Endpoint Of Heart Failure Research Articles

Losartan

Losartan

The Presage® ST2 Assay: analytical considerations and clinical applications for a high-sensitivity assay for measurement of soluble ST2

The Presage® ST2 Assay (Critical Diagnostics, CA, USA) is an in vitro diagnostic device that quantitatively measures soluble suppression of tumorigenicity 2 (sST2) in serum and plasma by ELISA. This assay is US FDA approved and is indicated to be used in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure. sST2 binds to IL-33 and functions as a ‘decoy’ receptor for IL-33, thereby attenuating the systemic effects of IL-33. Due to the role of IL-33/transmembrane isoform of suppression of tumorigenicity 2 signaling in cardiac remodeling, sST2 has emerged as a novel cardiovascular biomarker. In recent studies, it was shown that sST2 is a valuable predictor of several end points in heart failure, in acute coronary syndromes and in critically ill patients. In this review, analytical considerations and clinical applications of the Presage ST2 Assay will be discussed, as well as probable future concepts for adoption of sST2 measurements into clinical practice.

Blood pressure levels and risk of cardiovascular events and mortality in type-2 diabetes

The optimal blood pressure (BP) in persons with type-2 diabetes is debated. We investigated shapes of the associations of SBP and DBP levels with risk of cardiovascular events and mortality in a large primary care-based sample of diabetic patients. We investigated all 34 009 consecutive cardiovascular disease-free type-2 diabetes patients aged 35 years or older (mean age 64 years) at 84 primary care centers in central Sweden between 1999 and 2008. We followed this cohort until the end of 2009 in national registries for the incidence of major cardiovascular events (a composite endpoint of myocardial infarction, stroke, heart failure, or cardiovascular mortality) or total mortality. During up to 11 years of follow-up, 6344 patients (18.7%) had a first cardiovascular event, and 6235 died (18.3%). The associations of annually updated SBP and DBP with risk of major cardiovascular events were U-shaped. The lowest risk of cardiovascular events was observed at a SBP of 135-139 mmHg and a DBP of 74-76 mmHg, and the lowest mortality risk at a SBP of 142-150 mmHg and a DBP of 78-79 mmHg, in both antihypertensive drug-untreated and drug-treated persons. In a large primary care-based sample of patients with type-2 diabetes, associations of SBP and DBP with risk of major cardiovascular events and mortality were U-shaped. This may have implications for risk stratification of persons with diabetes.

Ramipril

Ramipril

Prevalence, Prospective Risk Markers, and Prognosis Associated With the Presence of Left Ventricular Diastolic Dysfunction in Young Adults

The authors sought to determine the prevalence, prospective risk markers, and prognosis associated with diastolic dysfunction in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The CARDIA Study cohort includes approximately equal proportions of white and black men and women. The authors collected data on risk markers at year 0 (1985-1986), and echocardiography was done at year 5 when the participants were 23-35 years of age. Participants were followed for 20 years (through 2010) for a composite endpoint of all-cause mortality, myocardial infarction, heart failure, and stroke. Diastolic function was defined according to a validated hierarchical classification algorithm. In the 2,952 participants included in the primary analysis, severe diastolic dysfunction was present in 1.1% and abnormal relaxation was present in 9.3%. Systolic blood pressure at year 0 was associated with both severe diastolic dysfunction and abnormal relaxation 5 years later, whereas exercise capacity and pulmonary function abnormalities were associated only with abnormal relaxation 5 years later. After multivariate adjustment, the hazard ratios for the composite endpoint in participants with severe diastolic dysfunction and abnormal relaxation were 4.3 (95% confidence interval: 2.0, 9.3) and 1.6 (95% confidence interval: 1.1, 2.5), respectively. Diastolic dysfunction in young adults is associated with increased morbidity and mortality, and the identification of prospective risk markers associated with diastolic dysfunction could allow for targeted primary prevention efforts.

