Giulia De Angelis

Background: Filamin C truncating variants ( FLNCtv ) cause a form of arrhythmogenic cardiomyopathy: the mode of presentation, natural history, and risk stratification of FLNCtv remain incompletely explored. We aimed to develop a risk profile for refractory heart failure and life-threatening arrhythmias in a multicenter cohort of FLNCtv carriers. Methods: FLNCtv carriers were identified from 10 tertiary care centers for genetic cardiomyopathies. Clinical and outcome data were compiled. Composite outcomes were all-cause mortality/heart transplantation/left ventricle assist device (D/HT/LVAD), nonarrhythmic death/HT/LVAD, and sudden cardiac death/major ventricular arrhythmias. Previously established cohorts of 46 patients with LMNA and 60 with DSP -related arrhythmogenic cardiomyopathies were used for prognostic comparison. Results: Eighty-five patients carrying FLNCtv were included (42±15 years, 53% men, 45% probands). Phenotypes were heterogeneous at presentation: 49% dilated cardiomyopathy, 25% arrhythmogenic left dominant cardiomyopathy, 3% arrhythmogenic right ventricular cardiomyopathy. Left ventricular ejection fraction was FLNCtv carriers did not significantly differ from LMNA carriers and DSP carriers. In FLNCtv carriers, left ventricular ejection fraction was associated with the risk of D/HT/LVAD and nonarrhythmic death/HT/LVAD. Conclusions: Among patients referred to tertiary referral centers, FLNCtv arrhythmogenic cardiomyopathy is phenotypically heterogeneous and characterized by a high risk of life-threatening arrhythmias, which does not seem to be associated with the severity of left ventricular dysfunction.

Le cardiomiopatie sono malattie primitive del miocardio con importante componente genetica. Esordiscono in genere tra i 30 e i 50 anni e sono le più comuni cause di morte improvvisa e scompenso cardiaco nel giovane adulto. Le principali cardiomiopatie riscontrate nella pratica clinica sono la cardiomiopatia dilatativa, la cardiomiopatia aritmogena e la cardiomiopatia ipertrofica. Nonostante il progresso delle conoscenze degli ultimi anni, reso possibile in particolare dalla diffusione di tecniche di sequenziamento genico di nuova generazione e da metodiche di imaging avanzate, la diagnosi, l’inquadramento eziologico e la gestione delle cardiomiopatie rimangono complessi e per alcuni aspetti controversi. Questa rassegna ha lo scopo di proporre delle flow-chart operative, integrando le più recenti evidenze scientifiche con i protocolli gestionali del Dipartimento Cardiotoracovascolare dell’Ospedale di Trieste, uno dei Centri di riferimento nazionali per le cardiomiopatie e lo scompenso cardiaco con esperienza trentennale in tale ambito.

The term dilated cardiomyopathy (DCM) defines a heterogeneous group of cardiac disorders, which are characterized by left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. In approximately one third of cases, DCM is familial with a genetic pathogenesis and various patterns of inheritance. Although the electrocardiogram (ECG) has been considered traditionally non-specific in DCM, the recently acquired knowledge of the genotype–phenotype correlations provides novel opportunities to identify patterns and abnormalities that may point toward specific DCM subtypes. A learned ECG interpretation in combination with an appropriate use of other ECG-based techniques including ambulatory ECG monitoring, exercise tolerance test and imaging modalities, such as echocardiography and cardiovascular magnetic resonance, may allow the early identification of specific genetic or acquired forms of DCM. Furthermore, ECG abnormalities may reflect the severity of the disease and provide a useful tool in risk stratification and management. In the present review, we discuss the current role of the ECG in the diagnosis and management of DCM. We describe various clinical settings where the appropriate use and interpretation of the ECG can provide invaluable clues, contributing to the important role of this basic tool as cardiovascular medicine evolves.

