Major Ventricular Arrhythmias Research Articles

207 RE-DEFINING ARRHYTHMOGENIC CARDIOMYOPATHY: CHARACTERIZATION AND LONG-TERM PROGNOSTIC IMPLICATIONS

Abstract Background Arrhythmogenic dilated cardiomyopathy (AR-DCM) combines phenotypical aspects of dilated cardiomyopathy (DCM) and risk of sudden cardiac death (SCD), typical of the arrhythmogenic form (ACM). However, AR-DCM is often ambiguously defined leaving clinicians uncertain on how to identify these high-risk patients. The aims of the study were to re-define AR-DCM based on outcome related arrhythmic markers and to test the usefulness of the novel AR-DCM definition in identifying arrhythmogenic genotypes (i.e., LMNA, FLNC, RBM20, and desmosomal genes). Materials and methods Consecutive DCM patients with genetic evaluation and Holter ECG monitoring or telemetry in two referral institution were analyzed. The arrhythmic markers tested to define AR-DCM were: SCD or major ventricular arrhythmias (MVA), unexplained syncope, rapid nonsustained ventricular tachycardia (nsTV), ≥1000 premature ventricular contractions/24 hours, or ≥50 ventricular couplets/24 hours. Patients were labeled as Early AR-DCM if criteria were met within 12 months from enrolment. The primary endpoint was a composite of SCD/MVA; the secondary endpoint was a composite of all-cause mortality/heart transplant/LVAD implantation (D/HTx/LVAD). Results Among the 743 DCM patients included, 290 had disease-related variants (39%), 94 (30%) of these carried arrhythmogenic genotype. Early AR-DCM was identified in 429 (58%) patients. During a median follow-up of 7.0 [2.2-13.8] years, among arrhythmic markers the occurrence of syncope and/or nsVT within 12 months from enrolment were the only arrhythmic markers independently associated with SCD/MVA (Figure), while the occurrence of early MVA and/or nsTV emerged as the strongest long-term predictors of D/ HTx/LVAD. Family history of MVA was also independently associated with primary and secondary endpoints, and together with MVA, nsTV or unexplained syncope increased the agreement between AR-DCM and arrhythmogenic genotypes in 1 out 2 patients. Conclusions A combination of early (i.e., within 1 year from diagnosis) MVA or nsVT or unexplained syncope might be proposed as a clinically useful new definition of AR-DCM, especially if associated to family history of MVA. This definition in fact allows clinicians to anticipates worse long-term arrhythmic and global outcomes, and to accurately identify malignant arrhythmogenic genotypes.

915 PHENOTYPIC EXPRESSION AND OUTCOMES OF CARDIOMYOPATHY CAUSED BY TITIN TRUNCATING VARIANTS: TRANSLATIONAL INSIGHTS

Abstract Background Titin truncating variants (TTNtv) represent the most prevalent genotype underlying dilated cardiomyopathy (DCM). Recent molecular studies provided initial evidence about different pathogenic mechanisms produced by different mutation sites of the truncating variant (A-Band vs non-A-band), possibly related to the presence or absence of truncated titin (TTN) peptides. However, to date, clinical studies on DCM patients carrying TTNtv failed to demonstrate any relevant clinical difference according to the titin band affected. We hypothesized this lack of variation could be partially explained by the selection bias of including only DCM phenotype patients. Thus, we studied the clinical phenotypes and outcomes of our entire population of subjects with pathogenic TTNtv regardless of phenotypic expression at the onset. Methods We retrospectively analyzed a population of pathogenic TTNtv carriers, enrolled in the Trieste Heart Muscle Disease Registry. TTNtv were classified according to their site (Z disk, I band, A band, A-M junction, M band) and further grouped for analysis in A-band and non-A band. Variables were expressed as mean±SD, median and interquartile range, or counts and percentage, as appropriate. Kaplan-Meier curves were estimated for the composite endpoints of (i) heart failure-related death, heart transplant, and destination left ventricular assist device implantation and (ii) first major ventricular arrhythmia (MVA, defined as SCD or life-threatening ventricular arrhythmia) and compared by the log-rank test. Results 154 TTNtv carriers were included in the study, of whom 66% were probands. The most prevalent phenotype was DCM (92%). The mean age of subjects at diagnosis was 43±16 years and 70% were males. There was no difference between groups in the first composite outcome of heart failure-related death, heart transplant, and destination left ventricular assist device implantation. Instead, major ventricular arrhythmias were significantly more frequent in the non-A-band group, in which 47% (n=14) of TTNtv carriers experienced MVA as compared to 19% (n=20) of subjects in the A-band group (p=0.001). Interestingly, we observed a tendency in MVA occurrence at a higher mean left ventricular ejection fraction (LVEF) in the non-A-band group as compared to the A-band group (42±13% vs 35±9%, respectively). Conclusions Among TTNtv carriers referred to a tertiary center, those with a mutation in the non-A band seem characterized by higher arrhythmic risk. This novel finding highlights the importance of considering the site of TTN truncating variants to guide the most appropriate clinical management for each patient.