Effect of admission oral diuretic dose on response to continuous versus bolus intravenous diuretics in acute heart failure: An analysis from Diuretic Optimization Strategies in Acute Heart Failure

Results from the DOSE-AHF study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in acute heart failure. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. The DOSE-AHF study randomized 308 patients within 24 hours of admission to high versus low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n = 177) versus low-dose (<120 mg furosemide equivalent, n = 131) outpatient diuretics. Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P = .01) and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P = .01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted hazard ratio 1.08 per 20-mg increment in dose, 95% CI 1.01-1.16, P = .03). In acute heart failure, patients on higher diuretic doses have greater disease severity and may benefit from an initial bolus strategy.

Effect of defibrillation threshold testing on heart failure hospitalization or death in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT)

Defibrillation threshold (DFT) testing is commonly practiced at the time of implantable cardioverter-defibrillator (ICD) implant. The clinical consequence of ICD shocks delivered during DFT testing is unknown. The purpose of this study was to determine the impact of ICD shocks and ICD shock energy level delivered during DFT testing in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) on clinical outcomes. Patients who underwent DFT testing within 1 month of device implant were categorized by the number of ICD shocks delivered during DFT testing (0, 1, 2, ≥3 shocks) and according to high vs low (>20 J vs ≤20 J) energy ICD shocks. Clinical outcomes consisting of heart failure (HF) or death, death alone, HF alone, and ventricular tachycardia or ventricular fibrillation were analyzed in each group. DFT testing was performed in 1,659 patients within 1 month of device implant (1 shock in 365 patients, 2 shocks in 896 patients, 3+ shocks in 398 patients). High-energy ICD shocks were delivered in 609 patients. Increasing number of ICD shocks during DFT testing was not associated with an increase risk for the primary end-point of HF or death or for any of the secondary end-points of HF alone, VT/VF alone, or death. Delivery of high vs low-energy ICD shocks was not associated with adverse clinical outcomes. In patients with mild symptoms of HF, increasing number of ICD shocks and delivery of high energy ICD shocks during DFT testing was not associated with increased risk for HF or death or future VT/VF episodes.

Therapy With a DPP-4 Inhibitor Increases Myocardial Glucose Uptake in Nonischemic Cardiomyopathy

Introduction: Glucose and fatty acids comprise the primary substrates for myocardial energy metabolism. Because glucose is the more efficient fuel, the normal myocardium switches metabolism toward glucose in the setting of stress the inability to affect such a switch is a fundamental mechanism behind “diabetic” or “insulin-resistant” cardiomyopathy. We sought to evaluate the effects of treatment with the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin on myocardial glucose uptake in patients with nonischemic cardiomyopathy. Methods: Twelve patients with nonischemic dilated cardiomyopathy on stable medical therapy were enrolled in the trial. Because the goal of the study was to assess the direct actions of sitagliptin on myocardial glucose uptake rather than sitagliptin’s effects as a hypoglycemic therapy for diabetes, diabetic patients were excluded. At baseline, all subjects underwent fasting metabolic testing (glucose, insulin, lipids) and assessment of myocardial glucose uptake by 18F-FDG-PET/CT imaging. All subjects were then treated with sitagliptin (100 mg orally once daily) for four weeks, and metabolic testing and PET-CT imaging was repeated. The primary endpoint of the study was change in myocardial glucose uptake preand post-sitagliptin therapy, measured 10-30 minutes post-FDG injection. Results: Sitagliptin therapy resulted in a significant increase in myocardial glucose uptake (19% increase, P50.04). While most patients had at least a slight increase in glucose uptake, there was an overall bimodal response e with six patients (“responders”) demonstrating large increases (O20%) in glucose uptake and six patients (“nonresponders”) demonstrating !5% increases or slight decreases. There were no associations between increases in glucose uptake and levels of serum/plasma glucose, insulin, or insulin resistance. Triglyceride:HDL ratios significantly dropped in the six “responders” compared with the six “nonresponders” (P!0.02). Conclusions: Therapy with sitagliptin results in increased myocardial glucose uptake in nondiabetic patients with nonischemic cardiomyopathy. These results provide mechanistic evidence to support a trial assessing clinical heart failure endpoints.

