Search

Background 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 coronar y arter y 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. Methods 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. Results 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). Conclusions The ischemic pattern of LGE is not uncommon among DCM patients without CAD and is independently associated with worse long-term outcomes. (Am Heart J 2022;246:117-124.)

Background Machine learning (ML) methods to build prediction models starting from electrocardiogram (ECG) signals are an emerging research field. The aim of the present study is to investigate the performances of two ML approaches based on ECGs for the prediction of new-onset atrial fibrillation (AF), in terms of discrimination, calibration and sample size dependence. Methods We trained two models to predict new-onset AF: a convolutional neural network (CNN), that takes as input the raw ECG signals, and an eXtreme Gradient Boosting model (XGB), that uses the signal’s extracted features. A penalized logistic regression model (LR) was used as a benchmark. Discrimination was evaluated with the area under the ROC curve, while calibration with the integrated calibration index. We investigated the dependence of models’ performances on the sample size and on class imbalance corrections introduced with random under-sampling. Results CNN's discrimination was the most affected by the sample size, outperforming XGB and LR only above a certain threshold. Calibration showed only a small dependence on the sample size for all the models considered. Balancing the training set with random undersampling did not improve discrimination in any of the models. Instead, the main effect of imbalance corrections was to worsen the models’ calibration. The sample size emerged as a fundamental point for developing the CNN model, especially in terms of discrimination. The effect of the sample size on the other two models was weaker. Imbalance corrections led to poorly calibrated models, for all the approaches considered, reducing the clinical utility of the models. Conclusions Our results suggest that the choice of approach in the analysis of ECG should be based on the amount of data available, preferring more standard models for small datasets. Moreover, imbalance correction methods should be avoided when developing clinical prediction models, where calibration is crucial.

Background For patients with heart failure, prescription of loop diuretics (LD) and of higher doses are associated with an adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM). Methods Associations between outcomes and both furosemide-equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were classified as (i) dose↑ (FED increase by ≥ 50% or newly initiated); (ii) dose↓ (FED decrease by ≥ 50%); (iii) stable dose (change in FED by Results Of 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04–1.22], p = 0.003). Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% were dose↓; 26% were stable dose and 14% were dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of the primary outcome (HR 2.42 [95% CI 1.19–4.93], p = 0.015), while dose↑ had the worst prognosis (HR 2.76 [95% CI 1.27–6.03], p = 0.011). Results were similar for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with an improved outcome (HR 0.43 [95% CI 0.28–0.65], p Conclusions In patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never receive LD have an excellent prognosis. Graphical abstract

Within the abstract, the following phrase in the ‘Methods’ section “According to FED trajectory, patients were classified as (i) dose (FED increase by ≥ 50% or newly initiated);” was corrected to read “According to FED trajectory, patients were classified as (i) dose ↑ (FED increase by ≥ 50% or newly initiated);”. In the ‘Results’ section of the abstract, the sentence “Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04–1.22, p = 0.003].” was corrected to “Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04–1.22], p = 0.003).” Finally, in Table 1, the LVEF, % for Dose↓ patients was given incorrectly whenit should have been “28 (22-34)” and the N value has been corrected from “263” to “282”. The original article has been corrected.

