Empagliflozin after Acute Myocardial Infarction.

BACKGROUND: Empagliflozin improves cardiovascular outcomes in patients with heart failure, patients with type 2 diabetes who are at high cardiovascular risk, and patients with chronic kidney disease. The safety and efficacy of empagliflozin in patients who have had acute myocardial infarction are unknown. METHODS: In this event-driven, double-blind, randomized, placebo-controlled trial, we assigned, in a 1:1 ratio, patients who had been hospitalized for acute myocardial infarction and were at risk for heart failure to receive empagliflozin at a dose of 10 mg daily or placebo in addition to standard care within 14 days after admission. The primary end point was a composite of hospitalization for heart failure or death from any cause as assessed in a time-to-first-event analysis. RESULTS: A total of 3260 patients were assigned to receive empagliflozin and 3262 to receive placebo. During a median follow-up of 17.9 months, a first hospitalization for heart failure or death from any cause occurred in 267 patients (8.2%) in the empagliflozin group and in 298 patients (9.1%) in the placebo group, with incidence rates of 5.9 and 6.6 events, respectively, per 100 patient-years (hazard ratio, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P = 0.21). With respect to the individual components of the primary end point, a first hospitalization for heart failure occurred in 118 patients (3.6%) in the empagliflozin group and in 153 patients (4.7%) in the placebo group (hazard ratio, 0.77; 95% CI, 0.60 to 0.98), and death from any cause occurred in 169 (5.2%) and 178 (5.5%), respectively (hazard ratio, 0.96; 95% CI, 0.78 to 1.19). Adverse events were consistent with the known safety profile of empagliflozin and were similar in the two trial groups. CONCLUSIONS: Among patients at increased risk for heart failure after acute myocardial infarction, treatment with empagliflozin did not lead to a significantly lower risk of a first hospitalization for heart failure or death from any cause than placebo. (Funded by Boehringer Ingelheim and Eli Lilly; EMPACT-MI ClinicalTrials.gov number, NCT04509674.).

Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial.

BACKGROUND: Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown. METHODS: EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of <45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes. RESULTS: Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; P=0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; P=0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all P<0.05). CONCLUSIONS: Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04509674.

Clinical Review of Hypertensive Acute Heart Failure.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year (from 20% to 36%) mortality. Considering the high rate of rehospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

Left Ventricular Function, Congestion, and Effect of Empagliflozin on Heart Failure Risk After Myocardial Infarction.

BACKGROUND: Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). OBJECTIVES: This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI. METHODS: In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months. RESULTS: Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. CONCLUSIONS: In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674).

El ácido úrico y la actividad de gammaglutamil transferasa se asocian a los índices de remodelado ventricular izquierdo en pacientes con insuficiencia cardiaca crónica / Uric acid and gamma-glutamyl transferase activity are associated with left ventricular remodeling indices in patients with chronic heart failure

Introducción y objetivos El ácido úrico y la gammaglutamil transferasa son indicadores pronósticos en la insuficiencia cardiaca crónica. No obstante, el mecanismo subyacente a la asociación observada entre ácido úrico, gammaglutamil transferasa y progresión y pronóstico de la insuficiencia cardiaca crónica sigue siendo en gran parte desconocido.MétodosSe estudió la asociación del ácido úrico y la gammaglutamil transferasa con la dilatación mediada por flujo y con los índices ecocardiográficos del remodelado cardiaco en 120 pacientes con insuficiencia cardiaca isquémica crónica. Para determinar la contribución independiente del ácido úrico y la gammaglutamil transferasa en la dilatación mediada por flujo y en los índices ecocardiográficos del remodelado, se construyó una serie de modelos de regresión lineal múltiple, basados en los factores de riesgo tradicionales y no tradicionales que influyen en estos parámetros. Resultados: El ácido úrico es un factor independiente predictivo de dilatación mediada por flujo, pero no la gammaglutamil transferasa. El ácido úrico se asocia a todos los índices ecocardiográficos de disfunción ventricular izquierda evaluados en tres modelos de regresión múltiple; también muestra correlación con los diámetros telesistólico (r = 0,337) y telediastólico (r = 0,340) y los volúmenes telesistólico (r = 0,321) y telediastólicos (r = 0,294) del ventrículo izquierdo (p = 0,001). La gammaglutamil transferasa es un factor independiente predictivo de los volúmenes telesistólico y telediastólico del ventrículo izquierdo tras introducir un ajuste por todas las variables. La gammaglutamil transferasa muestra correlación con los diámetros telesistólico (r = 0,238; p = 0,009) y telediastólico (r = 0,219; p = 0,016) y los volúmenes telesistólico (r = 0,359; p < 0,001) y telediastólico (r = 0,369; p = 0,001) del ventrículo izquierdo. Conclusiones: El ácido úrico y la actividad de gammaglutamil transferasa se asocian a los índices de remodelado ventricular izquierdo en pacientes con insuficiencia cardiaca isquémica crónica

