Changes in exercise capacity induced by heart transplantation: prognostic and therapeutic implications.

Survival and exercise performance are key targets of heart transplantation (HT). We designed this study to help in identifying (1) patients with chronic heart failure (CHF) at risk of poor exercise capacity after HT and (2) HT recipients presenting risk factors modifiable with exercise showing a potential impact on outcome. We enrolled 49 HT recipients (age 52 ± 12 years, 84% males) who underwent a cardiopulmonary exercise test before (9 ± 6 months) and after (20 ± 14 months) HT. In the CHF phase, lower peak oxygen consumption (VO(2) ) (odds ratio 0.69, P=0.017) independently predicted peak VO(2) improvement after HT. In the post-HT phase, body mass index (BMI) [adjusted hazard ratio (HR) 1.16, P=0.034] and VE (ventilation)/VCO(2) (carbon dioxide production) slope (adjusted HR 1.07, P=0.031) independently predicted mortality. In conclusion, CHF patients with only a moderate impairment of peak VO(2) are at a risk of failing to achieve a significant improvement of exercise performance after HT. In the post-HT phase, a BMI≥28 and/or a VE/VCO(2) slope ≥47 represent risk factors for death, which are potentially modifiable with exercise. Prospective randomized studies are needed to analyze the effects of training on functional capacity and outcome in the different subsets of HT recipients.

Recovery kinetics of oxygen uptake is abnormally prolonged in patients with Mustard/Senning repair for transposition of the great arteries.

The aim of this study was to evaluate the ability to recover from exercise in patients with a Mustard/Senning (M/S) repair for transposition of the great arteries and to identify the major determinants. A total of 40 consecutive patients with a M/S repair at a mean age of 10.0 +/- 9.8 months underwent maximal cardiopulmonary exercise testing at 19.5 +/- 11.3 years of age. Results were compared to those of a cohort of 153 healthy individuals. Decay of oxygen uptake (VO2), CO2 (VCO2), minute ventilation (VE), heart rate (HR) was calculated for the first minute of recovery. M/S patients had reduced peak VO2(22.9 +/- 7.2 vs 34.2 +/- 9.5 ml O2/kg/min, p < 0.0001) and VO2 slope (0.27 +/- 0.10 vs 0.47 +/- 0.2 L O2/min, p < 0.0001), Peak O2 pulse (p < 0.0001) and peak HR (p = 0.001) were reduced. VCO2 and VE slopes were reduced (p < 0.0001 for both), whereas HR slope was similar (p = 0.38). In M/S patients, the only independent determinants of VO2 slope during recovery were pulse O2 slope (p < 0.0001) and VCO2 slope (p < 0.0001). In M/S patients, a limited cardiopulmonary reserve affects not only maximal exercise responses but also the recovery phase. A prolonged recovery of O2 pulse and a prolonged CO2 retention with subsequent prolonged hyperpnea are the main determinants of the delayed recovery.

[Evaluation of cardiorespiratory function in children and adolescents with repaired tetralogy of Fallot]. / Valutazione della capacità funzionale cardiorespiratoria in bambini e giovani operati per tetralogia di Fallot.

METHODS: To evaluate the cardiopulmonary exercise response of children and youngs operated upon for Tetralogy of Fallot (ToF) and to establish possible relationship with clinical and echocardiographic parameters we studied 24 pts, 14 males and 10 females, aged 14.5 +/- years; the age at repair was 5.2 +/- years and follow-up after correction was 8.6 +/- 3.2 years. All the pts were in NYHA functional class I; 8 pts had residual hemodynamic sequelae and 3 pts were on oral treatment. Cardiopulmonary exercise response with bicycle ergometer and incremental workload (25 watts/2 minutes), respiratory gas measurement with peak oxygen consumption (peak VO2) and ventilatory anaerobic threshold (VAT), were investigated in each patient. The data obtained were compared with those of control group of 103 healthy children and adolescents (59 males, 44 females, age 12.9 +/- 2.4 years) to the purpose of statistical analysis. RESULTS: The series of operated ToF pts showed 15-20% reduction in cardio-respiratory parameters, compared to healthy controls. a) Pts operated after the age of 5 years showed a significant reduction in peak VO2 compared to those operated at an earlier age (21 +/- 3.4 vs 35.4 +/- 7.5, p = 0.001) with; b) inverse correlation between peak VO2 and age at operation (r = -0.5, p = 0.01); c) 8 pts with residual hemodynamic sequelae (pulmonary regurgitation and/or ventricular outflow obstruction) showed the worse cardio-pulmonary capacity (peak VO2 27.5 +/- 7 vs 36.1 +/-8.1, p<0.02; VAT 20.4 +/- 5.2 vs 29.5 +/- 4.4, p<0.02; d) a chronotropic limitation was also observed in the group of pts when compared to healthy controls (peak HR 177 +/- 17 vs 188 +/- 11, p<0.001). CONCLUSION: Our study on pts operated upon for ToF showed a significant relation between age at surgery, hemodynamic sequelae and cardiopulmonary exercise response. Since this study has considered pts repaired in the two past decades, we believe that the present approach to ToF with early correction through atriotomy if possible and small outflow patch, may further improve the exercise capacity at a long-term follow-up.

