Chagas' heart disease: gender differences in myocardial damage assessed by cardiovascular magnetic resonance.

BACKGROUND: Since a male-related higher cardiovascular morbidity and mortality in patients with Chagas' heart disease has been reported, we aimed to investigate gender differences in myocardial damage assessed by cardiovascular magnetic resonance (CMR). METHODS AND RESULTS: Retrospectively, 62 seropositive Chagas' heart disease patients referred to CMR (1.5 T) and with low probability of having significant coronary artery disease were included in this analysis. Amongst both sexes, there was a strong negative correlation between LV ejection fraction and myocardial fibrosis (male r = 0.64, female r = 0.73, both P < 0.001), with males showing significantly greater myocardial fibrosis (P = 0.002) and lower LV ejection fraction (P < 0.001) than females. After adjustment for potential confounders, gender remained associated with myocardial dysfunction, and 53% of the effect was mediated by myocardial fibrosis (P for mediation = 0.004). Also, the transmural pattern was more prevalent among male patients (23.7 vs. 9.9%, P < 0.001) as well as the myocardial heterogeneity or gray zone (2.2 vs. 1.3 g, P = 0.003). CONCLUSIONS: We observed gender-related differences in myocardial damage assessed by CMR in patients with Chagas' heart disease. As myocardial fibrosis and myocardial dysfunction are associated to cardiovascular outcomes, our findings might help to understand the poorer prognosis observed in males in Chagas' disease.

Alterations in lipid transfers to HDL associated with the presence of coronary artery disease in patients with type 2 diabetes mellitus.

BACKGROUND: We previously showed that unesterified-cholesterol transfer to high-density lipoprotein (HDL), a crucial step in cholesterol esterification and role in reverse cholesterol transport, was diminished in non-diabetic patients with coronary artery disease (CAD). The aim was to investigate whether, in patients with type 2 diabetes mellitus (T2DM), the occurrence of CAD was also associated with alterations in lipid transfers and other parameters of plasma lipid metabolism. METHODS: Seventy-nine T2DM with CAD and 76 T2DM without CAD, confirmed by cineangiography, paired for sex, age (40-80 years), BMI and without statin use, were studied. In vitro transfer of four lipids to HDL was performed by incubating plasma of each patient with a donor emulsion containing radioactive lipids during 1 h at 37 °C. Lipids transferred to HDL were measured after chemical precipitation of non-HDL fractions and the emulsion. Results are expressed as % of total radioactivity of each lipid in HDL. RESULTS: In T2DM + CAD, LDL-cholesterol and apo B were higher than in T2DM. T2DM + CAD also showed diminished transfer to HDL of unesterified cholesterol (T2DM + CAD = 7.6 ± 1.2; T2DM = 8.2 ± 1.5%, p < 0.01) and of cholesteryl-esters (4.0 ± 0.6 vs 4.3 ± 0.7, p < 0.01). Unesterified cholesterol in the non-HDL serum fraction was higher in T2DM + CAD (0.93 ± 0.20 vs 0.85 ± 0.15, p = 0.02) and CETP concentration was diminished (2.1 ± 1.0 vs 2.5 ± 1.1, p = 0.02). Lecithin-cholesterol acyltransferase activity, HDL size and lipid composition were equal. CONCLUSION: Reduction in T2DM + CAD of cholesterol transfer to HDL may impair cholesterol esterification and reverse cholesterol transport and altogether with simultaneous increased plasma unesterified cholesterol may facilitate CAD development in T2DM.

Myocardial tissue characterization in Chagas' heart disease by cardiovascular magnetic resonance.

