Predictors of embolism and death in left-sided infective endocarditis: the European Society of Cardiology EURObservational Research Programme European Infective Endocarditis registry.

BACKGROUND AND AIMS: Even though vegetation size in infective endocarditis (IE) has been associated with embolic events (EEs) and mortality risk, it is unclear whether vegetation size associated with these potential outcomes is different in left-sided IE (LSIE). This study aimed to seek assessing the vegetation cut-off size as predictor of EE or 30-day mortality for LSIE and to determine risk predictors of these outcomes. METHODS: The European Society of Cardiology EURObservational Research Programme European Infective Endocarditis is a prospective, multicentre registry including patients with definite or possible IE throughout 2016-18. Cox multivariable logistic regression analysis was performed to assess variables associated with EE or 30-day mortality. RESULTS: There were 2171 patients with LSIE (women 31.5%). Among these affected patients, 459 (21.1%) had a new EE or died in 30 days. The cut-off value of vegetation size for predicting EEs or 30-day mortality was >10 mm [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.13-1.69, P = .0015]. Other adjusted predictors of risk of EE or death were as follows: EE on admission (HR 1.89, 95% CI 1.54-2.33, P < .0001), history of heart failure (HR 1.53, 95% CI 1.21-1.93, P = .0004), creatinine >2 mg/dL (HR 1.59, 95% CI 1.25-2.03, P = .0002), Staphylococcus aureus (HR 1.36, 95% CI 1.08-1.70, P = .008), congestive heart failure (HR 1.40, 95% CI 1.12-1.75, P = .003), presence of haemorrhagic stroke (HR 4.57, 95% CI 3.08-6.79, P < .0001), alcohol abuse (HR 1.45, 95% CI 1.04-2.03, P = .03), presence of cardiogenic shock (HR 2.07, 95% CI 1.29-3.34, P = .003), and not performing left surgery (HR 1.30 95% CI 1.05-1.61, P = .016) (C-statistic = .68). CONCLUSIONS: Prognosis after LSIE is determined by multiple factors, including vegetation size.

AI Cardiac MRI Scar Analysis Aids Prediction of Major Arrhythmic Events in the Multicenter DERIVATE Registry.

Background Scar burden with late gadolinium enhancement (LGE) cardiac MRI (CMR) predicts arrhythmic events in patients with postinfarction in single-center studies. However, LGE analysis requires experienced human observers, is time consuming, and introduces variability. Purpose To test whether postinfarct scar with LGE CMR can be quantified fully automatically by machines and to compare the ability of LGE CMR scar analyzed by humans and machines to predict arrhythmic events. Materials and Methods This study is a retrospective analysis of the multicenter, multivendor CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry. Patients with chronic heart failure, echocardiographic left ventricular ejection fraction (LVEF) of less than 50%, and LGE CMR were recruited (from January 2015 through December 2020). In the current study, only patients with ischemic cardiomyopathy were included. Quantification of total, dense, and nondense scars was carried out by two experienced readers or a Ternaus network, trained and tested with LGE images of 515 and 246 patients, respectively. Univariable and multivariable Cox analyses were used to assess patient and cardiac characteristics associated with a major adverse cardiac event (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare model performances. Results In 761 patients (mean age, 65 years ± 11, 671 men), 83 MACEs occurred. With use of the testing group, univariable Cox-analysis found New York Heart Association class, left ventricle volume and/or function parameters (by echocardiography or CMR), guideline criterion (LVEF of ≤35% and New York Heart Association class II or III), and LGE scar analyzed by humans or the machine-learning algorithm as predictors of MACE. Machine-based dense or total scar conferred incremental value over the guideline criterion for the association with MACE (AUC: 0.68 vs 0.63, P = .02 and AUC: 0.67 vs 0.63, P = .01, respectively). Modeling with competing risks yielded for dense and total scar (AUC: 0.67 vs 0.61, P = .01 and AUC: 0.66 vs 0.61, P = .005, respectively). Conclusion In this analysis of the multicenter CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry, fully automatic machine learning-based late gadolinium enhancement analysis reliably quantifies myocardial scar mass and improves the current prediction model that uses guideline-based risk criteria for implantable cardioverter defibrillator implantation. ClinicalTrials.gov registration no.: NCT03352648 Published under a CC BY 4.0 license. Supplemental material is available for this article.

