Combined Endpoint Of Death Research Articles

Electrical optimization of cardiac resynchronization in chronic heart failure is associated with improved clinical long‐term outcome

Cardiac resynchronization therapy (CRT) is an established treatment option for symptomatic chronic heart failure (CHF) patients with pharmacological baseline therapy, but not all patients benefit from device therapy. One reason for this may be inadequate device settings. In real-world practice, echocardiographic evaluation of atrioventricular (AV) delay is not performed in a high proportion of patients, as the effect of electrical optimization of CRT is an issue open for investigation. We performed a retrospective observational study analysing the effect of AV-interval evaluation with echocardiography on long-term [32 (23?43) months] clinical outcome in 205 CHF patients. A stepwise Cox regression model including a co-morbidity score, failed AV-interval evaluation, satisfactory device function after the first implantation attempt, failure to reach 100% of the recommended renin-angiotensin system inhibitor and beta-blocker dose at follow-up and CRT device implantation compared with CRT in combination with an implanted cardioverter defibrillator (ICD) was applied. In the total study cohort, 124 (60.5%) patients had reached the primary combined endpoint death or cardiac hospitalization and 59 (28.8%) had died. Cox regression analysis revealed that failed AV-interval evaluation [HR = 1.72 (1.19-2.49), P = 0.004] non-optimized CHF pharmacotherapy dosages [HR = 2.12 (1.32-3.42), P = 0.002], the presence of a CRT/ICD combination device [HR = 1.87 (1.28-2.71), P = 0.001] and satisfactory device function after the first implantation attempt [HR = 0.44 (0.25-0.77), P = 0.004] were associated with the primary endpoint. Echocardiographic evaluation of the AV-interval in patients with CRT was independently associated with improved clinical outcome, impacting on daily clinical practice of HF patient care.

General Cardiology Perspective: Decision Making Regarding Revascularization of Patients With Type 2 Diabetes Mellitus and Cardiovascular Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial

The interest in the diabetic population undergoing coronary revascularization began with the reporting of the Bypass Angioplasty Revascularization Investigation (BARI) trial in 1996.1 In patients with multivessel disease, a post hoc analysis demonstrated a significant survival advantage for patients in the coronary artery bypass grafting (CABG) arm compared with those undergoing balloon angioplasty. This striking finding sensitized the cardiovascular community to the unique nature of diabetic coronary disease. A comprehensive meta-analysis of percutaneous coronary intervention (PCI) versus CABG trials before the drug-eluting era has confirmed the BARI findings.2 Over the next decade, there were tremendous advances in medical risk factor modification, particularly the widespread use of statin drugs and improvements in therapies for glycemic control. The BARI 2 Diabetes (BARI 2D) investigators posed the next important question about optimal management of coronary disease in patients with less severe symptomatology than those enrolled in the multivessel PCI versus CABG trials.3 About 80% of patients were either asymptomatic or had stable class I/II Canadian Cardiovascular Society angina. In this trial, the comparison was now between prompt revascularization on top of optimal medical therapy (OMT) versus OMT alone. BARI 2D heralded in a new era in National Heart, Lung, and Blood Institute–sponsored trials by exclusively studying patients with type 2 diabetes mellitus. BARI 2D demonstrated no difference in 5-year mortality between the prompt revascularization and OMT alone arms (11.7% versus 12.2%; P =0.97) as well as no difference in 5-year rates of the combined end point of death, myocardial infarction, and stroke (22.8% versus 24.1%; P =0.70). The most efficient way to evaluate the impact of BARI 2D on practice is to evaluate the patients studied and the interventions that were applied. ### The Patients BARI 2D randomized patients with demonstrated ischemia who were either asymptomatic or who had mild to moderate symptoms. …

Association Between Timeliness of Reperfusion Therapy and Clinical Outcomes in ST-Elevation Myocardial Infarction

