Real world comparison of spironolactone and eplerenone in patients with heart failure.

AIMS: In the absence of previous direct comparative studies, we aimed to evaluate the effectiveness of spironolactone and eplerenone in patients with heart failure and reduced ejection fraction (HFrEF) in a real-world clinical setting. METHODS: Using Fine-Gray´s competing risk regression, we compared the clinical outcomes of 293 patients with chronic HF and left ventricular ejection fraction <40% treated with eplerenone and 293 propensity-score matched individuals treated with spironolactone. Study subjects were selected from a prospective cohort of 1404 ambulatory patients with HFrEF seen since 2010 to 2019 in a single specialized HF clinic, among which 992 received a mineralocorticoid receptor antagonist at baseline. Median follow-up was 3.95 years. RESULTS: No statistically significant differences between patients treated with eplerenone versus spironolactone were observed with regard to the risk of the primary composite end-point cardiovascular death or HF hospitalization (HR 0.95; 95% CI 0.73-1.23; p= 0.677). However, eplerenone use was associated to lower cardiovascular mortality (HR 0.55; 95% CI 0.35-0.85; p= 0.008) and lower all-cause mortality (HR 0.67; 95% CI 0.47-0.95; p= 0.027). The incidence of drug suspension due to side effects (HR 0.58, 95% CI 0.40-0.85; p= 0.005) and drug suspension due to any reason (HR 0.70, 95% CI 0.51-0.97; p= 0.033) were lower among patients treated with eplerenone. CONCLUSIONS: In this observational, real-world, propensity-score matched study of patients with HFrEF, eplerenone was associated to lower cardiovascular mortality and lower all-cause mortality than spironolactone.

Rationale and design of the pragmatic clinical trial tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT).

AIMS: There is a lack of evidence regarding the benefits of ß-blocker treatment after invasively managed acute myocardial infarction (MI) without reduced left ventricular ejection fraction (LVEF). METHODS AND RESULTS: The tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT) trial is a pragmatic, controlled, prospective, randomized, open-label blinded endpoint (PROBE design) clinical trial testing the benefits of ß-blocker maintenance therapy in patients discharged after MI with or without ST-segment elevation. Patients eligible for participation are those managed invasively during index hospitalization (coronary angiography), with LVEF >40%, and no history of heart failure (HF). At discharge, patients will be randomized 1:1 to ß-blocker therapy (agent and dose according to treating physician) or no ß-blocker therapy. The primary endpoint is a composite of all-cause death, non-fatal reinfarction, or HF hospitalization over a median follow-up period of 2.75 years (minimum 2 years, maximum 3 years). Key secondary endpoints include the incidence of the individual components of the primary composite endpoint, the incidence of cardiac death, and incidence of malignant ventricular arrhythmias or resuscitated cardiac arrest. The primary endpoint will be analysed according to the intention-to-treat principle. CONCLUSION: The REBOOT trial will provide robust evidence to guide the prescription of ß-blockers to patients discharged after MI without reduced LVEF.

Differences in the Clinical Profile and Management of Atrial Fibrillation According to Gender. Results of the REgistro GallEgo Intercéntrico de Fibrilación Auricular (REGUEIFA) Trial.

To analyze the clinical profile and therapeutic strategy in atrial fibrillation (AF) according to gender in a contemporaneous patient cohort a prospective, multicenter observational study was performed on consecutive patients diagnosed with AF and assessed by cardiology units in the region of Galicia (Spain). A total of 1007 patients were included, of which 32.3% were women. The mean age of the women was significantly greater than that of the men (71.6 versus 65.7 years; p < 0.001), with a higher prevalence of hypertension (HTN) and valve disease. Women more often reported symptoms related to arrhythmia (28.2% in EHRA class I versus 36.4% in men), with a poorer level of symptoms (EHRA classes IIb and III). Thromboembolic risk was significantly higher among women (CHA2DS2-VASc 3 ± 1.3 versus 2 ± 1.5), in the same way as bleeding risk (HAS-BLED 0.83 ± 0.78 versus 0.64 ± 0.78) (p < 0.001), and women more often received anticoagulation therapy (94.1% versus 87.6%; p = 0.001). Rhythm control strategies proved significantly less frequent in women (55.8% versus 66.6%; p = 0.001), with a lesser electrical cardioversion (ECV) rate (18.4% versus 27.3%; p = 0.002). Perceived health status was poorer in women. Women were older and presented greater comorbidity than men, with a greater thromboembolic and bleeding risk. Likewise, rhythm control strategies were less frequent than in men, despite the fact that women had poorer perceived quality of life and were more symptomatic.