Central Sympathetic Inhibition by Mineralocorticoid Receptor But Not Angiotensin II Type 1 Receptor Blockade

See related article, pp 319–325 Chronic sympathetic hyperactivity, characteristic of the majority of patients with hypertension or heart failure, can contribute to cardiovascular morbidity and mortality via a number of actions. Pharmacological strategies to prevent these adverse effects have had variable success. β-Blockers clearly benefit patients with heart failure but have less definitive effects in patients with hypertension, whereas α1-blockers or centrally acting agents have shown mixed results, and all of these classes can cause bothersome adverse effects. Device-based approaches, such as baroreflex activation therapy and renal denervation, have been shown to lower sympathetic activity in patients with hypertension, but beneficial actions on cardiovascular outcomes have yet to be demonstrated. So, where do the central nervous system (CNS) actions of angiotensin II (Ang II), aldosterone, and, hence, Ang II type 1 (AT1) receptor and mineralocorticoid receptor (MR) blockers fit in? Experimental studies have demonstrated that both circulating Ang II and aldosterone act within the CNS to cause sympatho-excitation and raise blood pressure.1,2 Ang II stimulates AT1 receptors in nuclei of the lamina terminalis and thereby activates mainly angiotensinergic pathways to the paraventricular nucleus (PVN) and rostral ventrolateral medulla. Circulating Ang II, in addition, activates an MR-endogenous ouabain pathway. This slowly acting, neuromodulatory pathway appears responsible for most of the persistent neuronal activation in, for example, the PVN, and the progressive hypertension induced by circulating Ang II. Studies using central infusions of an aldosterone synthase inhibitor suggest that the CNS MR activation by Ang II largely depends on locally produced aldosterone rather than circulation-derived aldosterone.1 However, the progressive hypertension caused by a chronic increase in circulating aldosterone can also be prevented by specific CNS blockade of either MR or AT1 receptors,2 suggesting that both circulating aldosterone and Ang II may activate …

Regression of ECG-LVH is Associated with Lower Risk of New-Onset Heart Failure and Mortality in Patients with Isolated Systolic Hypertension; The LIFE Study

Hypertension and electrocardiographic left ventricular hypertrophy (ECG-LVH) are strong predictors of heart failure (HF). It is unclear whether regression of ECG-LVH during treatment predicts less new-onset HF in patients with isolated systolic hypertension (ISH). A total of 9,027 patients with hypertension and ECG-LVH and without a history of HF were randomized to losartan- or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension study. Incident HF and the combined endpoint of HF and death were evaluated in 1,280 ISH patients and as compared with 7,747 patients with systolic-diastolic hypertension or isolated diastolic hypertension (non-ISH) during mean 4.8 ± 0.9 years follow-up. New-onset HF and HF or death occurred in 57 (4.5%) and 179 (14.0%) ISH patients and 220 (2.8%) and 787 (10.2%) non-ISH patients. In Cox regression analyses adjusting for treatment and HF risk factors, time-varying Cornell product was associated with lower risk of new-onset HF in ISH (adjusted hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.67-0.94, P = 0.008, per 1,050 mm × ms (1 SD) lower Cornell product) and in non-ISH (adjusted HR 0.67, 95% CI 0.61-0.72, P < 0.001, per SD lower Cornell product). In parallel analyses, time-varying Cornell product was associated with lower risk of new-onset HF or death in ISH and non-ISH (adjusted HR 0.83, 95% CI 0.75-0.93, P = 0.001 and 0.82, 95% CI 0.77-0.87, P < 0.001, per SD lower Cornell product). Regression of time-varying Cornell product was associated with similar reductions in risk of new-onset HF and the combined endpoint of HF or death in ISH and non-ISH patients.

