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Cardiovascular complications are the most common cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). To understand this relationship, known cardiovascular risk factors were examined in ADPKD. Left ventricular hypertrophy (LVH) is a known, important risk factor for premature cardiovascular death in patients with essential hypertension. Hypertension is known to occur frequently and early in ADPKD patients. The frequency of LVH in ADPKD patients and its relation with hypertension and other risk factors, however, is not known. In this study, echocardiographic tests were performed in 116 consecutive adult ADPKD patients and 77 healthy control subjects. There was a significantly higher frequency of LVH in ADPKD men (46 versus 20%, P < 0.05) and women (37 versus 12%, P < 0.005) compared with control subjects. LVH in ADPKD patients was associated with higher systolic and diastolic arterial BP. There also was an association between LVH, diminished renal function, and increased renal volume. When comparing ADPKD patients with and without LVH, the former were older, weighed more, had a higher prevalence of hypertension, and had a lower hematocrit value and more renal impairment. LVH was also present in 23% of normotensive ADPKD patients and 16% of healthy control subjects (P = NS), but did not correlate with BP. The role of BP as a contributing factor to LVH in ADPKD patients may be due in part to earlier onset and inadequate treatment.

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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)

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BACKGROUND: The quality of life status of patients prior to and following percutaneous transluminal coronary angioplasty (PTCA) has not been comprehensively investigated. AIM: This study was carried out to determine the effect that PTCA has on patients' quality of life. METHODS: Data on 209 patients were collected one day pre-PTCA and at a mean of two and 11 months post-PTCA. Data on symptomatic status, functional capacity, life satisfaction and psychological well-being were analysed quantitatively. Clinical outcomes, patient perception of PTCA and employment status wee analysed by descriptive statistics. RESULTS: Highly significant improvement in all quality of life measures was found at the early follow-up (p < .001). This improvement was sustained at the late follow-up. At the late follow-up, 58% of patients felt that PTCA had been very beneficial to their health and well-being, and 79% of workers had returned to work. PTCA was primarily successful in 91% of vessels dilated. There were no procedural-related deaths, 12 patients (6%) developed acute occlusion and three patients (1.5%) experienced myocardial infarction (MI). A symptomatic restenosis rate of 16% was found, including 19 patients (9%) requiring repeat PTCA and 14 (7%) undergoing coronary artery bypass grafting (CABG). CONCLUSION: These findings suggest that, after PTCA, the majority of patients experienced improved quality of life which was sustained one year later.

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To evaluate the effect of percutaneous transluminal coronary angioplasty (PTCA) on quality of life, data on symptomatic status, functional capacity, life satisfaction, and psychological wellness were collected on 102 patients at 1 day pre-PTCA and 2 months post-PTCA, and on the first 50 of these patients at 10 months post-PTCA. There were highly significant changes (p < 0.001) in all quality of life measures between pre-PTCA and the 1st follow-up measurements. No further significant changes occurred in these measures between the 1st and 2nd follow-up measurements, indicating that the initial improvement in quality of life was sustained over this period. Data on primary success rate, complications, and pre- and post-PTCA risk factor scores are also reported.

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Bepridil is a calcium antagonist with a unique chemical composition and a long elimination half-life (42 hours). We evaluated the efficacy of bepridil 300 mg once/day in a crossover comparison with placebo in 45 patients with angina. Patients had an average of 7.6 anginal episodes/week during the placebo baseline phase of the trial. After 4 weeks of bepridil therapy, anginal frequency decreased to 2.9 episodes/week (p less than 0.05). Likewise, mean nitroglycerin consumption declined from 7.4 tablets/week during the placebo baseline phase to 4.0 tablets/week during bepridil therapy (p less than 0.05). Statistically significant increases over the previous period (placebo baseline or double-blind placebo) were seen in total exercise time, time to angina, and total work (p less than 0.05). During bepridil therapy, 13 of 45 patients (29%) no longer experienced angina as an exercise end point despite the increase in work and exercise time. Bepridil significantly prolonged both the QT and corrected QT (QTc) intervals; the mean increases were 10.0% and 5.6%, respectively. Side effects were reported with equal frequency in the placebo and bepridil arms of the trial, and no serious side effects were reported. In an intermediate fixed dose of 300 mg/day, bepridil relieved anginal symptoms with few side effects. Bepridil appears to be a safe and effective treatment for stable angina.