Valor pronóstico de la disfunción ventricular izquierda inducida por el ejercicio en pacientes hipertensos sin enfermedad arterial coronaria / Prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive patients without coronary artery disease

Introducción y objetivos El propósito de este estudio es evaluar el valor pronóstico de la disfunción sistólica ventricular izquierda inducida por el ejercicio en pacientes hipertensos con ecocardiograma en reposo normal y sin enfermedad arterial coronaria. Métodos De nuestra base de datos de pacientes referidos a ecocardiografía de ejercicio, se identificó a 93 pacientes hipertensos, con fracción de eyección del ventrículo izquierdo en reposo normal (≥ 50%), sin cardiopatía estructural ni evidencia de enfermedad arterial coronaria en la angiografía. Del total, 39 pacientes desarrollaron disfunción sistólica ventricular izquierda inducida por el ejercicio (definida como caída de la fracción de eyección del ventrículo izquierdo por debajo de 50% en el máximo ejercicio) y 54 mostraron una respuesta normal de la fracción de eyección del ventrículo izquierdo al ejercicio. El seguimiento medio fue 6,1 ± 3,7 años. Los objetivos primarios fueron muerte por cualquier causa, muerte cardiaca, aparición de insuficiencia cardiaca y el evento combinado de muerte cardiaca o insuficiencia cardiaca. Resultados La aparición de disfunción sistólica ventricular izquierda inducida por el ejercicio se asoció con mayor riesgo de muerte por cualquier causa (hazard ratio = 3,4; intervalo de confianza del 95%, 1,1-10,3), muerte cardiaca (hazard ratio = 5,6; intervalo de confianza del 95%, 1,1-29,4), insuficiencia cardiaca (hazard ratio=8,9; intervalo de confianza del 95%, 1,8-44,2) y del evento combinado (hazard ratio=5,7; intervalo de confianza del 95%, 1,7-19,0). En un análisis multivariable, la disfunción sistólica ventricular izquierda inducida por el ejercicio continuó asociándose de manera independiente con mayor riesgo de insuficiencia cardiaca (hazard ratio = 6,9; intervalo de confianza del 95%, 1,3-37,4) y del evento combinado de muerte cardiaca o insuficiencia cardiaca (hazard ratio = 4,5; intervalo de confianza del 95%, 1,2-16,0). Conclusiones: La aparición de disfunción sistólica ventricular izquierda inducida por el ejercicio en pacientes hipertensos con fracción de eyección del ventrículo izquierdo normal en reposo y ausencia de enfermedad arterial coronaria es un potente predictor de eventos cardiacos y podría ser un marcador precoz de cardiopatía hipertensiva

Introduction and objectives We sought to assess the prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive patients with normal resting echocardiography and absence of coronary artery disease. Methods From our database of patients referred for treadmill exercise echocardiography, we identified 93 hypertensive patients with preserved resting left ventricular ejection fraction (≥ 50%), no evidence of structural heart disease, and absence of coronary artery disease on angiography. Overall, 39 patients developed exercise-induced left ventricular systolic dysfunction (defined as a decrease in left ventricular ejection fraction below 50% at peak exercise) and 54 exhibited a normal left ventricular ejection fraction response to exercise. The mean follow-up was 6.1 (3.7) years. End points were all-cause mortality, cardiac death, heart failure, and the composite event of cardiac death or heart failure. Results Patients who developed exercise-induced left ventricular systolic dysfunction were at higher risk of death from any cause (hazard ratio = 3.4; 95% confidence interval, 1.1-10.3), cardiac death (hazard ratio = 5.6; 95%CI, 1.1-29.4), heart failure (hazard ratio = 8.9; 95% confidence interval, 1.8-44.2), and the composite end point (hazard ratio = 5.7; 95% confidence interval, 1.7-19.0). In the multivariate analysis, exercise-induced left ventricular systolic dysfunction remained an independent predictor of both heart failure (hazard ratio = 6.9; 95% CI, 1.3-37.4) and the composite event of cardiac death or heart failure (hazard ratio = 4.5; 95% confidence interval, 1.2-16.0).Conclusions In hypertensive patients with preserved resting left ventricular ejection fraction and absence of coronary artery disease, exercise-induced left ventricular systolic dysfunction is a strong predictor of cardiac events and may represent early hypertensive heart disease (AU)

Prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive patients without coronary artery disease.

