José Antonio Franchini Ramires

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.

Coronary Angioplasty Results in Leukocyte and Platelet Activation With Adhesion Molecule Expression: Evidence of Inflammatory Responses in Coronary Angioplasty

OBJECTIVES This study sought to characterize leukocyte and platelet activation and adhesion molecule expression after coronary angioplasty. BACKGROUND Coronary angioplasty can be regarded as a clinical model of postischemic inflammation because this intervention leads to the release of inflammatory mediators as a result of plaque rupture and endothelial injury. METHODS In 13 patients with stable angina (mean [ +/- SEM] age 56.0 +/- 2.4 years, range 44 to 79), blood samples were drawn from the aorta and coronary sinus immediately before and immediately and 15 min after coronary angioplasty. Subsequently, leukocyte and platelet functions were determined. Eleven control patients (57.5 +/- 2.3 years, range 52 to 78) underwent coronary arteriography. RESULTS Coronary arteriography and angioplasty showed no difference in number of leukocytes between the coronary sinus and the aorta. However, 15 min after coronary angioplasty, there was an increase in neutrophil CD18 and CD11b, monocyte CD14 and platelet glycoprotein IIb/IIIa expression and a decrease in neutrophil L-selectin expression (189 +/- 25%, 163 +/- 27%, 158 +/- 35%, 141 +/- 22% and 31 +/- 10%, respectively, p < 0.01). In the control subjects, no change in adhesion molecule expression occurred. Superoxide production and aggregation in ex vivo-stimulated neutrophils collected from the coronary sinus 15 min after coronary angioplasty was significantly decreased compared with that after coronary arteriography (54 +/- 12% vs. 106 +/- 30% and 58 +/- 11% vs. 102 +/- 29%, respectively, p < 0.01). The reduced responses to phorbol ester stimulation may be explained by previous in vivo activation of neutrophils during coronary angioplasty. CONCLUSIONS Coronary angioplasty increases neutrophil, monocyte and platelet adhesion molecule expression and induces a significant decrease in ex vivo-stimulated neutrophil superoxide generation and aggregation. These findings suggest that coronary angioplasty triggers cellular activation with an inflammatory response that could contribute to restenosis.

Coronary Angiography Is the Best Predictor of Events in Renal Transplant Candidates Compared With Noninvasive Testing

Abstract—Guidelines for the detection of coronary artery disease (CAD) and assess of risk in renal transplant candidates are based on the results of noninvasive testing, according to data originated in the nonuremic population. We evaluated prospectively the accuracy of 2 noninvasive tests and risk stratification in detecting CAD (≥70% obstruction) and assessing cardiac risk by using coronary angiography (CA). One hundred twenty-six renal transplant candidates who were classified as at moderate (≥50 years) or high (diabetes, extracardiac atherosclerosis, or clinical coronary artery disease) coronary risk underwent myocardial scintigraphy (SPECT), dobutamine stress echocardiography, and CA and were followed for 6 to 48 months. The prevalence of CAD was 42%. The sensitivities and negative predictive values for the 2 noninvasive tests and risk stratification were <75%. After 6 to 48 months, there were 18 cardiac events, 9 fatal. Risk stratification (P =0.007) and CA (P =0.0002) predicted the crude probability of surviving free of cardiac events. The probability of event-free survival at 6, 12, 24, 36, and 48 months were 98%, 98%, 94%, 94%, and 94% in patients with <70% stenosis on CA and 97%, 87%, 61%, 56%, and 54% in patients with ≥70% stenosis. Multivariate analysis showed that the sole predictor of cardiac events was critical coronary lesions (P =0.003). Coronary angiography may still be necessary for detecting CAD and determining cardiac risk in renal transplant candidates. The data suggest that current algorithms based on noninvasive testing in this population should be revised.

Sildenafil effects on exercise, neurohormonal activation, and erectile dysfunction in congestive heart failure: a double-blind, placebo-controlled, randomized study followed by a prospective treatment for erectile dysfunction.

