Evaluation of eplerenone in the subgroup of EPHESUS patients with baseline left ventricular ejection fraction <or=30%

AIMS: Because of the prognostic importance of LV dysfunction following an AMI and the increasing use of electrical and/or mechanical interventions in patients with LV systolic dysfunction, this retrospective analysis of EPHESUS patients with LVEF 相似文献   

Eplerenone improves prognosis in postmyocardial infarction diabetic patients with heart failure: results from EPHESUS

Background:  The Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) trial demonstrated that selective aldosterone blockade with eplerenone significantly reduced total mortality by 15%, combined cardiovascular (CV) mortality/CV hospitalization by 13%, CV mortality by 17% and sudden cardiac death by 21%, vs. placebo when added to standard care in patients with left ventricular systolic dysfunction (LVSD) and signs of congestive heart failure (CHF) following acute myocardial infarction (AMI). We retrospectively evaluated the effect of eplerenone vs. placebo in a subset of 1483 diabetic patients with LVSD and signs of CHF following AMI.
Methods:  Diabetic status was determined from medical histories at screening. Analyses were based on time to first occurrence of an event. Results were based on a Cox's proportional hazards regression model stratified by region with treatment, subgroup and treatment-by-subgroup interaction as factors. The 95% confidence intervals for the risk ratios were based on the Wald's test.
Results:  Treatment with eplerenone in diabetic patients with CHF following AMI reduced the risk of the primary endpoint, a composite of CV mortality or CV hospitalization, by 17% (p = 0.031). The absolute risk reduction of the primary endpoint was greater in the diabetic cohort (5.1%) than in the non-diabetic cohort (3%). Hyperkalaemia occurred more often with eplerenone than with placebo (5.6 vs. 3%, p = 0.015). Among the diabetic cohorts, the prespecified endpoint of 'any CV disorder' occurred in 28% of the eplerenone group and 35% of the placebo group (p = 0.007).
Conclusion:  Eplerenone treatment may reduce adverse CV events in diabetic patients with LVSD and signs of CHF following AMI.     

Cost-Effectiveness of Eplerenone in Patients with Left Ventricular Dysfunction after Myocardial Infarction—An Analysis of the EPHESUS Study from a Swiss Perspective

Objective The EPHESUS study demonstrated that aldosterone blockade with eplerenone decreased mortality in patients with left ventricular systolic dysfunction (LVSD) and heart failure after acute myocardial infarction (AMI). The EPHESUS pharmacoeconomic analysis was performed to evaluate the cost-effectiveness of eplerenone in the Swiss setting. Materials and methods A total of 6,632 patients with LVSD and heart failure after AMI were randomized to eplerenone or placebo and followed for a mean of 16 months. The co-primary endpoints were all-cause death and the composite of cardiovascular death/cardiovascular hospitalization. The evaluation of resource use included hospitalizations, outpatient services, and medications. Survival beyond the trial period was estimated using data from the Framingham Heart Study, the Saskatchewan Health database, and the Worcester Heart Attack Registry. The incremental cost-effectiveness of eplerenone in cost per life-year and quality-adjusted life-year gained was estimated. The perspective of the Swiss third party payers was used. Daily treatment costs of eplerenone were set at CHF 3.88. All other resources were valued on the basis of official tariffs. Discounting of the results was performed at a rate of 3%. Results The number of life-years gained with eplerenone was 0.1083 based on Framingham, 0.0661 with Saskatchewan and 0.1518 with Worcester survival estimates. Total costs were CHF 1,028 higher over the trial period in the eplerenone arm, due to drug cost. The incremental cost-effectiveness ratio was CHF 10,145 per life-year gained with Framingham, CHF 16,178 with Saskatchewan, and CHF 7,693 with Worcester survival estimates. The corresponding costs per QALY were CHF 15,219, CHF 23,965 and CHF 11,337, respectively. Conclusion Eplerenone is effective in reducing mortality and, in Switzerland, is also cost-effective in increasing years of life for patients with LVSD after AMI.     

