Clinical development and proof of principle testing of new regenerative vascular endothelial growth factor-D therapy for refractory angina: rationale and design of the phase 2 ReGenHeart trial.

BACKGROUND: Despite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment options. Adenoviral vascular endothelial growth factor-DΔNΔC (AdVEGF-D)-encoding gene therapy (GT) holds promise for the treatment of refractory angina. METHODS: ReGenHeart is an investigator-initiated, multicentre, randomised, placebo-controlled and double-blinded phase 2 clinical trial that aims to study the safety and efficacy of intramyocardially administered angiogenic AdVEGF-D GT for refractory angina. Patients will be randomised in a 2:1 ratio and blocks of six to receive either AdVEGF-D or placebo. Primary endpoints are improvements in functional capacity assessed with the 6 min walking test and angina symptoms with Canadian Cardiovascular Society class after 6 month follow-up. Secondary endpoints are improvements in myocardial perfusion assessed with either positron emission tomography or single-photon emission CT after 6 month follow-up and functional capacity and angina symptoms after 12 months. In addition, changes in the quality of life, the use of angina medication and the incidence of major adverse cardiac and cerebrovascular events will be evaluated. CONCLUSIONS: The phase 2 ReGenHeart trial will provide knowledge of the safety and efficacy of AdVEGF-D GT to ameliorate symptoms in refractory angina patients, extending and further testing positive results from the preceding phase 1/2a trial.

Global Circumferential and Radial Strain Among Patients With Immune Checkpoint Inhibitor Myocarditis.

BACKGROUND: Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS. OBJECTIVES: This study aimed to detail the role of GCS and GRS in ICI myocarditis. METHODS: In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death. RESULTS: Cases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n = 42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P < 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P < 0.001). Over a median follow-up of 30 days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95% CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95% CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95% CI: 0.70-0.91]) and GRS (AUC: 0.76 [95% CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95% CI: 0.58-0.82]), LVEF (AUC: 0.69 [95% CI: 0.56-0.81]), and age (AUC: 0.54 [95% CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002). CONCLUSIONS: GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.

Combined atrial fibrillation ablation and balloon mitral commissurotomy in patients with rheumatic mitral stenosis.

INTRODUCTION: Ablation of atrial fibrillation (AF) is usually not considered in patients with rheumatic mitral stenosis (RMS). We analyzed the results of a combined procedure of AF ablation and percutaneous balloon mitral commissurotomy (PBMC). METHODS: We prospectively included 22 patients with severe RMS to undergo a combined PBMC + AF ablation procedure. Noninvasive mapping of the atria was also performed. A historical sample of propensity-scored matched patients who underwent PBMC alone was used as controls. The primary endpoint was freedom from AF/AT at 1-year. Multivariate analysis evaluated sinus rhythm (SR) predictors. RESULTS: Successful pulmonary vein isolation and electrocardiographic imaging-based drivers ablation was performed in 20 patients following PBMC. At 1-year, 75% of the patients in the combined group were in SR compared to 40% in the propensity-score matched group (p = 0.004). The composite of AF recurrence, need for mitral surgery and all-cause mortality was also more frequent in the control group (65% vs. 30%; p = 0.005). Catheter ablation (odds ratio [OR] 1.58; 95% confidence interval [CI] [1.17-17.37]; p = 0.04) and AF type (OR 1.46; 95% CI [1.05-82.64]; p < 0.001) were the only independent predictors of SR at 1-year. Noninvasive mapping in the combined group showed that the number of simultaneous rotors (OR 2.10; 95% CI [1.41-10.2]; p = 0.04) was the only independent predictor of AF. CONCLUSION: A combined procedure of AF ablation and PBMC significantly increased the proportion of patients in sinus rhythm at 1-year. Noninvasive mapping may help to improve AF characterization and guide personalized AF treatment.

Atrial myxoma surgery and P-wave remodeling.

