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Background: Cardiac transplantation (CTX) is now a viable option for patients with end-stage heart failure, but there remains a paucity of available donor hearts relative to the demand for them. Establishing prognosis after CTX can help direct this resource to patients most likely to benefit, as well as to help guide therapy for CTX recipients. Clinical, exercise, and hemodynamic factors associated with survival after CTX have not been well established., Methods: One hundred seventy-four randomly selected patients who underwent heart transplantation between 1983 and 1999 at Rikshospitalet University Hospital were included in the study. Data were collected as a part of routine posttransplantation management a mean of 3.5 +/- 2.1 years (+/- SD) after CTX. Clinical, cardiopulmonary exercise testing, and hemodynamic measures were performed, including measures of peak oxygen uptake (O(2)), ejection fraction, cardiac index, pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure, creatinine, and the presence of coronary artery disease. Patients were followed up for a mean of 7.1 +/- 2.1 years; all-cause mortality was used as the end point for survival analysis., Results: During the follow-up period, 39 patients died; the average annual mortality was 3.6%. Peak O(2) was 19.6 +/- 5.6 mL/kg/min, representing 70.5 +/- 6.7% of the age-predicted value. Only right atrial pressure and PCWP differed between those who survived and those who died; both were slightly higher among those who died. By Cox proportional hazard analysis, there were no age-adjusted univariate or multivariate predictors of survival among continuous variables. Exploring various cut points revealed that serum creatinine > 118 micromol/L, PCWP > 12 mm Hg, and mean pulmonary artery pressure > 25 mm Hg were significant univariate predictors of mortality. These cut points for PCWP and pulmonary artery pressure generated hazard ratios of 2.3 and 2.9, respectively., Conclusion: Long-term survival after CTX was comparatively high in our cohort, with 5-year survival > 80%. Standard clinical, hemodynamic, and cardiopulmonary exercise test variables were not strong predictors of mortality in CTX patients a mean of 7 years after CTX. The association between elevated hemodynamic pressures and mortality, although weak, suggests that ventricular compliance, pulmonary vascular resistance, or both, may predict long-term survival after CTX.

Background: A gradual accommodation to increasing exercise loads has been recommended for exercise testing in denervated posttransplantation heart recipients. However, how the exercise protocol influence the hemodynamic, gas exchange, and hormonal response to exercise in this not been studied., Methods: Nine heart transplant recipients tests incremental maximal bicycle ergometry tests in random order. Exercise stages of 1 and 3 minute durations were compared with matched work rate increments ranging between 30 and 40 W. Expiratory gas was measured continuously and arterial blood was sampled at each of the matched work rates., Results: Total exercise duration was 6.4 +/- and 15.3 +/- 0.7 minutes for the 1-minute and 3-minute protocols, respectively. Maximal workload was significantly higher during the 1-minute versus the 3-minute protocol (238 +/- 9 versus 200 +/- 11 W, p < 0.001), but maximal oxygen uptake was not significantly different (25.5 +/- 1.1 versus 26.5 +/- 1.2 ml. min-1.kg-1). Hemodynamic, metabolic, and some hormonal parameters showed marked differences between the two protocols, with significantly higher responses observed during the 3-minute protocol for heart rate, ventilation, lactate, atrial natriuretic factor, and growth hormone. Catecholamine (epinephrine and norepinephrine) and insulin responses did not differ between the two tests. If expressed as a relative exercise intensity (percentage of maximal oxygen uptake) no differences in hormonal responses were observed between the two protocols, except for growth hormone response which remained higher during the 3-minute protocol., Conclusions: Although maximal oxygen uptake was independent of the exercise protocol in these heart transplant recipients, the exercise protocol has a major influence on the hormonal and metabolic response. The delayed response observed for oxygen uptake and hormonal responses suggests a significant physiologic lag time during the more rapidly incremental protocol. These differences should be taken into account when exercise is used as a method to evaluate the heart transplant recipient.

