Luís Henrique Wolff Gowdak

Prognostic Value of Nonobstructive and Obstructive Coronary Artery Disease Detected by Coronary Computed Tomography Angiography to Identify Cardiovascular Events

Background—The contribution of plaque extent to predict cardiovascular events among patients with nonobstructive and obstructive coronary artery disease (CAD) is not well defined. Our objective was to evaluate the prognostic value of plaque extent detected by coronary computed tomography angiography. Methods and Results—All consecutive patients without prior CAD referred for coronary computed tomography angiography to evaluate for CAD were included. Examination findings were classified as normal, nonobstructive (<50% stenosis), or obstructive (≥50%). Based on the number of segments with disease, extent of CAD was classified as nonextensive (⩽4 segments) or extensive (>4 segments). The cohort included 3242 patients followed for the primary outcome of cardiovascular death or myocardial infarction for a median of 3.6 (2.1–5.0) years. In a multivariable analysis, the presence of extensive nonobstructive CAD (hazard ratio, 3.1; 95% confidence interval, 1.5–6.4), nonextensive obstructive (hazard ratio, 3.0; 95% confidence interval, 1.3–6.9), and extensive obstructive CAD (hazard ratio, 3.9; 95% confidence interval, 2.2–7.2) were associated with an increased rate of events, whereas nonextensive, nonobstructive CAD was not. The addition of plaque extent to a model that included clinical probability as well as the presence and severity of CAD improved risk prediction. Conclusions—Among patients with nonobstructive CAD, those with extensive plaque experienced a higher rate of cardiovascular death or myocardial infarction, comparable with those who have nonextensive disease. Even among patients with obstructive CAD, greater extent of nonobstructive plaque was associated with higher event rate. Our findings suggest that regardless of whether obstructive or nonobstructive disease is present, the extent of plaque detected by coronary computed tomography angiography enhances risk assessment.

Screening for significant coronary artery disease in high-risk renal transplant candidates.

BackgroundRenal transplant candidates are at an increased risk for coronary artery disease (CAD), a strong predictor of cardiovascular events [major adverse coronary events (MACE)]. Coronary angiography is a costly, risky, invasive procedure. We sought to determine clinical predictors of significant CAD (stenosis ≥70%) in high-risk renal transplant candidates. MethodsClinical evaluation and coronary angiography were performed in 301 patients (57±8 years, 73% men) on hemodialysis for 32 months (median). Patients were followed-up for 22 months (median). Inclusion criteria were diabetes (type 1 or 2), evidence of cardiovascular disease, or age ≥50 years. Risk factors included hypertension (93.7%), overweight/obesity (54.3%), dyslipidemia (44.9%), diabetes (42.1%), and smoking (24.3%). Cardiovascular disease was found as follows: peripheral arterial disease (PAD) (31.2%), angina (28.1%), stroke (12.9%), myocardial infarction (MI) (10.3%), and heart failure (9.3%). ResultsSignificant CAD was found in 136 individuals (45.2%). Diabetes [odds ratio (OR)=1.82; 95% confidence interval (CI)=1.08–3.07], PAD (OR=2.50; 95% CI=1.44–4.37), and previous MI (OR=7.75; 95% CI=3.03–23.98) were associated with significant CAD. The prevalence of significant CAD increased with the number of clinical predictors from 26% (none) to 100% (all present) (P<0.0001). The incidence of fatal/nonfatal MACE increased two, four, and sixfold in those with diabetes, PAD, or previous MI, respectively (P<0.0001). ConclusionsIn high-risk patients with end-stage renal disease, the prevalence of CAD and the incidence of MACE were high. Significant CAD or cardiovascular complications were not related to the majority of classic risk factors. Patients with diabetes, PAD, or previous MI are at higher risk of CAD, MACE, or both and, thus, must be referred for invasive diagnostic procedures.

Multicenter randomized trial of cell therapy in cardiopathies – MiHeart Study

BackgroundCardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials.Method/DesignWe have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpsons rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group.DiscussionMany phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies.The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT00333827), acute myocardial infarction (NCT00350766) and Chronic Ischemic Heart Disease (NCT00362388).

