Combined Endpoint Of Death Research Articles

Early CRT Improves Long-Term Survival in Mild Heart Failure (MADIT-CRT)

The Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy [MADIT-CRT; Moss AJ et al. N Engl J Med 2009] trial evaluated the effect of CRT with biventricular pacing on the combined endpoint of death from any cause and nonfatal heart failure (HF) events in 1820 patients with mild HF. The benefit of a CRT plus ICD (CRT-D) was driven by a 41% reduction in the risk of nonfatal HF events and was observed only in patients with left bundle-branch block [Zareba W et al. Circulation 2011]. The aim of the long-term follow-up analysis [Goldenberg I et al. N Engl J Med 2014] was to prospectively assess the effect of CRT-D on long-term survival.

The association of angiographic collaterals with long-term clinical outcomes in patients with chronic stable angina.

To determine the impact of coronary collaterals in stable angina. Whether spontaneously visible coronary collaterals are associated with long-term clinical outcomes in stable angina remains unclear. We prospectively enrolled patients with stable angina referred for coronary angiography and followed them clinically for 1 year. A total of 1,134 consecutive patients were enrolled, and of these, 550 had at least single-vessel coronary artery disease (CAD) and were included. Patients with collaterals had more congestive heart failure (16% vs. 9%, P = 0.023), peripheral vascular disease (22% vs. 15%, P = 0.044), and 2-vessel (36% vs. 26%) and 3-vessel (28% vs. 10%) CAD compared to those without collaterals (P < 0.001). Patients with collaterals were less likely to undergo percutaneous intervention at the time of the index angiogram (32% vs. 61%, P < 0.001). At 1 year, there were no differences in angina (HR 0.74, 95% CI 0.50-1.10; P = 0.141), myocardial infarction (MI) (HR 1.22, 95% CI 0.46-3.21; P = 0.691), revascularization (HR 0.84, 95% CI 0.55-1.30; P = 0.431), death (HR 1.83, 95% CI 0.63-5.31; P = 0.269), or the combined end-point of death, MI, and revascularization (HR 0.87, 95% CI 0.61-1.24; P = 0.426) between patients with and without collaterals. When analyzed according to collateral grade, patients with Rentrop grade 1 had less angina (HR 0.48, 95% CI 0.26-0.89; P = 0.019). At 1 year, there was no difference in adverse events between patients with or without collaterals. The presence of Rentrop grade 1 collaterals, however, was associated with significantly less angina.

Effect of Metformin on Left Ventricular Function After Acute Myocardial Infarction in Patients Without Diabetes

Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function. To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI). Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013. Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months. The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure. At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed. Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting. clinicaltrials.gov Identifier: NCT01217307.

Impact of Multiple Complex Plaques on Short- and Long-Term Clinical Outcomes in Patients Presenting With ST-Segment Elevation Myocardial Infarction (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI] Trial)

It is not known whether the extent and severity of nonculprit coronary lesions correlate with outcomes in patients with ST-segment elevation myocardial infarction (STEMI) referred for primary percutaneous coronary intervention (PCI). We sought to quantify complex plaques in patients with STEMI referred for primary PCI and to determine their effect on short- and long-term clinical outcomes by examining the core laboratory database for plaque analysis from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction study. Baseline demographic, angiographic, and procedural details were compared between patients with single versus multiple complex plaques who underwent single-vessel PCI. Multivariable analysis was performed for predictors of long-term major adverse cardiac events (MACEs), a combined end point of death, reinfarction, ischemic target-vessel revascularization, or stroke, and for death alone. Single-vessel PCI was performed in 3,137 patients (87%): 2,174 (69%) had multiple complex plaques and 963 (31%) had a single complex plaque. Compared with those with a single complex plaque, patients with multiple complex plaques were older (p <0.0001) and had more co-morbidities. The presence of multiple complex plaques was an independent predictor of 3-year MACE (hazard ratio 1.58, 95% confidence interval 1.26 to 1.98, p <0.0001), and death alone (hazard ratio 1.68, 95% confidence interval 1.05 to 2.70, p = 0.03). In conclusion, multiple complex plaques are present in the majority of patients with STEMI who underwent primary PCI, and their presence is an independent predictor of short- and long-term MACE, including death (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966).

