Joseph S. Alpert

Clinical pharmacokinetics and efficacy of amiodarone for refractory tachyarrhythmias.

Using a high-pressure liquid chromatographic assay, we measured serum amiodarone concentrations serially in 122 patients treated with amiiodarone for 1.5–53 months (mean 9.3 months) for control of refractory symptomatic atrial or symptomatic and life-threatening ventricular tachyarrhythmias. The atrial tachyarrhythmias were successfully controlled in 45 of 54 patients (83%) during a mean follow-up of 10.0 months. In the ventricular tachyarrhythmia group, which included 22 survivors of sudden cardiac death, 38 of 50 patients (76%) responded to amiodarone during a mean follow-up of 10.9 months. Although the mean serum amiodarone concentration did not differ between responders and nonresponders, eight responders relapsed when their serum concentration fell below 1.0 mg/I. Side effects resulted in withdrawal of amiodarone in only 10 of 122 patients (9%) despite a 30% overall incidence of side effects. Central nervous system and gastrointestinal side effects became more frequent with serum concentrations > 2.5 mg/l, although only central nervous system side effects achieved statistical significance. Absorption and disposition kinetics of a single oral 800-mg dose of amiodarone were studied in eight patients. Serum values were measured for 24 hours in five patients during maintenance therapy, and elimination kinetics after long-term therapy were evaluated in three patients. The tissue concentration of amiodarone was determined in two patients who died during long-term amiodarone therapy and an attempt was made in 14 patients to correlate serum concentrations with daily dosages during maintenance therapy. The pharmacokinetics of oral amiodarone support the practice of using high loading dosages until arrhythmia suppression or apparent steady state is achieved (usually 2–4 weeks), followed by low-dose maintenance therapy (200400 mg once a day) for treatment of symptomatic atrial and ventricular tachyarrhythmias.

The impact of age on the incidence and prognosis of initial acute myocardial infarction: The Worcester Heart Attack Study

As part of a community-wide study examining time trends in the incidence and case-fatality rates (CFR) of patients hospitalized with acute myocardial infarction (MI) in sixteen hospitals in the Worcester, Massachusetts metropolitan area, the association of age to the incidence rates of initial acute MI and to in-hospital and long-term survival among 2115 patients with validated acute MI was examined. After selected age-specific changes in the incidence rates of initial events of acute MI between 1975 and 1981, the incidence rates of acute MI markedly declined between 1981 and 1984, resulting in decreases in the age-specific incidence rates of initial acute MI between 1975 and 1984. For the combined study periods, the in-hospital CFR of acute MI increased from 5.0% in patients less than 55 years of age to 7.9% in those 55 to 64 years, to 16.1% in those 65 to 74 years and to 32.1% in patients 75 years of age and older. Among discharged hospital survivors, increasing age was related to poorer long-term survival over a 5-year follow-up period. The results of this population-based study reinforce the need for, and importance of, modification of coronary risk factors in both young and older individuals, and of focused therapeutic efforts to salvage jeopardized myocardium in elderly patients hospitalized with acute MI.

Patient delay and receipt of thrombolytic therapy among patients with acute myocardial infarction from a community-wide perspective

The duration of patient delay from the time of onset of symptoms of acute myocardial infarction (AMI) to hospital presentation, and the relation of delay time and various patient characteristics to receipt of thrombolytic therapy were examined as part of a community-based study of patients hospitalized with AMI in the Worcester, Massachusetts, metropolitan area. In all, 800 patients with validated AMI hospitalized at 16 hospitals in the Worcester metropolitan area in 1986 and 1988 constituted the study sample. Patients delayed on average 4 hours between noting symptoms suggestive of AMI and presenting to area-wide emergency departments with no significant change observed between 1986 and 1988. The shorter the time interval of delay, the greater the likelihood of receiving thrombolytic therapy; patients arriving at the emergency department within 1 hour of the onset of acute symptoms were approximately 2.5 and 6.5 times more likely to receive thrombolytic agents than were those presenting to the hospital between 4 and 6, and greater than 6 hours, respectively, after the onset of symptoms. Results of a multivariate analysis showed increasing length of delay, older age, history of hypertension or AMI and non-Q-wave AMI to be significantly associated with failure to receive thrombolytic therapy.