Rationale and benefits of trimetazidine by acting on cardiac metabolism in heart failure

Heart failure is a systemic and multiorgan syndrome with metabolic failure as a fundamental mechanism. As a consequence of its impaired metabolism, other processes are activated in the failing heart, further exacerbating the progression of heart failure. Recent evidence suggests that modulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation represents a promising approach to the treatment of patients with heart failure. Clinical trials have demonstrated that the adjunct of trimetazidine to the conventional medical therapy improves symptoms, cardiac function and prognosis in patients with heart failure without exerting negative hemodynamic effects. This review focuses on the rationale and clinical benefits of trimetazidine by acting on cardiac metabolism in heart failure, and aims to draw attention to the readiness of this agent to be included in all the major guidelines dealing with heart failure.

Treatment of coronary artery disease in hemodialysis patients evaluated for transplant-a registry study.

Background. We assessed the results of a noninvasive therapeutic strategy on the long-term occurrence of cardiac events and death in a registry of patients with chronic kidney disease (CKD) and coronary artery disease (CAD). Methods. We analyzed 519 patients with CKD (56±9 years, 67% men, 67% whites) on maintenance hemodialysis with clinical or scintigraphic evidence of CAD by using coronary angiography. Results. In 230 (44%) patients, coronary angiography revealed significant CAD (lumen reduction≥70%). Subjects with significant CAD were kept on medical treatment (MT; n=184) or referred for myocardial revascularization (percutaneous transluminal coronary angioplasty/coronary artery bypass graft—intervention; n=30) according to American College of Cardiology/American Heart Association guidelines. In addition, 16 subjects refused intervention and were also followed-up. Event-free survival for patients on MT at 12, 36, and 60 months was 86%, 71%, and 57%, whereas overall survival was 89%, 71%, and 50% in the same period, respectively. Patients who refused intervention had a significantly worse prognosis compared with those who actually underwent intervention (events: hazard ratio=4.50; % confidence interval=1.48–15.10; death: hazard ratio=3.39; % confidence interval 1.41–8.45). Conclusions. In patients with CKD and significant CAD, MT promotes adequate long-term event-free survival. However, failure to perform a coronary intervention when necessary results in an accentuated increased risk of events and death.

High dose of N-acetylcystein prevents acute kidney injury in chronic kidney disease patients undergoing myocardial revascularization.

BACKGROUND The renoprotective effect of N-acetylcystein in patients undergoing coronary artery bypass graft surgery is controversial. METHODS We assessed the renoprotective effect of the highest dose of N-acetylcystein sanctioned for clinical use in a prospective, double-blind, placebo-controlled study including 70 chronic kidney disease patients, stage 3 or 4, who underwent coronary artery bypass graft surgery, on cardiopulmonary bypass (CPB) and off CPB, and were randomly allocated to receive either N-acetylcystein 150 mg/kg followed by 50 mg/kg for 6 hours in 0.9% saline or only 0.9% saline. Acute kidney injury was defined by the Acute Kidney Injury Network classification. RESULTS The incidence of kidney injury was reduced in the N-acetylcystein group (57.1% versus 28.6%, p=0.016). Nonuse of N-acetylcystein (relative risk 3.58, 95% confidence interval: 1.04 to 12.33, p=0.04) and cardiopulmonary bypass (relative risk 4.55, 95% confidence interval: 1.28 to 16.15, p=0.02) were independent predictors of kidney injury. In patients treated with CPB, N-acetylcystein reduced the incidence of kidney injury from 63% to 46%. Oxidative stress was increased in control subjects (p=0.01) and abolished in patients receiving N-acetylcystein. CONCLUSIONS Maximum intravenous doses of N-acetylcystein reduce the incidence of acute kidney injury in patients with kidney disease undergoing coronary artery bypass graft surgery, abolish oxidative stress, and mitigate the negative effect of CPB on renal function.

