Donald C. Harrison

Autonomic cardiac denervation in transplant recipients was associated with an increased incidence of ventricular arrhythmias and altered electrophysiologic responses compared to normal subjects.

BlotCirculation

Outlet strut fractures occurred in 0.7% of 86,000 implanted Björk-Shiley convexoconcave valves over 25 years, with current rates in 60-degree valves at <0.1% per year.

DeMariaJournal of the American College of Cardiology

A survey of cardiovascular specialists revealed that 76% participated in at least one HMO or PPO arrangement, despite concerns over quality of care and general philosophical opposition.

Oral propafenone exhibits complex pharmacokinetics with saturable first-pass hepatic elimination, marked interpatient variability, and may exacerbate ventricular arrhythmias in 20-15% of patients.

Synchrotron radiation transvenous coronary angiography successfully acquires diagnostic coronary angiograms in humans.

The risks and costs of the present method of visualizing the coronary arteries have limited the use of coronary angiography in long-term serial studies needed to establish the natural history of coronary atherosclerosis and its response to interventions. A less invasive method, in which the contrast agent is administered intravenously, has been developed using synchrotron radiation as the illuminating source. The present report describes the initial results in human subjects. The findings indicate that transvenous coronary angiograms can be acquired in this manner. Further refinements in the x-ray imaging system are expected to result in increased x-ray fluence and improved image quality.

Transient complete heart block occurred in 17.6% of aortic and 13% of mitral valve replacements, but no predictive factors were identified and it did not predict late recurrence of AV block.

ConnollyClinical Pharmacology & Therapeutics

Propafenone administration in patients with ventricular arrhythmias showed a terminal t1/2 of 5.0 +/- 3.6 hr, which increased to 6.2 +/- 3.3 hr after 5 days of oral dosing.

ConnollyCirculation

There was a greater than 90% reduction of ventricular premature beats in 10 subjects during dose ranging and in seven during double-blind crossover.

BristowNew England Journal of Medicine

Decreased Catecholamine Sensitivity and β-Adrenergic-Receptor Density in Failing Human Hearts

Metabolite cumulation during long-term oral encainide administration

Cumulation of encainide and its major metabolites, O-demethylencainide (ODE), 3-methoxy-ODE (MODE), and N-demethylencainide (NDE) was examined in patients with frequent complex ventricular ectopy. After 6 mo on encainide patients were admitted to Stanford University Hospital and the drug was discontinued for 24 hr. During this time blood samples were drawn to characterize the cumulation and disposition of the drug and metabolites. The mean steady-state concentrations of encainide, ODE, and MODE were 56.3, 214.6, and 184.6 ng/ml after doses ranging from 100 to 250 mg/day. The concentration ratios of ODE/encainide and MODE/encainide were 5.02 +/- 2.61 and 5.15 +/- 4.13. NDE was detected in the plasma of only one patient. Elimination half lifes of encainide and ODE were 1.16 +/- 0.5 and 11.41 +/- 9.58 hr. MODE disappeared slowly and at 24 hr the plasma concentration was still 59.8 +/- 39.9% of its mean steady-state concentration. Our data indicate that the metabolites of encainide cumulate in the plasma of patients on long-term oral therapy and must be considered when evaluating its clinical efficacy.

Quantitation Of Coronary Artery Dimensions Using Digital Image Processing

Sequential observations of coronary artery disease depend upon reproducibility of measurements of coronary dimensions. Because the coronary artery segment to be digitized for quantitation occupies only a small portion of the 35 mm cine frame, a cine projector was mounted on a movable X, Y stage so that the area of interest could be focused through a lens turret system onto a video camera. The lens turret provides lx, 3.5x, and 7x magnification. A digital image processing device operating under computer control permits direct application of smoothing and edge finding algorithms to the magnified coronary image. Using separately recorded grids, an external reference marker, and isocentering of the heart within a U-arm radiographic system, it is possible to adjust for distortion and magnification. A split screen technique provides capability for single plane or sequential biplane analyses. A digital lightpen is used to input fiducial points for segment identification and define an initial coronary margin which is superceded by computer defined edges. Final measurements include maximum, minimum and mean diameter of 1.0 cm long coronary segments and the absolute area of the segment profile, along with provision for hard copy image recording. Reproducibility of the minimum and maximum diameter measurements provided by the digitization system and edge finding algorithm are + .06 mm for vessels with an average diameter of 2.3 mm (+ S.D.). When duplicate coronary injections during the same catheterization procedure are made, the coefficient of variation of the minimum diameter is 9.5%, of the maximum diameter 5.0% and of the segment area 3.9%. The capability for area of interest selectivity, variable optical magnification and digital image analysis provides a unique and reproducible system for coronary segment quantitation.

