Role of ventricular tachycardia ablation in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive fibro-fatty replacement of the myocardium that represents the substrate for recurrent sustained ventricular tachycardia (VT). These arrhythmias characterize the clinical course of a sizeable proportion of patients and have significant implications for their quality of life and long-term prognosis. Antiarrhythmic drugs are often poorly tolerated and usually provide incomplete control of arrhythmia relapses. Catheter ablation is a potentially effective strategy to treat frequent VT episodes and ICD shocks in ARVC patients. The aims of this review are to discuss the electrophysiological and electroanatomic substrates of ventricular tachycardia in patients with ARVC and to analyze the role of catheter ablation in their management with particular reference to selection of patients, technical issues, potential complications and outcomes

Arrhythmogenic Right Ventricular Cardiomyopathy: Characterization of Left Ventricular Phenotype and Differential Diagnosis With Dilated Cardiomyopathy

Background This study assessed the prevalence of left ventricular (LV) involvement and characterized the clinical, electrocardiographic, and imaging features of LV phenotype in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Differential diagnosis between ARVC-LV phenotype and dilated cardiomyopathy (DCM) was evaluated. Methods and Results The study population included 87 ARVC patients (median age 34\ua0years) and 153 DCM patients (median age 51\ua0years). All underwent cardiac magnetic resonance with quantitative tissue characterization. Fifty-eight ARVC patients (67%) had LV involvement, with both LV systolic dysfunction and LV late gadolinium enhancement (LGE) in 41/58 (71%) and LV-LGE in isolation in 17 (29%). Compared with DCM, the ARVC-LV phenotype was statistically significantly more often characterized by low QRS voltages in limb leads, T-wave inversion in the inferolateral leads and major ventricular arrhythmias. LV-LGE was found in all ARVC patients with LV systolic dysfunction and in 69/153 (45%) of DCM patients. Patients with ARVC and LV systolic dysfunction had a greater amount of LV-LGE (25% versus 13% of LV mass; P<0.01), mostly localized in the subepicardial LV wall layers. An LV-LGE 6520% had a 100% specificity for diagnosis of ARVC-LV phenotype. An inverse correlation between LV ejection fraction and LV-LGE extent was found in the ARVC-LV phenotype (r=-0.63; P<0.01), but not in DCM (r=-0.01; P=0.94). Conclusions LV involvement in ARVC is common and characterized by clinical and cardiac magnetic resonance features which differ from those seen in DCM. The most distinctive feature of ARVC-LV phenotype is the large amount of LV-LGE/fibrosis, which impacts directly and negatively on the LV systolic function

Coronary artery calcium score: we know where we are but not where we may be

Cardiac computed tomography angiography (CCTA) has emerged as a cost-effective and time-saving technique for excluding coronary artery disease. One valuable tool obtained by CCTA is the coronary artery calcium (CAC) score. The use of CAC scoring has shown promise in risk assessment and stratification of cardiovascular disease. CAC scores can be complemented by plaque analysis to assess vulnerable plaque characteristics and further refine risk assessment. This paper aims to provide a comprehensive understanding of the value of the CAC as a prognostic tool and its implications for patient risk assessment, treatment strategies and outcomes. CAC scoring has demonstrated superior ability in stratifying patients, especially asymptomatic individuals, compared to traditional risk factors and scoring systems. The main evidence suggests that individuals with a CAC score of 0 had a good long-term prognosis, while elevated CAC score is associated with increased cardiovascular risk. Finally, the clinical power of CAC scoring and the develop of new models for risk stratification could be enhanced by machine learning algorithms

Importance of genotype for risk stratification in arrhythmogenic right ventricular cardiomyopathy using the 2019 ARVC risk calculator