INTRODUCTION: Data regarding atrial electrocardiographic parameters in patients with atrial myxomas are scarce. METHODS: We aimed to study atrial electrocardiographic features in patients with atrial myxomas, before and after surgery. We also analyze the incidence of atrial fibrillation during follow-up and its correlation with different P-wave indexes. In total 32 patients in sinus rhythm that underwent atrial myxoma surgery were included. RESULTS: Mean age was 55.0 ± 12.6 years and 18 (56.3%) were women. Ten patients had left atrial enlargement (31.3%). Only one myxoma was located in the right atrium. At baseline seven cases of partial interatrial block (IAB) were detected (21.9%), two in the absence of left atrial enlargement. There were significant differences in atrial electrocardiographic indexes before and after surgery, including P-wave duration (108.9 ± 17.9 ms vs. 93.0 ± 12.4 ms; p < .001), partial IAB (21.9% vs. 3.1%; p = .012) and duration of P-wave terminal force in lead V1 negativity (-0.6 ± 0.3 vs. -0.5 ± 0.3 mm; p = .034). At a mean follow-up of 10.0 ± 5.5 years, 10 patients (31.3%) had experienced at least one episode of atrial fibrillation. Post-operative P-wave duration was associated with atrial fibrillation occurrence during follow-up (Hazard ratio: 0.90, 95% confidence interval: 0.83-0.98; p = .020). CONCLUSIONS: Abnormalities in atrial electrocardiographic indexes are common in atrial myxomas and frequently improve after surgery. Post-operative P-wave duration is associated with atrial fibrillation occurrence during follow-up.

Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome.

MSCs products as well as their derived extracellular vesicles, are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. In recent years, various strategies designed for improving the therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning for enhanced cytokine production, improved cell homing and strengthening of immunomodulatory properties, have been developed but the manufacture and handling of these cells for their use as advanced therapy medicinal products (ATMPs) remains insufficiently studied, and available data are mainly related to non-industrial processes. In the present article, we will review this topic, analyzing current information on the specific regulations, the selection of living donors as well as MSCs from different sources (bone marrow, adipose tissue, umbilical cord, etc.), in-process quality controls for ensuring cell efficiency and safety during all stages of the manual and automatic (bioreactors) manufacturing process, including cryopreservation, the use of cell banks, handling medicines, transport systems of ATMPs, among other related aspects, according to European and US legislation. Our aim is to provide a guide for a better, homogeneous manufacturing of therapeutic cellular products with special reference to MSCs.

A comparison of the clinical efficacy of echocardiography and magnetic resonance for chronic aortic regurgitation.

AIMS: Timing surgery in chronic aortic regurgitation (AR) relies mostly on echocardiography. However, cardiac magnetic resonance (CMR) may be more accurate for quantifying regurgitation and left ventricular (LV) remodelling. We aimed to compare the technical and clinical efficacies of echocardiography and CMR to account for the severity of the disease, the degree of LV remodelling, and predict AR-related outcomes. METHODS AND RESULTS: We studied 263 consecutive patients with isolated AR undergoing echocardiography and CMR. After a median follow-up of 33 months, 76 out of 197 initially asymptomatic patients reached the primary endpoint of AR-related events: 6 patients (3%) were admitted for heart failure, and 70 (36%) underwent surgery. Adjusted survival models based on CMR improved the predictions of the primary endpoint based on echocardiography: R2 = 0.37 vs. 0.22, χ2 = 97 vs. 49 (P < 0.0001), and C-index = 0.80 vs. 0.70 (P < 0.001). This resulted in a net classification index of 0.23 (0.00-0.46, P = 0.046) and an integrated discrimination improvement of 0.12 (95% confidence interval 0.08-0.58, P = 0.02). CMR-derived regurgitant fraction (<28, 28-37, or >37%) and LV end-diastolic volume (<83, 183-236, or >236 mL) adequately stratified patients with normal EF. The agreement between techniques for grading AR severity and assessing LV dilatation was poor, and CMR showed better reproducibility. CONCLUSIONS: CMR improves the clinical efficacy of ultrasound for predicting outcomes of patients with AR. This is due to its better reproducibility and accuracy for grading the severity of the disease and its impact on the LV. Regurgitant fraction, LV ejection fraction, and end-diastolic volume obtained by CMR most adequately predict AR-related events.

Founder mutation in myosin-binding protein C with an early onset and a high penetrance in males.