Guidelines emphasize the importance of rapid reperfusion of patients with ST-elevation myocardial infarction (STEMI) and specify a maximum delay of 30 minutes for fibrinolysis and 90 minutes for primary percutaneous coronary intervention (PPCI). However, randomized trials and selective registries are limited in their ability to assess the effect of timeliness of reperfusion on outcomes in real-world STEMI patients. To obtain a complete interregional portrait of contemporary STEMI care and to investigate timeliness of reperfusion and outcomes. Systematic evaluation of STEMI care for 6 months during 2006-2007 in 80 hospitals that treated more than 95% of patients with acute myocardial infarction in the province of Quebec, Canada (population, 7.8 million). Death at 30 days and at 1 year and the combined end point of death or hospital readmission for acute myocardial infarction or congestive heart failure at 1 year by linkage to Quebec's medicoadministrative databases. Of 1832 patients treated with reperfusion, 392 (21.4%) received fibrinolysis and 1440 (78.6%) received PPCI. Fibrinolysis was untimely (>30 minutes) in 54% and PPCI was untimely (>90 minutes) in 68%. Death or readmission for acute myocardial infarction or heart failure at 1 year occurred in 13.5% of fibrinolysis patients and 13.6% of PPCI patients. When the 2 treatment groups were combined, patients treated outside of recommended delays had an adjusted higher risk of death at 30 days (6.6% vs 3.3%; odds ratio [OR], 2.14; 95% confidence interval [CI], 1.21-3.93) and a statistically nonsignificant increase in risk of death at 1 year (9.3% vs 5.2%; OR, 1.61; 95% CI, 1.00-2.66) compared with patients who received timely treatment. Patients treated outside of recommended delays also had an adjusted higher risk for the combined outcome of death or hospital readmission for congestive heart failure or acute myocardial infarction at 1 year (15.0% vs 9.2%; OR, 1.57; 95% CI, 1.08-2.30). At the regional level, after adjustment, each 10% increase in patients treated within the recommended time was associated with a decrease in the region-level odds of overall 30-day mortality (OR, 0.80; 95% CI, 0.65-0.98). Among patients in Quebec with STEMI, reperfusion delivered outside guideline-recommend delays was associated with significantly increased 30-day mortality, a statistically nonsignificant increase in 1-year mortality, and significantly increased risk of the composite of mortality or readmission for acute myocardial infarction or heart failure at 1 year.

Section 5: Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction

Section 5: Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction

Selective Head Cooling with Mild Systemic Hypothermia after Neonatal Hypoxic-Ischemic Encephalopathy: A Multicenter Randomized Controlled Trial in China

To investigate the efficacy and safety of selective head cooling with mild systemic hypothermia in hypoxic-ischemic encephalopathy (HIE) in newborn infants. Infants with HIE were randomly assigned to the selective head cooling or control group. Selective head cooling was initiated within 6 hours after birth to a nasopharyngeal temperature of 34 degrees+/-0.2 degrees C and rectal temperature of 34.5 degrees to 35.0 degrees C for 72 hours. Rectal temperature was maintained at 36.0 degrees to 37.5 degrees C in the control group. Neurodevelopmental outcome was assessed at 18 months of age. The primary outcome was a combined end point of death and severe disability. One hundred ninety-four infants were available for analysis (100 and 94 infants in the selective head cooling and control group, respectively). For the selective head cooling and control groups, respectively, the combined outcome of death and severe disability was 31% and 49% (OR: 0.47; 95% CI: 0.26-0.84; P=.01), the mortality rate was 20% and 29% (OR:0.62; 95% CI: 0.32-1.20; P=.16), and the severe disability rate was 14% (11/80) and 28% (19/67) (OR: 0.40; 95% CI: 0.17-0.92; P=.01). Selective head cooling combined with mild systemic hypothermia for 72 hours may significantly decrease the combined outcome of severe disability and death, as well as severe disability.

Prognostic value of myeloperoxidase in coronary artery disease: comparison of unstable and stable angina patients

