group A, and a significantly higher summed stress wall motion score. In group B, resting TPG was slightly lower (1.31 ± 0.29 vs. 1.37 ± 0.34, p <0.05), and further decreased after Dip, whilst in group A it increased (B = 1.20 ± 0.39, p < 0.0001 vs. rest and vs. A = 1.40 ± 0.43). The number of segments per patient with TPG <1 was higher than in group A (p < 0.001) and was a significant predictor of impaired LVEF reserve (OR 1.86, p < 0.02), together with wall thickness (OR 1.3, p < 0.02). CONCLUSION: Abnormal LVEF response is common in HCM patients following Dip, and is related to abnormal TPG, suggesting that subendocardial ischemia might occur under Dip and cause transient LV dysfunction. Although in vivo this effect may be hindered by the adrenergic drive associated with effort, these findings may have relevance in understanding exercise limitation and heart failure symptoms in HCM.

Role of quantitative myocardial positron emission tomography for risk stratification in patients with hypertrophic cardiomyopathy: a 2016 reappraisal.

AIMS: Myocardial blood flow <1.1 mL/min/g following dipyridamole (Dip-MBF) assessed by positron emission tomography (PET) was identified in 2003 as an important outcome predictor in hypertrophic cardiomyopathy (HCM), based on scans performed in the 90s. However, such extreme Dip-MBF impairment is rarely observed in contemporary cohorts. We, therefore, reassessed the Dip-MBF threshold defining high-risk HCM patients. METHODS: Dip-MBF was measured using 13N-ammonia in 100 HCM consecutive patients, prospectively enrolled and followed for 4.0 ± 2.2 years. Outcome was assessed based on tertiles of Dip-MBF. The study end-point was a combination of cardiovascular death, progression to severe functional limitation, cardioembolic stroke, life-threatening ventricular arrhythmias. RESULTS: Global Dip-MBF was 1.95 ± 0.85, ranging from 0.7 to 5.9 mL/min/g. Dip-MBF tertile cut-off values were: 0.73 to 1.53 mL/min/g (lowest), 1.54 to 2.13 mL/min/g (middle), and 2.14 to 5.89 mL/min/g (highest). During follow-up, lowest tertile Dip-MBF was associated with sevenfold independent risk of unfavorable outcome compared to the other two tertiles. Dip-MBF 1.35 mL/min/g was identified as the best threshold for outcome prediction. Regional perfusion analysis showed that all cardiac deaths (n = 4) occurred in patients in the lowest tertile of lateral wall Dip-MBF (≤1.72 mL/min/g); septal Dip-MBF was not predictive. CONCLUSIONS: Dip-MBF confirms its role as potent predictor of outcome in HCM. However, the threshold for prediction in a contemporary cohort is higher than that reported in earlier studies. Dip-MBF impairment in the lateral wall, possibly reflecting diffuse disease extending to non-hypertrophic regions, is a sensitive predictor of mortality in HCM.

Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in the young, although not all patients eligible for sudden death prevention with an implantable cardioverter-defibrillator are identified. Contrast-enhanced cardiovascular magnetic resonance with late gadolinium enhancement (LGE) has emerged as an in vivo marker of myocardial fibrosis, although its role in stratifying sudden death risk in subgroups of HCM patients remains incompletely understood. METHODS AND RESULTS: We assessed the relation between LGE and cardiovascular outcomes in 1293 HCM patients referred for cardiovascular magnetic resonance and followed up for a median of 3.3 years. Sudden cardiac death (SCD) events (including appropriate defibrillator interventions) occurred in 37 patients (3%). A continuous relationship was evident between LGE by percent left ventricular mass and SCD event risk in HCM patients (P=0.001). Extent of LGE was associated with an increased risk of SCD events (adjusted hazard ratio, 1.46/10% increase in LGE; P=0.002), even after adjustment for other relevant disease variables. LGE of ≥15% of LV mass demonstrated a 2-fold increase in SCD event risk in those patients otherwise considered to be at lower risk, with an estimated likelihood for SCD events of 6% at 5 years. Performance of the SCD event risk model was enhanced by LGE (net reclassification index, 12.9%; 95% confidence interval, 0.3-38.3). Absence of LGE was associated with lower risk for SCD events (adjusted hazard ratio, 0.39; P=0.02). Extent of LGE also predicted the development of end-stage HCM with systolic dysfunction (adjusted hazard ratio, 1.80/10% increase in LGE; P<0.03). CONCLUSIONS: Extensive LGE measured by quantitative contrast enhanced CMR provides additional information for assessing SCD event risk among HCM patients, particularly patients otherwise judged to be at low risk.

