Angiotensin-converting enzyme (ACE) inhibitors play an important role in protecting various organ... more Angiotensin-converting enzyme (ACE) inhibitors play an important role in protecting various organs in patients with congestive heart failure. The mechanisms of action of ACE inhibitors in congestive heart failure are multiple and may involve important effects on endothelial function in addition to the well known hemodynamic and neurohormonal effects. Skeletal muscle fatigue can play an important role in the pathophysiology of congestive heart failure, and only aggressive treatment with ACE inhibitors and exercise training can improve exercise tolerance and reduce the risk of further deterioration of cardiac function. ACE inhibitors should be introduced with caution in patients with severe heart failure and hypotension to prevent renal dysfunction. Unlike some other ACE inhibitors, perindopril seems to cause no first dose hypotension. It also appears to have a neutral effect on renal function in patients with severe congestive heart failure.
A woman with congestive heart failure and reduced left ventricular ejection fraction associated w... more A woman with congestive heart failure and reduced left ventricular ejection fraction associated with hyperthyroidism is reported. Congestive heart failure resolved and left ventricular ejection fraction normalized within three weeks of treatment of her hyperthyroidism. The literature on previously reported cases of reversible systolic heart failure associated with hyperthyroidism is reviewed and the possible mechanisms leading to systolic dysfunction and congestive heart failure in thyrotoxicosis are discussed. One such mechanism may be the action of thyroid hormone on altering gene expression in cardiac cells; another could be the chronic tachycardia associated with thyrotoxicosis. Although it is a not a common cause of systolic heart failure, thyrotoxicosis should be considered in the differential diagnosis of cardiomyopathies because it is a potentially reversible cause.
Dofetilide is a new, pure class III antiarrhythmic agent that prolongs the refractory period and ... more Dofetilide is a new, pure class III antiarrhythmic agent that prolongs the refractory period and action potential duration without having beta-blocking or calcium channel-blocking properties, making it unique among established class III agents. Dofetilide is effective in converting atrial and ventricular arrhythmias, and in maintaining sinus rhythm after cardioversion. Interestingly, it is more effective in converting atrial flutter than atrial fibrillation. It appears to be safe in patients with left ventricular dysfunction and postmyocardial infarction. In small studies, intravenous dofetilide was superior to flecainide, procainamide and amiodarone in converting atrial fibrillation and flutter. Dofetilide can be administered orally or intravenously with no significant effect on heart rate or blood pressure, but it can prolong QT interval and cause torsade de pointes in 3% to 4% of patients receiving it intravenously and in 0.8% to 1.5% of patients receiving it orally. So far, it is recommended that therapy be initiated in hospital under electrocardiogram monitoring for at least two days, with particular care to avoid torsade de pointes in high risk patients such as women, and those with bradycardia, hypokalemia, hypomagnesia and renal dysfunction. Studies have failed to show any extracardiac side effects.
The value of the ear-crease sign in predicting the presence of coronary artery disease was studie... more The value of the ear-crease sign in predicting the presence of coronary artery disease was studied in 340 consecutive patients who underwent coronary arteriography. In this selected population, 75.6% of whom had coronary artery disease, the sensitivity of the sign was 59.5%, the specificity 81.9% and the positive predictive value 91.1%. The sign was associated with increasing age but was also independently associated with obstructive coronary artery disease. No significant correlation was found between the sign and the presence of risk factors or other signs of such disease, except for corneal arcus. In symptomatic patients the sign suggested the presence of more extensive coronary artery disease. In an asymptomatic population with a low prevalence of coronary artery disease it appears to be of limited value in predicting obstructive coronary artery disease. However, it may identify a subset of patients prone to early ageing and to the early development of coronary artery disease, whose prognosis might be improved by early preventive measures.