History of hypertension and eplerenone in patients with acute myocardial infarction complicated by heart failure

In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (n=6632), eplerenone-associated reduction in all-cause mortality was significantly greater in those with a history of hypertension (Hx-HTN). There were 4007 patients with Hx-HTN (eplerenone: n=1983) and 2625 patients without Hx-HTN (eplerenone: n=1336). Propensity scores for eplerenone use, separately calculated for patients with and without Hx-HTN, were used to assemble matched cohorts of 1838 and 1176 pairs of patients. In patients with Hx-HTN, all-cause mortality occurred in 18% of patients treated with placebo (rate, 1430/10 000 person-years) and 14% of patients treated with eplerenone (rate, 1058/10 000 person-years) during 2350 and 2457 years of follow-up, respectively (hazard ratio [HR]: 0.71; 95% CI: 0.59 to 0.85; P<0.0001). Composite end point of cardiovascular hospitalization or cardiovascular mortality occurred in 33% of placebo-treated patients (3029/10 000 person-years) and 28% of eplerenone-treated patients (2438/10 000 person-years) with Hx-HTN (HR: 0.82; 95% CI: 0.72 to 0.94; P=0.003). In patients without Hx-HTN, eplerenone reduced heart failure hospitalization (HR: 73; 95% CI: 0.55 to 0.97; P=0.028) but had no effect on mortality (HR: 0.91; 95% CI: 0.72 to 1.15; P=0.435) or on the composite end point (HR: 0.91; 95% CI: 0.76 to 1.10; P=0.331). Eplerenone should, therefore, be prescribed to all of the post-acute myocardial infarction patients with reduced left ventricular ejection fraction and heart failure regardless of Hx-HTN.     

Update on aldosterone antagonists use in heart failure with reduced left ventricular ejection fraction. Heart Failure Society of America Guidelines Committee

Aldosterone antagonists (or mineralocorticoid receptor antagonists [MRAs]) are guideline-recommended therapy for patients with moderate to severe heart failure (HF) symptoms and reduced left ventricular ejection fraction (LVEF), and in postmyocardial infarction patients with HF. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) trial evaluated the MRA eplerenone in patients with mild HF symptoms. Eplerenone reduced the risk of the primary endpoint of cardiovascular death or HF hospitalization (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.54-0.74, P < .001) and all-cause mortality (adjusted HR 0.76, 95% CI 0.62-0.93, P < .008) after a median of 21 months. Based on EMPHASIS-HF, an MRA is recommended for patients with New York Heart Association (NYHA) Class II-IV symptoms and reduced LVEF (<35%) on standard therapy (Strength of Evidence A). Patients with NYHA Class II symptoms should have another high-risk feature to be consistent with the EMPHASIS-HF population (age >55 years, QRS duration >130 msec [if LVEF between 31% and 35%], HF hospitalization within 6 months or elevated B-type natriuretic peptide level). Renal function and serum potassium should be closely monitored. Dose selection should consider renal function, baseline potassium, and concomitant drug interactions. The efficacy of eplerenone in patients with mild HF symptoms translates into a unique opportunity to reduce morbidity and mortality earlier in the course of the disease.     

Eplerenone: A Selective Aldosterone Blocker

Recent studies suggest that aldosterone may play a larger role than once appreciated in normal physiologic function and cardiovascular disease. Some of the adverse cardiovascular effects that have been described include cardiac and vascular fibrosis, vascular necrosis and inflammation, impaired endothelial function, reduced fibrinolysis, hypertension, left ventricular hypertrophy (LVH), congestive heart failure, and cardiac arrhythmias. In light of these findings, the ability to block the actions of aldosterone has gained increased therapeutic importance. Eplerenone is a selective aldosterone receptor blocker that displays little interaction with androgen and progesterone receptors. Eplerenone has already been approved for the treatment of systemic hypertension and has been evaluated in numerous hypertension subgroups, including patients with low plasma renin activity; diabetes; LVH; uncontrolled blood pressure while receiving monotherapy with angiotensin‐converting enzyme inhibitors, angiotensin‐receptor blockers, calcium channel blockers, or beta‐blockers; and in black patients. Results of these trials indicate that eplerenone lowers blood pressure and reduces end‐organ damage. Further proof of the therapeutic importance of mineralocorticoid receptor blockade comes from the eplerenone post acute myocardial infarction survival and efficacy study (EPHESUS). In this large‐scale clinical outcome trial, eplerenone was shown to reduce total mortality by 15% as well as the combined endpoint of cardiovascular mortality/cardiovascular hospitalization by 13% when administered at a mean of 7.3 days post myocardial infarction to patients with evidence of systolic left ventricular dysfunction and symptoms of heart failure. Eplerenone is well tolerated, with an adverse effect profile comparable to placebo. The advent of selective aldosterone blockers, such as eplerenone, should prove to be of great therapeutic value in hypertension control and prevention of cardiovascular disease and associated end‐organ damage.     