Reinfarction after percutaneous coronary intervention or medical management using the universal definition in patients with total occlusion after myocardial infarction: Results from long-term follow-up of the Occluded Artery Trial (OAT) cohort

The OAT study randomized 2,201 patients with a totally occluded infarct-related artery on days 3 to 28 (>24 hours) after myocardial infarction (MI) to percutaneous coronary intervention (PCI) or medical treatment (MED). There was no difference in the primary end point of death, reinfarction, or heart failure at 2.9 or 6-year mean follow-up. However, in patients randomized to PCI, there was a trend toward a higher rate of reinfarction. We analyzed the characteristics and types of reinfarction according to the universal definition. Independent predictors of reinfarction were determined using Cox proportional hazard models with follow-up up to 9 years. There were 169 reinfarctions: 9.4% PCI vs 8.0% MED, hazard ratio 1.31, 95% CI 0.97-1.77, P = .08. Spontaneous reinfarction (type 1) occurred with similar frequency in the groups: 4.9% PCI vs 6.7% MED, hazard ratio 0.78, 95% CI 0.53-1.15, P = .21. Rates of type 2 (secondary) and 3 (sudden death) MI were similar in both groups. There was an increase in type 4a reinfarctions (related to protocol or other PCI) (0.8% PCI vs 0.1% MED, P = .01) and type 4b reinfarctions (stent thrombosis) (2.7% PCI vs 0.6% MED, P < .001). Multivariate predictors of reinfarction were history of PCI before study entry (P = .001), diabetes (P = .005), and absence of new Q waves with the index infarction (P = .01). There was a trend for reinfarctions to be more frequent with PCI. Opening an occluded infarct-related artery in stable patients with late post-MI may expose them to a risk of subsequent reinfarction related to reocclusion and stent thrombosis.

Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial

Intracoronary administration of an abciximab bolus during a primary percutaneous coronary intervention results in a high local drug concentration, improved perfusion, and reduction of infarct size compared with intravenous bolus application. However, the safety and efficacy of intracoronary versus standard intravenous bolus application in patients with ST-elevation myocardial infarction (STEMI) undergoing this intervention has not been tested in a large-scale clinical trial. The AIDA STEMI trial was a randomised, open-label, multicentre trial. Patients presenting with STEMI in the previous 12 h with no contraindications for abciximab were randomly assigned in a 1:1 ratio by a central web-based randomisation system to intracoronary versus intravenous abciximab bolus (0·25 mg/kg bodyweight) during percutaneous coronary intervention with a subsequent 12 h intravenous infusion 0·125 μg/kg per min (maximum 10 μg/min). The primary endpoint was a composite of all-cause mortality, recurrent infarction, or new congestive heart failure within 90 days of randomisation. Secondary endpoints were the time to occurrence of the primary endpoint, each individual component of that endpoint, early ST-segment resolution, thrombolysis in myocardial infarction (TIMI) flow grade, and enzymatic infarct size. A masked central committee adjudicated the primary outcome and its components. Treatment allocation was not concealed from patients and investigators. This trial is registered with ClinicalTrials.gov, NCT00712101. Between July, 2008, and April, 2011, 2065 patients were randomly assigned intracoronary abciximab (n=1032) or intravenous abciximab (n=1033). Intracoronary, as compared with intravenous abciximab, resulted in a similar rate of the primary composite clinical endpoint at 90 days in 1876 analysable patients (7·0%vs 7·6%; odds ratio [OR] 0·91; 95% CI 0·64-1·28; p=0·58). The incidence of death (4·5%vs 3·6%; 1·24; 0·78-1·97; p=0·36) and reinfarction (1·8%vs 1·8%; 1·0; 0·51-1·96; p=0·99) did not differ between the treatment groups, whereas less patients in the intracoronary group had new congestive heart failure (2·4%vs 4·1%; 0·57; 0·33-0·97; p=0·04). None of the secondary endpoints or safety measures differed significantly between groups. In patients with STEMI undergoing primary percutaneous coronary intervention, intracoronary as compared to intravenous abciximab did not result in a difference in the combined endpoint of death, reinfarction, or congestive heart failure. Since intracoronary abciximab bolus administration is safe and might be related to reduced rates of congestive heart failure the intracoronary route might be preferred if abciximab is indicated. Lilly, Germany. University of Leipzig-Heart Centre. University of Leipzig, Clinical Trial Centre Leipzig, supported by the Federal Ministry of Education and Research (BMBF).