Background Patients with ST-elevation myocardial infarction (STEMI) with multivessel disease (MVD) may be treated with different revascularisation strategies. However, the potential predictors of outcomes on top of different revascularisation strategies are poorly studied. This study aimed to evaluate the prognostic impact of two different revascularisation strategies and the potential impact of medical therapy. Methods Using a propensity score approach, the impact of two treatment strategies was analysed –staged non-culprit revascularisation group vs culprit-lesion-only percutaneous coronary intervention (PCI) group -- on a composite outcome of cardiovascular death (CVD), myocardial infarction, and repeated revascularisation. Moreover, models were further adjusted for medication at discharge. Results Among 1,385 STEMI patients treated with primary PCI, a subgroup of 433 with MVD was analysed. At the median follow-up of 41 (IQR, 21–65) months, after propensity-score adjustment, the multivariable Cox proportional hazard analysis showed that the staged non-culprit revascularisation group was associated with a lower composite endpoint (HR, 0.44; 95% CI, 0.24–0.82; p=0.01), lower CVD (HR, 0.34; 95% CI, 0.14–0.82; p=0.02), and lower all-cause death (HR, 0.46; 95% CI, 0.24–0.86; p=0.02). Use of renin-angiotensin inhibitors was associated with lower CVD (HR, 0.51; 95% CI, 0.27–0.95; p=0.03), and both renin-angiotensin inhibitors (HR, 0.52; 95% CI, 0.32–0.86; p=0.01) and beta blockers (HR, 0.48; 95% CI, 0.29–0.79; p=0.01) were associated with lower all-cause death. Conclusions In a real-word STEMI population with multivessel disease, staged non-culprit revascularisation was associated with lower cardiovascular mortality compared with a culprit-only PCI strategy. However, both revascularisation and medical therapy played a role in the improvement of mortality outcomes. Medical therapy amplified the benefit of myocardial revascularisation.

Background The combined prognostic role of cardiac magnetic resonance (CMR) and genotype in cardiomyopathies has not been fully investigated. The aim of this study was to identify specific genotype-CMR phenotype correlations in a well-characterized cohort of patients with a spectrum of left-sided cardiomyopathies spanning from arrhythmogenic (ACM) to dilated cardiomyopathy (DCM), and analyze patients’ outcome. Methods and Results One-hundred and seventy-four patients with DCM (127) and left sided ACM (47), who underwent a comprehensive evaluation including genetic testing and CMR imaging, were enrolled in this study. The phenotype was classified as DCM or ACM according to current consensus criteria. The primary outcome was a composite of sudden cardiac death/life-threatening ventricular arrhythmias (SCD/MVA). DCM patients showed more frequently pathogenic or likely pathogenic (P/LP) variants of non-arrhythmic genes (34% vs. 7%, p < 0.001), whereas ACM patients reported more frequently P/LP variants of arrhythmic genes (47% vs. 8%, p < 0.001) and non-ischemic free-wall LGE (30% vs. 10%, p = 0.002). After a median follow-up of 92 months (interquartile range 46 - 168), 39 patients (22%) reached the combined endpoint. Carrying a P/LP variant of arrhythmic genes (hazard ratio (HR) 2.2, 95% confidence interval (CI) 1.1 - 4.4, p = 0.024) along with presence of LGE (HR 4.5, 95% CI 1.99 - 11.5, p < 0.001) were independently associated with the study endpoint. Conclusion In cohort of well-characterized left sided cardiomyopathies patients spanning from ACM to DCM, a P/LP variant of arrhythmic genes along with presence of LGE were independent predictors of SCD/MVA.

Background For patients with heart failure, prescription of loop diuretics (LD) and higher doses are associated with adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM). Methods Associations between outcomes and both furosemide equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were divided in i) dose↑ (FED increase by ≥50% or newly initiated); ii) dose↓ (FED decrease by ≥50%); iii) stable dose (change in FED by Results Of 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20mg increase: 1.12 [95% CI 1.04-1.22, p=0.003]. Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% dose↓; 26% stable dose and 14% dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of primary outcome (HR 2.42 [95% CI: 1.19-4.93], p=0.015), while dose↑ had the worst prognosis (HR 2.76 [95% C.I. 1.27-6.03], p=0.011). The results were consistent for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with improved outcome (HR 0.43 [95% C.I. 0.28-0.65], p Conclusions In a large cohort of patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never require LD have an excellent prognosis.

