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.

Morbidity and Mortality Associated With Heart Failure in Acute Coronary Syndrome: A Pooled Analysis of 4 Clinical Trials.

BACKGROUND: Heart failure (HF) may complicate acute coronary syndrome (ACS) and is associated with a high burden of short- and long-term morbidity and mortality. Only limited data regarding future ischemic events and rehospitalization are available for patients who suffer HF before or during ACS. METHODS: A secondary analysis of 4 large ACS trials (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) using Cox proportional hazards models was performed to investigate the association of HF status (no HF, chronic HF, de novo HF) at presentation for ACS with all-cause and cardiovascular death, major adverse cardiovascular event (MACE ), myocardial infarction, stroke, and hospitalization for heart failure (HHF) by 1 year. Cumulative incidence plots are presented at 30 days and 1 year. RESULTS: A total of 11.1% of the 47,474 patients presenting with ACS presented with evidence of acute HF, 55.0% of whom presented with de novo HF. Patients with chronic HF presented with evidence of acute HF at a higher rate than those with no previous HF (40.3% vs 6.9%). Compared to those without HF, those with chronic and de novo HF had higher rates of all-cause mortality (adjusted hazard ratio [aHR] 2.01, 95% confidence interval [CI] 1.72-2.34 and aHR 1.47, 95% CI1.15-1.88, respectively), MACE (aHR 1.47, 95% CI1.31-1-.66 and aHR 1.38, 95% CI1.12-1.69), and HHF (aHR 2.29, 95% CI2.02-2.61 and aHR 1.48, 95% CI 1.20-1.82) at 1 year. CONCLUSION: In this large cohort of patients with ACS, both prior and de novo HF complicating ACS were associated with significantly higher risk-adjusted rates of death, ischemic events and HHF at 30 days and 1 year. Further studies examining the association between HF and outcomes in this high-risk population are warranted, especially given the advent of more contemporary HF therapies.

Inhaled nitric oxide in adults with in-hospital cardiac arrest: A feasibility study.

BACKGROUND: While inhaled nitric oxide (iNO) has revealed benefit in cardiac arrest in an animal model, no published data has yet demonstrated the impact of iNO in humans with cardiac arrest. METHODS: In this pilot study, we administered iNO, along with standard post-resuscitative care, in adults with in-hospital cardiac arrest (IHCA) following achievement of return of spontaneous circulation (ROSC) at an academic tertiary medical center. Patients receiving iNO were compared to age-matched controls with IHCA receiving standard care from an institutional registry. The primary outcome was survival to discharge; secondary outcome was favorable neurologic outcome, defined by a Glasgow Outcome Score of 4 or 5. Propensity-score (PS) matching analysis was performed between patients receiving iNO versus controls. RESULTS: Twenty adults with IHCA receiving iNO were compared to 199 controls with IHCA. Similar age, Charlson comorbidity index, and initial rhythm were noted in both groups. Patients receiving iNO had higher rates of survival to discharge compared to controls (35% vs 11%, p < 0.0001) but no difference in favorable neurologic outcome (15% vs 9%, p = 0.39) in the unmatched population. In the PS-matched analysis, patients receiving iNO had higher survival to discharge (35% vs 20%, p = 0.0344) than the control group but no difference in favorable neurologic outcome (15% vs 20%, p = 0.13) were noted between both groups. CONCLUSIONS: In this pilot study, iNO was associated with significantly higher rates of survival to discharge but not favorable neurologic outcome among patients with IHCA compared to controls. This benefit was also observed in the PS-matched analysis. A large scale randomized controlled trial comparing standard of care supplemented with iNO to standard of care alone is warranted in patients with cardiac arrest (Funded by Stony Brook University Renaissance School of Medicine, ClinicalTrials.gov number, NCT04134078).

Distressed Communities Index in Patients Undergoing Transcatheter Aortic Valve Implantation in an Affluent County in New York.