To evaluate the possible role of atrial natriuretic peptides ANF (1-98) and ANF (99-126) as diagnostic parameters of atrial distension, measurements of peptide levels were performed in 47 patients with chronic ischemic and/or left sided valvular heart disease. Plasma samples were drawn from the pulmonary artery (PA) and superior vena cava (SVC) during diagnostic right heart catheterization. Forty of the patients also underwent left heart haemodynamic measurements, and in 28 patients two dimensional echocardiography with determination of left atrial diameter was performed. Enhanced plasma concentrations of both peptides were observed with increasing severity of heart failure assessed by the NYHA classification. Mean plasma levels of both peptides were closely correlated to mean pulmonary artery pressure (ANF (1-98): n = 47, r = 0.69 (SVC)/r = 0.72 (PA), p < 0.0001; ANF (99-126): n = 46, r = 0.75 (SVC)/r = 0.68 (PA), p < 0.0001) and mean pulmonary capillary wedge pressure (ANF (1-98): n = 47, r = 0.69 (SVC)/r = 0.72 (PA), p < 0.0001; ANF (99-126): n = 46, r = 0.70 (SVC)/r = 0.64 (PA), p < 0.0001). Positive correlations were also obtained between peptide levels and mean right atrial pressure and left ventricular end-diastolic pressure. When patients with high right atrial pressures (n = 2) were excluded from analysis, a significant correlation was found between peptide levels and echocardiography assessed left atrial diameter. The present study demonstrates the close correlation between concentrations of both atrial peptides and cardiopulmonary haemodynamics in patients with chronic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

The acute haemodynamic effects of the new calcium antagonist isradipine have been studied in ten hypertensive cardiac transplant recipients. Isradipine 0.01 mg.kg-1 was given IV during right heart catheterization and noninvasively automatic blood pressure measurements. From a baseline blood pressure of 164/114 mmHg the maximum blood pressure reduction was 35 mmHg systolic, 30 mmHg diastolic, and mean 34 mmHg, due to a reduction in systemic vascular resistance, maximum 43%. Cardiac index increased 32%, mainly due to an increase in the stroke volume, as the heart rate rose only by 10%. Left ventricular filling pressure was slightly reduced. We conclude that the main effect of isradipine was a major reduction in left ventricular afterload, comparable to that previously found in other patient groups.

Sympathetic stimulation with epinephrine (EPI) combined with parasympathetic blockade with atropine was studied in 10 healthy volunteers premedicated with placebo or three different beta-adrenoceptor blockers: atenolol (62.5 micrograms/kg, beta 1-selective), propranolol (62.5 micrograms/kg, nonselective), and pindolol (7.5 micrograms/kg, nonselective with intrinsic sympathomimetic activity, ISA). EPI infusion (0.06 microgram/kg/min) after placebo increased heart rate (HR) and systolic blood pressure (SBP) and decreased diastolic BP (DBP). Pretreatment with atenolol reduced the HR increase, and caused similar changes in BP. In contrast, pretreatment with propranolol and pindolol decreased HR and increased BP. Combined EPI and atropine (15 micrograms/kg) after placebo increased HR by 40% without causing BP changes. Similar HR changes were observed after administration of all beta-adrenoceptor blockers, but whereas a marked pressor response was observed after propranolol and pindolol a blunted response was observed after atenolol. Propranolol and pindolol reduced myocardial oxygen demand estimated by the HR x BP product after EPI, but this response was abolished by atropine. Serum potassium decreased from 3.9 +/- 0.2 to 3.2 +/- 0.3 mM after EPi and atropine. This effect was less after atenolol, and potassium increased after premedication with propranolol and pindolol. Our results show that nonselective beta-adrenoceptor blockade has a favorable effect on potassium homeostasis and oxygen demand parameters during EPI infusion but causes a marked pressor response, contrary to a beta 1-selective agent, during combined sympathetic stimulation and parasympathetic blockade. They also highlight the importance of the vasodilator cholinergic system as a defense mechanism in such situations.

