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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.

Left ventricular hypertrophy (LVH) is a frequent imaging finding in the general population. In order to identify the precise etiology, a comprehensive diagnostic approach should be adopted, including the prevalence of each entity that may cause LVH, family history, clinical, electrocardiographic and imaging findings. By providing a detailed evaluation of the myocardium, cardiovascular magnetic resonance (CMR) has assumed a central role in the differential diagnosis of left ventricular hypertrophy, with the technique of parametric imaging allowing more refined tissue characterization. This article aims to establish a parallel between pathophysiological features and imaging findings through the broad spectrum of LVH entities, emphasizing the role of CMR in the differential diagnosis.

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.

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: 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.

Introduction Whether obesity, a modifiable risk factor in patients with hypertrophic cardiomyopathy (HCM), can influence coronary microvascular dysfunction (CMD) is unknown. Objective To assess the relationship between body weight and CMD measured with myocardial blood flow (MBF) at positron emission tomography (PET) in patients with HCM. Methods All consecutive patients with HCM referred to PET scan from 2010 to 2020 were reviewed. Only patients with PET and cardiac magnetic resonance (CMR) analysis, Patients were classified into three groups according to baseline BMI: BMI30 kg/m2. Results Of 1512 patients with HCM, 134 (8.9%) had been referred to a PET scan and 79 (5.2%) met the inclusion criteria (29% were women, median age was 44 [28-53] years). Overall, 52% had a BMI30 kg/m2. At PET, average MBF was 2.08 [1.52-2.40] ml/min/g and was similar among BMI groups (p=0.288) irrespective of fibrosis at CMR. Prevalence of severe microvascular dysfunction was similar (MBF Conclusions Obesity is not associated with worsening of CMD in HCM patients. These findings support the hypothesis that the worse symptomatic profile in obese HCM patients is due to increased prevalence of obstruction rather than accentuation of structural phenotype. Thus, the symptomatic handicap associated with obesity may be reversible following appropriate weight-reduction strategies

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.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.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 common35 years (135/1124, 11%), but rare at 19-35 years (91/4442, 2%), very rare18 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.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.

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 diagnostic timing in transthyretin (TTR) cardiac amyloidosis (CA) predisposes patients to worse outcomes is unresolved. We aimed to describe the long-term association of diagnostic timing (time from first onset of symptoms consistent with CA leading to medical contact to definitive diagnosis) with mortality in patients with wild-type TTR-CA (ATTRwt-CA). Overall, we reviewed the medical records of 160 patients seen at a tertiary care amyloidosis unit from January 1, 2016, to January 1, 2020 (median [interquartile range] follow-up, 21 [10 to 34] months), and compared them by survival. Median diagnostic timing was 4 (2 to 12) months and was longer in nonsurvivors (9 [3 to 15] vs 3 [1 to 7] months; P.001). Patients diagnosed 6 or more months after symptom onset had higher mortality, with a median survival of 30 months (95% CI, 22 to 37 months). On Cox multivariable analysis, timing was independently associated with all-cause mortality (hazard ratio per month increase, 1.049 [95% CI, 1.017 to 1.083]) together with age at diagnosis, disease stage, New York Heart Association class, and coronary artery disease. In conclusion, diagnostic timing of ATTRwt-CA is associated with mortality. Timely diagnosis is warranted whenever "red flags" are present.

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Background Current understanding of the lifetime mortality of patients with hypertrophic cardiomyopathy (HCM) has been extrapolated from cohorts with 8–10 years follow-up. Real survival rates and long-term burden of HCM are largely unresolved. Objective To describe HCM lifetime mortality over 28-years of observation. Methods We analyzed clinical/instrumental data of the historic cohort of 202 patients diagnosed from 1970s. ECG, echocardiographic, clinical records until last follow-up were recorded. Reasons for death were classified as HCM related (Sudden Death (SD), Heart Failure related (HF)) and non-HCM related deaths. Results Patients were followed-up for 28±6 years (41±17 to 69±14 years), 63% were males. Patients progressively dilated the Left Atrium (40±6 to 50±9mm, p Conclusions HCM-related mortality at 10 years significantly underestimated the lifetime rates of HF death, which doubled in the second/third decade of observation. Conversely, SD rates remained constantly low. Real burden of HCM is time dependent and can be appreciated only after prolonged exposure to the disease. Funding Acknowledgement Type of funding source: None