Background Many prognostic risk scores have been developed for ambulatory Heart Failure (HF) patients, but none of these has been validated in Dilated Cardiomyopathy (DCM), that is a peculiar model of HF. Aims To evaluate and compare the applicability and performance of major HF risk models in a large real-world population of DCM patients Methods This was a retrospective study including 784 consecutive non ischemic DCM patients, both inpatients and outpatients, enrolled in the Heart Muscle Disease Registry (HMDR) of Trieste between January 2000 and December 2017. The following scores designed to estimate 1- to 3-year all-cause mortality were calculated in each participant: CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality), MAGGIC (Meta-analysis Global Group in Chronic Heart Failure), simplified-SHFM (Seattle Heart Failure Model), 3-CHF (Cardiac and Comorbid Conditions), GISSI-HF (Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico-Heart Failure), MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes), Barcelona Bio-HF, Krakow score. Results During the follow-up (5,83 ± 4,9 years) 191 patients (20% of the population) met the primary composite endpoint (158 deaths, 30 heart transplantations and 3 LVAD implants). Due to the high quote of missing parameters, only four of the prognostic models (MAGGIC, CHARM, 3-CHF and simplified-SHFM) could be tested in the final statistical analysis. The observed-to-predicted mortality ratios suggested an overestimation of mortality by all scores. The prognostic accuracy of the scales was suboptimal in DCM patients for MAGGIC (AUC 0.754) and CHARM (AUC 0.720) scores, worse for 3-CHF (AUC 0,677) and simplified-SHFM (AUC 0,667) scores, with the MAGGIC and simplified-SHFM respectively providing the best and worst performance. Conclusions The performance of HF prognostic risk scores is suboptimal for DCM patients. The need for new precise risk models tailored for this disease has to be considered.

Background although cardiopulmonary exercise testing (CPET) is a recognized tool for prognostic stratification in patients with dilated cardiomyopathy (DCM), there are no data about the prognostic value of its repetition during follow-up in this setting. The aim of this study was to test the prognostic value of repeating CPET during follow-up, among a large cohort of DCM patients. Methods in this multicenter, retrospective study, we analyzed DCM patients who consecutively performed at least two CPET during a clinical stable phase of disease. All patients performed CPET and echocardiogram within 10 days. The study end-point was a composite of death from all causes, heart transplantation, implantation of durable left ventricular assist device, life-threatening ventricular arrhythmias or hospitalization for HF. Results 216 DCM patients were enrolled (52±12 years, 78% male, NYHA I-II 82%, LVEF 32±9%, 94% on ACE inhibitors, 95% on beta-blockers); the duration of the disease at the time of first CPET was 68 months. The interval between the two CPETs was 15 (11;23) months. During a median follow-up of 38 months from the second CPET, 108 (47%) patients went through the end-point. Time-dependent ROC curves revealed that to repeat during a follow-up of 12 months both CPET and echocardiogram gives a more accurate prognostic stratification than basal echocardiography + basal CPET. Despite an higher AUC (0.91 vs 0.85) there were no significant different accuracies (95% CI: 83.6 - 98 vs 75.5–96.5; p-value: 0.2) between the repetition of CPET plus echocardiogram vs. the repetition of the echocardiogram alone. Among patients who experienced the study outcome, there was a substantial stability of echocardiographic values (relative variation of LVEF +2.7%, LVEDV +1.3%) but a significant worsening of functional capacity (relative variation of percentage predicted VO2 peak +6%, p-value: 0.002). Conversely, there were a significant improvement in echocardiographic values and CPET values in events-free patients (LVEF relative variation -8.6% p-value: 0.002; ppVO2 peak relative variation -6.8%, p-value: 0.002). Conclusion in a large population of clinically stable DCM patients, the systematic repetition of echocardiography or both CPET and echocardiography showed no significant prognostic impact, in presence of stable or worsened echocardiogram. Nevertheless, when there is a clinical variation of symptoms or a failing in the reverse remodeling process, 1-year repetition of CPET can identify higher risk patients.