BACKGROUND: Chagas' heart disease is an important public health problem in South America. Several aspects of the pathogenesis are not fully understood, especially in its subclinical phases. On pathology Chagas' heart disease is characterized by chronic myocardial inflammation and extensive myocardial fibrosis. The latter has also been demonstrated by late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR). In three clinical phases of this disease, we sought to investigate the presence of LGE, myocardial increase in signal intensity in T2-weighted images (T2W) and in T1-weighted myocardial early gadolinium enhancement (MEGE), previously described CMR surrogates for myocardial fibrosis, myocardial edema and hyperemia, respectively. METHODS: Fifty-four patients were analyzed. Sixteen patients with the indeterminate phase (IND), seventeen patients with the cardiac phase with no left ventricular systolic dysfunction (CPND), and twenty-one patients with the cardiac phase with left ventricular systolic dysfunction (CPD). All patients underwent 1.5 T CMR scan including LGE, T2W and MEGE image sequences to evaluate myocardial abnormalities. RESULTS: Late gadolinium enhancement was present in 72.2 % of all patients, in 12.5 % of IND, 94.1 % of the CPND and 100 % of the CPD patients (p < 0.0001). Myocardial increase in signal intensity in T2-weighted images (T2W) was present in 77.8 % of all patients, in 31.3 % of the IND, 94.1 % of the CPND and 100 % of the CPD patients (p < 0.0001). T1-weighted myocardial early gadolinium enhancement (MEGE) was present in 73.8 % of all patients, in 25.0 % of the IND, 92.3 % of the CPND and 94.1 % of the CPD (p < 0.0001). A good correlation between LGE and T2W was observed (r = 0.72, and p < 0.001). CONCLUSIONS: Increase in T2-weighted (T2W) myocardial signal intensity and T1-weighted myocardial early gadolinium enhancement (MEGE) can be detected by CMR in patients throughout all phases of Chagas' heart disease, including its subclinical presentation (IND). Moreover, those findings were parallel to myocardial fibrosis (LGE) in extent and location and also correlated with the degree of Chagas' heart disease clinical severity. These findings contribute to further the knowledge on pathophysiology of Chagas' heart disease, and might have therapeutic and prognostic usefulness in the future.

Effects of cardiac resynchronization therapy on muscle sympathetic nerve activity.

INTRODUCTION: Muscle sympathetic nerve activity (MSNA) is an independent prognostic marker in patients with heart failure (HF). Therefore, its relevance to the treatment of HF patients is unquestionable. OBJECTIVES: In this study, we investigated the effects of cardiac resynchronization therapy (CRT) on MSNA response at rest and during exercise in patients with advanced HF. METHODS: We assessed 11 HF patients (51 ± 3.4 years; New York Heart Association class III-IV; left ventricular ejection fraction 27.8 ± 2.2%; optimal medical therapy) submitted to CRT. Evaluations were made prior to and 3 months after CRT. MSNA was performed at rest and during moderate static exercise (handgrip). Peak oxygen consumption (VO2 ) was evaluated by means of cardiopulmonary exercise test. HF patients with advanced NYHA class without CRT and healthy individuals were also studied. RESULTS: CRT reduced MSNA at rest (48.9 ± 11.1 bursts/min vs 33.7 ± 15.3 bursts/min, P < 0.05) and during handgrip exercise (MSNA 62.3 ± 13.1 bursts/min vs 46.9 ± 14.3 bursts/min, P < 0.05). Among HF patients submitted to CRT, the peak VO2 increased (12.9 ± 2.8 mL/kg/min vs 16.5 ± 3.9 mL/kg/min, P < 0.05) and an inverse correlation between peak VO2 and resting MSNA (r = -0.74, P = 0.01) was observed. CONCLUSIONS: In patients with advanced HF and severe systolic dysfunction: (1) a significant reduction of MSNA (at rest and during handgrip) occurred after CRT, and this behavior was significantly superior to HF patients receiving only medical therapy; (2) MSNA reduction after CRT had an inverse correlation with O2 consumption outcomes.

Impact of diabetes on 10-year outcomes of patients with multivessel coronary artery disease in the Medicine, Angioplasty, or Surgery Study II (MASS II) trial.

INTRODUCTION: Diabetes mellitus is a major cause of coronary artery disease (CAD). Despite improvement in the management of patients with stable CAD, diabetes remains a major cause of increased morbidity and mortality. There is no conclusive evidence that either modality is better than medical therapy alone for the treatment of stable multivessel CAD in patients with diabetes in a very long-term follow-up. Our aim was to compare 3 therapeutic strategies for stable multivessel CAD in a diabetic population and non-diabetic population. METHODS: It was compared medical therapy (MT), percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) in 232 diabetic patients and 379 nondiabetic patients with multivessel CAD. Endpoints evaluated were overall and cardiac mortality. RESULTS: Patients (n = 611) were randomized to CABG (n = 203), PCI (n = 205), or MT (n = 203). In a 10-year follow-up, more deaths occurred among patients with diabetes than among patients without diabetes (P = .001) for overall mortality. In this follow-up, 10-year mortality rates were 32.3% and 23.2% for diabetics and non-diabetics respectively (P = .024). Regarding cardiac mortality, 10-year cardiac mortality rates were 19.4% and 12.7% respectively (P = .031).Considering only diabetic patients and stratifying this population by treatment option, we found mortality rates of 31.3% for PCI, 27.5% for CABG and 37.5% for MT (P = .015 for CABG vs MT) and cardiac mortality rates of 18.8%, 12.5% and 26.1% respectively (P = .005 for CABG vs MT). CONCLUSIONS/INTERPRETATION: Among patients with stable multivessel CAD and preserved left ventricular ejection fraction, the 3 therapeutic regimens had high rates of overall and cardiac-related deaths among diabetic compared with non-diabetic patients. Moreover, better outcomes were observed in diabetic patients undergoing CABG compared to MT in relation to overall and cardiac mortality in a 10-year follow-up.

