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Transthyretin (TTR) is a tetrameric protein synthesized mostly by the liver. As a result of gene mutations or as an ageing-related phenomenon, TTR molecules may misfold and deposit in the heart and in other organs as amyloid fibrils. Cardiac involvement in TTR-related amyloidosis (ATTR) manifests typically as left ventricular pseudohypertrophy and/or heart failure with preserved ejection fraction. ATTR is an underdiagnosed disorder as well as a crucial determinant of morbidity and mortality, thus justifying the current quest for a safe and effective treatment. Therapies targeting cardiac damage and its direct consequences may yield limited benefit, mostly related to dyspnoea relief through diuretics. For many years, liver or combined heart and liver transplantation have been the only available treatments for patients with mutations causing ATTR, including those with cardiac involvement. The therapeutic options now include several pharmacological agents that inhibit hepatic synthesis of TTR, stabilize the tetramer, or disrupt fibrils. Following the positive results of a phase 3 trial on tafamidis, and preliminary findings on patisiran and inotersen in patients with ATTR-related neuropathy and cardiac involvement, we provide an update on this rapidly evolving field, together with practical recommendations on the management of cardiac involvement., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objective: To investigate differences in cardiac manifestations of patients affected by laminopathy, according to the presence or absence of neuromuscular involvement at presentation., Methods: We prospectively analyzed 40 consecutive patients with a diagnosis of laminopathy followed at a single centre between 1998 and 2017. Additionally, reports of clinical evaluations and tests prior to referral at our centre were retrospectively evaluated., Results: Clinical onset was cardiac in 26 cases and neuromuscular in 14. Patients with neuromuscular presentation experienced first symptoms earlier in life (11 vs 39 years; p <  0.0001) and developed atrial fibrillation/flutter (AF) and required pacemaker implantation at a younger age (28 vs 41 years [p = 0.013] and 30 vs 44 years [p = 0.086] respectively), despite a similar overall prevalence of AF (57% vs 65%; p = 0.735) and atrio-ventricular (A-V) block (50% vs 65%; p = 0.500). Those with a neuromuscular presentation developed a cardiomyopathy less frequently (43% vs 73%; p = 0.089) and had a lower rate of sustained ventricular tachyarrhythmias (7% vs 23%; p = 0.387). In patients with neuromuscular onset rhythm disturbances occurred usually before evidence of cardiomyopathy. Despite these differences, the need for heart transplantation and median age at intervention were similar in the two groups (29% vs 23% [p = 0.717] and 43 vs 46 years [p = 0.593] respectively)., Conclusions: In patients with laminopathy, the type of disease onset was a marker for a different natural history. Specifically, patients with neuromuscular presentation had an earlier cardiac involvement, characterized by a linear and progressive evolution from rhythm disorders (AF and/or A-V block) to cardiomyopathy.

Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized. In this paper, Part 2 of a series, a panel of international experts from multiple societies define the diagnostic criteria for cardiac amyloidosis and appropriate utilization of echocardiography, cardiovascular magnetic resonance imaging, and radionuclide imaging in the evaluation of patients with known or suspected cardiac amyloidosis., (Copyright © 2019. Published by Elsevier Inc.)

: Regular physical activity is a cornerstone in the prevention and treatment of atherosclerotic cardiovascular disease (CVD) due to its positive effects in reducing several cardiovascular risk factors. Current guidelines on CVD suggest for healthy adults to perform at least 150 min/week of moderate intensity or 75 min/week of vigorous intensity aerobic physical activity. The current review explores the effects of physical activity on some risk factors, specifically: diabetes, dyslipidemia, hypertension and hyperuricemia. Physical activity induces an improvement in insulin sensitivity and in glucose control independently of weight loss, which may further contribute to ameliorate both diabetes-associated defects. The benefits of adherence to physical activity have recently proven to extend beyond surrogate markers of metabolic syndrome and diabetes by reducing hard endpoints such as mortality. In recent years, obesity has greatly increased in all countries. Weight losses in these patients have been associated with improvements in many cardiometabolic risk factors. Strategies against obesity included caloric restriction, however greater results have been obtained with association of diet and physical activity. Similarly, the beneficial effect of training on blood pressure via its action on sympathetic activity and on other factors such as improvement of endothelial function and reduction of oxidative stress can have played a role in preventing hypertension development in active subjects. The main international guidelines on prevention of CVD suggest to encourage and to increase physical activity to improve lipid pattern, hypertension and others cardiovascular risk factor. An active action is required to the National Society of Cardiology together with the Italian Society of Sports Cardiology to improve the prescription of organized physical activity in patients with CVD and/or cardiovascular risk factors.

Background: Although imaging techniques have demonstrated the existence of microvascular abnormalities in hypertrophic cardiomyopathy (HCM), a detailed histopathological assessment is lacking as well as a comparison between different phases of the disease. We aimed to compare microvasculopathy and myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) versus end-stage (ES) HCM., Methods: 27 myectomy specimens of HOCM patients and 30 ES-HCM explanted hearts were analyzed. Myocardial fibrosis was quantitatively determined with dedicated software and qualitatively classified as scar-like or interstitial. Intramural coronary arteries were evaluated separately according to lumen diameter: 100-500 μ versus <100 μ. Microvasculopathy assessment included the description of medial and intimal abnormalities and stenosis grading. The two subgroups were compared considering only the anterobasal septum of ES explanted hearts., Results: Median value of fibrosis in the anterobasal septum of explanted hearts was 34.6% as opposed to 10.3% of myectomy specimens (p < 0.001). Scar-like fibrosis was widely found in ES hearts while interstitial fibrosis was distinctive of HOCM (p < 0.001). All slides showed 100-500 μ microvasculopathy without any differences between subgroups in terms of lumen narrowing, extent of the disease and type of parietal involvement. Among ES hearts these lesions were associated with scar-like fibrosis (p = 0.034). <100-μ microvasculopathy was also frequent with no differences between subgroups., Conclusions: Microvasculopathy is an intrinsic feature of HCM with similar characteristics across the natural phases of the disease. Conversely, myocardial fibrosis changes over time with ES hearts showing a three-fold greater amount, mainly scar-like. ES showed a closer association between microvasculopathy and replacement fibrosis., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

New therapeutic strategies aimed to tackle the rising socio-economic burden of heart failure (HF) have become an impelling priority. The new pharmacological class of angiotensin (Ang) receptor-neprilysin inhibitors (ARNI) prompted a real conceptual change in the treatment of HF moving from only the inhibition of the renin-Ang-aldosterone system and sympathetic nervous system to a strategy based on the concomitant pharmacological enhancement of endogenous natriuretic peptides. Sacubitril/valsartan, a first-in-class ARNI, has reduced the primary composite endpoint of cardiovascular death or HF hospitalisation, sudden cardiac death, disease progression and improved quality of life, compared with enalapril, in patients on evidence-based contemporary medical therapy. Our review underlines the increasing body of evidence supporting the efficacy of sacubitril/valsartan, which may be considered a new disease-modifying therapy and, after about 30 years of research, a real step forward in HF pharmacological therapy.