Eight of nine patients had more than 90% suppression of premature ventricular complexes for 3-36 hours.

Verapamil administration in patients with chronic atrial fibrillation showed 35% oral bioavailability, with long-term oral therapy yielding plasma concentrations twice the predicted single-dose value.

Coronary Bypass: The First 10 Years

The combination of cyclosporin A and dipyridamole prevented the development of graft arteriosclerosis in transplanted rat hearts at 20 and 50 days postoperatively.

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.

Once-daily atenolol reduces anginal attacks and suppresses 24-hour resting and exercise heart rates.

The physiology, pharmacokinetics and efficacy of atenolol, a cardioselective beta-adrenergic blocking agent, were evaluated in 10 patients with stable angina pectoris in a single-blind, dose-ranging study. After a 1-month control placebo period, atenolol was administered once daily at dosages of 25, 50, 100 and 200 mg for 2-week periods. All patients had fewer anginal attacks and consumed fewer nitroglycerin tablets than mg for 2-week periods. All patients had fewer anginal attacks and consumed fewer nitroglycerin tablets than during the placebo period. Twenty-four-hour ambulatory ECG recordings showed a decrease in mean hourly heart rate throughout the dosing period, with preservation of diurnal variation. Maximal, symptom-limited, treadmill exercise tests performed 3 hours after drug ingestion showed significantly increased exercise time and decreased double products for all doses, but especially with 100-mg and 200-mg doses. Exercise time 24 hours after drug ingestion continued to show a decrease in maximum heart rate and double product, with 100-mg and 200-mg doses again being most effective. Atenolol serum levels correlated with percent reduction in exercise heart rate and increased exercise time. Serum levels rose linearly, with an average elimination half-life of about 10 hours after chronic oral dosing. Thus, atenolol was an effective antianginal agent and suppressed resting and exercise-stressed heart rate for 24 hours after ingestion when given in a 100-mg or 200-mg dose once daily.

Noninvasive cardiac instrumentation enables quantification of cardiac function and disease severity.

In the past three decades, techniques that permit noninvasive quantitation of the function of the heart have been developed. Exercise electrocardiography has been widely used to determine the presence or absence of ischemic heart disease. Echocardiography permits detection of valvular, congenital and arteriosclerotic disease and quantitation of its severity. Selective use of isotopes allows nuclear angiogarphy, myocardial perfusion studies and detection of damage to cellular myocardium. New techniques such as computerized axial tomography, magnetometry, focused pulsed Doppler, and wider application of computer-enhanced image processing are important future directions for noninvasive monitoring.

Influence of congestive heart failure on prazosin kinetics

The kinetics of oral prazosin was studied in 10 healthy normal subjects (NS) and in 9 patients with congestive heart failure (CHF). NS received a single 5-mg dose, and blood concentrations of prazosin (CB) were measured, using a specific HPLC assay, during an 8-hr period. CHF patients received a 2-mg dose after which CB was measured for 10 hr. These patients then received 2 to 5 mg prazosin every 8 hr for 48 hr. After the last dose of prazosin, CB was measured for 24 hr. After the initial dose, time to peak CB did not differ significantly between that of the NS (123 +/- 19 SEM min) and of patients with CHF (132 +/- 31.3 min). AUC/mg prazosin was greater (p less than 0.001) in patients with CHF (3,385 +/- 380 Ng x min/ml) than in NS (1,603 +/- 208 ng x min/ml). Elimination of prazosin from blood was slower in CHF patients (t1/2 = 374 +/- 33.4 min) than in NS (t1/2 = 144.5 +/- 4.3 min) (p less than 0.001). These data suggest that in patients with CHF the elimination of prazosin is substantially slower than in NS and therefore higher steady-state prazosin concentrations can be expected in CHF patients than in NS.

Should lidocaine be administered routinely to all patients after acute myocardial infarction?