Usefulness of programmed stimulation in idiopathic dilated cardiomyopathy.

The response to programmed electrical stimulation and the clinical outcome was determined in 47 patients with nonischemic dilated cardiomyopathy (DC). Thirteen patients (group 1) presented with sustained uniform ventricular tachycardia (VT), 14 (group 2) presented with cardiac arrest and 20 (group 3) presented with nonsustained VT. The mean ejection fraction of the study population was 28 +/- 9%. The response to programmed stimulation was related to arrhythmia presentation. In all patients in group 1 sustained, uniform VT was induced, compared with 1 patient in group 2 and 2 patients in group 3 (p less than 0.001). There were 14 sudden cardiac deaths and 1 cardiac arrest during a mean follow-up of 18 +/- 14 months. The only 4 patients who presented with sustained VT or a cardiac arrest in whom sustained arrhythmia induction was suppressed with antiarrhythmic therapy remain alive. Nine of the 23 patients (4 in group 2 and 5 in group 3) in whom no sustained ventricular arrhythmia was induced died suddenly, with 5 of the 9 receiving empiric antiarrhythmic therapy. Three other patients, who had a slower and hemodynamically tolerated VT at the time of arrhythmia induction, died suddenly. Thus, in patients with nonischemic DC, uniform, sustained VT is always and almost solely initiated in patients who present with this arrhythmia; although few patients presenting with sustained VT or cardiac arrest have inducibility of the arrhythmias suppressed with therapy, if it is suppressed the patient appears to have a good prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Idiopathic aldosteronism in pregnancy.

This is the first reported case of the idiopathic type of primary aldosteronism in pregnancy. The severely hypertensive patient was unresponsive to treatment with high doses of four antihypertensive agents administered concurrently. A drastic improvement in blood pressure was noted within 24 hours of beginning enalapril maleate, although subsequent deterioration in fetal status led to delivery at 26 weeks' gestation. Alternatives to standard medical therapy may be necessary for this rare but potentially life-threatening disease during pregnancy.

Acute cardiac failure and hepatic ischemia induced by disopyramide phosphate.

Two patients abruptly developed congestive heart failure and elevation in serum transaminase levels when given disopyramide phosphate; enzyme abnormalities and hemodynamic status corrected upon withdrawal of the drug. Both patients had underlying ischemic cardiomyopathy. Myocardial infarction, pulmonary embolism, and viral hepatitis were ruled out in both patients. One patient had a liver biopsy documenting central hepatic necrosis with congestion, consistent with hepatic ischemia and not toxic hepatitis. In the other patient, cardiac decompensation and hepatocellular enzyme elevation were reproduced on rechallenge with the drug. Disopyramide should be used with caution in patients with heart failure.

Liver microsomal beta-glucuronidase and UDP-glucuronyltransferase.

Both UDP-glucuronyltransferase (GT) and beta-glucuronidase (betaG) were assayed in untreated liver microsomes. Optimum assay conditions were established with rat liver microsomes using p-nitrophenol (pNP) and its glucuronide (pNPGA) at the pH optima of GT (7.5) and betaG (4.5). The activities of the two enzymes were compared using microsomes from rats, mice, pigs, cattle and horses, with pNP, pNPGA, and phenolphthalein as substrate, in the presence of various cofactors and inhibitors at pH 7.5 and 4.5. These data disclose pronounced differences with respect to species, substrate and other experimental conditions, thereby precluding the establishment of general optimum conditions. The two enzymes were also assayed under strictly identical conditions using pNP and pNPGA and rat liver microsomes at pH 7.5 in the presence and absence of UDP-glucuronate disodium (UDPGA), activators (ATP;UDP-N-acetylglucosamine) and inhibitors. When provided with a functional level of UDPGA, both enzymes proved active under those conditions, and a conjugation-deconjugation interplay was indicated. The two processes could be selectively and totally inhibited by Zn2+ and saccharolactone. The results suggest that conjugation-deconjugation-reconjugation cycles may be operative in the metabolism of drugs in vivo, taking place already at the level of the liver endoplasmic reticulum.

Sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy: electrophysiologic testing and lack of response to antiarrhythmic drug therapy.

Eleven consecutive patients with idiopathic dilated cardiomyopathy and spontaneous, sustained ventricular tachycardia (VT) of uniform morphology underwent programmed ventricular stimulation and serial antiarrhythmic drug testing. The mean ejection fraction was 30 +/- 6.4%. Sustained VT was induced by programmed electrical stimulation in all 11 patients. A mean of 3.7 +/- 2.4 antiarrhythmic drugs were evaluated by programmed stimulation, including at least one experimental agent in eight patients. In nine of 11 patients VT remained inducible on all drug therapy. During a mean follow-up period of 21 +/- 14 months there were four sudden deaths and two patients with recurrences of VT. In all six patients with sudden death or recurrence of VT, the arrhythmia remained inducible on drug therapy. Three patients who died suddenly had a hemodynamically stable, induced tachycardia on antiarrhythmic therapy. Of eight patients treated with amiodarone, only two were successfully treated. We conclude that in patients with sustained VT and idiopathic dilated cardiomyopathy, VT can be induced by programmed electrical stimulation. VT will usually remain inducible on antiarrhythmic therapy, and sudden death can occur despite slowing and improved tolerance of the induced arrhythmia. Amiodarone may have limited efficacy, and more aggressive therapy, such as surgery or implantation of an automatic internal defibrillator, should be considered in this patient population.

A comparison of the care of hypertension in Hunan and Connecticut.