To develop standards for distinguishing antiarrhythmic drug effect from spontaneous variability o... more To develop standards for distinguishing antiarrhythmic drug effect from spontaneous variability of premature ventricular complexes (PVCs), 21 males (mean age 56 ± 8 years) with chronic ischemic heart disease and PVCs underwent symptom-limited treadmill exercise testing and 24-hour ambulatory monitoring before and after 2 weeks of placebo medication. Linear regression analysis was used to describe the relationship between baseline and placebo PVC frequency for various indexes of ventricular ectopic activity and to establish 95% and 99% one-tailed confidence intervals for this relationship within the group of 21 patients. The lower limit of baseline PVC frequency for which the procedure could distinguish a placebo from a true drug response, termed the "sensitivity threshold," was an average frequency of 2.2 PVCs/hour for ambulatory electrocardiographic monitoring and 1.2 PVCs/min for treadmill exercise testing. All patients exceeded the sensitivity threshold on baseline ambulatory ECGs, but only 38% of patients did so on baseline treadmill exercise tests. To establish antiarrhythmic efficacy with 95% confidence, the minimal percent reduction of PVCs between baseline and placebo visits was 68% for treadmill exercise testing and 65% for ambulatory electrocardiography. Although these standards were developed in patients with chronic ischemic heart disease, the model can be used to establish antiarrhythmmic drug efficacy in any patient group.
In hypertensive patients, the development of left ventricular hypertrophy seems to increase the r... more In hypertensive patients, the development of left ventricular hypertrophy seems to increase the risk of cardiovascular death. Although some antihypertensive agents have been associated with regression in left ventricular hypertrophy, diuretics, the most widely used ones, have not. Indapamide is a new, nonthiazide diuretic and vasodilator. To test its effects on left ventricular hypertrophy, patients with essential hypertension and left ventricular hypertrophy were studied before and at the end of 6 months of therapy with 2.5 mg of indapamide daily. Candidates had to have moderate, uncontrolled essential hypertension with echocardiographically documented left ventricular hypertrophy (left ventricular mass index greater than or equal to 130 gm/m2 for men and greater than or equal to 110 gm/m2 for women). Patients with complicated hypertension or with significant cardiovascular or metabolic diseases were excluded. Patients could remain on antihypertensive drugs other than diuretics, provided doses remained stable for 3 months before entry and there was no know regression of left ventricular hypertrophy. Of 13 patients selected, 2 dropped out. The remaining 11 patients successfully completed 6 months of therapy. The average age was 56 +/- 10 years. Indapamide was associated with a significant reduction of mean systolic blood pressure from 172 to 142 mm Hg (p less than 0.001), diastolic blood pressure from 101 to 83 mm Hg (p less than 0.001), and left ventricular mass index from 146 +/- 22 to 124 +/- 22 gm/m2 (mean +/- SD) (p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)
a commonly used H, receptor antagonist, was found to adversely interact with many drugs metaboliz... more a commonly used H, receptor antagonist, was found to adversely interact with many drugs metabolized by the liver, including class I antiarrhythmic agents, lidocaine and quinidine. Mexiletine is a new class I antiarrhythmic agent similar to lidocaine which when used orally may have significant gastric side effects. Since some patients with peptic ulcer disease or gastric hyperacidity on mexiletine may benefit from the addition of cimetidine, it was important to rule out any significant adverse interaction between the two drugs in such patients. Eleven patients currently receiving long-term oral mexiletine for the treatment of complex ventricular arrhythmia underwent a double-blind crossover trial where they were maintained on their usual dose of mexiletine, and cimetidine, 300 mg orally every 6 hours, or placebo were added for a l-week period each. Peak and trough mexiletine blood levels were not significantly altered by cimetidine. Similarly, there was no significant change in the frequency and severity of ventricular arrhythmia when cimetidtne was added to mexiletine. Cimetidine reduced gastric side effects of mexiletine in 50% of patients who had complained of such symptoms on mexiletine alone or on mexiletine and placebo. We conclude that cimetidine can effectively reduce gastric side effects of mexiletine in many patients without adversely affecting the plasma concentration or the efficacy of the drug.