Cardiomyopathy is a manifestation of transthyretin amyloidosis (ATTR), which is an underrecognized systemic disease whereby the transthyretin protein misfolds to form fibrils that deposit in various tissues and organs. ATTR amyloidosis is debilitating and associated with poor life expectancy, especially in those with cardiac dysfunction, but a variety of treatment options have recently become available. Considered a rare disease, ATTR amyloidosis may be more prevalent than thought, particularly in older persons. Diagnosis is often delayed because of a lack of disease awareness and the heterogeneity of symptoms at presentation. Given the recent availability of effective treatments, early recognition and diagnosis are especially critical because treatment is likely more effective earlier in the disease course. The Amyloidosis Research Consortium recently convened a group of experts in ATTR amyloidosis who, through an iterative process, agreed on best practices for suspicion, diagnosis, and characterization of disease. This review describes these consensus recommendations for ATTR associated with cardiomyopathy as a resource to aid cardiologists and others in the recognition and diagnosis of ATTR associated with cardiomyopathy. Included in this review is an overview of red flag signs and symptoms and a recommended diagnostic approach, including testing for monoclonal protein, scintigraphy, or biopsy and, if ATTR associated with cardiomyopathy is identified, TTR genotyping.

Timely diagnosis of hereditary variant transthyretin (ATTRv) amyloidosis is critical for appropriate treatment and optimal outcomes. Significant differences are seen between patients receiving treatment and those who are not, though disease progression may continue despite treatment in some patients. Healthcare professionals caring for patients with ATTRv amyloidosis therefore need reliable ongoing assessments to understand the continuing course of disease and make appropriate treatment choices on an individual basis. Various signs and symptoms experienced by patients may be evaluated as indicators of disease progression, though there is currently no validated score that can be used for such ongoing assessment. Recognizing this situation, a group of clinicians highly experienced in ATTR amyloidosis developed an approach to understand and define disease progression in diagnosed and treated patients with ATTRv amyloidosis. The suggested approach is based on the recognition of distinct phenotypes which may usefully inform the particular tools, tests and investigations that are most likely to be appropriate for individual patients. It is aimed at implementing appropriate and ongoing assessment of patients being treated for ATTRv amyloidosis, such that the effectiveness of management can be usefully assessed throughout the course of disease and management can be tailored according to the patient's requirements.

Myocarditis is an inflammatory disease of the myocardium, which may occur in isolation or as part of systemic infectious/immune/autoimmune conditions, characterized by vast aetiologic, clinical and histopathologic heterogeneity. The broad spectrum of myocarditis can be categorized according to the prevalent histopathologic pattern including lymphocytic, lympho-histiocytic, eosinophilic and neutrophilic forms, giant cell myocarditis and myocarditis with granulomata. Diverse histopathologic substrates generally reflect different aetiologies and pathogenetic mechanisms and may be critical to clinical decision-making. Active vasculitis, when present, completes the inflammatory spectrum. Unfortunately, the correlation of histopathologic patterns, clinical presentation and disease course in myocarditis is still largely unresolved, due to limited availability of bioptic samples at specific stages of disease and impracticality of serial sampling. We here review the elements supporting an aetiology-driven diagnostic work-up in myocarditis, emphasizing the importance of integrating pathologic studies with clinical features and information derived from multimodality imaging. Furthermore, we explore myocardial inflammation in genetic cardiomyopathies, its role in driving clinical variability and the potential of transcriptomic and proteomic analysis in our understanding of these complex interrelations.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening, progressive, infiltrative disease caused by the deposition of transthyretin amyloid fibrils in the heart, and can often be overlooked as a common cause of heart failure. Delayed diagnosis due to lack of disease awareness and misdiagnosis results in a poorer prognosis. Early accurate diagnosis is therefore key to improving patient outcomes, particularly in the context of both the recent approval of tafamidis in some countries (including the United States) for the treatment of ATTR-CM, and of other promising therapies under development. With the availability of scintigraphy as an inexpensive, noninvasive diagnostic tool, the rationale to screen for ATTR-CM in high-risk populations of patients is increasingly warranted. Here the authors propose a framework of clinical scenarios in which screening for ATTR-CM is recommended, as well as diagnostic "red flags" that can assist in its diagnosis among the wider population of patients with heart failure., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and ∼10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Objective: In 2014, the European Society of Cardiology (ESC) recommended the use of a novel risk prediction model (HCM Risk-SCD) to guide use of implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We sought to determine the performance of HCM Risk-SCD by conducting a systematic review and meta-analysis of articles reporting on the prevalence of SCD within 5 years of evaluation in low, intermediate and high-risk patients as defined by the 2014 guidelines (predicted risk <4%, 4%-<6% and ≥6%, respectively)., Methods: The protocol was registered with PROSPERO (registration number: CRD42017064203). MEDLINE and manual searches for papers published from October 2014 to December 2017 were performed. Longitudinal, observational cohorts of unselected adult patients, without history of cardiac arrest were considered. The original HCM Risk-SCD development study was included a priori. Data were pooled using a random effects model., Results: Six (0.9%) out of 653 independent publications identified by the initial search were included. The calculated 5-year risk of SCD was reported in 7291 individuals (70% low, 15% intermediate; 15% high risk) with 184 (2.5%) SCD endpoints within 5 years of baseline evaluation. Most SCD endpoints (68%) occurred in patients with an estimated 5-year risk of ≥4% who formed 30% of the total study cohort. Using the random effects method, the pooled prevalence of SCD endpoints was 1.01% (95% CI 0.52 to 1.61) in low-risk patients, 2.43% (95% CI 1.23 to 3.92) in intermediate and 8.4% (95% CI 6.68 to 10.25) in high-risk patients., Conclusions: This meta-analysis demonstrates that HCM Risk-SCD provides accurate risk estimations that can be used to guide ICD therapy in accordance with the 2014 ESC guidelines., Registration Number: PROSPERO CRD42017064203;Pre-results., Competing Interests: Competing interests: MMA reports being supported by an unrestricted educational grant from Sanofi Genzyme, outside the submitted work. LM is an employee and a stakeholder of Health in Code SL. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Far from only being a modern disease, atherosclerosis has also been reported also in ancient civilizations, as shown in some studies conducted on Mummies from different latitudes. Conventional cardiovascular (CV) risk factors can explain more than 90% of the attributable risk of coronary artery disease (CAD). In this regard, Tsimane Aborigenous of Amazon rainforest, conducting a subsistence lifestyle with low prevalence of CV risk factors, present the lowest reported prevalence of CAD in the world, despite an elevated inflammatory burden. Experimental and clinical studies have supported the theory that other factors, like genetics and inflammation, are involved in atherosclerosis. Indeed, a large clinical randomized study (CANTOS trial) tested the anti-inflammatory properties of canakinumab, and provided the first evidence to support the 'inflammation hypothesis'. Another field of research, based on Mendelian randomization studies, supports the appealing hypothesis that correcting CV risk factors earlier in life, may prevent or delay the progression of CAD. All these data prove that atherosclerosis is the expression of a complex, dynamic, and continuous interaction between environment and genetics that begins at conception and continues through adulthood.

