Abnormal conduction-induced cardiomyopathy: a poorly explored entity.

A dyssynchronous biventricular activation, which can be determined by left bundle branch block, chronic right ventricular pacing, frequent premature ventricular complexes, or pre-excitation, can cause a global abnormal contractility, thus leading to systolic dysfunction and left ventricular remodelling in a unique nosological entities: abnormal conduction-induced cardiomyopathies. In this clinical scenario, the mainstay therapy is eliminating or improving LV dyssynchrony, removing the trigger. This usually ensures the improvement and even recovery of cardiac geometry and left ventricular function, especially in the absence of genetic background. A multidisciplinary approach, integrating advanced multimodal imaging, is essential for the systematic aetiological definition and the subsequent evaluation and aetiology-guided therapies of patients and their families. This review aims to describe mechanisms, prevalence, risk factors, and diagnostic and therapeutic approach to the various abnormal conduction-induced cardiomyopathies, starting from reasonable certainties and then analysing the grey areas requiring further studies.

Clinical Use of Biomarkers in Cardiac Amyloidosis.

Amyloidosis is a systemic condition characterized by multiple organs involvement. A multidisciplinary and multimodal approach in assessing patients is pivotal and recommended by the international scientific societies. Biomarkers represent an essential noninvasive tool to increase the suspicion of disease and orient further workup and clinical management of patients. This review provides an updated contemporary focus on the clinical use of biomarkers in cardiac amyloidosis, emphasizing their role in both the diagnostic and prognostic setting and discussing future perspective of emerging biomarkers.

Tafamidis in the Treatment of ATTR-related Cardiomyopathy: Indications and Grey Zones.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is caused by the myocardial extracellular deposition of amyloid fibrils formed from the dissociation of TTR tetramer into monomers. The rate-limiting step in TTR amyloidogenesis is the dissociation of the TTR tetramer into monomers: Tafamidis is an effective TTR-stabilizer in its native homotetrameric structure. Tafamidis is a safe and effective drug in reducing symptoms, hospitalization and mortality in accurately selected patients affected by hereditary and wild-type transthyretin amyloid cardiomyopathy.

Arrhythmic risk stratification in non-ischaemic dilated cardiomyopathy.

Dilated cardiomyopathy is a primary disease of the heart muscle, which affects relatively young patients with a low comorbidity profile. It is characterized by structural and/or functional abnormalities leading to systolic dysfunction of the left ventricle or of both ventricles, often associated with dilatation, in the absence of an ischaemic, valvular, or pressure overload cause sufficient to explain the phenotype. Although the prognosis of the disease has greatly improved over the last few decades, prognostic stratification remains a fundamental objective, especially about the prediction of potentially life-threatening arrhythmic events. An accurate diagnostic work-up and an appropriate aetiopathogenetic characterization affect the patients' outcome and represent the essential basis of an adequate prognostic stratification. It is necessary to adopt a multiparametric approach, especially when the aim is the prediction of arrhythmic risk; it includes an integration of medical history and physical examination with cardiac imaging and genetic testing, in order to obtain a personalized diagnosis and therapeutic strategies. Furthermore, the evaluation should be repeated at every clinical check-up, considering the dynamic trend of the pathology and the arrhythmic risk changes over time. This article aims to illustrate how, starting from an exhaustive aetiological and clinical-instrumental characterization, including all diagnostic methods available at present time, it is possible to obtain a tailored diagnostic evaluation and stratification of the arrhythmic risk as accurate as possible.

Sudden Cardiac Death in Athletes: Facts and Fallacies.

The benefits of exercise for cardiovascular and general health are many. However, sudden cardiac death (SCD) may occur in apparently healthy athletes who perform at the highest levels. A diverse spectrum of diseases is implicated in SCD in athletes, and while atherosclerotic coronary artery disease predominates in individuals of >35 years of age, primary cardiomyopathies and ion channelopathies are prevalent in young individuals. Prevention of SCD in athletes relies on the implementation of health policies aimed at the early identification of arrhythmogenic diseases (such as cardiac screening) and successful resuscitation (such as widespread utilization of automatic external defibrillators and training members of the public on cardiopulmonary resuscitation). This review will focus on the epidemiology and aetiologies of SCD in athletes, and examine fallacies in the approach to this controversial field. Furthermore, potential strategies to prevent these tragic events will be discussed, analysing current practice, gaps in knowledge and future directions.

Impact of SARS-CoV-2 infection in patients with cardiac amyloidosis: Results of a multicentre registry.