OBJECTIVE: One of the challenges in hypertrophic cardiomyopathy (HCM) is to determine the pathogenicity of genetic variants and to establish genotype/phenotype correlations. This study aimed to: (1) demonstrate that MYBPC3 c.2149-1G>A is a founder pathogenic variant, (2) describe the phenotype and clinical characteristics of mutation carriers and (3) compare these patients with those with the most frequent pathogenic HCM variants: MYBPC3 p.Arg502Trp/Gln. METHODS: We reviewed genetic tests performed in HCM probands at our institution. We carried out transcript analyses to demonstrate the splicing effect, and haplotype analyses to support the founder effect of MYBPC3 c.2149-1G>A. Carriers with this mutation were compared with those from MYBPC3 p.Arg502Trp/Gln in terms of presentation features, imaging and outcomes. RESULTS: MYBPC3 c.2149-1G>A was identified in 8 of 570 probands and 25 relatives. Penetrance was age and sex dependent, 50.0% of the carriers over age 36 years and 75.0% of the carriers over 40 years showing HCM. Penetrance was significantly higher in males: in carriers older than 30 years old, 100.0% of males vs 50.0% of females had a HCM phenotype (p=0.01). Males were also younger at diagnosis (32±13 vs 53±10 years old, p<0.001). MYBPC3 c.2149-1G>A resulted in an abnormal transcript that led to haploinsufficiency and was segregated in two haplotypes. However, both came from one founder haplotype. Affected carriers showed a better functional class and higher left ventricular ejection fraction (LVEF) than patients with MYBPC3 p.Arg502Trp/Gln (p<0.05 for both). Nevertheless, the rate of major adverse outcomes was similar between the two groups. CONCLUSIONS: MYBPC3 c.2149-1G>A splicing variant is a founder mutation. Affected males show an early onset of HCM and with higher penetrance than women. Carriers show better functional class and higher LVEF than MYBPC3 p.Arg502Trp/Gln carriers, but a similar rate of major adverse outcomes.

Preclinical Evaluation of the Safety and Immunological Action of Allogeneic ADSC-Collagen Scaffolds in the Treatment of Chronic Ischemic Cardiomyopathy.

The use of allogeneic adipose-derived mesenchymal stromal cells (alloADSCs) represents an attractive approach for treating myocardial infarction (MI). Furthermore, adding a natural support improves alloADSCs engraftment and survival in heart tissues, leading to a greater therapeutic effect. We aimed to examine the safety and immunological reaction induced by epicardial implantation of a clinical-grade collagen scaffold (CS) seeded with alloADSCs for its future application in humans. Thus, cellularized scaffolds were myocardially or subcutaneously implanted in immunosuppressed rodent models. The toxicological parameters were not significantly altered, and tumor formation was not found over the short or long term. Furthermore, biodistribution analyses in the infarcted immunocompetent rats displayed cell engraftment in the myocardium but no migration to other organs. The immunogenicity of alloADSC-CS was also evaluated in a preclinical porcine model of chronic MI; no significant humoral or cellular alloreactive responses were found. Moreover, CS cellularized with human ADSCs cocultured with human allogeneic immune cells produced no alloreactive response. Interestingly, alloADSC-CS significantly inhibited lymphocyte responses, confirming its immunomodulatory action. Thus, alloADSC-CS is likely safe and does not elicit any alloreactive immunological response in the host. Moreover, it exerts an immunomodulatory action, which supports its translation to a clinical setting.

Serum biomarkers of acute rejection: Towards precision medicine in heart transplant.

Despite the important changes in the management of heart transplantation in the recent decades, the use of endomyocardial biopsy is still necessary for the follow-up of these patients. However, this technique has several limitations, the most important being the substantial interobserver variability. In the last years multiple attempts have been made to find non-invasive assays for cardiac allograft surveillance, such as imaging modalities and serum biomarkers. This state-of-the-art review focuses on describing the different serum biomarkers that have been proposed for non-invasive diagnosis of acute rejection and that are paving the way towards precision medicine in the field of heart transplantation.

Cardiac troponin and infective endocarditis prognosis: a systematic review and meta-analysis.

AIMS: Infective endocarditis (IE) is associated with high mortality and morbidity. Cardiac troponin (Tn) elevation seems to be common in patients with IE and could be associated with a poor prognosis. The aim of this study was to synthesize the prognostic value of Tn in patients with IE. METHODS AND RESULTS: We searched in MEDLINE, EMBASE, and the Cochrane library, including the Cochrane Central Register of Controlled Trials (CENTRAL) until February 2020. Observational studies reporting on the association between Tn and in-hospital and 1-year mortality, and IE complications were considered eligible. As each centre uses different conventional or ultra-sensitive Tn, with different normality threshold, we considered them as normal or elevated according to the criteria specified in each article. Articles were systematically selected, assessed for bias, and, when possible, meta-analysed using a random effect model. After retrieving 542 articles, 18 were included for qualitative synthesis and 9 for quantitative meta-analysis. Compared with patients with normal Tn levels, patients with Tn elevation presented higher in-hospital mortality [odds ratio (OR) 5.96, 95% confidence interval (CI) 3.46-10.26; P < 0.0001], 1-year mortality (OR 2.67, 95% CI 1.42-5.02; P = 0.002), and surgery rates (OR 2.34, 95% CI 1.42-3.85; P = 0.0008). They also suffered more frequent complications: central nervous system events (OR 8.85, 95% CI 3.23-24.26; P < 0.0001) and cardiac abscesses (OR 4.96, 95% CI 1.94-12.70; P = 0.0008). CONCLUSION: Tn elevation is associated with a poor prognosis in patients with IE. Troponin determination seems to provide additional help in the prognostic assessment of these patients.