BACKGROUND: The clinical impact of the distressed communities index (DCI), a composite measure of economic well-being based on the U.S. zip code, is becoming increasingly recognized. Ranging from 0 (prosperous) to 100 (distressed), DCI's association with cardiovascular outcomes remains unknown. We aimed to study the association of the DCI with presentation and outcomes in adults with severe symptomatic aortic stenosis (AS) undergoing transcatheter aortic valve intervention (TAVR) in an affluent county in New York. METHODS: The study population included 286 patients with severe symptomatic AS or degeneration of a bioprosthetic valve who underwent TAVR with a newer generation transcatheter heart valve (THV) from December 2015 to June 2018 at an academic tertiary medical center. DCI for each patient was derived from their primary residence zip code. Patients were classified into DCI deciles and then categorized into 4 groups. The primary and secondary outcomes of interest were 30-day, 1-year, and 3-year mortality, respectively. RESULTS: Among 286 patients studied, 26%, 28%, 28%, and 18% were categorized into DCI groups 1-4, respectively (DCI <10: n = 73; DCI 10-20: n = 81; DCI 20-30: n = 80; DCI >30: n = 52). Patients in group 4 were younger with worse kidney function compared to patients in groups 1 and 2. They also had smaller aortic annuli and were more likely to receive a smaller THV. No significant difference in hospital length of stay or distribution of in-hospital, 30-day, 1-year, and 3-year mortality was demonstrated. CONCLUSIONS: While the DCI was associated with differences in the clinical and anatomic profile, it was not associated with differences in clinical outcomes in this prospective observational study of adults undergoing TAVR suggesting that access to care is the likely discriminator.

Women with chronic kidney disease undergoing transcatheter aortic valve replacement: Caveat emptor.

Over 60% of women presenting for transcatheter aortic valve replacement (TAVR) have coexisting chronic kidney disease (CKD). In women undergoing TAVR, CKD was associated with significantly higher rates of adverse events, including a twofold higher rate of risk-adjusted mortality at 1 year. This study is an important step forward in our understanding of risk stratification in women with CKD undergoing TAVR and suggests that measures to optimize outcomes warrant further investigation in this high-risk group of patients.

Closing the gender gap (but not the generation gap) in acute coronary syndromes.

In patients with acute coronary syndromes (ACS) undergoing coronary angiography, elderly women have nearly 50% lower rates of adverse events compared to elderly men, primarily driven by lower cardiovascular mortality. Nonelderly men and women patients with ACS have similar risk-adjusted rates of adverse events. Elderly ACS patients have lower rates of and delays in coronary revascularization than younger patients.

Trends in Management and Mortality in Adults Hospitalized With Cardiac Arrest in the United States.

BACKGROUND: We sought to examine temporal trends in management (ie, use of extracorporeal membrane oxygenation [ECMO], therapeutic hypothermia [TH], coronary angiogram, and percutaneous coronary intervention [PCI]) and in-hospital mortality in adults hospitalized with cardiac arrest. METHODS: Utilizing the Nationwide Inpatient Sample, medical history, clinical management, and in-hospital mortality were assessed in 942 495 hospitalizations in adults with cardiac arrest (identified through International Classification of Diseases-9 codes) from 2006 to 2012. RESULTS: From 2006 to 2012, there was an overall rise in the use of coronary angiogram (12.8%, 13.0%, 14.7%, 15.0%, 14.3%, 14.7%, and 15.8%), PCI (7.5%, 7.1%, 8.4%, 8.1%, 8.1%, 8.4%, and 8.9%), TH (0.2%, 0.3%, 0.6%, 1.2%, 1.9%, 2.8%, and 3.0%), and ECMO (0.1%, 0.1%, 0.1%, 0.2%, 0.2%, 0.3%, and 0.4%; P < .001 for all). In-hospital mortality significantly decreased over the 7-year study period (65.5%, 63.4%, 59.3%, 57.9%, 57.0%, 56.0%, and 56.3% from 2006 to 2012). In multivariable analysis, a 31% decrease in mortality was accompanied by a concomitant 24% and 27% increase in coronary angiogram and PCI, respectively, during the study period. Therapeutic hypothermia and ECMO were associated with an approximate 11-fold and 7-fold increase, respectively, from 2006 to 2012. The strongest predictors of use of ECMO, TH, coronary angiogram, and PCI were younger age and the presence of coronary artery disease. CONCLUSION: During 2006 to 2012, a decline in mortality was accompanied by a steady rise in the use of ECMO, TH, coronary angiogram, and PCI in adults hospitalized with cardiac arrest. Patients of younger age and with coronary artery disease were more likely to receive these advanced therapies.