Atorvastatin treatment improves myocardial and peripheral blood flow in familial hypercholesterolemia subjects without evidence of coronary atherosclerosis.

BACKGROUND: Hypercholesterolemia induces early microcirculatory functional and structural alterations that are reversible by cholesterol reduction. Real time myocardial contrast echocardiography (RTMCE) and vascular ultrasound evaluate the effects of hyperlipidemia on peripheral and central blood flow reserve. This study investigated the effects of lipid-lowering therapy on coronary and peripheral artery circulation in patients with familial hypercholesterolemia (FH). METHODS: RTMCE and vascular ultrasound were performed in 10 healthy volunteers (validation group) at baseline and after 12-week clinical observation, and in 16 age- and sex-matched FH patients without obstructive coronary artery disease (CAD) by computed tomography angiography at baseline and after 12-week atorvastatin treatment. Indexes of relative myocardial blood flow (MBF) were obtained at rest and during adenosine infusion. RESULTS: In validation group, there was no significant difference between flow-mediated dilation (FMD) at baseline and after 12 weeks (0.15 ± 0.02 vs. 0.14 ± 0.03; P = 0.39). Similarly, no differences were observed in MBF reserve at baseline and after 12 weeks (3.31 ± 0.63 vs. 3.48 ± 0.89; P = 0.89). FMD was blunted in FH patients, at baseline, as compared with validation group (0.08 ± 0.04 vs. 0.15 ± 0.02; P < 0.001) and became similar to that group (0.13 ± 0.05 vs. 0.14 ± 0.03; P = 0.07) after treatment. MBF reserve was blunted at baseline in FH patients in comparison with the validation group (2.78 ± 0.71 vs. 3.31 ± 0.63; P = 0.003). After treatment, MBF reserve values were no longer different (3.43 ± 0.66 and 3.48 ± 0.89; P = 0.84, respectively, for FH and validation groups). CONCLUSION: Patients with FH and no obstructive CAD have blunted MBF reserve and lower FMD values as compared with healthy volunteers. Both FMD and MBF reserve were normalized after atorvastatin treatment.

The Impact of Sonothrombolysis on Left Ventricular Diastolic Function and Left Atrial Mechanics Preventing Left Atrial Remodeling in Patients With ST Elevation Acute Myocardial Infarction.

BACKGROUND: The diagnostic ultrasound-guided high mechanical index impulses during an intravenous microbubble infusion (sonothrombolysis) improve myocardial perfusion in acute ST segment elevation myocardial infarction, but its effect on left ventricular diastolic dysfunction (DD), left atrial (LA) mechanics and remodeling is unknown. We assessed the effect of sonothrombolysis on DD grade and LA mechanics. METHODS: One hundred patients (59 ± 10 years; 34% women) were randomized to receive either high mechanical index impulses plus percutaneous coronary intervention (PCI) (therapy group) or PCI only (control group) (n = 50 in each group). Diastolic dysfunction grade and LA mechanics were assessed immediately before and after PCI and at 48 to 72 hours, 1 month, and 6 months of follow-up. Diastolic dysfunction grades were classified as grades I, II, and III. The LA mechanics was obtained by two-dimensional speckle-tracking echocardiography-derived global longitudinal strain (GLS). RESULTS: As follow-up time progressed, increased DD grade was observed more frequently in the control group than in the therapy group at 1 month and 6 months of follow-up (all P < .05). The LA-GLS values were incrementally higher in the therapy group when compared with the control group at 48 to 72 hours, 24.0% ± 7.3% in the therapy group versus 19.6% ± 7.2% in the control group, P = .005; at 1 month, 25.3% ± 6.3% in the therapy group versus 21.5% ± 8.3% in the control group, P = .020; and at 6 months, 26.2% ± 8.7% in the therapy group versus 21.6% ± 8.5% in the control group, P = .015. The therapy group was less likely to experience LA remodeling (odds ratio, 2.91 [1.10-7.73]; P = .03). LA-GLS was the sole predictor of LA remodeling (odds ratio, 0.79 [0.67-0.94]; P = .006). CONCLUSION: Sonothrombolysis is associated with better DD grade and LA mechanics, reducing LA remodeling.