Association of Body Mass Index With Cardiac Reverse Remodeling and Long-Term Outcome in Advanced Heart Failure Patients With Cardiac Resynchronization Therapy

The effect of adiposity on response to cardiac resynchronization therapy (CRT) and long-term outcome in patients undergoing CRT has not been previously reported. This study assessed the impact of baseline body mass index (BMI) on cardiac reverse remodeling and prognosis following CRT. METHODS AND RESULTS: A total of 247 CRT patients were included and divided into 4 groups according to baseline BMI. During 6-month follow-up, overweight and obese patients (BMI, 24-28 kg/m(2), ≥28 kg/m(2), respectively) were inclined to have better clinical and echocardiographic improvements (P<0.05) as well as higher response rate (P<0.001) than underweight and normal weight patients (BMI, <18.5 kg/m(2), 18.5-24 kg/m(2), respectively). During long-term follow-up, overweight and obese patients had lower all-cause mortality (P=0.015) and combined endpoint of death or HF hospitalizations (P=0.001) than underweight and normal weight patients. Compared with normal weight patients, underweight patients had a 2.29-fold increase in risk of combined endpoint events whereas overweight and obese patients had a reduction in the risk of death (66% and 58%, respectively) and combined endpoint events (52% and 38%, respectively). Patients with obesity and overweight derived more benefit from CRT. Higher BMI was independently associated with better clinical outcome in CRT patients.

Asymptomatic cryptococcal antigenemia is associated with mortality among HIV‐positive patients in Indonesia

IntroductionPrevious studies, mostly from Africa, have shown that serum cryptococcal antigenemia may precede the development of cryptococcal meningitis and early death among patients with advanced HIV infection. We examined cryptococcal antigenemia as a risk factor for HIV-associated mortality in Indonesia, which is experiencing a rapidly growing HIV epidemic.MethodsWe included ART-naïve HIV patients with a CD4 cell count below 100 cells/μL and no signs of meningitis in an outpatient HIV clinic in Bandung, West Java, Indonesia. Baseline clinical data and follow-up were retrieved from a prospective database, and cryptococcal antigen was measured in stored serum samples using a semiquantitative lateral flow assay. Cox regression analysis was used to identify factors related to mortality.ResultsAmong 810 patients (median CD4 cell count 22), 58 (7.1%) had a positive cryptococcal antigen test with a median titre of 1:80 (range: 1:1 to 1:2560). Cryptococcal antigenemia at baseline was strongly associated with the development of cryptococcal meningitis and early death and loss to follow-up. After one year, both death (22.4% vs. 11.6%; p=0.016; adjusted HR 2.19; 95% CI 1.78–4.06) and the combined endpoint of death or loss to follow-up (67.2% vs. 40.4%; p<0.001; adjusted HR 1.57; 95% CI 1.12–2.20) were significantly higher among patients with a positive cryptococcal antigen test.ConclusionsCryptococcal antigenemia is common and clinically relevant among patients with advanced HIV in this setting. Routine screening for cryptococcal antigen followed by lumbar puncture and pre-emptive antifungal treatment for those who are positive may help in reducing early mortality.

Is Men's Health Just a Single Letter?