Background:: The role of thrombus aspiration plus primary percutaneous coronary intervention in ST-segment elevation myocardial infarction remains controversial., Methods:: We performed a meta-analysis of 25 randomised controlled trials in which 21,740 ST-segment elevation myocardial infarction patients were randomly assigned to thrombus aspiration plus primary percutaneous coronary intervention or primary percutaneous coronary intervention. Study endpoints were: death, myocardial infarction, stent thrombosis and stroke., Results:: On pooled analysis, the risk of death (4.3% vs. 4.8%, odds ratio (OR) 0.90, 95% confidence interval (CI) 0.79-1.03; P=0.123), myocardial infarction (2.4% vs. 2.5%, OR 0.95, 95% CI 0.80-1.13; P=0.57) and stent thrombosis (1.3% vs. 1.6%, OR 0.80, 95% CI 0.63-1.01; P=0.066) was similar between thrombus aspiration plus primary percutaneous coronary intervention and primary percutaneous coronary intervention. The risk of stroke was higher in the thrombus aspiration plus primary percutaneous coronary intervention than the primary percutaneous coronary intervention group (0.84% vs. 0.59%, OR 1.401, 95% CI 1.004-1.954; P=0.047). However, on sensitivity analysis after removing the TOTAL trial, thrombus aspiration plus primary percutaneous coronary intervention was not associated with an increased risk of stroke (OR 1.01, 95% CI 0.58-1.78). The weak association between thrombus aspiration and stroke was also confirmed by the fact that the lower bound of the 95% CI was slightly below unity after removing either the study by Kaltoft or the ITTI trial. There was no interaction between the main study results and follow-up, evidence of coronary thrombus, or study sample size., Conclusions:: In patients with ST-segment elevation myocardial infarction, thrombus aspiration plus primary percutaneous coronary intervention does not reduce the risk of death, myocardial infarction or stent thrombosis. Thrombus aspiration plus primary percutaneous coronary intervention is associated with an increased risk of stroke; however, this latter finding appears weak.

Aim: We carried out this study to investigate mid-term effects of cardiac resynchronization therapy (CRT) on right ventricular (RV) function and neurohormonal response, expressed by N-terminal pro-brain natriuretic peptide (NT-proBNP), in heart failure patients stratified by baseline RV ejection fraction (RVEF)., Methods and Results: Thirty-six patients with nonischemic dilated cardiomyopathy underwent technetium-99m radionuclide angiography with bicycle exercise immediately after CRT implantation (during spontaneous rhythm and after CRT activation) and 3 months later. Plasma NT proBNP was assessed before implantation and after 3 months. At baseline, RVEF was impaired (≤35%) in 14 patients, preserved (>35%) in 22. At 3 months, RVEF improved during rest and exercise (P = .02) in patients with impaired RV function, while remaining unchanged in patients with preserved RV function. Rest and exercise RV dyssynchrony decreased in both groups at follow-up (P < .05). A similar mid-term improvement in left ventricular (LV) function and NT-proBNP was observed in patients with impaired and preserved RVEF. In the former, the decrease in NT-proBNP correlated with the improvements both in LV and RV dyssynchrony and functions., Conclusion: CRT may improve RV performance, during rest and exercise, and neurohormonal response in heart failure patients with nonischemic dilated cardiomyopathy and baseline RV dysfunction. RV dysfunction should not be considered per se a primary criterion for excluding candidacy to CRT.

Cardiac amyloidosis, once considered untreatable, is now gaining well-deserved attention due to advances in imaging and the recent approval of targeted breakthrough therapies. In this paper, we discuss the role of radionuclide imaging in the evaluation and management of patients with the most common form of amyloidosis-cardiac transthyretin amyloidosis (ATTR). We provide a comprehensive summary of the literature interspersed with our institutional experience as appropriate, to deliver our perspective.