INTRODUCTION AND OBJECTIVES: We sought to assess the prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive patients with normal resting echocardiography and absence of coronary artery disease. METHODS: From our database of patients referred for treadmill exercise echocardiography, we identified 93 hypertensive patients with preserved resting left ventricular ejection fraction (≥ 50%), no evidence of structural heart disease, and absence of coronary artery disease on angiography. Overall, 39 patients developed exercise-induced left ventricular systolic dysfunction (defined as a decrease in left ventricular ejection fraction below 50% at peak exercise) and 54 exhibited a normal left ventricular ejection fraction response to exercise. The mean follow-up was 6.1 (3.7) years. End points were all-cause mortality, cardiac death, heart failure, and the composite event of cardiac death or heart failure. RESULTS: Patients who developed exercise-induced left ventricular systolic dysfunction were at higher risk of death from any cause (hazard ratio=3.4; 95% confidence interval, 1.1-10.3), cardiac death (hazard ratio=5.6; 95%CI, 1.1-29.4), heart failure (hazard ratio=8.9; 95% confidence interval, 1.8-44.2), and the composite end point (hazard ratio=5.7; 95% confidence interval, 1.7-19.0). In the multivariate analysis, exercise-induced left ventricular systolic dysfunction remained an independent predictor of both heart failure (hazard ratio=6.9; 95% CI, 1.3-37.4) and the composite event of cardiac death or heart failure (hazard ratio=4.5; 95% confidence interval, 1.2-16.0). CONCLUSIONS: In hypertensive patients with preserved resting left ventricular ejection fraction and absence of coronary artery disease, exercise-induced left ventricular systolic dysfunction is a strong predictor of cardiac events and may represent early hypertensive heart disease.

Long-term prognostic value of mitral regurgitation in patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

The presence of mitral regurgitation (MR) is associated with an impaired prognosis in patients with ischemic heart disease. However, data with regard to the impact of this condition in patients with ST-segment elevation myocardial infarction (STEMI) treated by means of primary percutaneous coronary intervention (PPCI) are lacking. Our aim was to assess the effect of MR in the long-term prognosis of patients with STEMI after PPCI. We analyzed a prospective registry of 1,868 patients (mean age 62 ± 13 years, 79.9% men) with STEMI treated by PPCI in our center from January 2006 to December 2010. Our primary outcome was the composite end point of all-cause mortality or admission due to heart failure during follow-up. After exclusions, 1,036 patients remained for the final analysis. Moderate or severe MR was detected in 119 patients (11.5%). Those with more severe MR were more frequently women (p <0.001), older (p <0.001), and with lower ejection fraction (p <0.001). After a median follow-up of 2.8 years (1.7 to 4.3), a total of 139 patients (13.4%) experienced our primary end point. There was an association between the unfavorable combined event and the degree of MR (p <0.001). After adjustment for relevant confounders, moderate or severe MR remained as an independent predictor of the combined primary end point (adjusted hazard ratio [HR] 3.14, 95% confidence interval [CI] 1.57 to 6.27) and each event separately (adjusted HR death 3.1, 95% CI 1.34 to 7.2; adjusted HR heart failure 3.3, 95% CI 1.16 to 9.4). In conclusion, moderate or severe MR detected early with echocardiography was independently associated with a worse long-term prognosis in patients with STEMI treated with PPCI.