For several years, a marketing campaign to peddle T prescriptions has cleverly centered on the question: “Is it low T? Have an honest conversation with your doctor about all of the symptoms you are experiencing.” “Low T” has become a part of the popular vernacular to describe all sorts of symptoms that might (or might not) be associated with a low serum T level in men. T sales have surged in many countries (1). With the advent of the increased sales of T formulations to treat aging men, questions about the potential adverse effects of T therapy including cardiovascular disease and prostate cancer have emerged. There have been concerns that T might increase adverse cardiovascular events since at least the 1960s. The Coronary Drug Project was designed in 1965 to test the hypothesis that estrogen therapy might decrease recurrent cardiovascular ischemic events in men by raising highdensity lipoprotein cholesterol and lowering serum T levels (2). A high dosage of conjugated estrogen (enough to suppress the male gonadal axis) was associated with increased cardiovascular events (3). Later, a number of epidemiological studies demonstrating an association between cardiovascular disease and low serum T levels in men generated the opposing hypotheses that low T levels might increase the risk of cardiovascular events in men or that normal T might even be protective against cardiovascular events (4). Three recent epidemiological studies have fueled the debate on the effects of T on all-cause mortality and cardiovascular disease. Shores et al (5) reported in a retrospective database study of veterans with low serum T levels that T therapy was not associated with increased mortality or cardiovascular disease. Shores et al (5) reported lower mortality in the subset of men treated with T therapy than men who were not treated; this effect remained after adjustment for age, diabetes mellitus, and prevalent cardiovascular disease. In another retrospective database study of veterans, Vigen et al (6) reported an association between T therapy and an increase in the combined incidence of myocardial infarction, stroke, and overall mortality in men who underwent coronary angiography for evaluation of chest pain and were subsequently found to have low serum total T levels. In the Vigen et al (6) study of veterans, the unadjusted absolute rate of the combined endpoint (myocardial infarction, stroke, and death) was 21% for the untreated men and 10% for the T-treated men. After analysis with a sophisticated adjustment model, this pattern reversed with a lower rate of the combined endpoint (19.9%) in the untreated group compared to the T-treated group (25.7%). A third important epidemiological study on the association between T, cardiovascular disease, and overall mortality appears in this issue of the JCEM. Yeap et al (7) suggest that there is a U-shaped association between serum total or calculated free serum T levels and all-cause mortality, with a similar trend between T levels and cardiovascular mortality. In the Yeap et al study (7), over 4000 Western Australian older men ( 70 years of age) who were a subset of a larger cohort study had total T, dihydrotestosterone, and estradiol levels measured on an early morning blood sample with a highly accurate liquid chromatography-tandem mass spectrometry assay. Free T levels were calculated using a validated empiric formula. The men were followed for an average of 7 years. The primary outcomes were death of any cause and death due to ischemic heart disease as reported to the Western Australia Database Linkage System (WADLS), an intricate, publicly funded database that captures health outcomes including deaths of citizens of Western Australia. Because all residents of Western

Association of Glomerular Filtration Rate With Outcomes of Acute Stroke in Type 2 Diabetic Patients: Results From the China National Stroke Registry

OBJECTIVE We aim to explore whether a link exists between different levels of estimated glomerular filtration rate (eGFR) and poor outcomes of acute stroke in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Between 2007 and 2009, 6,261 patients with cerebrovascular events and diabetes were included in the final analysis from the China National Stroke Registry (CNSR) and substudy of CNSR (Abnormal Glucose Regulation in Patients with Acute Stroke Across China [ACROSS]).The period of follow-up was 1 year after stroke onset. eGFR was calculated with the Chinese modification of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The association between eGFR and poor stroke outcomes, including all-cause death, recurrent stroke, combined end point (stroke or death), and stroke disability, was evaluated by multivariate analysis with the adjustment for demographic and clinical features. RESULTS Of 4,836 patients with stroke, low eGFR (<45 mL/min/1.73 m(2)) occurred in 268 (5.5%) and high eGFR (≥120 mL/min/1.73 m(2)) in 387 (8.0%). The median value for eGFR in all patients was 92.6 mL/min/1.73 m(2). Low eGFR was independently associated with risks of all clinical outcomes in stroke/transient ischemic attack patients or patients with ischemic events, but not in patients with hemorrhagic stroke. Additionally, high eGFR was positively associated with an increased risk of adverse outcomes in all stroke subtypes, including hemorrhagic stroke. CONCLUSIONS Low and high eGFRs (<45 or ≥120 mL/min/1.73 m(2), respectively) are independent predictors of all-cause mortality and other poor outcomes after acute stroke in patients with type 2 diabetes.