Objectives: The study objectives were to describe the aortic histopathologic substrates in patients with type A surgically treated acute aortic syndromes, to provide clinico-pathological correlations, and to identify the possible prognostic role of histology., Methods: We assessed the aortic wall degenerative or inflammatory alterations of 158 patients according to the histopathologic consensus documents. Moreover, we correlated these histologic patterns with the patients' clinical data and long-term follow-up for mortality, major aorta-related events, and nonaorta-related events (including cardiovascular ones)., Results: We identified 2 histopathologic patterns: 122 patients (77%) with degenerative alterations and 36 patients (23%) with mixed degenerative-atherosclerotic lesions. Patients with mixed alterations were older (mean 69.6 ± 8.7 years vs 62.2 ± 12.4 years, P = .001) and more hypercholesterolemic (33.3% vs 13.9%, P = .017). The degenerative subgroup showed more intralamellar-mucoid extracellular matrix accumulation (86% vs 66.7%, P = .017) and a lower prevalence of translamellar collagen increase (9.8% vs 50%, P < .001). Patients with mixed degenerative-atherosclerotic abnormalities more frequently had long-term nonaorta-related events compared with those with degenerative abnormalities alone (P = .046); no differences were found between the groups with respect to mortality, major aorta-related events, and cardiovascular nonaorta-related events., Conclusions: Although degenerative lesions of the medial layer were present in all specimens, substantial atherosclerosis coexisted in approximately one quarter of cases. Patients with mixed degenerative-atherosclerotic abnormalities had a coherent clinical risk profile, a clinical presentation frequently mimicking acute coronary syndrome, and a higher incidence of nonaorta-related events during follow-up. Histopathologic characterization may improve the long-term prognostic stratification of patients after surgical treatment., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Aims: Cardiac amyloidosis remains a great challenge for the cardiologist. One of the three main aetiological forms, transthyretin-related hereditary amyloidosis (ATTRm), can present with several phenotypes, depending mainly on the specific mutation. We aimed to characterize the phenotype of patients with ATTRm due to Ile68Leu mutation, comparing them to patients with wild-type transthyretin amyloidosis (ATTRwt)., Methods and Results: Data of 67 Ile68Leu ATTRm patients from two Italian referral centres (Bologna and Florence) were retrospectively analysed and compared to those of 82 ATTRwt patients. Fifty-five unaffected mutation carriers were also analysed. Cumulative disease onset was 50% at age 71. A total of 56/67 (84%) patients had a predominantly cardiac phenotype at presentation with concentric increase in left ventricular wall thickness [median 17 mm], and normal or near normal left ventricular ejection fraction (79% of patients). Low QRS voltages were present only in 29% of patients but voltage/mass ratio was low (0.5). Carpal tunnel syndrome was noted in 43%. The overall phenotypic profile was similar to ATTRwt but Ile68Leu ATTRm patients typically presented younger (median 71 vs. 78 years) and were more likely to have (mild) symptomatic neurological involvement (19% vs. 2%). Male prevalence was 44% in unaffected mutation carriers and 78% in affected patients. Age-adjusted survival was comparable between groups., Conclusions: Ile68Leu ATTRm is a cause of familial amyloidotic cardiomyopathy endemic in central-northern Italy and presents as hypertrophic/restrictive cardiomyopathy quite similar to ATTRwt. Male preponderance is present in affected patients but not in unaffected mutation carriers. Age-adjusted survival is similar to ATTRwt., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Background: Transthyretin amyloid cardiomyopathy is caused by the deposition of transthyretin amyloid fibrils in the myocardium. The deposition occurs when wild-type or variant transthyretin becomes unstable and misfolds. Tafamidis binds to transthyretin, preventing tetramer dissociation and amyloidogenesis., Methods: In a multicenter, international, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 441 patients with transthyretin amyloid cardiomyopathy in a 2:1:2 ratio to receive 80 mg of tafamidis, 20 mg of tafamidis, or placebo for 30 months. In the primary analysis, we hierarchically assessed all-cause mortality, followed by frequency of cardiovascular-related hospitalizations according to the Finkelstein-Schoenfeld method. Key secondary end points were the change from baseline to month 30 for the 6-minute walk test and the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS), in which higher scores indicate better health status., Results: In the primary analysis, all-cause mortality and rates of cardiovascular-related hospitalizations were lower among the 264 patients who received tafamidis than among the 177 patients who received placebo (P<0.001). Tafamidis was associated with lower all-cause mortality than placebo (78 of 264 [29.5%] vs. 76 of 177 [42.9%]; hazard ratio, 0.70; 95% confidence interval [CI], 0.51 to 0.96) and a lower rate of cardiovascular-related hospitalizations, with a relative risk ratio of 0.68 (0.48 per year vs. 0.70 per year; 95% CI, 0.56 to 0.81). At month 30, tafamidis was also associated with a lower rate of decline in distance for the 6-minute walk test (P<0.001) and a lower rate of decline in KCCQ-OS score (P<0.001). The incidence and types of adverse events were similar in the two groups., Conclusions: In patients with transthyretin amyloid cardiomyopathy, tafamidis was associated with reductions in all-cause mortality and cardiovascular-related hospitalizations and reduced the decline in functional capacity and quality of life as compared with placebo. (Funded by Pfizer; ATTR-ACT ClinicalTrials.gov number, NCT01994889 .).

We evaluated the performance of 3 different left ventricular leads (LV) for resynchronization therapy: bipolar (BL), quadripolar (QL) and active fixation leads (AFL). We enrolled 290 consecutive CRTD candidates implanted with BL (n = 136) or QL (n = 97) or AFL (n = 57). Over a minimum 10 months follow-up, we assessed: (a) composite technical endpoint (TE) (phrenic nerve stimulation at 8 V@0.4 ms, safety margin between myocardial and phrenic threshold <2V, LV dislodgement and failure to achieve the target pacing site), (b) composite clinical endpoint (CE) (death, hospitalization for heart failure, heart transplantation, lead extraction for infection), (c) reverse remodeling (RR) (reduction of end systolic volume >15%). Baseline characteristics of the 3 groups were similar. At follow-up the incidence of TE was 36.3%, 14.3% and 19.9% in BL, AFL and QL, respectively (p < 0.01). Moreover, the incidence of RR was 56%, 64% and 68% in BL, AFL and QL respectively (p = 0.02). There were no significant differences in CE (p = 0.380). On a multivariable analysis, "non-BL leads" was the single predictor of an improved clinical outcome. QL and AFL are superior to conventional BL by enhancing pacing of the target site: AFL through prevention of lead dislodgement while QL through improved management of phrenic nerve stimulation.

We sought to investigate the prognostic significance of prodromal angina (PA) in unselected patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) and its additive predictive value to the GRACE score.We prospectively enrolled 3015 consecutive STEMI patients undergoing PPCI. Patients were divided in 2 groups according to the presence or absence of PA. Multivariable Cox regression was used to establish the relation to 2-year cardiac mortality of PA.The mean age of the study population was 68 (±14) years; 2178 patients (72%) were male. During follow-up, 395 (13%) patients died with 278 of these (9.2%) suffering from cardiac mortality. Kaplan-Meier estimates showed a survival rate of 95% and 87% for patients with PA and no PA, respectively (log rank test < 0.001). After multivariable analysis, patients with PA had still a lower risk of 2 years' cardiac mortality compared with patients without PA (adjusted hazard ratio = 0.50; 95% confidence interval [CI] 1.06-1.81, P = .001). Evaluation of net reclassification improvement showed that reclassification improved by 0.16% in case patients, whereas classification worsened in control patients by 1.08% leading to a net reclassification improvement of -0.93% (95% CI: -0.98, -0.88).In patients with STEMI undergoing PPCI the presence of PA is independently associated with a lower risk of 2-year cardiac mortality. However, the incorporation of this variable to the GRACE score slightly worsened the classification of risk. Accordingly, it seems unlikely that the evaluation of PA may be useful in clinical practice.