CarDiac magnEtic Resonance for prophylactic Implantable-cardioVerter defibrillAtor ThErapy in Non-Ischaemic dilated CardioMyopathy: an international Registry.

AIMS: The aim of this registry was to evaluate the additional prognostic value of a composite cardiac magnetic resonance (CMR)-based risk score over standard-of-care (SOC) evaluation in a large cohort of consecutive unselected non-ischaemic cardiomyopathy (NICM) patients. METHODS AND RESULTS: In the DERIVATE registry (www.clinicaltrials.gov/registration: RCT#NCT03352648), 1000 (derivation cohort) and 508 (validation cohort) NICM patients with chronic heart failure (HF) and left ventricular ejection fraction <50% were included. All-cause mortality and major adverse arrhythmic cardiac events (MAACE) were the primary and secondary endpoints, respectively. During a median follow-up of 959 days, all-cause mortality and MAACE occurred in 72 (7%) and 93 (9%) patients, respectively. Age and >3 segments with midwall fibrosis on late gadolinium enhancement (LGE) were the only independent predictors of all-cause mortality (HR: 1.036, 95% CI: 1.0117-1.056, P < 0.001 and HR: 2.077, 95% CI: 1.211-3.562, P = 0.008, respectively). For MAACE, the independent predictors were male gender, left ventricular end-diastolic volume index by CMR (CMR-LVEDVi), and >3 segments with midwall fibrosis on LGE (HR: 2.131, 95% CI: 1.231-3.690, P = 0.007; HR: 3.161, 95% CI: 1.750-5.709, P < 0.001; and HR: 1.693, 95% CI: 1.084-2.644, P = 0.021, respectively). A composite clinical and CMR-based risk score provided a net reclassification improvement of 63.7% (P < 0.001) for MAACE occurrence when added to the model based on SOC evaluation. These findings were confirmed in the validation cohort. CONCLUSION: In a large multicentre, multivendor cohort registry reflecting daily clinical practice in NICM work-up, a composite clinical and CMR-based risk score provides incremental prognostic value beyond SOC evaluation, which may have impact on the indication of implantable cardioverter-defibrillator implantation.

Echocardiography-Derived Hemodynamic Forces Are Associated with Clinical Outcomes in Patients with Non-Ischemic Dilated Cardiomyopathy.

Introduction: Non-ischemic dilated cardiomyopathy (NIDCM) is characterized by a reduced left ventricular (LV) ejection fraction (LVEF, <50%) and a high risk for heart failure (HF) and death. Echocardiography-derived hemodynamic forces (HDFs) may provide important information on LV mechanics, but their prognostic value is unknown. Aim: To explore the features of echocardiography-derived HDFs in NIDCM and their association with clinical endpoints. Methods: Asymptomatic, non-hospitalized NIDCM patients free from coronary artery disease and moderate or severe valvular heart disease were included in this single-center observational retrospective longitudinal study. Those with atrial fibrillation and a follow-up <12 months were excluded. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death, HF hospitalization, and ambulatory intravenous diuretics administration. LV HDFs were analyzed with a prototype software. Apex-base (HDFs-ab), lateral-septal (HDFs-ls), and HDFs-angle were computed. Results: Ninety-seven patients were included, sixty-seven (69%) were males, mean age was 62 ± 14 years, and mean LVEF was 39.2 ± 8.6%. During a median follow-up of 4.2 (3.1-5.1) years, 19 (20%) patients experienced MACE. These patients had a higher HDFs-angle (71.0 (67.0-75.0) vs. 68.0 (63.0-71.0)°, p = 0.005), lower HDFs-ls (1.36 (1.01-1.85) vs. 1.66 ([1.28-2.04])%, p = 0.015), but similar HDFs-ab (5.02 (4.39-6.34) vs. 5.66 (4.53-6.78)%, p = 0.375) compared to those without MACE. in a Cox regression analysis, HDFs-angle (HR 1.16 (95%-CI 1.04-1.30), p = 0.007) was associated with MACE, while other conventional echocardiography parameters, including LVEF and LV longitudinal strain, were not. Conclusions: HDFs-angle is associated with clinical endpoints in NIDCM. A higher HDFs-angle may be a marker of impaired myocardial performance in patients with reduced LVEF.