The antiarrhythmic efficacy of encatnide and qulnidine was compared in 20 ambulatory men (mean ag... more The antiarrhythmic efficacy of encatnide and qulnidine was compared in 20 ambulatory men (mean age 56 * 8 years) with a, history of premature ventricular complexes. All but one patient had a history of chronic ischemit heart disease. A longitudinal crossover design was used to study the effects of encainide and qulnidine on premature ventricular complexes recorded on treadmill excerdise tests and on 24 hour ambulatory electrocardiograms. Afler a baseline evaluation, patients were randomized to one of two drug sequences consisting of 2 weeks of treatment with placebo followed by 2 weeks of treatment with the first drug, after which the same sequence was repeated for the second drug. Encalnide was generally better tolerated than quinldine. The reduction in the average number of premature ventricular complexes/hour on ambulatory electrocardlograms and in the average number of premature ventricular complexes/min on treadmill exercise tests was greater v&h encainide than with quinidine (b X0.01 and <0.025, respectively). Encainide suppressed all premature ventricular complexes recorded on ambulatory electrocardiograms in 44 percent of patients, reduced them by at least 80 percent in 88 percent of patients and suppressed complex forms in 100 percent of patients. Ety contrast, no patient demonstrated total suppression of premature ventricular complexes with quinidine, only 44 percent demonstrated at least 80 percent reduction and only 53 percent demonstrated suppression of complex forms on 24 hour ambulatory electrocardiograms. Encalnide is safe and effective for the treatment of chronic ventricular ectopic activity. In this study, it appeared to be superior to average doses of quinidine.
Journal of the American College of Cardiology, Mar 1, 2013
Background: We aim to evaluate whether performing a left atrial appendectomy in the context of th... more Background: We aim to evaluate whether performing a left atrial appendectomy in the context of the modified Maze procedure reduces the longterm risk of stroke even after stopping oral anticoagulation. methods: This is a cohort study of all patients who underwent the Maze procedure from June 2005 to January 2012, excluding patients who received a mechanical valve replacement. All patients also received concomitant cardiac surgery along with amputation of the left atrial appendage. Data was prospectively collected at 3 months, 6 months, 1 year, 2 years and 3 years after the surgery with an interview and Holter monitoring. All patients received anticoagulation for 3 months, after which time, anticoagulation was decided by the treating physician's preference. Patients were divided at the 6 months time point into two groups: those on and off of anticoagulants. results: In total, there were 96 patients, of whom 61 were treated with anticoagulation (Group A) and 35 were not (Group B). There were no significant differences between the two groups in terms of stroke or bleeding risk, in particular, the persistence or recurrence of atrial fibrillation
Despite significant advances in recent years in the diagnosis and treatment of congestive heart f... more Despite significant advances in recent years in the diagnosis and treatment of congestive heart failure, sudden unexpected cardiac death is still considered a major epidemiologic problem among those patients. This article lists some of the predisposing factors to the development of cardiac arrhythmias and sudden death in patients with congestive heart failure. These include electrolyte or autonomic nervous system inbalance, the use of certain anti-arrhythmic drugs, or intermittent myocardial ischemia.
Little is known about differences in practice patterns or outcomes in the management of patients ... more Little is known about differences in practice patterns or outcomes in the management of patients who have atrial fibrillation in Canada compared with those in the United States (US). We evaluated the effect that the country of enrollment may have on the management patterns and clinical outcomes in patients who participated in the AFFIRM study. Three thousand four hundred patients came from the US and 660 from Canada. In the US, patients were more likely to have a history of coronary artery disease (39% vs 35%, p = 0.03), hypertension (72% vs 67%, p = 0.01), or congestive heart failure (24% vs 18%, p = 0.0002). More US participants were &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;65 years of age (25% vs 19%, p = 0.003). Although at randomization the use of warfarin was comparable, during follow-up Canadians were more likely to be treated with warfarin and to be therapeutically anticoagulated. Mortality rate at 5 years was higher in US patients (24% vs 16%, p = 0.001), and the composite end point (death, disabling stroke, major bleeding, cardiac arrest, or anoxic encephalopathy) was also higher in US patients (30% vs 22%, p = 0.0005). Even after adjusting for known differences in baseline characteristics, the risk of death was lower in Canada (hazard ratio 0.70, p = 0.02). In conclusion, in the AFFIRM study, US subjects were more likely to have preexisting cardiovascular diseases despite being younger (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;65 years old) than those in Canada. Effective warfarin therapy was more commonly employed in Canada. After correcting for the known differences in baseline characteristics, Canadian patients who had atrial fibrillation had a lower mortality risk.