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 and channelopathies are heterogeneous disorders that increase the risk of sudden cardiac death (SCD). Implantable cardioverter-defibrillator (ICD) therapy is safe and effective for preventing SCD in patients at risk for malignant ventricular arrhythmias. Because of the poor positive predictive value of current risk stratification tools, the majority of patients implanted with an ICD will never receive a life-saving therapy but will be exposed to the risk of complications such as device infection, lead failure and inappropriate therapy. Subcutaneous ICD (S-ICD) now constitutes a valuable alternative to conventional transvenous ICD in patients with cardiomyopathies and channelopathies as it provides protection from SCD while avoiding the risks of intravascular lead infection or failure. This may be particularly advantageous for young patients with a very long life expectancy. On the other hand, S-ICD cannot deliver antitachycardia pacing or antibradycardia pacing. The purpose of this article is to review the available evidence and the future perspectives of S-ICD therapy in patients with cardiomyopathies or channelopathies.

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.

Background MHealth technologies are revolutionizing cardiovascular medicine. However, a low-cost, user-friendly smartphone-based electrocardiograph is still lacking. D-Heart® is a portable device that enables the acquisition of the ECG on multiple leads which streams via Bluetooth to any smartphone. Because of the potential impact of this technology in low-income settings, we determined the accuracy of D-Heart® tracings in the stratification of ECG morphological abnormalities, compared with 12-lead ECGs. Methods Consecutive African patients referred to the Ziguinchor Regional Hospital (Senegal) were enrolled (n=117; 69 males, age 39±11years). D-Heart® recordings (3 peripheral leads plus V5) were obtained immediately followed by 12 lead ECGs and were assessed blindly by 2 independent observers. Global burden of ECG abnormalities was defined by a semi-quantitative score based on the sum of 9 criteria, identifying four classes of increasing severity. Results D-Heart® and 12-lead ECG tracings were respectively classified as: normal: 72 (61%) vs 69 (59%); mildly abnormal: 42 (36%) vs 45 (38%); moderately abnormal: 3 (3%) vs 3 (3%). None had markedly abnormal tracings. Cohen's weighted kappa (k w ) test demonstrated a concordance of 0,952 (p w =0,893; p Conclusions D-Heart® proved effective and accurate stratification of ECG abnormalities comparable to the 12-lead electrocardiographs, thereby opening new perspectives for low-cost community cardiovascular screening programs in low-income settings.

Background: Subcutaneous ICD (S-ICD) is a promising option for Hypertrophic Cardiomyopathy (HCM) patients at risk of Sudden Cardiac Death (SCD). However, its effectiveness in terminating ventricular arrhythmias in HCM is yet unresolved.Methods: Consecutive HCM patients referred for S-ICD implantation were prospectively enrolled. Patients underwent one or two attempts of VF induction by the programmer. Successful conversion was defined as any 65 J shock that terminated VF (not requiring rescue shocks). Clinical and instrumental parameterswere analyzed to study predictors of conversion failure.Results: Fifty HCMpatients (34males, 40 +/- 16 years) with amean BMI of 25.2 +/- 4.4 kg/m(2) were evaluated. Mean ESC SCD risk of was 6.5 +/- 3.9% and maximal LV wall thickness (LVMWT) was 26 +/- 6 mm. In 2/50 patients no arrhythmias were inducible, while in 7 (14%) only sustained ventricular tachycardia was induced and cardioverted. In the remaining 41 (82%) patients, 73 VF episodes were induced (1 episode in 14 and > 1 in 27 patients). Of these, 4 (6%) spontaneously converted. In 68/69 (98%) the S-ICD successfully cardioverted, but failed in 1 (2%) patient, who needed rescue defibrillation. This patient was severely obese (BMI 36) and LVMWT of 25 mm. VF was re-induced and successfully converted by the 80 J reversed polarity S-ICD.Conclusions: Acute DT at 65 J at the implant showed the effectiveness of S-ICD in the recognition and termination of VT/VF in all HCM patients except one. Extreme LVH did not affect the performance of the device, whereas severe obesity was likely responsible for the single 65 J failure. (C) 2017 Elsevier Ireland Ltd. All rights reserved.

