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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 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.

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.

Aims: the role of sex in determining the profile and the outcomes of patients with myocarditis is largely unexplored. We evaluated the impact of sex as a modifier factor in the clinical characterization and natural history of patients with definite diagnosis of myocarditis. Methods and results: we retrospectively analysed a single-centre cohort of consecutive patients with definite diagnosis of myocarditis (i.e. endomyocardial biopsy or cardiac magnetic resonance proven). Specific sub-analyses were performed in cohorts of patients with chest pain, ventricular arrhythmias, and heart failure as different main symptoms at presentation. The primary outcome measure was a composite of all-cause mortality or heart transplantation (HTx). We included 312 patients, of which 211, 68% of the whole population, were males. Despite no clinically relevant differences found at baseline presentation, males had a higher indexed left ventricular end-diastolic volume (62 ± 23 mL/m2 vs. 52 ± 20 mL/m2, P = 0.011 in males vs. females, respectively) at follow-up evaluation. At a median follow-up of 72 months, 36 (17%) males vs. 8 (8%) females experienced death or HTx (P = 0.033). Male sex emerged as predictors of all-cause mortality or HTx in every combination of covariates (HR 2.600; 1.163–5.809; P = 0.020). Results were agreeable regardless of the main symptom of presentation. Conclusions: in a large cohort of patients with definite diagnosis of myocarditis, females experienced a more favourable long-term prognosis than males, despite a similar clinical profile at presentation.

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

Patients with type 2 diabetes mellitus (T2DM) have more than twice the risk of developing heart failure (HF) compared to patients without diabetes. The present study is aimed to build an artificial intelligence (AI) prognostic model that takes in account a large and heterogeneous set of clinical factors and investigates the risk of developing HF in diabetic patients. We carried out an electronic health records- (EHR-) based retrospective cohort study that included patients with cardiological clinical evaluation and no previous diagnosis of HF. Information consists of features extracted from clinical and administrative data obtained as part of routine medical care. The primary endpoint was diagnosis of HF (during out-of-hospital clinical examination or hospitalization). We developed two prognostic models using (1) elastic net regularization for Cox proportional hazard model (COX) and (2) a deep neural network survival method (PHNN), in which a neural network was used to represent a non-linear hazard function and explainability strategies are applied to estimate the influence of predictors on the risk function. Over a median follow-up of 65 months, 17.3% of the 10,614 patients developed HF. The PHNN model outperformed COX both in terms of discrimination (c-index 0.768 vs 0.734) and calibration (2-year integrated calibration index 0.008 vs 0.018). The AI approach led to the identification of 20 predictors of different domains (age, body mass index, echocardiographic and electrocardiographic features, laboratory measurements, comorbidities, therapies) whose relationship with the predicted risk correspond to known trends in the clinical practice. Our results suggest that prognostic models for HF in diabetic patients may improve using EHRs in combination with AI techniques for survival analysis, which provide high flexibility and better performance with respect to standard approaches.

Aims Prognostic stratification of acute myocarditis (AM) presenting with normal left ventricular (LV) ejection fraction (EF) relies mostly on late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) imaging. In this specific AM population, LV peak global longitudinal strain (LV-GLS) measured by feature tracking (FT) analysis might provide further prognostic information. Methods and results Data of patients undergoing CMR for clinically suspected AM in seven European Centres, between January 2013 and August 2020, were retrospectively analysed. Those patients fulfilling CMR Lake Louise Criteria (LLC) for the diagnosis of AM and presenting with normal LVEF (≥50%) were included. Patients presenting with heart failure (HF) or significant arrhythmic events, LVEF -20% or quartiles), diffuse and mid-wall LGE were associated with a significantly higher rate of ACEs. LV-GLS remained independently associated with ACEs after adjustment for diffuse or mid-wall LGE as covariate at bivariable analysis. Conclusions In AM with LVEF ≥50%, LV-GLS provides independent prognostic value over LGE, improving risk stratification and providing a rationale for further studies of therapy in this cohort. 100 Figure