Oculomeningovascular amyloidosis is a variant of transthyretin (TTR) amyloidotic polyneuropathy, which is associated with blindness and brain ischemia, microhemorrages, and siderosis due to prominent production of the abnormal TTR in the eye and in the choroid plexuses. Tafamidis is a TTR stabilizer that is orally administered and, by interfering with amyloid fibril formation and deposition, is capable of slowing progression of TTR polyneuropathy and of early-stage cardiomyopathy. However, the ocular manifestations of amyloid deposition progressed despite tafamidis therapy in Val30Met TTR amyloidosis, and the effects of tafamidis on meningovascular amyloidosis are unknown. We observed failure of tafamidis to halt progression of oculomeningovascular amyloid deposition in a patient with familial Ala36Pro TTR amyloidosis. She received molecular diagnosis at age 24 and presented at age 26 with paresthesias of the lower limbs and bowel dysfunction. Echography showed minimal amyloid opacities in the corpus vitreum. Treatment with tafamidis meglumine was started. Sixteen months later, she complained of severe headache followed by left hemiparesthesias and numbness lasting 20 minutes. Magnetic resonance imaging showed multiple focal and diffuse hemosiderin deposits compatible with microbleeds and early siderosis. Echography showed a marked increase of "vitreal opacities." Our observation confirms that tafamidis fails in halting increase of vitreal amyloid deposits and indicates that it is presumably ineffective in preventing clinical onset due to progression of meningovascular amyloidosis. These failures may be due to the incapability of tafamidis to cross the blood-retina and blood-brain barriers. Therapeutic options targeting oculomeningovascular TTR amyloidoses in humans are required., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: The aim was to assess the long-term outcome of patients diagnosed with type A and type B acute aortic syndromes (AAS) and the mortality risk predictors., Methods: A single centre retrospective observational study was performed on consecutive patients diagnosed with AAS and discharged between 2000 and 2016: 242 surgically treated type A, 87 uncomplicated, medically treated type B, and 80 complicated type B who received endovascular/surgical/hybrid treatment. Follow up of discharged patients (5 ± 3.9 years) was almost complete by the end of the study (December 2017)., Results: The mean age was 65.3 ± 12.5 years, and 70.2% were men. Long-term all cause mortality was 5.4 per 100 patients per year in surgically treated type A AAS patients and 6.7 per 100 patients per year in type B AAS patients (p = .236). The rates of major aorta related events were 6.1 per 100 patients per year and 13.4 per 100 patients per year, respectively (p < .001). Non-aorta related events during long-term follow up occurred in 18.2 per 100 patients per year in type A and 13.8 per 100 patients per year in type B (p = .055). At the end of follow up 279/409 (68.2%) patients (165/242 type A and 114/167 type B) experienced at least one event., Conclusions: Among patients with either type A or type B AAS surviving the acute phase, the risk of adverse aorta and non-aorta related events, including death, persists during follow up, so that eventually two thirds of patients will experience at least one event. Notably, all cause mortality after type B AAS exceeds that of type A AAS after three years., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Aims: We explored the possible predictors of long-term prognosis after transvenous lead extraction (TLE) for a cardiac implantable device related infection (CIEDI), including the modified Duke score result., Methods and Results: We performed a single centre prospective observational study in a population of consecutive patients referred for TLE to a teaching hospital to treat a CIEDI without associated valve-endocarditis. 121 patients were enrolled between January 2012 and March 2016. According to the modified Duke criteria, the presence of CIED-related endocarditis was rejected in 54.5%, possible in 21.5%, and definite in 24.0%. 20/121 patients died after a mean follow-up of 46.0 ± 2.5 months, while 7 patients reported hospitalization for CIEDI recurrence/relapse in the same period. Modified Duke score was significantly associated with a poor prognosis at univariate Cox regression analysis (HR 1.847, 95% CI 1.160-2.941; P = 0.010). However, the three factors independently associated with death and/or CIEDI relapse/recurrence were: a 'closed' CIED pocket (HR 2.720; 95% CI 1.135-6.520), presence of ghost at post-TLE transoesophageal echocardiography (HR 3.469; 95% CI 1.420-8.878), and a GFR <60 (HR 4.565; 95% CI 1.668-12.493)., Conclusion: CIEDI has a poor long-term prognosis despite an effective TLE. Renal failure, presence of 'ghosts' at post-TLE transoesophageal echocardiography and a closed CIED pocket are associated with a worse prognosis.

Importance: Predictors of lethal arrhythmic events (LAEs) after a pediatric diagnosis of hypertrophic cardiomyopathy (HCM) are unresolved. Existing algorithms for risk stratification are limited to patients older than 16 years because of a lack of data on younger individuals., Objective: To describe the long-term outcome of pediatric-onset HCM and identify age-specific arrhythmic risk factors., Design, Setting, and Participants: This study assessed patients with pediatric-onset hypertrophic cardiomyopathy diagnosed from 1974 to 2016 in 2 national referral centers for cardiomyopathies in Florence, Italy. Patients with metabolic and syndromic disease were excluded., Exposures: Patients were assessed at 1-year intervals, or more often, if their clinical condition required., Main Outcomes and Measures: Lethal arrhythmic events (LAEs) and death related to heart failure., Results: Of 1644 patients with HCM, 100 (6.1%) were 1 to 16 years old at diagnosis (median [interquartile range], 12.2 [7.3-14.1] years). Of these, 63 (63.0%) were boys. Forty-two of the 100 patients (42.0%) were symptomatic (defined as an New York Heart Association classification higher than 1 or a Ross score greater than 2). The yield of sarcomere gene testing was 55 of 70 patients (79%). During a median of 9.2 years during which a mean of 1229 patients were treated per year, 24 of 100 patients (24.0%) experienced cardiac events (1.9% per year), including 19 LAEs and 5 heart failure-related events (3 deaths and 2 heart transplants). Lethal arrhythmic events occurred at a mean (SD) age of 23.1 (11.5) years. Two survivors of LAEs with symptoms of heart failure experienced recurrent cardiac arrest despite an implantable cardioverter defibrillator. Risk of LAE was associated with symptoms at onset (hazard ratio [HR], 8.2; 95% CI, 1.5-68.4; P = .02) and Troponin I or Troponin T gene mutations (HR, 4.1; 95% CI, 0.9-36.5; P = .06). Adult HCM risk predictors performed poorly in this population. Data analysis occurred from December 2016 to October 2017., Conclusions and Relevance: Pediatric-onset HCM is rare and associated with adverse outcomes driven mainly by arrhythmic events. Risk extends well beyond adolescence, which calls for unchanged clinical surveillance into adulthood. In this study, predictors of adverse outcomes differ from those of adult populations with HCM. In secondary prevention, the implantable cardioverter defibrillator did not confer absolute protection in the presence of limiting symptoms of heart failure.

