Guy B. Pelletier

Aspirin, heparin, or both to treat acute unstable angina

We tested the usefulness of aspirin (325 mg twice daily), heparin (1000 units per hour by intravenous infusion), and a combination of the two in the early management of acute unstable angina pectoris in a double-blind, randomized, placebo-controlled trial involving 479 patients. The patients entered the study as soon as possible after hospital admission (at a mean [+/- SD] of 7.9 +/- 8.0 hours after the last episode of pain), and the study was ended after 6 +/- 3 days, when definitive therapy had been selected. Major end points--refractory angina, myocardial infarction, and death--occurred in 23, 12, and 1.7 percent of the 118 patients receiving placebo, respectively. Heparin was associated with a decrease in the occurrence of refractory angina (P = 0.002). The incidence of myocardial infarction was significantly reduced in the groups receiving aspirin (3 percent; P = 0.01), heparin (0.8 percent; P less than 0.001), and aspirin plus heparin (1.6 percent, P = 0.003), and no deaths occurred in these groups. There were too few deaths overall to permit evaluation of the effect of treatment on this end point. The combination of aspirin and heparin had no greater protective effect than heparin alone but was associated with slightly more serious bleeding (3.3 vs. 1.7 percent). We conclude that in the acute phase of unstable angina, either aspirin or heparin treatment is associated with a reduced incidence of myocardial infarction, and there is a trend favoring heparin over aspirin. Heparin treatment is also associated with a reduced incidence of refractory angina.

Unstable Angina and Progression of Coronary Atherosclerosis

We studied the progression of atherosclerotic coronary lesions in 38 patients who had previously undergone angiography and were later hospitalized for an episode of unstable angina pectoris, and in 38 matched patients with stable angina who had also undergone prior catheterization. Patients with unstable angina and those with stable angina were similar in terms of age (mean, 49 and 50 years, respectively), number of risk factors (1.5 per patient in both groups), interval between studies (mean +/- S.D., 44 +/- 31 and 35 +/- 31 months, respectively), number of diseased vessels on the first angiogram (1.52 in both groups), and initial ejection fraction (65 and 63 per cent, respectively). Progression of coronary lesions was demonstrated in 29 of the 38 patients with unstable angina, as compared with 12 of the 38 with stable angina (P less than 0.0005). Progression to 70 per cent or more stenosis was recorded in 21 of the patients with unstable angina but in only 5 of those with stable angina (P less than 0.0005). Also more frequent in the patients with unstable angina were multifocal progression (11 vs. 2, P less than 0.01) and progression of the left main or preseptal left anterior descending artery or both (9 vs. 1, P less than 0.01). Thus, we have demonstrated by angiography that unstable angina is associated with progression in the extent and severity of coronary atherosclerosis.

A randomized study comparing propranolol and diltiazem in the treatment of unstable angina

One hundred consecutive patients hospitalized in the coronary care unit for unstable angina, excluding patients with Prinzmetals variant angina, were randomized within 24 hours of admission to treatment with diltiazem (50 patients) or propranolol (50 patients). Also excluded were patients with previous coronary artery bypass surgery and those receiving a beta-receptor blocking agent at the time of hospital admission. Left ventricular function and the extent of coronary artery disease were similar in the two groups. During the hospital stay, the number of chest pain episodes decreased from a mean (+/- SD) of 0.75 +/- 0.1 per patient per day to 0.26 +/- 0.07 (p less than 0.05) with diltiazem and 0.29 +/- 0.1 (p less than 0.05) with propranolol therapy. The circadian distribution of chest pain episodes was affected similarly. After 1 month, 14 of the patients treated with diltiazem were symptom-free compared with 13 treated with propranolol. At a mean follow-up time of 5.1 months (range 1 to 15), death had occurred in two patients in each group and myocardial infarction in five diltiazem- and four propranolol-treated patients (difference not significant). Coronary artery bypass surgery had been performed in 21 diltiazem- and 19 propranolol-treated patients (difference not significant). Only 15 patients were symptom-free, 9 treated with diltiazem and 6 with propranolol. This similar result observed with the two forms of treatment suggests that coronary artery spasm may not be the main factor involved in unstable angina when Prinzmetals variant angina is excluded. It also suggests that diltiazem can be used as an alternative to the usual treatment with beta-receptor blocking drugs.