Aims The role of sex in determining the profile and the outcomes of patients with myocarditis is widely unexplored. Our study seeks to evaluate the impact of sex as a modifier factor in the clinical characterization and natural history of patients with definite diagnosis of myocarditis. Methods and results We retrospectively analysed a single-centre cohort of consecutive patients with definite diagnosis (i.e., endomyocardial biopsy or cardiac magnetic resonance proven) of myocarditis. A sub-analysis was performed after division of population according to the main symptom of presentation (i.e., chest pain, ventricular arrhythmias, and heart failure). Clinical and echocardiographic data were evaluated at diagnosis and at last available evaluation (i.e., median of 30 months). The study outcome measure was a composite of all-cause mortality or heart transplantation. We enrolled 312 patients (187; 60% presenting with chest pain; 19; 6% with ventricular arrhythmias; 106; 34% with heart failure). Most of patients (211, 68% of the whole population) were males, consistently in the three modes of presentation. Despite no clinically relevant differences were found at baseline presentation, males presented a larger indexed left ventricular end-diastolic volume (LVEDVi) (62 ± 23 vs. 52 ± 20, P = 0.011 in males vs. females respectively) at follow-up evaluation. At a median follow-up of 62 months, 36 (17%) males vs. females experienced death or heart transplantation (Log-rank P = 0.037). At multivariable Cox analysis, male sex emerged as a predictor of mortality (HR: 2.358; 1.044–5.322; P = 0.039 and left ventricular ejection fraction (LVEF) < 50% (HR: 8.169; 1.226–54.425; P = 0.030)]. Results were consistent in patients presenting with heart failure and chest pain, while arrhythmic group was too small to be reliably interpreted. Conclusions In a large cohort of patients with definite diagnosis of myocarditis, females experienced a more favorable long-term prognosis than male, despite a similar clinical profile at baseline.

Aims Practice guidelines suggest implantable cardioverter defibrillators (ICD) in patients with left ventricular ejection fraction (LVEF) ≤35% despite 3–6 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 remodelling for up to 24 months after initiation of GDMT. We sought to assess the longitudinal dynamic relationship between LVEF ≤35% and arrhythmic risk in patients with recent onset non-ischaemic DCM under GDMT. Methods and results We performed a competitive risk analysis on patients with recent onset DCM (≤6 months) and recent initiation of GDMT (≤3 months), consecutively enrolled in a longitudinal registry. We assessed risk of major ventricular arrhythmic events or sudden cardiac death (MVAs/SCD) in relationship to LVEF ≤35% at enrollment, 6-months and 24-months post initiation of GDMT. 544 patients met inclusion criteria. LVEF ≤35% identified patients with increased risk of MVAs/SCD starting from 24-months after initiation of GDMT (hazards ratio: 2.126, 95% confidence interval: 1.065–4.245, P = 0.03). However, LVEF ≤35% at presentation or at 6 months post enrollment did not have prognostic significance. 67% of patients with LVEF ≤35% at 6 months after initiation of GDMT improved their LVEF to > 35% by 24 months. This late LVEF improvement correlated with a lower arrhythmic risk (P = 0.012) and was preceded by a reduction of LV dimensions in the first 6 months of GDMT. Conclusions In patients with DCM, risk stratification based on LVEF ≤35% is effective after 2 years of GDMT, but not after 6 months.

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 >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 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.

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% males, LVEF 62%) with available CV characterization within ±12 months from CT surgery were included. Abnormal loading conditions causing cardiac hypertrophy (LVH) were investigated to distinguish explained LVH (Ex-LVH) from unexplained LVH (Un-LVH). The primary outcome of the study was all-cause mortality. The secondary outcome measures were the occurrence of (i) new-onset heart failure (HF) or worsening HF requiring hospitalization (HHF) or (ii) pacemaker implantation. New-onset HF was defined as the development of HF signs and symptoms requiring an unplanned cardiologic examination or hospitalization. Median follow-up was 63 months [interquartile range (IQR): 30–95]. LVH was found in 65 (50%) patients, 33% of them presented Un-LVH. Compared to the others, Un-LVH patients were older (77, 75 vs. 70 years in Un-LVH, Ex-LVH, and non-LVH, respectively; P = 0.002), had higher rates of ECG-echo discrepancy (70%, 14.3% and 1.6%, respectively; P Conclusions At the time of CT surgery, Un-LVH was found in more than 30% of patients with LVH and 24% of them showed echocardiographic features suggesting an underdiagnosed CA. Un-LVH was associated with higher all-cause mortality and HF development.