1117 FAMILY SCREENING IN DILATED CARDIOMYOPATHY: CLINICAL CHARACTERIZATION AND FOLLOW UP OF RELATIVES

Abstract Background Familial patterns of inheritance and genetic mutations have been identified as pathogenic in nearly 40-50% of previously defined “idiopathic” Dilated Cardiomyopathy (DCM). Genetic testing in the proband allows cascade genetic screening in relatives, in order to promote an early diagnosis even in a pre-clinical stage of the disease, as recommended by international guidelines. This study aims to describe the clinical characteristics of screened relatives of Dilated Cardiomyopathy (DCM) patients, at baseline and during follow-up. Methods Screened relatives of patients affected by DCM were enrolled retrospectively and followed from January 2000 to August 2021. At baseline, the family screening included a clinical evaluation, ECG and echocardiogram. If likely pathogenetic (LP) or pathogenetic (P) variant was identified in the proband Genetic testing was offered and performed on relatives according to available consensus documents from the age of 10-12 years. The onset of disease was defined as left ventricular (LV) dilation and/or LV systolic dysfunction. The following information was obtained during the follow-up: all-cause death, cardiovascular death, sudden cardiac death (SCD), hospitalization for heart failure (HF), heart transplantation, ventricular assist device (VAD) implantation, ICD or CRT-D implantation and major ventricular arrhythmias (MVA). Results We enrolled 203 relatives from 32 families with DCM. The median follow-up was 94 months. At baseline, symptomatic relatives for dyspnea (NYHA II-III class) were 29 (14%), versus 174 (86%) of asymptomatic (NYHA I). All these subjects showed initial signs of DCM and experienced more frequently adverse outcomes, such as hospitalization for HF (p<0,001) and MVA (p<0,001) during follow-up. Among asymptomatic relatives, patients with initial signs of disease were 46 (26%), 20 (43%) with LV dilation and dysfunction, 18 (39%) with LV dysfunction and 7 (15%) with LV dilatation. During follow-up, 5 of them (11%) died and 2 (4%) experienced SCD (one carrier of FLNC variant). Globally, affected relatives at baseline carried a LP/P variant in more than half of the cases (57%), the remaining part being relative of proband with no or negative genetic testing. Non-affected relatives were 128 (74%) at baseline. 15 relatives (12%) developed initial signs of DCM (5 with LV dilation, 5 with LV dysfunction, 5 with LV dilation and dysfunction) during follow-up. Of those, 13 patients (87%) carried a LP/P variant. The genes mostly involved were TTN (9 cases,69%), followed by DSP and FLNC. Conclusions Familial screening allows an early diagnosis of DCM-affected patients. Asymptomatic relatives at the baseline showed a better outcome compared with symptomatic ones. However, SCD events were only detected in the asymptomatic group. Moreover, subjects who develop the disease during follow-up were carriers of a LP/P variant. Seriate follow-up is mandatory in relatives independently by symptoms at the baseline: genetic testing supports a focused clinical screening of high-risk relatives.

Natural history and clinical parameters of chemotherapy-induced dilated cardiomyopathy

Abstract Background 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 All consecutive DCM patients enrolled in the Trieste Muscle Heart Disease Registry were analyzed. 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. Results The study included 551 patients (499 iDCM and 52 CI-DCM). At enrolment, compared to 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 (35%±10 vs 32%±9, 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 to 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 to 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% CI 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 to iDCM. Conversely, the incidence of life-threatening ventricular arrhythmic events was higher among patients with iDCM. Funding Acknowledgement Type of funding sources: None.