This study evaluates the effectiveness and safety of intravenous diltiazem for the treatment of a... more This study evaluates the effectiveness and safety of intravenous diltiazem for the treatment of atrial fibrillation and atrial flutter. A double-blind, parallel, randomized, placebo-controlled protocol was used, and 6 large, urban hospitals, both universityaffiliated and private, participated. The study involved 113 patients with atrial fibrillation or flutter, a ventricular rate 1120 beats/min and systolic blood pressure 190 mm Hg without severe heart failure. The dose of intravenous diltiazem (or identical placebo) was 0.25 mg/kg/2 minutes followed 15 minutes later by 0.35 mg/kg/2 minutes if the first dose was tolerated but ineffective. If a patient did not respond, the code was broken and the patient was allowed to receive open-label diltiazem if placebo had been given. Of 56 patients, 42 (75%) randomized to receive diltiazem responded to 0.25 mg/kg and 10 of 14 responded to 0.35 mg/kg, for a total response rate of 52 of 56 patients (93%), whereas 7 of 57 patients (12%) responded to placebo (p <O.OOl). After the double-blind protocol, 49 of the 57 patients who received placebo were then given diltiazem; 47 of 49 responded, for an overall response rate of 99 of 105 patients (94%) with diltiazem. The median time from the start of drug infusion to the maximal decrease in heart rate was 4.3 minutes. Side effects occurred in 14 patients, 7 of whom had asymptomatic hypotension not requiring intervention. Thus, intravenous diltiazem was rapidly effective for slowing the ventricular response in most patients with atrial fibrillation or atrial flutter. Blood pressure decreased slightly. Side effects were mild.
Serial treadmill exercise testing (mean 5.5 tests/patient) was used to evaluate the prognosis of ... more Serial treadmill exercise testing (mean 5.5 tests/patient) was used to evaluate the prognosis of 200 males (mean age 53 years) without clinical heart failure or unstable angina pectoris 3 weeks after acute myocardial infarction (MI). Exercise-induced ischemic ST-segment depression 0.2 mV 3 weeks after MI was significantly more prevalent in patients with subsequent cardiac arrest (100%) or coronary artery bypass graft surgery (64%) than in patients without subsequent events within 2 years of infarction (35%) (p < 0.05). Exercise-induced ventricular arrhythmia on multiple tests 5-52 weeks after MI was more prevalent in patients with recurrent myocardial infarction (90%) than in patients without subsequent events (47%) (p < 0.001). By contrast, exercise-induced ventricular arrhythmia on a single test at 3 weeks was a less powerful predictor of subsequent cardiac events. Exercise-induced ischemia 3 weeks after MI predicted early fatal events, while ventricular arrhythmia on serial testing predicted later nonfatal events.
Amiodarone is a new and powerful antiarrhythmic agent currently under investigation in North Amer... more Amiodarone is a new and powerful antiarrhythmic agent currently under investigation in North America. In the past two years, there have been increasing reports of serious side effects associated with its use, including 14 cases of pneumonitis or pulmonary fibrosis. This report describes a case of acute necrotizing pneumonitis, a complication that has not been observed previously with amiodarone therapy. Amiodarone also appeared to alter carbohydrate metabolism in this patient. Metabolic changes induced by this drug may be mediated by superoxide radicals. A high index of suspicion for pulmonary complications should be maintained in patients taking amiodarone, and nonspecific respiratory complaints should be investigated carefully.
It is important to consider the hemodynamic effects of antiarrhythmic drugs, because the majority... more It is important to consider the hemodynamic effects of antiarrhythmic drugs, because the majority of patients who require these drugs already have compromised cardiac function. The presently available antiarrhythmic agents vary in their potential for producing negative inotropic effects on the myocardium; they vary, as well, as to the mechanisms by which these effects are produced. The drugs in each of the Vaughan-Williams' classes are discussed in terms of the extent to which they affect cardiac output and the mechanisms by which they may depress cardiac function. Practically all antiarrhythmic agents can decrease cardiac output when administered intravenously. However, when given orally to patients with congestive heart failure, amongst Class I agents, encainide and mexilitine appear to have a reasonably good safety record with respect to the worsening of congestive heart failure. Class III antiarrhythmics also appear to be well tolerated in patients with severe LV dysfunction.