Aims 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 after 60 years of age (i.e. late-onset DCM). The aim is to investigate the prevalence, type, and prognostic impact of disease-associated rare variants in late-onset DCM patients. Methods and results We analysed a population of late-onset DCM patients who had undergone genetic testing in seven international tertiary referral centres worldwide. A positive genotype was defined as the presence of ‘pathogenic’ or ‘likely pathogenic’ (P/LP) variants. The study outcome was all-cause mortality. 184 patients over age 60 years (56% females, mean age 67 ± 6 years, mean left ventricular ejection fraction 32 ± 10%) were studied. Sixty-six patients (36%) were carriers of a P/LP variant. Titin truncating variants (TTNtv) were the most prevalent (present in 25% of the total population and accounting for 69% of all genotype-positive patients). During a median follow-up of 42 months (interquartile range: 10–115), 23 patients (13%) died; 17 of these (25%) were carriers of P/LP variants while six patients (5.1%) were genotype-negative (P Conclusions In the largest series worldwide, to date, of patients with late-onset DCM, we found a high prevalence of female sex and a high genetic mutation burden, largely due to TTNtv. Patients with a positive genetic test had higher mortality than genotype-negative patients. These findings support the extended use of genetic testing also in the elderly.

Aims Therapy with antineurohormonal drugs at target doses has a prognostic benefits in heart failure with reduced ejection fraction. Dilated cardiomyopathy (DCM) represents a particular setting where the possible benefit of target doses of antineurohormonal drugs is unexplored. Methods and results All patients enrolled from 1/1/1992 to 1/3/2020 in the Trieste Muscle Heart Disease register affected by DCM with data on the dosage of therapy available both enrollment and at follow-up visit (i.e., 6–12 month) were included. The population was divided according to the percentage of recommended dose prescribed (0–49%, 50–99%, 100%) of both renin-angiotensin system inhibitors (RASi) and beta blockers (BB). A composite of death/heart transplant/hospitalization for heart failure was considered as the primary endpoint; a composite of sudden cardiac death/major ventricular arrythmias/defibrillator intervention was evaluated as a secondary endpoint. Prognostic associations were explored with uni- and multivariate analyses, Cox regressions, Kaplan–Meier, cumulative incidence curves and propensity score matching. 826 patients were included. At baseline 789 (96%) were taking a RASi and 627 (76%) a BB. The target dose of RASi was prescribed in 29% and 36% of patients at enrolment and at follow-up visit, respectively. The percentage of patients taking the maximum recommended dose of BB was 10% at baseline and 17% after optimization. Predictors of reaching target dose for RASi were BMI Conclusions In DCM a significant number of patients do not tolerate maximal therapy doses, mainly due to hypotension. The achievement of the target dose of RASi and BB, after adjustment for confounders had a neutral effect on the incidence of heart failure-related events. Uptitration of BB to the recommended dose has a strong protective effect on arrhythmic events.

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.

Aims Patients with ST-elevation myocardial infarction (STEMI) with multivessel disease (MVD) may be treated with different revascularization strategies. However, the potential predictors of outcomes on top of different revascularization strategies are poorly studied. This study aimed to evaluate the prognostic impact of two different revascularization strategies and the potential impact of medical therapy. Methods and results Using a propensity score approach, the impact of two treatment strategies was analysed—staged non-culprit revascularization group vs. culprit-lesion-only percutaneous coronary intervention (PCI) group—on a composite outcome of cardiovascular death (CVD), myocardial infarction, and repeated revascularization. Moreover, models were further adjusted for medication at discharge. Among 1385 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 revascularization 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 revascularization was associated with lower cardiovascular mortality compared with a culprit-only PCI strategy. However, both revascularization and medical therapy played a role in the improvement of mortality outcomes. Medical therapy amplified the benefit of myocardial revascularization.

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 2 (HR: 7.08, 95% CI: 2.50–20.1, P 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.