Cardiac MRI for Detection of Unrecognized Myocardial Infarction in Patients With End-Stage Renal Disease: Comparison With ECG and Scintigraphy

OBJECTIVE The purposes of this study were to use the myocardial delayed enhancement technique of cardiac MRI to investigate the frequency of unrecognized myocardial infarction (MI) in patients with end-stage renal disease, to compare the findings with those of ECG and SPECT, and to examine factors that may influence the utility of these methods in the detection of MI. SUBJECTS AND METHODS We prospectively performed cardiac MRI, ECG, and SPECT to detect unrecognized MI in 72 patients with end-stage renal disease at high risk of coronary artery disease but without a clinical history of MI. RESULTS Fifty-six patients (78%) were men (mean age, 56.2 +/- 9.4 years) and 16 (22%) were women (mean age, 55.8 +/- 11.4). The mean left ventricular mass index was 103.4 +/- 27.3 g/m(2), and the mean ejection fraction was 60.6% +/- 15.5%. Myocardial delayed enhancement imaging depicted unrecognized MI in 18 patients (25%). ECG findings were abnormal in five patients (7%), and SPECT findings were abnormal in 19 patients (26%). ECG findings were false-negative in 14 cases and false-positive in one case. The accuracy, sensitivity, and specificity of ECG were 79.2%, 22.2%, and 98.1% (p = 0.002). SPECT findings were false-negative in six cases and false-positive in seven cases. The accuracy, sensitivity, and specificity of SPECT were 81.9%, 66.7%, and 87.0% (not significant). During a period of 4.9-77.9 months, 19 cardiac deaths were documented, but no statistical significance was found in survival analysis. CONCLUSION Cardiac MRI with myocardial delayed enhancement can depict unrecognized MI in patients with end-stage renal disease. ECG and SPECT had low sensitivity in detection of MI. Infarct size and left ventricular mass can influence the utility of these methods in the detection of MI.

Underuse of American College of Cardiology/American Heart Association Guidelines in Hemodialysis Patients

Patients with end-stage renal disease (ESRD) are at high risk for cardiovascular disease (CVD) and therefore should be treated according to ACC/AHA Guidelines. Scant data are available concerning the actual use of cardioprotective drugs in this population. The use of angiotensin-converting enzyme inhibitors (ACE-I), β-blockers, aspirin, and statins was assessed in 271 (72% males, 66% Caucasians) high-risk ESRD patients on hemodialysis. The study population comprised 27% smokers, 95% with hypertension, 38% with diabetes, and 44% with dyslipidemia; 44% of patients had overt CVD at baseline, including 9% with heart failure, 9% with prior myocardial infarction, and 3% with previous myocardial revascularization. One-third of all patients were not receiving any cardioprotective drugs; among those patients who were, 42% were on one drug, 21% were on two, 3.7% were on three, and 1.5% were on four. The most prescribed agent was ACE-I (35.8%), followed by aspirin (30.6%), and β-blockers (28.0%). The use of statins was remarkably and significantly low (4.1%) (p < 0.001), even in the higher risk subgroups (patients with diabetes or macrovascular disease). ACE-I plus aspirin was the most prescribed combination (8.5%). Cardioprotective agents recommended for risk-factor modification by the ACC/AHA Guidelines for their well-established efficacy in the general population were underutilized in this cohort of high-risk hypertensive hemodialysis patients, despite an elevated prevalence of clinically evident CVD. Speculatively, this fact may be relevant to better understand the known increased cardiovascular morbidity-mortality associated with chronic renal disease.

Coronary calcium score as predictor of stenosis and events in pretransplant renal chronic failure