Angiotensin-converting enzyme (ACE) inhibitors play an important role in protecting various organ... more Angiotensin-converting enzyme (ACE) inhibitors play an important role in protecting various organs in patients with congestive heart failure. The mechanisms of action of ACE inhibitors in congestive heart failure are multiple and may involve important effects on endothelial function in addition to the well known hemodynamic and neurohormonal effects. Skeletal muscle fatigue can play an important role in the pathophysiology of congestive heart failure, and only aggressive treatment with ACE inhibitors and exercise training can improve exercise tolerance and reduce the risk of further deterioration of cardiac function. ACE inhibitors should be introduced with caution in patients with severe heart failure and hypotension to prevent renal dysfunction. Unlike some other ACE inhibitors, perindopril seems to cause no first dose hypotension. It also appears to have a neutral effect on renal function in patients with severe congestive heart failure.
A woman with congestive heart failure and reduced left ventricular ejection fraction associated w... more A woman with congestive heart failure and reduced left ventricular ejection fraction associated with hyperthyroidism is reported. Congestive heart failure resolved and left ventricular ejection fraction normalized within three weeks of treatment of her hyperthyroidism. The literature on previously reported cases of reversible systolic heart failure associated with hyperthyroidism is reviewed and the possible mechanisms leading to systolic dysfunction and congestive heart failure in thyrotoxicosis are discussed. One such mechanism may be the action of thyroid hormone on altering gene expression in cardiac cells; another could be the chronic tachycardia associated with thyrotoxicosis. Although it is a not a common cause of systolic heart failure, thyrotoxicosis should be considered in the differential diagnosis of cardiomyopathies because it is a potentially reversible cause.
Dofetilide is a new, pure class III antiarrhythmic agent that prolongs the refractory period and ... more Dofetilide is a new, pure class III antiarrhythmic agent that prolongs the refractory period and action potential duration without having beta-blocking or calcium channel-blocking properties, making it unique among established class III agents. Dofetilide is effective in converting atrial and ventricular arrhythmias, and in maintaining sinus rhythm after cardioversion. Interestingly, it is more effective in converting atrial flutter than atrial fibrillation. It appears to be safe in patients with left ventricular dysfunction and postmyocardial infarction. In small studies, intravenous dofetilide was superior to flecainide, procainamide and amiodarone in converting atrial fibrillation and flutter. Dofetilide can be administered orally or intravenously with no significant effect on heart rate or blood pressure, but it can prolong QT interval and cause torsade de pointes in 3% to 4% of patients receiving it intravenously and in 0.8% to 1.5% of patients receiving it orally. So far, it is recommended that therapy be initiated in hospital under electrocardiogram monitoring for at least two days, with particular care to avoid torsade de pointes in high risk patients such as women, and those with bradycardia, hypokalemia, hypomagnesia and renal dysfunction. Studies have failed to show any extracardiac side effects.
The value of the ear-crease sign in predicting the presence of coronary artery disease was studie... more The value of the ear-crease sign in predicting the presence of coronary artery disease was studied in 340 consecutive patients who underwent coronary arteriography. In this selected population, 75.6% of whom had coronary artery disease, the sensitivity of the sign was 59.5%, the specificity 81.9% and the positive predictive value 91.1%. The sign was associated with increasing age but was also independently associated with obstructive coronary artery disease. No significant correlation was found between the sign and the presence of risk factors or other signs of such disease, except for corneal arcus. In symptomatic patients the sign suggested the presence of more extensive coronary artery disease. In an asymptomatic population with a low prevalence of coronary artery disease it appears to be of limited value in predicting obstructive coronary artery disease. However, it may identify a subset of patients prone to early ageing and to the early development of coronary artery disease, whose prognosis might be improved by early preventive measures.