Prognostic value of six minute walk test in cystic fibrosis adults

The 6 min walk test (6MWT) provides prognostic information in various respiratory diseases, but limited data exist in cystic fibrosis (CF) adults. Consecutive CF adults who performed 6MWT at Cochin Hospital (Paris, France) over 12 years were analyzed. The cut-off 6 min walking distance (6MWD) value that best predicted a combined endpoint (death without transplant or lung transplant) was established using a receiver operating curve. Determinants of low 6MWD or of desaturation (SpO2 ≤ 90%) during 6MWT were examined using multivariate logistic regressions. Prognostic value of these variables was assessed using Kaplan-Meier and Cox analyses. 6MWT was performed in 286 CF adults (median: age, 28 yr; FEV1, 45% predicted) of whom 14% (n = 40) had lung transplant and 6% (n = 18) died without transplant. 6MWD correlated with FEV1% predicted (r = 0.43; P < 0.001), but markedly differed in subjects within the same range of FEV1. A 6MWD ≤ 475 m predicted death or transplant and was mostly found in patients with FEV1 ≤ 60% predicted. Desaturation during the 6MWT occurred in 29% of patients, exclusively in subjects with FEV1 ≤ 60% predicted. Both 6MWD ≤ 475 m and desaturation during the 6MWT were independent predictors of death or transplant. The 6MWT provides prognostic information in CF adults, especially in subjects with FEV1 ≤ 60% predicted.

Poor Prognosis of Rare Sarcomeric Gene Variants in Patients with Dilated Cardiomyopathy

In dilated cardiomyopathy (DCM), the clinical and prognostic implications of rare variants in sarcomeric genes remain poorly understood. To address this question, we analyzed the outcome of rare sarcomeric gene variants in patients enrolled in our Familial Cardiomyopathy Registry. DCM families harboring rare sarcomeric variants in MYH6, MYH7, MYBPC3, TNNT2, and TTN were identified. Genotype-phenotype association analysis was performed, and long-term survival-free from death or heart transplant was compared between carriers and noncarriers. We found 24 rare variants (3 in MYH6, 3 in MYH7, 3 in MYBPC3, 2 in TNNT2, and 13 in TTN) affecting 52 subjects in 25 families. The phenotypes of variant carriers were severe (3 sudden deaths, 6 heart failure deaths, 8 heart transplants, 2 ventricular fibrillations). There was no difference in the overall long-term survival between carriers and the 33 noncarriers (p = 0.322). However after 50 years of age, the combined endpoint of death or transplant was decreased in carriers as compared to noncarriers (p = 0.026). Patients with DCM carrying rare variants in sarcomeric genes manifest a poorer prognosis as compared to noncarriers after the age of 50 years. These data further support the role of genetic testing in DCM for risk stratification.

Race Influences the Safety and Efficacy of Spironolactone in Severe Heart Failure

The incidence of hyperkalemia caused by mineralocorticoid receptor antagonists may vary by race, but whether race influences efficacy of mineralocorticoid receptor antagonists in heart failure (HF) is unknown. We assessed hyperkalemia and outcomes in African Americans (AAs; n=120) and non-AAs (n=1543; white 93%) with New York Heart Association (NYHA) class III or IV HF and left ventricular dysfunction who were randomized to spironolactone, titrated to 25 or 50 mg daily or placebo, in the Randomized Aldactone Evaluation Study (RALES). AA participants were significantly younger, less likely to have an ischemic HF pathogenesis, more likely to be NYHA functional class IV, and more likely to have a higher estimated glomerular filtration rate and heart rate, less hypertension, diabetes mellitus, or history of myocardial infarction compared with non-AA participants. Potassium increased with spironolactone in non-AAs (4.29±0.5-4.55±0.49 mmol/L) but not in AAs (4.32±0.54-4.31±0.49 mmol/L; race by treatment interaction, P=0.03) during the first month and remained higher throughout the trial. Compared with AAs, non-AAs were more likely to attain maximal spironolactone dose (13.9% versus 5.8%; P=0.04) and had higher rates of hyperkalemia (potassium>5.5 mmol/L; 9.7% versus 4.2%; P<0.046), as well as lower rates of hypokalemia (potassium<3.5 mmol/L; 5.6% versus 17.9%; P<0.001). After adjustment for differences in baseline characteristics and achieved study drug dose, spironolactone reduced the combined end point of death or hospitalization for HF in non-AAs (hazard ratio, 0.63; 95% confidence interval, 0.55-0.73) but not in AAs (hazard ratio, 1.07; 95% confidence interval, 0.67-1.71; P value for interaction=0.032). AAs with HF exhibited less hyperkalemia and more hypokalemia with spironolactone compared with non-AAs and seemed to derive less clinical benefit. These hypothesis-generating findings suggest that safety and efficacy of mineralocorticoid receptor antagonists may differ by race.