none41siTo study the impact of genotype on the performance of the 2019 risk model for arrhythmogenic right ventricular cardiomyopathy (ARVC).Protonotarios, Alexandros; Bariani, Riccardo; Cappelletto, Chiara; Pavlou, Menelaos; García-García, Alba; Cipriani, Alberto; Protonotarios, Ioannis; Rivas, Adrian; Wittenberg, Regitze; Graziosi, Maddalena; Xylouri, Zafeirenia; Larrañaga-Moreira, José M; de Luca, Antonio; Celeghin, Rudy; Pilichou, Kalliopi; Bakalakos, Athanasios; Lopes, Luis Rocha; Savvatis, Konstantinos; Stolfo, Davide; Dal Ferro, Matteo; Merlo, Marco; Basso, Cristina; Freire, Javier Limeres; Rodriguez-Palomares, Jose F; Kubo, Toru; Ripoll-Vera, Tomas; Barriales-Villa, Roberto; Antoniades, Loizos; Mogensen, Jens; Garcia-Pavia, Pablo; Wahbi, Karim; Biagini, Elena; Anastasakis, Aris; Tsatsopoulou, Adalena; Zorio, Esther; Gimeno, Juan R; Garcia-Pinilla, Jose Manuel; Syrris, Petros; Sinagra, Gianfranco; Bauce, Barbara; Elliott, Perry MProtonotarios, Alexandros; Bariani, Riccardo; Cappelletto, Chiara; Pavlou, Menelaos; García-García, Alba; Cipriani, Alberto; Protonotarios, Ioannis; Rivas, Adrian; Wittenberg, Regitze; Graziosi, Maddalena; Xylouri, Zafeirenia; Larrañaga-Moreira, José M; de Luca, Antonio; Celeghin, Rudy; Pilichou, Kalliopi; Bakalakos, Athanasios; Lopes, Luis Rocha; Savvatis, Konstantinos; Stolfo, Davide; Dal Ferro, Matteo; Merlo, Marco; Basso, Cristina; Freire, Javier Limeres; Rodriguez-Palomares, Jose F; Kubo, Toru; Ripoll-Vera, Tomas; Barriales-Villa, Roberto; Antoniades, Loizos; Mogensen, Jens; Garcia-Pavia, Pablo; Wahbi, Karim; Biagini, Elena; Anastasakis, Aris; Tsatsopoulou, Adalena; Zorio, Esther; Gimeno, Juan R; Garcia-Pinilla, Jose Manuel; Syrris, Petros; Sinagra, Gianfranco; Bauce, Barbara; Elliott, Perry