Cardiac (tele)rehabilitation in routine clinical practice for patients with coronary artery disease: protocol of the REHAB + trial.

Introduction: Cardiac rehabilitation programs face the challenge of suboptimal participation, despite being a level Ia recommendation. Cardiac telerehabilitation, with its potential to engage patients who might otherwise not show interest, necessitates the adaption of existing center-based cardiac rehabilitation programs to facilitate rehabilitation at home. REHAB + is a mobile cardiac telerehabilitation program cocreated with patients and rehabilitation centers, aiming to future-proof cardiac rehabilitation and improve accessibility. The REHAB + application enables users to remotely communicate with their coach, receive on-demand feedback on health goal progression, and reduces the need for frequent in-person meetings at the cardiac rehabilitation center. The REHAB + study seeks to compare patient-related outcomes and characteristics of patients between those offered the option to participate in cardiac telerehabilitation and those attending center-based cardiac rehabilitation over a twelve-month period. Methods: The REHAB + study is a multicenter, prospective, matched controlled, observational study that includes (N)STEMI patients eligible for cardiac rehabilitation. We aim to enroll 300 participants for cardiac telerehabilitation and 600 for center-based cardiac rehabilitation. Participants opting for cardiac telerehabilitation (REHAB+) will be matched with center-based cardiac rehabilitation participants. Additionally, characteristics of patients unwilling to participate in either center-based rehabilitation or telerehabilitation but are willing to share their demographics will be collected. The primary endpoint is quality of life measured with the SF-36 questionnaire at three and twelve months, with patient-related characteristics driving intervention choice as the most important secondary endpoint. Secondary endpoints include physical activity, modifiable risk factors, and digital health experience. The trial is registered at clinicaltrials.gov with registration number NCT05207072. Discussion: The REHAB + trial is unique by offering patients freedom to choose between cardiac telerehabilitation and center-based rehabilitation. The integration of digital components into cardiac rehabilitation has the potential to complement behavioral change strategies for specific patient groups. Offering patients the option of cardiac telerehabilitation next to center-based rehabilitation could enhance overall cardiac rehabilitation participation rates.

Effectiveness and safety of alirocumab and evolocumab for hypercholesterolemia in a population with high cardiovascular risk.

BACKGROUND AND AIMS: The criteria for the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) more restrictive than those approved were established in Catalonia by the Health System (CatSalut) to improve their efficiency, with different LDL-C values from which to start treatment according to risk factors. The aim of the study is to analyse adherence to these criteria and results. METHODS: A retrospective study of patients treated with PCSK9i at Vall d'Hebron University Hospital between 2016 and 2021 was performed using data from the Registry of Patients and Treatments and medical records. The degree of agreement with the CatSalut criteria, LDL-C-responders (decrease ≥30%), cardiovascular events and discontinuations were analysed. RESULTS: A total of 193 patients treated with PCSK9i were followed for a median of 27 months (IQR 23). The median age was 61 (IQR 15); 62.7% were men. Seventy percent of the patients had non-familial hypercholesterolemia. Treatment was for secondary prevention of cardiovascular disease in 82.4% of cases. The median LDL-C decreased from 139 (IQR 52) to 59 (IQR 45) mg/dL. The percentage of LDL-C reduction was 61.0% (IQR 30). In 72.5% of patients, all CatSalut criteria for starting treatment were met. The rate of responders was 85.4%. During follow-up, 19 patients (9.8%) had a cardiovascular event, and 15 (7.7%) discontinued treatment, in two cases due to toxicity. CONCLUSION: PCSK9i were used according to CatSalut criteria in three out of four cases. In this high-risk population, incidence of cardiovascular events was similar to that in clinical trials.

Risk of Stroke and Incident Atrial Fibrillation in Patients in Sinus Rhythm With Nonischemic Dilated Cardiomyopathy.