BACKGROUND: Descriptions on impact of SARS-CoV-2 infection in patients with cardiac amyloidosis (CA) are lacking. Our aim was to describe the prognosis of those patients. METHODS: Retrospective observational study of unvaccinated patients with CA who developed SARS-CoV-2 infection enrolled in eleven centres (March 2020 to May 2021). Descriptive analysis of basal characteristics, hospitalization, mortality, and severe clinical course was performed. Comparisons to a population-based control group were made. RESULTS: Forty-one patients were identified. Most patients had wild-type transthyretin CA (61%) and were on NYHA Class II-III (80.5%). CA patients were commonly hospitalized (73.2%) and those were more symptomatic than outpatients (p=0.035). The 24.4% of CA patients died as consequence of SARS-CoV-2 infection. Patients with CA had an increased risk of hospitalization [OR 6.23 (3.05-12.74), p<0.001] and mortality [OR 2.18 (1.01-4.68), p=0.047] when compared to control population after adjustment by age and sex. After a medium follow-time of 311 days, 41.5% of the CA cohort died. CONCLUSIONS: SARS-CoV-2 infection is associated with high mortality and hospitalization rates in patients with CA, which exceed that expected by their sex and advanced age.

Re-Definition of the Epidemiology of Cardiac Amyloidosis.

The epidemiology of cardiac amyloidosis (CA), traditionally considered a rare and incurable disease, has changed drastically over the last ten years, particularly due to the advances in diagnostic methods and therapeutic options in the field of transthyretin CA (ATTR-CA). On the one hand, the possibility of employing cardiac scintigraphy with bone tracers to diagnose ATTR-CA without a biopsy has unveiled the real prevalence of the disease; on the other, the emergence of effective treatments, such as tafamidis, has rendered an early and accurate diagnosis critical. Interestingly, the following subgroups of patients have been found to have a higher prevalence of CA: elderly subjects > 75 years, patients with cardiac hypertrophy hospitalized for heart failure with preserved ejection fraction, subjects operated on for bilateral carpal tunnel syndrome, patients with cardiac hypertrophy not explained by concomitant factors and individuals with aortic valve stenosis. Many studies investigating the prevalence of CA in these particular populations have contributed to rewriting the epidemiology of the disease, increasing the awareness of the medical community for a previously underappreciated condition. In this review, we summarized the latest evidence on the epidemiology of CA according to the different clinical settings typically associated with the disease.

Clinical characterization and natural history of chemotherapy-induced dilated cardiomyopathy.

AIMS: Chemotherapy-induced dilated cardiomyopathy (CI-DCM) is a well-recognized phenotype of non-ischemic dilated cardiomyopathy (DCM), characterized by poor outcomes. However, a detailed comparison between idiopathic DCM (iDCM) and CI-DCM is still lacking. METHODS AND RESULTS: All consecutive DCM patients enrolled in the Trieste Muscle Heart Disease Registry were analysed. CI-DCM and iDCM were defined according to current recommendations. The primary study outcome measure was all-mortality death and secondary outcomes were a) a composite of cardiovascular death/heart-transplantation/ventricular-assist-device implantation, and b) major ventricular arrhythmias. The study included 551 patients (499 iDCM and 52 CI-DCM). At enrolment, compared with iDCM, CI-DCM patients were older (51 ± 14 years vs. 58 ± 3 years, respectively, P < 0.001) and had a higher left ventricular ejection fraction (32% ± 9 vs. 35% ± 10, respectively, P = 0.03). Over a median follow-up of 90 months (IQR 54-140 months), CI-DCM patients had a higher incidence of all-cause mortality compared with iDCM (36.5% vs. 8.4% in CI-DCM and iDCM respectively, P < 0.001), while the incidence of major ventricular arrhythmias was higher in the iDCM group compared with CI-DCM (4% vs. 0%, in CI-DCM and iDCM respectively, P = 0.03). The risk of the composite outcome was comparable between the two groups (P = 0.91). At Cox multivariable analysis, the diagnosis of CI-DCM emerged as independently associated to primary outcome (HR 6.42, 95% C.I. 2.52-16.31, P < 0.001). CONCLUSIONS: In a well-selected DCM cohort, patients with a chemotherapy-induced aetiology had a higher incidence of all-cause mortality compared with iDCM. Conversely, the incidence of life-threatening ventricular arrhythmic events was higher among patients with iDCM.

Evolving trends in epidemiology and natural history of cardiac amyloidosis: 30-year experience from a tertiary referral center for cardiomyopathies.