Reparative cell therapy for the heart: critical internal appraisal of the field in response to recent controversies.

The concept that cell-based repair of myocardial injury might be possible was introduced almost two decades ago; however, the field of cardiovascular reparative medicine has been criticized as translation to clinically effective approaches has been slow. The recent retraction of a series of papers has further impacted perception of this area of research. As researchers, clinicians, and teachers in this field, we felt it incumbent to critically appraise the current state of cardiac cell repair, determine what can be learned from past mistakes, and formulate best practices for future work. This special communication summarizes an introspective assessment of what has fallen short, how to prevent similar issues, and how the field might best move forward in the service of science and patients.

Influence of left ventricular systolic function on the long-term benefit of beta-blockers after ST-segment elevation myocardial infarction.

INTRODUCTION: Beta-blockers are recommended after ST-elevation myocardial infarction (STEMI), but their benefit in patients with preserved left ventricular ejection fraction (LVEF) is unclear. METHODS: Consecutive patients discharged in sinus rhythm after STEMI between January 2010 and April 2015 were followed until December 2017. Percutaneous coronary intervention (PCI) was performed in 969 (99.7%, including 112 with rescue PCI) and three (0.3%) received only thrombolytic therapy without rescue PCI. RESULTS: Of these 972 patients, mean age 62.6±13.5 years, 212 (21.8%) were women and 835 (85.9%) were prescribed beta-blockers at discharge. Patients who did not receive beta-blockers had more comorbidities than those who did, including chronic obstructive pulmonary disease (14.6% vs. 4.2%), anemia (8.0% vs. 3.7%), and cancer (7.3% vs. 2.8%), and more frequently had inferior STEMI (75.9% vs. 56.0%) and high-grade atrioventricular block (13.1% vs. 5.3%) (all p<0.01). After a mean follow-up of 49.6±24.9 months, beta-blocker treatment at discharge was independently associated with lower mortality (HR 0.61, 95% confidence interval [CI] 0.38-0.96, p=0.03). This effect was present in 192 patients with LVEF ≤40% (HR 0.57, 95% 95% CI 0.34-0.97, p=0.04) but was not clear in 643 patients with LVEF >40% (HR 0.67, 95% 95% CI 0.25-1.76, p=0.42). CONCLUSION: In the LVEF >40% group, the results raise reasonable doubts about the real benefit of systematic use of beta-blockers as treatment for these patients. These findings reinforce the need for large randomized clinical trials within this group of patients.

Tratamiento con radiofrecuencia de la tormenta eléctrica: evolución y seguimiento / Radiofrequency treatment for electrical storm: evolution and monitoring

Resumen Introducción y objetivos: La tormenta eléctrica (TE) se caracteriza por episodios repetidos de taquicardia ventricular o fibrilación ventricular relacionados con mal pronóstico a corto y largo plazos. El objetivo fue evaluar la prevalencia, resultados y supervivencia de los pacientes sometidos a tratamiento intervencionista por TE en un centro de referencia. Métodos: Estudio unicéntrico, observacional y retrospectivo. Se revisaron los procedimientos de ablación por TE y se evaluaron las características basales de los pacientes, tipo de procedimiento, mortalidad total, recurrencia de arritmia, mortalidad cardiovascular y necesidad de trasplante. Resultados: Desde enero de 2009 hasta diciembre de 2016 se realizaron 67 procedimientos (38% de complejos: 19% de ablación endoepicárdica, 7.5% de crioablación epicárdica quirúrgica, 3% de simpatectomía, 3% de inyección coronaria con alcohol; 6% de apoyo con oxigenación con membrana extracorpórea) en 41 pacientes (61% de causa isquémica) por TE. La mortalidad intraprocedimiento fue del 1.5%. La mediana de seguimiento fue de 23.5 meses (RIQ, 14.2-52.7). Tras el primer ingreso por TE (uno o varios procedimientos), la mortalidad a un año fue de 9.8%. La incidencia acumulada de trasplante cardiaco por TE fue de 2.4%. En el análisis multivariado, el riesgo de recurrencias arrítmicas o muerte por cualquier causa fue significativamente mayor en pacientes con arritmias clínicas inducibles (HR, 9.03; p = 0.017). Conclusiones: El tratamiento de pacientes con TE, instituido en un centro de referencia y con experiencia, se relacionó con una tasa baja de recurrencia y supervivencia elevada, con una tasa de trasplante cardiaco por TE muy baja. Ante una recurrencia temprana es recomendable practicar un nuevo procedimiento durante el ingreso.