Timing and dose of statin therapy define its impact on inflammatory and endothelial responses during myocardial infarction.

OBJECTIVE: Clinical trials of statins during myocardial infarction (MI) have differed in their therapeutic regimes and generated conflicting results. This study evaluated the role of the timing and potency of statin therapy on its potential mechanisms of benefit during MI. METHODS AND RESULTS: ST-elevation MI patients (n=125) were allocated into 5 groups: no statin; 20, 40, or 80 mg/day simvastatin starting at admission; or 80 mg/day simvastatin 48 hours after admission. After 7 days, all patients switched their treatment to 20 mg/day simvastatin for an additional 3 weeks and then underwent flow-mediated dilation in the brachial artery. As of the second day, C-reactive protein (CRP) differed between non-statin users (12.0±4.1 mg/L) and patients treated with 20 (8.5±4.0 mg/L), 40 (3.8±2.5 mg/L), and 80 mg/day (1.4±1.5 mg/L), and the daily differences remained significant until the seventh day (P<0.0001). The higher the statin dose, the lower the elevation of interleukin-2 and tumor necrosis factor-α, the greater the reduction of 8-isoprostane and low-density lipoprotein(-), and the greater the increase in nitrate/nitrite levels during the first 5 days (P<0.001). Later initiation of statin was less effective than its early introduction in relation to attenuation of CRP, interleukin-2, tumor necrosis factor-α, 8-isoprostane, and low-density lipoprotein(-), as well as in increase in nitrate/nitrite levels (P<0.0001). At the 30th day, there was no longer a difference in lipid profile or CRP between groups; the flow-mediated dilation, however, was proportional to the initial statin dose and was higher for those who started the treatment early (P=0.001). CONCLUSIONS: This study demonstrates that the timing and potency of statin treatment during MI are key elements for their main mechanisms of benefit. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00906451.

Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial.

BACKGROUND: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. METHODS/DESIGN: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. DISCUSSION: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.

Coronary atherosclerotic burden assessed by SYNTAX scores and outcomes in surgical, percutaneous or medical strategies: a retrospective cohort study.

INTRODUCTION: Coronary atherosclerotic burden and SYNTAX Score (SS) are predictors of cardiovascular events. OBJECTIVES: To investigate the value of SYNTAX scores (SS, SYNTAX Score II (SSII) and residual SYNTAX Score (rSS)) for predicting cardiovascular events in patients with coronary artery disease (CAD). DESIGN: Retrospective cohort study. SETTING: Single tertiary centre. PARTICIPANTS: Medicine, Angioplasty or Surgery Study database patients with stable multivessel CAD and preserved ejection fraction. INTERVENTIONS: Patients with CAD undergoing coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI) or medical treatment (MT) alone from January 2002 to December 2015. PRIMARY AND SECONDARY OUTCOMES: Primary: 5-year all-cause mortality. Secondary: composite of all-cause death, myocardial infarction, stroke and subsequent coronary revascularisation at 5 years. RESULTS: A total of 1719 patients underwent PCI (n=573), CABG (n=572) or MT (n=574) alone. The SS was not considered an independent predictor of 5-year mortality in the PCI (low, intermediate and high SS at 6.5%, 6.8% and 4.3%, respectively, p=0.745), CABG (low, intermediate and high SS at 5.7%, 8.0% and 12.1%, respectively, p=0.194) and MT (low, intermediate and high SS at 6.8%, 6.9% and 6.5%, respectively, p=0.993) cohorts. The SSII (low, intermediate and high SSII at 3.6% vs 7.9% vs 10.5%, respectively, p<0.001) was associated with a higher mortality risk in the overall population. Within each treatment strategy, SSII was associated with a significant 5-year mortality rate, especially in CABG patients with higher SSII (low, intermediate and high SSII at 1.8%, 9.7% and 10.0%, respectively, p=0.004) and in MT patients with high SSII (low, intermediate and high SSII at 5.0%, 4.7% and 10.8%, respectively, p=0.031). SSII demonstrated a better predictive accuracy for mortality compared with SS and rSS (c-index=0.62). CONCLUSIONS: Coronary atherosclerotic burden alone was not associated with significantly increased risk of all-cause mortality. The SSII better discriminates the risk of death. TRIAL REGISTRATION NUMBER: ISRCTN66068876.

Ten-year follow-up survival of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.