To develop standards for distinguishing antiarrhythmic drug effect from spontaneous variability o... more To develop standards for distinguishing antiarrhythmic drug effect from spontaneous variability of premature ventricular complexes (PVCs), 21 males (mean age 56 ± 8 years) with chronic ischemic heart disease and PVCs underwent symptom-limited treadmill exercise testing and 24-hour ambulatory monitoring before and after 2 weeks of placebo medication. Linear regression analysis was used to describe the relationship between baseline and placebo PVC frequency for various indexes of ventricular ectopic activity and to establish 95% and 99% one-tailed confidence intervals for this relationship within the group of 21 patients. The lower limit of baseline PVC frequency for which the procedure could distinguish a placebo from a true drug response, termed the "sensitivity threshold," was an average frequency of 2.2 PVCs/hour for ambulatory electrocardiographic monitoring and 1.2 PVCs/min for treadmill exercise testing. All patients exceeded the sensitivity threshold on baseline ambulatory ECGs, but only 38% of patients did so on baseline treadmill exercise tests. To establish antiarrhythmic efficacy with 95% confidence, the minimal percent reduction of PVCs between baseline and placebo visits was 68% for treadmill exercise testing and 65% for ambulatory electrocardiography. Although these standards were developed in patients with chronic ischemic heart disease, the model can be used to establish antiarrhythmmic drug efficacy in any patient group.
In hypertensive patients, the development of left ventricular hypertrophy seems to increase the r... more In hypertensive patients, the development of left ventricular hypertrophy seems to increase the risk of cardiovascular death. Although some antihypertensive agents have been associated with regression in left ventricular hypertrophy, diuretics, the most widely used ones, have not. Indapamide is a new, nonthiazide diuretic and vasodilator. To test its effects on left ventricular hypertrophy, patients with essential hypertension and left ventricular hypertrophy were studied before and at the end of 6 months of therapy with 2.5 mg of indapamide daily. Candidates had to have moderate, uncontrolled essential hypertension with echocardiographically documented left ventricular hypertrophy (left ventricular mass index greater than or equal to 130 gm/m2 for men and greater than or equal to 110 gm/m2 for women). Patients with complicated hypertension or with significant cardiovascular or metabolic diseases were excluded. Patients could remain on antihypertensive drugs other than diuretics, provided doses remained stable for 3 months before entry and there was no know regression of left ventricular hypertrophy. Of 13 patients selected, 2 dropped out. The remaining 11 patients successfully completed 6 months of therapy. The average age was 56 +/- 10 years. Indapamide was associated with a significant reduction of mean systolic blood pressure from 172 to 142 mm Hg (p less than 0.001), diastolic blood pressure from 101 to 83 mm Hg (p less than 0.001), and left ventricular mass index from 146 +/- 22 to 124 +/- 22 gm/m2 (mean +/- SD) (p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)
a commonly used H, receptor antagonist, was found to adversely interact with many drugs metaboliz... more a commonly used H, receptor antagonist, was found to adversely interact with many drugs metabolized by the liver, including class I antiarrhythmic agents, lidocaine and quinidine. Mexiletine is a new class I antiarrhythmic agent similar to lidocaine which when used orally may have significant gastric side effects. Since some patients with peptic ulcer disease or gastric hyperacidity on mexiletine may benefit from the addition of cimetidine, it was important to rule out any significant adverse interaction between the two drugs in such patients. Eleven patients currently receiving long-term oral mexiletine for the treatment of complex ventricular arrhythmia underwent a double-blind crossover trial where they were maintained on their usual dose of mexiletine, and cimetidine, 300 mg orally every 6 hours, or placebo were added for a l-week period each. Peak and trough mexiletine blood levels were not significantly altered by cimetidine. Similarly, there was no significant change in the frequency and severity of ventricular arrhythmia when cimetidtne was added to mexiletine. Cimetidine reduced gastric side effects of mexiletine in 50% of patients who had complained of such symptoms on mexiletine alone or on mexiletine and placebo. We conclude that cimetidine can effectively reduce gastric side effects of mexiletine in many patients without adversely affecting the plasma concentration or the efficacy of the drug.