Natural history of MYH7-related dilated cardiomyopathy

Abstract Background Variants in MYH7 are responsible for disease in 1–5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. Objectives We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. Methods We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% females, 35.6±19.2 years) recruited from 29 international centers. Results At initial evaluation, 106 patients (72.1%) had DCM (LVEF 34.5±11.7%). Median follow-up was 4.5 years (interquartile range: 1.7–8.0). 23.7% carriers who were initially phenotype-negative developed DCM. Disease penetrance by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years. Thirty-six percent of patients with DCM met imaging criteria for LV non-compaction. During follow-up, 28% showed left ventricular reverse remodeling (LVRR). Overall incidence of end-stage heart failure (heart transplantation or heart failure related death) was 11.6% at 5 years. Overall major ventricular arrhythmia rate was low (1.0% at 5 years) even among patients with LVEF ≤35% (2.1% at 5 years). LV non-compaction was more prevalent in patients with variants in head domain (S1) (44.2%) compared with other domains (P<0.001). No differences among domain groups were found regarding LVRR, major ventricular arrhythmias or end-stage heart failure. Conclusions MYH7-related DCM is characterized by early age of onset, high penetrance, low rate of LVRR, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, even among patients with severe systolic disfunction. Funding Acknowledgement Type of funding sources: None.

Natural History of MYH7-Related Dilated Cardiomyopathy

BackgroundVariants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. ObjectivesWe sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. MethodsWe studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. ResultsAt initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. ConclusionsMYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.

Clinical profile and long-term follow-up of a cohort of patients with desmoplakin cardiomyopathy.

Desmoplakin (DSP) genetic variants have been reported in arrhythmogenic cardiomyopathy with particular regard to predominant left ventricular (LV) involvement. The purpose of this study was to improve our understanding of clinical phenotype and outcome of DSP variant carriers. The clinical picture and outcome of 73 patients (36% probands) harboring a pathogenic/likely pathogenic DSP variant were evaluated. The phenotype during follow-up (mean 11 years; range 1-39 years) changed in 25 patients (35%), arrhythmogenic LV cardiomyopathy (ALVC) forms being the most frequent (n = 26 [36%]), followed by biventricular (BIV; n = 20 [27%]) and arrhythmogenic right ventricular cardiomyopathy (ARVC; n = 16 [22%]) forms. Major ventricular arrhythmias were detected in 21 patients (29%), and they were more common in ARVC (n = 6, 56%) and BIV forms (n = 8, 40%) than in ALVC forms (n = 4, 15%). In patients with ALVC, major ventricular arrhythmias occurred in the setting of a normal/mildly reduced systolic function. Heart failure (HF) occurred in 6patients(8%); none affected with ALVC. Females showed more commonly LV involvement, while ARVC forms were more frequently detected in males (21 [61%] vs 15 [38%]; P = .147). Males showed a higher incidence of major ventricular arrhythmias (18 [52%] vs 9 [24%]; P = .036), HF (11 [31%] vs 1 [3%]; P = .004), and cardiac death (11 [31%] vs 0 [0%]; P < .001). The clinical phenotype in pathogenic/likely pathogenic DSP variant carriers is wide. Although most patients show LV involvement, 16 (22%) has right ventricular abnormalities in keeping with a "classical" arrhythmogenic cardiomyopathy form. In ALVC, HF and major ventricular arrhythmias seem less common than in right ventricular and BIV variants. Females show more frequently LV involvement and a better outcome.

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.

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

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. 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±14years vs. 58±3years, 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 90months (IQR 54-140months), 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). 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.

