Kenneth F. Hossack

The Sudden Unexplained Death Syndrome in Epilepsy: Demographic, Clinical, and Postmortem Features

Summary: Sudden unexplained death syndrome (SUDS) accounts for about 10% of deaths in patients with epilepsy. It is associated with subtherapeutic postmortem serum antiepileptic drug (AED) levels but no anatomic cause of death on autopsy. The mechanisms of death are not known. We investigated 44 cases of SUDS for details of seizure history, treatment, medical and psychological history, events at the time of death, and postmortem findings. Cases of status epilepticus, drowning or other identifiable causes of death were excluded. Two groups emerged: five children with uncontrolled seizures receiving multiple AEDs and good compliance with medications, and 39 adults with less frequent seizures, often receiving monotherapy, but noncompliant with medications. Four children (80%) but only one adult (3%) had fully therapeutic postmortem AED levels. Sixty‐three percent of adults recently had experienced an unusually stressful life event. Investigation of the circumstances at the time of death suggested two possible modes of death: (a) a seizure with an immediately fatal arrhythmia, or, (b) a seizure, recovery, then delayed secondary respiratory arrest or arrhythmia. Even though the mechanisms of death are unknown, the risk of SUDS may be reduced by encouraging patients to be compliant with medications, especially in times of unusual life stress.

Echocardiographic Findings in Autosomal Dominant Polycystic Kidney Disease

Echocardiography, including Doppler analysis, was performed to assess the prevalence of cardiac abnormalities in 163 patients with autosomal dominant polycystic kidney disease, 130 unaffected family members, and 100 control subjects. In these three groups, the prevalence of mitral-valve prolapse was 26, 14, and 2 percent, respectively (P less than 0.0005). A higher prevalence of mitral incompetence (31, 14, and 9 percent, respectively; P less than 0.005), aortic incompetence (8, 3, and 1 percent, respectively; P less than 0.05), tricuspid incompetence (15, 7, and 4 percent, respectively; P less than 0.02), and tricuspid-valve prolapse (6, 2, and 0 percent, respectively; P less than 0.02) was also found in the patients with polycystic kidney disease. These findings reflect the systemic nature of polycystic kidney disease and support the hypothesis that the disorder involves a defect in the extracellular matrix and the cardiac abnormalities are an expression of that defect.

Efficacy of diltiazem in angina on effort: a multicenter trial.

During a multicenter study 57 patients with exercise-induced angina were evaluated with serial exercise testing to assess the efficacy of diltiazem, a calcium slow channel blocking agent, compared with a placebo. The study consisted of a 1 week single-blind placebo stabilization period followed by a double-blind triple crossover between diltiazem and placebo. Three dose levels were tested (120, 180 and 240 mg/day) in each patient. For the three time-related variables there was a significant dose-related response, with 240 mg/day being the most effective. The increases, over the washout placebo stabilization values, of the time-related variables for the 240 mg/day week compared with the corresponding placebo week were total duration of exercise 1.87 versus 1.05 minutes (p less than 0.002), time to onset of angina 1.81 versus 1.17 minutes (p less than 0.01) and time to appearance of 1 mm S-T segment depression 1.81 versus 1.01 minutes (p less than 0.002). Analysis of exercise variables indicated a significant reduction in heart rate, diastolic blood pressure, and pressure-rate product at submaximal exercise after administration of diltiazem. Diastolic blood pressure was significantly reduced at maximal exercise. Heart rate and pressure-rate product were unchanged at rest during submaximal or maximal exercise. Submaximal and maximal exercise S-T depression was not significantly altered by diltiazem. The reduction in pressure-rate product at submaximal exercise was a possible mechanism for the drugs beneficial effect in enhancing the three time-related variables.

Validation of exercise-enhanced risk assessment of coronary heart disease events: Longitudinal changes in incidence in Seattle community practice

Noninvasive criteria developed in a learning series for exercise-enhanced risk assessment for events due to coronary heart disease have been applied to a test series in a later population sample. Men in the same age and risk groups for each pretest clinical classification show similar gradients of risk. Thus, exercise-enhanced criteria for risk assessment are validated. Age-standardized event rates show a reduction longitudinally in healthy men and patients who have had coronary bypass surgery.

Amlodipine in chronic stable angina: Results of a multicenter double-blind crossover trial

The efficacy and safety of amlodipine, 10 mg, a new long-acting calcium antagonist, was compared with placebo in 103 patients with stable angina pectoris in a multicenter double-blind crossover study. The trial consisted of an initial 2-week single-blind placebo period followed by a first period of 4 weeks of double-blind therapy, which was followed by a 1 week washout period and then a second 4-week double-blind period after treatments were crossed over. Twenty-four-hour Holter electrocardiographic monitoring was carried out in 12 patients at three centers. In the first double-blind period amlodipine produced a significantly greater increase in symptom-limited exercise duration (amlodipine 478.5 to 520.6 vs placebo 484.6 to 485.2 seconds; change +8.8% vs +0.1%, respectively; p = 0.0004) and total work (amldipine 2426 to 2984 vs placebo 2505 to 2548 kilopondmeters; change +24% vs +1.7%, respectively; p = 0.0006) and a decrease in angina attack frequency (from 3 to 1 per week; p = 0.016) and nitroglycerin consumption (from 2 to 0.5 tablets/wk; p = 0.01) compared with placebo. Holter monitoring revealed significant reductions in numbers (amlodipine 4.65 to 2.22 vs placebo 1.84 to 1.54; change -52% vs +84%, respectively; p = 0.06), absolute total area (amlodipine 87.66 to 11.43 vs placebo 5.76 to 35.24; change -87% vs +513%, respectively; p = 0.02), and duration (amlodipine 12.29 to 2.95 vs 1.66 to 7.74 seconds; change -76% vs +367%, respectively; p = 0.008) of ST-segment depressions after treatment with amlodipine compared with placebo. After the treatments were crossed over changes continued to favor amlodipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Transvenous biopsy diagnosis of cardiac lymphoma in an AIDS patient