Background: This study investigates the effects of sodium nitroprusside on regional vascular capacitance in eight patients with severe congestive heart failure (New York Heart Association class IV) and pulmonary hypertension., Methods and Results: Regional relative blood volumes in the splanchnic and pulmonary region were determined by equilibrium blood pool scintigraphy. Hepatic venous wedge pressure and the mean of pulmonary artery and pulmonary capillary wedge pressure were used to represent the distending pressures of the splanchnic and pulmonary capacitance vessels, respectively. The dose of sodium nitroprusside was increased stepwise until systolic pulmonary artery pressure decreased below 50 mm Hg. This caused reductions in mean aortic pressure from 89 +/- 5 to 66 +/- 3 mm Hg (p less than 0.005), in pulmonary capillary wedge pressure from 31 +/- 1 to 16 +/- 2 mm Hg (p less than 0.001), and in hepatic venous wedge pressure from 10.0 +/- 1.0 to 5.9 +/- 0.6 mm Hg (p less than 0.005). Intestinal blood volume increased by 26 +/- 7% (p less than 0.005), whereas hepatic blood volume decreased by 9 +/- 3% (p less than 0.02). Pulmonary blood volume was unchanged. Analysis of intestinal and pulmonary vascular pressure-volume relations showed larger or equal blood volumes contained at lower distending pressures, indicating that sodium nitroprusside reduced smooth muscle tone of the capacitance vessels in these regions. The reduction of hepatic blood volume was compatible with passive expulsion of blood subsequent to reduced venous pressure. There was no change in the count rate from the spleen., Conclusions: Nitroprusside reduced venous pressure in patients with congestive heart failure by active relaxation of intestinal and pulmonary capacitance vessels. Hepatic vascular volume was probably reduced by a passive mechanism.

Seventy-three patients with a CarboMedics aortic bileaflet valve prosthesis were examined by Doppler ultrasonography, and 27 of them were also assessed by transseptal catheterization. The ultrasonic mean systolic gradient was 17.1 +/- 5.6 mm Hg for valve size 19 mm, falling gradually with increasing valve size to 6.8 +/- 2.5 mm Hg for size 27 mm. The catheter mean systolic gradient was consistently smaller than the ultrasonic gradient (4.3 +/- 4.8 mm Hg), but Tobit regression analysis showed a significant association between the two methods. In all patients both methods revealed negligible to small amounts of retrograde leakage, which is assumed to be a normal finding for this valve. The effective flow areas of the valves calculated from the ultrasonic data were similar to the in vitro calculated flow areas. The hemodynamic potential of this valve is therefore completely utilized in vivo. The effective orifice area corrected for body surface area increased with increasing valve size, which demonstrates a moderate valve-patient mismatch.

The effect of verapamil (Isoptin) on coronary hemodynamics was studied in 18 patients with coronary heart disease. The continuous infusion thermodilution technique was used to measure cardiac venous blood flow. At rest, verapamil produced a 13% decrease in coronary arteriolar resistance, a 5% decrease in coronary arteriovenous oxygen difference and a 19% increase in left ventricular efficiency index. No significant effect was noted on myocardial blood flow, oxygen consumption or oxygen consumption per unit of left ventricular pressure work. No change occurred in any of the measured parameters during a submaximal stress test after drug administration. The findings are discussed in relation to the general hemodynamic effects of the drug. It is concluded that verapamil is a mild coronary vasodilator and that myocardial oxygen consumption, in relation to performed left ventricular work, is unaltered by the drug up to a near-maximal work-load.

The effects of timolol (2.5 mg i.v.) on coronary haemodynamics and myocardial metabolism were studied in 26 patients with angina pectoris. Cardiac venous flow (CVF) was measured by thermodilution technique. Blood was sampled for metabolic studies. Angina pectoris was induced by atrial pacing and the same heart rate was regained after timolol. Metabolic ischaemia was defined as reduction in myocardial lactate extraction ratio (MLE) by at least 50% and to a ratio below 0.15. The study was completed in 22 patients, 9 of whom fulfilled the metabolic criteria for ischaemia. This subgroup did not differ from the total group in any other respect than in lactate metabolism. Beta-adrenergic blockade reduced myocardial oxygen consumption (MVO2) and CVF significantly at rest, but MVO2, CVF, myocardial glucose uptake and MLE were unchanged during pacing despite a decrease in systolic aortic pressure, ejection time and reduced myocardial free fatty acid uptake. Conclusively, timolol did not reduce MVO2 and metabolic ischaemia during pacing-induced angina.