Atherosclerosis is a chronic inflammatory process, and myeloperoxidase (MPO) seems to contribute directly to the pathogenesis of acute coronary syndrome (ACS). To compare MPO levels among the patients with stable and unstable ischemic heart disease and to evaluate their independent prognostic value for cardiovascular events. MPO and C-reactive protein (CRP) were assessed in two cohorts of coronary artery disease patients, including 178 patients with stable angina and 130 patients with ACS evaluated at the emergency department. MPO and CRP levels were significantly higher among patients with ACS [MPO 93 (54-127) vs. 9.9 pmol/l (5-21) and high sensitivity-CRP 11 (3-27) vs. 2.6 mg/l (1-5)]. Among patients with stable angina, high sensitivity-CRP levels greater than 3 mg/l were associated with a three-fold risk of further cardiovascular events during a mean follow-up period of 13+/-4 months, although there was no significant association between MPO levels and outcomes. Among patients with ACS, baseline MPO level was an independent predictor of major adverse cardiac events during hospitalization, odds ratio of 3.8 (95% confidence interval: 1.2-12) for the combined endpoint (death, recurrent angina, heart failure, and arrhythmia). CRP levels were associated with hospital mortality in patients with ACS, but were not independently related to cardiovascular events. Elevated MPO levels among the ACS patients suggest that this marker may participate in plaque vulnerability and instability process, whereas higher CRP levels were predictive of cardiac events only among the stable angina patients. These findings suggest distinct role of the inflammatory markers studied in the pathophysiology of coronary artery disease.

Bypasschirurgie versus perkutane koronare Intervention bei Patienten mit Diabetes mellitus

At present, in patients with diabetes mellitus and coronary multivessel disease no fixed general recommendation can be given in favor or to the disadvantage of surgical revascularization or in favor or to the disadvantage of percutaneous coronary intervention (PCI). In cases with an evidence-based indication for coronary revascularization because of clinical symptoms and/or proven ischemia, both therapeutic alternatives of bypass surgery or PCI are electable. The decision, which method of revascularization to prefer, must be based on close analyses of individual risk profile, individual comorbidity, and individual coronary morphology. With correct indication, both therapeutic methods are equivalent regarding the prognostically important combined endpoint of death, nonfatal myocardial infarction, and stroke. For PCI, however, there is a higher probability of restenosis depending on the complexity of lesion morphology, requiring more often repeat interventions or revascularizations. Before deciding in subfavor of or against a surgical or nonsurgical revascularization procedure, the complexity of the coronary artery disease should be analyzed, for example using the SYNTAX Score. In patients with SYNTAX Scores > or = 33 and no contraindications to bypass surgery, a surgical revascularization should be preferred. In the intermediate group with SYNTAX Scores between 23 und 32, the advantages and disadvantages of bypass surgery or PCI, for instance, the increased probability of restenosis with a higher necessity of repeat revascularizations after PCI, should be extensively discussed with the patient. In patients with SYNTAX Scores between 0 and 22, the nonsurgical, interventional therapy using drug-eluting stents (DES) can be recommended as an equivalent alternative to bypass surgery. In meta-analyses of randomized controlled trials and meta-analyses of large registries with PCI in patients with diabetes mellitus, clear advantages of DES in comparison with bare-metal stents (BMS) could be shown. Especially for patients with diabetes mellitus, there is still no clear evidence in favor of or against a special DES type or in favor of or against a special stent covering. Further sufficiently powered randomized controlled trials with hard clinical endpoints comparing bypass surgery with PCI (e.g., FREEDOM trial) and comparing different types of DES in patients with diabetes mellitus and clear PCI indications must be awaited, before further recommendations can be given.

Impact of Lipid-Lowering Therapy on Outcomes in Atrial Fibrillation

Lipid-lowering therapy (LLT) decreases mortality in select patient populations. LLT has also been shown to have antiarrhythmic effects, thus favorably influencing the incidence and recurrence of atrial fibrillation (AF). However, data are lacking regarding the effect of LLT on mortality in patients with AF. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study was the one of the largest multicenter trials comprising of 4,060 patients with AF at high risk for stroke and death. This is a post hoc analysis of the National Heart, Lung, and Blood Institute limited-access dataset of AFFIRM patients who were on LLT at the time of randomization (n = 913). The control group consisted of AFFIRM patients who were not on LLT (n = 3,147). Cox proportional hazards analysis was performed controlling for baseline differences. The end point was all-cause mortality, cardiovascular mortality, and ischemic stroke. A separate analysis was carried out for the combined end point of death, ventricular tachycardia, ventricular fibrillation, cardiac arrest, ischemic stroke, major bleeding, systemic embolism, pulmonary embolism, and myocardial infarction. Patients on LLT were younger and on more cardioactive medications but also had more cardiovascular morbidities. On multivariate analysis, LLT use was associated with lower all-cause mortality (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.62 to 0.95, p = 0.01), cardiovascular mortality (HR 0.71, 95% CI 0.53 to 0.95, p = 0.02), ischemic stroke (HR 0.56, 95% CI 0.36 to 0.89, p = 0.01), and combined end point (HR 0.81, 95% CI 0.69 to 0.96, p = 0.01). In conclusion, a decrease in mortality and adverse cardiovascular events was observed using LLT in AF.