Hospital protocols and evidence-based therapies: the importance of integrating aldosterone blockade into the management of patients with post-acute myocardial infarction heart failure

Left ventricular systolic dysfunction (LVSD) and clinical heart failure are common complications of acute myocardial infarction (AMI) and result in substantially increased mortality and morbidity. Evidence-based cardiovascular protective therapies, including angiotensin-converting enzyme inhibitors, beta blockers, antiplatelet agents, and lipid-lowering medications, improve outcomes for these patients. However, this population is significantly undertreated with these guideline-recommended agents. Critical pathways have been demonstrated to improve the quality and consistency of treatment; as such, the new American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of patients with ST-elevation myocardial infarction (STEMI) recommend that critical pathways be implemented for the management of these patients. The recent Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) demonstrates that eplerenone, a selective aldosterone blocker, has incremental benefit in decreasing mortality and morbidity when used with standard care therapies in patients post AMI with heart failure and LVSD. The clinical trial evidence coupled with the national guidelines provides a strong rationale for routine incorporation of aldosterone blockade into new or already established critical pathways for AMI complicated by LVSD and heart failure.     

Hypo- and hyperglycemia predict outcome in patients with left ventricular dysfunction after acute myocardial infarction: data from EPHESUS

BackgroundHyperglycemia predicts death in cardiovascular disease, but intensive glucose-lowering strategies increase mortality rates in diabetes. The present analysis investigated the prognostic value of postadmission blood glucose (BG) concentration on clinical outcomes in high-risk patients with heart failure after acute myocardial infarction.Methods and ResultsA total of 6,496 patients from the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) were categorized into 4 groups by plasma glucose concentration: ≤4.5 mmol/L (hypoglycemia), 4.5–5.5 mmol/L (normoglycemia), 5.5–8.3 mmol/L (elevated glucose level), and >8.3 mmol/L (severe hyperglycemia). We evaluated the time to all-cause death (primary end point) and time to cardiovascular death or hospitalization (secondary end point). Hypo- and severe hyperglycemia were prevalent in 509 (8%) and 1,588 (24%) patients, respectively. There was a U-shaped relationship between BG level and incidence of all-cause death (11.8% in patients with normoglycemia vs 15.1% and 19.9% in those with hypo- and severe hyperglycemia; P < .001). The incidence of the secondary end point was increased only in hyperglycemic patients (36% vs 23% in normoglycemic patients; P < .001). In multivariate Cox regression analysis, hypoglycemia (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.06–1.81; P = .002) and severe hyperglycemia (HR 1.52, CI 1.27–1.83; P < .0001) proved to be strong predictors of all-cause death. There was no significant interaction between eplerenone treatment and blood glucose levels regarding clinical outcomes.ConclusionsIn heart failure after acute myocardial infarction, both hypo- and hyperglycemia at the postacute phase identify patients with increased risk of death during long-term follow-up.     

Usefulness of either or both left and right bundle branch block at baseline or during follow-up for predicting death in patients following acute myocardial infarction

The presence or onset of bundle branch block (BBB) is associated with increased mortality in patients after acute myocardial infarction (AMI). The risk increases with age. We assessed the prognostic power of BBB patterns for predicting clinical outcomes in patients after high-risk AMI. In the OPTIMAAL trial, the effects of losartan versus captopril were compared in 5,477 patients with heart failure and/or evidence of left ventricular dysfunction after MI. The association between clinical outcomes and the presence of left or right BBB at randomization (median 3 days after AMI) or occurring during follow-up (mean 2.7 years) was assessed using Cox regression models. At randomization, 8% of patients (n = 438) showed BBB patterns; 3.7% (n = 203) showed left BBB and 4.3% (n = 235) showed right BBB patterns. In patients with left BBB, there was an increased risk of all-cause death and cardiovascular death. In patients with right BBB, there was increased risk of sudden cardiac death/resuscitated cardiac arrest. During follow-up, another 4.9% (n = 272) developed BBB patterns; 2.8% (n = 153) developed left BBB and 2.17% (n = 119) developed right BBB. Left BBB was associated with increased risk for all-cause death, cardiovascular death, and sudden cardiac death/resuscitated cardiac arrest, whereas right BBB was related to increased risk of sudden cardiac death/resuscitated cardiac arrest. In conclusion, our results confirm and quantify previous observations showing substantially increased mortality in patients with BBB patterns at baseline or occurring soon after AMI.     