Objective: Natural history of cardiac amyloidosis (CA) is poorly understood. We aimed to examine the changing mortality of different types of CA over a 30-year period. Patients and methods: Consecutive patients included in the "Trieste CA Registry" from January 1, 1990 through December 31, 2021 were divided into a historical cohort (diagnosed before 2016) and a contemporary cohort (diagnosed after 2016). Light chain (AL), transthyretin (ATTR) and other forms of CA were defined according to international recommendations. The primary and secondary outcome measures were all-cause mortality and cardiac death, respectively. Results: We enrolled 182 patients: 47.3% AL-CA, 44.5% ATTR-CA, 8.2% other etiologies. The number of patients diagnosed with AL and ATTR-CA progressively increased over time, mostly ATTR-CA patients (from 21% before 2016 to 67% after 2016) diagnosed non-invasively. The more consistent increase in event-rate was observed in the long-term (after 50 months) in ATTR-CA compared to the early increase in mortality in AL-CA. In the contemporary cohort, during a median follow up of 16 [4-30] months, ATTR-CA was associated with improved overall and cardiac survival compared to AL-CA. At multivariable analysis, ATTR-CA (HR 0.42, p = 0.03), eGFR (HR 0.98, p = 0.033) and ACE-inhibitor therapy (HR 0.24, p < 0.001) predicted overall survival in the contemporary cohort. Conclusion: Incidence and prevalence rates of ATTR-CA and, to a less extent, of AL-CA have been increasing over time, with significant improvements in 2-year survival of ATTR-CA patients from the contemporary cohort. Reaching an early diagnosis and starting disease-modifying treatments will improve long-term survival in CA.

Impact of SARS-CoV-2 infection in patients with cardiac amyloidosis: Results of a multicentre registry / Impacto de la infección por SARS-CoV-2 en pacientes con amiloidosis cardiaca: resultados de un registro multicéntrico

Background Descriptions on impact of SARS-CoV-2 infection in patients with cardiac amyloidosis (CA) are lacking. Our aim was to describe the prognosis of those patients. Methods Retrospective observational study of unvaccinated patients with CA who developed SARS-CoV-2 infection enrolled in eleven centres (March 2020 to May 2021). Descriptive analysis of basal characteristics, hospitalization, mortality, and severe clinical course was performed. Comparisons to a population-based control group were made. Results Forty-one patients were identified. Most patients had wild-type transthyretin CA (61%) and were on NYHA Class II–III (80.5%). CA patients were commonly hospitalized (73.2%) and those were more symptomatic than outpatients (p=0.035). The 24.4% of CA patients died as consequence of SARS-CoV-2 infection. Patients with CA had an increased risk of hospitalization [OR 6.23 (3.05–12.74), p<0.001] and mortality [OR 2.18 (1.01–4.68), p=0.047] when compared to control population after adjustment by age and sex. After a medium follow-time of 311 days, 41.5% of the CA cohort died. Conclusions SARS-CoV-2 infection is associated with high mortality and hospitalization rates in patients with CA, which exceed that expected by their sex and advanced age (AU)

Antecedentes El impacto de la infección por SARS-CoV-2 en pacientes con amiloidosis cardíaca (AC) es desconocido. El principal objetivo de este estudio es describir el pronóstico de estos pacientes. Métodos Estudio observacional retrospectivo de pacientes con AC no vacunados que desarrollaron infección por SARS-CoV-2 identificados en 11 centros (marzo 2020/mayo 2021). Se realiza un análisis descriptivo de características basales, hospitalización, mortalidad y curso clínico grave, y se comparan los resultados con una cohorte poblacional. Resultados Cuarenta y un pacientes fueron identificados. La mayoría eran AC por transtirretina wild-type (61%) y estaban en clase NYHA II-III (80,5%). La mayoría de los pacientes fueron hospitalizados (73,2%), los cuales tenían peor clase funcional que los ambulatorios (p=0,035). El 24,4% de los pacientes fallecieron como consecuencia de la infección. Los pacientes con AC tenían un mayor riesgo de hospitalización (OR: 6,23; 3.05-12.74; p<0,001) y fallecimiento (OR: 2,18; 1,01-4,68; p=0,047) que la cohorte poblacional tras ajuste por sexo y edad. Tras un seguimiento medio de 311 días, el 41,5% de los pacientes fallecieron. Conclusiones La infección por SARS-CoV-2 presenta alto riesgo de mortalidad y hospitalización en pacientes con AC, mayor que la esperada por su sexo y edad (AU)