Clinical Implications of Electrocardiographic Left Ventricular Strain and Hypertrophy in Asymptomatic Patients With Aortic Stenosis

Background— The prognostic impact of ECG left ventricular strain and left ventricular hypertrophy (LVH) in asymptomatic aortic stenosis is not well described. Methods and Results— Data were obtained in asymptomatic patients randomized to simvastatin/ezetimibe combination versus placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Primary end point was the first of myocardial infarction, nonhemorrhagic stroke, heart failure, aortic valve replacement, or cardiovascular death. The predictive value of ECG left ventricular strain (defined as T-wave inversion in leads V 4 through V 6 ) and LVH, assessed by Sokolow-Lyon voltage criteria (R V5–6 +S V1 ≥35 mV) and Cornell voltage-duration criteria {[RaVL+S V3 +(6 mV in women)]×QRS duration ≥2440 mV · ms}, was evaluated by adjustment for other prognostic covariates. A total of 1533 patients were followed for 4.3±0.8 years (6592 patient-years of follow-up), and 627 cardiovascular events occurred. ECG strain was present in 340 patients (23.6%), with LVH by Sokolow-Lyon voltage in 260 (17.1%) and by Cornell voltage-duration product in 220 (14.6%). In multivariable analyses, ECG left ventricular strain was associated with 3.1-fold higher risk of in-study myocardial infarction (95% confidence interval, 1.4–6.8; P =0.004). Similarly, ECG LVH by both criteria predicted, compared with no ECG LVH, 5.8-fold higher risk of heart failure (95% confidence interval, 2.0–16.8), 2.0-fold higher risk of aortic valve replacement (95% confidence interval, 1.3–3.1; both P =0.001), and 2.5-fold higher risk of a combined end point of myocardial infarction, heart failure, or cardiovascular death (95% confidence interval, 1.3–4.9; P =0.008). Conclusions— ECG left ventricular strain and LVH were independently predictive of poor prognosis in patients with asymptomatic aortic stenosis. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00092677.

Abstract P195: Nuclear Translocation of GRK5 Following Hypertrophic Stimuli Is a Calmodulin-Dependent Process

Maladaptive ventricular hypertrophy often precedes the pathological endpoint of Heart Failure (HF). G protein Coupled Receptors (GPCRs), such as the β-adrenergic receptor, play a crucial role in the development of cardiac hypertrophy. GPCR Kinase 5 (GRK5) is a primary GRK expressed in cardiomyocytes. Traditionally, it phosphorylates and desensitizes agonist-bound GPCRs. Recent, exciting data from our lab shows that GRK5 translocates into the nucleus and phosphorylates Histone Deacetylase 5 (HDAC5) in response to hypertrophic stimuli. This novel kinase activity of GRK5 causes nuclear export of HDAC5, enhancing transcription of hypertrophic genes regulated by myocyte elongation factor 2 (MEF2). We hypothesize that that nuclear GRK5 activity plays a critical role in cardiomyocytes, facilitating pathological hypertrophy and HF, and that hypertrophic GPCR signaling induces GRK5 nuclear translocation. To test this hypothesis, we utilized neonatal rat ventricular cardiomyocytes (NRVMs) to determine GRK5 localization following the hypertrophic stimulus of phenylephrine (PE) treatment. To determine the mechanism causing nuclear translocation, we analyzed the effects targeted inhibition of key post-GPCR hypertrophic signaling pathways on GRK5 cellular localization. Treatment of NRVMs with PE for 1 hour increases nuclear GRK5 accumulation by 100%. Chronic infusion of PE also lead to a 50% increase in nuclear GRK5 in the hearts of mice overexpressing cardiac-specific GRK5. Calmodulin inhibition (CaM) in NRVMs via calmidizolium chloride decreases nuclear GRK5 accumulation, while inhibition of PKC and PKD shows no significant effect. Using a luciferase assay, we have shown that overexpression of CaM increases MEF2 activity 3-fold and causes increased nuclear accumulation of GRK5. Further, overexpression of a GRK5 mutant that lacks CaM binding activity, results in a lack of PE- and CaM-induced nuclear translocation. We have now found that hypertrophic stimuli increases myocyte GRK5 nuclear translocation via a CaM-dependent process. Defining the role of CaM signaling in pathological GRK5 nuclear localization may offer a new therapeutic target for maladaptive hypertrophy and HF.