Background—Erectile dysfunction (ED) is common in patients with congestive heart failure (CHF). ED reduces quality of life, and it may affect compliance, thereby impairing the success of CHF treatment. Methods and Results—In the first phase (fixed-dose double-blind, randomized, placebo-controlled, two-way crossover study), we studied in 23 men with CHF the effects of 50 mg sildenafil on exercise and neurohormonal activation. Patients underwent a treadmill 6-minute cardiopulmonary walking (6′WT) test followed by a maximal cardiopulmonary exercise test (ET). In the second phase, patients received sildenafil, taken as required for ED. Sildenafil reduced the heart rate (HR) (bpm) before the 6′WT (from 75±15 to 71±14, P =0.02) and ET (from 75±15 to 71±15, P =0.02); the systolic blood pressure (mm Hg) before the 6′WT (from 116±18 to 108±18, P =0.004) and ET (from 116±15 to 108±17, P =0.001); the diastolic blood pressure before the 6′WT (from 69±9 to 63±11, P =0.01) and ET (from 70±8 to 65±10, P =0.004); and the Ve/Vco2 slope during the 6′WT (from 32±7 to 31±6, P =0.04) and ET (from 33±8 to 31±5, P =0.03). Sildenafil attenuated the HR increment during the 6′WT (P =0.003) and ET (P =0.000). Sildenafil increased the peak ˙ o2 from 16.6±3.4 to 17.7±3.4 mL/kg per min (P =0.025) and the exercise time from 12.3±3.4 to 13.7±3.2 minutes (P =0.003). Sildenafil improved most scores of International Index of Erectile Function. Conclusions—Sildenafil was tolerated and effective for ED treatment in CHF, and improved the exercise capacity. The reduction of HR during exercise with sildenafil could theoretically decrease the myocardial oxygen consumption during sexual activity.

Additional reduction in blood pressure after cholesterol-lowering treatment by statins (lovastatin or pravastatin) in hypercholesterolemic patients using angiotensin-converting enzyme inhibitors (enalapril or lisinopril)

Blood pressure (BP) reduction was compared between patients receiving angiotensin-converting enzyme inhibitors alone and patients receiving these medications plus statins after 3 months of dietary intervention. Although BP was similarly reduced at week 4, the statin-treated group had a greater reduction in BP and total cholesterol levels at week 16, suggesting a synergistic effect between cholesterol lowering with statins and angiotensin-converting enzyme inhibitor treatment for hypertensive patients.

Effectiveness of the Maze Procedure Using Cooled-Tip Radiofrequency Ablation in Patients With Permanent Atrial Fibrillation and Rheumatic Mitral Valve Disease

Background—Although the Cox-Maze III procedure is effective for treating permanent atrial fibrillation (AF), its high complexity limits its use. The Saline-Irrigated Cooled-tip Radiofrequency Ablation (SICTRA) System is an alternative source of energy used to ablate AF. The aim of this study was to evaluate the effectiveness of the SICTRA for the treatment of permanent AF in patients with rheumatic mitral valve (MV) disease. Methods and Results—Between February 2002 and April 2003, 70 patients with permanent AF and rheumatic MV disease were randomly assigned to undergo a modified Maze III procedure using SICTRA associated with MV surgery (group A) or MV surgery alone (group B). Groups A and B were similar in terms of baseline characteristics. The in-hospital mortality rate was 2.3% (1 death) in group A versus 0% (no deaths) in group B (P>0.99). The additional time required for the left-sided radiofrequency ablation in group A was 14.2±5.1 minutes and for right-sided ablation was 12.3±4.2 minutes. The mean postoperative follow-up periods were 13.8±3.4 and 11.5±7.3 months, respectively, in groups A and B. The overall mid-term survival rate was 95.1% in group A and 92.8% in group B (P>0.99). The cumulative rates of sinus rhythm were 79.4% in group A and 26.9% in group B (P=0.001). Doppler echocardiography documented biatrial transport function in 90.3% of group A patients in sinus rhythm. Conclusions—The SICTRA is effective for treating permanent AF associated with rheumatic MV disease.

