Do omega-3 polyunsaturated fatty acids reduce risk of sudden cardiac death and ventricular arrhythmias? A meta-analysis of randomized trials.

INTRODUCTION: Omega-3 polyunsaturated fatty acids (PUFA) have demonstrated to have antiarrhythmic properties. However, randomized studies have shown inconsistent results. OBJECTIVE: We aimed to analyze the effect of omega-3 PUFA on preventing potentially fatal ventricular arrhythmias and sudden cardiac death. METHODS: Randomized trials comparing omega-3 PUFA to placebo and reporting sudden cardiac death (SCD) or first implanted cardioverter-defibrillator (ICD) event for ventricular tachycardia or fibrillation were included in this study. A meta-analysis using a random effects model was performed and results were expressed in terms of Odds Ratio (OR) and 95% Confidence Interval (CI) after evaluating for interstudy heterogeneity using I(2). The reported data were extracted on the basis of the intention-to-treat principle. RESULTS: A total of 32,919 patients were included in nine trials; 16,465 patients received omega-3 PUFA and 16,454 received placebo. When comparing omega-3 PUFA to placebo, there was nonsignificant risk reduction of SCD or ventricular arrhythmias (OR = 0.82 [95% CI: 0.60-1.21], p = 0.21 I(2) = 49.7%). CONCLUSION: Dietary supplementation with omega-3 PUFA does not affect the risk of SCD or ventricular arrhythmias.

Low admission triglyceride and mortality in acute coronary syndrome patients.

BACKGROUND: The relationship between admission triglyceride (TG) levels and long-term outcomes has not been established in patients with acute coronary syndrome. We tested the hypothesis that patients who develop non-ST segment elevation myocardial infarction (NSTEMI) despite low TG have a worse cardiovascular outcome in the long term. METHODS: Patients admitted with NSTEMI between 1 January 1997 and 31 December 2000 and with fasting lipid profiles measured within 24 hours of admission were included for analysis. Baseline characteristics and three-year all-cause mortality were compared between the patients with TG above and below the median. Multivariate analysis was used to determine the predictors of all-cause mortality and adjusted survival was analyzed using the Cox proportional hazard model. RESULTS: Of 517 patients, 395 had TG £ 200 mg/dL and 124 had TG > 200 mg/dL. Patients with low TG were more often Caucasian, with no significant differences in gender or severity of coronary artery disease between the two groups. There was a trend for increased all-cause mortality at six months (9% vs 3%, p = 0.045) and three years (13.4% vs 5.6%, p = 0.016) in patients with low TG. In multivariate analysis, low TG level at admission was an independent predictor of increased mortality at three years (adjusted OR 2.5, 95% CI = 1.04-5.9, p = 0.04). CONCLUSIONS: In our cohort, lower TG at admission is associated with increased three-year mortality in patients with NSTEMI. Whether this is a result of current therapy, or a marker for worse baseline characteristics, needs to be studied further.

Low admission LDL-cholesterol is associated with increased 3-year all-cause mortality in patients with non ST segment elevation myocardial infarction.

BACKGROUND: The relationship between admission low-density lipoprotein (LDL) levels and long-term outcomes has not been established in patients with acute coronary syndrome. We tested the hypothesis that patients who develop non-ST segment elevation myocardial infarction (NSTEMI) despite low LDL have a worse cardiovascular outcome in the long term. METHODS: Patients admitted with NSTEMI between 1 January 1997 and 31 December 2000 and with fasting lipid profiles measured within 24 hours of admission were selected for analysis. Baseline characteristics and 3-year all-cause mortality were compared between the patients with LDL above and below the median. Multivariate analysis was used to determine the predictors of all-cause mortality, and adjusted survival was analyzed using the Cox proportional hazard model. RESULTS: Of the total of 517 patients, 264 had LDL 105 mg/dL. There was no difference in age, gender, severity of coronary artery disease, and left ventricular ejection fraction between the 2 groups. Thirty-six percent of patients with LDL 105 mg/dL were on lipid-lowering therapy on admission. After 3 years, patients with admission LDL 105 mg/dL (14.8% vs. 7.1%, p = 0.005). The higher all-cause mortality persisted (OR 1.8, 95% CI 1.0-3.5, p = 0.05) even after adjustment for confounding variables. CONCLUSIONS: In our cohort, lower LDL-cholesterol at admission was associated with decreased 3-year survival in patients with NSTEMI. Whether this was a result of current therapy or a marker for worse baseline characteristics needs to be studied further.