Aims The prognostic role of bone tracer uptake in transthyretin cardiac amyloidosis (ATTR-CA) is controversial. The study investigated the potential prognostic significance of biventricular (BiV) uptake in ATTR-CA. Methods Consecutive ATTR-CA patients who had cardiac scintigraphy with acquisition of planar and single-photon emission computed tomography (SPECT) images from the National Amyloidosis Centre (NAC) and four Italian centres were included. Planar BiV uptake was defined in presence of right ventricle (RV) uptake and graded in combination with SPECT imaging. The primary outcome was all-cause mortality. Results Among 1422 patients with ATTR-CA, BiV uptake was found in 85% of cases on planar scintigraphy and in 100% of cases on SPECT images. During a median follow-up of 39 months, BiV uptake at planar scintigraphy was associated with a higher all-cause mortality compared to isolated LV uptake (40.5% vs 10.7%, p Conclusions Planar RV uptake leading to BiV uptake identified ATTR-CA patients with worse outcome, potentially serving as a novel prognostic marker.

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.

Background Tricuspid regurgitation (TR) is common in chronic heart failure (HF) and is associated with negative prognosis. However, evidence on prognostic implications of TR in acute HF (AHF) is lacking. Objectives We sought to investigate the association between TR and mortality and the interaction with pulmonary hypertension (PH) in patients admitted for AHF. Methods We enrolled 1176 consecutive patients with a primary diagnosis of AHF and with available non-invasive estimation of TR and pulmonary arterial systolic pressure (PASP). Results Moderate-severe TR was present in 352 patients (29.9%) and was associated with older age and more comorbidities. The prevalence of PH (i.e., PASP>40mmHg), right ventricular dysfunction (RVD) and mitral regurgitation (MR) was higher in moderate-severe TR. At 1 year, 184 (15.6%) patients died. Moderate-severe TR was associated with higher 1-year mortality risk after adjustment for other echocardiographic parameters (PASP, left ventricle ejection fraction – LVEF, RVD and MR; HR=1.623, p=0.004) and the association with outcome was maintained when clinical variables were added to the multivariable model (HR=1.515, p=0.035). The association between moderate-severe TR and outcome was consistent in patients with vs without PH, with vs without RVD, and with vs without LVEF Conclusions In patients hospitalized for AHF, the severity of TR is associated with 1-year survival, regardless of the presence of PH. However, the combination of moderate-severe TR and PH conferred a further incremental mortality risk.

Aims Carpal tunnel (CT) syndrome is a recognized red‐flag of cardiac amyloidosis (CA) and increased cardiovascular (CV) morbidity. We designed this study to characterize the CV profile of patients with CT syndrome at the time of first surgery and to identify high‐risk presentations. Methods and results We retrospectively reviewed 643 patients who underwent CT surgery between 2007 and 2019. Of them, 130 patients (77 years, 45% male patients, left ventricular ejection fraction 62%) with available CV characterization within ±12 months from CT surgery were included. Abnormal loading conditions causing cardiac left ventricular hypertrophy (LVH) were investigated to distinguish explained LVH (Ex‐LVH) from unexplained LVH (Un‐LVH). LVH was found in 66 (51%) patients, 33% of them presented Un‐LVH. Compared with the others, Un‐LVH patients were older (77 and 75 vs. 70 years in Un‐LVH, Ex‐LVH, and non‐LVH, respectively; P = 0.002), had higher rates of electrocardiogram‐echo discrepancy (70%, 14.3%, and 1.6%, respectively; P

Background Prognostic stratification of acute myocarditis (AM) presenting with normal left ventricular ejection fraction (LVEF) relies mostly on late gadolinium enhancement (LGE) characterization. Left ventricular peak global longitudinal strain (LV-GLS) measured by feature tracking analysis might improve prognostication of AM presenting with normal LVEF. Methods Data of patients undergoing cardiac magnetic resonance (CMR) for clinically suspected AM in seven European Centres (2013-2020) were retrospectively analysed. Patients with AM confirmed by CMR and LVEF >= 50% were included. LGE was visually characterized: localized versus. non-localized, subepicardial versus midwall. LV-GLS was measured by dedicated software. The primary outcome was the first occurrence of an adverse cardiovascular event (ACE) including cardiac death, life-threatening arrhythmias, development of heart failure or of LVEF Of 389 screened patients, 256 (66%) fulfilled inclusion criteria: median age 36 years, 71% males, median LVEF 60%, median LV-GLS -17.3%. CMR was performed at 4 days from hospitalization. At 27 months, 24 (9%) patients experienced >= 1 ACE (71% developed LVEF -20% or quartiles), non-localized and midwall LGE were associated with ACEs. Patients with LV-GLS = 50%, LV-GLS provides independent prognostic value over LGE characterization, improving risk stratification and representing a rationale for further studies of therapy in this cohort.

