Guy Pelletier

Programmed ventricular stimulation in survivors of an acute myocardial infarction.

The prognostic significance of programmed ventricular stimulation and its usefulness in relation to other forms of invasive and noninvasive testing was evaluated in 150 survivors of acute myocardial infarction. Ventricular tachyarrhythmias of 6 beats or more were induced in 35 (23%) patients. No significant differences existed between patients with inducible ventricular tachyarrhythmias and those without inducible ventricular tachycardia with respect to occurrence of spontaneous ventricular arrhythmias in the acute and early recovery phase of infarction or predischarge exercise-induced ischemia or arrhythmias, severity of coronary artery disease, or degree of left ventricular dysfunction. A higher incidence of inferior myocardial infarction was observed in patients with inducible ventricular tachycardia when compared with those without inducible ventricular tachycardia (66% vs 41%, p less than .01). During a mean follow-up of 10 +/- 5 months (range 2 to 19), there were two sudden deaths, three nonsudden deaths, and two additional patients developed sustained ventricular tachyarrhythmias. There was no significant difference between patients with and those without inducible ventricular tachyarrhythmias with respect to the occurrence of these events. In this study population, a lower mean ejection fraction (p less than .01), the presence of a ventricular aneurysm (p less than .05), and exercise-induced ventricular premature contractions (p less than .05) were predictors of sudden death and of spontaneous ventricular tachycardia. Thus, the findings of this study do not support the hypothesis that the induction of ventricular tachyarrhythmias in patients recovering from acute myocardial infarction identifies a group at high risk for sudden cardiac death.

Long-term prognosis of patients with variant angina.

The long-term prognosis of variant angina and the factors influencing it were assessed in 217 consecutive patients hospitalized in our coronary care unit and followed for a mean of 65 months (range 2 to 123). Cardiac death occurred in 30 patients and an additional 54 experienced a nonfatal myocardial infarction. Survival at 1 and 5 years was 95% and 89%, respectively; survival without infarction was 83% and 69%. Coronary disease and the degree of disease activity were strong predictors of survival by Cox analysis. Survival at 1 year was 99%, and that at 5 years was 95% and 94%, respectively, for patients with one-vessel disease (n = 81) and for those without stenoses of 70% or greater (n = 87). Survival at 1 and 5 years was only 87% and 77% for those with multivessel disease (n = 40). The Cox analysis selected left ventricular function, initial treatment, extent score, duration of angina at rest, and disease activity as multivariate predictors of survival without infarction. Coronary disease was a strong predictor (p less than .0001) of survival without infarction by univariate analysis. Treatment with nifedipine, diltiazem, or verapamil improved survival without infarction compared with other medical treatment (p = .002). Myocardial infarction occurred most commonly soon after diagnosis in patients with a short history of angina at rest. Late coronary events were almost never preceded by resting angina.

Early postinfarction ischemia: clinical, angiographic, and prognostic significance.

Early ischemia, defined as angina with transient ST-T changes during hospitalization, 24 hr or more after an acute myocardial infarction (MI), was observed in 79 (18%) of a consecutive series of 449 patients surviving an MI and catheterized a mean of 10 +/- 3 days after admission. Three clinical factors present 24 hr after admission could identify patients at low, medium, and high risk of factors had a risk greater than 50% and the 118 patients with Q wave MI, no previous angina, and absence of risk factors had a risk of less than 8%. The angiographic correlates of early ischemia were number of vessels with 70% or more stenosis (2.1 +/- 0.8 vs 1.7 +/- 0.8/patient, p less than .0001), number of diseased coronary artery segments (2.8 +/- 1.4 vs 2.1 +/- 1.2, p less than .0001), left anterior descending coronary involvement (77% vs 62% of patients, p = .01), number of normally contractile segments at jeopardy because of a coronary stenosis (1.9 +/- 1.3 vs 1.3 +/- 1.1/patient, p less than .0002), collateral circulation at jeopardy (24% vs 15% of patients, p less than .005), and fewer collateral vessels distal to a tight stenosis (59 vs 72% of patients, p = .04). The stepwise logistic regression retained one angiographic and two clinical independent predictors of early ischemia: number of diseased vessels (p = .0008), presence of a non-Q wave MI (p = .0027), and previous angina (p = .017).(ABSTRACT TRUNCATED AT 250 WORDS)

Symptom-limited versus low level exercise testing before hospital discharge after myocardial infarction.