Aims: Left ventricular global longitudinal strain (GLS) by cardiac magnetic resonance feature tracking (CMR-FT) analysis has shown an incremental prognostic value compared to classical parameters in non-ischemic dilated cardiomyopathy (NICM). However, less is known about the role of right ventricular (RV) GLS. Our objective was to evaluate the prognostic impact of RV-GLS by CMR-FT analysis in a population of NICM patients.Methods: In this multicenter study, we examined NICM patients evaluated with a comprehensive CMR-FT study. Major cardiac events (MACEs) were considered as the study primary outcome measure and were defined as a composite of (a) cardiovascular death, (b) cardiac transplant or destination therapy ventricular assist device, (c) hospitalization for life-threatening ventricular arrhythmias or implantable cardiac defibrillator appropriate intervention. Heart failure (HF) related events, including hospitalizations and life-threatening arrhythmia-related events were considered as secondary end-points. Receiver operating time-dependent analysis were used to calculate the possible additional effect of RV-GLS to standard evaluation.Results: We consecutively enrolled 273 patients. During a median follow-up of 39 months, 41 patients (15%) experienced MACEs. RV-GLS and LV late gadolinium emerged as the strongest prognostic CMR-FT variables: their association provided an estimated 3-year MACEs rate of 29%. The addition of RV-GLS significantly improved the prognostic accuracy in predicting MACEs with respect to the standard evaluation including LGE (areas under the curve from 0.71 [0.66–0.82] to 0.76 [0.66–0.86], p = 0.03). On competing risk analysis, RV-GLS showed a significant ability to reclassify overall both HF-related and life-threatening arrhythmia-related events, regardless of LV and RV ejection fraction.Conclusions: In NICM patients, RV-GLS showed a significant prognostic role in reclassifying the risk of MACEs, incremental with respect to standard evaluation with standard prognostic parameters.

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Background Genotype-phenotype correlations in dilated cardiomyopathy (DCM) and, in particular, the effects of gene variants on clinical outcomes remain poorly understood. Objectives The purpose of this study was to investigate the prognostic role of genetic variant carrier status in a large cohort of DCM patients. Methods A total of 487 DCM patients were analyzed by next-generation sequencing and categorized the disease genes into functional gene groups. The following composite outcome measures were assessed: 1) all-cause mortality; 2) heart failure–related death, heart transplantation, or destination left ventricular assist device implantation (DHF/HTx/VAD); and 3) sudden cardiac death/sustained ventricular tachycardia/ventricular fibrillation (SCD/VT/VF). Results A total of 183 pathogenic/likely pathogenic variants were found in 178 patients (37%): 54 (11%) Titin; 19 (4%) Lamin A/C (LMNA); 24 (5%) structural cytoskeleton-Z disk genes; 16 (3.5%) desmosomal genes; 46 (9.5%) sarcomeric genes; 8 (1.6%) ion channel genes; and 11 (2.5%) other genes. All-cause mortality was no different between variant carriers and noncarriers (p = 0.99). A trend toward worse SCD/VT/VF (p = 0.062) and DHF/HTx/VAD (p = 0.061) was found in carriers. Carriers of desmosomal and LMNA variants experienced the highest rate of SCD/VT/VF, which was independent of the left ventricular ejection fraction. Conclusions Desmosomal and LMNA gene variants identify the subset of DCM patients who are at greatest risk for SCD and life-threatening ventricular arrhythmias, regardless of the left ventricular ejection fraction.

The relationship between left ventricular ejection fraction (LVEF) and outcomes after cardiac rehabilitation (CR) is not well established; therefore we assessed the prognostic role of LVEF at the end of ambulatory CR program in patients (pts) who received coronary revascularization. LVEF was evaluated at hospital discharge and re-assessed at the end of CR in all ST-elevation myocardial infarction and coronary artery bypass graft pts, while in pts with non-ST-elevation MI or elective percutaneous coronary intervention the echocardiography was repeated if they had an impaired LVEF at discharge. New hospitalizations for cardiovascular causes at 1-year, and cardiovascular mortality during long-term follow-up were analyzed. We enrolled in CR 3078 pts, 86% showed LVEF ≥40% and 9% LVEF