The recognition of acute coronary ischemia in the outpatient setting.

BACKGROUND: The missed diagnosis of acute myocardial infarction has been studied in the Emergency Department, but few studies have investigated how often coronary ischemia is correctly identified in the outpatient setting. METHODS: This was a single center retrospective observational study of patients with Health Alliance Plan medical insurance hospitalized at a US tertiary center with acute myocardial infarction in 2004. Outpatient encounters in the 30 days preceding acute myocardial infarction were reviewed by two independent cardiologists for presenting symptoms and diagnostic decision-making in order to classify patient presentations as acute coronary ischemia, stable angina or neither. RESULTS: There were 331 patients with acute myocardial infarction, including 190 (57%) with a primary diagnosis of AMI and evaluated by a physician in the preceding 30 days. This group included 68 patients with 95 documented outpatient encounters by a primary care physician, cardiologist, or other internal medicine specialist which formed the final study population. Mean interval between these encounters and AMI was 17 +/- 11 days. Of these patients, 7 (10%) had symptoms of acute coronary ischemia, 5 (7%) had stable angina symptoms, and 56 (83%) had no symptoms of coronary ischemia at their outpatient encounters. Of the 7 patients with acute coronary ischemic symptoms, 5 were correctly identified and 2 were misidentified. CONCLUSION: A majority of patients with subsequent AMI visit an outpatient provider in the month preceding AMI. However, few present with symptoms of coronary ischemia in the outpatient setting (10%) and these symptoms are not always identified as such.

R-wave amplitude changes measured by electrocardiography during early transmural ischemia.

BACKGROUND: Changes in the amplitude of the R wave (RWA) on the electrocardiogram (ECG) have been described during acute myocardial ischemia and infarction. However, this has not been well studied in a controlled setting. We hypothesized that significant increase in RWA occurs during early transmural myocardial ischemia. METHODS: We prospectively evaluated changes in RWA in 50 patients during brief episodes of transmural ischemia induced by first balloon occlusion (mean, 38 seconds at 6-10 atmospheric pressures) during elective percutaneous coronary intervention. We recorded 12-lead ECGs at 20-second intervals before and during balloon inflation in 16 right coronary arteries, 14 left circumflex arteries, and 20 left anterior descending arteries. R wave amplitude was digitally measured in each of the 12 leads in every ECG using the ECG interval editor (General Electric HC, Menomonee Falls, WI). Intracoronary (IC) ECGs were also recorded in 4 patients. The mean of the RWA in each lead before balloon inflation was compared to the mean RWA during balloon inflation. RESULTS: R wave amplitude significantly increased during balloon inflation from baseline in limb leads I, II, aVL, and all the precordial leads with the exception of lead V(1). The RWA increase did not reach statistical significance in leads III, aVF, and V(1). Mean RWA increase was consistent in all leads except aVR during the brief episodes of ischemia during initial balloon inflation because of the inverse polarity of this lead. The increase in RWA was seen in most patients (mean, 75%) in whom transmural ischemia was induced by first balloon inflation. Besides, the RWA showed an increase from baseline in 3 patients who had IC-lead recordings. CONCLUSION: R wave amplitude increases significantly in precordial leads (V(2)-V(6)) and limb leads (I, II, aVL) of the surface ECG during brief episodes of transmural ischemia. The increase in RWA might be consistent with the expansion of the left ventricular cavity during ischemia and/or alterations in conduction that are intrinsic to the myocardium.