Validation of pixel-wise parametric mapping of myocardial blood flow with ¹³NH3 PET in patients with hypertrophic cardiomyopathy.

PURPOSE: Transmural abnormalities in myocardial blood flow (MBF) are important causes of ischaemia in patients with left ventricular (LV) hypertrophy. The study aimed to test whether pixel-wise parametric mapping of (13)NH3 MBF can reveal transmural abnormalities in patients with hypertrophic cardiomyopathy (HCM). METHODS: We submitted 11 HCM patients and 9 age-matched controls with physiological LV hypertrophy to rest and stress (dipyridamole) (13)NH3 PET. We measured MBF using a compartmental model, and obtained rest and stress parametric maps. Pixel MBF values were reorganized to obtain subendocardial and subepicardial MBF of LV segments. RESULTS: MBF at rest was higher in the subendocardial than in the subepicardial layer: 0.78 ± 0.19 vs. 0.60 ± 0.18 mL/min/g in HCM patients; 0.92 ± 0.24 vs. 0.75 ± 0.24 mL/min/g in controls (both p < 0.0001). Transmural perfusion gradient (TPG = subendocardial MBF/subepicardial MBF) at rest was similar: 1.35 ± 0.31 in HCM patients; 1.28 ± 0.27 in controls (NS). During stress, controls maintained higher subendocardial MBF: 2.44 ± 0.54 vs. 1.96 ± 0.67 mL/min/g tissue (p < 0.0001), with a TPG of 1.33 ± 0.35 (NS vs. rest). In HCM patients, the difference between subendocardial and subepicardial MBF was reduced (1.46 ± 0.48 vs. 1.36 ± 0.48 mL/min/g tissue, p < 0.01) and TPG decreased to 1.11 ± 0.34 (p < 0.0001 vs. rest and vs. controls). In HCM patients 8 of 176 segments had subendocardial MBF less than -2 × SD of the mean, versus none of 144 segments in controls (p < 0.01). CONCLUSION: Pixel-wise parametric mapping of (13)NH3 MBF enables the identification of transmural abnormalities in patients with HCM.

Anaerobic digestion of bio-waste: A mini-review focusing on territorial and environmental aspects.

Scientific and industrial experiences, together with economical and policies changes of last 30 years, bring anaerobic digestion among the most environmental friendly and economically advantageous technologies for organic waste treatment and management in Europe. In this short review, the role of anaerobic digestion of organic wastes is discussed, considering the opportunity of a territorial friendly approach, without barriers, where different organic wastes are co-treated. This objective can be achieved through two proposed strategies: one is the anaerobic digestion applied as a service for the agricultural and farming sector; the other as a service for citizen (biowaste, diapers and wastewater treatment integration). The union of these two strategies is an environmental- and territorial-friendly process that aims to produce renewable energy and fertiliser material, with a low greenhouse gas emission and nutrients recovery. The advantage of forthcoming application of anaerobic digestion of organic wastes, even for added value bioproducts production and new energy carriers, are finally discussed. Among several advantages of anaerobic digestion, the role of the environmental controller was evaluated, considering the ability of minimising the impacts exploiting the biochemical equilibrium and sensitivity as a quality assurance for digestate.

The role of echocardiography in sports cardiology: An expert opinion statement of the Italian Society of Sports Cardiology (SIC sport).

Transthoracic echocardiography (TTE) is routinely required during pre-participation screening in the presence of symptoms, family history of sudden cardiac death or cardiomyopathies <40-year-old, murmurs, abnormal ECG findings or in the follow-up of athletes with a history of cardiovascular disease (CVD). TTE is a cost-effective first-line imaging modality to evaluate the cardiac remodeling due to long-term, intense training, previously known as the athlete's heart, and to rule out the presence of conditions at risk of sudden cardiac death, including cardiomyopathies, coronary artery anomalies, congenital, aortic and heart valve diseases. Moreover, TTE is useful for distinguishing physiological cardiac adaptations during intense exercise from pathological behavior due to an underlying CVD. In this expert opinion statement endorsed by the Italian Society of Sports Cardiology, we discussed common clinical scenarios where a TTE is required and conditions falling in the grey zone between the athlete's heart and underlying cardiomyopathies or other CVD. In addition, we propose a minimum dataset that should be included in the report for the most common indications of TTE in sports cardiology clinical practice.

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.

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.