Objective The objective was to provide an exhaustive characterization of ECG features in a large cohort of dilated cardiomyopathies (DCMs) and then investigate their possible prognostic role in the long term. Background ECG is an accessible, reproducible, low-cost diagnostic and prognostic tool. However, an extensive description of ECG features and their long-term prognostic role in a large cohort of DCM is lacking. Methods All available baseline ECGs of DCM patients enrolled from 1992 to 2013 were systematically analysed. Patients underwent to a complete clinical-laboratory evaluation. The study outcome measures were death or heart transplant (D/HT) and sudden death or malignant ventricular arrhythmias (SD/MVA). Results Four hundred and fourteen DCM patients were enrolled. During a median follow-up of 125 months, 55 and 57 patients experienced D/HT and SD/MVA, respectively. At multivariate analysis, left ventricular hypertrophy (P = 0.017), heart rate (HR, P = 0.005) and anterolateral T-wave inversion (P = 0.041) predicted D/HT. Regarding SD/MVA, S wave amplitude in V2 (P = 0.008), R wave amplitude in DIII (P = 0.007), anterolateral T-wave inversion (P = 0.017) emerged as predictors. At receiver-operating curve analyses, the addition of ECG models to the clinical-laboratory evaluation significantly increased the area under the curve both for D/HT (from 0.68 to 0.74, P = 0.042) and SD/MVA (from 0.70 to 0.77, P = 0.048). Conclusion The exhaustive systematic evaluation of ECG has an incremental impact in the prognostication of a large cohort of DCM patients, also regarding the arrhythmic stratification.

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

Interpretability is fundamental in healthcare problems and the lack of it in deep learning models is currently the major barrier in the usage of such powerful algorithms in the field. The study describes the implementation of an attention layer for Long Short-Term Memory (LSTM) neural network that provides a useful picture on the influence of the several input variables included in the model. A cohort of 10,616 patients with cardiovascular diseases is selected from the MIMIC III dataset, an openly available database of electronic health records (EHRs) including all patients admitted to an ICU at Boston’s Medical Centre. For each patient, we consider a 10-length sequence of 1-hour windows in which 48 clinical parameters are extracted to predict the occurrence of death in the next 7 days. Inspired from the recent developments in the field of attention mechanisms for sequential data, we implement a recurrent neural network with LSTM cells incorporating an attention mechanism to identify features driving model’s decisions over time. The performance of the LSTM model, measured in terms of AUC, is 0.790 (SD = 0.015). Regard our primary objective, i.e. model interpretability, we investigate the role of attention weights. We find good correspondence with driving predictors of a transparent model (r = 0.611, 95% CI [0.395, 0.763]). Moreover, most influential features identified at the cohort-level emerge as known risk factors in the clinical context. Despite the limitations of study dataset, this work brings further evidence of the potential of attention mechanisms in making deep learning model more interpretable and suggests the application of this strategy for the sequential analysis of EHRs.

Funding Acknowledgements Type of funding sources: None. Background. A consistent proportion of patients with dilated cardiomyopathy (DCM) experience left ventricular reverse remodelling (LVRR) during the first 24 months of guideline-directed medical therapy (GDMT). However, important decisions, such as the need for ICD, are requested after 3 months of GDMT. The evolution of left ventricular ejection fraction (LVEF) during the first years after GDMT in DCM is unknown. Purpose. Our study aims to investigate the proportion and characterise DCM patients experiencing late LVEF improvement. Methods. We analysed DCM patients consecutively enrolled with short disease duration, recent initiation of GDMT (≤ 3 months) and a LVEF ≤ 35% at 6-month follow-up evaluation. LVEF > 35% at 24-month was the primary end-point of the study. Results. Among 131 patients (mean age 53 ± 14, male sex 74%), 88 (67%) improved their LVEF at 24 months above 35%. A > 10% reduction of the indexed left ventricular end-diastolic diameter (LVEDDi) between enrolment and 6-month evaluation emerged as the only independent predictor of late LVEF improvement. During the subsequent follow-up, the late LVEF improvement was associated with a lower cumulative incidence of major arrhythmic events, compared to patients with persistent LVEF ≤ 35% (p = 0.010). Conclusions. A high proportion of DCM patients improve their LVEF after more than 3-6 months of GDMT, which is associated with lower long-term arrhythmic risk. The early evaluation of dynamic parameters, such as the reduction of LVEDDi could help to identify those patients. Baseline population characteristics Total (131) LVEF > 35% at 24 months (88) LVEF ≤ 35% at 24 months (43) p Age (years) 53 ± 14 52 ± 14 54 ± 14 0.52 LVEF (%) 28.4 ± 5.6 29.2 ± 5.3 26.7 ± 5.8 0.02 LVEDDi (mm/m2) 34.9 ± 4.6 34.1 ± 4.7 36.5 ± 4.1 0.01 LVEDVi (ml/m2) 89.4 ± 34.2 83.7 ± 28.5 101.0 ± 41.5 0.01 RV dysfunction normalisation or persistence of normal RV function* 92 (84.4) 59 (84.3) 33 (84.6) 0.96 RFP disappearance* 115 (93.5) 80 (95.2) 35 (89.7) 0.25 MR improvement or persistence of mild/absent MR* 91 (72.2) 66 (78.6) 25 (59.5) 0.02 LVEF improvement* 30 (22.9) 21 (23.9) 9 (20.9) 0.7 LVEDDi reduction* 28 (23.7) 25 (32.1) 3 (7.5) 0.003 Values are presented as n (%) or mean ± SD. *Dynamic parameters are evaluated as change from enrollment to the 6-months evaluation. LVEDDi left ventricular end-diastolic diameter indexed; LVEDVi: left ventricular end diastolic volume indexed; LVEF: left ventricular ejection fraction; MR: mitral regurgitation; RFP: restrictive filling pattern; RV: right ventricular. Abstract Figure. Major outcome