mass compressed the left atrium and was not an artifact due to far-field imaging and poor lateral resolution.7 Luminal pressure may have been sufficient to compress the left atrium, since motor activity may increase pressure throughout the esophagus if the lumen is not ob1iterated.s In addition, the hydrostatic pressure exerted by a column of fluid may contribute to the increase in luminal pressure.2 Thus changes in lower esophageal tone and intermittent esophageal emptying may have resulted in dynamic changes in luminal pressure sufficient to compress and decompress the left atrium. Our case illustrates that functional as well as structural disorders of the esophagus hould be considered in the differential diagnosis of extracardiac masses that compress the left atrium. It also highlights the superiority of CT scanning over two-dimensional echocardiography for the characterization of extracardiac masses.

Patterns of Oxygen Consumption during Exercise Testing in Peripheral Vascular Disease

Exercise testing on a treadmill was performed in 15 patients with peripheral vascular disease to determine the pattern of oxygen consumption during exercise. A plateau in the oxygen consumption over the final 90 s of exercise was used as a criterion for maximal effort and only 4 out of 15 (27%) obtained a plateau of oxygen consumption compared to 20 out of 26 (77%) normal subjects (chi 2 7.9, p less than 0.005). These findings may account for the limited value of exercise testing in detecting coronary artery disease in patients with peripheral vascular disease.

Effects of the limiting symptom on the achievement of maximal oxygen consumption in patients with coronary artery disease

This study was conducted to determine if the limiting symptom in patients with coronary artery disease (CAD) influenced the pattern of oxygen consumption (VO2) over the final 90 seconds of a maximal exercise test. The pattern was classified according to the presence or absence of a plateau. Twenty-six normal persons and 55 patients with CAD were studied. They rated the severity of fatigue, dyspnea and angina at end exercise using the Borg scale and designated which symptom was the limiting factor. A plateau of VO2 over the final 90 seconds of exercise was observed in 77% of normal subjects and patients with CAD. Eighty percent of patients limited by angina achieved a plateau. In normal subjects and patients with CAD, peak VO2 was more reproducible than the pattern of VO2 over the final 90 seconds of exercise. There were no differences in the cardiac responses to exercise at maximal effort between patients who achieved a plateau of VO2 and those who did not. These results indicate that the limiting symptom of exercise, even angina pectoris, does not influence the ability to exercise maximally. Therefore, the peak value of VO2 during symptom-limited treadmill exercise is a valid measure of maximal cardiovascular capacity irrespective of the limiting symptom or the pattern of VO2 in the final 90 seconds of exercise.

Psychosocial coping strategies and cardiac capacity before and after coronary artery bypass surgery.

One hundred patients, eighty-nine men and eleven women, with chronic stable angina who were previously selected for aortocoronary bypass grafting gave informed consent for non-invasive and invasive testing of hemodynamic responses to symptom-limited maximal exercise before surgery. Psychosocial coping strategies were evaluated preoperatively by structured interviews and assessment of patients perceptions of symptoms (Cornell Medical Index) and life changes (Holmes and Rahe Schedule of Recent Experiences). Preoperatively forty-one patients were “compartmentalized,” forty-two “generalized” and seventeen “vacillated” according to Jostens classification of coping strategies. The Berle Index of social assets was lower and the prevalence of psychiatric symptoms (Cornell categories M to R) was greater in the vacillators preoperatively. Despite less ischemic ST depression in vacillators, no other significant physiological differences were noted between these categories preoperatively. Postoperatively more of the vacillators refused follow-up evaluation, and of vacillators who returned, only one-half were adequately revascularized at operation. Of sixty-five reevaluated after surgery, eight improved, twelve worsened and forty-five did not change classification of coping strategies, yet physiological variables of cardiac function when invasively measured in sixty patients were significantly improved in all three groups. Amounts of improvement, both absolutely and relative to sex- and age-adjusted normal values, were least in vacillators with virtually normal cardiac capacity, and/or inadequate revascularization. Compartmentalized patients were more frequently working, yet only sixty-four in all psychosocial classifications worked before surgery. After this event only forty-five resumed working; none of the non-workers or retired returned to work. Both physiologic improvement and working status were independent of postoperative psychosocial status.

Amlodipine in Angina Pectoris: Effect on Maximal and Submaximal Exercise Performance

Amlodipine, a dihydropyridine calcium antagonist, was compared with placebo in a double-blind cross-over study in 16 patients with angina. After a 2-week single-blind placebo period, patients entered a double-blind crossover phase alternating between 4 weeks of placebo and 4 weeks of amlodipine, 10 mg once daily. The two 4-week periods were separated by a 1-week single-blind placebo washout period. The efficacy of drug therapy was measured using frequency of angina, nitroglycerin consumption, peak oxygen consumption during a maximal treadmill exercise test, and endurance time during a separate submaximal exercise test performed at 70% of the peak work capacity that had been determined before randomization. Compared with single-blind placebo there was a reduction in angina frequency during double-blind placebo and amlodipine, whereas nitroglycerin consumption was significantly reduced only by amlodipine. Amlodipine produced a significant increase in peak oxygen consumption and endurance time during the submaximal exercise test when compared with single-blind and double-blind placebo periods. Patients tolerated both placebo and amlodipine without clinically significant side effects.