Long-term prognostic benefit of field triage and direct transfer of patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

Direct transfer (DT) to the catheterization laboratory has been demonstrated to reduce delays in primary percutaneous coronary intervention (PPCI). However, data with regard to its effect on long-term mortality are sparse. The aim of this study was to investigate the effect of DT on long-term mortality in patients with ST-segment elevation myocardial infarctions treated with PPCI. A cohort study was conducted of 1,859 patients (mean age 63.1 ± 13 years, 80.2% men) who underwent PPCI from May 2005 to December 2010. From the whole series, 425 patients (23%) were admitted by DT and 1,434 (77%) by emergency departments. DT patients were younger (mean age 61 ± 12 vs 64 ± 12 years, p = 0.017), were more frequently men (86% vs 76%, p = 0.001), and had a higher proportion of abciximab use (77% vs 64%, p <0.0001). The DT group had a shorter median contact-to-balloon time (105 vs 122 minutes, p <0.0001) and a shorter time to treatment (185 vs 255 minutes, p <0.0001) compared with the emergency department group. Thirty-day and long-term mortality (median follow-up 2.4 years, interquartile range 1.6 to 3.2) were lower in the DT group (3% vs 6%, p = 0.049, and 9.4% vs 14.4%, p = 0.008, respectively). An adjusted Cox regression analysis proved that the DT group had an improved prognosis during follow-up (hazard ratio 0.71, 95% confidence interval 0.50 to 0.99). In conclusion, DT of patients with ST-segment elevation myocardial infarctions for PPCI was associated with fewer delays and improved survival. This benefit was maintained after long follow-up. This strategy should be emphasized in all networks of ST-segment elevation myocardial infarction care.

Effect of atrioventricular optimization on circulating N-terminal pro brain natriuretic peptide following cardiac resynchronization therapy.

AIMS: Following CRT, atrioventricular (AV) optimization is not routinely practised. To evaluate its clinical utility, we examined the effect of AV delay optimization on the prognostic biomarker NT-proBNP. METHODS AND RESULTS: We prospectively studied 72 patients (mean age 73 ± 12.5 years, 70.8% male, 55.6% ischaemic) undergoing iterative AV optimization. Patients were divided into those whose nominal setting appeared ideal and not changed (Group 1, n = 22) and those whose AV delay was optimized (Group 2, n = 50). All patients underwent NT-proBNP assessment prior to CRT, and pre- and a median 5 days post-optimization. Compared with Group 1, NT-proBNP fell significantly in Group 2 patients (median 474 pg/mL) following optimization (P = 0.00001). A significant change in filling pattern (defined as a change in AV delay >50 ms) was required in 30% of patients, and it was this subgroup that derived the greater reduction in NT-proBNP levels [-1407 pg/mL, interquartile range (IQR) -3042 to -346 pg/mL] compared with those requiring <50 ms AV delay change (-125 pg/mL, IQR -1038 to 6 pg/mL), P = 0.0011. The benefit of AV optimization was principally observed in reverse remodelling non-responders (median -2167 pg/mL, IQR -3042 to -305 pg/mL) and in patients with a pseudonormal or restrictive filling pattern (median -1407 pg/mL, IQR -2809 to -342 pg/mL), compared with those with more benign diastolic filling (median - 264 pg/mL, IQR -1038 to -21 pg/mL), P = 0.033. CONCLUSIONS: In one-third of patients, major filling pattern changes are achieved with AV optimization, associated with subsequent rapid falls in NT-proBNP. The greater the AV delay change, the larger the NT-proBNP fall, and non-responders and those with restrictive or pseudonormal filling despite CRT are most likely to benefit.

Rate-adaptive AV delay and exercise performance following cardiac resynchronization therapy.