Active Lipid Management In Coronary Artery Disease (ALMICAD) study.

PURPOSE: Many providers have implemented specialized lipid clinics to more effectively identify, monitor, and treat hyperlipidemia in patients with coronary artery disease. The effectiveness of such a strategy is not known. We sought to investigate whether a specialized clinic achieves better lipid results and clinical outcomes than standard care. SUBJECTS AND METHODS: A total of 1233 patients who had coronary disease documented by coronary angiography were randomized to lipid clinic or standard care groups by their providers and followed for 2 years. The primary end point was a composite of death, myocardial infarction, repeat revascularization, and stroke. RESULTS: Lipid clinic (n=617) and standard care (n=616) groups had no significant baseline differences. After 2 years, the lipid clinic group had similar total cholesterol (166+/-42 mg/dL vs 166+/-41 mg/dL, P=.83), low-density lipoprotein cholesterol levels (84+/-32 vs 85+/-32, P=.28), and percentage of patients with low-density lipoprotein cholesterol less than 100 mg/dL (77.5% vs 77.6%, P=.97). There were no significant differences in the primary end point (12.3% vs 11.4%, P=.60) and mortality (7.6% vs 7.3%, P=.80) between the lipid clinic and standard care groups. CONCLUSIONS: In patients identified by diagnostic coronary angiography and managed within a single health care system, implementation of a specialized lipid clinic did not achieve greater attainment of hyperlipidemia treatment goals or improved cardiac outcomes.

Temporal trends, safety, and efficacy of bivalirudin in elective percutaneous coronary intervention: insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium.

OBJECTIVE: To evaluate the safety and efficacy of bivalirudin based therapy among patients undergoing percutaneous coronary intervention (PCI) for stable coronary artery disease in a large multicenter registry. BACKGROUND: The REPLACE I trial demonstrated the non-inferiority of a strategy of bivalirudin compared with heparin and glycoprotein (GP) IIbIIIa inhibition in patients undergoing PCI. There is a paucity of outcome data with bivalirudin use in the setting of real-world PCI practice. METHODS: We evaluated the outcome of 11,719 patients who underwent elective PCI for stable coronary artery disease (CAD) from 2002 to 2004 in a large regional consortium, and who were treated with bivalirudin (n = 2051) or with heparin and GP IIbIIIa inhibitors (n = 9,668). The primary endpoints were transfusion and in-hospital major adverse cardiovascular events (MACE) defined as the composite of death, MI, stroke, and any coronary artery bypass grafting (CABG) or target lesion revascularization. RESULTS: Compared with patients who received heparin plus GP IIbIIIa inhibitors, patients who received bivalirudin had a similar incidence of post-procedural MI, stroke, in-hospital death, MACE (2.88 vs. 2.48, P = 0.30), or transfusion (2.83% vs. 2.41%, P = 0.27). Patients at greater risk of bleeding were more likely to be treated with bivalirudin. After adjusting for the propensity to receive bivalirudin and for baseline co-morbidities, there was no difference in the odds of MACE or the need for transfusion between the two groups. CONCLUSION: Compared with heparin plus GP IIbIIIa inhibition, use of bivalirudin in patients undergoing PCI for stable CAD is associated with similar ischemic and bleeding complications. Given the ease of administration and lower cost, bivalirudin provides an attractive treatment option in this patient population.

Left atrial reverse remodeling in dogs with moderate and advanced heart failure treated with a passive mechanical containment device: an echocardiographic study.