The antiarrhythmic efficacy of encatnide and qulnidine was compared in 20 ambulatory men (mean ag... more The antiarrhythmic efficacy of encatnide and qulnidine was compared in 20 ambulatory men (mean age 56 * 8 years) with a, history of premature ventricular complexes. All but one patient had a history of chronic ischemit heart disease. A longitudinal crossover design was used to study the effects of encainide and qulnidine on premature ventricular complexes recorded on treadmill excerdise tests and on 24 hour ambulatory electrocardiograms. Afler a baseline evaluation, patients were randomized to one of two drug sequences consisting of 2 weeks of treatment with placebo followed by 2 weeks of treatment with the first drug, after which the same sequence was repeated for the second drug. Encalnide was generally better tolerated than quinldine. The reduction in the average number of premature ventricular complexes/hour on ambulatory electrocardlograms and in the average number of premature ventricular complexes/min on treadmill exercise tests was greater v&h encainide than with quinidine (b X0.01 and <0.025, respectively). Encainide suppressed all premature ventricular complexes recorded on ambulatory electrocardiograms in 44 percent of patients, reduced them by at least 80 percent in 88 percent of patients and suppressed complex forms in 100 percent of patients. Ety contrast, no patient demonstrated total suppression of premature ventricular complexes with quinidine, only 44 percent demonstrated at least 80 percent reduction and only 53 percent demonstrated suppression of complex forms on 24 hour ambulatory electrocardiograms. Encalnide is safe and effective for the treatment of chronic ventricular ectopic activity. In this study, it appeared to be superior to average doses of quinidine.
Journal of the American College of Cardiology, Mar 1, 2013
Background: We aim to evaluate whether performing a left atrial appendectomy in the context of th... more Background: We aim to evaluate whether performing a left atrial appendectomy in the context of the modified Maze procedure reduces the longterm risk of stroke even after stopping oral anticoagulation. methods: This is a cohort study of all patients who underwent the Maze procedure from June 2005 to January 2012, excluding patients who received a mechanical valve replacement. All patients also received concomitant cardiac surgery along with amputation of the left atrial appendage. Data was prospectively collected at 3 months, 6 months, 1 year, 2 years and 3 years after the surgery with an interview and Holter monitoring. All patients received anticoagulation for 3 months, after which time, anticoagulation was decided by the treating physician's preference. Patients were divided at the 6 months time point into two groups: those on and off of anticoagulants. results: In total, there were 96 patients, of whom 61 were treated with anticoagulation (Group A) and 35 were not (Group B). There were no significant differences between the two groups in terms of stroke or bleeding risk, in particular, the persistence or recurrence of atrial fibrillation
Despite significant advances in recent years in the diagnosis and treatment of congestive heart f... more Despite significant advances in recent years in the diagnosis and treatment of congestive heart failure, sudden unexpected cardiac death is still considered a major epidemiologic problem among those patients. This article lists some of the predisposing factors to the development of cardiac arrhythmias and sudden death in patients with congestive heart failure. These include electrolyte or autonomic nervous system inbalance, the use of certain anti-arrhythmic drugs, or intermittent myocardial ischemia.
Little is known about differences in practice patterns or outcomes in the management of patients ... more Little is known about differences in practice patterns or outcomes in the management of patients who have atrial fibrillation in Canada compared with those in the United States (US). We evaluated the effect that the country of enrollment may have on the management patterns and clinical outcomes in patients who participated in the AFFIRM study. Three thousand four hundred patients came from the US and 660 from Canada. In the US, patients were more likely to have a history of coronary artery disease (39% vs 35%, p = 0.03), hypertension (72% vs 67%, p = 0.01), or congestive heart failure (24% vs 18%, p = 0.0002). More US participants were &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;65 years of age (25% vs 19%, p = 0.003). Although at randomization the use of warfarin was comparable, during follow-up Canadians were more likely to be treated with warfarin and to be therapeutically anticoagulated. Mortality rate at 5 years was higher in US patients (24% vs 16%, p = 0.001), and the composite end point (death, disabling stroke, major bleeding, cardiac arrest, or anoxic encephalopathy) was also higher in US patients (30% vs 22%, p = 0.0005). Even after adjusting for known differences in baseline characteristics, the risk of death was lower in Canada (hazard ratio 0.70, p = 0.02). In conclusion, in the AFFIRM study, US subjects were more likely to have preexisting cardiovascular diseases despite being younger (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;65 years old) than those in Canada. Effective warfarin therapy was more commonly employed in Canada. After correcting for the known differences in baseline characteristics, Canadian patients who had atrial fibrillation had a lower mortality risk.