BACKGROUND: Physiological shortening of the atrioventricular (AV) interval with increasing heart rate is well documented in normal human beings and is an established component of dual-chamber pacing for bradycardia. OBJECTIVES: To assess the effect of exercise on optimal AV delay and the impact of a patient-specific rate-adaptive AV delay (RAAVD) on exercise capacity in patients with heart failure following cardiac resynchronization therapy. METHODS: Phase 1: We performed iterative AV optimization at rest and exercise in 52 cardiac resynchronization therapy patients in atrial-sensed mode (mean age 71.6 ± 9.2 years, 25% females). Phase 2: Subsequently, 20 consecutive volunteers from this group (mean age 69.2 ± 9.6 years, 15% females) underwent cardiopulmonary exercise testing with RAAVD individually programmed ON (RAAVD-ON) or OFF (RAAVD-OFF). RESULTS: Phase 1: In 94% of the patients, there was a marked reduction (mean 50%) in optimal AV delay with exercise. The optimal resting vs exercise AV delay was 114.2 ± 29 ms at a heart rate of 64.4 ± 7.1 beats/min vs 57 ± 31 ms at a heart rate of 103 ± 13 beats/min (P < .001). No patients required an increase in AV delay with exercise, and 3 (6%) showed no change. Phase 2: With RAAVD-ON, significantly better exercise times were achieved (8.7 ± 3.2 minutes) compared with RAAVD-OFF (7.9 ± 3.2 minutes; P = .003), and there was a significant improvement in Vo(2)max (RAAVD-ON 16.1 ± 4.0 vs RAAVD-OFF 14.9 ± 3.7 mL/(kg · min); P = .024). CONCLUSIONS: There was a dramatic reduction in optimal AV delay with physiological exercise in the majority of this heart failure cardiac resynchronization therapy cohort. Replicating this physiological response with a programmable RAAVD translated into a 10% improvement in exercise capacity.

Renal insufficiency and vascular complications after primary angioplasty via femoral route. Impact of vascular closure devices use.

INTRODUCTION AND OBJECTIVES: We sought to determine the incidence of vascular complications in patients with chronic kidney disease undergoing primary angioplasty via the femoral route; we also evaluated the safety and efficacy of the use of vascular closure devices in this setting. METHODS: Registry of 527 patients undergoing primary angioplasty via the femoral route from January 2003 to December 2008. Chronic kidney disease was defined as creatinine clearance less than 60 mL/min. The primary endpoint was the presence of major vascular complications. RESULTS: Baseline chronic kidney disease was observed in 166 (31.5%) patients. Patients with chronic kidney disease experienced higher rates of major vascular complications compared to those without worsening of renal function (8.4% vs 4.2%; P=.045), especially those requiring transfusion (6.6% vs 1.9%; P=.006). Among patients with chronic kidney disease, 129 (77.7%) received a vascular closure device and manual compression was used in 37 patients (22.3%). The risk of major vascular complications was significantly lower with vascular closure device use compared to manual compression (4.7% vs 21.6%; P=.003). Multivariable logistic regression analysis showed that the use of a vascular closure device was independently associated with a decreased risk of major vascular complications in patients with chronic kidney disease undergoing primary angioplasty (odds ratio=0.11; 95% confidence interval, 0.03-0.41; P=.001). CONCLUSIONS: Patients with chronic kidney disease undergoing primary angioplasty via the femoral route experience higher rates of major vascular complications. The use of vascular closure devices in this group of patients is safe and is associated with lower rates of major vascular complications compared to manual compression.

Safety and efficacy of femoral vascular closure devices in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: The use of vascular closure devices (VCDs) for the reduction of access site complications following percutaneous coronary intervention (PCI) remains controversial. Patients undergoing primary PCI for acute ST-segment elevation myocardial infarction (STEMI) are at high risk of femoral artery complications. A lack of information exists regarding the use of VCDs in this group of patients because they have been routinely excluded from randomized trials. This study sought to evaluate the safety and efficacy of the routine use of VCDs after primary PCI. METHODS: A total of 558 consecutive patients undergoing primary PCI for STEMI via femoral route were studied for in-hospital outcomes through a prospective registry from January 2003 to December 2008. The primary end point was the presence of major vascular complication (MVC) defined as a composite of fatal access site bleeding, access site complication requiring interventional or surgical correction, or access site bleeding with ≥3 g/dL drop in hemoglobin or requiring blood transfusion. RESULTS: Of the total patients, 464 (83.2%) received a VCD; and manual compression was used in 94 patients (16.8%). Major vascular complication occurred in 5.2% of patients. The risk of MVC was significantly lower with VCDs compared with manual compression (4.3% vs 9.6%, P = .036). Multivariable logistic regression analysis determined that VCD use remained an independent predictor of lower rate of MVC (odds ratio 0.38, 95% CI 0.17-0.91). CONCLUSIONS: The use of VCDs in patients undergoing primary PCI for STEMI is safe and is associated with lower rates of MVC compared with manual compression.