Long term outcome after rotablation for bail-out in severely calcified coronary lesions

Background: Rotablation is mostly used to enable stent implantation in severely calcified coronary lesions. There is a lack of long term data regarding the outcome after rotablation in severe calcified lesions with either failed balloon crossing or in case of failed balloon expansion. Methods: To assess the 1-year outcome of rotabloation in this setting, we analyzed 210 consecutive patients undergoing rotablation required for preparation of stent implantation in severely calcified coronary lesions. Complete 1-year follow-up data was available for all patients. Results: Patients were on average 71 years old. The reasons for rotablation were in 42% inability to cross the lesion with the balloon and in 58% inability to expand the balloon in severe calcified lesion. Sixteen % of patients needed rotablation during PCI for acute coronary syndrom (ACS). The procedural success was 99,5%. Drug eluting stents (DES) were implanted in 88%. The majority of patients received initial rotablation with 1,5 mm burr. Elevated troponin a day post rotablation was measured in 38% of patients and elevated creatine kinase (CK) in 12%. Target vessel revascularisation (TVR) after 1 year post index PCI was performed in 13,2% of patients. The combined endpoint of death and myocardial infarction (MI) as marker for safety was reached by 14,4%. Death during 1-year follow-up occurred in 10,4%. Conclusions: Rotablation as a part of lesion preparation for stent implantation in otherwise untreatable severe calcified coronary lesions is associated with high procedural success rate. One-year event rates, however, indicate that patients in need for bail-out rotablation represent a high risk subset.

Long-term results for treatment of patients with unprotected left main stenosis by CABG or PCI with Drug Eluting Stents. A prospective registry

Background: Up to the guidelines CABG is the prefered therapy for treatment of unprotected left main stenosis. Over the last decade a growing number of patients with this diagnosis have been treated by PCI. There are few long term results comparing both therapies. We present long-term result of a prospective registry of patients with unprotected left main stenosis treated by bypass revascularisation or PCI with drug eluting stents. Methods: From 04/2003 to 12/2010 1.590 patients with significant left main stenosis were recruited for the study. Patients with cardiogenic shock or acute myocardial infarction were excluded. The dedication of patients to the PCI- or CABG-group carried out at the discretion of the doctor particularly with regard to the baseline variables. Primary endpoint were death, stroke, acute myocardial infarction and reintervention. 246 patients were treated by PCI and 1.344 patients by CABG. There were significant differences in baseline characteristics with respect to age (72.0 vs 68.7 years), gender distribution, left ventricular function, NYHA-class and CCI-class between the PCI- and CABG group. No differences were seen in history of myocardial infarction, stroke, diabetes, hyperlipidemia, smoking and medication. Mean follow-up period was 3.8 years. We evaluated the results with propensity score analysis. Results: All patients received a complete revascularisation. We observed a low peri-interventional mortality of 0.4% in the PCI-group and 3.1% in the CABG-group. Over a cumulative period of 43 month, 24 pat. (12.4%) from the PCI-group and 228 pat. (21.0%) from CABG-cohort died. The stroke rate was 3.6% in both groups. 2.4% and 1.5% (PCI-/CABG-group) had a myocardial infarction. Target vessel revascularisation (TVR) rate was considerably higher for the PCI-cohort (23.9% vs 11.5%, p < 0.001). After adjustment of confounding variables there were no differences in the combined endpoint of death, stroke, myocardial infarction and TVR (p =0.092). For itemised endpoint analysis, only TVR was significant different to the disadvantage of PCI. There was a trend for lower mortality in the PCI-group (p=0.053). Conclusion: In patients with unprotected left main stenosis both CABG and PCI with DES can be performed with little procedural risk. Also for a longer follow up period of nearly 4 years, the rate for Death, Stroke and MI did not differ between PCI and CABG. TVR rate was significant higher in PCI group.