Abstract 9371: Diuretic Use and the Benefit of Cardiac Resynchronization Therapy to Prevent Heart Failure and Death: Secondary Analysis of Data from MADIT-CRT.

MADIT-CRT demonstrated a reduction in the composite endpoint of heart failure (HF) or death with CRT-D vs. ICD-only therapy in patients with NYHA class I-II, ejection fraction &lt;0.30, and QRS &gt;130ms. Additional predictive variables would aid in selecting patients for preventive CRT-D. We hypothesized that diuretic use at study enrollment might identify patients with more advanced cardiac impairment and incipient HF and thus greater potential for reduction in later overt HF or death with CRT-D. At baseline, 1228 patients were diuretic users and 592 were diuretic non-users. Kaplan-Meier graphs are shown for the two subgroups. Diuretic users showed a relatively high probability of overt HF or death with ICD alone plus a large, highly significant reduction in the risk of this end point with CRT-D therapy. Nonusers had fewer of these events with ICD and modest reduction of borderline statistical significance with CRT-D. As anticipated, the predictive information derived from diuretic use was not unique: when adjusted for imbalances in relevant baseline characteristics (e.g., serum creatinine), diuretic users and non-users experienced similar benefit from CRT-D therapy. Conclusion: in MADIT-CRT, the physician's pre-enrollment decision to use diuretics discriminated between a subgroup achieving a strikingly significant benefit from CRT-D therapy and one receiving little likelihood of benefit. This finding may aid in selecting optimal management for patients resembling MADIT-CRT enrollees.

Pharmacoinvasive therapy for ST elevation myocardial infarction in China: a pilot study

Most patients with acute ST-elevation myocardial infarction (STEMI) cannot receive timely primary percutaneous coronary intervention (PCI) because of lack of facilities or delays in patient transfer or catheterization team mobilization. In these patients, early routine post-thrombolysis PCI might be a reasonable, useful strategy. This study investigated feasibility and safety of early PCI after successful half-dose alteplase reperfusion in a Chinese population. Patients with STEMI received half-dose alteplase if expected time delay to PCI was ≥90min. Patients who reached clinical criteria of successful thrombolysis reperfusion were recommended to undergo diagnostic angiography within 3-24h after thrombolysis. Patients with residual stenosis ≥70% in the infarct-related artery underwent PCI, regardless of flow or patency status. Epicardial arterial flow was assessed using thrombolysis in myocardial infarction (TIMI) flow grade and TIMI frame count (CTFC). Myocardial perfusion was assessed using myocardial blush grade (MBG) and TIMI myocardial perfusion frame count (TMPFC). Forty-nine patients were enrolled and underwent diagnostic angiography 3-11.3h (median 6.5h) after thrombolysis. Forty-six patients underwent PCI. No procedure-related complications occurred, except two patients who had no reflow after PCI. Twenty-two (47.8%) patients had TIMI grade 3 flow before PCI and 33 (71.7%) after PCI. CTFC was significantly improved after PCI (48.5±32.1 vs. 37.9±25.6, P=0.01). MBG and TMPFC exhibited a similar improving trend after PCI, and the best myocardial perfusion tended to be achieved 3-12h after lysis. During the 30-day follow-up, there were two deaths. The composite end point of death, cardiogenic shock, heart failure, reinfarction, and recurrent ischemia occurred in four patients. TIMI minor bleeding occurred in four patients. No TIMI major bleeding and stroke occurred. Early routine PCI after half-dose alteplase thrombolysis in Chinese population appears feasible. A larger clinical trial should be designed to further elucidate its efficacy and safety. Early PCI after thrombolysis in STEMI: The EARLY-PCI pilot feasibility study, ChiCTR-TNC-11001363.

End Point Selection in Acute Decompensated Heart Failure Clinical Trials: Economic End Points

The selection of economic end points in acute decompensated heart failure (ADHF) clinical trials requires prospectively planned evaluations that are developed in tandem with clinical end points. Integrating economic end points with concrete clinical outcomes postdischarge will provide meaningful data to evaluate a treatment's incremental value in the setting of ADHF.