CLINICAL FEATURES AND FOLLOW-UP ANALYSIS OF PATIENTS AFFECTED WITH ARRHYTHMOGENIC LEFT VENTRICULAR CARDIOMYOPATHY ​

Background. Arrhythmogenic cardiomyopathy (ACM) is a genetically determined myocardial disease characterized by myocyte necrosis and fibro-adipose replacement, leading to ventricular dysfunction and onset of life-threatening ventricular arrhythmias (LTA). In the last years mainly through cardiovascular magnetic resonance (CMR) studies, a left-dominant form of the disease was described (arrhythmogenic left ventricular cardiomyopathy: ALVC). Aims. To characterize the genetic background, the clinical features, and the outcome of an ALVC cohort of patients and to compare this phenotype with the right dominant (ARVC) and biventricular (BIV) forms. Moreover, we sought to investigate possible prognostic predictive factors for LTA in ALVC patients. Methods. From the entire cohort of 544 patients (both probands and family members), we selected 434 patients affected by ACM (80%). According to phenotype the patients were divided into three groups: ARVC, ALVC and BIV. Family and personal history, genetic analysis, instrumental findings (ECG, 24-h Holter ECG, and CMR) and follow-up data were compared. Results. The study population was composed of 436 ACM patients, of whom 273 (63%) were male and 284 (65%) were probands. According to the phenotype, the general population was divided into three groups: 184 ARVC patients (42%), 112 ALVC (26%), 140 BIV (32%). In ALVC cohort 70 patients (63%) were male and 66 (59%) were probands. The median age at diagnosis was 38 years (IQR 26-49). Genetic analysis identified the presence of a pathogenic/likely pathogenic genetic variant in a causative gene in 61 patients (54%) with the most common disease-genes being Desmoplakin (DSP) (39, 63%). The ECG was abnormal in 74 (66%) cases, mainly due to the presence of low QRS complex voltages in the peripheral leads in (52, 46%) and T wave inversion (TWI) in V4-V6 (22, 20%). A total of 106 patients (95%) underwent CMR. A significant negative association was observed between LV ejection fraction and the extent of LV-LGE (β= -0.853, p=0,007). Overall, 18 patients (16%) had LTA episodes and in 9 (8%) this was the first clinical manifestation of the disease leading to ACM diagnosis. Five patients (5%) experienced heart failure (HF) and 2 (2%) underwent cardiac transplantation, while 2 (2%) died due to refractory HF. Four patients (4%) died suddenly, in all cases as first manifestation of the disease. Finally, 11 patients (10%) presented at least one hot phase episode. Proband status (HR 1.21), history of syncope (HR 2.53), and TWI in V4-V6 (HR 1.26) were associated with an increased arrhythmic burden. Comparison between the three phenotypes revealed that patients belonging to ALVC group showed a significantly lower incidence of LTA (16%), compared to ARVC (30%) and BIV (37%), p=0.001. HF was more frequent in BIV forms (20%) than in ALVC (5%) and ARVC (1%), p<0.001. Similarly, mortality rate was observed to be significantly higher in BIV patients (11%), compared to ALVC (2%) and ARVC (1%), as well as heart transplantation (0% in ARVC, 2% in ALVC and 10% BIV, p<0.001). No statistical differences between the three groups were observed regarding incidence of hot phase episodes (p=0.121). Conclusions. Differential diagnosis between ALVC and phenocopies can be challenging. Padua criteria seem to improve the diagnostic sensitivity, allowing a significant increase in definite diagnoses in ALVC patients. Genetic test showed the presence of a causative genetic variant in 54% of patients, mostly on the DSP gene. Proband status, history of syncope and presence of TWI from V4-V6 were found to be associated with an increased risk of LTA in the ALVC population. The comparison between the three phenotypes revealed that ALVC showed a lower incidence of LTA, HF and death compared to BIV and ARVC groups.Background. Arrhythmogenic cardiomyopathy (ACM) is a genetically determined myocardial disease characterized by myocyte necrosis and fibro-adipose replacement, leading to ventricular dysfunction and onset of life-threatening ventricular arrhythmias (LTA). In the last years mainly through cardiovascular magnetic resonance (CMR) studies, a left-dominant form of the disease was described (arrhythmogenic left ventricular cardiomyopathy: ALVC). Aims. To characterize the genetic background, the clinical features, and the outcome of an ALVC cohort of patients and to compare this phenotype with the right dominant (ARVC) and biventricular (BIV) forms. Moreover, we sought to investigate possible prognostic predictive factors for LTA in ALVC patients. Methods. From the entire cohort of 544 patients (both probands and family members), we selected 434 patients affected by ACM (80%). According to phenotype the patients were divided into three groups: ARVC, ALVC and BIV. Family and personal history, genetic analysis, instrumental findings (ECG, 24-h Holter ECG, and CMR) and follow-up data were compared. Results. The study population was composed of 436 ACM patients, of whom 273 (63%) were male and 284 (65%) were probands. According to the phenotype, the general population was divided into three groups: 184 ARVC patients (42%), 112 ALVC (26%), 140 BIV (32%). In ALVC cohort 70 patients (63%) were male and 66 (59%) were probands. The median age at diagnosis was 38 years (IQR 26-49). Genetic analysis identified the presence of a pathogenic/likely pathogenic genetic variant in a causative gene in 61 patients (54%) with the most common disease-genes being Desmoplakin (DSP) (39, 63%). The ECG was abnormal in 74 (66%) cases, mainly due to the presence of low QRS complex voltages in the peripheral leads in (52, 46%) and T wave inversion (TWI) in V4-V6 (22, 20%). A total of 106 patients (95%) underwent CMR. A significant negative association was observed between LV ejection fraction and the extent of LV-LGE (β= -0.853, p=0,007). Overall, 18 patients (16%) had LTA episodes and in 9 (8%) this was the first clinical manifestation of the disease leading to ACM diagnosis. Five patients (5%) experienced heart failure (HF) and 2 (2%) underwent cardiac transplantation, while 2 (2%) died due to refractory HF. Four patients (4%) died suddenly, in all cases as first manifestation of the disease. Finally, 11 patients (10%) presented at least one hot phase episode. Proband status (HR 1.21), history of syncope (HR 2.53), and TWI in V4-V6 (HR 1.26) were associated with an increased arrhythmic burden. Comparison between the three phenotypes revealed that patients belonging to ALVC group showed a significantly lower incidence of LTA (16%), compared to ARVC (30%) and BIV (37%), p=0.001. HF was more frequent in BIV forms (20%) than in ALVC (5%) and ARVC (1%), p<0.001. Similarly, mortality rate was observed to be significantly higher in BIV patients (11%), compared to ALVC (2%) and ARVC (1%), as well as heart transplantation (0% in ARVC, 2% in ALVC and 10% BIV, p<0.001). No statistical differences between the three groups were observed regarding incidence of hot phase episodes (p=0.121). Conclusions. Differential diagnosis between ALVC and phenocopies can be challenging. Padua criteria seem to improve the diagnostic sensitivity, allowing a significant increase in definite diagnoses in ALVC patients. Genetic test showed the presence of a causative genetic variant in 54% of patients, mostly on the DSP gene. Proband status, history of syncope and presence of TWI from V4-V6 were found to be associated with an increased risk of LTA in the ALVC population. The comparison between the three phenotypes revealed that ALVC showed a lower incidence of LTA, HF and death compared to BIV and ARVC groups