BACKGROUND: Assessment of global left ventricular (LV) remodeling is important in evaluating the efficacy of pharmacologic and device therapies for the treatment of chronic heart failure (HF). The effects of pharmacologic or device therapies on global left atrial (LA) remodeling in HF, although also important, are not often examined. We showed that long-term therapy with the Acorn Cardiac Support Device (CSD), a passive mechanical ventricular containment device, prevents or reverses LV remodeling in dogs with HF. This study examined the effects of the CSD on global LA remodeling in dogs with moderate and advanced HF. METHODS AND RESULTS: Studies were performed in 24 dogs with coronary microembolization-induced HF. Of these, 12 had moderate HF (ejection fraction, EF 30% to 40%) and 12 advanced HF (EF < or = 25%). In each group, the CSD was implanted in 6 dogs and the other 6 served as controls. Dogs were followed for 3 months in the moderate group and 6 months in the advanced HF group. LA maximal volume (LAVmax), LA volume at the onset of the p-wave (LAVp), LA minimal volume (LAVmin), LA active emptying volume (LAAEV), and LA active emptying fraction (LAAEF) were measured from 2-dimensional echocardiograms obtained before CSD implantation and at the end of the treatment period. Treatment effect (delta) comparisons between CSD-treated dogs and controls showed that CSD therapy significantly decreased LA volumes (deltaLAVmax: 3.33 +/- 0.70 vs. -2.87 +/- 1.31 mL, P = .002; 7.77 +/- 1.76 versus -0.37 +/- 0.87 mL, P = .002) and improved LA function (deltaLAAEF: -6.00 +/- 1.53 versus 1.85 +/- 1.32%, P = .003; -2.39 +/- 1.10 versus 3.13 +/- 1.66%, P = .02) in the moderate HF and advanced HF groups, respectively. CONCLUSIONS: Progressive LA enlargement and LA functional deterioration occurs in untreated dogs with HF. Monotherapy with the CSD prevents LA enlargement and improves LA mechanical function in dogs with moderate and advanced HF indicating prevention or reversal of adverse LA remodeling.

Prolongation of the QTc interval is seen uniformly during early transmural ischemia.

OBJECTIVES: In order to more clearly understand the electrocardiographic manifestations of early transmural ischemia, we studied electrocardiograms (ECGs) in patients undergoing balloon angioplasty. BACKGROUND: Decisions regarding reperfusion strategies in patients with acute myocardial infarction rely largely on the presence of ST-segment elevation (STE) in the ECG, consequently with significant limitations. Studies of the "ischemic cascade" show that ST-segment changes occur well after the onset of wall motion abnormalities. METHODS: We prospectively analyzed ECGs obtained at 20-s intervals in 74 patients undergoing elective balloon angioplasty. The ECGs were analyzed using 3 methodologies. In 74 patients, the ST-segment, the T-wave, and the QT-interval were analyzed using the MUSE (General Electric HC, Menomonee Falls, Wisconsin) automated system (MUSE). Fifty patients were also analyzed using the Interval Editor automated system (IE; General Electric HC). In 20 patients, measurements were made manually. RESULTS: Transmural ischemia prolonged the QTc interval (using the Bazett's formula) in 100% of patients. In all 74 patients analyzed with MUSE, QTc interval prolonged from 423 +/- 25 ms to 455 +/- 34 ms (p < 0.001). In the 50 patients analyzed with IE, QTc interval prolonged in 50 of 50 (100%) patients (from 424 +/- 27 ms to 458 +/- 33 ms [p < 0.001]). Mean time to maximal QTc interval prolongation, changes in T-wave polarity, > or =1 mm STE, and ST-segment depression (STD) were 22, 24, 29, and 35 s, respectively. Although QTc interval prolonged in 100% of patients, T-wave changes, STE, and STD (> or =1 mm) occurred in 7%, 15%, and 7%, respectively. CONCLUSIONS: The QTc interval prolongs in 100% of patients with early transmural ischemia. When compared with clinically accepted indexes of transmural ischemia (i.e., STD and STE [> or =1 mm]) it is the earliest ECG abnormality.

The efficacy and safety of combination glycoprotein IIbIIIa inhibitors and reduced-dose thrombolytic therapy-facilitated percutaneous coronary intervention for ST-elevation myocardial infarction: a meta-analysis of randomized clinical trials.