Nonischemic dilated cardiomyopathy (NIDCM) is associated with an increased risk of atrial fibrillation (AF) and stroke, especially in patients with high CHA2DS2-VASc. We aimed to identify variables associated with incident AF or stroke using left atrial deformation analysis and its prognostic value added to CHA2DS2-VASc score. Patients with NIDCM and left ventricular ejection fraction <50% in sinus rhythm were included between January 2015 and December 2019. Left atrial volume index (LAVI) and atrial strain were used in combination with the CHA2DS2-VAS score to predict ischemic stroke or incident AF. Proportional hazards Cox regression was used to provide hazard ratios (HRs). There were 338 patients included. After a median follow-up of 3.6 years, the end point occurred in 41 patients (12.1%). LAVI outperformed other echocardiographic parameters, with a significant improvement in risk reclassification compared with CHA2DS2-VASc alone (net reclassification index 0.6, increase in Harrell's C from 0.63 to 0.73, p = 0.003), and remained significant after multivariate adjustment. LAVI was associated with both components of the end point separately. The best cutoff for LAVI was 44 ml/m2. LAVI ≥44 ml/m2 increased the risk of the end point among those with CHA2DS2-VASc ≥3 (HR 6.0, 95% confidence interval 2.6 to 13.5) but not in those with CHA2DS2-VASc <3 (HR 1.2, 95% confidence interval 0.3 to 4.5). Competing risk analysis did not alter the results. In conclusion, LAVI might be used to assess the risk of incident AF or stroke in NIDCM. Patients with LAVI ≥44 ml/m2 and CHA2DS2-VASc ≥3 could be at high risk of AF and stroke and may benefit from more intensive surveillance.

Left atrial deformation analysis in patients with non-ischaemic dilated cardiomyopathy in atrial fibrillation.

Aims: Atrial fibrillation (AF) is a common comorbidity in non-ischaemic dilated cardiomyopathy (NIDCM) affecting conventional measures of left atrial (LA) function. We aimed to determine whether LA function analysis could identify patients at higher risk of major cardiovascular events (MACEs). Methods and results: A retrospective study of patients with NIDCM in AF referred to a single centre for transthoracic echocardiography (TTE) between 2015 and 2019. Peak atrial longitudinal strain (PALS) was measured along with LA emptying fraction and LA filling index (LAFI = E wave/PALS). Cox regression analysis was conducted. A total of 153 patients were included [median age 74 years, left ventricular ejection fraction (LVEF) 35%], and 57 (37.3%) had MACE after a median follow-up of 3.2 years. LAFI was the only independent TTE parameter associated with MACE after adjustment for age, diabetes, LVEF, left ventricular global longitudinal strain (LV-GLS), and LA volume index [adjusted hazard ratio (HR) = 1.02 per point increase, P = 0.024], with the best cut-off at ≥15. LAFI ≥15 predicted each of MACE components when separately analysed: MACE HR = 1.95, 95% confidence interval (CI) 1.16-3.30; cardiovascular death HR = 3.68, 95% CI 1.41-9.56, heart failure admission HR = 2.13, 95% CI 1.19-3.80, and ventricular arrhythmia HR = 4.72, 95% CI 1.52-14.67. Higher LAFI was associated with worsening LV-GLS, E/e', systolic pulmonary artery (PA) pressure, tricuspid annular plane systolic excursion, and right ventricular to PA coupling. Conclusion: LA deformation analysis is feasible in patients with NIDCM presenting with AF. LAFI may identify patients at higher risk of MACE and correlates with higher pulmonary pressures and worse right ventricular function, suggesting an elevation of left-sided ventricular pressures in patients with higher LAFI.

Cardiac magnetic resonance for prophylactic implantable-cardioverter defibrillator therapy international study: prognostic value of cardiac magnetic resonance-derived right ventricular parameters substudy.