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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.

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We tested the hypothesis that increased plasma glucagon concentration resulting from portal-systemic shunting or liver dysfunction causes arterial vasodilation and thereby stimulates sodium retention in cirrhosis. Twenty-seven studies were performed in patients with alcoholic liver disease, 11 of whom had ascites. Liver function was quantitated as the elimination rate of antipyrine, caffeine, and stable isotopes of cholic acid administered both orally (2,2,4,4-2H) and intravenously (24-13C). Portal-systemic shunt fraction was calculated as the ratio of the intravenous and oral clearances of the isotopes of cholic acid. Cardiac output was measured by using Doppler echocardiography. Plasma glucagon concentration was increased in patients with ascites when compared with that in patients without ascites (474 +/- 180 pg/ml vs 245 +/- 120 pg/ml, p = 0.0007) but was unrelated to urinary sodium excretion, heart rate, mean arterial pressure, cardiac output, and systemic vascular resistance (r = -0.48, 0.35, -0.13, 0.18, and 0.22, respectively). Plasma glucagon concentration correlated with the half-lives of all model compounds (r = 0.58, p = 0.002; r = 0.62, p = 0.0008; r = 0.62, p = 0.001; and r = 0.64, p = 0.0005; for caffeine, antipyrine, oral and intravenous cholic acid, respectively) but not with shunt fraction (r = 0.14). Increased plasma glucagon concentration in cirrhosis is probably a result of diminished hepatic clearance. However, increased plasma concentration of glucagon does not appear to cause a hyperdynamic circulatory state or sodium retention.

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Increased blood volume, atrial size, and plasma concentration of atrial natriuretic factor are described in cirrhosis. Their interrelationships were examined in 17 men with alcoholic liver disease, 7 with and 10 without ascites. Atrial size was determined by two-dimensional echocardiography. Patients with cirrhosis had significantly increased left atrial volume and plasma concentration of atrial natriuretic factor when compared with normal male subjects. Right atrial volume was normal in patients with cirrhosis, as was left ventricular function. Patients with ascites had significantly increased blood volume and plasma atrial natriuretic factor concentration compared with patients without ascites. Left and right atrial volume did not differ between the groups. Blood volume correlated significantly with left atrial volume, which correlated significantly with plasma concentration of atrial natriuretic factor. Cirrhosis is associated with related increases in vascular volume, left atrial size, and plasma atrial natriuretic factor concentration. Increased blood volume probably contributes to the increase in left atrial volume, which is in turn one reason for the elevation of plasma atrial natriuretic factor concentration.

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Nitroglycerin is reportedly an effective treatment for portal hypertension. However, the effects of graded doses have not been examined. We administered nitroglycerin intravenously to 10 patients with alcoholic cirrhosis, beginning at 10 micrograms/min and doubling the dose every 10 min thereafter until mean arterial pressure fell 10-15 mmHg. We compared the response to that of 10 patients receiving a control infusion. The median infusion rate of nitroglycerin was 40 micrograms/min (range 10-160 micrograms/min). Nitroglycerin significantly reduced cardiac output as well as pulmonary artery, pulmonary capillary and mean arterial pressure. The overall effects of nitroglycerin on the hepatic venous pressure gradient and azygous (gastroesophageal collateral) blood flow were heterogeneous. However, the hepatic venous pressure gradient significantly increased in nitroglycerin-treated patients with high pulmonary capillary pressures (greater than or equal to 12 mmHg) compared to control patients with similar cardiac filling pressures at both median and maximum rates of infusion. Nitroglycerin is therefore not a uniformly effective treatment for portal hypertension. Cardiac filling pressure may be a determinant of the splanchnic hemodynamic response to nitroglycerin.