Objectives The aim of our study was to investigate the benefit of antiarrhythmic drugs (AAD) - beta-blockers, sotalol or amiodarone - in a cohort of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) patients with long-term longitudinal follow up. Background AAD are prescribed in ARVC to prevent ventricular arrhythmias and control symptoms. However, there are no controlled clinical trials and knowledges regarding the efficacy of AAD in ARVC are limited. Methods The study population included 123 patients with definite diagnosis of ARVC and ≥ 2 clinical evaluations. The primary outcome was a composite of sudden cardiac death (SCD)/recurrent major ventricular arrythmias (MVA): sudden cardiac arrest, sustained ventricular tachycardia (VT) and appropriate implantable cardioverter defibrillator interventions, including recurrent events in patients with >1 MVA. Time to first event (SCD or MVA) was considered as secondary composite endpoint. Results Sixteen patients were taking AAD at baseline and 75 started at least one AAD during a median follow-up of 132 months [61–255]. A total of 37 patients experienced ≥1 MVA with a total count of 83 recurrent MVA. After adoption of a propensity score analysis, no AAD were associated with lower risk of recurrent MVA. However, if dosage of AAD was considered, beta-blockers at >50% target dose were associated with a significant reduction in the risk of MVA compared to patients not taking beta-blockers (HR 0.10, 95% CI 0.02–0.46, p = 0.004). Conclusions In a large cohort of ARVC patients with a long-term follow-up, only beta-blockers administrated at >50% target dose were associated with lower risk of SCD/recurrent MVA.

Left ventricular ejection function (LVEF) is not reliable in identifying subtle systolic dysfunction. Speckle Tracking (ST) plays a promising role and hemodynamic forces (HDFs) are emerging as marker of LV function. The role of LV myocardial deformation and HDFs was investigated in a cohort of patients with aortic stenosis (AS) and normal LVEF. Two hundred fifty three patients (median age 79 years, IQR 73 - 83 years) with mild (n = 87), moderate (n =77) and severe AS (n =89) were retrospectively enrolled. 2D echocardiographic global longitudinal strain (GLS), circumferential strain (GCS) and HDFs were determined. The worsening of AS was associated with raising inappropriate LV mass (p < 0.001) and declined LVEF, despite being in the normal range (p < 0.001). ST and HDFs parameters declined as the AS became severe (p -19,9%) and LV systolic longitudinal force (LVsysLF) value (< 12,49), patients with impaired ST and lower HDFs components had increased incidence of aortic valve replacement (AVR) and worse survival (p

Aims The incidence and risk factors of pacemaker (PM) implantation in patients with cardiac amyloidosis (CA) are largely unexplored. We sought to characterize the trends in the incidence of permanent PM and to identify baseline predictors of future PM implantation in light-chain (AL) and transthyretin (ATTR) CA. Methods and results Consecutive patients with AL and ATTR-CA diagnosed at participating centres (2017-2020) were included. Clinical data recorded within +/- 1 month from diagnosis were collected from electronic medical records. The primary study outcome was the need for clinically-indicated PM implantation. Patients with PM (n = 41) and/or permanent defibrillator in situ (n = 13) at CA diagnosis were excluded. The study population consisted of 405 patients: 29.4% AL, 14.6% variant ATTR and 56% wild-type ATTR; 82.5% were male, median age 76 years. During a median follow-up of 33 months (interquartile range 21-46), 36 (8.9%) patients experienced the primary outcome: 10 AL-CA, 2 variant ATTR-CA and 24 wild-type ATTR-CA (p = 0.08 at time-to-event analysis). At multivariable analysis, history of atrial fibrillation (hazard ratio [HR] 3.80, p = 0.002), PR interval (HR 1.013, p = 0.002) and QRS >120 ms (HR 4.7, p = 0.001) on baseline electrocardiogram were independently associated with PM implantation. The absence of these three factors had a negative predictive value of 92% with an area under the curve of 91.8% at 6 months. Conclusion In a large cohort of AL and ATTR-CA patients, 8.9% received a PM within 3 years after diagnosis. History of atrial fibrillation, PR >200 ms and QRS >120 ms predicted future PM implantation.