BACKGROUND: This study compared the 10-year follow-up of percutaneous coronary intervention (PCI), coronary artery surgery (CABG), and medical treatment (MT) in patients with multivessel coronary artery disease, stable angina, and preserved ventricular function. METHODS AND RESULTS: The primary end points were overall mortality, Q-wave myocardial infarction, or refractory angina that required revascularization. All data were analyzed according to the intention-to-treat principle. At a single institution, 611 patients were randomly assigned to CABG (n=203), PCI (n=205), or MT (n=203). The 10-year survival rates were 74.9% with CABG, 75.1% with PCI, and 69% with MT (P=0.089). The 10-year rates of myocardial infarction were 10.3% with CABG, 13.3% with PCI, and 20.7% with MT (P<0.010). The 10-year rates of additional revascularizations were 7.4% with CABG, 41.9% with PCI, and 39.4% with MT (P<0.001). Relative to the composite end point, Cox regression analysis showed a higher incidence of primary events in MT than in CABG (hazard ratio 2.35, 95% confidence interval 1.78 to 3.11) and in PCI than in CABG (hazard ratio 1.85, 95% confidence interval 1.39 to 2.47). Furthermore, 10-year rates of freedom from angina were 64% with CABG, 59% with PCI, and 43% with MT (P<0.001). CONCLUSIONS: Compared with CABG, MT was associated with a significantly higher incidence of subsequent myocardial infarction, a higher rate of additional revascularization, a higher incidence of cardiac death, and consequently a 2.29-fold increased risk of combined events. PCI was associated with an increased need for further revascularization, a higher incidence of myocardial infarction, and a 1.46-fold increased risk of combined events compared with CABG. Additionally, CABG was better than MT at eliminating anginal symptoms. Clinical Trial Registration Information- URL: http://www.controlled-trials.com. REGISTRATION NUMBER: ISRCTN66068876.

Five-year follow-up of a randomized comparison between off-pump and on-pump stable multivessel coronary artery bypass grafting. The MASS III Trial.

BACKGROUND: Coronary artery bypass graft surgery with cardiopulmonary bypass is a safe, routine procedure. Nevertheless, significant morbidity remains, mostly because of the body's response to the nonphysiological nature of cardiopulmonary bypass. Few data are available on the effects of off-pump coronary artery bypass graft surgery (OPCAB) on cardiac events and long-term clinical outcomes. METHODS AND RESULTS: In a single-center randomized trial, 308 patients undergoing coronary artery bypass graft surgery were randomly assigned: 155 to OPCAB and 153 to on-pump CAB (ONCAB). Primary composite end points were death, myocardial infarction, further revascularization (surgery or angioplasty), or stroke. After 5-year follow-up, the primary composite end point was not different between groups (hazard ratio 0.71, 95% CI 0.41 to 1.22; P=0.21). A statistical difference was found between OPCAB and ONCAB groups in the duration of surgery (240±65 versus 300±87.5 minutes; P<0.001), in the length of ICU stay (19.5±17.8 versus 43±17.0 hours; P<0.001), time to extubation (4.6±6.8 versus 9.3±5.7 hours; P<0.001), hospital stay (6±2 versus 9±2 days; P<0.001), higher incidence of atrial fibrillation (35 versus 4% of patients; P<0.001), and blood requirements (31 versus 61% of patients; P<0.001), respectively. The number of grafts per patient was higher in the ONCAB than the OPCAB group (2.97 versus 2.49 grafts/patient; P<0.001). CONCLUSIONS: No difference was found between groups in the primary composite end point at 5-years follow-up. Although OPCAB surgery was related to a lower number of grafts and higher episodes of atrial fibrillation, it had no significant implications related to long-term outcomes. Clinical Trial Registration-URL: http://www.controlled-trials.com. Unique identifier: ISRCTN66068876.

Influence of coronary artery disease assessment and treatment in the incidence of cardiac events in renal transplant recipients.

UNLABELLED: BACKGROUND: The best strategy for pre-transplant investigation and treatment of coronary artery disease (CAD) is controversial. METHODS: We evaluated 167 renal transplant recipients before transplantation to determine the incidence of cardiac events and death. We performed clinical evaluations and myocardial scans in all patients and coronary angiography in select patients. RESULTS: Asymptomatic patients with normal myocardial scans (n=57) had significantly fewer cardiac events (log-rank=0.0002) and deaths (log-rank=0.0005) than did patients with abnormal scans but no angiographic evidence of CAD (n=76) and individuals with CAD (n=34) documented angiographically. CAD increased the probability of events (HR=2.27, % CI 1.007-5.11; p=0.04). The incidence of cardiac events (log-rank=0.349) and deaths (log-rank=0.588) was similar among patients treated medically (n=23) or by intervention (n=11). CONCLUSION: Asymptomatic patients with normal myocardial scans had a better cardiac prognosis than did patients with or without CAD and positive for myocardial ischemia. Patients with altered scan and CAD had the poorer outcome. Guideline-oriented medical treatment is safe and yields results comparable to coronary intervention in renal transplant patients with CAD. The data do not support preemptive myocardial revascularization for renal transplant candidates.