OBJECTIVE This study was undertaken to compare a low level and a symptom-limited test performed before hospital discharge after an uncomplicated myocardial infarction. BACKGROUND Exercise testing after myocardial infarction provides useful prognostic information. Usually either a low level test is performed before hospital discharge or a symptom-limited test is performed at 3 weeks. METHODS The study group comprised 202 patients with an uncomplicated myocardial infarction; 58 patients had a non-Q wave infarction and 115 patients had received thrombolytic therapy. Both a low level and a symptom-limited exercise test were performed in 200 of the 202 study patients in randomized order on consecutive days, a mean of 7.4 +/- 2.3 days after infarction. RESULTS The symptom-limited test required a considerably greater effort than the low level test: exercise duration was 554 +/- 209 versus 389 +/- 125 s (p less than 0.0001), and peak work load was 5.7 +/- 1.8 versus 4.2 +/- 1.1 METs (p less than 0.0001). The peak heart rate was higher during the symptom-limited test (121 +/- 20 vs. 108 +/- 14 beats/min, p less than 0.0001), as was the rate-pressure product. The number of patients who developed ST segment depression greater than or equal to 1 mm increased from 56 during the low level test to 89 during the symptom-limited test (p less than 0.0001). ST segment depression greater than or equal to 2 mm occurred in 22 patients during the low level test and in 41 patients during the symptom-limited test, an 86% increase (p less than 0.0001). The number of patients with either angina or ST depression greater than or equal to 1 mm increased from 66 to 105 (p less than 0.0001) with the symptom-limited test. Exercise test results were similar for patients with a Q wave or a non-Q wave infarction. Exercise duration was longer and exercise-induced ST depression less frequent in patients who had received thrombolytic therapy. CONCLUSIONS A symptom-limited exercise test performed before hospital discharge after uncomplicated myocardial infarction provides a significantly greater cardiovascular stress than does a low level test and is associated with an ischemic response nearly twice as frequently. The prognostic significance of a positive response at higher work loads has not been defined.

A 10-year experience with intravenous thymoglobuline in induction of immunosuppression following heart transplantation

BACKGROUND Intravenous thymoglobuline (125 mg a day for 3 days, Institut Mérieux, France) has been used to induce immunosuppression following heart transplantation. Cyclosporine and prednisone, with and without azathioprine or mycophenolate mofetil were used as maintenance immunosuppression. OBJECTIVE The objective of the study was to determine the clinical effect of antibody induction of immunosuppression following heart transplantation. METHODS A retrospective analysis of the clinical experience at the Montreal Heart Institute. From 1988 to 1998, 163 patients were administered a 3-day course of intravenous thymoglobuline immediately following heart transplantation (Group 1). From 1983 to 1987 and during an isolated period in 1994, intravenous and oral cyclosporine was used immediately following heart transplantation in 48 patients (Group 2). Routine endomyocardial biopsies were performed in all patients and only moderate and severe rejection was treated. RESULTS One, 5- and 10-year actuarial survival rate averaged 85%+/-3, 77%+/-4 and 67%+/-5 in Group 1 compared with 88%+/-5, 81%+/-6 and 76%+/-6 in Group 2 (p = 0.5). At 1 year, the freedom rate from an episode of acute rejection averaged 43%+/-4 in Group 1 and 30%+/-7 in Group 2 (p = 0.03) and the freedom rate from an episode of infection averaged 44%+/-4 in Group 1 and 31%+/-7 in Group 2 (p = 0.2). At 1, 5 and 10 years, the freedom rate from graft coronary artery disease averaged 93%+/-2, 68%+/-5 and 50%+/-7 in Group 1 compared with 93%+/-4, 58%+/-8 and 30%+/-8 in Group 2 (p = 0.1) and the freedom rate from cancer averaged 98%+/-1, 91%+/-3 and 67%+/-8 in Group 1 compared with 100%, 95%+/-3 and 77%+/-8 in Group 2 (p = 0.2). There was no side-effect related to the systemic injection of thymoglobuline. CONCLUSION In a cyclosporine based protocol of immunosuppression, induction with an initial 3-day course of intravenous thymoglobuline is associated with a lower rate of acute rejection. Moreover, the risk of infection and of developing cancer is not increased whereas there was a trend towards a lower incidence of coronary atherosclerosis 5 and 10 years after transplantation.