Objectives: To define the incidence of vascular complications (VC) after balloon aortic valvuloplasty (BAV) in recent years, and to compare the performance of two vascular closure devices (VCD)., Background: VC remain the most frequent drawback of BAV and are associated with adverse clinical outcomes., Methods: All BAV procedures performed at 2 high-volume centers over a 6-year period (n = 930) were collected in prospective registries and investigated to assess the incidence of Valve Academic Research Consortium-2 (VARC-2) defined VC. Incidence of life-threatening, major and minor bleeding was also assessed. In-hospital major adverse cardiac and cerebrovascular events (MACCE) rate (composite of in-hospital death, myocardial infarction, TIA/stroke, and life-threatening bleeding) as well as 30-day survival was compared between a suture-mediated closure system and a collagen plug hemostatic device., Results: A 9 Fr arterial sheath was used in most of the patients (84.1%). Vascular closure was obtained with the Angio-Seal in 643 patients (69.1%) and the ProGlide in 287 (30.9%). The overall incidence of major VC was 2.7%, and minor VC 6.6%, without significant differences between groups. The Angio-Seal group was associated with a higher rate of small hematomas (6.9% vs. 3.5%, P = 0.042), whilst blood transfusions were more frequent in the ProGlide group (6.6% vs. 3.5%, P = 0.034). Rates of in-hospital MACCE and 30-day survival were similar. Use of either VCD was not independently associated with major VC., Conclusions: VC rate after BAV is fairly low in experienced centers without major differences between the 2 most used VCD., (© 2017 Wiley Periodicals, Inc.)

Background: Patients with heart failure (HF) and severe symptomatic functional mitral regurgitation (FMR) may benefit from MitraClip implantation. With increasing numbers of patients being treated the success of procedure becomes a key issue. We sought to investigate the pre-procedural predictors of device failure in patients with advanced HF treated with MitraClip., Methods: From April 2012 to November 2016, 76 patients with poor functional class (NYHA class III-IV) and severe left ventricular (LV) remodeling underwent MitraClip implantation at University Hospitals of Trieste and Bologna (Italy). Device failure was assessed according to MVARC criteria. Patients were subsequently followed to additionally assess the patient success after 12months., Results: Mean age was 67±12years, the mean Log-EuroSCORE was 23.4±16.5%, and the mean LV end-diastolic volume index and ejection fraction (EF) were 112±33ml/m 2 and 30.6±8.9%, respectively. At short-term evaluation, device failure was observed in 22 (29%) patients. Univariate predictors of device failure were LVEF, LV and left atrial volumes and anteroposterior mitral annulus diameter. Annulus dimension (OR 1.153, 95% CI 1.002-1.327, p=0.043) and LV end-diastolic volume (OR 1.024, 95% CI 1.000-1.049, p=0.049) were the only variables independently associated with the risk of device failure at the multivariate model., Conclusions: Pre-procedural anteroposterior mitral annulus diameter accurately predicted the risk of device failure after MitraClip in the setting of advanced HF. Its assessment might aid the selection of the best candidates to percutaneous correction of FMR., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Amyloidosis is a life threatening disease caused by deposition of various types of blood serum proteins in organs and tissues. Knowing the type of protein involved is the basis of a correct diagnosis and personalized medical treatment. While the classical approach uses immunohistochemistry, in recent years, laser micro-dissection, followed by high resolution LC-MS/MS, has been shown to provide superior diagnostic sensitivity and specificity. This techniques, however, is only available at major reference proteomics centers., Objective: To perform clinical amyloid protein typing using low-resolution mass spectrometry and no laser micro dissection (LMD), we developed a targeted proteomics approach for the determination of both frequently encountered amyloid proteins (i.e., κ and -λ immunoglobulin light chains and transthyretin (TTR)) and specific reference proteins (i.e., actin (A) for cardiac muscle tissue, or fatty acid binding protein 4 (FBP4) for subcutaneous adipose tissue) in histologic specimens., Method: Small tissue fragments and/or histological sections were digested to yield a protein mixture that was subsequently reduced, alkylated and trypsinized to obtain a peptide mixture. After SPE purification and LC separation, proteotypic peptides were detected by their MRM transitions., Results: The method showed high specificity and sensitivity for amyloid protein proteotypic peptides. LODs were 1.0, 0.1, 0.2 picomoles in cardiac muscle tissue (CMT) and 0.1, 0.2, 0.5 picomoles in subcutaneous adipose tissue (SAT) for TTR, κ-, and λ-LC proteins, respectively. Amyloid to tissue-specific protein signal ratios correlated with the presence of amyloid deposits in clinical samples., Conclusions: This targeted proteomics approach enables sensitive and specific discrimination of amyloidosis affected tissues for the purpose of clinical research., (© 2018 The Association for Mass Spectrometry: Applications to the Clinical Lab (MSACL). Published by Elsevier B.V.)

Objectives: To compare the effectiveness and safety of balloon aortic valvuloplasty (BAV) performed with or without rapid ventricular pacing (RP)., Background: BAV technique is poorly standardized., Methods: One hundred consecutive patients were randomly assigned 1:1 between BAV performed with or without RP. Exclusion criteria were an immediate indication for surgical or transcatheter aortic valve replacement, presentation in cardiogenic shock or pulmonary edema refractory to medical stabilization., Results: There were 51 patients in the BAV group performed with RP, 49 in the BAV group without RP (noRP). Procedural success (50% hemodynamic gradient reduction) was achieved in 37.3% and 55.1%, respectively (P = 0.16). Fewer people in the noRP group complained of poor tolerance to the procedure (16% vs 41%). The primary efficacy endpoint, a 50% reduction in the mean echocardiographic trans-aortic gradient, was met in 21/49 patients in the noRP group compared to 20/51 in the RP (42.9% vs 39.2%; P = 0.84). No significant difference between the groups was observed in the primary safety endpoint, a 30-day composite of death, myocardial infarction, stroke, acute aortic regurgitation, and BARC bleeding ≥3 (8.2% noRP vs 13.7%; P = 0.53). The noRP group required fewer bailout temporary pacemakers (P = 0.048) and had a lower incidence of moderate/severe renal function worsening (4.1% vs 17.6%; P = 0.052)., Conclusions: Rapid ventricular pacing did not influence BAV efficacy or safety and tolerance was slightly worse., (© 2017, Wiley Periodicals, Inc.)