The immediate haemodynamic and electrophysiologic effects of intravenous prenalterol 2.5-75 micrograms/kg in patients with coronary heart disease without clinical heart failure were investigated during fixed rate atrial pacing. Right ventricular peak dP/dt increased pronounced and serum concentration dependent after prenalterol concomitant with an increase in stroke volume and a moderate decrease in peripheral vascular resistance. The effects on haemodynamics after prenalterol were thus serum concentration dependent but with marked interindividual variation. AV nodal conduction velocity increased significantly. It is concluded that prenalterol possess pronounced inotropic properties. The haemodynamic response to prenalterol intravenously is to a lesser degree dependent on the chronotropic effects of the drug and it is often unpredictable.

In 80 male patients with coronary heart disease maximum diastolic pressure in the left ventricle (LVMDP) (usually the top of the a wave), and 'post a' end-diastolic pressure (LVEDP) before and 2 and 3 minutes after ventriculography were correlated to angiographic estimates of left ventricular function (aneurysm, ejection fraction (EF), and to lesions shown by selective coronary arteriography using a score system (coronary artery lesions index, CALI). A significant correlation between CALI and LVEDP (or LVMDP) could not be shown either before or after ventriculography. Before ventriculography, however, LVEDP and LVMDP were good predictors of left ventricular dyskinesia (aneurysm and/or EF less than 50%). A positive and significant correlation between CALI and the LVEDP (and LVMDP) increments following ventriculography (delta LVEDP, delta LVMDP) was found in patients with LVEDP (or LVMDP) below 12 mmHg before ventriculography. Using delta LVEDP the correlation coefficient was 0-51 (n = 41, P less than 0-001, 95 per cent confidence interval 0-24 to 0-88). Using delta LVMDP r = 0-47 (n = 41, 0-001 less than P less than 0-01). Delta LVEDP greater than 12 mmHg was found only in patients with triple vessel disease.

To investigate if the intrinsic sympathomimetic activity of pindolol could modify its beta-blocking effects on the responses to an adrenaline infusion, 10 healthy volunteers were studied. At an interval of 1-4 weeks each subject received pindolol and atenolol in randomized order before the infusion of adrenaline 0.06 microgram.kg-1.min-1. Pindolol prevented hypokalaemia and significantly decreased the heart rate during the adrenaline infusion. These effects were not observed after atenolol. The diastolic blood pressure was slightly increased during the infusion of adrenaline after pindolol, whereas it remained unchanged after atenolol.

Fifty-two patients with isolated congenital ventricular septal defects (VSDs), studied for the first time at age 10 or older, were restudied an average of 16 years later (range 4 to 21). The study protocol included a symptom-limited bicycle ergometer test, M mode echocardiographic examination, and hemodynamic studies at rest and during mild supine exercise. Of the 52, 17 had been operated on an average of 19 years earlier (range 11 to 21) (group 1) and 35 with smaller defects were not operated on (group 2). Although more pronounced findings were made in group 1, a similar pattern was observed in group 2: In most subjects in both groups a subnormal working capacity was observed. A subnormal left ventricular fractional shortening and circumferential shortening velocity was noted in a high proportion at echocardiography. A number of hemodynamic aberrations were observed in a high proportion of patients during exercise but not at rest. Thus a subnormal increase in left and right ventricular cardiac output was found in addition to pathologic increase in right and left ventricular end-diastolic, pulmonary arterial, and pulmonary capillary wedge pressures. In group 1, elevated pulmonary arterial pressures before operation and/or small residual VSDs were associated with a poor hemodynamic outcome. In neither group could significant correlations be observed between hemodynamic aberrations, shunt size, and/or age. Among patients who underwent surgery, the earlier surgical trauma might have contributed to the functional aberrations, but in group 2 the only likely explanation for the findings seems to be the VSD itself. Possibly a long-standing VSD--found unnecessary to repair according to commonly accepted criteria--may lead to disturbed systolic function and increase in compliance of both ventricles via a chronic pressure and volume overload.