Abstract Introduction and objective: Electrical storm (ES) is characterized by repeated episodes of ventricular tachycardia or ventricular fibrillation, with poor short and long term prognosis. Our objective was to evaluate the prevalence, results of interventional treatment and survival of patients undergoing interventional treatment for ES in our center. Methods: Retrospective, unicentric and observational study. ES ablation procedures were revised and data regarding baseline characteristics of the patients, type of procedure, total mortality, recurrence of arrhythmia, cardiovascular mortality and the need for transplantation were evaluated. Results: From January 2009 to December 2016, 67 procedures (38% complex procedures: 19% epicardial ablation, 7.5% surgical epicardial crioablation, 3% simpatectomy, 3% coronary alcohol injection, 6% extracorporeal membrane oxygenation support) were performed in 41 patients (61% Ischemic etiology) due to ES. Intraprocedural mortality was 1.5%. The median follow-up was 23.5 months (IQR [14.2-52.7]). After the first admission for ES (one or several procedures), 1-year mortality was 9.8%. The cumulative incidence of cardiac transplantation was 2.4%. The risk of arrhythmic recurrences or death was significantly higher in patients with inducible clinical arrhythmias after ablation (HR: 9.03, p = 0.017). Conclusions: The treatment of patients with ES, performed in a reference center, allows obtaining good rates of recurrence and survival, with very low rates of cardiac transplantation for ES. In the presence of an early recurrence, it is advisable to perform a new procedure during admission.

The effect of intracoronary infusion of bone marrow-derived mononuclear cells on all-cause mortality in acute myocardial infarction: the BAMI trial.

AIMS: Bone marrow-derived mononuclear cell (BM-MNC) therapy may improve myocardial recovery in patients following acute myocardial infarction (AMI), though existing trial results are inconsistent. METHODS AND RESULTS: Originally an open-label, multicentre Phase III trial, BAMI was designed to demonstrate the safety and efficacy of intracoronary infusion of BM-MNCs in reducing the time to all-cause mortality in patients with reduced left ventricular ejection fraction (LVEF, ≤45%) after primary angioplasty (PPCI) for ST-elevation AMI. Unexpectedly low recruitment means the trial no longer qualifies as a hypothesis-testing trial, but is instead an observational study with no definitive conclusions possible from statistical analysis. In total, 375 patients were recruited: 185 patients were randomized to the treatment arm (intracoronary infusion of BM-MNCs 2-8 days after PPCI) and 190 patients to the control arm (optimal medical therapy). All-cause mortality at 2 years was 3.26% [6 deaths; 95% confidence interval (CI): 1.48-7.12%] in the BM-MNC group and 3.82% (7 deaths; 95% CI: 1.84-7.84%) in the control group. Five patients (2.7%, 95% CI: 1.0-5.9%) in the BM-MNC group and 15 patients (8.1%, CI : 4.7-12.5%) in the control group were hospitalized for heart failure during 2 years of follow-up. Neither adverse events nor serious adverse events differed between the two groups. There were no patients hospitalized for stroke in the control group and 4 (2.2%) patients hospitalized for stroke in the BM-MNC group. CONCLUSIONS: Although BAMI is the largest trial of autologous cell-based therapy in the treatment of AMI, unexpectedly low recruitment and event rates preclude any meaningful group comparisons and interpretation of the observed results.

Troponin elevation is very common in patients with infective endocarditis and is associated with a poor outcome.