Optimizing care of heart failure after acute MI with an aldosterone receptor antagonist

The presence of heart failure or left ventricular systolic dysfunction in the setting of acute myocardial infarction is associated with poor prognosis. Aldosterone is an important downstream mediator of the reninangiotensin-aldosterone system that promotes myocardial collagen deposition, myocardial fibrosis, apoptosis, ventricular remodeling, and endothelial dysfunction. It may play an important role in the increased morbidity and mortality and the development and progression of heart failure after acute myocardial infarction. Extending the findings from the Randomized Aldactone Evaluation Study (RALES) in patients with chronic heart failure, the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) demonstrated that the selective aldosterone blocker eplerenone offered a significant survival benefit, attenuation of progression of heart failure, and prevention of sudden cardiac death when used in addition to optimal medical therapy. The current evidence-based guidelines now suggest that aldosterone blockade should be an integral component of heart failure therapy to improve outcomes in this high-risk population.     

Long-term outcome of intravenous magnesium therapy in thrombolysis-ineligible acute myocardial infarction patients

The aim of our study was to analyze the long-term survival and cardiac function in 194 consecutive, thrombolysis-ineligible acute myocardial infarction (AMI) patients receiving 48-hour intravenous magnesium sulfate (22 g) - 96 patients, compared with placebo - 98 patients. After a mean 4.8-year follow-up, all-cause mortality and cardiac mortality were significantly lower in the magnesium compared to the placebo group [(18 vs. 33 patients, p < 0.01) and (12 vs. 30 patients, p < 0.001), respectively]. Rest radionuclide ventriculography tests for left-ventricular ejection fraction (LVEF) were assessed in surviving patients up to completion of follow-up. Magnesium-treated patients had a significantly higher LVEF (0.51 +/- 0.10 vs. 0.44 +/- 0.14, p < 0.05) and a lower incidence of heart failure compared to placebo-treated patients (12 vs. 3 patients, p = 0.02). Beneficial effects of intravenous magnesium therapy in thrombolysis-ineligible AMI patients appeared to last for at least 4.8 years, concomitant with preserved LVEF, suggesting a favorable role for acute magnesium treatment in these patients.     

心力衰竭加重并左室射血分数降低患者的QRS时限与预后

目的观察住院期间QRs时限对心力衰竭并左室射血分数降低预后的影响。方法回顾性分析心力衰竭并左室射血分数降低（≤40％）或正常的住院患者住院期间的QRs波群时限。结果3002例患者纳入研究,其中正常QRS波群时限1745例（〈120ms）,QRS波群延长（≥120ms）1257例。平均随访10个月,基础QRS波群时限正常患者全因死亡率为18．8％,基础QRS波群延长患者为28．3％（nR。1．62,95％CIL38～1．88）。基础QRS波群正常患者心血管死亡和心力衰竭住院率为31．5％和35．8％,延长者则为39．0％和43．6％（朋=1．40、1．42;95％CIL25-1．60、1．18-1．72）。QRS波群时限延长与增加全因死亡率危险性相关（HR=1．25：95％C11．03～1．52）,并增加心血管死亡或心力衰竭住院率（HR=1．21、1．28,95％CIL10～1．40、1．12～1．38）。基础Qas波群延长患者最后住院心电图QRS波群正常者仅为4．0％。结论延长的QRS波群在LVEF降低患者中十分多见,是出院后高患病率和高死亡率的独立预测因素。     

Effect of invasive coronary revascularization in acute myocardial infarction on subsequent death rate and frequency of chronic heart failure