This study evaluates the effectiveness and safety of intravenous diltiazem for the treatment of a... more This study evaluates the effectiveness and safety of intravenous diltiazem for the treatment of atrial fibrillation and atrial flutter. A double-blind, parallel, randomized, placebo-controlled protocol was used, and 6 large, urban hospitals, both universityaffiliated and private, participated. The study involved 113 patients with atrial fibrillation or flutter, a ventricular rate 1120 beats/min and systolic blood pressure 190 mm Hg without severe heart failure. The dose of intravenous diltiazem (or identical placebo) was 0.25 mg/kg/2 minutes followed 15 minutes later by 0.35 mg/kg/2 minutes if the first dose was tolerated but ineffective. If a patient did not respond, the code was broken and the patient was allowed to receive open-label diltiazem if placebo had been given. Of 56 patients, 42 (75%) randomized to receive diltiazem responded to 0.25 mg/kg and 10 of 14 responded to 0.35 mg/kg, for a total response rate of 52 of 56 patients (93%), whereas 7 of 57 patients (12%) responded to placebo (p <O.OOl). After the double-blind protocol, 49 of the 57 patients who received placebo were then given diltiazem; 47 of 49 responded, for an overall response rate of 99 of 105 patients (94%) with diltiazem. The median time from the start of drug infusion to the maximal decrease in heart rate was 4.3 minutes. Side effects occurred in 14 patients, 7 of whom had asymptomatic hypotension not requiring intervention. Thus, intravenous diltiazem was rapidly effective for slowing the ventricular response in most patients with atrial fibrillation or atrial flutter. Blood pressure decreased slightly. Side effects were mild.
Serial treadmill exercise testing (mean 5.5 tests/patient) was used to evaluate the prognosis of ... more Serial treadmill exercise testing (mean 5.5 tests/patient) was used to evaluate the prognosis of 200 males (mean age 53 years) without clinical heart failure or unstable angina pectoris 3 weeks after acute myocardial infarction (MI). Exercise-induced ischemic ST-segment depression 0.2 mV 3 weeks after MI was significantly more prevalent in patients with subsequent cardiac arrest (100%) or coronary artery bypass graft surgery (64%) than in patients without subsequent events within 2 years of infarction (35%) (p < 0.05). Exercise-induced ventricular arrhythmia on multiple tests 5-52 weeks after MI was more prevalent in patients with recurrent myocardial infarction (90%) than in patients without subsequent events (47%) (p < 0.001). By contrast, exercise-induced ventricular arrhythmia on a single test at 3 weeks was a less powerful predictor of subsequent cardiac events. Exercise-induced ischemia 3 weeks after MI predicted early fatal events, while ventricular arrhythmia on serial testing predicted later nonfatal events.
Amiodarone is a new and powerful antiarrhythmic agent currently under investigation in North Amer... more Amiodarone is a new and powerful antiarrhythmic agent currently under investigation in North America. In the past two years, there have been increasing reports of serious side effects associated with its use, including 14 cases of pneumonitis or pulmonary fibrosis. This report describes a case of acute necrotizing pneumonitis, a complication that has not been observed previously with amiodarone therapy. Amiodarone also appeared to alter carbohydrate metabolism in this patient. Metabolic changes induced by this drug may be mediated by superoxide radicals. A high index of suspicion for pulmonary complications should be maintained in patients taking amiodarone, and nonspecific respiratory complaints should be investigated carefully.
It is important to consider the hemodynamic effects of antiarrhythmic drugs, because the majority... more It is important to consider the hemodynamic effects of antiarrhythmic drugs, because the majority of patients who require these drugs already have compromised cardiac function. The presently available antiarrhythmic agents vary in their potential for producing negative inotropic effects on the myocardium; they vary, as well, as to the mechanisms by which these effects are produced. The drugs in each of the Vaughan-Williams' classes are discussed in terms of the extent to which they affect cardiac output and the mechanisms by which they may depress cardiac function. Practically all antiarrhythmic agents can decrease cardiac output when administered intravenously. However, when given orally to patients with congestive heart failure, amongst Class I agents, encainide and mexilitine appear to have a reasonably good safety record with respect to the worsening of congestive heart failure. Class III antiarrhythmics also appear to be well tolerated in patients with severe LV dysfunction.
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