Ten-Year Follow-Up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II)

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.

Chylomicron metabolism is markedly altered in systemic lupus erythematosus

OBJECTIVE To verify the in vivo status of chylomicron metabolism in systemic lupus erythematosus (SLE) since there is a high incidence of atherosclerosis in this disease and chylomicrons may have an important role in atherogenesis. METHODS A chylomicron-like emulsion labeled with 14C-cholesteryl esters and 3H-triglycerides was injected intravenously into 10 female patients with inactive SLE and 10 healthy age- and sex-matched control subjects to determine the plasma kinetics of the emulsion lipids from consecutive plasma samples taken at regular intervals for 1 hour. Lipolytic activity was determined in vitro after incubation of the labeled emulsion with postheparin plasma. RESULTS The decay curves for the emulsion were markedly slowed in SLE. Chylomicron lipolysis, indicated by the fractional clearance rate (FCR) of emulsion 3H-triglyceride, was 2-fold smaller in SLE patients than in controls (mean +/- SD 0.023 +/- 0.011 versus 0.047 +/-0.015 minute(-1); P = 0.010). Chylomicron removal, indicated by emulsion 14C-cholesteryl ester FCR, was 3-fold smaller in SLE patients than in controls (0.007 +/-0.007 versus 0.023 +/- 0.011 minute(-1); P = 0.009). In vitro lipolysis in SLE patients was nearly half that of the controls (mean +/- SD 10,199 +/- 2,959 versus 6,598 +/-2,215; P = 0.014). Higher levels of very-low-density lipoprotein cholesterol and triglycerides and lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I were also observed in the SLE patients. CONCLUSION SLE patients have disturbances in chylomicron metabolism that are characterized by decreased lipolysis and chylomicron remnant removal from the plasma. This finding, together with other alterations in lipid profiles that were confirmed in the present study, is largely accountable for the accelerated atherosclerotic process of the disease.

Effect of Spironolactone on ventricular arrhythmias in congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy

Epidemiologic studies have shown an important increase in the high mortality of patients with congestive heart failure (CHF) despite optimal medical management. Ventricular arrhythmia was recognized as the most common cause of death in this population. Electrolyte imbalance, myocardial fibrosis, left ventricular dysfunction, and inappropriate neurohumoral activation are presumed responsible for sudden cardiac death. In this study, we focused on the deleterious effects of the overproduction of aldosterone that occurs in patients with CHF. Secondary hyperaldersteronism can be part of several factors thought to be responsible for sudden cardiac death. We randomized 35 patients (32 men, aged 48 +/- 9 years) with systolic dysfunction (ejection fraction 33 +/- 5%) and New York Heart Association class III CHF secondary to dilated or ischemic cardiomyopathy into 2 groups. The treatment group received spironolactone, an aldosterone receptor antagonist, along with standard medical management using furosemide, angiotensin-converting enzyme inhibitors, and digoxin. The control group received only the standard medical treatment. Holter monitoring was used to assess the severity of ventricular arrhythmia. After 20 weeks, patients who received spironolactone had a reduced hourly frequency of ventricular premature complexes (VPCs) (65 +/- 18 VPCs/hour at week 0 and 17 +/- 9 VPCs/hour at week 16) and episodes of nonsustained ventricular tachycardia (VT) (3.0 +/- 0.8 episodes of VT/24-hour period at week 0, and 0.6 +/- 0.3 VT/24-hour period at week 16). During monitored treadmill exercise, a significant improvement in ventricular arrhythmia was found in the group receiving spironolactone (39 +/- 10 VPCs at week 0, and 6 +/- 2 VPCs at week 16). These findings suggest that aldosterone may contribute to the incidence of ventricular arrhythmia in patients with CHF, and spironolactone helps reduce this complication.

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 bodys 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.