Objective: To determine, in patients with ST-segment Elevation Myocardial Infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), the prognostic weight of cardiac arrest (CA) according to the type of rhythm (shockable vs. non-shockable)., Methods: We prospectively enrolled 3278 consecutive STEMI patients undergoing PPCI. Multivariable Cox regression was used to establish the relation to 1-year cardiac mortality of both type of CA. In patients suffering from CA we identified predictors of both poor neurological outcome (cerebral performance categories 3-5) and cardiac mortality at 1year., Results: The incidence of CA was 7.26% (n=238). Of these, 196 (5.98%) had an initial shockable rhythm and 42 (1.28%) a non shockable rhythm. During 1-year follow up 311(9.48%) patients died from cardiac causes. Shockable rhythm (adjusted-HR=1.61; 95%CI 1.08-2.43, p=0.02) and non-shockable rhythm (adjusted-HR=3.83; 95%CI 2.36-6.22, p<0.001) were independently associated with 1-year cardiac mortality. Among patients with CA those with shockable rhythm had a lower risk of poor neurological outcome at 1year follow up (adjusted OR=0.22: 95%CI; 0.08-0.55, p=0.001). Independent predictors of 1-y cardiac mortality were: non shockable rhythm (adjusted HR=2.6; 95%CI; 1.48-4.5, p=0.001), crew-witnessed CA, diabetes mellitus, left ventricle ejection fraction and creatinine on admission. There was a significant interaction between type of rhythm and crew-witnessed CA (p=0.026)., Conclusions: In patients with STEMI undergoing PPCI patients with both shockable and non shockable CA are at increased risk of 1-year cardiac mortality. Among patients with CA those with non shockable rhythm have an higher risk of both poor neurological outcome and cardiac mortality at 1year., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The late sodium current inhibitor ranolazine reverses the main electrophysiological and mechanical abnormalities of human hypertrophic cardiomyopathy (HCM) cardiomyocytes in vitro, suggesting potential clinical benefit. We aimed to assess the effect of ranolazine on functional capacity, symptomatic status, diastolic function, and arrhythmias in HCM., Methods and Results: In this multicenter, double-blind, phase 2 study, 80 adult patients with nonobstructive HCM (age 53±14 years, 34 women) were randomly assigned to placebo (n=40) or ranolazine 1000 mg bid (n=40) for 5 months. The primary end point was change in peak VO 2 compared with baseline using cardiopulmonary exercise test. Echocardiographic lateral and septal E/E' ratio, prohormone brain natriuretic peptide levels, 24-hour Holter arrhythmic profile, and quality of life were assessed. Ranolazine was safe and well tolerated. Overall, there was no significant difference in VO 2 peak change at 5 months in the ranolazine versus placebo group (delta 0.15±3.96 versus -0.02±4.25 mL/kg per minute; P =0.832). Ranolazine treatment was associated with a reduction in 24-hour burden of premature ventricular complexes compared with placebo (>50% reduction versus baseline in 61% versus 31%, respectively; P =0.042). However, changes in prohormone brain natriuretic peptide levels did not differ in the ranolazine compared with the placebo group (geometric mean median [interquartile range], -3 pg/mL [-107, 142 pg/mL] versus 78 pg/mL [-71, 242 pg/mL]; P =0.251). Furthermore, E/E' ratio and quality of life scores showed no significant difference., Conclusions: In patients with nonobstructive HCM, ranolazine showed no overall effect on exercise performance, plasma prohormone brain natriuretic peptide levels, diastolic function, or quality of life. The drug showed an excellent safety profile and was associated with reduced premature ventricular complex burden. Late sodium current inhibition does not seem to improve functional capacity in HCM., Clinical Trial Registration: URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2011-004507-20., (© 2018 American Heart Association, Inc.)

Background: Trastuzumab-related cardiotoxicity has been reported in patients receiving trastuzumab concurrently with other agents, especially with anthracyclines. Cardiac function damage is generally rare, precox and mild with trastuzumab alone., Case Presentation: We report the case of a 49 year-old woman affected by metastatic breast cancer who developed trastuzumab-related cardiogenic shock due to pump failure (with LVEF of about 15%) after three months of treatment. After a long hospitalization in the cardiac intensive care unit and a proper treatment, LVEF increased to 50% and, due to a severe progression of disease, trastuzumab was resumed and continued for more than one year., Conclusion: This is a case of particularly severe cardiotoxicity related to trastuzumab treatment, which was recovered with pharmacological treatment and the temporary discontinuation of the treatment. Trastuzumab was safely resumed after clinical and echocardiographic parameters improvement.

Purpose: To evaluate the relationship between aortic inflammation as assessed by 18 F-fluorodeoxyglucose-positron emission tomography ( 18 F-FDG-PET) and features of plaque vulnerability as assessed by frequency domain-optical coherence tomography (FD-OCT)., Methods: We enrolled 30 consecutive non-ST-segment elevation acute coronary syndrome patients undergoing percutaneous coronary intervention. All patients underwent three-vessel OCT before intervention and 18 F-FDG-PET before discharge. Univariable and C-reactive protein (CRP)-adjusted linear regression analyses were performed between features of vulnerability [namely:lipid-rich plaques with and without macrophages and thin cap fibroatheromas (TCFA)] and 18 F-FDG uptake in both ascending (AA) and descending aorta (DA) [measured either as averaged mean and maximum target-to-blood ratio (TBR) or as active slices (TBR max  ≥ 1.6)]., Results: Mean age was 62 years, and 26 patients were male. On univariable linear regression analysis TBR mean and TBR max in DA was associated with the number of lipid-rich plaques (β = 4.22; 95%CI 0.05-8.39; p = 0.047 and β = 3.72; 95%CI 1.14-6.30; p = 0.006, respectively). TBR max in DA was also associated with the number of lipid-rich plaques containing macrophages (β = 2.40; 95%CI 0.07-4.72; p = 0.044). A significant CRP adjusted linear association between the TBR max in DA and the number of lipid-rich plaques was observed (CRP-adjusted β = 3.58; 95%CI -0.91-6.25; p = 0.01). TBR max in DA showed a trend towards significant CRP-adjusted association with number of lipid-rich plaques with macrophages (CRP-adjusted β = 2.30; 95%CI -0.11-4.71; p = 0.06). We also observed a CRP-adjusted (β = 2.34; 95%CI 0.22-4.47; p = 0.031) linear association between the number of active slices in DA and the number of lipid-rich plaques. No relation was found between FDG uptake in the aorta and the number of TCFAs., Conclusions: In patients with first NSTEACS , 18 F-FDG uptake in DA is correlated with the number of OCT detected lipid-rich plaques with or without macrophages. This association may be independent from CRP values.