Myocardial metabolism was studied during coronary vasodilatation by carbocromen during atrial pacing in patients with coronary arteriosclerotic disease. Coronary sinus flow was measured by the continuous infusion thermodilution technique. Carbocromen increased myocardial flow by the same amount at rest and during pacing-induced tachycardia. The administration of carbocromen did not interfere with myocardial oxygen consumption, free fatty acid (FFA) uptake, pulmonary or systemic hemodynamics. Atrial pacing above the anginal threshold increased lactate and hypoxanthine excretion to the coronary sinus, but to a greater extent during carbocromen treatment. Thus, carbocromen is a specific coronary vasodilator acting independently of pacing induced vasodilatation. Metabolic data indicate a small but unfavourable effect on ischemic metabolism which might be due to a "coronary steal".

A consecutive series of 97 patients with a left ventricular aneurysm (LVA) was evaluated for aneurysmectomy. A wide range in left ventricular (LV) function was found. Angina pectoris was the primary indication (51%) in 55 patients who were operated upon, whereas poor LV function was the main reason (67%) for rejecting surgery in 42 patients. Operative mortality was 9% and exclusively seen in patients with congestive heart failure and/or sustained ventricular arrhythmias. Functional status improved from (NYHA) 3.0 +/- 0.7 to 2.3 +/- 0.5 (P less than 0.0001) after surgery, while haemodynamics at rest remained unchanged. In the medically treated group, 10 patients underwent heart transplantation without mortality during follow-up. Of the remaining 32, 7 had died (22%), all with severely impaired LV function. The best prognosis with no deaths was observed in the 14 medically treated patients with moderate complaints and well preserved LV function. Those with poor LV function and/or ventricular arrhythmias had a poor prognosis whether they were treated medically or by conventional aneurysm surgery. In young selected patients with a short life expectancy, heart transplantation may represent an alternative.

Haemodynamic responses to 50% nitrous oxide in oxygen during coronary artery surgery were investigated in 10 patients. Morphine, diazepam and pancuronium were given intravenously as both induction and maintenance anaesthesia. A significant decrease was seen in heart rate, arterial pressure, pulmonary artery pressure, heart rate-systolic arterial pressure product, peripheral vascular resistance, left ventricular end-diastolic pressure, dP/dT of the left ventricle and resistance as measured in the graft to the left anterior descending coronary artery (LAD). No variations occurred in cardiac output, stroke volume, flow in the LAD-graft, pulmonary artery pressure or heart rate-systolic pulmonary artery pressure product or in dP/dT of the right ventricle. Pulmonary vascular resistance increased. It was concluded that left ventricular performance did not decrease and that no deterioration of the oxygenation to the myocardium seemed to occur.

Thirty-nine vectorcardiographic (VCG) data from 45 patients with pure adult aortic stenosis have been tested as to their ability to reflect quantitatively the peak systolic left ventricular pressure (LVPSP), the left ventricular end diastolic pressure (LVEDP), and the X-ray estimated heart volume. VCG was recorded with the axial lead system and simple and multiple linear regression analyses were applied. Eight VCG data correlated significantly (p less than 0.001) with LVPSP, the best indicator being the maximum posterior dislocation in the Z lead (r = 0.65). Through multiple regression analysis a formula was derived which gave a correlation coefficient between observed and calculated pressures of 0.82. The best indicator of LVEDP was the maximum positive P amplitude in the X lead (r = 0.41). The relationship was, however, too poor to have practical significance. A good correlation was found between ST segment dislocation and heart volume (r = 0.65), in good accordance with previous observations as to the effect of right ventricular dilatation on the ECG. The study illustrates how ventricular volume and pressure exert different effects on the ECG, and how all the important hemodynamic aspects in aortic stenosis to some degree are reflected. Only the pressure correlations have, however, practical importance.

Disopyramide exerts a quinidinelike effect on the heart and is a valuable drug for treating atrial and, especially, ventricular tachyarrhythmias. The therapeutic plasma concentration of disopyramide is thought to be 2.0-4.0 (5.0) microgram/ml. We here report the cardiac effects of a high dose of disopryamide in a patient with extensive coronary artery disease complicated by ventricular extrasystoles. At plasma levels above approximately 7.0 micrograms/ml, heart rate was decreased, while PQ interval, width, and QT interval were increased. At concentrations above approximately 6.0 micrograms/ml, disopyramide exerted negative intropic effects as judged by increases in mean right atrial, pulmonary arteriolar, and pulmonary capillary venous pressures and a decrease in cardiac output.