A new score for life-threatening ventricular arrhythmias and sudden cardiac death in adults with transposition of the great arteries and a systemic right ventricle

To investigate the incidence of major adverse ventricular arrhythmias and related events (MAREs) and to develop a stratification tool predicting MAREs in adults with a systemic right ventricle (sRV). In a multicentre approach, all adults (≥16 years old) with a sRV undergoing follow-up between 2000 and 2018 were identified. The incidence of MAREs, defined as sudden cardiac death, sustained ventricular tachycardia, and appropriate implantable cardioverter-defibrillator (ICD) therapy, was analysed. The association of MAREs with clinical, electrical, and echocardiographic parameters was evaluated. A total of 1184 patients (median age 27.1 years; interquartile range 19.9-34.9 years; 59% male; 70% with atrial switch repair for D-transposition of the great arteries) were included. The incidence of MAREs was 6.3 per 1000 patient-years. On multivariate analysis, age, history of heart failure, syncope, QRS duration, severe sRV dysfunction and at least moderate left ventricular outflow tract obstruction were retained in the final model with a C-index of 0.78 [95% confidence interval (CI) 0.72-0.83] and a calibration slope of 0.93 (95% CI 0.64-1.21). For every five ICDs implanted in patients with a 5-year MARE risk >10%, one patient may potentially be spared from a MARE. Sudden cardiac death remains a devastating cause of death in a contemporary adult cohort with a sRV. A prediction model based on clinical, electrocardiographic, and echocardiographic parameters was devised to estimate MARE risk and to identify high-risk patients who may benefit from primary prevention ICD implantation.

C22 SYNCOPE UNIT AND REMOTE CONTROL IN THE ERA OF COVID–19 PANDEMIC: EXPERIENCE OF A SINGLE CENTER

IntroductionDuring the pandemic, many Syncope Units were closed due to inclusion of them and staff in Covid departments. In our experience, in order to meet the numerous requests of patients suffering from syncope, the care strategy was chosen to carry out all outpatient procedures within a single access. The use of this protocol made it possible to satisfy user requests, breaking down all barriers, including the fear of Covid–19.Materials and MethodsThe procedural process used in this period at our O.U. was: initial evaluation, execution of Active Stand Test, carotid sinus massage and implantation of loop recorder in a single access. Immediately after implantation, the patient was equipped with remote monitoring. Patients without events were followed only remotely and underwent telephone follow–up approximately every 3 months to update the center on their general state of health and any symptoms. In patients with events, the individual events were examined by the cardiologist and, by telephone follow–up, the presence of symptoms was assessed, correlating the recorded event with the reported symptom. These were subsequently summoned to the clinic.ResultsWith this operating model in the years 2020/2021 we managed 53 patients in the Syncope Unit. Of these, 5 underwent PM implantation for loop recorder’s remote monitoring of the paroxysmal AVB, and one patient, for the detection of major ventricular arrhythmias, was protected with Life Vest pending completion of cardiological screening. The remaining patients, thanks to the remote control, are constantly followed at home and monitored with periodic telephone follow–up.ConclusionsIn line with the literature, also in our ER there was a notable reduction in accesses for syncope. Our operating model was virtuous as it served to decongest the ER and the wards, concentrating all patients with syncope in our Syncope Unit and also reducing the number of tests necessary to arrive at an etiological diagnosis of syncope. The Covid–19 pandemic has accelerated the transformation process of the Syncope Unit which is no longer just an elective place for the diagnosis of syncope, but also a fundamental reference for the remote control of ICM wearers.

Transversal Arch Clamping for Complete Resection of Aneurysms of the Distal Ascending Aorta without Open Anastomosis.

Background: The extent of aortic replacement for aneurysms of the distal ascending aorta remains controversial and opinions vary between standard cross-clamp resection and open hemiarch anastomosis in circulatory arrest and selective cerebral perfusion. As the deleterious effects of extended circulatory arrest are well-known, borderline indication for distal ascending aorta aneurysm repair must be outweighed against the potential risk of complications related to the open anastomosis. In the present study, we describe our own approach consisting of “transversal arch clamping” for exhaustive resection of aneurysms of the distal ascending aorta without open anastomosis and we present the postoperative outcomes. Methods: Between May 2017 and December 2019, 35 patients with aneurysm of the ascending aorta (20 male, 15 female) underwent replacement with repair of the lesser curvature without circulatory arrest. Pre-operative, intraoperative, and postoperative clinical outcomes were retrospectively withdrawn from our institutional database and analyzed. Results: Maximal diameter of distal ascending aorta was 47.5 mm. Patient median age was 66 years (IQR 14) (range 42–86). Preoperative logistic median EuroSCORE II was 17% (IQR 11.3). Median duration of cardiopulmonary bypass and cardiac arrest were 137 (IQR 64) and 93 (IQR 59) min, respectively. In-hospital and 30-day mortality were 0%. There were no cases with acute low output syndrome, surgical re-exploration for bleeding, kidney injury requiring dialysis, or wound infection. Disabling stroke was observed in one patient (2.9%). There was one case of major ventricular arrhythmia (2.9%). Conclusions: Our institutional experience suggests that this novel technique is safe and feasible. It facilitates complete resection of the aortic ascending aneurysm avoiding circulatory arrest, antegrade cerebral perfusion, additional peripheral cannulation, and all related complications.