Strict glycaemic control in diabetic patients with CKD or ESRD: beneficial or deadly?

The evidence in CKD Information about the effect of strict glycaemic control on outcome in diabetic patients with CKD is very limited. In the PROactive study (Prospective Pioglitazone Clinical Trial in Macrovascular Events), patients with type 2 diabetes and CKD (n = 597; 11.6% of the 5154 patients) had a particularly high CV risk and cardiovascular disease (CVD) [7]. The incidence of the combined end point (non-fatal myocardial infarction, stroke and death) was 18.3% in patients with CKD compared with 11.5% in patients without CKD (HR 1.65; P < 0.0001). In addition, all-cause mortality was 10.9% compared to 5.9% (HR 1.86) in those without CKD. Remarkably, patients who had CKD and were treated with pioglitazone were less likely to reach the combined end point (HR 0.66; P < 0.001) independently of the severity of renal impairment [7]. Since at study end the HbA1c difference between pioglitazone and placebo was only 0.5% (6.9 vs 7.4%), presumably a variety of well-documented anti-atherogenic effects of pioglitazone [8] were responsible for CV protection in diabetic patients presenting with CVD.

Incidence of Caffeine in Serum of Patients Undergoing Dipyridamole Myocardial Perfusion Stress Test by an Intensive Versus Routine Caffeine History Screening

The coronary vasodilatory effect of dipyridamole is competitively blocked by caffeine. The purposes of this study were to (1) assess the incidence of having detectable serum caffeine and (2) evaluate whether an intensive caffeine history screening strategy was superior to routine history screening before dipyridamole myocardial perfusion imaging. One hundred ninety-four patients who were randomized to an intensive or a routine screening history strategy were prospectively evaluated. Serum caffeine levels were determined in all patients. Outcomes data, including death, nonfatal myocardial infarction, and history of revascularization, were obtained at 24 months. Nearly 1 in 5 patients (19%) who screened negative by history had detectable serum caffeine. In patients who screened negative by history, there was no statistically significant difference in the percentage of caffeine seropositivity between the intensive and routine arms (16% vs 22%, respectively, p = 0.31). The incidence of combined end points of death, myocardial infarction, or revascularization was 22.9% and 7.3% in patients with and without detectable serum caffeine, respectively (p = 0.01). In conclusion, despite initial negative results on screening by history, a considerably high percentage of patients had positive serum caffeine levels. These results do not support the use of an intensive screening strategy. Detectable serum caffeine was associated with a higher incidence of adverse outcomes.

The Second (Main) Phase of an Open, Randomised, Multicentre Study to Investigate the Effectiveness of an Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (Interact2)

The INTERACT pilot study demonstrated the feasibility of the protocol, safety of early intensive blood pressure lowering and effects on haematoma expansion within 6 h of onset of intracerebral haemorrhage. This article describes the design of the second, main phase, INTERACT2. To compare the effects of a management strategy of early intensive blood pressure lowering with a more conservative guideline-based blood pressure management policy in patients with acute intracerebral hemorrhage. INTERACT2 is a prospective, randomized, open label, assessor-blinded end-point (PROBE). Patients with a systolic blood pressure greater than 150 mmHg and no definite indication for or contraindication to blood pressure-lowering treatment are centrally randomised to either of two treatment groups within 6 h onset of intracerebral haemorrhage. Those allocated to intensive blood pressure lowering will receive primarily intravenous, hypotensive agents to achieve a systolic blood pressure target of <140 mmHg within 1 h of randomisation and to maintain this level for up to 7 days in hospital. The control group will receive blood pressure-lowering treatment to a target systolic blood pressure of <180 mmHg. Both groups are to receive similar acute stroke unit care, therapy and active management. Oral antihypertensive therapy is recommended in patients before hospital discharge with a long-term systolic blood pressure goal of 140 mmHg according to secondary stroke prevention guidelines. A projected 2800 subjects are to be enrolled from approximately 140 centres worldwide to provide 90% power (alpha 0.05) to detect a 14% difference in the risk of death and dependency between the groups, which equates to one or more cases of a poor outcome prevented in every 15 patients treated. The primary outcome is the combined end-point of death and dependency according to the modified Rankin Scale at 90 days. The secondary outcomes are the separate components of the primary end-point in patients treated <4 hours of ICH onset, grades of physical function on the modified Rankin Scale, health-related quality of life on the EuroQoL, recurrent stroke and other vascular events, days of hospitalisation, requirement for permanent residential care and unexpected serious adverse events.