Comparison of clinical variables and variables derived from a limited predischarge exercise test as predictors of early and late mortality after myocardial infarction

An exercise test limited to 5 METS or 70% of age-predicted maximal heart rate was performed 1 day before hospital discharge by 225 survivors of acute myocardial infarction, all of whom were subsequently followed up for at least 5 years. The mortality rate was 11.1% during the first year, but averaged only 2.9% per year from the second to fifth year. Over the entire follow-up period, the five variables that predicted mortality by multivariate analysis were QRS score, an exercise-induced ST segment shift, previous infarction, failure to achieve target heart rate or work load and ventricular arrhythmia during the exercise test. Because mortality differed markedly before and after 1 year, Cox regression analyses were performed separately for both of these periods. The factors that were predictive of mortality during the first year were an exercise-induced ST shift (p less than 0.0001, relative risk 7.8), failure to increase systolic blood pressure by 10 mm Hg or more during exercise (p = 0.0039, relative risk 4.3) and angina in hospital 48 hours or longer after admission (p = 0.0046, relative risk 3.4). None of these three variables was predictive of mortality after 1 year. Previous infarction (p = 0.0007), QRS score (p = 0.0042) and ventricular arrhythmia during the exercise test (p = 0.016) were predictive of mortality after the first year. Thus, clinical and exercise test variables are complementary predictors of mortality after myocardial infarction. An abnormal ST segment response during an early limited exercise test and angina in the hospital are common strong predictors of mortality to 1 year, but not thereafter. Late mortality correlates with markers of poor left ventricular function.

Long-term reproducibility and significance of provokable ventricular arrhythmias after myocardial infarction

The long-term reproducibility and significance of inducible ventricular arrhythmias were assessed in 21 survivors of a myocardial infarction. Programmed ventricular stimulation performed a mean of 12 +/- 2 days (range 8 to 18) after infarction provoked ventricular fibrillation in 2 patients, sustained monomorphic ventricular tachycardia in 8 and nonsustained ventricular tachycardia in 11. Patients were restudied using the same protocol a mean of 8 +/- 2 months (range 4 to 11) after infarction. All patients underwent programmed ventricular stimulation studies in the absence of antiarrhythmic drug treatment. Ventricular tachyarrhythmias could be reinitiated in 16 patients (76%): ventricular fibrillation in 2, sustained ventricular tachycardia in 5 (monomorphic in 4) and nonsustained ventricular tachycardia in 9. A preponderance of inferior infarction was observed among patients with reinducible tachycardias (9 of 16 patients versus 0 of 5 with noninducible tachycardias) (p less than 0.05). No significant difference existed between patients with and without reinducible arrhythmias with respect to severity of coronary artery disease, degree of left ventricular dysfunction, occurrence of ventricular fibrillation in the acute phase of infarction and ventricular arrhythmias detected by 24 hour ambulatory electrocardiographic (Holter) monitoring. There was no significant difference between patients with and without a positive late study in stimulation thresholds, ventricular refractory periods, time interval between initial and repeat testing and use of beta-adrenergic blocking agents. During a mean follow-up period of 17 months (range 10 to 23) one patient with inducible sustained monomorphic ventricular tachycardia at both studies died suddenly. The remaining patients have survived follow-up without experiencing an arrhythmic event.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and angiographic features and prognostic significance of early postinfarction angina with and without electrocardiographic signs of transient ischemia