Prevalence and prognostic significance of ischemic late gadolinium enhancement pattern in non-ischemic dilated cardiomyopathy

Typical late gadolinium enhancement (LGE) patterns in dilated cardiomyopathy (DCM) include intramyocardial and subepicardial distribution. However, the ischemic pattern of LGE (subendocardial and transmural) has also been reported in DCM without coronary artery disease (CAD), but its correlates and prognostic significance are still not known. On these bases, this study sought to describe the prevalence and prognostic significance of the ischemic LGE pattern in DCM. A total of 611 DCM patients with available cardiac magnetic resonance were retrospectively analyzed. A composite of all-cause-death, major ventricular arrhythmias (MVAs), heart transplantation (HTx) or ventricular assist device (VAD) implantation was the primary outcome of the study. Secondary outcomes were a composite of sudden cardiac death or MVAs and a composite of death for refractory heart failure, HTx or VAD implantation. Ischemic LGE was found in 7% of DCM patients without significant CAD or history of myocardial infarction, most commonly inferior/inferolateral/anterolateral. Compared to patients with non-ischemic LGE, those with ischemic LGE had higher prevalence of hypertension and atrial fibrillation or flutter. Ischemic LGE was associated with worse long-term outcomes compared to non-ischemic LGE (36% vs 23% risk of primary outcome events at 5 years respectively, P=.006), and remained an independent predictor of primary outcome after adjustment for clinically and statistically significant variables (adjusted hazard ratio 2.059 [1.055-4.015], P=.034 with respect to non-ischemic LGE). The ischemic pattern of LGE is not uncommon among DCM patients without CAD and is independently associated with worse long-term outcomes.

73 Prevalence and prognostic significance of ischaemic late gadolinium enhancement pattern in non-ischaemic dilated cardiomyopathy

Abstract Aims Typical late gadolinium enhancement (LGE) patterns in dilated cardiomyopathy (DCM) include intramyocardial and subepicardial distribution. However, the ischaemic pattern of LGE (subendocardial and transmural) has also been reported in DCM without coronary artery disease (CAD), but its correlates and prognostic significance are still not known. On these bases, this study sought to describe the prevalence and prognostic significance of the ischaemic LGE pattern in DCM. Methods and results 611 DCM patients with available cardiac magnetic resonance were retrospectively analysed. A composite of all-cause-death, major ventricular arrhythmias (MVAs), heart transplantation (HTx) or ventricular assist device (VAD) implantation was the primary outcome of the study. Secondary outcomes were a composite of sudden cardiac death or MVAs and a composite of death for refractory heart failure, HTx or VAD implantation. Ischaemic LGE was found in 7% of DCM patients without significant CAD or history of myocardial infarction, most commonly inferior/inferolateral/anterolateral. Compared to patients with non-ischaemic LGE, those with ischaemic LGE had higher prevalence of hypertension and atrial fibrillation or flutter. Ischaemic LGE was associated with worse long-term outcomes compared to non-ischaemic LGE (36% vs. 23% risk of primary outcome events at 5 years, respectively, P = 0.006), and remained an independent predictor of primary outcome after adjustment for clinically and statistically significant variables [adjusted hazard ratio 2.059 (1.055–4.015), P = 0.034 with respect to non-ischaemic LGE]. Conclusions The ischaemic pattern of LGE is not uncommon among DCM patients without CAD and is independently associated with worse long-term outcomes.