Objective. To evaluated possible clinical and instrumental, natural history and prognostic divergences in women and men with idiopathic dilated cardiomyopathy (IDCM). Patients and Methods. From 1988 to 2012, we evaluated 803 consecutive patients with IDCM recorded in the Heart Muscle Disease Registry of Trieste (Italy). All patients had serial follow-up evaluations at 6, 12, and 24 months, and subsequently every two years, or more frequently if clinically indicated. Results. Two hundred and twenty-seven patients (28%) were female. At first evaluation women were significantly older (48 vs. 45 years old, p = 0.008); presented more frequently left bundle branch block at ECG (38% vs. 28%, p = 0.01), smaller left ventricular end-diastolic indexed volume at echocardiography (85 vs. 93 ml/m2, p

Adult patients with simple congenital heart disease (sACHD) represent an expanding population vulnerable to atrial arrhythmias (AA). CHA2DS2-VASc score estimates thromboembolic risk in non-valvular atrial fibrillation patients. We investigated the prognostic role of CHA2DS2-VASc score in a non-selected sACHD population regardless of cardiac rhythm. Between November 2009 and June 2018, 427 sACHD patients (377 in sinus rhythm, 50 in AA) were consecutively referred to our ACHD service. Cardiovascular hospitalization and/or all-cause death were considered as composite primary end-point. Patients were divided into group A with CHA2DS2-VASc score = 0 or 1 point, and group B with a score greater than 1 point. Group B included 197 patients (46%) who were older with larger prevalence of cardiovascular risk factors than group A. During a mean follow-up of 70 months (IQR 40–93), primary end-point occurred in 94 patients (22%): 72 (37%) in group B and 22 (10%, p < 0.001) in group A. Rate of death for all causes was also significantly higher in the group B than A (22% vs 2%, respectively, p < 0.001). Multivariable Cox regression analysis revealed that CHA2DS2-VASc score was independently related to the primary end-point (HR 1.84 [1.22–2.77], p = 0.004) together with retrospective AA, stroke/TIA/peripheral thromboembolism and diabetes. Furthermore, CHA2DS2-VASc score independently predicted primary end-point in the large subgroup of 377 patients with sinus rhythm (HR 2.79 [1.54–5.07], p = 0.01). In conclusion, CHA2DS2-VASc score accurately stratifies sACHD patients with different risk for adverse clinical events in the long term regardless of cardiac rhythm.

Right ventricular involvement in inferior myocardial infarction (MI) was historically associated with a poor prognosis. However, few studies addressed the impact of right ventricular (RV) dysfunction in the primary percutaneous intervention (pPCI) era. Our aim was to assess the prognostic significance of RV dysfunction in right coronary artery (RCA) related MI treated with pPCI. Methods: A total of 298 patients with a RCA related MI undergone pPCI between January 2011 and June 2015 were included. RV dysfunction was defined by a RV-FAC