There is debate about whether therapies that reduce mortality in acute myocardial infarction (AMI) will increase the risk for heart failure. In this study, an inception cohort of patients hospitalized with AMIs from April 1, 1994, to March 31, 1999 (without previous diagnoses of heart failure or myocardial infarction), were followed for a mean of 32 months to explore whether invasive coronary revascularization during the index AMI hospitalization was associated with a trade-off between reduced mortality in the short term and increased heart failure in the intermediate term. Of 13,472 patients (mean age 65 +/- 13 years, 70% men), 3,278 (24%) underwent invasive coronary revascularization during their index AMI hospitalizations. Patients who underwent invasive revascularization during their index AMI hospitalizations were less likely to die (171 of 3,278 [5%] vs 1,688 of 10,194 [17%], p <0.0001) and were less likely to develop heart failure, either during the AMI hospitalization (571 of 3,278 [17%] vs 2,422 of 10,194 [24%], p <0.0001) or after discharge (144 of 3,278 [4%] vs 754 of 10,194 [7%], p <0.0001). These associations persisted after covariate adjustment (for heart failure, hazard ratio 0.68, 95% confidence interval 0.56 to 0.81; for death or heart failure, hazard ratio 0.60, 95% confidence interval 0.51 to 0.70). In conclusion, invasive coronary revascularization during AMI hospitalization is associated with lower rates of death and subsequent heart failure; there is no trade-off of 1 outcome for the other.     

Usefulness of adiponectin as a predictor of all cause mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

Substantial evidence points to a protective role of adiponectin against atherosclerosis and cardiovascular (CV) disease. However, in the setting of an acute myocardial infarction (AMI), the role of adiponectin has not previously been studied. Consequently, the aim of this study was to investigate the prognostic role of adiponectin after AMI in a large population of patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. A total of 735 consecutive patients with ST-segment elevation myocardial infarction admitted to a single high-volume invasive heart center and treated with primary percutaneous coronary intervention from September 2006 to December 2008 were included. Blood samples were drawn immediately before the invasive procedure. Plasma adiponectin was measured using a validated immunoassay. End points were all-cause mortality, CV mortality, and admission for new AMI or heart failure. The median follow-up time was 27 months (interquartile range 22 to 33). Patients with high adiponectin (quartile 4) had increased mortality compared to patients with low adiponectin (quartiles 1 to 3) (log-rank p <0.001). After adjustment for conventional risk factors (age, gender, smoking, hypertension, hypercholesterolemia, diabetes, body mass index, C-reactive protein, peak troponin I, creatinine, estimated glomerular filtration rate, previous AMI, multivessel disease, complex lesions, left anterior descending coronary artery lesion, and symptom-to-balloon time) by Cox regression analysis, high adiponectin remained an independent predictor of all-cause mortality (hazard ratio 2.1, 95% confidence interval 1.3 to 3.2, p = 0.001) and CV mortality (hazard ratio 2.6, 95% confidence interval 1.5 to 4.5, p = 0.001). In conclusion, increased plasma adiponectin independently predicts all-cause and CV mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.     

Prevalence of dyssynchrony and relation with long-term outcome in patients after acute myocardial infarction

The impact of left ventricular (LV) dyssynchrony on the long-term outcomes of patients with acute myocardial infarction (AMI) remains unknown. The purpose of the present study was to evaluate the prevalence of LV dyssynchrony after AMI and the potential relation with adverse events. A total of 976 consecutive patients admitted with AMI treated with primary percutaneous coronary intervention were evaluated. Two-dimensional echocardiography was performed <48 hours after admission. LV dyssynchrony was assessed with speckle-tracking imaging and calculated as the time difference between the earliest and latest activated segments. Patients were followed up for the occurrence of all-cause mortality (the primary end point) or the composite secondary end point (heart failure hospitalization and all-cause mortality). Within 48 hours of admission for the index infarction, mean LV dyssynchrony was 61 ± 79 ms, and 14% of the patients demonstrated a ≥130-ms time difference, defined as significant LV dyssynchrony. During a mean follow-up period of 40 ± 17 months, 82 patients (8%) reached the primary end point. In addition, 36 patients (4%) were hospitalized for heart failure. The presence of LV dyssynchrony was associated with an increased risk for all-cause mortality and hospitalization for heart failure during long-term follow-up (adjusted hazard ratio 1.06, 95% confidence interval 1.05 to 1.08, p <0.001, per 10-ms increase). Moreover, LV dyssynchrony provided incremental value over known clinical and echocardiographic risk factors for the prediction of adverse outcomes. In conclusion, LV dyssynchrony is a strong predictor of long-term mortality and hospitalization for heart failure in a population of patients admitted with ST-segment elevation AMI treated with primary percutaneous coronary intervention.     

Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study

BackgroundCoronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF.Methods and ResultsWe assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54–159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0–68, P = .023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization.ConclusionsIn this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV- and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.     

Elevated pulmonary artery pressure by Doppler echocardiography predicts hospitalization for heart failure and mortality in ambulatory stable coronary artery disease: the Heart and Soul Study.

OBJECTIVES: We compared the predictive ability of tricuspid regurgitation (TR) and end-diastolic pulmonary regurgitation (EDPR) gradients in outpatients with coronary artery disease. BACKGROUND: The TR and EDPR gradients, in conjunction with right atrial pressure, provide Doppler estimates of pulmonary artery systolic and diastolic pressures. We hypothesized that increases in TR or EDPR gradients in stable coronary artery disease would predict heart failure (HF) hospitalization or cardiovascular (CV) death. METHODS: We measured TR and EDPR gradients in 717 adults with completed outcome adjudications who were recruited for the Heart and Soul Study. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for HF hospitalization, CV death, all-cause death, and the combined end point. Multivariate adjustments were made for age, gender, race, history of CV or pulmonary disease, functional class, and left ventricular ejection fraction. RESULTS: There were 63 HF hospitalizations, 19 CV deaths, and 86 all-cause deaths at the 3-year follow-up. There were 466 measurable EDPR gradients and 573 measurable TR gradients. Age-adjusted ORs for EDPR >5 mm Hg predicted HF hospitalization (2.7, 95% CI 1.3 to 5.5, p = 0.006), all-cause death (2.5, 95% CI 1.4 to 4.4, p = 0.002), and HF hospitalization or CV death (2.7, 95% CI 1.4 to 5.2, p = 0.004). Age-adjusted OR for TR >30 mm Hg predicted HF hospitalization (3.4, 95% CI 1.9 to 6.2, p < 0.0001) and HF hospitalization or CV death (3.0, 95% CI 1.7 to 5.3, p = 0.0001). Multivariate adjusted OR per 5-mm Hg incremental increases in EDPR predicted HF hospitalization or CV death (1.9, 95% CI 1.01 to 3.6, p = 0.046) and all-cause death (1.7, 95% CI 1.05 to 2.8, p = 0.03). Multivariate adjusted OR per 10-mm Hg incremental increases in TR predicted HF hospitalization or CV death (1.6, 95% CI 1.1 to 2.4, p = 0.008). CONCLUSIONS: Increases in EDPR or TR gradients predict HF hospitalization or CV death among ambulatory adults with coronary artery disease.     

MERIT-HF mortality and morbidity data

This survival study was designed to address whether beta-1-blockade utilizing metoprolol CR/XL (controlled release/extended release) once daily added to standard therapy reduces mortality and morbidity in patients with decreased ejection fraction and symptoms of heart failure. Enrolled in a double-blind randomized study were 3991 patients with chronic heart failure in NYHA functional class II-IV and ejection fraction h 0.40 stabilized on optimal standard therapy. Randomization was preceded by a 2-week single blind placebo run-in period. The study medication was uptitrated during 8 weeks starting with 12.5 mg (NYHA functional class III-IV) or 25 mg once daily (NYHA functional class II). The target dose was 200 mg once daily. The primary endpoints were all-cause mortality and combined all-cause mortality and hospitalization (time to first event) and other objectives were cause-specific data on hospitalization, NYHA functional class and quality of life. Mean follow-up time was 1 year. All-cause mortality was reduced in the metoprolol CR/XL group compared with the placebo group, 145 versus 217 deaths, 7.2% per patient year of follow-up versus 11.0% with a relative risk of 0.66 (95% CI 0.53-0.81, nominal p = 0.00009, p adjusted for interim analysis = 0.0062). This effect was consistent across all predefined subgroups. Sudden deaths were fewer in the metoprolol group (79 versus 132 deaths), RR 0.59 (P = 0.0002). Also deaths from worsening heart failure were fewer in the metoprolol group (30 versus 58 deaths), RR 0.51 (P = 0.0023). The combined endpoint total mortality or all-cause hospitalizations was also reduced by metoprolol (641 versus 767 events), RR 0.81 (p = 0.00012). Total mortality or hospitalizations due to worsening heart failure was also reduced (311 versus 439 events), RR 0.69 (p < 0.00001). The number of hospitalizations due to worsening heart failure (317 versus 451, p < 0.00001) and days in hospital due to worsening heart failure (3401 versus 5303 days, p < 0.00001) were also reduced by metoprolol. There was also an improvement in NYHA functional class, assessed by the physicians as well as the McMaster Overall Treatment Evaluation questionnaire (OTE), assessed by the patients (p = 0.028 and p = 0.089, respectively). Permanent early discontinuation was 13.9% in the metoprolol group and 15.3% in the placebo group (RR = 0.90). In conclusion, in patients with symptomatic heart failure metoprolol CR/XL once daily improved survival by 34%, sudden death by 41%, and deaths from worsening of heart failure by 49%. In addition to improvement of survival there was also a reduced need of hospitalizations for worsening heart failure and an improved NYHA functional class and of quality of life assessed in a substudy. Metoprolol was well tolerated with no difference in early discontinuation rate from placebo treatment.     