423 Prevalence and prognostic significance of atrial arrhythmias in arrhythmogenic cardiomyopathy

Abstract Aims Limited data are available concerning atrial arrhythmias (AA) role in arrhythmogenic cardiomyopathy (AC). The aim of the present study was to assess the prevalence and incidence of AA in a large cohort of AC patients and to evaluate its association with clinical outcomes. Methods and results We retrospectively analysed 115 patients with definite diagnosis of ARVC, according to 2010 Task Force Criteria, enrolled in the Trieste Heart Muscle Disease Registry. Subjects were further classified into two phenotypic variants, based on ventricular involvement: right-dominant and biventricular form. Uni- and multivariable, extended Kaplan-Meier and cumulative incidence function analysis were performed, as appropriate, for the primary composite endpoint of death and heart transplant (HTx) and for the two distinct secondary endpoints of: (i) death, HTx and first heart failure (HF) hospitalization; (ii) first major ventricular arrhythmias (MVA). Mean age of patients at the time of enrollment was 39 ± 16 years and 80% were male. 73 patients (63%) had a right-dominant form, while 42 (37%) presented a biventricular involvement. AA occurred in the 26% of our study population at baseline or during a median follow-up of 214 months (IQR: 105–311), with a non-significant trend in higher cumulative incidence of AA in patients with biventricular form. At baseline, patients experiencing AA were older (44 ± 18 vs. 37 ± 15 years, P = 0.044) and had larger atrial dimensions, in particular of the right atrium (RA) (23, IQR: 19–27 vs. 18, IQR: 15–25 cm2, P &amp;lt; 0.007). AA emerged as independently associated to death/HTx (HR 2.68, 95% CI: 1.02–7.05, P = 0.046) along with NYHA class &amp;gt;2 (HR: 7.08, 95% CI: 2.50–20.1, P &amp;lt; 0.001) and RA area (HR: 1.05, 95% CI: 1.01–1.09, P = 0.011). Consistently, AA were also independently associated with the secondary endpoint of death/HTx/HF hospitalization (HR: 2.50, 95% CI: 1.06–5.88, P = 0.036), together with NYHA &amp;gt;2, the presence of biventricular involvement, higher RA and left atrium area. Finally, AA did not emerge as independently correlated to MVA during follow-up. Conclusions This observational long-term study suggests that AA were common in patients with AC and were independently associated with poor outcomes, mostly related to HF events. A prompt identification throughout the follow-up of AA appears relevant in improving the clinical management of AC patients.

358 Clinical characteristic and natural history of chemotherapy induced dilated cardiomyopathy

Abstract Chemotherapy can lead to chemotherapy-induced dilated cardiomyopathy (CI-DCM), recognized as one of the Non-ischaemic Dilated Cardiomyopathy (DCM) phenotypes characterized by worse outcome. Evidences on a direct comparison between idiopathic-DCM (iDCM) and CI-DCM still lack. We included all the consecutive patients enrolled in the Trieste Muscle Heart Disease Registry. C-DCM was defined according to current recommendations. Uni- and multivariable analysis and Kaplan-Meier were performed. The primary outcome was all-cause death and the secondary outcomes were cardiac death and a composite of heart failure hospitalization, heart transplantation, ventricular assist-device implantation and major ventricular arrhythmias. The study included 511 patients (499 patients affected by iDCM and 52 patients affected by CI-DCM). Compared to iDCM, CI-DCM patients were older (51 ± 14 years vs. 58 ± 3 years respectively, P &amp;lt; 0.001) and had a higher LVEF (35%±10 vs. 32%±9, P = 0.03). CI-DCM patients had a higher incidence of all-cause of death compared to iDCM (36.5% vs. 8.4%, P &amp;lt; 0.001), while the incidence of cardiac death (7% in the CI-DCM group vs. 4% in the iDCM group, P = 0. 232) and of the composite secondary outcome was comparable amongst the two groups. At multivariable analysis, the diagnosis of CI-DCM was an independent predictor of primary outcome incidence (HR: 5.79, 95% CI: 1.83–18.27), P = 0.003, together atrial fibrillation. In a well-selected DCM cohort, patients with a chemotherapic etiology had a higher incidence of all-cause mortality compared to iDCM, while the incidence of cardiac adverse events was comparable among CI-DCM and iDCM.

