Pier Giuseppe Agostoni

Isolated ultrafiltration in moderate congestive heart failure.

OBJECTIVES The aim of this study was to evaluate whether ultrafiltration is beneficial in patients with moderate congestive heart failure. BACKGROUND Ultrafiltration is beneficial in patients with severe congestive heart failure. METHODS We studied 36 patients in New York Heart Association functional classes II and III in stable clinical condition. Eighteen patients (group A) were randomly selected and underwent a single session of ultrafiltration (venovenous bypass, mean [+/- SEM] ultrafiltrate 1,880 +/- 174 ml, approximately 600 ml/h) and 18 (group B) served as control subjects. RESULTS Two patients in group A and three in group B did not complete the 6-month follow-up study. In group A, soon after ultrafiltration there were significant reductions in right atrial pressure (from 8 +/- 1 to 3.4 +/- 0.7 mm Hg, pulmonary wedge pressure (from 18 +/- 2.5 to 10 +/- 1.9 mm Hg) and cardiac index (from 2.8 +/- 0.2 to 2.3 +/- 0.2 liters/min). During the follow-up period, lung function improved, extravascular lung water (X-ray score) decreased and peak oxygen consumption (ml/min per kg) increased significantly from 15.5 +/- 1 (day -1) to 17.6 +/- 0.9 (day 4), to 17.8 +/- 0.9 (day 30), to 18.9 +/- 1 (day 90) and to 19.1 +/- 1 (day 180). Oxygen consumption at anaerobic threshold (ml/min per kg) also increased significantly from 11.6 +/- 0.8 (day -1) to 13 +/- 0.7 (day 4), to 13.7 +/- 0.5 (day 30), to 15.5 +/- 0.8 (day 90) and to 15.2 +/- 0.8 (day 180). These changes were associated with increased ventilation, tidal volume and dead space/tidal volume ratio at peak exercise. The improvement in exercise performance was associated with a decrease in norepinephrine at rest, a downward shift of norepinephrine kinetics at submaximal exercise and an increase in norepinephrine during orthostatic tilt. None of these changes were recorded in group B. CONCLUSIONS In patients with moderate congestive heart failure, ultrafiltration reduces the severity of the syndrome.

Medium-term effectiveness of L-thyroxine treatment in idiopathic dilated cardiomyopathy

BACKGROUND In dilated cardiomyopathy, short-term administration of L-thyroxine (100 micrograms/ day) improves cardiac and exercise performance without changing the hearts adrenergic sensitivity. The aim of this study was to test the medium-term (3 months) efficacy of L-thyroxine (10 patients) compared with placebo (10 patients) and to find out whether later effects are obtainable. METHODS Echocardiographic parameters in the control state and during acute changes of left ventricular afterload, cardiopulmonary exercise test, and hemodynamic parameters, including cardiac beta 1 responses to dobutamine, were obtained before and at the end of treatment. RESULTS Significant (P < 0.05) changes were observed only with the active drug. After L-thyroxine, patients did not show evidence of chemical hyperthyroidism, despite the increase in thyroxine and the reduction in thyroid-stimulating hormone plasma levels. Cardiac performance improved, as shown by the increase in the left ventricular ejection fraction and rightward shift of the slope of the relation left ventricular ejection fraction/end-systolic stress. Resting cardiac output increased, and the left ventricular diastolic dimensions and systemic vascular resistances decreased. The responses of cardiac output and heart rate to dobutamine infusion were also enhanced. Functional capacity markedly improved, together with an increase in peak exercise cardiac output. CONCLUSION L-thyroxine does not lose its beneficial effects on cardiac and exercise performance on medium-term administration and does not induce adverse effects. In addition to the short-term study, the left ventricular diastolic dimensions were decreased. An upregulation of beta 1 receptors might explain the cardiac response to dobutamine.

Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation. Part I: definition of cardiopulmonary exercise testing parameters for appropriate use in chronic heart failure

Cardiopulmonary exercise testing (CPET) provides a global assessment of the integrated response to exercise involving the pulmonary, cardiovascular, haematopoietic, neuropsychological, and skeletal muscle systems. This information cannot be obtained through investigation of the individual organ systems in isolation. The non-invasive, dynamic physiological overview permits the evaluation of both submaximal and peak exercise responses, providing the physician with relevant information for clinical decision making. The use of CPET in management of the chronic heart failure patient is increasing with the understanding that resting pulmonary and cardiac function testing cannot reliably predict exercise performance and functional capacity and that, furthermore, overall health status and prognosis are predicted better by indices of exercise tolerance than by resting measurements. Our aim is to produce a statement which provides recommendations on the interpretation and clinical application of CPET in heart failure, based on contemporary scientific knowledge and technical advances: the focus is on clinical indications, issues of standardization, and interpretative strategies for CPET. Eur J Cardiovasc Prev Rehabil 13:150–164

Usefulness of L-thyroxine to improve cardiac and exercise performance in idiopathic dilated cardiomyopathy

The short-term effects of L-thyroxine (100 micrograms/day, 10 patients) and placebo (10 patients) on idiopathic dilated cardiomyopathy were compared. Before and at the end of the treatment, a hemodynamic study was performed in the control state and during dobutamine infusion. A cardiopulmonary exercise test was also performed with hemodynamic monitoring. An echocardiogram was recorded in the control state and during acute changes of left ventricular afterload. Plasma levels of triiodothyronine, thyroxine, thyroid-stimulating hormone and norepinephrine were measured. Placebo was ineffective. After administration of L-thyroxine all patients had normal thyroid function. The increase in left ventricular ejection fraction and the rightward shift of the slope of left ventricular ejection fraction/end-systolic stress relation (p < 0.05) indicated an improvement in the cardiac inotropic state. This proved to be independent of adrenergic influences by the unchanged beta 1 response to dobutamine. A decrease in resting systemic vascular resistances and an increase in cardiac output (p < 0.05) were also observed. Cardiopulmonary effort parameters improved (p < 0.05) without hemodynamic changes at peak exercise. It is concluded that L-thyroxine short-term administration improves cardiac and exercise performance in patients with chronic heart failure, without modifying the adrenergic support to the heart and the circulatory parameters at peak exercise.

Lung-heart interaction as a substrate for the improvement in exercise capacity after body fluid volume depletion in moderate congestive heart failure

We investigated exercise capacity after fluid depletion in patients with moderate congestive heart failure (CHF). Twenty-one patients underwent ultrafiltration (mean volume +/- SEM: 1,770 +/- 135 ml). Echocardiography, tests of pulmonary function, and a cardiopulmonary exercise test with hemodynamic and esophageal pressure monitoring were performed before ultrafiltration and 3 months later. Tests without invasive measurements were repeated 4 and 30 days after ultrafiltration. Twenty-one control patients followed the same protocol but did not have ultrafiltration. Patients who underwent ultrafiltration and increased their oxygen consumption at peak exercise (peak VO2) by > 10% at the 3-month evaluation (group A1, n = 9) were separated from those who did not (group A2, n = 8); 3 patients did not complete the follow-up. Four days after the procedure, peak VO2 had risen from 17.3 +/- 0.8 to 19.3 +/- 0.9 ml/min/kg in group A1, and from 11.9 +/- 0.7 to 14.1 +/- 0.7 ml/min/kg in group A2 (p < 0.01). Plasma norepinephrine and pulmonary function were consistent with a greater severity of the syndrome in group A2. At 3 months in group A1, the relations of filling pressure to cardiac index of the right and left ventricles were shifted upward; the esophageal pressure swing (differences between end-expiratory and end-inspiratory pressure) for a given tidal volume was lower; the peak exercise dynamic lung compliance had increased from 0.10 +/- 0.05 to 0.14 +/- 0.03 L/mm Hg (p < 0.01). None of these changes were detected in group A2 and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A Four-Minute Submaximal Constant Work Rate Exercise Test to Assess Cardiovascular Functional Class in Chronic Heart Failure

To develop a submaximal constant work rate exercise test able to grade cardiovascular dysfunction in patients with chronic heart failure, 80 patients and 59 control subjects performed a symptom-limited incremental exercise test and a constant work rate exercise test at a fixed work rate (50 W for 4 minutes). The time constant of VO2 at the start of constant work rate exercise and time for gas exchange ratio (respiratory exchange ratio) to equal 1 were independent predictors of cardiovascular functional class and correctly classified the functional class in 89 +/- 9% and 83 +/- 11% of patients, respectively.