Sudden cardiac death and arrhythmia-related events in patients with non-ischaemic dilated cardiomyopathy (NICM) have been significantly reduced over the last couple of decades as a result of evidence-based pharmacological and non-pharmacological therapeutic strategies. Nevertheless, the arrhythmic stratification in patients with NICM remains extremely challenging, and the simple indication based on left ventricular ejection fraction appears to be insufficient. Therefore, clinicians need to go beyond the current criteria for implantable cardioverter-defibrillator implantation in the direction of a multiparametric evaluation of arrhythmic risk. Several parameters for arrhythmic risk stratification, ranging from electrocardiographic, echocardiographic, imaging-derived and genetic markers, are crucial for proper arrhythmic risk stratification and a multiparametric evaluation of risk in patients with NICM. In particular, integration of cardiac magnetic resonance parameters (mostly late gadolinium enhancement) and specific genetic information (ie, presence of LMNA, PLN, FLNC mutations) appears fundamental for proper implementation of the current arrhythmic risk stratification. Finally, a novel approach focused on both arrhythmic risk and prediction of left ventricular reverse remodelling during follow-up might be useful for effective multiparametric and dynamic arrhythmic risk stratification in NICM. In the future, a complete and integrated evaluation might be mandatory to implement arrhythmic risk prediction in patients with NICM and to discriminate the competing risk between heart failure-related events and life-threatening arrhythmias.

Lake Louise Criteria (LLC) are time-dependent and some acute myocarditis (AM) with preserved left ventricular ejection fraction (LVEF) could be missed, due to the limited accessibility of Cardiac Magnetic Resonance (CMR). We aimed to assess the potential value of cardiac strain measured by feature tracking (FT) imaging in this population.

Cardiovascular diseases show many sex-related differences in prevalence, etiology, phenotype expression, and outcomes. Complex molecular mechanisms underlie this diverse pathological manifestation, from sex-determined differential gene expression to sex hormones interaction with their specific receptors in different tissues. More recently, differential non-coding RNAs regulation also turned out to be an involved mechanism. This review focuses on sex impact on the various heart failure syndromes, including coronary artery disease, heart failure with preserved ejection fraction and with reduced ejection fraction, with particular attention to dilated cardiomyopathy. Despite similar genetic predisposition in terms of identified causative mutations, other causes, such as cardiotoxic drugs exposure or stress-induced cardiomyopathy, are more prevalent in women. Beyond this, differences in disease presentation and natural history reveal a more severe clinical onset with otherwise better long-term outcomes in women compared to men. Understanding the varying characteristics of disease manifestation and outcomes is warranted for a prompt and tailored treatment for both men and women. This is a mandatory step in the road to the personalized medicine. Moreover, despite a higher enrollment in the last years, the under-representation of females in clinical trials is the first obstacle to overcome in the long way to develop appropriate sex-based therapy approach.

Aims: Arrhythmic risk stratification is a challenging issue in patients with dilated cardiomyopathy (DCM), particularly when left ventricular ejection fraction (LVEF) is more than 35%. We studied the prevalence and predictors of sudden cardiac death or malignant ventricular arrhythmias (SCD/MVAs) in DCM patients categorized at low arrhythmic risk because of intermediate left ventricular dysfunction under optimal medical treatment (OMT). Methods: DCM patients considered at low arrhythmic risk (LVEF >35% and New York Heart Association class I-III after 6 ± 3 months of OMT) were analysed. An arrhythmogenic profile was defined as the presence of at least one among a history of syncope, nonsustained ventricular tachycardia, at least 1000 premature ventricular contractions/24 h, at least 50 ventricular couplets/24 h at Holter ECG monitoring. SCD/MVAs was considered as the study end-point. Results: During a median follow-up of 152 months (interquartile range 100–234), 30 out of 360 (8.3%) patients at low arrhythmic risk (LVEF 47 ± 7%) experienced the study end-point [14 (3.9%) SCD and 16 (4.4%) MVA]. Compared with survivors, patients who experienced SCD/MVAs had more frequently an arrhythmogenic profile and a larger left atrium. Their LVEF at the last available evaluation before the arrhythmic event was 36 ± 12%. At multivariable analysis, left atrial end-systolic area [hazard ratio 1.107; 95% confidence interval (95% CI) 1.039–1.179, P = 0.002 for 1 mm² increase] and arrhythmogenic profile (hazard ratio 3.667; 95% CI 1.762–7.632, P = 0.001) emerged as predictors of SCD/MVAs during follow-up. Conclusion: A consistent quota of DCM patients with intermediate left ventricular dysfunction receiving OMT experienced SCD/MVA during follow-up. Left atrial dilatation and arrhythmogenic pattern were associated with a higher risk of SCD/MVA.