The demographic, clinical, and social characteristics of 300 hypertensive patients (150 seen in the Hypertension Clinic at Yale University and 150 seen in a newly opened clinic at the First Affiliated Hospital of the Hunan Medical College) were compared at their initial visit to the clinic. The mean blood pressure of both treated and untreated patients and the frequency of mild hypertension and rarity of secondary causes of hypertension were similar. Americans drank more alcohol and were more likely to be heavy smokers, and the Chinese were older, had more end organ damage, and had many more symptoms. The majority of patients in China (77%) were being treated most often with combination pills containing multiple agents. We feel that hypertensive patients are similar in the United States and China, though the Chinese patients appeared to have been seen at a later stage of their disease.

Abnormal signal-averaged electrocardiograms in patients with nonischemic congestive cardiomyopathy: relationship to sustained ventricular tachyarrhythmias.

We assessed whether signal-averaged electrocardiography could identify patients with sustained ventricular arrhythmias in 41 patients with non-ischemic cardiomyopathy. Twelve of these patients presented with sustained ventricular arrhythmia and 29 patients had no history of sustained ventricular arrhythmias. The mean ejection fractions in the groups were 30 +/- 9% and 24 +/- 9%, respectively. Results were compared with signal-averaged electrocardiograms in 55 normal individuals. The filtered QRS duration was longest in patients with sustained ventricular arrhythmias (130.2 +/- 19.5 vs 105.0 +/- 13.1 msec in the group without sustained ventricular arrhythmia, p less than .001 and 95.9 +/- 9.1 in the normal group, p less than .001). The voltage in the last 40 msec of the filtered QRS was lower in the sustained ventricular arrhythmia group (11.3 +/- 9.3 microV) than the group without sustained ventricular arrhythmia (53.5 +/- 28.3 microV; p less than .001) or the normal group (53.7 +/- 25.2 microV; p less than .001). Eighty-three percent of patients in the sustained ventricular arrhythmia group had an abnormal signal-averaged electrocardiogram characterized by both a long filtered QRS duration and a late potential of low voltage level; only 2% of normal subjects and 14% of patients without sustained ventricular arrhythmias had an abnormal signal-averaged electrocardiogram. The signal-averaged electrocardiogram can identify patients with nonischemic congestive cardiomyopathy and sustained ventricular arrhythmias.

Surgical therapy of variant angina associated with nonobstructive coronary disease.

Patients with variant angina refractory to medical therapy pose a difficult management problem. We report two patients with variant angina who had focal spasm in coronary arteries with fixed obstructions of less than 20% of the luminal diameter. Ischemic episodes were accompanied by malignant ventricular arrhythmias and third degree atrioventricular block. Symptoms were refractory to intensive medical management with nitrates and calcium blocking agents in one patient and with nitrates in the other who was treated before calcium blockers were available. Surgery was done; a bypass graft was placed distal to the area of focal spasm and the native artery was ligated proximally. Both patients are asymptomatic 24 and 66 months after surgery and neither takes anginal medication regularly. The surgical procedure outlined should be considered only if therapy to control life threatening ischemic symptoms with nitrates and calcium blocking agents fails.

A comparison of the treatment of hypertension with Chinese herbal and Western medication.

Forty-five patients with diastolic blood pressure (DBP) greater than or equal to 105 mmHg were randomly assigned to receive Western (group 1, n = 21) or a classical Chinese herbal preparation (group 2, n = 24) to treat their hypertension (HBP). All remained hypertensive after 4 days in the hospital without treatment. Except for baseline Na+ excretion (higher in group 1) and somewhat more evidence of end organ damage in group 1, the patient groups were comparable. Those in group 1 were given a thiazide diuretic and propranolol if needed, and those in group 2, a mixture of 12 herbs. Patients on active therapy in group 1 had a drop in blood pressure (BP) from 172.6 +/- 27.8/107.4 +/- 13.6 to 141.2 +/- 26.2/89.6 +/- 12.0 mmHg, whereas those in group 2 had no change in BP, 168.8 +/- 22.0/107.7 +/- 9.8 mmHg to 165.7 +/- 23.7/106.0 +/- 11.8 mmHg. Although 66% of patients in group 1 had a DBP under 90 mmHg by discharge, only 8% of those in group 2 did. Except for a fall in serum K+ in group 1, there were no significant biochemical or clinical problems in either group. We conclude that standard Western medication is more effective than a classical Chinese herbal preparation used to treat HBP.

Endocardial catheter mapping in patients in sinus rhythm: relationship to underlying heart disease and ventricular arrhythmias.

Catheter mapping during sinus rhythm was performed in 132 patients with coronary artery disease and 26 patients with congestive noncoronary cardiomyopathy. Each of the patients had a clinical history of one of the following: no ventricular arrhythmia, nonsustained ventricular tachycardia, cardiac arrest, or sustained ventricular tachycardia. The characteristics of the endocardial electrogram and other measured indexes of slow endocardial conduction were compared between patients with different types of disease and in different arrhythmia groups to determine if differences existed. The cardiomyopathic group had a higher percent of normal endocardial electrograms than the coronary artery disease group, with no evidence of slow endocardial conduction. The sustained ventricular tachycardia group exhibited a greater percent of abnormal endocardial electrograms and more evidence of slow endocardial conduction, distinguishing this group from the three other arrhythmia groups. We conclude the following: The underlying electrophysiologic substrate varies in patients with different ventricular arrhythmias. It is therefore inappropriate to analyze all patients with ventricular arrhythmias as a single group. Patients with congestive noncoronary cardiomyopathy, regardless of the type of their arrhythmia, have a relatively normal endocardium. Those patients with serious ventricular arrhythmias should not be considered candidates for surgery directed at removing abnormal endocardium.