Early percutaneous coronary intervention after thrombolysis in STEMI: the early-PCI pilot feasibility study

IntroductionPrimary percutaneous coronary intervention (PCI) is the preferred treatment for patients with STEMI now. But few patients can receive it within 90 min recommended by the guideline in the real...

Hypoalbuminaemia and incident heart failure in older adults

To test the hypothesis that baseline hypoalbuminaemia is associated with incident heart failure (HF) in community-dwelling older adults. Of the 5795 community-dwelling adults aged ≥65 years in the Cardiovascular Health Study, 5450 were free of centrally adjudicated prevalent HF at baseline, and also had data on baseline serum albumin. Of these, 599 (11%) had hypoalbuminaemia, defined as baseline serum albumin levels ≤3.5 mg/dL. Propensity scores for hypoalbuminaemia were calculated for each patient and used to assemble a matched cohort of 582 pairs of participants with and without hypoalbuminaemia, who were well balanced on 58 baseline characteristics. Using Cox regression models, we estimated the association of hypoalbuminaemia with centrally adjudicated incident HF during 9.6 years of median follow-up. Matched participants had a mean (±SD) age of 74 (±6) years, 62% were women, and 16% were African Americans. Incident HF occurred in 25 and 20% of matched participants with and without hypoalbuminaemia, respectively [hazard ratio when hypoalbuminaemia was compared with normoalbuminaemia, 1.40; 95% confidence interval, 1.05-1.85; P = 0.020]. Pre-match unadjusted, multivariable-adjusted, and propensity-adjusted hazard ratios (95% confidence intervals) for incident HF associated with hypoalbuminaemia were 1.33 (1.12-1.58; P = 0.001), 1.33 (1.11-1.60; P = 0.002), and 1.25 (1.04-1.50; P= 0.016), respectively. The combined endpoint of incident HF or all-cause mortality occurred in 59 and 50% of matched participants with and without hypoalbuminaemia, respectively (hazard ratio, 1.33; 95% confidence interval, 1.11-1.61; P= 0.002). Among community-dwelling older adults without HF, baseline hypoalbuminaemia was associated with increased risk of incident HF during 10 years of follow-up.

Cardiac Resynchronization Therapy Reduces Left Atrial Volume and the Risk of Atrial Tachyarrhythmias in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy)

We hypothesized that reductions in left atrial volume (LAV) with a cardiac resynchronization therapy-defibrillator (CRT-D) would translate into a subsequent reduction in the risk of atrial tachyarrhythmias (AT). There is limited information regarding the effect of CRT-D on the risk of AT. Percent reduction in LAV at 1 year following CRT-D implantation (pre-specified as low [lowest quartile: <20% reduction in LAV] and high [≥20% reduction in LAV] response to CRT-D) were related to the risk of subsequent AT (comprising atrial fibrillation, atrial flutter, atrial tachycardia, and supraventricular tachyarrhythmias) among patients enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy). The cumulative probability of AT 2.5 years after assessment of echocardiographic response was lowest among high LAV responders to CRT-D (3%) and significantly higher among both low LAV responders to CRT-D (9%) and implantable cardioverter-defibrillator-only patients (7%; p = 0.03 for the difference among the 3 groups). Consistently, multivariate analysis showed that high LAV responders to CRT-D experienced a significant 53% (p = 0.01) reduction in the risk of subsequent AT as compared with implantable cardioverter-defibrillator-only patients, whereas low LAV responders did not derive a significant risk reduction with CRT-D therapy (hazard ratio [HR]: 1.05 [95% confidence interval (CI): 0.54 to 2.00]; p = 0.89). Patients who developed in-trial AT experienced significant increases in the risk for both the combined endpoint of heart failure or death (HR: 2.28 [95% CI: 1.45 to 3.59]; p < 0.001) and the separate occurrence of all-cause mortality (HR: 1.89 [95% CI: 1.08 to 3.62]; p = 0.01). In the MADIT-CRT study, favorable reverse remodeling of the left atrium with CRT-D therapy was associated with a significant reduction in risk of subsequent AT. (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271).