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The pathogenesis of variceal hemorrhage is not well understood. Portal pressure and gastroesophageal collateral (azygous) blood flow are similar in patients with cirrhosis with or without a history of variceal bleeding. However, acute increases in these parameters in individual patients might predispose them to variceal rupture. Fifteen patients with alcoholic cirrhosis and portal hypertension were evaluated to test the hypothesis that ethanol intake acutely increases portal pressure or gastroesophageal blood flow and is a possible risk factor in variceal hemorrhage. A 10% solution of ethanol in 5% dextrose in water was infused intravenously at a rate sufficient to raise the blood-alcohol level to 100 mg/dl over 30 min. Eight patients received ethanol 5% dextrose in water; seven patients received a placebo (5% dextrose in water alone). Ethanol did not produce a significant change in wedged hepatic-vein pressure, free hepatic-vein pressure, azygous blood flow, mean arterial pressure or heart rate compared with the effects of 5% dextrose in water alone. Acute administration of ethanol does not increase portal pressure or gastroesophageal blood flow. It is unlikely that acute ethanol ingestion is a risk factor for variceal hemorrhage.

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In an attempt to determine factors that are related to atrial natriuretic factor (ANF) release in normal subjects, 10 male volunteers were studied at rest supine, sitting and during treadmill exercise. Echocardiography was used to measure atrial volumes, and a Swan-Ganz catheter was used to measure right atrial pressure and pulmonary artery wedge pressure. Right ventricular ANF increased from 33 +/- 22 pg/ml supine to 72 +/- 32 pg/ml at peak exercise (p less than 0.001). When heart rate, atrial volume and atrial phasic pressure were combined to calculate atrial minute circumferential wall stress, a significant relationship between left and right atrial values for this variable and ANF was present. An association between norepinephrine (NE) and ANF was also present, but in a multivariate analysis it was not significant. This probably does not represent cause and effect but rather an association due to the relationship between NE and heart rate.

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An atrial septal defect was successfully repaired in a young woman despite the presence of pulmonary hypertension and right to left shunting. Before repair both isoprenaline infusion and 100% inspired oxygen produced significant falls in pulmonary artery pressure and pulmonary vascular resistance. A lung biopsy specimen at operation indicated a considerable decrease in the concentration of parenchymal pulmonary arteries and an absence of intimal fibrosis or medial hypertrophy. Pulmonary artery banding performed in infancy, as part of the management of a ventricular septal defect, may have contributed to the underdevelopment of the pulmonary vascular tree. The reduced number of pulmonary arteries is a possible explanation for the pulmonary hypertension.

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We measured the coronary, systemic, and splanchnic effects of vasopressin and vasopressin plus nitroglycerin in 8 stable patients with alcoholic cirrhosis. Vasopressin (0.1-0.8 U/min) increased pressure in the hepatic vein, pulmonary artery and pulmonary capillaries. Wedged hepatic (portal) vein pressure was unchanged; the hepatic venous pressure gradient (wedged-free hepatic vein pressure) fell. Insignificant declines occurred in cardiac output, gastroesophageal collateral (azygous) blood flow, hepatic blood flow and coronary sinus (cardiac) blood flow. The addition of nitroglycerin (40-70 micrograms/min) reduced pressure in the hepatic vein, pulmonary artery and pulmonary capillaries, while increasing the hepatic venous pressure gradient. Wedged hepatic vein pressure did not change. Gastroesophageal collateral (azygous) flow increased markedly; cardiac output rose to a lesser degree. Coronary sinus and hepatic blood flow did not change. Nitroglycerin ameliorated the increases in systemic and pulmonary artery pressure produced by vasopressin but also tended to reverse the decline in the hepatic venous pressure gradient and markedly increased gastroesophageal flow. Neither drug significantly affected coronary blood flow.

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We measured total blood volume (125I-albumin), cardiac dimensions and function (echocardiography with Doppler), systemic hemodynamics (blood pressure and pulse), and plasma renin activity and norepinephrine levels in cirrhotic patients with and without ascites to assess the likelihood that either diminished central or arterial filling is the stimulus to sodium retention. Patients with ascites (n = 9) had significantly increased total blood volume, cardiac output, pulse rate, plasma renin activity, and plasma norepinephrine concentration, as well as decreased systemic vascular resistance and arterial blood pressure compared with patients without ascites (n = 8). Left atrial size was similar in the two groups but significantly larger than in normal control subjects. Right and left atrial pressures were also similar in retrospectively studied patients with and without ascites. Sodium retention in cirrhosis is probably not triggered by diminished central filling. Increased blood volume is compatible with either a primary hepatorenal stimulus to sodium retention or a signal arising from a region of underfilling within an otherwise expanded circulation. If the latter model is correct, a "hyperdynamic" systemic circulation and increased plasma neurohormone concentrations may indicate "effective" arterial underfilling in patients with ascites.