Influence of Direct Thrombin Inhibitor and Low Molecular Weight Heparin on Platelet Function in Patients with Coronary Artery Disease: A Prospective Interventional Trial.

INTRODUCTION: The interaction between anticoagulants and platelet function is complex. Previous publications showed mixed results regarding the role of heparins in platelet aggregation. On the other hand, the direct thrombin inhibitor (DTI) dabigatran might enhance the risk of myocardial infarction in patients with atrial fibrillation, which could be related to increased platelet aggregability. METHODS: This was a prospective, interventional study of patients with chronic coronary artery disease (CAD) taking low-dose aspirin. The objective of the current study was to compare the effects of dabigatran versus enoxaparin on platelet aggregability. Subjects initially were on orally administered dabigatran for 5 days followed by subcutaneously administered enoxaparin after a 30-day washout period. Platelet function was assessed at baseline and after each intervention by multiple electrode aggregometry (MEA-ASPI) (primary endpoint), serum thromboxane B2 (TXB2), VerifyNow Aspirin™, and coagulation tests (secondary endpoints). RESULTS: Compared to baseline MEA-ASPI values, dabigatran increased platelet aggregation while enoxaparin decreased platelet aggregation (+ 5 U ± 24.1 vs - 6 U ± 22.2, respectively, p = 0.012). The TXB2 assay showed the same pattern (+ 2 pg/ml for dabigatran vs - 13 pg/ml for enoxaparin, p = 0.011). None of the additional tests showed significant differences between the groups. Individually, compared to baseline TXB2 results, enoxaparin significantly decreased platelet activation [33 (16.5-95) pg/mL vs 20 (10-52) pg/mL, respectively, p = 0.026], but no significant differences were observed with dabigatran. CONCLUSIONS: DTI and anti-Xa drugs exert opposite effects on platelet function. A significant decrease in platelet activation through COX1 (also known as prostaglandin G/H synthase 1) was observed with enoxaparin, but no significant differences in platelet function were observed with dabigatran. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02389582.

Effect of ischemic preconditioning on cardiovascular outcomes in patients with symptomatic coronary artery disease: a cohort study.

BACKGROUND: Despite the powerful myocardial protection of ischemic preconditioning (IP) observed in experimental studies, it remains a challenge to observe such protection in humans. Thus, the aim of this study was to evaluate the possible effects of IP on clinical outcomes in patients with coronary artery disease (CAD). PATIENTS AND METHODS: In this cohort study, patients with multivessel CAD, preserved systolic ventricular function, and stable angina were prospectively selected. They underwent two sequential exercise stress tests (EST) to evaluate IP presence. IP was considered present if patients had an improvement in the time to the onset of 1.0-mm STsegment deviation in the second EST. The primary end point was the composite rate of cardiac death, nonfatal myocardial infarction, or revascularization during 1-year follow-up. Patients with (IP+) and without (IP-) the cardioprotective mechanism were compared regarding clinical end points. RESULTS: A total of 229 patients completed EST and had IP evaluated: 165 (72%) were IP+ and 64 (28%) were IP - patients. Of these, 218 patients had complete follow-up. At 1-year, event-free survival regarding the primary end point was 95.5 versus 83.6% (P = 0.0024) and event-free survival regarding cardiac death or myocardial infarction was 99.4 versus 91.7% (P=0.0020), respectively, in IP + and IP - groups. The unadjusted hazard ratio (IP + /IP-) for the primary end point was 4.63 (1.52-14.08). After multivariate analysis, IP was still significantly associated with better clinical outcomes (P = 0.0025). CONCLUSION: This data suggest that IP may contribute to better clinical outcomes in patients with ischemic heart disease.

Lipid transfer to high-density lipoproteins in coronary artery disease patients with and without previous cerebrovascular ischemic events.