OBJECTIVE: We reviewed the literature and performed a meta-analysis comparing the safety and efficacy of adjunctive use of reduced-dose thrombolytics and glycoprotein (Gp) IIbIIIa inhibitors to the sole use of Gp IIbIIIa inhibitors before percutaneous coronary intervention (PCI) in patients presenting with acute ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Early reperfusion in STEMI is associated with improved outcomes. The use of reduced-dose thrombolytic and Gp IIbIIIa inhibitors combination before PCI in the setting of acute STEMI remains controversial. METHODS: We performed a literature search and identified randomized trials comparing the use of combination therapy-facilitated PCI versus PCI done with Gp IIbIIIa inhibitor alone. Included studies were reviewed to determine Thrombolysis in Myocardial Infarction (TIMI)-3 flow at baseline, major bleeding, 30-day mortality, TIMI-3 flow after PCI, and 30-day reinfarction. We performed a random-effect model meta-analysis. We quantified heterogeneity between studies with I2. A value >50% represents substantial heterogeneity. RESULTS: We identified 4 clinical trials randomizing 725 patients; 424 patients were pretreated with combination therapy before PCI, and 301 patients had Gp IIbIIIa inhibitor alone during PCI. Combination therapy-facilitated PCI was associated with a 2-fold increase in TIMI-3 flow upon arrival to the catheterization laboratory compared with the sole use of upstream Gp IIbIIIa inhibitors (192/390 patients [49%] versus 60/284 [21%]; relative risk [RR], 2.2; P < .00001). However, post-PCI TIMI-3 flow was similar between the 2 groups (279/319 patients [87%] versus 188/212 [88%]; RR, 0.99; P = .85). Major bleeding events significantly increased in the combination therapy group (40/420 patients [9.5%] versus 14/299 [4.7%]; RR, 2.2; P = .007). The 30-day mortality (15/424 patients [3.5%] versus 5/301 [1.7%]; RR, 1.47; P = .46) and 30-day reinfarction rate (5/424 patients [1.1%] versus 3/301 [1.0%]; RR, 0.96; P = .96) were similar in the 2 treatment groups. CONCLUSIONS: Awaiting the results of the ongoing clinical trials, the current cumulative evidence does not support the routine use of combination of reduced-dose thrombolytic and Gp IIbIIIa inhibitor therapy-facilitated PCI for the treatment of STEMI.

Long-term pharmacological activation of PPARgamma does not prevent left ventricular remodeling in dogs with advanced heart failure.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) activators affect the myocardium through inhibition of inflammatory cytokines and metabolic modulation but their effect in the progression of heart failure is unclear. In the present study, we examined the effects of the PPARgamma activator, GW347845 (GW), on the progression of heart failure. METHODS AND RESULTS: Heart failure was produced in 21 dogs by intracoronary microembolizations to LV ejection fraction (EF) less than 30% and randomized to 3 months of therapy with high-dose GW (10 mg/Kg daily, n = 7), low-dose GW (3 mg/Kg daily, n = 7), or no therapy (control, n = 7). In control dogs, EF significantly decreased (28 +/- 1 vs. 22 +/- 1%, p < 0.001) and end-diastolic volume (EDV) and end-systolic volume (ESV) increased during the 3 months of the follow-up period (64 +/- 4 vs. 76 +/- 5; p = 0.003, 46 +/- 3 vs. 59 +/- 4 ml, p = 0.002, respectively). In dogs treated with low-dose GW, EDV increased significantly (69 +/- 4 vs.81 +/- 5 ml, p = 0.01), whereas ESV remained statistically unchanged (50 +/- 3 vs. 54 +/- 3 ml, p = 0.10) resulting in modestly increased ejection fraction (27 +/- 1 vs. 32 +/- 3%, p = 0.05). In dogs treated with high-dose GW, both EDV and ESV increased (72 +/- 4 vs. 79 +/- 5 ml, p = 0.04; 53 +/- 3 vs. 62 +/- 5 ml, p = 0.04) and EF decreased (26 +/- 1 vs. 23 +/- 1%, p = 0.04) as with control dogs. There was significantly increased myocardial hypertrophy as evidenced by increased LV weight to body weight ratio and myocyte cross-section area in the GW treated animals compared to controls. Compared to control, treatment with GW had no effect on mRNA expression of PPARgamma, inflammatory cytokines, stretch response proteins, or transcription factors that may induce hypertrophy. CONCLUSIONS: Long-term PPARgamma activation with GW did not prevent progressive LV remodeling in dogs with advanced heart failure.