Background Differential diagnosis of genetic causes of left ventricular hypertrophy (LVH) is crucial for disease-specific therapy. We aim to describe the prevalence of Cardiac Amyloidosis (CA) among patients ≥40 years with an initial diagnosis of HCM referred for second opinion to national cardiomyopathy centres. Methods Consecutive patients aged ≥40 years referred with a tentative HCM diagnosis in the period 2014–2017 underwent clinical evaluation and genetic testing for HCM (including trans-thyretin-TTR). Patients with at least one red flag for CA underwent blood/urine tests, abdominal fat biopsy and/or bone-scintigraphy tracing and eventually ApoAI sequencing. Results Out of 343 patients (age 60 ± 13 years), 251 (73%) carried a likely/pathogenic gene variant, including 12 (3.5%) in the CA-associated genes TTR (n = 11) and ApoAI (n = 1). Furthermore, 6 (2%) patients had a mutation in GLA. Among the remaining, mutation-negative patients, 26 with ≥1 CA red-flag were investigated further: 3 AL-CA and 17 wild-type-TTR-CA were identified. Ultimately, 32(9%) patients were diagnosed with CA. Prevalence of CA increased with age: 1/75 (1%) at age 40–49, 2/86 (2%) at age 50–59, 8/84 (9%) at age 60–69, 13/61 (21%) at age 70–79, 8/31 (26%) at age ≥80 (p for trend Conclusions Among patients referred with and initial diagnosis of HCM, CA was the most common unrecognized mimic (9% prevalence) and increased with age (from 1% at ages 40–49 years to 26% >80 years). Age at diagnosis should be considered one of the most relevant red flags for CA in patients with HCM phenotypes; however, there is no clear age cut-off mandating scintigraphy and other second level investigations in the absence of other features suggestive of CA.

Introduction The presence of sarcomere mutations is a powerful predictor of heart failure-related outcomes in Hypertrophic Cardiomyopathy (HCM). However, whether the prevalence of left ventricular (LV) dysfunction differs in patients with mutations in the two most prevalent HCM-associated genes (i.e. MYBPC3 and MYH7) is unclear. Purpose To ascertain lifetime trends in prevalence of LV dysfunction in HCM associated with pathogenic or likely-pathogenic MYBPC3 versus MYH7 mutations. Methods Clinical and instrumental records of 402 HCM patients with MYBPC3 (N=251) or MYH7 (N=151) mutations were retrospectively reviewed. Presence of systolic dysfunction (ejection fraction [EF] Results Patients were diagnosed at a mean age of 39±17 years and 63% were men. At first evaluation MYBPC3-HCM patients were less frequently obstructive (15% vs 26% in MYH7; p=0.005) and had lower LVEF (61±11% vs 64±9%; p=0.01). Prevalence of diastolic dysfunction increased with age and was lowest in MYBPC3 patients No significant differences were observed in terms of NYHA class change, atrial fibrillation, stroke, heart failure, appropriate ICD intervention or cardiovascular death. However, prevalence of NSVT was higher for MYBPC3 (39% vs 14% in MYH7, p In vitro cross-sectional evaluation of myocardial samples taken during septal myectomy at different ages showed a decline in contraction-relaxation properties after age 40 in MYPBC3 carriers, but preserved function in MYH7 patients (Figure). Kinetic of myosin cross-bridges Conclusions In HCM patients, mutations in the MYBPC3 gene and early diagnosis are associated with slowly progressing systolic impairment leading to overt dysfunction in 15% compared to 5% in MYH7-HCM. However, outcome was similar in the two subsets. These differences in lifetime myocardial performance between the two most common HCM-associated genes suggest diverse pathways of disease progression, potentially amenable to requiring different molecular approaches.

The pharmacological class of β-blockers includes a plea of molecules with largely different pharmacokinetic and pharmacodynamic characteristics with a protective effect that may span far beyond the cardiovascular system. Although all these compounds share the pharmacological blockade of the adrenergic receptors, each of them is characterized by specific pharmacological properties, including selectivity of action depending on the adrenergic receptors subtypes, intrinsic sympathomimetic activity (ISA), lipid solubility, pharmacokinetic profile, and also other ancillary properties that impact their clinical effect. Their use in the treatment of hypertension has been extensively debated and at the moment a class indication is not present. However, in specific niche of patients, such as in those young individuals in which hypertension is mainly driven by a sympathetic hyperactivation, strong evidence pose β-Blockers as a highly reasonable first-line treatment. Lipophilic β-blockers, specifically propranolol and metoprolol, can cross the Blood Brain Barrier and have a Class A indication for the prophylactic treatment of migraine attacks. Moreover, since β-adrenergic receptors affect the proliferative process of both cancer and immune cells, their blockade has been associated with metastasis reduction in several epithelial and solid organ tumors posing β-Blockers as a new attractive, inexpensive and relatively safe therapeutic strategy in patients with several types of cancer. However, further dedicated prospective, randomized, placebo-controlled studies are needed to determine the real efficacy of these compounds.