PURPOSEnThe goal of the study was to characterize the clinical and angiographic characteristics and the prognostic significance of early postinfarction angina associated or unassociated with ST-T changes.nnnPATIENTS AND METHODSnFour hundred forty-nine consecutive patients surviving an acute myocardial infarction and catheterized before hospital discharge were included. They were closely monitored in the coronary care unit and a 12-lead electrocardiogram (ECG) was promptly obtained before the administration of nitroglycerin whenever chest pain suggestive of ischemia occurred. Complete follow-up information was obtained for all patients a mean of 14 +/- 8 months after the qualifying infarction.nnnRESULTSnEarly postinfarction angina occurred in 164 patients. Transient ST-T changes were documented during pain in 79 patients and were absent in 85. Compared with patients without postinfarction angina, patients with angina without ST-T changes were older and had a more frequent past history of angina (42% versus 28%, p = 0.01). They also more often had a non-Q-wave myocardial infarction with lower peak creatine kinase blood level elevation. At angiography, patients with angina had more extensive coronary artery disease (1.9 +/- 0.8 diseased vessels per patient versus 1.6 +/- 0.8, p less than 0.05) and more left ventricular segments at jeopardy by a significant coronary artery stenosis (1.5 +/- 1.1 versus 1.2 +/- 1.1, p less than 0.05). The presence of ST-T changes during chest pain was associated with a further increase in the severity of coronary artery disease (2.1 +/- 0.8 diseased vessels per patient, p less than 0.05) and with a less well-developed collateral circulation (18% versus 34% of patients, p = 0.01) that was more often compromised by a coronary artery stenosis (22% versus 8% of patients, p = 0.008). In-hospital infarct extension occurred in 2% of patients without angina, 3.5% of patients with angina without ECG changes, and 28% of patients with angina and ST-T changes (p less than 0.01). The 2-year survival was similar in the first two groups (90% and 96%), and poorer (83%, p = 0.02) in patients with ST-T changes. Survival rates without myocardial infarction were respectively 80%, 78%, and 67% (p less than 0.004).nnnCONCLUSIONnA gradient in the severity of coronary artery disease and in the extent of myocardium at jeopardy exists from patients with no postinfarction angina to patients with angina and to patients with angina accompanied by ECG signs of ischemia. The presence of ST-T changes during pain indicates a much less favorable clinical outcome.

Ten-year follow-up of critically ill patients undergoing heart transplantation.

BACKGROUNDnThe long-term result following heart transplantation appears very good despite complications of coronary atherosclerosis and cancer. Critically ill patients supported with mechanical devices remain a growing and difficult group in which long-term results need to be defined. The objective of this study was to review the 10-year follow-up of critically ill patients who underwent heart transplantation after support with mechanical devices.nnnMETHODSnWe retrospectively analyzed all patients who underwent heart transplantation from 1986 to 1999 at the Montreal Heart Institute.nnnRESULTSnTwenty-two patients (22/199, 11%) underwent heart transplantation after support with intra-aortic balloon pumps (n = 17) and total artificial hearts (n = 5). One hundred seventy-seven patients (177/199, 89%) underwent heart transplantation without pre-operative mechanical assistance. Patients with pre-operative mechanical assistance were younger (41 +/- 12 vs 48 +/- 10 years old, p = 0. 002), underwent a shorter waiting time to transplantation (2 +/- 2 vs 19 +/- 27 weeks, p = 0.004), and donor hearts had longer ischemic time (166 +/- 63 vs 137 +/- 49 minutes, p = 0.002) compared with patients without pre-operative mechanical assistance. One-month, 1-, 5-, and 10-year survival averaged 86% +/- 7%, 67% +/- 10%, 67% +/- 10%, and 59% +/- 12%, respectively, in patients with pre-operative mechanical assistance compared with 95% +/- 2%, 88% +/- 2%, 81% +/- 3%, and 74% +/- 4%, respectively, in patients without assistance, a significant difference (p = 0.04) that is mainly related to higher operative mortality in the former group. Although, we found no difference between the 2 groups in the 10-year freedom rate from acute rejection, infection, cancer, and coronary atherosclerosis, sepsis was the cause of 4 early deaths among patients with pre-operative mechanical assistance.nnnCONCLUSIONnEarly and long-term survival was significantly decreased in critically ill patients with pre-operative mechanical assistance compared with other patients without pre-operative assistance. Sepsis is a dominant threat among patients who underwent heart transplantation with pre-operative mechanical assistance, and the lower survival is due mainly to the increased early mortality.

Hemodynamic and Clinical Benefits Associated With Chronic Sildenafil Therapy in Advanced Heart Failure: Experience of the Montréal Heart Institute

BACKGROUNDnPulmonary hypertension is highly prevalent in advanced heart failure (HF) despite optimal medical and device therapies. The objective of this investigation was to report on a single centres experience of open-label chronic sildenafil therapy in patients with advanced HF.nnnMETHODSnWe conducted a retrospective systematic medical record review of all patients evaluated at our institution for heart transplantation who had also been treated with chronic sildenafil therapy. Baseline demographics, comorbidities, and concomitant medications, as well as the results of laboratory investigations and physiological testing, were abstracted from patient medical records. Change in systolic and mean pulmonary artery pressure (PAP), transpulmonary gradient, cardiac output and cardiac index, and selected laboratory parameters was analyzed by means of the Wilcoxon rank sum test. Outcomes of interest included New York Heart Association (NYHA) functional class after 6 months of therapy and adverse effects attributable to sildenafil.nnnRESULTSnThe 16 patients undergoing evaluation for cardiac transplantation combined for 4166 patient-days on sildenafil, with a mean dose of 102.5 ± 54.0 mg/d. None discontinued because of side effects. At 6 months, there was an improvement in the cardiac index (P = 0.014) and systolic PAP (P = 0.049) without any significant change in other hemodynamic parameters. Ten patients (62.5%) experienced an improvement in their NYHA functional class, 8 (50%) received a heart transplantation, and 2 (12.5%) improved sufficiently to be removed from the transplant list.nnnCONCLUSIONnChronic sildenafil therapy was well tolerated and associated with improved functional capacity and decreased systolic PAP. Properly controlled randomized studies of the long-term usefulness of sildenafil therapy in advanced HF populations are warranted.