Cardiomyopathies are primary myocardial disorders, genetically determined, with clinical onset between the third and the fifth decade of life. They represent the main causes of sudden cardiac death and heart failure in the youth. The more common myocardial diseases in clinical practice are dilated cardiomyopathy, arrhythmogenic cardiomyopathy and hypertrophic cardiomyopathy. Next generation sequencing techniques, recently available for genetics researches, together with the diffusion of advanced imaging techniques, permitted in the last years a deeper knowledge of these pathologies. Nevertheless, diagnosis, etiology and several aspects of patients' clinical management remain complex and controversial. This review paper aims to propose some operative flow-charts, derived from scientific evidences and the internal protocol of the Cardiothoracovascular Department of Trieste Hospital, Italian referral Center for cardiomyopathies and heart failure, with more than 30 years of experience in diagnosis and management of patients who suffer from primary myocardial disorders.

Background: The early diagnosis of genetically determined dilated cardiomyopathy (DCM) could improve the prognosis in mutation carriers. Left ventricular global longitudinal strain (LV GLS) and peak left atrial longitudinal strain (PALS) are promising techniques for the detection of subtle systolic and diastolic dysfunction. We sought to evaluate the prevalence of subtle systolic and diastolic dysfunction by LV GLS and PALS in a cohort of genotype-positive phenotype-negative (GPFN) DCM relatives. Methods and results: In this retrospective study, we analyzed echocardiograms of forty-one GPFN relatives of DCM patients. They were compared with age and sex matched healthy individuals (control group). Reduced LV GLS and PALS were defined as >18% and

Background: Little is known about the role of different types of atrial fibrillation (AF) in dilated cardiomyopathy (DCM). We investigated the epidemiological and prognostic impact of different types of AF in DCM during long-term follow-up. Method: We evaluated consecutive DCM patients enrolled in the Trieste Muscle Heart Disease Registry. Uni- and multivariable, extended Kaplan-Meier and propensity score-matching analyses were performed for a composite outcome including death/heart transplantation/ventricular-assist device implantation. Results: Out of 1181 DCM patients (71% males, age 49 ± 15 years, left ventricular ejection fraction 33 ± 11%), 46 (3.9%) had baseline permanent AF (permAF), while 66 (5.6%) had a history of paroxysmal/persistent AF. Compared with sinus rhythm (SR) patients, permAF patients were older (48 ± 15 vs. 61 ± 11 respectively, p = 0.001), were more frequently in NYHA class III-IV (18% vs. 30%, p = 0.002) and had larger left atrium diameter (40 ± 8 vs. 50 ± 10 mm, respectively). Paroxysmal/persistent AF patients had intermediate characteristics between permAF and SR. During a median follow-up of 135 (75–210) months, 63 patients developed permAF (0.45 new cases/100patients/year). At multivariable analysis, permAF as a time-dependent variable was an independent outcome predictor (HR 2.45; 95% C.I. 2.61–3.63, p < 0.001), together with creatinine, NYHA class, restrictive filling pattern and moderate-severe mitral regurgitation, while paroxysmal/persistent AF was neutral. Propensity score-matching analysis confirmed the higher rate of primary outcome events in patients with baseline or incident permAF versus patients without permAF during a very long-term follow-up (70% vs. 20%, p < 0.001). Conclusions: PermAF in a large DCM cohort had low prevalence and incidence but had a relevant. prognostic role on hard outcomes.