Introduction and objectives Uric acid and gamma-glutamyl transferase are prognostic indicators in chronic heart failure. Nevertheless, the mechanism underlying the association between uric acid, gamma-glutamyl transferase, and chronic heart failure progression and prognosis remains largely unknown.MethodsThe association of uric acid and gamma-glutamyl transferase with flow-mediated dilation and echocardiographic indices of cardiac remodeling was addressed in 120 patients with chronic ischemic heart failure. To determine the independent contribution of uric acid and gamma-glutamyl transferase to the flow-mediated dilation and echocardiographic indices of remodeling, a series of multiple linear regression models, based on traditional and nontraditional risk factors impacting upon these parameters, were constructed.ResultsUric acid, but not gamma-glutamyl transferase, was an independent predictor of flow-mediated dilation. Uric acid was associated with all the echocardiographic indices of left ventricular in patients with chronic ischemic heart failure

Preditores de função ventricular esquerda global na síndrome metabólica / Predictors of global left ventricular function in metabolic syndrome / Predictores de función ventricular izquierda global en el síndrome metabólico

FUNDAMENTO: A síndrome metabólica (SM) representa um conjunto de fatores de risco cardiovascular que agem de forma sinérgica. OBJETIVO: O objetivo desse estudo foi determinar quais parâmetros estavam associados de forma independente à função global do ventrículo esquerdo (VE) em indivíduos com SM, estimada através do índice Tei. MÉTODOS: O estudo incluiu 234 indivíduos com SM e 96 controles ajustados por idade. A SM foi definida pela presença de três ou mais critérios da ATP-NCEP III. Todos os indivíduos foram submetidos a testes laboratoriais e ecocardiograma bidimensional e com Doppler pulsátil e tecidual. Intervalos de tempo apropriados no Doppler tecidual para a estimativa do índice Tei também foram avaliados. RESULTADOS: O índice Tei estava aumentado em todos os indivíduos com SM (0,35 ± 0,05 vs 0,49 ± 0,10, p < 0,001). Análise de regressão múltipla dos parâmetros clínicos mostrou que a pressão arterial sistólica (β= 0,289, p < 0,001), glicemia de jejum (β= 0,205, p = 0,009), índice de massa do VE (β= 0,301, p < 0,001), E/e'septal (β= 0,267, p < 0,001) e e'septal (β= -0,176, p = 0,011) estavam independentemente associados com a função ventricular esquerda global estimada pelo índice Tei. CONCLUSÃO: A SM teve um impacto significante na função global do VE. A pressão arterial sistólica, glicemia de jejum, índice de massa do VE E/e'septal, e e'septal estavam independentemente associados com a função global do VE.

BACKGROUND: The metabolic syndrome (MS) represents a cluster of cardiovascular risk factors that act synergistically. OBJECTIVE: The aim of this study was to determine which parameters were independently associated with the global left ventricular (LV) function in subjects with MS estimated with the Tei index. METHODS: The study included 234 subjects with MS and 96 controls adjusted by age. MS was defined by the presence of three or more of ATP- NCEP III criteria. All subjects underwent laboratory blood tests and two-dimensional, pulsed and tissue Doppler echocardiography. Appropriate tissue Doppler time intervals for the estimation of the Tei index were also assessed. RESULTS: The Tei index was increased in subjects with MS (0.35 ± 0.05 vs 0.49 ± 0.10, p < 0.001). Multiple regression analysis of the clinical parameters showed that systolic blood pressure (β= 0.289, p < 0.001), fasting glucose (β= 0.205, p = 0.009), LV mass index (β= 0.301, p < 0.001), E/e'septal (β= 0.267, p < 0.001), and e'septal (β= -0.176, p = 0.011) were independently associated with the global left ventricular function estimated by Tei index. CONCLUSION: MS has a significant impact on LV global function. Systolic blood pressure, fasting glucose, LV mass index, E/e'septal, and e'septal were independently associated with the LV global function.

FUNDAMENTO: El síndrome metabólico (SM) representa un conjunto de factores de riesgo cardiovascular que actúan de forma sinérgica. OBJETIVO: El objetivo de este estudio fue determinar cuales parámetros estaban asociados de forma independiente a la función global del ventrículo izquierdo (VI) en individuos con SM, estimada a través del índice Tei. MÉTODOS: El estudio incluyó 234 individuos con SM y 96 controles ajustados por edad. El SM fue definido por la presencia de tres o más criterios ATP-NCEP III. Todos los individuos fueron sometidos a tests de laboratorio y ecocardiograma bidimensional y con Doppler pulsado y tisular. Intervalos de tiempo apropiados en el Doppler tisular para la estimativa del índice Tei también fueron evaluados. RESULTADOS: El índice Tei estaba aumentado en todos los individuos con SM (0,35 ± 0,05 vs 0,49 ± 0,10, p < 0,001). Análisis de regresión múltiple de los parámetros clínicos mostró que la presión arterial sistólica (β = 0,289, p < 0,001), glucemia de ayuno (β = 0,205, p = 0,009), índice de masa del VI (β = 0,301, p < 0,001), E/e'septal (β = 0,267, p < 0,001) y e'septal (β = -0,176, p = 0,011) estaban independientemente asociados con la función ventricular izquierda global estimada por el índice Tei. CONCLUSIÓN: El SM tuvo un impacto significativo en la función global del VI. La presión arterial sistólica, glucemia de ayuno, índice de masa del VI E/e'septal, y e'septal estaban independientemente asociados con la función global del VI. (Arq Bras Cardiol 2011;96(5):377-385).