Demographics, treatment and outcome of acute coronary syndromes: 17 years of experience in a specialized cardiac centre.

BACKGROUNDnEpidemiological information on patients with acute coronary syndromes managed in specialized cardiac centres is limited.nnnOBJECTIVEnTo report the evolution of demographics, treatment and outcome of patients admitted to a tertiary coronary care unit (CCU) over a 17-year period.nnnMETHODSnA prospective database of 18,719 patients admitted from April 1986 to March 2003 in a 21-bed CCU was analyzed.nnnRESULTSnFrom 1986 to 2003, the number of admissions increased from 937 to 1577 per year, while the length of stay declined from 7.5 to 3.5 days. The mean age increased from 58.4 to 63.4 years, and the proportion of men remained stable at approximately 70%. The use of coronary angiograms increased from 49.8% to 81.1% in all patients, while fibrinolysis dropped to 0.4%. In-hospital mortality decreased from 9% to 1.5%. The percentage of overall instrumentation (arterial line, central venous catheter, temporary pacemaker, Swan-Ganz catheter and intra-aortic balloon pump) decreased from 38% to 8.1%. From 1995 to 2003, the proportion of stenting during percutaneous transluminal coronary angioplasty increased dramatically from 0% to 86%. In the past five years, surgical revascularization has remained stable at approximately 20% of all admissions. The proportion of patients discharged with a noncoronary chest pain diagnosis has remained constant at approximately 4%.nnnINTERPRETATIONnThere has been a tremendous increase in efficiency, with an approximate doubling of the admissions turnover rate in a tertiary CCU. Patients with acute coronary syndromes are stratified faster and treated more invasively. Therapeutic advances are reflected by an almost linear 0.5% per year decrease in in-hospital mortality.

Changes in Outcomes of Cardiac Allograft Vasculopathy Over 30 Years Following Heart Transplantation

OBJECTIVESnThis study investigated temporal changes in the demographics and the prognosis of cardiac allograft vasculopathy (CAV) over 30 years following heart transplantation (HTx).nnnBACKGROUNDnEffects of the changing HTx demographics on CAV outcomes, based on International Society for Heart and Lung Transplantation (ISHLT) classification of CAV, have been incompletely investigated.nnnMETHODSnPatients who underwent HTx at the Montreal Heart Institute were classified according to the severity of CAV (CAV 0 is no presence of CAV; CAV 1 is mild, CAV 2 to 3 is moderate to severe) and era of HTx (early: 1983 to 1998; recent: 1999 to 2011). We compared the risk of progression, survival, and independent predictors of outcomes among the groups.nnnRESULTSnA total of 298 patients were followed for 11.6 ± 6.6 years. Patients who received transplants in the early eraxa0exhibited a higher risk for progression from CAV 1 to a higher grade (adjusted odds ratio: 8.0; 95% confidence interval [CI]: 1.01 to 62.6). The presence of CAV was associated with a significantly increased risk for all-cause mortality in the early era (hazard ratio [HR]: 1.6; 95% CI: 1.1 to 2.5) but not in the recent era (HR: 1.1; 95% CI: 0.2 to 4.9). Regardless of thexa0era,xa0CAV classes 2 to 3 and CAV 1 were associated with a significantly increased risk for all-cause mortality compared to CAV 0 (HR: 6.5; 95% CI: 2.7 to 15.7; and HR: 1.750; 95% CI: 1.001 to 3.046, respectively).nnnCONCLUSIONSnThe progression and prognosis of CAV have improved over 30 years. The ISHLT CAV classification accurately and independently predicts long-term outcome following HTx.