A meta-analysis of randomized control trials comparing minimally invasive direct coronary bypass grafting versus percutaneous coronary intervention for stenosis of the proximal left anterior descending artery.

Percutaneous intervention (PCI) and minimally invasive direct coronary bypass grafting (MIDCAB) are both well-accepted treatment options for isolated high-grade stenosis of proximal left anterior descending coronary artery. Small studies comparing the two modalities have yielded conflicting results. We performed a meta-analysis of randomized control trials to compare percutaneous intervention with minimally invasive coronary bypass grafting for isolated proximal left anterior descending artery stenosis. Five randomized trials with a total of 711 patients and average follow-up of 2.3 years were included in the analysis; 380 patients received stents and 331 underwent surgery. Only one trial used drug eluting stents. There were a small number of events overall in each trial. Difference between mortality was 12 events versus 15 between the PCI versus MIDCAB group. Similarly, the difference in myocardial infarction was 14 versus 10, and target vessel revascularization was 56 versus 19. The relative risk for stenting versus MIDCAB was 0.96 [(95% CI: 0.47, 1.99), p=0.92, I(2)=17.5%], for mortality and myocardial infarction, 0.77 [(95% CI: 0.30, 2.01), p=0.60, I(2)=10.4%] for mortality and 1.81 [(95% CI: 0.80, 4.06), p=0.15, I(2)=65.9%] for the composite end point of mortality, myocardial infarction and target vessel revascularization. Excluding the trial with drug eluting stents the relative risk for the composite outcome of mortality, myocardial infarction and target vessel revascularization was significantly higher for PCI [RR=2.27 (95% CI: 1.32, 3.90), p=0.003, I(2)=18.9%]. Overall mortality and myocardial infarction rates are similar for bare metal stents versus MIDCAB, but surgery was associated with significantly lower rates of repeat revascularization. The number of randomized patients and events were small. The effect of drug eluting stents might close the gap of repeat revascularization compared to MIDCAB for this disease.

Blood transfusion and in-hospital outcomes in anemic patients with myocardial infarction undergoing percutaneous coronary intervention.

Studies have shown poor prognostic implications of anemia in patients with myocardial infarction (MI) and in patients undergoing percutaneous coronary intervention (PCI). The impact of blood transfusion in these populations remains controversial. The objective of this study was to examine the effect of transfusion on in-hospital mortality in anemic patients undergoing PCI for MI. Data from 67,051 PCIs (June 1, 1997 to January 31, 2004) were prospectively collected in a multicenter registry (Blue Cross Blue Shield of Michigan Cardiovascular Consortium). Of these, 4,623 patients who were classified as anemic according to the World Health Organization criteria underwent PCI within 7 days of presentation with acute MI. A propensity score for being transfused was estimated for each patient, and propensity matching and a prediction model for in-hospital death were developed. The average age was 67.8 years, 57.7% of patients were men, and 22.3% of patients received a transfusion during hospitalization. Transfused patients, compared to nontransfused patients, were more likely to be older, female, have lower preprocedure hemoglobin levels, more comorbidities, and a higher unadjusted in-hospital mortality rate (14.52% vs. 3.01%, p < 0.0001). After adjustment for comorbidities and propensity for transfusion, blood transfusion was associated with a higher risk of in-hospital mortality (adjusted odds ratio = 2.02, 95% confidence interval 1.47-2.79, p < 0.0001). In anemic patients undergoing PCI for MI, transfusion was associated with an increased crude and adjusted rate of in-hospital mortality. A randomized controlled trial is needed to determine the value of transfusion and the ideal transfusion criteria.