Evaluation of the dead space/tidal volume ratio in patients with chronic congestive heart failure

Dead space/tidal volume ratio (VD/VT) evaluation is currently performed in patients with respiratory and cardiac disorders, and includes measurement of arterial CO2 partial pressure (PaCO2). PaCO2 is generally derived from either PETCO2 (end-expiratory CO2 pressure) or PJCO2 (calculated as PJCO2 = 5.5 + 0.9 PETCO2 - 2.1 VT). The applicability of these methods may be questionable in chronic heart failure due to its frequent association with lung dysfunction. In 63 patients with congestive heart failure, the authors compared PaCO2 versus PETCO2 and PJCO2 and VD/VT measured with PaCO2 versus VD/VT estimated with PETCO2 (estimation 1) or PJCO2 (estimation 2). Comparisons were made at rest, at submaximal exercise, and at peak exercise. Considering all 326 measurements, there was a strong correlation, but not an identity, between PaCO2 and PETCO2 (PaCO2 = 7.25 + 0.80 PETCO2, r = .84, P < .0001) and between PaCO2 and PJCO2 (PaCO2 = 6.18 + 0.84 PJCO2, r = .85, P < .0001). Results were comparable concerning PaCO2 versus PJCO2. Measured VD/VTs also strongly correlated with estimated VD/VTs (VD/VT measured = -0.03 + 1.11 VD/VT [estimation 1], r = .90, P < .0001, and VD/VT measured = 0.03 + 0.92 VD/VT [estimation 2], r = .90, P < .0001). However, only at rest and, solely for estimation 1, at submaximal exercise were the slopes and y intercepts of measured versus estimated VD/VT not different from 1 and 0, respectively; in this regard, lung dysfunction was more influential than the severity of cardiac failure. Although PaCO2 strongly correlates with PETCO2 and PJCO2, these measurements may not be reliable for a noninvasive calculation of VD/VT in chronic congestive heart failure.

Monitoring gas exchange during a constant work rate exercise in patients with left ventricular dysfunction treated with carvedilol.

In patients with heart failure, carvedilol ameliorated cardiac function, but it did not affect oxygen uptake, kinetics, and ventilatory efficiency during 6-minute exercise at a constant 50-W workload. Persistence of respiratory incompetence may prevent improvement in submaximal oxygen uptake kinetics.

Cardiopulmonary exercise testing in syndrome X

Patients with syndrome X have been found to have an abnormal coronary blood flow reserve. The physical performance during exercise, however, has been incompletely investigated. Cardiopulmonary exercise testing (CPX) is a reliable noninvasive method to provide indexes of lung, heart, circulation, and muscle functions. In 15 patients (10 women) with syndrome X and in age and sex-matched normal individuals, CPX was performed twice a day (8 AM and 4 PM) on two separate occasions 2 months apart. Time and oxygen consumption at peak exercise, at ventilatory anaerobic and electrocardiographic thresholds, as well as norepinephrine plasma concentrations at each work load and at peak exercise in both tests were obtained. In syndrome X in both evaluations, the 4 PM performance was characterized by an earlier onset of both ventilatory anaerobic and electrocardiographic thresholds despite lower values of VO2 and double-product, and by a greater peak ST segment depression despite similar total exercise time, VO2, and double-product. No difference between tests was found in the norepinephrine response to exercise. Normal subjects showed reproducible CPX and hormonal responses in the two tests. Thus these data may suggest a circadian variation of coronary vascular response to exercise in patients with syndrome X, leading to a lower ischemic threshold early in the afternoon. The parallel earlier onset of the ventilatory anaerobic threshold may reflect a concomitant abnormal muscular blood flow response (that is, vasoconstriction of working muscle arteries), suggesting a link between coronary and peripheral circulations.

Obituary: Romualdo Belardinelli

Romy, a good friend to all of us, was a board member of the cardiac rehabilitation section of the European Association of Preventive Cardiology (EAPC) for many years and was a founding member of the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score research initiative. His career was brilliant. Romy had a worldwide working experience and had many partnerships in Italy and abroad. He was a cardiopulmonary exercise testing (CPET) expert and his works on cardiac rehabilitation and exercise-induced cardiac ischaemia are still milestones. He was a research fellow at UCLA – Harbor Medical Center, Division of Cardiopulmonary Physiology and Critical Care Medicine, Torrance, CA, USA (Director Prof. K Wasserman) from 1991