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Autosomal dominant polycystic kidney disease (ADPKD) has been shown to be associated with a greater than 50 percent incidence of hypertension prior to deterioration in renal function as assessed by glomerular filtration rate. The present study provides evidence for increased cardiac pre-load, as assessed by plasma atrial natriuretic factor (ANF) and cardiac index, in hypertensive as compared to normotensive ADPKD. The hypertensive ADPKD patients exhibited an increased renal vascular resistance as compared to the normotensive patients in spite of comparable glomerular filtration rates. It is hypothesized that the renal involvement of hypertensive ADPKD patients causes an impaired renal response to the observed increase in cardiac index, and also may release a venoconstrictor (such as angiotensin) which contributes to the enhanced cardiac pre-load and thus the hypertension.

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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.

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The utility of using an endurance test as well as a maximal exercise test to assess the effect of amlodipine, a dihydropyridine calcium antagonist, was evaluated in 16 patients with angina pectoris. Amlodipine, 10 mg/day, was compared with placebo in a double blind crossover study. 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. The two 4 week periods were separated by a 1 week single blind placebo washout period. The efficacy of drug therapy was assessed by frequency of angina, nitroglycerin consumption, peak oxygen consumption during a maximal treadmill exercise test and endurance time during a separate exercise test performed at 70% of the peak work capacity determined before randomization. There was a reduction in angina frequency during the double blind placebo and amlodipine studies (single blind placebo 14 +/- 2 episodes/2 weeks, double blind placebo 7 +/- 2 episodes/2 weeks [p less than 0.005], amlodipine 6 +/- 3 episodes/2 weeks, [p less than 0.005]), whereas nitroglycerin consumption was reduced with amlodipine (single blind placebo 12 +/- 4 tablets/2 weeks, double blind placebo 8 +/- 3 tablets/2 weeks, amlodipine 5 +/- 3 tablets/2 weeks [p less than 0.01]). Amlodipine produced a significant increase in peak oxygen consumption (single blind placebo 18.7 +/- 1.1 ml/kg per min, double blind placebo 18.2 +/- 1.8 ml/kg per min, amlodipine 20.4 +/- 1.6 ml/kg per min [p less than 0.05]) and endurance time (single blind placebo 15.2 +/- 1.5 min, double blind placebo 15.8 +/- 2.1 min, amlodipine 20.2 +/- 2.5 min [p less than 0.005]).(ABSTRACT TRUNCATED AT 250 WORDS)

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Cirrhosis is frequently associated with increased arterial plasma renin activity. This could be the result of increased renin production or diminished renin clearance. We measured plasma renin activity in simultaneous portal, hepatic vein, and femoral artery blood samples in 7 patients with clinically stable alcoholic cirrhosis to determine whether hepatic extraction of renin is reduced and whether, as has been suggested, there is a splanchnic source of plasma renin activity in this condition. Plasma renin activity (mean +/- S.E. in ng/ml/min) was similar in portal, arterial, and hepatic venous samples (portal: 8.0 +/- 3.7; arterial: 7.6 +/- 3.1; hepatic vein: 6.4 +/- 2.3). Hepatic extraction of plasma renin activity, calculated as [arterial-hepatic vein)/arterial) X 100, was 14 +/- 6%, not significantly different from reported normal values (26 +/- 3%, n = 46). The intrinsic hepatic clearance of plasma renin activity (235 +/- 89 ml/min) and the hepatic renin extraction rate (1.801 +/- 1.032 micrograms/min) were also similar to estimated normal values. The intrinsic clearance and extraction rates of renin correlated with arterial plasma renin activity (r = 0.93, P less than 0.01 and r = 0.79, P less than 0.05). These data indicate that in clinically stable patients with alcoholic cirrhosis: (1) hepatic renin clearance is not significantly impaired; and (2) there is not a splanchnic source of plasma renin activity. Therefore, increased peripheral plasma renin activity in this condition is due solely to increased renal renin production.

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