Genetic cardiomyopathies are complex diseases with heterogeneous clinical presentation and phenotypes. Early descriptions of cardiomyopathies originated from case studies involving individuals with severe, paradigmatic presentation, which provided insight into the worst-case scenarios of these conditions. With time, improved diagnostic sensitivity and awareness of cardiomyopathies has uncovered a more heterogeneous disease spectrum, including mild phenotypes overlapping with physiological variation. This diagnostic 'grey area' poses important dilemmas, particularly in athletes. Current screening policies have the potential to identify affected individuals at very early stages, leading to effective prevention of cardiomyopathy-related complications such as sudden cardiac death. Conversely, however, some physicians actively impose diagnoses on individuals who perceive themselves to be disease-free. In addition, the high sensitivity of contemporary diagnostic techniques carries a serious risk of misinterpreting physiological variation as disease. In this Review, three of the most common and controversial areas are discussed, including left ventricular hypertrophy; left ventricular dilatation, noncompaction, and fibrosis; and arrhythmias originating from the right ventricle. A systematic and cautious approach is necessary in patients with mild phenotypes suggestive of, but not definitely diagnostic for, cardiomyopathies. Preventing the mislabelling of healthy individuals and overdiagnosis should be a priority, with the aim to combine adequate counselling and optimal protection.

Due to an increasingly aging population, Alzheimer disease (AD) represents a crucial issue for the healthcare system because of its widespread prevalence and the burden of its care needs. Several hypotheses on AD pathogenesis have been proposed and current therapeutical strategies have shown limited effectiveness. In the last decade, more evidence has supported a role for neuroinflammation and immune system dysregulation in AD. It remains unclear whether astrocytes, microglia and immune cells influence disease onset, progression or both. Amyloid-β peptides that aggregate extracellularly in the typical neuritic plaques generate a constant inflammatory environment. This causes a prolonged activation of microglial and astroglial cells that potentiate neuronal damage and provoke the alteration of the blood brain barrier (BBB), damaging the permeability of blood vessels. Recent data support the role of the BBB as a link between neuroinflammation, the immune system and AD. Hence, a thorough investigation of the neuroinflammatory and immune system pathways that impact neurodegeneration and novel exciting findings such as microglia-derived microvesicles, inflammasomes and signalosomes will ultimately enhance our understanding of the pathological process. Eventually, we should proceed with caution in defining a causal or consequential role of neuroinflammation in AD, but rather focus on identifying its exact pathological contribution.

Aims Exercise performance is known to predict outcome in hypertrophic cardiomyopathy (HCM), but whether sex-related differences exist is unresolved. We explored whether functional impairment, assessed by exercise echocardiography, has comparable predictive accuracy in females and males with HCM. Methods We retrospectively evaluated 292 HCM patients (46 ± 16 years, 72% males), consecutively referred for exercise echocardiography; 242 were followed for 5.9 ± 4.2 years. Results Peak exercise capacity was 6.5 ± 1.6 metabolic equivalents (METs). Sixty patients (21%) showed impaired exercise capacity (≤5 METs). Exercise performance was reduced in females, compared with males (5.6 ± 1.6 vs 6.9 ± 1.5 METs, p 50 years of age. At multivariable analysis, female sex was independently associated with impaired exercise capacity (odds ratio: 4.67; 95% confidence interval (CI): 1.83–11.90; p = 0.001). During follow-up, 24 patients (10%) met the primary endpoint (a combination of cardiac death, heart failure requiring hospitalization, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator discharge, resuscitated sudden cardiac death and cardioembolic stroke). Event-free survival was reduced in females (p = 0.035 vs males). Peak METs were inversely related to outcome in males (hazard ratio (HR) per unit increase: 0.57; 95% CI: 0.39–0.84; p = 0.004) but not in females (HR: 1.22; 95% CI: 0.66–2.24; p = 0.53). Conclusions Female patients with HCM showed significant age-related impairment in functional capacity compared with males, particularly evident in post-menopausal age groups. While women were at greater risk of HCM-related complications and death, impaired exercise capacity predicted adverse outcome only in men. These findings suggest the need for sex-specific management strategies in HCM.