INTRODUCTION: We sought to study the prevalence of cardiac troponin T (TnT) elevation in patients with infective endocarditis (IE) and its association with in-hospital outcomes. METHODS AND RESULTS: Retrospective single-center study. From 2008 to 2018, 528 patients were diagnosed with IE and 250 (47.3%) had at least a TnT determination during hospital admission, 103 with conventional TnT assay and 147 with high-sensitive assay. Elevated TnT levels were found in 210 patients (84.0%). Compared with patients with normal TnT levels, patients with TnT elevation presented higher in-hospital mortality (5 [12.5%] vs. 77 [36.7%], p < 0.001) and more frequent complications: heart failure (9 [22.5%] vs. 106 [50.5%], p < 0.001), cardiac abscesses (4 [10.0%] vs 58 [27.6%], p = 0.03), conduction disorders (0 vs. 26 [12,4%]; p = 0.04), and involvement of the central nervous system (1 [2.5%] vs. 38 [18.1%];p = 0.02). Patients with elevated TnT had more frequent indication for surgery (24 [60.0%] vs. 179 [85.2%], p < 0.001) and were operated on more frequently (16 [40.0%] vs 123 [58.6%], p = 0.03). TnT elevation was an independent predictor of in-hospital mortality (OR 3.31; 95% CI 1.02-10.72, p = 0.05). Adding TnT data to conventional clinical models improved the predictive capability of in-hospital mortality (R2: 0.407 vs. 0.388, χ2: 85.03 vs. 80.40, p < 0.001), resulting in a net reclassification improvement of 0.29 (95% CI: 0.13-0.46, p < 0.01). CONCLUSIONS: TnT elevation is very common in patients with IE and is associated with increased in-hospital mortality and complications, thus routine monitoring should be recommended.

Clinical profile, anatomical features and long-term outcome of acute coronary syndromes in human immunodeficiency virus-infected patients.

BACKGROUND: Long-term prognosis of acute coronary syndromes (ACS) in human immunodeficiency virus (HIV)-infected patients is unknown. AIMS: To compare outcomes after ACS in HIV-infected and uninfected patients. METHODS: Retrospective observational study. HIV cases were matched with two HIV-uninfected controls for age, sex and type of ACS. RESULTS: In 92 HIV patients (mean age 51.3 ± 9.0 years, 7.6% women), the prevalence of cardiovascular risk factors was high (smoking 71.7%; hypertension 41.3%; diabetes 14.1%); dyslipidaemia was more frequent (53 (57.6%) vs 79 (42.9%), P = 0.02) and obesity less common (8 (8.7%) vs 41 (22.3%), P = 0.002) than in controls. Eighty-seven (94.6%) HIV patients had undetectable viral load and 85 (92.4%) were under anti-retroviral therapy. Multivessel disease was more common in HIV patients than in controls (44 (47.8%) vs 71 (39.1%); P = 0.05) as was Killip class 3-4 on admission (9 (9.8%) vs 6 (3.3%); P = 0.04). The rate of in-hospital mortality was similar in both groups (2%), and there were no significant differences in 3-year mortality (10.2% vs 5.7%; P = 0.27). Non-cardiovascular readmissions at 3 years were more frequent in HIV patients than in controls (36.5% vs 7.4%; P < 0.001). Multivariate analysis identified previous coronary artery disease as the strongest predictor of mortality in HIV patients (hazard ratio 4.7, 95% confidence interval 1.4-15.7, P = 0.01), whereas HIV infection was not associated with prognosis. CONCLUSION: HIV patients with ACS had more frequent multivessel disease and heart failure than matched controls. However, in-hospital and long-term mortality was similar in both groups. Non-cardiovascular re-hospitalisations were more common in HIV patients.

Clinical characteristics of patients with sustained ventricular arrhythmias after sacubitril/valsartan initiation.

Our aim was to describe the clinical profile of patients presenting sustained ventricular arrhythmias after sacubitril/valsartan (SV) initiation. All cases of sustained ventricular arrhythmias in patients receiving SV were consecutively recorded in two centers. Nineteen patients had sustained ventricular arrhythmias after SV. All were men and were previously receiving angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers before SV initiation. Fifteen patients (78.9%) had electrical stability in the previous 6 months. Nine patients (47.4%) initiated SV at the lowest available dose (24/26 mg). Globally, in all but five patients alive at discharge, SV was discontinued after the event. Six patients presented new arrhythmic events after discontinuation of SV. Two deaths and three heart transplants occurred (one due to heart failure and the other two due to persistent ventricular arrhythmias). All patients had a high arrhythmic risk, and 17 (89.5%) had an implanted cardioverter defibrillator. No specific triggers for the arrhythmic event were found. Male sex and previous episodes of ventricular arrhythmias could be associated with an increased risk of sustained ventricular tachycardia after SV initiation. Discontinuation of the drug might be an additional approach to enable a better control of ventricular arrhythmias in some patients.