Delay in invasive risk stratification of women with acute coronary syndrome is associated with worse outcomes.

BACKGROUND: Invasive risk stratification in patients with acute coronary syndromes (ACS) has been shown to improve outcomes. There is paucity of data on women undergoing invasive risk stratification. We investigated whether the time to coronary angiography affects survival of female patients admitted with ACS. METHOD: Female patients admitted to the coronary intensive care unit with ACS between 1/1/97 and 12/31/00 and undergoing coronary angiography during same hospitalization were divided into three groups based on the time to angiography: same day, 1-2 days and >2 days. The baseline clinical features, angiography results and outcomes were compared between the angiography groups. RESULTS: Of the total 350 female patients who fulfilled the inclusion criteria, 63% underwent angiography within two days of presentation. Three year mortality rates in women undergoing angiography on the same day, 1-2 days and >2-days were 7%, 7% and 22% respectively (p = 0.001). Using multivariate analysis, angiography beyond 2 days was a significant predictor of mortality among women (OR 2.6, 95% CI 1.3-5.0, p = 0.006) after adjusting for confounding variables. CONCLUSION: Later invasive risk stratification after 2 days of presentation in women with ACS is associated with worse survivial. Gender should not be a reason to defer early coronary angiography in these patients.

Cyclosporine A attenuates mitochondrial permeability transition and improves mitochondrial respiratory function in cardiomyocytes isolated from dogs with heart failure.

We used isolated cardiomyocytes to investigate a possible role of mitochondrial permeability transition pore in mitochondrial abnormalities associated with heart failure. Cardiomyocytes were isolated from LV myocardium of normal control dogs and dogs with heart failure produced by intracoronary microembolizations. Mitochondrial permeability transition was measured in isolated cardiomyocytes with intact sarcolemma with and without 0.2 microM cyclosporin A using calcein AM and the fluorometer. State-3 mitochondrial respiration was also measured with the Clark electrode. Mitochondrial membrane potential was measured with JC-1 probe using the fluorometer. Propidium iodide was used to ensure sarcolemma integrity. 200 min after loading with calcein AM, mitochondria of failing cardiomyocytes showed only 50% of maximal level of calcein fluorescence while it remained unchanged in normal cells. The mitochondrial membrane potential in failing cardiomyocytes was significantly decreased by 38% compared to normal cardiomyocytes. Cyclosporine A significantly slowed the exit of calcein from mitochondria of failing cardiomyocytes and increased mitochondrial membrane potential by 29%. State-3 respiration was not affected with cyclosporine A in normal cardiomyocytes while it was significantly increased in failing cardiomyocytes by 20%. Exit of calcein (m.w. 1.0 kDa) from mitochondria of viable failing cardiomyocytes with intact sarcolemma suggests an existence of a reversible transitory permeability transition opening in high conductance mode. Attenuation of calcein exit, DeltaPsi(m) and improvement of state-3 respiration achieved with CsA (0.2 microM) show that permeability transition opening could be a cause of mitochondrial dysfunction described in the failing heart.

Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry.