To assess the accuracy of cardiac magnetic resonance (CMR) for the diagnosis of angiographic stenosis after percutaneous coronary intervention (PCI) of left main coronary artery (LMCA). Patients undergone in the last year PCI of unprotected LMCA and scheduled for conventional X-ray coronary angiography (CXA) were evaluated with stress perfusion CMR within 2 weeks before CXA. Main contraindications to CMR were exclusion criteria. Stress perfusion CMR was performed to follow a bolus of contrast Gadobutrol after 3 min of adenosine infusion. Between the 50 patients enrolled, only 1 did not finish the CMR protocol and 49 patients with median age 71 (65-75) years (38 male, 11 female) were analyzed. Between 784 coronary angiographic segments evaluated we found 75 stenosis or occlusions (prevalence 9.5%), but only 13 stenosis or occlusions in proximal segments (prevalence 6.6%). Patients with coronary stenosis (n = 12, 24%) showed a significantly (p = 0.002) higher prevalence of diabetes (7 of 12, 58%). At CMR examination, late gadolinium enhancement was present in 25 (51%), reversible perfusion defects in 12 (24%), and fixed perfusion defects in 6 subjects (12%). The only patient with LMCA restenosis resulted positive at perfusion CMR. The accuracy of stress perfusion CMR in diagnosis of coronary stenosis was higher when the analysis was performed only in proximal coronary arteries (95%, CI 86-99) compared to overall vessels (84%, CI 70-92). Stress perfusion CMR could strongly reduce the need for elective CXA in follow up of LMCA PCI and should be validated in further multicenter prospective studies.

Aims: Although cardiac amyloidosis (CA) is characterized by significant left atrial (LA) dilatation, the characteristics of LA function remain to be fully investigated., Methods and Results: We assessed LA function by speckle-tracking echocardiography in 124 patients with CA and sinus rhythm: 68 with light chain (AL), 29 with mutant (ATTRm), 27 with wild-type (ATTRwt) transthyretin amyloidosis. Conventional and strain-derived parameters, including LA peak longitudinal strain (LS) and strain rate (peak LSR: reservoir function; early LSR: conduit function; late LSR: active function), were assessed compared between CA patients and 20 healthy controls of similar age and gender. All LA function phases, including LA longitudinal strain, peak LSR, early and late LSR were significantly impaired in CA compared to healthy controls after adjusting for LA size, LV ejection fraction and LV filling pressures (E/E') (all P < 0.05). Peak LA LS was moderately correlated with LV global LS (R = -0.60, P < 0.001); late LSR was correlated with A wave at the level of LV inflow (R = -0.69, P < 0.001). Among the different CA subtypes, peak LS and LA active emptying fraction were worse in ATTRwt than AL and ATTRm [P < 0.05 after adjustment for age, sex, body mass index, systolic blood pressure, heart rate, LA volume index, severity of mitral regurgitation, left ejection fraction, and left ventricular end-diastolic pressure (E/E')]., Conclusion: In CA, LA function was severely impaired and highly correlated with LV deformation. Differences in LA function between amyloid subtypes suggest that amyloid aetiology plays a role in the pathophysiology of cardiac dysfunction in CA., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

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.

Background: Prognosis of hypertrophic cardiomyopathy (HCM) is particularly heterogeneous. Patients with nonobstructive HCM (NOCM) are thought to be at relatively low-risk as compared with obstructive HCM (HOCM) with no need of major treatment options. However, available evidence of NOCM comes mainly from tertiary centers where a referral bias is likely to occur. Aim of this study was to perform a systematic review and meta-analysis of the published literature on hypertrophic cardiomyopathy (HCM) in order to outline differences in presenting features and long-term outcome between NOCM and HOCM., Methods: MEDLINE/Pubmed, EMBASE and Cochrane databases up to December 31, 2016, and reviewed cited references to identify relevant studies were used. The primary endpoints were HCM-related overall mortality rate and yearly rate of cardiac death. Other endpoints were incidences of sudden and congestive heart failure deaths., Results: A total of 20 studies entered the meta-analysis on the long-term outcome of NOCM vs HOCM. They included a total of 7731 patients, 5058 patients with NOCM (65%) and 2673 patients with HOCM (35%). During the follow-up, annual mortality related to HCM averaged 1.55% in NOCM and 1.77% in HOCM (Relative Risk: 0.89, 95% confidence intervals: 0.68 to 1.17, p=0.40). Overall, 5 studies reported significantly higher mortality for HOCM, 3 higher mortality for NOCM, and 12 no significant differences., Conclusion: This large study-level meta-analysis shows that long-term mortality of patients with NOCM is not negligible and not significantly different from HOCM., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We report the unique case of a primary cardiac leiomyoma originating from the right ventricle and involving the tricuspid valve in a 43-year-old woman. Echocardiography showed a giant mass causing severe pulmonary stenosis and tricuspid valve regurgitation. The patient underwent surgical excision and histologic examination revealed a primary cardiac leiomyoma. To the best of our knowledge only three cases of primary cardiac leiomyoma have so far been reported, and this is the first case of primary cardiac leiomyoma involving the tricuspid valve apparatus., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Mucopolysaccharidoses (MPS) represent a group of rare lysosomal storage disorders, with a heterogeneous clinical presentation in terms of inheritance (autosomal and X-linked recessive), age of onset (infants, children, and adults), systemic and cardiac manifestations (mild to severe disease forms). Evidence-based recommendations on the diagnosis and management of cardiovascular disease in MPS are scarce. GICEM (Gruppo Italiano Cardiologi Esperti Malattie Metaboliche) is a group of cardiologists, cardiac surgeons and pediatricians with a specific expertise in metabolic diseases including MPS. In this paper, we report our experience and recommendations on the diagnosis and management of cardiovascular aspects in MPS, with a tailored approach based on current evidence, and taking into account MPS phenotype (particularly, I, II, IVa, VI), age at presentation, and severity of systemic and cardiac manifestations.