Association of Arterial Oxygen Tension During In-Hospital Cardiac Arrest With Return of Spontaneous Circulation and Survival.

BACKGROUND: Despite numerous advances in the delivery of resuscitative care, in-hospital cardiac arrest (IHCA) continues to be associated with high morbidity and mortality. We sought to study the impact of arterial oxygen tension (Pao2) on return of spontaneous circulation (ROSC) and survival to discharge in patients with IHCA. METHODS: The study population included 255 consecutive patients who underwent advanced cardiac life support-guided resuscitation from January 2012 to December 2013 for IHCA at an academic tertiary medical center. Of these patients, 167 underwent arterial blood gas testing at the time of the arrest. Baseline demographic, clinical, laboratory, and clinical outcome data were recorded. The primary outcome of interest was survival to hospital discharge. Secondary outcome of interest was presence of ROSC. RESULTS: Of the 167 patients studied, Pao2 categorization included the following: Pao2 < 60 mm Hg (n = 38), Pao2 of 60-92 mm Hg (n = 44), Pao2 of 93 to 159 mm Hg (n = 43), Pao2 of 160 to 299 mm Hg (n = 24), and Pao2 ≥ 300 mm Hg (n = 18). Patients with higher Pao2 levels during the time of cardiac arrest were noted to have higher rates of hypertension and chronic kidney disease. Clinical presentation of IHCA, in particular, the initial rhythm, location of IHCA, and duration of cardiopulmonary resuscitation, was similar in all groups. Patients with higher Pao2 levels had higher platelet count, higher arterial pH, and lower arterial carbon dioxide tension (Pco2). With respect to outcomes, patients with higher intra-arrest Pao2 levels had progressively higher rates of ROSC (58% vs 71% vs 72% vs 79% vs 100%, P = .021) and survival to discharge (16% vs 23% vs 30% vs 33% vs 56%, P = .031). In multivariate analysis, Pao2 ≥ 300 mm Hg was independently associated with higher survival to discharge (odds ratio 60.68; 95% confidence interval: 3.04-1210.28; P = .007; referent Pao2 < 60 mm Hg). CONCLUSION: Higher intra-arrest Pao2 is independently associated with higher rates of survival to discharge in adults with IHCA.

Gender Disparities in Presentation, Management, and Outcomes of Acute Myocardial Infarction.

PURPOSE OF REVIEW: This review provides updates in gender disparities in the symptom profile, risk factors, quality and timeliness of guideline-based medical care, and clinical outcomes, including mortality, bleeding, and vascular complications, in patients with acute myocardial infarction (AMI). RECENT FINDINGS: While AMI continues to be a leading cause of mortality in both men and women, significant gender differences exist in presentation, management, and outcomes. Women with AMI are older, suffer atypical symptoms, and more often present with HF and cardiogenic shock. Delays in medical care and hence longer ischemic times exist in women, partly due to decreased awareness and lack of symptom recognition. Women continue to be less likely to receive guideline-based pharmacological therapies and revascularization than men with AMI. While women suffer from significantly higher risk-adjusted rates of bleeding, vascular complications, and short-term mortality, the risk-adjusted rates of long-term mortality remain similar between men and women. Further investigations and efforts are needed to aggressively modify risk factors, reduce delays in care, and address the higher rates of adverse events seen in women with AMI. Significant sex disparities are prevalent in presentation, management, and outcomes of adults with AMI. Further investigations and efforts are needed to aggressively modify risk factors, reduce delays in care, and address the higher rates of adverse events seen in women with AMI.