Klinisches Profil des neuen Antiarrhythmikums Dronedaron

The new antiarrhythmic drug dronedarone (SR 33 589) is a benzofuran derivative structurally similar to amiodarone, however is noniodinated. The additional methansulfonylgroup renders it less lipophilic, with a substantially shorter half-life, compared to the parent compound. The electrophysiological properties of both agents are similar with inhibition of Na+, K+, and Ca++ currents (all Vaughan-Williams classes). The agent has been evaluated in a large clinical study program. The daily dose of dronedarone 800 mg has been shown (DAFNE) to be effective and well tolerated. In two design-identical randomised clinical trials (EURIDIS and ADONIS trial) the efficacy of dronedarone to maintain sinus rhythm in patients with chronic atrial fibrillation/flutter was shown to be clearly superior to placebo. The ERATO study showed the rate control properties of dronedarone. In the ATHENA morbidity/mortality study, the combined endpoint death or hospitalisation due to cardiovascular events occurred significantly less often in the dronedarone group compared to the placebo group. Particularly due to its beneficial effects on clinical outcomes such as cardiovascular hospitalizations and death in the context of high tolerability dronedarone appears to be a promising new antiarrhythmic compound.

Metabolic Syndrome Is Not Associated With Increased Mortality or Cardiovascular Risk in Nondiabetic Patients With a New Diagnosis of Coronary Artery Disease

Metabolic syndrome (MetSyn) is associated with increased cardiovascular risk in the general population. Its prognostic implications are less well defined in patients with coronary artery disease. We analyzed patients in the Duke Database for Cardiovascular Disease with a diagnosis of incident obstructive coronary artery disease. Diabetes mellitus (DM) was classified as a clinical history of DM, use of hypoglycemic drugs, or fasting glucose of >or=126 mg/dL. MetSyn was defined as having 3 of 5 characteristics: fasting glucose >or=100 and <126 mg/dL, low high-density lipoprotein cholesterol (men, <40 mg/dL; women, <50 mg/dL), triglycerides >150 mg/dL, blood pressure >or=130/85 mm Hg, or use of antihypertensive therapy, or body mass index >or=27. Death, myocardial infarction, or stroke was assessed at 6 months, 1 year, then annually. Cox proportional hazards models were generated to compare mortality and cardiovascular events between groups. The primary cohort consisted of 5744 patients; 1831 (31.9%) had DM, 2491 (43.4%) had MetSyn, and 1422 (24.7%) had no DM/MetSyn. Median follow-up was 5 years. Compared with no DM/MetSyn patients, DM patients had a higher adjusted risk for mortality (hazard ratio, 1.47; 95% CI, 1.28 to 1.69) but MetSyn patients did not (hazard ratio, 0.94; 95% CI, 0.81 to 1.08). Similar results were found for the combined end points of death or myocardial infarction, and death, myocardial infarction, or stroke. In a population of consecutive patients with a new diagnosis of coronary artery disease by angiography, MetSyn without DM was not an independent predictor of mortality or cardiovascular events.

