Charles M. Blatt

Aggravation of arrhythmia by antiarrhythmic drugs—Incidence and predictors

Aggravation of arrhythmia by antiarrhythmic drugs is a potentially serious complication. In over 1,287 noninvasive drug studies involving 11 antiarrhythmic drugs, arrhythmia aggravation occurred in 117 tests (9%). During 248 electrophysiologic tests, 45 cases (18%) of aggravation occurred. In an attempt to define predictors of this complication, 51 patients with aggravated arrhythmia were compared with 102 patients without this complication. Arrhythmia aggravation was not associated with age, sex, type or extent of heart disease, baseline electrocardiogram, drug-induced changes on electrocardiogram or density of baseline arrhythmia on monitoring or exercise testing. Aggravation with 1 drug did not predict occurrence with another drug of the same class. The only statistically important relation was the type of presenting arrhythmia. Patients with a history of a sustained tachyarrhythmia (ventricular tachycardia or ventricular fibrillation) had a risk of this complication that was 2.5 times greater than that of patients presenting with only nonsustained ventricular tachycardia or ventricular premature beats (p = 0.01). There was also a relation to the presence of left ventricular dysfunction (p = 0.04). For the most part, however, aggravation of arrhythmia is not predictable, and cautious use of antiarrhythmic drugs is essential.

Determinants of survival in patients with malignant ventricular arrhythmia associated with coronary artery disease

The long-term survival data in patients with coronary artery disease and a history of malignant ventricular arrhythmia, defined as noninfarction ventricular fibrillation (VF) or hemodynamically compromising ventricular tachycardia (VT) followed for up to 9 years, were analyzed. In this group of 161 patients there was a total of 57 deaths, of which 35 (63%) were sudden. Life-table analysis demonstrated a 10% sudden death rate for all patients in the first year and a 7% annual rate in the subsequent 4 years. In patients managed noninvasively, the overall mortality rate was 27% over 9 years, or 3% per year. Suppression of ventricular tachycardia on both ambulatory monitoring and exercise testing was associated with improved survival. In patients evaluated by electrophysiologic testing the sudden death rate was 1.4% per year over an average of 5 years. This survival rate was not different compared with the noninvasive group (p = 0.09). Measures of left ventricular dysfunction and the frequency of ventricular arrhythmia before and after drug therapy were associated with a risk of sudden cardiac death by univariate analysis. Multivariate regression analysis identified 4 variables as independent predictors of sudden cardiac death: rales (p = 0.009), the number of runs of VT during exercise testing while receiving antiarrhythmic drug therapy (p = 0.0003), a history of congestive heart failure (p = 0.0009) and the number of premature beats on Holter monitoring (p = 0.01). These findings support the concept that suppression of repetitive arrhythmia on Holter monitor and exercise testing is a marker for improved survival among patients with malignant ventricular arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)

Thermal Panting in Dogs: The Lateral Nasal Gland, a Source of Water for Evaporative Cooling

Two lateral nasal glands appear to provide a large part of the water for evaporative cooling in the panting dog; their function is analogous to that of sweat glands in man. Each gland drains through a single duct which opens about 2 centimeters inside the opening of the nostril. This location may be essential to avoid desiccation of the nasal mucosa during thermal panting. The rate of secretion from one gland increased from 0 to an average of 9.6 g (gland � hour)-1 as air temperature was increased from 10� to 50�C. Evaporation of the fluid from the paired glands could account for between 19 and 36 percent of the increase in respiratory evaporation associated with thermal panting. The fluid secreted by the gland was hypoosmotic to plasma.

Central serotonergic agents raise the repetitive extrasystole threshold of the vulnerable period of the canine ventricular myocardium.

Systemic administration of three central serotonergic agents, melatonin, 5-methoxytryptophol, and 6-chloro-2-(l-piperazinyl)-pyrazine (MK-212), produced significant increases in the threshold of the vulnerable period for repetitive electrical activity in the canine cardiac ventricle. MK-212 was effective despite bilateral vagotomy. The specific serotonin antagonist, metergoline, blocked the effect of MK-212 on the threshold. An increase in central serotonergic activity may inhibit the flow of arrhythmogenic sympathetic nerve traffic from the brain to the heart. Cirv Res 44: 723-730, 1979

Exercise performance-based outcomes of medically treated patients with coronary artery disease and profound ST segment depression

OBJECTIVES We sought to determine the relationship between exercise duration and cardiovascular outcomes in patients with profound (> or =2 mm) ST segment depression during exercise treadmill testing (ETT). BACKGROUND Patients with stable symptoms but profound ST segment depression during ETT are often referred for a coronary intervention on the basis that presumed severe coronary artery disease (CAD) will lead to unfavorable cardiovascular outcomes, irrespective of symptomatic and functional status. We hypothesized that good exercise tolerance in such patients treated medically is associated with favorable long-term outcomes. METHODS We prospectively followed 203 consecutive patients (181 men; mean age 73 years) with known stable CAD and > or =2 mm ST segment depression who are performing ETT according to the Bruce protocol for an average of 41 months. The primary end point was occurrence of myocardial infarction (MI) or death. RESULTS Eight (20%) of 40 patients with an initial ETT exercise duration < or =6 min developed MI or died, as compared with five (6%) of 84 patients who exercised between 6 and 9 min and three (3.8%) of 79 patients who exercised > or =9 min (p = 0.01). Compared with patients who exercised < or =6 min, increased ETT duration was significantly associated with a reduced risk of MI/death (6 to 9 min: relative risk [RR] = 0.25, 95% confidence interval [CI] 0.08 to 0.76; >9 min: RR = 0.14, 95% CI 0.04 to 0.53). This protective effect persisted after adjustment for potentially confounding variables. We observed a 23% reduction in MI/death for each additional minute of exercise the patient was able to complete during the index ETT. CONCLUSIONS Optimal medical management in stable patients with CAD with profound exercise-induced ST segment depression but good ETT duration is an appropriate alternative to coronary revascularization and is associated with low rates of MI and death.