[The 24-hour hemodynamic changes after percutaneous mitral valvuloplasty]. / Modificazioni emodinamiche 24 ore dopo valvuloplastica mitralica percutanea.

Hemodynamic studies were performed immediately before, within 1/2 hour and 24 hours after percutaneous mitral valvuloplasty in 31 patients with severe mitral stenosis and pulmonary hypertension. Single rubber-nylon balloon (Inoue balloon) technique was used in all the procedures. Mean transmitral gradient fell from 12.7 +/- 5.4 mmHg to 6.1 +/- 3.1 mmHg (p < 0.001). Mitral valve area increased from 0.9 +/- 0.2 cm2 to 1.8 +/- 0.3 cm2 (p < 0.001). Mean pressure in the left atrium decreased from 21.8 +/- 7.1 mmHg to 16.9 +/- 5.1 mmHg (p < 0.001). After 24 hours there was a significant further drop in left atrial pressure (or pulmonary capillary wedge pressure), that decreased to 11.5 +/- 5 mmHg (p < 0.001). Mean cardiac output increased from 4.1 +/- 0.8 l/min to 4.5 +/- 0.9 l/min immediately after successful valvuloplasty and after 24 hours was significantly higher (5.4 +/- 1.2 l/min; p < 0.001). Mean pulmonary pressure immediately decreased from 29.2 +/- 9.7 mmHg to 26.5 +/- 6 mmHg (p < 0.05) and after 24 hours was 19.4 +/- 6 mmHg (p < 0.001). Left ventricular end-diastolic pressure increased from 9.9 +/- 3.8 mmHg to 13.8 +/- 5 mmHg (p < 0.001). In conclusion, pulmonary hemodynamic and cardiac output improve immediately after percutaneous mitral valvuloplasty and get progressively better up to 24 hours from the procedure.

Evaluation by cardiopulmonary exercise test of DDDR versus DDD pacing.

UNLABELLED: In eight patients (age 62 +/- 6 years) a DDDR pacemaker was implanted for sick sinus syndrome (three cases) or second- and third-degree AV block (five cases). In five subjects chronotropic incompetence (maximal heart rate on effort < 110 beats/min) was present before implantation. One month after implantation the patients were randomized to DDDR or DDD pacing for 3 weeks each, with subsequent crossover, and at the end of each period a symptom limited cardiopulmonary exercise test (25 watts/2 min) was performed and the patients were requested to fill a symptoms questionnaire. RESULTS: DDDR pacing, compared to DDD, was associated with higher maximal heart rates (127 +/- 20 vs 110 +/- 27 beats/min, P < 0.02), higher [VO2 max (25.4 +/- 6.1 vs 21.5 +/- 7.8 mL/kg/per min, P < 0.03) and higher VO2 at the anaerobic threshold (20.3 +/- 5.0 vs 15.8 +/- 4.9 mL/kg per min, P < 0.03), without significant differences in mean exercise time (526 +/- 193 vs 472 +/- 216 sec, NS). The increase in VO2 max obtained in DDDR versus DDD was significantly related to the increase in maximal heart rate (r = 0.72, P < 0.05) and the increase in VO2 at the anaerobic threshold obtained in DDDR versus DDD was related to the increase in heart rate at the anaerobic threshold (r = 0.81, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of felodipine in congestive heart failure.

The hemodynamic effects of increasing dosages of felodipine, a new calcium antagonist with selective vasodilator properties, were studied in 13 patients with chronic cardiac failure. A Swan-Ganz thermodilution catheter was positioned in the pulmonary artery and hemodynamic parameters were monitored from 9 am to 6 pm for five days. On the first and the fifth day patients received placebo (P) and on the second, third, and fourth day patients received felodipine 5, 10, and 20 mg, respectively. Symptom-limited exercise tests with a bicycle ergometer were performed on both days of P and on the fourth day. A marked reduction of systemic vascular resistance (SVR) and a significant increase of cardiac index without increments of heart rate (HR) were observed after felodipine at rest. A dose response effect could be demonstrated. During exercise a significant increment of cardiac index and decrease of pulmonary wedge pressure was observed after felodipine. Felodipine showed a potent vasodilator action on systemic circulation with significant changes on both stroke volume and filling pressures at rest and during exercise without side effects.

Genetic heterogeneity of hypertrophic cardiomyopathy.

We studied the pattern of inheritance of hypertrophic cardiomyopathy among 111 first-degree relatives of 30 patients with the disease. Results of segregation analysis suggest a genetic heterogeneity for hypertrophic cardiomyopathy in that both autosomal dominant and autosomal recessive mode of inheritance can occur.