362 Trends in the use/non-use of guideline-directed medical therapy in non-ischaemic dilated cardiomyopathy with improved ejection fraction

Abstract Aims Guideline-directed medical therapy (GDMT) is associated with significant improvement of left ventricular function in an important fraction of patients with non-ischaemic dilated cardiomyopathy (NICM), and the recent definition of heart failure with improved ejection fraction (HFimpEF) highlights the importance of longitudinal assessment of left ventricular ejection fraction (LVEF); however, little is known about the long-term outcome of GDMT downtitration in patients with NICM who develop HFimpEF. We sought to assess the functional and prognostic impact of GDMT downtitration in this subgroup. Methods and results All consecutive NICM patients enrolled from 1991 to 2018 in the Trieste Heart Muscle Disease Registry with baseline LVEF ≤40% and with ≥1 LVEF assessment after baseline were included. ImpEF was defined as a baseline LVEF ≤40%, a ≥ 10 point increase from baseline LVEF, and a second measurement of LVEF &amp;gt;40%. GDMT downtitration was defined as any dose reduction or drug withdrawal of renin-angiotensin system inhibitors (RASi) or beta-blockers (BB). The outcome measures were a loss of impEF criteria, a composite of all-cause death and heart transplantation (ACD/HTx), a composite of HF hospitalization, heart transplantation and left ventricular assist device (HFH/HTx/LVAD), and a composite of sudden death and major ventricular arrhythmias (SD/MVA). The prognostic role of GDMT downtitration was assessed with Kaplan–Meier analysis and curves of cumulative incidence, considering GDMT downtitration, loss of impEF, and the composites of outcome as time-dependent variables. Among 452 NICM patients with impEF, 186 (41.2%) downtitrated GDMT (median time to downtitration 35 months). Loss of impEF criteria occurred in 186 patients (median time to loss of impEF 51 months). While no significant differences in terms of ACD/HTx, HFH/HTx/LVAD, or SD/MVA among those who downtitrated GDMT and those who didn’t were observed, the population that downtitrated GDMT had a higher cumulative incidence of loss of impEF (P &amp;lt; 0.001). Conclusions In NICM patients who develop impEF, we observed a ≈ 40% rate of recurrent decline of LVEF. GDMT downtitration seems to be associated with this functional deterioration, although no differences in terms of major cardiovascular outcomes emerged.

Supraventricular Tachycardia Causing Left Ventricular Dysfunction

There is limited evidence on characterization and natural history of supraventricular tachycardia (SVT)-induced left ventricular (LV) dysfunction. The aim of this work was to characterize clinical features and long-term evolution of SVT-induced LV dysfunction. Patients consecutively admitted with sustained SVT and heart rate >100 bpm as the only known cause of a new onset LV systolic dysfunction (i.e., LV ejection fraction [EF] <50%) were analyzed. Patients were then revaluated periodically. Recovered LVEF (i.e., ≥50%) and a composite of death, heart transplant or first episode of major ventricular arrhythmias were evaluated as study end-points. We enrolled 83 patients. After SVT therapy, 56 (67%) showed a recovered LVEF at the last follow-up of median 54 (interquartile range 36 to 87) months. Seventeen (30%) of those patients had a temporary new drop in LVEF during follow-up associated to high-rate SVT relapse. At presentation, patients with recovered LVEF were younger (52 vs 67 years respectively, p <0.001) and had higher LVEF (34% vs 27% respectively, p=0.005) compared to non-recovered LVEF patients. Finally, 4% of recovered LVEF patients vs 26% of nonrecovered LVEF patients experienced death/heart transplant/major ventricular arrhythmias during follow-up (p=0.004). In conclusion, after almost 5 years of follow-up, two-thirds of patients with high-rate SVT causing a newly diagnosed LV systolic dysfunction recovered and maintained normal LV function after SVT control, with a subsequent benign outcome. Long term individual surveillance is required in those patients, as arrhythmic recurrences and new drops in LVEF are common in the long term.