BACKGROUND: Patients with coronary artery disease (CAD) and previous ischemic cerebrovascular events (ICVE, ischemic stroke, or transitory ischemic attack) constitute a high-risk subgroup for cardiovascular outcomes. High-density lipoprotein cholesterol (HDL-C) levels are correlated with cardiovascular events. Lipid transfer to HDL affects structure size and HDL subclass profile. Impairment of this transfer could influence ischemic risk seen in patients with CAD + ICVE. The objective was to evaluate the HDL ability to receive the lipids in patients with CAD with or without ICVE. METHODS: Patients with CAD + ICVE (n = 60) and patients with CAD only (n = 60) were matched by age, sex, acute coronary syndromes (ACS) event type, and time elapsed between the ACS event and inclusion in the study. Lipid transfer to HDL was evaluated by incubating donor lipid nanoparticles labeled with radioactive unesterified cholesterol (UC) and esterified cholesterol (EC), phospholipid (PL), and triglyceride (TG) with whole plasma. After the chemical precipitation of non-HDL fractions and nanoparticles, the supernatant was counted for HDL radioactivity. RESULTS: CAD + ICVE group presented with impaired lipid transfer to HDL for PL (CAD + ICVE: 21.14 ± 2.7% vs CAD: 21.67 ± 3.1%, P = .03), TG (CAD + ICVE: 4.88 ± 0.97% vs CAD: 5.63 ± 0.92%, P = .002), and UC (CAD + ICVE: 5.55 ± 1.19% vs CAD: 6.16 ± 1.14%, P = .009). Lipid transfer to HDL was similar in both groups for EC. Adjusted models showed similar results. CONCLUSION: Patients with CAD and ICVE have reduced lipid transfer to HDL compared to those with CAD only. Dysfunctional HDL may account for the higher incidence of ischemic outcomes observed in this population.

Five-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.

BACKGROUND: Despite routine use of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), no conclusive evidence exists that either modality is superior to medical therapy (MT) alone for treating multivessel coronary artery disease with stable angina and preserved ventricular function. METHODS AND RESULTS: The primary end points were total mortality, Q-wave myocardial infarction, or refractory angina requiring revascularization. The study comprised 611 patients randomly assigned to undergo CABG (n=203), PCI (n=205), or MT (n=203). At the 5-year follow-up, the primary end points occurred in 21.2% of patients who underwent CABG compared with 32.7% treated with PCI and 36% receiving MT alone (P=0.0026). No statistical differences were observed in overall mortality among the 3 groups. In addition, 9.4% of MT and 11.2% of PCI patients underwent repeat revascularization procedures compared with 3.9% of CABG patients (P=0.021). Moreover, 15.3%, 11.2%, and 8.3% of patients experienced nonfatal myocardial infarction in the MT, PCI, and CABG groups, respectively (P<0.001). The pairwise treatment comparisons of the primary end points showed no difference between PCI and MT (relative risk, 0.93; 95% confidence interval, 0.67 to 1.30) and a significant protective effect of CABG compared with MT (relative risk, 0.53; 95% confidence interval, 0.36 to 0.77). CONCLUSIONS: All 3 treatment regimens yielded comparable, relatively low rates of death. MT was associated with an incidence of long-term events and rate of additional revascularization similar to those for PCI. CABG was superior to MT in terms of the primary end points, reaching a significant 44% reduction in primary end points at the 5-year follow-up of patients with stable multivessel coronary artery disease.

Prognostic value of left atrial volume in patients who underwent dobutamine stress echocardiography for known or suspected coronary artery disease.

BACKGROUND: Left atrial volume indexed (LAVI) has been reported as a predictor of cardiovascular events. We sought to determine the prognostic value of LAVI for predicting the outcome of patients who underwent dobutamine stress echocardiography (DSE) for known or suspected coronary artery disease (CAD). METHODS: From January 2000 to July 2005, we studied 981 patients who underwent DSE and off-line measurements of LAVI. The value of DSE over clinical and LAVI data was examined using a stepwise log-rank test. RESULTS: During a median follow-up of 24 months, 56 (6%) events occurred. By univariate analysis, predictors of events were male sex, diabetes mellitus, previous myocardial infarction, left ventricular ejection fraction (LVEF), left atrial diameter indexed, LAVI, and abnormal DSE. By multivariate analysis, independent predictors were LVEF (relative risk [RR] = 0.98, 95% CI 0.95-1.00), LAVI (RR = 1.04, 95% CI 1.02-1.05), and abnormal DSE (RR = 2.70, 95% CI 1.28-5.69). In an incremental multivariate model, LAVI was additional to clinical data for predicting events (chi(2) 36.8, P < .001). The addition of DSE to clinical and LAVI yielded incremental information (chi(2) 55.3, P < .001). The 3-year event-free survival in patients with normal DSE and LAVI < or =33 mL/m(2) was 96%; with abnormal DSE and LAVI < or =33 mL/m(2), 91%; with normal DSE and LAVI >34 mL/m(2), 83%; and with abnormal DSE and LAVI >34 mL/m(2), 51%. CONCLUSION: Left atrial volume indexed provides independent prognostic information in patients who underwent DSE for known or suspected CAD. Among patients with normal DSE, those with larger LAVI had worse outcome, and among patients with abnormal DSE, LAVI was still predictive.