Diastolic functional class improvement is associated with more favorable outcomes in patients with acute nonischemic cardiomyopathy

Background: Patients with recent onset non-ischemic cardiomyopathy (ROCM) have variable clinical course related to left ventricular (LV) systolic recovery. It is unknown if temporal changes in diastolic function (DF) class can predict outcomes independent of LV systolic functional recovery in these patients. Methods: In the multicenter IMAC-2 (Intervention in Myocarditis and Acute Cardiomyopathy) study, there were 147 patients with ROCM (ejection fraction (EF) ≤40%, <6 months of symptoms) consistent with idiopathic cardiomyopathy or myocarditis who were prospectively studied by echocardiography. Systolic function was measured by biplane Simpson's rule EF and DF by mitral inflow velocities and mitral annular tissue Doppler at presentation and 6-month follow-up. Cox proportional hazards modeling was used to risk-adjust comparisons for the combined endpoint of death, transplantation and heart failure hospitalization. Results: Of 147 patients, (mean age 46±14 yrs, 40% female), baseline LVEF was 23±8%. At 6-months, LVEF improved to 41±12%, with 68% increasing by at least 10% EF units. DF improved in 55%, was unchanged in 27% and worsened in 13%. Over a mean follow-up of 1.8±1.2 yrs, there were 3 deaths, 4 transplants and 11 heart failure hospitalizations. LVEF at 6 months (HR=0.95, 95% CI 0.92-0.99,p=0.03) and improvement or maintaining DF class at 6-months were independently associated with lower likelihood for the combined end-point (HR=0.26, 95% CI 0.09-0.73, p=0.01). ![Figure][1] 6-Month Diastolic function and outcomes Conclusion: In patients with ROCM, improvement in or maintaining DF class was associated with more favorable outcomes, independent of LV systolic functional recovery. The association of DF with clinical outcomes suggest DF as a potential important prognostic marker in these patients. [1]: pending:yes

Ventricular-Arterial Coupling, Remodeling, and Prognosis in Chronic Heart Failure

The objective of this study was to compare the physiological determinants of ejection fraction (EF)-ventricular size, contractile function, and ventricular-arterial (VA) interaction-and their associations with clinical outcomes in chronic heart failure (HF). EF is a potent predictor of HF outcomes, but represents a complex summary measure that integrates several components including left ventricular size, contractile function, and VA coupling. The relative importance of each of these parameters in determining prognosis is unknown. In 466 participants with chronic systolic HF, we derived quantitative echocardiographic measures of EF: cardiac size (end-diastolic volume [EDV]); contractile function (the end-systolic pressure volume relationship slope [Eessb] and intercept [V0]); and VA coupling (arterial elastance [Ea]/Eessb). We determined the association between these parameters and the following adverse outcomes: 1) the combined endpoint of death, cardiac transplantation, or ventricular assist device (VAD) placement; and 2) cardiac hospitalization. Over a median follow-up of 3.4 years, there were 76 deaths, 52 transplantations, 14 VAD placements, and 684 cardiac hospitalizations. EF was independently associated with death, transplantation, and VAD placement (adjusted hazard ratio [HR]: 3.0; 95% confidence interval [CI]: 1.8 to 5.0 comparing third and first tertiles), as were EDV (HR: 2.6; 95% CI: 1.5 to 4.2); V0 (HR: 3.6; 95% CI: 2.1 to 6.1); and Ea/Eessb (HR: 2.1; 95% CI: 1.3 to 3.3). EDV, V0, and Ea/Eessb were also associated with risk of cardiac hospitalization. Eessb was not significantly associated with any adverse outcomes in adjusted analyses. Left ventricular size, V0, and VA coupling are associated with prognosis in systolic HF, but end-systolic elastance (Eessb) is not. Assessment of VA coupling via Ea/Eessb is an additional noninvasively derived metric that can be used to gauge prognosis in human HF.