Prognostic value of stress-gated Tc-99m sestamibi SPECT after acute myocardial infarction

Stress-gated technetium-99m (Tc-99 m) sestamibi single-photon emission computed tomography (SPECT) is used to risk stratify patients after acute myocardial infarction (AMI). In clinical practice, results of this test are used primarily to identify patients with myocardial ischemia for intervention. The value of this test to risk stratify patients with AMI not at high ischemic risk has not been addressed. More than 1-year follow-up was undertaken in 124 patients who underwent predischarge gated Tc-99m sestamibi SPECT studies and who did not undergo subsequent revascularization. Clinical variables and test-derived variables were evaluated to predict cardiac death, recurrent AMI, and hospitalization for unstable angina, congestive heart failure, or coronary revascularization. Independent predictors by multivariate analysis for cardiac death or recurrent AMI were a history of prior AMI (relative risk [RR] = 5.32, confidence interval [CI] 2.17 to 12.96), a low exercise capacity (RR = 6.84, CI 1.99 to 23.48), and left ventricular (LV) ejection fraction (EF) <40% (RR = 2.63, CI 1.04 to 6.38). The incidence of cardiac death or recurrent AMI was 29.8% in patients with a low exercise capacity versus 4.5% in those with good exercise capacity, and 38.1% in patients with LVEF <40% versus 9.4% in those with LVEF >40%. Independent predictors of cardiac death, AMI, or hospitalization for unstable angina, congestive heart failure, or revascularization were a history of prior AMI (RR = 2.24, CI 1.11 to 4.50) and LVEF <40% (RR = 3.13, CI 1.64 to 5.95). Among patients followed after AMI without revascularization Tc-99m sestamibi SPECT can identify a high-risk subset. The strongest independent predictors are poor exercise capacity and LVEF < 40%.     

Metabolic treatment with L-carnitine in acute anterior ST segment elevation myocardial infarction. A randomized controlled trial

BACKGROUND: Administration of L-carnitine in patients with anterior acute myocardial infarction (AMI) prevents left ventricular remodeling. Current study was aimed to assess the effect of L-carnitine administration on mortality and heart failure in patients with anterior AMI. METHODS: CEDIM 2 trial was a randomized, double-blind, multicenter, placebo-controlled trial planned to enroll 4,000 patients with acute anterior AMI. The trial was interrupted after the enrolment of 2,330 patients because of the lower than expected enrolment rate. The primary end point was a composite of death and heart failure at 6 months; 5-day mortality was the secondary end point. RESULTS: During the 6-month follow-up, the primary end-point was not significantly different between the L-carnitine and placebo group (9.2 vs. 10.5%, p = 0.27). A reduction in mortality was seen in the L-carnitine arm on day 5 (secondary end-point) from randomization (HR = 0.61, 95% CI 0.37-0.98, p = 0.041). CONCLUSIONS: In CEDIM 2 trial L-carnitine therapy led to a reduction in early mortality (secondary end-point) without affecting the risk of death and heart failure at 6 months in patients with anterior AMI, leading to a non-significant finding with respect to the primary end-point.