Aim: Contemporary survival trends in dilated cardiomyopathy (DCM) are largely unknown. The aim of this study is to investigate clinical descriptors, survival trends and the prognostic impact of aetiological characterization in DCM patients. Methods and results: Dilated cardiomyopathy patients were consecutively enrolled and divided into four groups according to the period of enrolment (1978-1984; 1985-1994; 1995-2004; and 2005-2015). A subset of patients with DCM of specific aetiology, enrolled from 2005 to 2015, was also analysed. Over a mean follow-up of 12 ± 8 years, 1284 DCM patients (52 in the 1978-1984 group, 326 in the 1985-1994 group, 379 in the 1995-2004 group, and 527 in the 2005-2015 group) were evaluated. Despite older age (mean age 51 ± 15, 43 ± 15, 45 ± 14, and 52 ± 15 years for the 1978-1984, 1985-1994, 1995-2004, and 2005-2015 groups, respectively; P < 0.001), most of the baseline clinical characteristics improved in the 2005-2015 group, suggesting a less advanced disease stage at diagnosis. Similarly, at competing risk analysis, the annual incidence of all outcome parameters progressively decreased over time (global P < 0.001). At multivariable analysis, the last period of enrolment emerged as independently associated with a reduction in all-cause mortality/heart transplantation (HTx)/ventricular assist device (VAD) implantation (1.46 events/100 patients/year), cardiovascular death/HTx/VAD implantation (0.82 events/100 patients/year) and sudden cardiac death (0.15 events/100 patients/year). Lastly, in 287 patients with DCM of specific aetiology, patients with environmental, toxic, or removable factors appeared to have different phenotypes and prognosis compared to those with genetic, post-myocarditis, or idiopathic DCM (P < 0.001). Conclusions: Contemporary survival trends in DCM significantly improved, mainly due to a reduction of cardiovascular events. Appropriate aetiological characterization might help in prognostication of DCM patients.

Funding Acknowledgements None Background Left ventricular global longitudinal strain (LV-GLS) and peak left atrial longitudinal strain (PALS) are promising techniques for the detection of a subtle systolic and diastolic dysfunction for an early diagnosis of genetically determined dilated cardiomyopathy (DCM). Purpose. We sought to evaluate the prevalence of subtle systolic and diastolic dysfunction by LV-GLS and PALS in a cohort of genotype-positive phenotype-negative (GPFN) DCM relatives. Methods. We analysed echocardiograms (including LV-GLS and PALS) of 41 GPFN relatives of DCM patients (GPFN group - 37 ± 14 years, 48.8% male). They were compared with a matched group of 52 healthy individuals (control group). Reduced LV-GLS and PALS were defined as >-18% and Abstract 1040 Figure. Mean LV-GLS and PALS in GPFN and control

Defining short-term prognosis in nonischemic cardiomyopathy (NICM) is challenging in clinical practice. Although left ventricular reverse remodeling (LVRR) is a key prognostic marker in NICM there are few parameters able to predict it. We investigated whether a complete structural and functional cardiac magnetic resonance imaging (cMRI) evaluation was incremental to the classic clinical-echocardiographic approach in predicting LVRR in a large cohort of NICM patients receiving evidence-based treatment. Patients with a recent diagnosis of NICM (

AIM To assess adverse outcomes attributable to non-cardiac co-morbidities and to compare their effects by left ventricular ejection fraction (LVEF) group [LVEF

BACKGROUND: Extensive evidence exists about the prognostic role of systolic blood pressure (SBP) reduction ≤140mmHg. Recently, the SPRINT trial successfully tested the strategy of lowering SBP