Resting Heart Rate and Heart Rate Reserve in Advanced Heart Failure Have Distinct Pathophysiologic Correlates and Prognostic Impact: A Prospective Pilot Study

The purpose of this study was to compare the prognostic impact of clinical and biomarker correlates of resting heart rate (HR) and chronotropic incompetence in heart failure (HF) patients. The mechanisms and underlying pathophysiological influences of HR abnormalities in HF are incompletely understood. In a prospective pilot study, 81 patients with advanced systolic HF (97% were receiving beta-blockers) and 25 age-, sex-, and body-size matched healthy controls underwent maximal cardiopulmonary exercise testing with sampling of neurohormones and biomarkers. Two-thirds of HF patients met criteria for chronotropic incompetence. Resting HR and HR reserve (HRR, a measure of chronotropic response) were not correlated with each other and were associated with distinct biomarker profiles. Resting HR correlated with increased myocardial stress (B-type natriuretic peptide [BNP]: r = 0.26; pro-A-type natriuretic peptide: r = 0.24; N-terminal-proBNP: r = 0.32) and inflammation (leukocyte count: r = 0.28; high-sensitivity C-reactive protein assay: r = 0.25). In contrast, HRR correlated with the neurohumoral response to HF (copeptin: r = -0.33; norepinephrine: r = -0.29) but not with myocyte stress or injury reflected by natriuretic peptides or hs-troponin I. Patients in the lowest chronotropic incompetence quartile (HRR ≤0.38) displayed more advanced HF, reduced exercise capacity, ventilatory inefficiency, and poorer quality of life. Over a median follow-up of 17 months, the combined endpoint of death or urgent transplant/assist device implantation occurred more frequently in patients with higher resting HR (>67 beats/min) or lower HRR, with both markers providing additive prognostic information. Increased resting HR and chronotropic incompetence may reflect different pathophysiological processes, provide incremental prognostic information, and represent distinct therapeutic targets.

Proton Pump Inhibitors and Risk of 1-Year Mortality and Rehospitalization in Older Patients Discharged From Acute Care Hospitals

The use of proton pump inhibitors (PPIs) has rapidly increased during the past several years. However, concern remains about risks associated with their long-term use in older populations. To investigate the relationship between the use of PPIs and the risk of death or the combined end point of death or rehospitalization in older patients discharged from acute care hospitals. We investigated the relationship between PPI use and study outcomes using time-dependent Cox proportional hazards regression in patients 65 years or older discharged from acute care medical wards from April 1 to June 30, 2007. Eleven acute care medical wards. Four hundred ninety-one patients (mean [SD] age, 80.0 [5.9] years). Mortality and the combined end point of death or rehospitalization. RESULTS The use of PPIs was independently associated with mortality (hazard ratio, 1.51 [95% CI, 1.03-2.77]) but not with the combined end point (1.49 [0.98-2.17]). An increased risk of mortality was observed among patients exposed to high-dose PPIs vs none (hazard ratio, 2.59 [95% CI, 1.22-7.16]). In older patients discharged from acute care hospitals, the use of high-dose PPIs is associated with increased 1-year mortality. Randomized controlled studies including older frail patients are needed. In the meantime, physicians need to use caution and balance benefits and harms in long-term prescription of high-dose PPIs.

The Reliability and Prognosis of In-Hospital Diagnosis of Metabolic Syndrome in the Setting of Acute Myocardial Infarction