Intravenous diltiazem in acute myocardial infarction. Diltiazem as adjunctive therapy to activase (DATA) trial.

OBJECTIVES This study was defined as a pilot investigation of the usefulness and safety of intravenous diltiazem as adjunctive therapy to tissue plasminogen activator in acute myocardial infarction, followed by oral therapy for 4 weeks. BACKGROUND Experimental studies have documented that calcium antagonists protect the myocardial cell against the damage caused by coronary artery occlusion and reperfusion, yet no benefits have been conclusively demonstrated in acute myocardial infarction (AMI) in humans. METHODS In this pilot study, 59 patients with an AMI treated with tissue-type plasminogen activator (t-PA) were randomized, double blinded, to intravenous diltiazem or placebo for 48 h, followed by oral therapy for 4 weeks. The primary objective was to detect an effect on indices of regional left ventricular function and perfusion. Patients were also closely monitored for clinical events, coronary artery patency and indices of infarct size and of left ventricular function. RESULTS Creatine kinase elevation, Q wave score, global and regional left ventricular function and coronary artery patency at 48 h were not significantly different between the diltiazem and placebo groups. A greater improvement observed in regional perfusion and function with diltiazem was likely explained by initial larger defects. Diltiazem, compared to placebo, reduced the rate of death, reinfarction or recurrent ischemia at 35 days from 41% to 13% (p=0.027) and prevented the need for an urgent intervention. The rate of death or myocardial infarction was reduced by 65% (p=0.15). These benefits could not be explained by differences in baseline characteristics such as age, site and extent of infarction, time of inclusion or concomitant therapy. Heart rate and blood pressure were reduced throughout the study with active diltiazem treatment. Side effects of diltiazem were bradycardia and hypotension that required transient or permanent discontinuation of the study drug in 27% of patients, vs. 17% of patients with placebo. CONCLUSIONS A protective effect for clinical events related to early postinfarction ischemia and reinfarction was suggested in this study, with diltiazem administered intravenously with t-PA followed by oral therapy for 1 month, with no effect on coronary artery patency and left ventricular function and perfusion.

Long-term prognosis after myocardial infarction in patients with previous coronary artery bypass surgery.

A group of 205 patients hospitalized with myocardial infarction 2 to 162 months (mean 66) after bypass surgery and 205 control patients with myocardial infarction were compared and followed up for 34 +/- 25 months after hospital discharge. At baseline the postbypass group contained more men (p less than 0.03) and more patients with previous myocardial infarction (p less than 0.06), but the groups were otherwise comparable. Indexes of infarct size were lower in postbypass patients: sum of ST elevation, QRS score, peak serum creatine kinase (CK) (1,115 +/- 994 versus 1,780 +/- 1,647 IU/liter) and peak MB CK (all p less than or equal to 0.001). Postmyocardial infarction ejection fraction was 45 +/- 15% in the postbypass group and 43 +/- 15% in the control group (p = NS); in-hospital mortality rate was 4 and 5%, respectively (p = NS). When patent grafts were taken into account, the two groups were comparable in extent of coronary artery disease. At 5 years after discharge, cumulative mortality was similar in the postbypass and control groups (30 versus 25%, respectively, p = NS). However, postbypass patients had more reinfarctions (40 versus 23%, p = 0.007), more admissions for unstable angina (23 versus 18%, p = 0.04) and more revascularization procedures (34 versus 20%, p = 0.04) than did control patients. The total for these events at 5 years was 70% in the postbypass group and 49% in the control group (p = 0.001). Thus, although patients with previous bypass surgery who develop acute myocardial infarction have a smaller infarct, their subsequent survival is no better than that of other patients with acute myocardial infarction. They experience more reinfarctions and unstable angina. Previous bypass surgery is an important clinical marker for recurrent cardiac events after myocardial infarction.

Angiographic findings after myocardial infarction in patients with previous bypass surgery: explanations for smaller infarcts in this group compared with control patients.