AIMS: Right ventricular systolic dysfunction (RVSD) is an important determinant of outcomes in heart failure (HF) cohorts. While the quantitative assessment of RV function is challenging using 2D-echocardiography, cardiac magnetic resonance (CMR) is the gold standard with its high spatial resolution and precise anatomical definition. We sought to investigate the prognostic value of CMR-derived RV systolic function in a large cohort of HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy registry who had HFrEF and had simultaneous baseline CMR and echocardiography (n = 2449). RVSD was defined as RV ejection fraction (RVEF) <45%. Kaplan-Meier curves and cox regression were used to investigate the association between RVSD and all-cause mortality (ACM). Mean age was 59.8 ± 14.0 years, 42.0% were female, and mean left ventricular ejection fraction (LVEF) was 34.0 ± 10.8. Median follow-up was 959 days (interquartile range: 560-1590). RVSD was present in 936 (38.2%) and was an independent predictor of ACM (adjusted hazard ratio = 1.44; 95% CI [1.09-1.91]; P = 0.01). On subgroup analyses, the prognostic value of RVSD was more pronounced in NYHA I/II than in NYHA III/IV, in LVEF <35% than in LVEF ≥35%, and in patients with renal dysfunction when compared to those with normal renal function. CONCLUSION: RV systolic dysfunction is an independent predictor of ACM in HFrEF, with a more pronounced prognostic value in select subgroups, likely reflecting the importance of RVSD in the early stages of HF progression.

Cardiac Magnetic Resonance for Prophylactic Implantable-Cardioverter Defibrillator Therapy in Ischemic Cardiomyopathy: The DERIVATE-ICM International Registry.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy against sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) and left ventricle ejection fraction (LVEF) ≤35% as detected by transthoracic echocardiograpgy (TTE). This approach has been recently questioned because of the low rate of ICD interventions in patients who received implantation and the not-negligible percentage of patients who experienced SCD despite not fulfilling criteria for implantation. OBJECTIVES: The DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy; NCT03352648) is an international, multicenter, and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to TTE in patients with ICM. METHODS: A total of 861 patients with ICM (mean age 65 ± 11 years, 86% male) with chronic heart failure and TTE-LVEF <50% participated. Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints. RESULTS: During a median follow-up of 1,054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007 [95% CI: 1.000-1.011]; P = 0.05), CMR-LVEF (HR: 0.972 [95% CI: 0.945-0.999]; P = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010 [95% CI: 1.002-1.018]; P = 0.015) were independent predictors of MAACE. A multiparametric CMR weighted predictive derived score identifies subjects at high risk for MAACE compared with TTE-LVEF cutoff of 35% with a NRI of 31.7% (P = 0.007). CONCLUSIONS: The DERIVATE-ICM registry is a large multicenter registry showing the additional value of CMR to stratify the risk for MAACE in a large cohort of patients with ICM compared with standard of care.

Predictors of cardiovascular outcomes after surgery in severe tricuspid regurgitation: clinical, imaging and hemodynamic prospective study.

INTRODUCTION AND OBJECTIVES: Severe tricuspid regurgitation (TR) is a prevalent valve disease with a high mortality rate. Current guidelines do not define specific thresholds at which patients should be considered for surgery or percutaneous procedures. Thus, patients are usually referred for intervention at a late stage of the disease. This study aimed to assess predictors of cardiovascular outcomes in a prospective cohort of patients with severe TR referred for surgery. METHODS: This was an observational, prospective, nonrandomized study. All patients underwent surgery for severe TR based on current clinical guidelines. Complete anamnesis, blood test, echocardiogram, cardiovascular magnetic resonance and right and left catheterization were performed. Patients were followed up in the outpatient department and a combined endpoint (hospitalization for heart failure and cardiovascular mortality) was registered. RESULTS: Forty-three consecutive patients were included (age: 66.9 ± 9.6 years, 67.4% female). Tricuspid annuloplasty was performed in all patients. After a median follow-up of 38 months, 12 patients (27.9%) showed the combined endpoint and 7 (16.3%) died. Above all clinical, blood and imaging data, the indexed right ventricular end-diastolic volume constituted the best predictor of the combined endpoint (HR, 1.1; P = .02) and cardiovascular mortality (HR, 1.1; P = .05). Furthermore, indexed right ventricular end-diastolic volume was associated with TR recurrence after surgery, with no impact on clinical outcomes. CONCLUSIONS: In patients with severe TR referred for surgery, right ventricular remodeling assessed by cardiovascular magnetic resonance constituted the best independent predictor of cardiovascular outcomes at follow-up.