Combination Antithrombotic Therapies

Atherothrombosis is the major pathophysiological process responsible for the occurrence of severe ischemic events in patients with cardiovascular diseases. In the United States, atherothrombosis strongly influenced mortality in 2004: One in 2.8 deaths was due to CVD, 1 in 5 deaths to coronary heart disease, and 1 in 17 deaths to stroke.1 Because cardiovascular disease is a progressive and systemic disease, long-term antithrombotic therapies that effectively target the entire arterial vasculature and modulate the key components responsible for thrombus generation are essential to improve patient outcomes. Because platelet activation is determined by multiple receptor-mediated signaling pathways, clinical studies have evaluated the efficacy of multidrug administration in the prevention of atherothrombotic complications.2,3 The major concern with these therapies is the critical balance between anti-ischemic effect and bleeding risk. This review summarizes our understanding of the role of combination antiplatelet therapies in the treatment and prevention of atherothrombosis. Platelet activation and aggregation play a pivotal role in the generation of occlusive thrombus at the site of coronary arterial plaque rupture. In addition, platelets influence various endothelial and inflammatory responses during the initiation and progression of atherosclerosis. Under normal conditions, anucleate circulating platelets are in a quiescent state. Healthy vascular endothelium prevents adhesion and activation of platelets by producing antithrombotic factors such as CD39 (ectoADPase), prostaglandin I2, nitric oxide, heparin, matrix metalloproteinase-9, protein S, and thrombomodulin.3,4 Endothelial activation and denudation and frank atherosclerotic plaque rupture expose the subendothelial matrix and release prothrombotic factors during acute coronary syndromes (ACS) and percutaneous interventions. These processes result in localized platelet adhesion and platelet activation. After adhesion to the exposed subendothelial matrix, platelets are activated by shear and the soluble agonists thromboxane A2 (TxA2), ADP, and thrombin. TxA2 is produced from arachidonic acid, which originates from membrane phospholipids and …

N-Terminal Pro–B-Type Natriuretic Peptide–Guided, Intensive Patient Management in Addition to Multidisciplinary Care in Chronic Heart Failure: A 3-Arm, Prospective, Randomized Pilot Study

This study was designed to investigate whether the addition of N-terminal pro-B-type natriuretic peptide-guided, intensive patient management (BM) to multidisciplinary care (MC) improves outcome in patients following hospitalization due to heart failure (HF).Patients hospitalized due to HF experience frequent rehospitalizations and high mortality.Patients hospitalized due to HF were randomized to BM, MC, or usual care (UC). Multidisciplinary care included 2 consultations from an HF specialist who provided therapeutic recommendations and home care by a specialized HF nurse. In addition, BM included intensified up-titration of medication by HF specialists in high-risk patients. NT-proBNP was used to define the level of risk and to monitor wall stress. This monitoring allowed for anticipation of cardiac decompensation and adjustment of medication in advance.A total of 278 patients were randomized in 8 Viennese hospitals. After 12 months, the BM group had the highest proportion of antineurohormonal triple-therapy (difference among all groups). Accordingly, BM reduced days of HF hospitalization (488 days) compared with the hospitalization for the MC (1,254 days) and UC (1,588 days) groups (p < 0.0001; significant differences among all groups). Using Kaplan-Meier analysis, the first HF rehospitalization (28%) was lower in the BM versus MC groups (40%; p = 0.06) and the MC versus UC groups (61%; p = 0.01). Moreover, the combined end point of death or HF rehospitalization was lower in the BM (37%) than in the MC group (50%; p < 0.05) and in the MC than in the UC group (65%; p = 0.04). Death rate was similar between the BM (22%) and MC groups (22%), but was lower compared with the UC group (39%; vs. BM: p < 0.02; vs. MC: p < 0.02).Compared with MC alone, additional BM improves clinical outcome in patients after HF hospitalization. (BNP Guided Care in Addition to Multidisciplinary Care; NCT00355017).