Impact of number of vessels disease on outcome of patients with stable coronary artery disease: 5-year follow-up of the Medical, Angioplasty, and bypass Surgery study (MASS).

OBJECTIVE: To evaluate whether the number of vessels disease has an impact on clinical outcomes as well as on therapeutic results accordingly to medical, percutaneous, or surgery treatment in chronic coronary artery disease. METHODS: We evaluated 825 individuals enrolled in MASS study, a randomized study to compare treatment options for single or multivessel coronary artery disease with preserved left ventricular function, prospectively followed during 5 years. The incidence of overall mortality and the composite end-point of death, myocardial infarction, and refractory angina were compared in three groups: single vessel disease (SVD n=214), two-vessel disease (2VD n=253) and three-vessel disease (3VD n=358). The relationship between baseline variables and the composite end-point was assessed using a Cox proportional hazards survival model. RESULTS: Most baseline characteristics were similar among groups, except age (younger in SVD and older in 3VD, p<0.001), lower incidence of hypertension in SVD (p<0.0001), and lower levels of total and LDL-cholesterol in 3VD (p=0.004 and p=0.005, respectively). There were no statistical differences in composite end-point in 5 years among groups independent of the kind of treatment; however, there was a higher mortality rate in 3VD (p<0.001). When we stratified our analysis for each treatment option, bypass surgery was associated with a lower number of composite end-point in all groups (SVD p<0.001, 2VD p=0.002, 3VD p<0.001). In multivariate analysis, we found higher mortality risk in 3VD comparing to SVD (p=0.005, HR 3.14, 95%CI 1.4-7.0). CONCLUSION: Three-vessel disease was associated with worse prognosis compared to single- or two-vessel disease in patients with stable coronary disease and preserved ventricular function at 5-year follow-up. In addition, event-free survival rates were higher after bypass surgery, independent of the number of vessels diseased in these subsets of patients.

Value of real time three-dimensional echocardiography in patients with hypertrophic cardiomyopathy: comparison with two-dimensional echocardiography and magnetic resonance imaging.

UNLABELLED: Real time three-dimensional echocardiography (RT3DE) has been demonstrated to be an accurate technique to quantify left ventricular (LV) volumes and function in different patient populations. We sought to determine the value of RT3DE for evaluating patients with hypertrophic cardiomyopathy (HCM), in comparison with cardiac magnetic resonance imaging (MRI). METHODS: We studied 20 consecutive patients with HCM who underwent two-dimensional echocardiography (2DE), RT3DE, and MRI. Parameters analyzed by echocardiography and MRI included: wall thickness, LV volumes, ejection fraction (LVEF), mass, geometric index, and dyssynchrony index. Statistical analysis was performed by Lin agreement coefficient, Pearson linear correlation and Bland-Altman model. RESULTS: There was excellent agreement between 2DE and RT3DE (Rc = 0.92), 2DE and MRI (Rc = 0.85), and RT3DE and MRI (Rc = 0.90) for linear measurements. Agreement indexes for LV end-diastolic and end-systolic volumes were Rc = 0.91 and Rc = 0.91 between 2DE and RT3DE, Rc = 0.94 and Rc = 0.95 between RT3DE and MRI, and Rc = 0.89 and Rc = 0.88 between 2DE and MRI, respectively. Satisfactory agreement was observed between 2DE and RT3DE (Rc = 0.75), RT3DE and MRI (Rc = 0.83), and 2DE and MRI (Rc = 0.73) for determining LVEF, with a mild underestimation of LVEF by 2DE, and smaller variability between RT3DE and MRI. Regarding LV mass, excellent agreement was observed between RT3DE and MRI (Rc = 0.96), with bias of-6.3 g (limits of concordance = 42.22 to-54.73 g). CONCLUSION: In patients with HCM, RT3DE demonstrated superior performance than 2DE for the evaluation of myocardial hypertrophy, LV volumes, LVEF, and LV mass.