BACKGROUND Coronary artery disease (CAD) is the major cause of death among chronic renal failure (CRF) patients. Traditional, non-invasive exams to detect CAD and to predict events have shown insufficient results in this group. CT Scan evaluation of Coronary Calcium Score (CCS) has proven to be of prognostic value for the population reporting no renal condition. OBJECTIVE To investigate CCS accuracy in detecting obstructive CAD and in predicting cardiovascular events in candidates to renal transplant as compared to quantitative invasive coronary angiography (ICA). METHODS Ninety-seven (97) CRF patients aged > or =35 were evaluated. Obstructive CAD was considered as > or =50% or > or =70% stenosis on ICA. Descriptive data, concordance, diagnostic tests, Kaplan-Meier, and multivariate analysis were used. RESULTS Agatston mean score was 580.6 +/- 1,102.2. Minimum and maximum values were 0 and 7,994, with median at 176. Only 14 patients had zero calcium score. No differences were reported in regard to ethnicity. Highest regional calcium was associated to the highest probability of coronary stenosis in the same segment. Agatston calcium score showed high accuracy for the diagnosis of > or =50% and > or =70% stenosis, with area under ROC curve (AUC) of 0.75 and 0.70, respectively. At the threshold of 400, calcium score identified a subgroup with a higher rate of cardiovascular events at an average follow-up time of 29+/-11.0 months. CONCLUSION CCS proved to have good diagnostic and prognostic performance for cardiovascular events evaluation in CRF patients.FUNDAMENTO: A doenca arterial coronariana (DAC) e a principal causa de obito em pacientes com insuficiencia renal cronica (IRC). Os exames nao invasivos tradicionais para deteccao de DAC e predicao de eventos tem apresentado resultados insuficientes nesse grupo. A avaliacao do escore de calcio coronariano (ECC) por tomografia computadorizada tem comprovado valor prognostico na populacao sem doenca renal. OBJETIVO: Avaliar a acuracia do ECC para detectar DAC obstrutiva e prever eventos cardiovasculares em candidatos a transplante renal comparada a angiografia coronariana invasiva (ACI) quantitativa. METODOS: Foram avaliados 97 pacientes com IRC e idade > 35anos. Foi considerada DAC obstrutiva a presenca de estenose >50% ou >70% pela ACI. Dados descritivos, concordância, testes diagnosticos, Kaplan-Meier e analise multivariada foram utilizados. RESULTADOS: O escore de Agatston medio foi de 580,6 ± 1.102,2; os valores minimos e maximos foram 0 e 7.994, e mediana de 176. Apenas 14 pacientes tinham escore de calcio de zero. Nao houve diferencas entre as etnias e a maior presenca de calcio regional associou-se a maior probabilidade de estenose coronaria no mesmo segmento. O escore de calcio de Agatston apresentou boa acuracia para o diagnostico de estenose, >50% e >70% com area sob a curva ROC de 0,75 e 0,70, respectivamente. No limiar de 400, o escore de calcio identificou o subgrupo com maior taxa de eventos cardiovasculares em tempo medio de seguimento de 29,1±11,0 meses. CONCLUSAO: O ECC na avaliacao de DAC apresentou boa performance diagnostica e prognostica para eventos cardiovasculares em pacientes com insuficiencia renal cronica (IRC).

[Cell therapy plus transmyocardial laser revascularization: a proposed alternative procedure for refractory angina].

OBJECTIVE We tested the hypothesis that TMLR combined with intramyocardial injection of BMC is safe, and may help increase the functional capacity of patient with refractory angina. METHODS Nine patients (eight men), 65+/-5 years old, with refractory angina for multivessel disease and previous myocardial revascularization procedures (CABG/PCI), not candidates for another procedure due to the extension of the disease were enrolled. TMLR (11+/-3 laser drills) was performed via a limited thoracotomy using a CO2 Heart Laser System. BMC were obtained immediately prior to surgery, and the lymphomonocytic fraction separated by density gradient centrifugation. During surgery, 5 mL containing approximately 1.9+/-0.3 x 10(8) BMC were delivered by multiple injections in the ischemic myocardium. Before (B) and 6 months (6M) after the procedure, patient underwent clinical evaluation and myocardial perfusion assessment by cardiac magnetic resonance imaging (MRI) during pharmacological stress with dypiridamole. RESULTS No major complications or deaths occurred during the procedure. One patient died after 2 years (non cardiac cause). There was a reduction in the ischemic score as assessed by MRI from 1.64+/-0.10 (B) to 0.88+/-0.09 (6M) (P=0.01). Clinically, there was a reduction in functional class of angina from 3.7+/-0.2 (B) to 1.3+/-0.2 (6M) (P<0.0001). CONCLUSIONS In this initial experience, the combined strategy of TMLR plus cell therapy appeared to be safe, and may have synergistically acted to reduce myocardial ischemia, with clinically relevant improvement in functional capacity. Provided these data are confirmed in a larger, randomized, controlled trial with longer follow-up, this strategy could be used as a novel therapeutic option for treating pt with refractory angina.