Echocardiographic evaluation of the response to afterload stress test in young asymptomatic patients with chronic severe aortic regurgitation: sensitivity of the left ventricular end-systolic pressure-volume relationship.

The detection of myocardial depression is an important goal in the management of patients with chronic severe aortic regurgitation but may be quite difficult at an early stage by the conventional basal measures of contractility. The response to afterload stress determined by angiotensin challenge and the end-systolic pressure-volume relationship was evaluated echocardiographically in 16 asymptomatic or mildly symptomatic patients with chronic severe aortic regurgitation, ages 15 to 56 years (mean 32 +/- 12). Nine normal subjects, ages 25 to 41 years (mean 31 +/- 5), served as a control group. In the group with aortic regurgitation, end-systolic dimensions were greater than 55 mm in five of 16 patients and fractional shortening was 25% or less in two of 16. In the control group angiotensin caused a decrease of stroke volume index in six out of nine patients (15% at the most) and a mild increase in three. In the group with aortic regurgitation stroke volume index decreased by 15% or more of the basal value in nine of 16 patients and increased or decreased by less than 15% in seven of 16. Ejection fraction decreased in both groups, from 61 +/- 6% to 52 +/- 7% in the control group and from 56 +/- 6% to 45 +/- 5% in the group with aortic regurgitation. Ventricular function curves were derived by relating end-diastolic volume index to stroke work index; seven of 16 patients had abnormal responses reflecting an afterload mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)

Haemodynamic effects of prenalterol in acute myocardial ischaemia in open chest pigs.

The haemodynamic effects of prenalterol, a new sympathomimetic agent, have been studied in anaesthetized open-chest pigs with acute myocardial ischaemia provoked by left anterior descending coronary artery ligation. A group of eight animals was infused with saline and served as control (C). In both groups the ligation of the left anterior descending coronary artery determined a significant (P less than 0.05) reduction of aortic flow, maximum left ventricular (LV) dp/dt with no changes in heart rate. The infusion of a first dose of 30 micrograms/kg of prenalterol restored the depressed haemodynamics but increased significantly the heart rate in the prenalterol group while the saline infused group did not show any significant changes. The haemodynamic effects of prenalterol were still evident 25 min after the infusion. The subsequent administration of a second dose of 60 micrograms/kg of prenalterol resulted in a further improvement of the aortic flow, LV dp/dt and heart rate which reached values higher than in the basal condition. The positive inotropic effect was not associated with changes in stroke volume, therefore the increase in aortic flow was essentially due to an increase of the heart rate. It is concluded that prenalterol is a powerful inotropic agent in acutely infarcted animals. Its action on aortic flow appears to be related to an increase in heart rate in contrast to some previous observations.

Prenalterol in primary dilated cardiomyopathy: hemodynamic and angiographic evaluation.

The hemodynamic effects of an acute infusion of prenalterol (PN), a new inotropic beta-adrenoceptor agonist, have been evaluated by cardiac catheterization in 10 patients with primary dilated (congestive) cardiomyopathy. A single dose of 20 micrograms/kg was administered over 5 min after basal hemodynamic and angiographic measurements. The administration of prenalterol caused a significant increase in mean cardiac index, from 2.3 to 3.3 l/min/m2 (P less than 0.01) and mean stroke volume, from 47 to 62 ml (P less than 0.01) without a change in heart rate. Mean left ventricular end-diastolic pressure was reduced from 19 to 13 mm Hg (P less than 0.05) and left ventricular dp/dt rose from 902 to 1089 mm Hg/s (P less than 0.01). Stroke work index increased from 27 to 40 g m/m2 (P less than 0.01) and ejection fraction from 31 to 36% (P less than 0.05). Mean blood pressure did not change and the systemic vascular resistance decreased from 24 to 17 RU (P less than 0.01). The favorable effect of prenalterol on left ventricular relaxation was shown by an increase of peak negative left ventricular dp/dt from 946 to 1159 mm Hg/s and by a decrease of the time constant of left ventricular pressure fall from 49 to 39 s. These results demonstrated a positive inotropic effect of prenalterol on patients with diffuse and severely reduced contractility.

[Hemodynamic effects of disopyramide and procainamide in open-chest animals]. / Effetti emodinamici della diisopiramide e della procainamide nell'animale a torace aperto.

Hemodynamic effects of two antiarrhythmic agents, disopyramide and procainamide, have been evaluated in anesthetized open-chest healthy pigs after random administration. At therapeutic plasma concentrations none of these agents proved to have deleterious hemodynamic effects. The most important action was observed after disopyramide infusion and consisted in significant bradycardia which confirmed the known effect on sinus node automaticity of the drug. Left ventricular dp/dt, an index of cardiac contractility, was unchanged after infusion of both drugs. On the ECG intervals, only procainamide provoked a significant prolongation of QTc. It is concluded that at therapeutic dosage disopyramide does not present deleterious hemodynamic effects in animals and proves to be a valid alternative to other traditional antiarrhythmic agents.