BACKGROUND: Cut-out is the most common mechanical complication of the osteosynthesis of pertrochanteric fractures. This complication determines a significant increase in morbidity in elderly patient. Cut-out is defined as the varus collapse of the femoral head-neck fragment with the extrusion of the cephalic screw. Surgical treatment of cut-out might lead to further complications, longer rehabilitation, increased social burden and healthcare system costs. The aim of the study is to identify the predictors of cut-out to prevent its occurrence. MATERIALS AND METHODS: Study population included all patients affected by extracapsular fracture of the proximal femur who were admitted and treated with short cephalomedullary nailing at the Cattinara Hospital-ASUITS of Trieste between 2009 and 2014. A retrospective analysis of clinical and radiographic data was carried out and cut-out cases recorded. The data collected on the study population were analyzed to find an eventual correlation with the occurrence of cut-out. The independent variables were age, gender, side of the fracture, ASA class, Evans classification, nailing system, quality of reduction, TAD, CalTAD, and Parker ratio. RESULTS: The study population counted 813 cases, with an F:M ratio of 4:1 and a mean age of 84.7 years. The cut-out was recorded in 18 cases (2.2%). There was no statistically significant association between cut-out and age, sex, side of fracture, ASA class, and nailing system. The Evans classification, the quality of reduction, the TAD, the CalTAD, and the Parker's ratio demonstrated a significant correlation at univariate analysis with cut-out. The results of multivariate analysis confirmed that TAD, Parker AP, and quality of reduction were independently significantly correlated to cut-out. CONCLUSION: The results of the present study demonstrate that good quality of reduction and correct position of the lag screw are likely to decrease the risk of cut-out complication. A nomogram for cut-out prediction is proposed for clinical validation.

BACKGROUND AND OBJECTIVES: Bicuspid aortic valve (BAV) disease is the most common congenital cardiac malformation. The aim of the present article is to determine clinical and echocardiographic prognostic factors and provide a predictive model of outcome of a large cohort of patients with BAV. METHODS: We retrospectively enrolled 337 patients consecutively assessed for echocardiography at our Cardiology Department from 1993 to 2014. We considered aortic valve replacement, aortic surgery and cardiovascular death as a clinical combined end-point. Predictors of outcome were determined by Cox regression. RESULTS: Mean age was 29.2 ± 19.8 years, median 27.1 years. A total of 38.4% patients presented a history of hypertension. Mean duration of follow-up was 8.4 ± 6.1 years, range 0-21 years. A total of 73 patients underwent aortic valve replacement and/or aortic surgery during follow-up. Age at surgery was 45.2 ± 15.6 years. Seven patients died because of cardiovascular causes. At multivariate analysis, baseline clinical predictors were history of hypertension [hazard ratio (HR) 2.289, 95% confidence interval (CI) 1.350-3.881, P = 0.002], larger ascending aortic diameter (HR 2.537, 95% CI 1.888-3.410, P

Adult patients with simple congenital heart disease (sACHD) represent an expanding population vulnerable to atrial arrhythmias (AA). CHA

Background Limited data are available on mid‐range ejection fraction (mr EF ) patients with dilated cardiomyopathy. We sought to define the characteristics, evolution, and long‐term prognosis of dilated cardiomyopathy patients with mr EF at diagnosis. Methods and Results We analyzed all dilated cardiomyopathy patients consecutively evaluated in the Trieste Heart Muscle Disease Registry from 1988 to 2013. mr EF and reduced ejection fraction ( rEF ) were defined as baseline left ventricular ( LV ) ejection fraction values between 40% and 49% and EF at presentation. At baseline, as compared with the rEF group, mr EF patients had lower rates of moderate–severe mitral regurgitation and restrictive LV filling pattern. During a median follow‐up period of 120 (60–204) months, the mr EF group presented a lower rate of death/heart transplantation (9% versus 36%, P P rEF patients. Moreover, 29 out of 175 mr EF patients (17%) evolved to rEF . Restrictive LV filling pattern emerged as the strongest predictor of rEF development following multivariable analysis. Conclusions mr EF identified a consistent subgroup of dilated cardiomyopathy patients diagnosed in an earlier stage with subsequent apparent better long‐term evolution. However, 17% of these patients evolved into rEF despite the use of medical therapy. A baseline restrictive LV filling pattern was independently associated with subsequent evolution to rEF .