The incidence of previous coronary artery bypass surgery (CABS) in patients with acute myocardial infarction admitted to our hospital has risen from 2.3% to 11.2% in 6 years. We compared infarct size and the angiographically determined cause of infarction in 52 control patients and in 52 consecutive patients with acute myocardial infarction at least 2 months after they had undergone CABS. Baseline characteristics were similar in both groups except for a higher incidence of preexisting Q waves in the post-CABS group (22 vs 10; p less than .05). Indexes of myocardial infarct size were smaller in the post-CABS group compared with those in control patients: peak creatine kinease (CK) level (IU/liter) 1113 +/- 1094 (mean +/- SD) vs 1824 +/- 1932 (p less than .01), peak CK-MB level (IU/liter) 173 +/- 230 vs 272 +/- 332 (p less than .02), peak summed ST segment elevation (mm) 3.5 +/- 4.8 vs 8.2 +/- 9.9 (p less than .005), and QRS score on days 7 to 10, 1.9 +/- 3.0 vs 4.3 +/- 3.4 (p less than .001). Postinfarction left ventricular ejection fraction was higher in the post-CABS group (53 +/- 13%) compared with that in control patients (47 +/- 12%; p less than .05). The incidence of total occlusion of the artery to the infarct zone was similar in the post-CABS and control patients (33 vs 27), as was the incidence of one-, two-, and three-vessel disease (artery plus graft). Collateral blood flow to the infarct zone was found in 27 post-CABS patients and in 23 control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Sternal wound infection after heart transplantation: incidence and results with aggressive surgical treatment.

BACKGROUND Sternal wound infection remains a significant complication. We reviewed the incidence and the treatment of sternal wound infection after heart transplantation. METHODS Of 226 patients who had a heart transplantation, 20 (8.8%) underwent postoperative wound debridement for superficial or deep sternal wound infection. The incidence and the survival of patients with sternal wound infection were analyzed. RESULTS The incidence of sternal wound infection was similar among patients treated with four protocols of immunosuppressive drugs: cyclosporine and prednisone (0 of 22; 0%); cyclosporine, prednisone, and azathioprine (2 of 24; 8.3%); cyclosporine, prednisone, azathioprine, and antithymocyte globulin (15 of 139; 10.8%); and cyclosporine, prednisone, mycophenolate mofetil, and antithymocyte globulin (3 of 41; 7.3%) (p = 0.4). Six-month and 5-year survival of patients with sternal wound infection averaged 85% +/- 8% and 74% +/- 10% compared with 92% +/- 2% and 82% +/- 3% in patients without wound infection (p = 0.15). Patients with deep sternal wound infection, debridement, and reconstruction had a 5-year survival averaging 80% +/- 10%. CONCLUSIONS The incidence of sternal wound infection remains similar between patients treated with the triple drug therapy. Surgical debridement and reconstruction can result in long-term survival after heart transplantation.

Incidence and prognosis of cancer following heart transplantation using RATG induction therapy

Cancer limits survival following heart transplantation. The studys objectives were to evaluate the incidence and risk factors for cancers after heart transplantation and to assess the association between i.v. thymoglobuline induction therapy [rabbit antithymocyte immunoglobulin, (RATG)] and neoplasia. From 1982 to 2002, prospective data were gathered for 207 heart transplant recipients. Except from 1982 to 1987, all patients received a 3‐day course of i.v. RATG following transplantation. Forty‐three malignant neoplasms (21%) were diagnosed. The most common were: skin (42%), lung (12%), prostate (9%), genitourinary (9%) and lymphoma (5%). Mean length of follow‐up after transplantation was 99 ± 57 months. Mean survival after diagnosis was 52 ± 44 months. Multivariate analysis showed no significant increase in the incidence of cancer with recipient age, sex, number of rejection episodes, the type of immunosuppression or the use of RATG. Patients receiving RATG developed their malignancies significantly earlier after transplantation (P =0.007) and succumbed faster after the diagnosis (P = 0.06). Cancer is a limiting event for long‐term survival after heart transplantation. No individual risk factors allow predicting its development. In the present cohort, RATG does not have carcinogenic effects following transplantation, but is associated with a more precocious development of malignancies.