The role of noninvasive ventilation in acute cardiogenic pulmonary edema

A total of 1069 patients (mean [±SD] age, 77.7±9.7 years; female sex, 56.9%) were assigned to standard oxygen therapy (367 patients), CPAP (346 patients), or NIPPV (356 patients). There was no signifi cant diff erence in 7-day mortality between patients receiving standard oxygen therapy (9.8%) and those undergoing noninvasive ventilation (9.5%, P=0.87). There was no signifi cant diff erence in the combined end point of death or intubation within 7 days between the two groups of patients undergoing noninvasive ventilation (11.7% for CPAP and 11.1% for NIPPV, P=0.81). As compared with standard oxygen therapy, noninvasive ventilation was associated with greater mean improvements at 1 hour after the beginning of treatment in patient-reported dyspnea (treatment diff erence, 0.7 on a visual-analogue scale ranging from 1 to 10; 95% confi dence interval [CI], 0.2 to 1.3; P=0.008), heart rate (treatment diff erence, 4 beats per minute; 95% CI, 1 to 6; P=0.004), acidosis (treatment diff erence, pH 0.03; 95% CI, 0.02 to 0.04; P<0.001), and hypercapnia (treatment diff erence, 0.7 kPa [5.2 mm Hg]; 95% CI, 0.4 to 0.9; P<0.001). There were no treatment-related adverse events.

Original research Perfusion assessed by real-time contrast echocardiography correlates with clinical and echocardiographic parameters in patients with first STEMI treated with PCI – 6-month follow-up

IntroductionAngiographic flow in an epicardial artery does not define perfusion at a microvascular level in patients with acute myocardial infarction (AMI). The aim of the study was assessing microvascular reperfusion by myocardial contrast echocardiography (MCE) and left ventricular (LV) functional recovery by echocardiographic methods in patients treated with primary PTCA.Material and methods100 consecutive patients with first ST-elevation AMI with single vessel disease treated successfully with primary PCI were enrolled. Regional contrast score index (RCSI), ejection fraction (EF), wall motion score index (WMSI), and end-systolic and end-diastolic volume (ESV, EDV) were evaluated during hospitalization and at 6-month follow-up. The patients were divided into 2 groups according to the absence (Group 1) or presence (Group 2) of perfusion defects on MCE.ResultsGroup 1 had lower WMSI (p = 0.0009), higher EF than Group 2 (44.7 and 55.9% respectively, p = 0.000067), and lower ESV (66.0 and 52.6 ml respectively, p = 0.003185). In Group 1 LVEF increased significantly on 6-month follow-up (p = 0.026), while in Group 2 it decreased (p = 0.0175). Both EDV and ESV were significantly lower in Group 1 (p = 0.0106 and p = 0.002882, respectively). There was a correlation between the presence of perfusion defects in the initial contrast echo and unfavourable change in ejection fraction during the follow-up (ANOVA for repeated measures, F[1.91] = 5.85, p = 0.0175). The combined clinical end-point (death and reinfarction) was significantly lower in patients without perfusion defect (p = 0.039).ConclusionsMyocardial contrast echocardiography results correlated with clinical outcome and recovery of systolic left ventricular function at 6-month follow-up.

Improved outcome in acute coronary syndrome by establishing a chest pain unit

Chest pain units (CPUs) have been established to optimize treatment of patients with acute coronary syndrome (ACS) and to early and accurately discharge patients with non-coronary chest pain. The aim of this analysis was to elucidate whether treatment of ACS patients in the CPU versus emergency department (ED) has prognostic implications. Patients presenting with suspected ACS to either the ED between August 2004 and June 2005 or the CPU between July 2005 and May 2006 were retrospectively analyzed. Of 1,796 included patients, 483 had the discharge diagnosis ACS. When compared to patients with exclusion of ACS they had more cardiovascular risk factors and higher troponin, creatinine and C-reactive protein levels (P < 0.001) at admission. Within 1 year, 37 patients of the ACS group suffered an event. Treatment in the ED compared with the CPU showed a significant increase in hazard ratio of 2.1 (P = 0.034) for the combined endpoint death, myocardial infarction and stroke, remaining unchanged after adjusting for confounders. Event-free 1-year survival was higher in CPU patients for the combined endpoint (P (logrank) = 0.02). These results demonstrate a better 1-year prognosis for ACS patients treated in the CPU instead of the ED, therefore, supporting the idea to establish CPUs in Europe.