BACKGROUND: Although drug-eluting stents (DES) significantly reduce restenosis, they require 3 to 6 months of thienopyridine therapy to prevent stent thrombosis. The rate and consequences of prematurely discontinuing thienopyridine therapy after DES placement for acute myocardial infarction (MI) are unknown. METHODS AND RESULTS: We used prospectively collected data from a 19-center study of MI patients to examine the prevalence and predictors of thienopyridine discontinuation 30 days after DES treatment. We then compared the mortality and cardiac hospitalization rates for the next 11 months between those who stopped and those who continued thienopyridine therapy. Among 500 DES-treated MI patients who were discharged on thienopyridine therapy, 68 (13.6%) stopped therapy within 30 days. Those who stopped were older, less likely to have completed high school or be married, more likely to avoid health care because of cost, and more likely to have had preexisting cardiovascular disease or anemia at presentation. They were also less likely to have received discharge instructions about their medications or a cardiac rehabilitation referral. Patients who stopped thienopyridine therapy by 30 days were more likely to die during the next 11 months (7.5% versus 0.7%, P<0.0001; adjusted hazard ratio=9.0; 95% confidence interval=1.3 to 60.6) and to be rehospitalized (23% versus 14%, P=0.08; adjusted hazard ratio=1.5; 95% confidence interval=0.78 to 3.0). CONCLUSIONS: Almost 1 in 7 MI patients who received a DES were no longer taking thienopyridines by 30 days. Prematurely stopping thienopyridine therapy was strongly associated with subsequent mortality. Strategies to improve the use of thienopyridines are needed to optimize the outcomes of MI patients treated with DES.

Spontaneous late thrombolysis of an occluded saphenous vein graft subsequent to acute myocardial infarction treated with percutaneous coronary intervention to the native culprit vessel.

A 67-year-old male with prior history of myocardial infarction and coronary artery bypass grafting (individual vein grafts to the left anterior descending artery [LAD] and right coronary artery) presented with an acute anterior ST elevation myocardial infarction and cardiogenic shock. The vein graft to the LAD was occluded with heavy thrombus burden and there was severe native CAD. Given the degree of thrombus burden and other anatomic considerations, percutaneous intervention with stenting was performed to the native proximal LAD. Three months later, after complaining of atypical chest pain, repeat angiogram revealed a spontaneous widely patent vein graft to the LAD and occluded proximal LAD.

Association of a continuous quality improvement initiative with practice and outcome variations of contemporary percutaneous coronary interventions.

BACKGROUND: The objective of this study was to evaluate the association of a continuous quality improvement program with practice and outcome variations of percutaneous coronary intervention (PCI). METHODS AND RESULTS: Data on consecutive PCI were collected in a consortium of 5 hospitals; 3731 PCIs reflected care provided at baseline (January 1, 1998, to December 31, 1998), and 5901 PCIs reflected care provided after implementation of a continuous quality improvement intervention (January 1, 2002, to December 31, 2002). The intervention included feedback on outcomes, working group meetings, site visits, selection of quality indicators, and use of bedside tools for quality improvement and risk assessment. Postintervention data were compared with baseline and with 10,287 PCIs from 7 hospitals added to the consortium in 2002. Quality indicators included use of preprocedural aspirin or clopidogrel, use of glycoprotein IIb/IIIa receptor blockers and postprocedural heparin, and amount of contrast media per case. Outcomes selected included emergency CABG, contrast nephropathy, myocardial infarction, stroke, transfusion, and in-hospital death. Compared with baseline and the control group, the intervention group at follow-up had higher use of preprocedural aspirin and glycoprotein IIb/IIIa blockers, lower use of postprocedural heparin, and a lower amount of contrast media per case (P<0.05). These changes were associated with lower rates of transfusions, vascular complications, contrast nephropathy, stroke, transient ischemic attack, and combined end points (all P<0.05). CONCLUSIONS: Our nonrandomized, observational data suggest that implementation of a regional continuous quality improvement program appears to be associated with enhanced adherence to quality indicators and improved outcomes of PCI. A randomized clinical trial is needed to determine whether this is a "causal" or a "casual" relationship.

Selective matrix metalloproteinase inhibition attenuates progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure.

Matrix metalloproteinases (MMPs) contribute to the progression of left ventricular (LV) dysfunction and remodeling associated with heart failure (HF). The present study examined the long-term effects of a selective MMP inhibitor PG-530742 (PG) on the progression of LV dysfunction and remodeling in dogs with HF. Chronic HF [LV ejection fraction (LVEF),