This study sought to examine the reliability and prognostic importance of an in-hospital diagnosis of metabolic syndrome (MetS) in the setting of acute myocardial infarction (AMI). Because the factors that comprise MetS are believed to be altered in the setting of AMI, the diagnosis of MetS during AMI hospitalization and its prognostic significance have not been studied. We assessed patients within a multicenter registry for metabolic factors at baseline and 1 month post-AMI and followed them for mortality and rehospitalizations. The accuracy of an inpatient diagnosis of MetS was calculated using a 1-month follow-up as the gold standard. Patients were categorized based on MetS diagnosis at baseline and 1 month, and the combined endpoint of death or rehospitalization over 12 months was compared between groups. Of the 1,129 patients hospitalized for AMI, diagnostic criteria for MetS were met by 69% during AMI hospitalization and 63% at 1 month. Inpatient MetS diagnosis had a sensitivity and specificity for outpatient diagnosis of 87% and 61%, respectively, and was associated with an 11 times increased odds of an outpatient diagnosis (C-index 0.74). Compared with patients without MetS during hospitalization and follow-up, patients classified as MetS during AMI but not follow-up had worse outcomes, whereas those classified MetS at follow-up had the worst outcomes (rates for combined endpoint 27% vs. 37% vs. 38%; log-rank p = 0.01). In a large cohort of patients with AMI, the diagnosis of MetS is common and can be made with reasonable accuracy during AMI. MetS is associated with poor outcomes, regardless of whether the diagnosis is confirmed during subsequent outpatient visit, and identifies a high-risk cohort of patients that may benefit from more aggressive risk factor modification.

Acetylcysteine for the Prevention of Renal Outcomes in Patients With Diabetes Mellitus Undergoing Coronary and Peripheral Vascular Angiography

Diabetes mellitus represents an independent risk factor for contrast-induced acute kidney injury. We report the results of a prespecified substudy of patients with diabetes mellitus included in the Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT), the largest randomized study evaluating the effects of acetylcysteine for the prevention of contrast-induced acute kidney injury conducted to date. From the 2308 patients included in the ACT, 1395 had diabetes mellitus and were considered for the present analysis. The study drugs (acetylcysteine 1200 mg or matching placebo) were administered orally twice daily for 2 doses before and 2 doses after the procedure. The allocation was concealed (central Web-based randomization). Participants, healthcare staff, data collectors, and outcome assessors were blinded. All analysis followed the intention-to-treat principle. The incidence of contrast-induced acute kidney injury (primary end point) was 13.8% in the acetylcysteine group and 14.7% in the control group (relative risk 0.93; 95% confidence interval, 0.69-1.26; P=0.64). A combined end point of death or need for dialysis at 30 days was also similar in both the groups (2.2% and 2.1%, respectively; hazard ratio, 1.07; 95% confidence interval, 0.52-2.19; P=0.86). In this subanalysis, acetylcysteine did not reduce the risk of contrast-induced acute kidney injury or other clinically relevant outcomes in patients with diabetes mellitus undergoing coronary and peripheral vascular angiography. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00736866.

Peak systolic velocity using color-coded tissue Doppler imaging, a strong and independent predictor of outcome in acute coronary syndrome patients

BackgroundTraditional echocardiographic methods like left ventricular ejection fraction(EF) and wall motion scoring (WMS) and new methods like speckle tracking (ST) based 2D strain carry important prognostic information in acute coronary syndrome (ACS) patients. Parameters from tissue Doppler imaging (TDI), with its high time resolution, may further increase the prognostic value. Peak systolic velocity (PSV) of the basal segments of the left ventricle from TDI is a robust and user independent parameter. The aim was to investigate the prognostic value of PSV compared to EF, WMS, 2D strain and E/e'.MethodsEchocardiographic images were collected and post processed in 227 ACS patients. Additional clinical data was prospectively gathered and patients were followed for 3-5 years regarding the combined endpoint of death or re-admission due to ACS or heart failure.ResultsThe combined endpoint occurred in 85 (37%) patients. Those with an event had lower median PSV than those without (4,4 cm/s) vs. (5,3 cm/s), (p<0.001). In a ROC analysis, the AUC was larger for PSV (0.75) than for EF (0.68), WMS (0.63), 2D strain (0.67) and E/e'(0.70). The combined endpoint increased with decreasing PSV. When adjusting for differences in baseline characteristics in a COX-regression model, PSV remained independently associated with outcome where the others did not. PSV was also less sensitive to image quality with fewer values missing or unacceptable for analysis.ConclusionPeak systolic velocity (PSV) is a robust measurement that seems to have a strong and independent association with outcome compared to traditional echocardiographic measurements in ACS patients.