Clinical Outcome 2 Years After Intracoronary Administration of Bone Marrow–Derived Progenitor Cells in Acute Myocardial Infarction

The aim of this study was to investigate the clinical outcome 2 years after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). Using a double-blind, placebo-controlled, multicenter trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone marrow-derived progenitor cells (BMC) or placebo medium into the infarct artery 3 to 7 days after successful infarct reperfusion therapy. At 2 years, the cumulative end point of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (hazard ratio, 0.58; 95% CI, 0.36 to 0.94; P=0.025). Likewise, the combined end point death and recurrence of myocardial infarction and rehospitalization for heart failure, reflecting progression toward heart failure, was significantly reduced in the BMC group (hazard ratio, 0.26; 95% CI, 0.085 to 0.77; P=0.015). Intracoronary administration of BMC remained a significant predictor of a favorable clinical outcome by Cox regression analysis when adjusted for classical predictors of poor outcome after AMI. There was no evidence of increased restenosis or atherosclerotic disease progression after BMC therapy nor any evidence of increased ventricular arrhythmias or neoplasms. In addition, regional left ventricular contractility of infarcted segments, as assessed by MRI in a subgroup of patients at 2-year follow-up, was significantly higher in the BMC group compared with the placebo group (P<0.001). Intracoronary administration of BMC is associated with a significant reduction of the occurrence of major adverse cardiovascular events maintained for 2 years after AMI. Moreover, functional improvements after BMC therapy may persist for at least 2 years. Larger studies focusing on clinical event rates are warranted to confirm the effects of BMC administration on mortality and progression of heart failure in patients with AMIs. Clinical Trial Registration- clinicaltrials.gov. Identifier: NCT00279175.

New players in the field of antiplatelet and anticoagulant therapy in coronary heart disease - current therapeutic issues and hot topics

The development of anticoagulants started in the 1930s with the discovery and availability of parenteral heparin. In the 1950s, oral vitamin K antagonists found their way into clinical therapeutics. Although both components are flawed with considerable limitations such as a narrow therapeutic window, an unpredictable anticoagulatory effect, drug-interactions and the necessity of continuous aPTT/INR-monitoring, they have been the only anticoagulants for prophylaxis and therapy of thromboembolic disorders for several decades [Alban, 2005]. The first step toward more predictable anticoagulatory activity of unfractionated heparin (UFH) was the development of low molecular weight heparins (LMWHs) in the 1980s. This family of heparins features a higher ratio of anti-Xa and anti-IIa activity, lower plasma protein interactions and renal elimination and, as a consequence, they do not require routine monitoring of their antithrombotic effect. Today, enoxaparin and dalteparin are the only LMWHs which are also indicated for use in patients with unstable angina/NSTEMI, STEMI with percutaneous coronary intervention (PCI) (enoxaparin) and in combination with aspirin for patients with unstable angina/NSTEMI (dalteparin) [Anderson et al. 2007]. Aspirin therapy is still a cornerstone of antiplatelet therapy in cardiovascular medicine since the early 1980s when the Veterans Administration Cooperative Study revealed significantly protective effects, reducing nonfatal myocardial infarction and the combined endpoint of death or myocardial infarction (MI), by 51% [Lewis et al. 1983]. Aspirin therapy in combination with P2Y12-inhibition with clopidogrel (which binds highly selectively to the P2Y12receptor on the surface of platelets and selectively blocks ADP-induced platelet aggregation) is today still the recommended platelet inhibitory treatment regimen for patients presenting with an acute coronary syndrome (ACS) and in those undergoing PCI and stent implantation [Anderson et al. 2007]. Although undoubtedly beneficial in reducing the risk for adverse thrombotic events in a broad range of cardiovascular patients, we are nowadays more and more recognizing several limitations to this treatment regimen: On the one hand, 15 40% of patients are poor responders to treatment, as evaluated by ADP-induced platelet aggregation and several trials show that such patients are at increased risk of stent thrombosis, MI and death [Wallentin, 2009]. On the other hand, the risk for bleeding is substantially increased by dual antiplatelet therapy. Assuming a baseline risk for major bleeding of 1.9% over a 13 month period based on the mean event rate in patients treated with aspirin alone in the 4 longer term clinical trials, an 80% increase in the odds of major bleeding is equivalent to an absolute risk increase of 1.5% [Bowry et al. 2008]. In other words, the number needed to treat (NNT) for 13 months to cause one additional major haemorrhage is only 66. It is assumed today that the use of dual therapy in patients with acute coronary syndrome (ACS), especially in the acute phase, has a favourable risk/benefit ratio, whereas in stable patients with cardiovascular disease, it is associated with an increased risk for bleeding [Eshaghian et al. 2007].