BACKGROUND: Subcutaneous implantable cardioverter-defibrillator (S-ICD) is a promising option for patients with hypertrophic cardiomyopathy (HCM). Patients with HCM can present markedly abnormal electrocardiograms (ECGs), and there are no data on what percentage of patients with HCM fail the prerequisite S-ICD vector screening. OBJECTIVE: The purpose of this study was to determine the failure rate of the prerequisite vector screening using 1 or 2 acceptable vectors stratified for risk profile for sudden cardiac death and predictors of failure. METHODS: ECG recordings from consecutive patients with HCM simulating the S-ICD sensing vectors were analyzed with the S-ICD screening tool. Eligibility was defined by 1 or 2 appropriate vectors. Medical history, ultrasound characteristics, and 12-lead ECG characteristics were analyzed and the individual arrhythmic risk at 5 year was determined to study potential predictors of failure. RESULTS: One hundred sixty-five (118 men; mean age 51 ± 16 years) patients were analyzed. Twenty-two patients (13%) had a high risk of sudden cardiac death, 33 (20%) had intermediate to high risk, and 110 (67%) had low risk. Twenty-six patients (16%) had no suitable vector, including 8 of 22 high-risk patients (36%). The primary cause of failure was high T-wave voltages in 25% of the vectors analyzed. T-wave inversions in >2 leads on the surface 12-lead ECG (odds ratio 15.6; 95% confidence interval 4.9-50.3; P < .001) and prior myectomy (odds ratio 8.4; 95% confidence interval 2.1-33.1; P = .002) were significantly associated with screening failure in a multivariable model. CONCLUSION: Currently available preimplant screening algorithms recommended by the manufacturer are associated with a significant failure rate in patients with HCM, particularly in the high-risk subgroup.

D-Heart® is a portable, smartphone-based device, which streams tracing via Bluetooth, enabling multiple leads electrocardiograms (ECGs) acquisition, currently used in human cardiology. The aim was to determine the accuracy of D­Heart® compared with the gold standard non­portable 6­lead electrocardiograph in the evaluation of cardiac rhythm in dogs. Standard 6­lead and D­Heart® ECGs were acquired in conscious dogs. Concordance between methods was assessed by weighted k Cohen index, with its relative significance, taking as end point variable standard 6­lead ECG group. Bland ­ Altman method (95% confidence level) was applied for P, PR, QRS, T and QT. Since differences didn’t follow a normal distribution, a non­parametric approach was used to determine limits of agreement. P was significant when < 0.05. Amplitude of waves was not considered because currently the software doesn’t allow voltage variation. 115 dogs of different weights and breeds admitted to the Cardiology Service of DIMEVET were enrolled. Mean age was 7,5±4 years. Most were intact males (45%, n=51). The most represented breed was mongrel (27%, n=32). Weighted Cohen's kappa test demonstrated excellent concordance in the evaluation of the heart rhythm (0.989, p, International Journal of Health, Animal Science and Food Safety, V. 4, N. 1s (2017)

Importance Diagnostic screening for Anderson-Fabry cardiomyopathy (AFC) is performed in the presence of specific clinical red flags in patients with hypertrophic cardiomyopathy (HCM) older than 25 years. However, left ventricular outflow tract obstruction (LVOTO) has been traditionally considered an exclusion criteria for AFC. Objective To examine a series of patients diagnosed with HCM and severe basal LVOTO undergoing myectomy in whom the diagnosis of AFC was suspected by the cardiac surgeon intraoperatively and confirmed by histological and genetic examinations. Design, Setting, and Participants This retrospective analysis of patients undergoing surgical septal reduction strategies was conducted in 3 European tertiary referral centers for HCM from July 2013 to December 2016. Patients with a clinical diagnosis of obstructive HCM referred for surgical management of LVOTO were observed for at least 18 months after the procedure (mean [SD] follow-up, 33 [14] months). Main Outcomes and Measures Etiology of patients with HCM who underwent surgical myectomy. Results From 2013, 235 consecutive patients with a clinical diagnosis of HCM underwent septal myectomy. The cardiac surgeon suspected a storage disease in 3 patients (1.3%) while inspecting their heart samples extracted from myectomy. The mean (SD) age at diagnosis for these 3 patients was 42 (4) years; all were male. None of the 3 patients presented with extracardiac features suggestive of AFC. All patients showed asymmetrical left ventricular hypertrophy, with maximal left ventricular thickness in the basal septum (19-31 mm), severe basal LVOTO (70-120 mm Hg), and left atrial dilatation (44-57 mm). Only 1 patient presented with late gadolinium enhancement on cardiovascular magnetic resonance at the right ventricle insertion site. The mean (SD) age at surgical procedure was 63 (5) years. On tactile sensation, the surgeon felt a spongy consistency of the surgical samples, different from the usual stony-elastic consistency typical of classic HCM, and this prompted histological examinations. Histology showed evidence of intracellular storage, and genetic analysis confirmed a GLA A gene mutation (p.Asn215Ser) in all 3 patients. Conclusions and Relevance Screening for AFC should be performed even in the absence of red flags in patients with HCM older than 25 years.