IMPORTANCE: Dilated cardiomyopathy (DCM) is frequently caused by genetic factors. Studies identifying deleterious rare variants have predominantly focused on early-onset cases, and little is known about the genetic underpinnings of the growing numbers of patients with DCM who are diagnosed when they are older than 60 years (ie, late-onset DCM). OBJECTIVE: To investigate the prevalence, type, and prognostic impact of disease-associated rare variants in patients with late-onset DCM. DESIGN, SETTING, AND PARTICIPANTS: A population of patients with late-onset DCM who had undergone genetic testing in 7 international tertiary referral centers worldwide were enrolled from March 1990 to August 2020. A positive genotype was defined as the presence of pathogenic or likely pathogenic (P/LP) variants. MAIN OUTCOMES AND MEASURES: The study outcome was all-cause mortality. RESULTS: A total of 184 patients older than 60 years (103 female [56%]; mean [SD] age, 67 [6] years; mean [SD] left ventricular ejection fraction, 32% [10%]) were studied. Sixty-six patients (36%) were carriers of a P/LP variant. Titin-truncating variants were the most prevalent (present in 46 [25%] of the total population and accounting for 46 [69%] of all genotype-positive patients). During a median (interquartile range) follow-up of 42 (10-115) months, 23 patients (13%) died; 17 (25%) of these were carriers of P/LP variants, while 6 patients (5.1%) were genotype-negative. CONCLUSIONS AND RELEVANCE: Late-onset DCM might represent a distinct subgroup characterized by and a high genetic variation burden, largely due to titin-truncating variants. Patients with a positive genetic test had higher mortality than genotype-negative patients. These findings support the extended use of genetic testing also in older patients.

Practice guidelines suggest the use of implantable cardioverter-defibrillators in patients with left ventricular ejection fractions (LVEF) ≤ 35% despite 3 to 6 months of guideline-directed medical therapy (GDMT). It remains unclear whether this strategy is appropriate for patients with dilated cardiomyopathy (DCM), who can experience reverse ventricular remodeling for up to 24 months after the initiation of GDMT. The aim of this study was to assess the longitudinal dynamic relationship between LVEF ≤ 35% and arrhythmic risk in patients with recent-onset nonischemic DCM on GDMT.A retrospective analysis was conducted among patients with recent-onset DCM (≤6 months) and recent initiation of GDMT (≤3 months) consecutively enrolled in a longitudinal registry. Risk for major ventricular arrhythmic events or sudden cardiac death was assessed in relationship to LVEF ≤ 35% at enrollment and 6 and 24 months after initiation of GDMT.Five hundred forty-four patients met the inclusion criteria. LVEF ≤ 35% identified patients with increased risk for major ventricular arrhythmic events or sudden cardiac death starting from 24 months after initiation of GDMT (hazard ratio, 2.126; 95% CI, 1.065-4.245; P = .03). However, LVEF ≤ 35% at presentation or 6 months after enrollment did not have prognostic significance. Sixty-seven percent of 131 patients with LVEF ≤ 35% at 6 months after initiation of GDMT had improved LVEFs (to35%) by 24 months. This late LVEF improvement correlated with lower arrhythmic risk (P = .012) and was preceded by a reduction of LV dimensions in the first 6 months of GDMT.In patients with DCM, the present findings suggest that risk stratification for major ventricular arrhythmic events or sudden cardiac death on the basis of LVEF ≤ 35% is effective after 2 years of GDMT, but not after 6 months. In selected patients with DCM, it would be appropriate to wait 24 months before primary prevention ICD implantation.

In many clinical applications to evaluate the effect of a treatment, randomized control trials are difficult to carry out. On the other hand, clinical observational registries are often available and they contain longitudinal data regarding clinical parameters, drug therapies, and outcomes. In the past, much research has addressed causal methods to estimate treatment effects from observational studies. In the context of time-varying treatments, marginal structural models are often used. However, most analyses have focused on binary outcomes or time-to-the-first event analyses. The novelty of our approach is to combine the marginal structural methodology with the case where correlated recurrent events and survival are the outcomes of interest. Our work focuses on solving the nontrivial problem of defining the measures of effect, specifying the model for the time-dependent weights and the model to estimate the outcome, implementing them, and finally estimating the final treatment effects in this life-history setting. Our approach provides a strategy that allows obtaining treatment effect estimates both on the recurrent events and the survival with a clear causal and clinical interpretation. At the same time, the strategy we propose is based on flexible modeling choices such as the use of joint models to capture the correlation within events from the same subject and the specification of time-dependent treatment effects. The clinical problem which motivated our work is the evaluation of the treatment effect of beta-blockers in arrhythmogenic right ventricular cardiomyopathy (ARVC/D), and the dataset comes from the Trieste Heart Muscle Disease Registry.