Acute Blood Pressure Elevation and Ventricular Fibrillation Threshold During Coronary Occlusion and Reperfusion In the Dog

The effect of acute elevation of arterial blood pressure on the ventricular fibrillation threshold was examined in 19 closed chest dogs anesthetized with chloralose during 10 minutes of occlusion followed by abrupt reperfusion of the left anterior descending coronary artery. Ventricular fibrillation threshold was determined using two methods of electrical testing: sequential R/T pulsing and the train of stimuli method. Blood pressure was increased with an intravenous injection of the alpha adrenergic stimulator phenylephrine. Acute hypertension significantly diminished the enhanced vulnerability associated with coronary occlusion. After denervation of the carotid sinus and aortic arch baroreceptors, elevation of blood pressure failed to affect vulnerability during occlusion. In both intact and denervated animals, the predisposition to ventricular fibrillation after reperfusion was unchanged by the increase in blood pressure. It is suggested that withdrawal of sympathetic tone mediated by the baroreceptor reflex is the basis for the protection against ventricular fibrillation resulting from elevation of blood pressure. The failure of acute hypertension to alter vulnerability during reperfusion suggests that the predisposition to ventricular fibrillation during reperfusion is due to mechanisms other than those operating during coronary occlusion.

Clinical experience with technetium-99m stannous polyphosphate for myocardial imaging.

Myocardial imaging with technetium-99m stannous polyphosphate was performed on 46 patients. Eleven patients had no cardiac disease, 22 had acute myocardial infarction, and 13 had stable arteriosclerotic heart disease. Distinct patterns of myocardial activity were noted: (1) the patients with no obvious cardiac disease showed no cardiac activity; (2) stable arteriosclerotic heart disease showed faint, ill-defined cardiac activity, primarily in the anterior or inferior aspect of the left ventricle; (3) acute myocardial infarction showed intense, focal, well-defined activity, with a shape that characterized the location of the infarct.

Considerations of current methods for drug selection in treating malignant ventricular arrhythmias

The current burgeoning interest in antiarrhythmic drugs derives in large measure from a growing concern with the enormous problem of sudden cardiac death. Until the latter half of the twentieth century, beyond a nodding acknowledgment of its massive prevalence, this syndrome received but scant attention from the medical profession. In the early 1960s a number of insights changed perceptions as well as practice. These related to 4 postulates: (1) sudden cardiac death, in the majority of victims, was due to ventricular tachyarrhythmias either initiated by or culminating rapidly in ventricular fibrillation; (2) the lethal arrhythmia was not the consequence of irreversible pathomorphologic impairment of the contractile apparatus, but rather the expression of an electrophysiologic derangement; (3) the triggering of ventricular fibrillation was the result of an electrical accident both reversible as well as preventable; (4) the potential victim was identifiable either by the presence of certain grades of ventricular ectopic activity or by exposure of repetitive ectopic activity or by exposure of repetitive ventricular arrhythmias by electrophysiologic techniques. The innovations that have led to these insights and their consequences have been numerous and continuous. Among these are direct current defibrillation, cardioversion, coronary care units, bystander-initiated cardiopulmonary resuscitation, ambulatory electrocardiographic monitoring and exercise stress testing for exposing ventricular arrhythmias, electrophysiologic provocative testing and mapping techniques, overdrive programmable pacemakers as well as implantable defibrillators and cardioverters, and surgical, electrical and laser techniques for ablating the nidus or interrupting the pathways of the arrhythmias.

Precordial mechanical stimulation for exposing electrical instability in the ischemic heart

Sequenital mechanical pulsing of the chest wall with three stimuli failed to induce arrhythmias in normal dogs. After coronary arterial occlusion, this technique evoked in 11 of 12 animals repetitive ventricular tachycardia in 2. These responses corresponded closely to those elicited by electrical testing. In four conscious animals after recovery from myocardial infarction, precordial pulsing induced repetitive ventricular arrhythmias. The type of arrhythmia produced depended on the degree of prematurity of the third pulse in the sequence. The use of precordial mechanical stimulation can perhaps be modified and adapted as a method of detecting persons at high risk for sudden cardiac death.

A Noninvasive Means for Assessing Glycoside Toxicity: Mechanically Induced Repetitive Ventricular Response

Summary An external mechanical cardiac thump was used to induce a repetitive ventricular response (RVR) in dogs receiving acetyl strophanthidin (AS), a rapidly acting glycoside. The presence of RVR prior to and after termination of AS-in-duced ventricular tachycardia was confirmed by both mechanical and electrical cardiac testing. Mechanically induced RVR may provide a rapid, noninvasive method for assessing the degree of digitalization.