A theoretically and practically more effective method for interruption of ventricular tachycardia: self-adapting autodecremental overdrive pacing.

The efficacy and safety of a new antitachycardia pacing technique, self-adapting decremental overdrive pacing, was assessed in patients with clinical ventricular tachyarrhythmias who underwent programmed ventricular stimulation and serial drug testing. The three phases of this study involved a learning/experience phase, followed by intrapatient comparison of decremental overdrive pacing with conventional antitachycardia pacing modalities of overdrive burst ventricular pacing, and diastolic scanning with single (S2) and double (S2S3) ventricular extrastimuli. The final phase involved an intrapatient comparison of automated decremental overdrive pacing with overdrive burst ventricular pacing in patients with ventricular tachycardia (VT) cycle lengths of 280 msec or greater. Decremental overdrive pacing was superior to overdrive burst pacing and diastolic scanning (S2S3 and S2) (83% vs 38%, 50%, 9%) in patients with VT cycle lengths of 280 msec or greater. Automated decremental overdrive pacing as applied in the final phase was the most efficacious modality, terminating 92% of VT episodes compared with 56% for overdrive burst pacing in the same patients.

Preliminary experience with synchronized coronary sinus retroperfusion in humans.

Synchronized coronary sinus retroperfusion (SCSR) with arterial blood has been extensively tested in animals. This intervention offers temporary support to areas of ischemic myocardium while a method of definitive revascularization is being sought. The feasibility and safety of this procedure for patients with unstable angina was therefore tested. A No. 7F autoinflatable retroperfusion balloon catheter (USCI) was inserted percutaneously into the coronary sinus of the study patients. Arterial blood was obtained through a No. 8F catheter placed in the femoral artery. Arterial blood was infused in a retrograde fashion into the coronary venous system during cardiac diastole by means of a piston-driven pump that was electrocardiographically synchronized with the drainage of the venous system during systole. This procedure was performed in five patients with unstable angina refractory to maximum medical therapy. SCSR significantly decreased the frequency of anginal episodes and the requirement for antianginal medications. SCSR also provided time for patient stabilization before diagnostic cardiac catheterization or therapeutic intervention. This preliminary experience suggests that synchronized coronary sinus retroperfusion is a feasible and safe procedure. It can be performed at the bedside with no apparent adverse effects to the patient. Retroperfusion also appears to be effective in relieving ischemic symptoms as assessed by clinical parameters. Based on our preliminary experience, further delineation of its clinical applications is warranted.

Dissection of the thoracic aorta. Medical or surgical therapy

Abstract Both medical and surgical therapy are available for the treatment of aortic dissection. To help determine which form of treatment is indicated for which patients, all cases of aortic dissection at the Peter Bent Brigham Hospital from 1963 to 1973 were reviewed. The most important feature in determining the patients clinical status and response to therapy was the site of dissection, that is, the ascending or descending aorta. Of 31 patients with dissection of the ascending aorta, 26 had one or more of the following contraindications to medical therapy: congestive heart failure (8 patients), hemopericardium (8 patients), new aortic insufficiency (13 patients) or jeopardized carotid or coronary arteries (4 patients). Medical therapy was successful in only 1 of 9 patients with dissection of the ascending aorta; 17 of 22 patients having surgical correction of this lesion did well and were discharged. The clinical status of the 14 patients with dissection limited to the descending aorta was quite different. None had a contraindication to medical therapy. Medical therapy was instituted in all 14, and was successful in 6; dissection progressed in 8 patients despite medical therapy, and subsequent surgery was successful in only 2. We conclude that the treatment of choice for dissection of the ascending aorta is prompt surgical therapy. In patients with dissection limited to the descending aorta, medical therapy is usually feasible and often successful.