Long-term mortality benefit of CRT-D vs. CRT-P upgrade procedures from conventional devices without prior ventricular arrhythmias

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the ÚNKP-20-3-I New National Excellence Program if the Ministry for Innovation and Technology in Hungary, the National Research, Development, and Innovation Office of Hungary (NKFIA; NVKP_16-1-2016-0017 National Heart Program), and the Higher Education Institutional Excellence Program of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development thematic program of the Semmelweis University. This work was also supported by the Artificial Intelligence Research Filed Excellence Program of the National Research, Development and Innovation Office of the Ministry of Innovation and Technology in Hungary (TKP/ITM/NKFIH). The research was also financed by the Thematic Excellence Program (Tématerületi Kiválósági Program, 2020-4.1.1-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Bioimaging thematic program of the Semmelweis University. Background Cardiac Resynchronization Therapy (CRT) upgrade can reverse pacing-induced cardiomyopathy (PiCMP) and related major ventricular arrhythmias (MVA). However, there is a lack of data comparing mortality benefit of adding an ICD to CRT during upgrade procedures in those without prior malignant ventricular arrhythmias (VAs). Purpose We aimed to compare the all-cause mortality, echocardiographic response, MVA occurrence and the rate of complications of patients with prior pacemakers (PM) upgraded to CRT-P or CRT-D devices. Methods Between 2000-2018 patients who underwent a successful CRT upgrade procedure from conventional pacemaker without a prior MVAs were collected. From 270 patients 83 (30.7%) upgraded to CRT-D, 187 (69.3%) to CRT-P device. The primary endpoint was all-cause mortality, secondary endpoints were echocardiographic response defined as left ventricular ejection fraction (LVEF) increase ≥5%, the occurrence of subsequent MVAs and the rate of periprocedural complications. Results CRT-D upgrade patients were more likely to be males, have a favourable renal function and lower LVEF compared to CRT-P group. During the median follow-up time of 3.7 years, 25 (30%) CRT-D and 131 (70%) CRT-P upgrade patients reached the primary endpoint. By univariate analysis, CRT-D upgrade patients showed 45% (HR 0.55; 95%CI 0.38-0.78; p &amp;lt; 0.01) lower all-cause mortality risk than CRT-P group. By multivariate analysis CRT-D (HR 0.39; 95%CI 0.23-0.66; p &amp;lt; 0.01), male sex (HR 1.60; 95%CI 1.03-2.47; p = 0.04), LVEF (HR 0.97; 95%CI 0.94-0.99; p &amp;lt; 0.01) have confirmed as independent predictors of all-cause mortality. Assessing secondary endpoints, LVEF response (66% vs 63%; p = 0.72), MVA occurrence (3.4% vs 0.8%; p &amp;lt; 0.01) and the rate of periprocedural complications were comparable in the two groups (14.8% vs 7%; p = 0.87), despite the higher number of lead explantations during CRT-D procedures than CRT-P upgrade (13% vs 1%; p &amp;lt; 0.001). Conclusions Adding an ICD during CRT upgrade procedures showed 45% lower all-cause mortality risk than CRT-P alone in patients with a pacemaker and no previous ventricular arrhythmias. This beneficial effect was independent of the echocardiographic response, safety or subsequent ventricular arrhythmias. Abstract Figure.

Catheter Ablation of Life-Threatening Ventricular Arrhythmias in Athletes.

A recent surveillance analysis indicates that cardiac arrest/death occurs in ≈1:50,000 professional or semi-professional athletes, and the most common cause is attributable to life-threatening ventricular arrhythmias (VAs). It is critically important to diagnose any inherited/acquired cardiac disease, including coronary artery disease, since it frequently represents the arrhythmogenic substrate in a substantial part of the athletes presenting with major VAs. New insights indicate that athletes develop a specific electro-anatomical remodeling, with peculiar anatomic distribution and VAs patterns. However, because of the scarcity of clinical data concerning the natural history of VAs in sports performers, there are no dedicated recommendations for VA ablation. The treatment remains at the mercy of several individual factors, including the type of VA, the athlete’s age, and the operator’s expertise. With the present review, we aimed to illustrate the prevalence, electrocardiographic (ECG) features, and imaging correlations of the most common VAs in athletes, focusing on etiology, outcomes, and sports eligibility after catheter ablation.