microRNA and Cardiac Regeneration

Heart diseases are a very common health problem in developed as well as developing countries. In particular, ischemic heart disease and heart failure represent a plague for the patients and for the society. Loss of cardiac tissue after myocardial infarction or dysfunctioning tissue in nonischemic cardiomyopathies may result in cardiac failure. Despite great advancements in the treatment of these diseases, there is a substantial unmet need for novel therapies, ideally addressing repair and regeneration of the damaged or lost myocardium. Along this line, cardiac cell based therapies have gained substantial attention. Three main approaches are currently under investigation: stem cell therapy with either embryonic or adult stem cells; generation of patient-specific induced pluripotent stem cells; stimulation of endogenous regeneration trough direct reprogramming of fibroblasts into cardiomyocytes, activation of resident cardiac stem cells or induction of native resident cardiomyocytes to reenter the cell cycle. All these strategies need to be optimized since their efficiency is low.It has recently become clear that cardiac signaling and transcriptional pathways are intimately intertwined with microRNA molecules which act as modulators of cardiac development, function, and disease. Moreover, miRNA also regulates stem cell differentiation. Here we describe how miRNA may circumvent hurdles that hamper the field of cardiac regeneration and stem cell therapy, and how miRNA may result as the most suitable solution for the damaged heart

Desmoplakin Cardiomyopathy: Comprehensive Review of an Increasingly Recognized Entity

Desmoplakin (DSP) is a desmosomal protein that plays an essential role for cell-to-cell adhesion within the cardiomyocytes. The first association between DSP genetic variants and the presence of a myocardial disease referred to patients with Carvajal syndrome. Since then, several reports have linked the DSP gene to familial forms of arrhythmogenic (ACM) and dilated cardiomyopathies. Left-dominant ACM is the most common phenotype in individuals carrying DSP variants. More recently, a new entity—“Desmoplakin cardiomyopathy”—was described as a distinct form of cardiomyopathy characterized by frequent left ventricular involvement with extensive fibrosis, high arrhythmic risk, and episodes of acute myocardial injury. The purpose of this review was to summarize the available evidence on DSP cardiomyopathy and to identify existing gaps in knowledge that need clarification from upcoming research

Adaptive Interpolation Algorithm for Fast and Efficient Video Encoding in H.264

Publication in the conference proceedings of EUSIPCO, Florence, Italy, 200

Role of Exercise as a Modulating Factor in Arrhythmogenic Cardiomyopathy

The review addresses the role of exercise in triggering ventricular arrhythmias and promoting disease progression in arrhythmogenic cardiomyopathy (AC) patients and gene-mutation carriers, the differential diagnosis between AC and athlete's heart and current recommendations on exercise activity in AC

Genetic Background and Clinical Features in Arrhythmogenic Left Ventricular Cardiomyopathy: A Systematic Review

In recent years a phenotypic variant of Arrhythmogenic cardiomyopathy has been described, characterized by predominant left ventricular (LV) involvement with no or minor right ventricular abnormalities, referred to as Arrhythmogenic left ventricular cardiomyopathy (ALVC). Different disease-genes have been identified in this form, such as Desmoplakin (DSP), Filamin C (FLNC), Phospholamban (PLN) and Desmin (DES). The main purpose of this critical systematic review was to assess the level of knowledge on genetic background and clinical features of ALVC. A search (updated to April 2022) was run in the PubMed, Scopus, and Web of Science electronic databases. The search terms used were "arrhythmogenic left ventricular cardiomyopathy" OR "arrhythmogenic cardiomyopathy" and "gene" OR "arrhythmogenic dysplasia" and "gene". The most represented disease-gene turned out to be DSP, accounting for half of published cases, followed by FLNC. Overall, ECG abnormalities were reported in 58% of patients. Major ventricular arrhythmias were recorded in 26% of cases; an ICD was implanted in 29% of patients. A total of 6% of patients showed heart failure symptoms, and 15% had myocarditis-like episodes. DSP is confirmed to be the most represented disease-gene in ALVC patients. An analysis of reported clinical features of ALVC patients show an important degree of electrical instability, which frequently required an ICD implant. Moreover, myocarditis-like episodes are common