Assessment of left ventricular function in severe aortic regurgitation

SUMMARY Echocardiographic (echo) measurements of left ventricular ejection phase indices — ejection fraction, percent shortening of the minor diameter (%ΔD), and velocity of circumferential fiber shortening (Vcf) — are said to be accurate reflections of their angiographic (angio) counterparts. Most studies correlating echo and angio left ventricular function parameters have induded relatively few patients with aortic regurgitation. Echo and angio measurements of left ventricular ejection phase indices thus might not correlate in these patients in whom left ventricular geometry may have been altered due to the volume overload. To test this hypothesis, left ventricular ejection phase indices were determined by angiography and echocardiography and compared in 20 patients with isolated, symptomatic, severe aortic regurgitation. Ejection fraction, %ΔD, and Vcf by LAO cineangiograms and echo were uniformly higher than corresponding meaurements from RAO angio, and were often normal in the presence of other indicators of significant left ventricular dysfunction. We conclude that the usual, linear echocardiographic measurement of left ventricular wall motion may not reflect sigpificant myocardial dysfunction in patients with severe aortic regurgitation.

Regional left ventricular function in acute myocardial infarction: Evaluation with quantitative radionuclide ventriculography

Regional and global left ventricular performance was noninvasively assessed with quantitative gated equilibrium radionuclide ventriculography in 43 patients an average of 40 hours after the onset of a first acute transmural myocardial infarction. In all 16 patients with anterior infarction, regional ejection fraction, a quantitative measure of regional left ventricular performance, was uniformly depressed in the infarcted zone. In patients with inferior infarction the abnormalities of regional performance were less severe. Fourteen of 20 patients (70 percent) with inferior infarction had depressed performance in the infarcted zone. Function in noninfarcted zones was abnormal in only 6 of the 20 patients (30 percent) with inferior infarction, but it was abnormal in 11 of the 16 patients (69 percent) with anterior infarction, particularly in those with severe pump failure. As a consequence, global left ventricular ejection fraction was significantly lower in patients with anterior than in those with inferior infarction (mean +/- standard error of the mean 31 +/- 3 percent versus 51 +/- 3 percent, less than 0.005). Prognosis and clinical functional class were related to performance not only in infarcted zones, but also in noninfarcted zones as assessed with electrocardiography. It is concluded that depressed function in apparently noninfarcted left ventricular zones contributes significantly to left ventricular dysfunction after acute myocardial infarction, particularly in patients with anterior infarction.

Effects of Physical Training on Hemodynamics and Pulmonary Function at Rest and during Exercise in Patients with Chronic Obstructive Pulmonary Disease

Five patients with severe chronic obstructive pulmonary disease (COPD) underwent detailed evaluation of pulmonary function (PF), respiratory mechanics and hemodynamics before and after 18 weeks of physical training (PT). PT consisted of daily progressive upright bicycle exercise. All patients demonstrated marked subjective and objective improvement in exercise tolerance. After PT exercise heart rates were significantly decreased (p

Therapy of symptomatic pericarditis after myocardial infarction: Retrospective and prospective studies of aspirin, indomethacin, prednisone, and spontaneous resolution

We studied the efficacy of aspirin and indomethacin therapy in relieving the discomfort of postmyocardial infarction pericarditis (PMIP) in two studies: (1) a retrospective evaluation of patients with symptomatic PMIP during a 5-year period and (2) a prospective, randomized, single-blind comparison of aspirin and indomethacin in similar patients. In the retrospective study, 36 episodes of symptomatic PMIP in 34 patients were identified; in the prospective study, 25 episodes of PMIP in 24 patients occurred. Relief from the discomfort of PMIP was noted within 48 hours in almost all patients with either indomethacin or aspirin therapy. Minor gastrointestinal bleeding developed in two patients in the retrospective study and in two patients in the prospective study. In the retrospective study, mild discomfort of PMIP abated within 48 hours in five of eight patients who received either no treatment or minor analgesic therapy. Aspirin and indomethacin are equally efficacious in relieving the discomfort of PMIP.