Giovanni B. Perego

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.

Monitoring Intrathoracic Impedance with an Implantable Defibrillator Reduces Hospitalizations in Patients with Heart Failure

Purpose: Some implantable cardioverter‐defibrillators (ICDs) are now able to monitor intrathoracic impedance. The aim of the study was to describe the use of such monitoring in clinical practice and to evaluate the clinical impact of the fluid accumulation alert feature of these ICDs.

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)

Cost-Utility Analysis of the EVOLVO Study on Remote Monitoring for Heart Failure Patients With Implantable Defibrillators: Randomized Controlled Trial

Background Heart failure patients with implantable defibrillators place a significant burden on health care systems. Remote monitoring allows assessment of device function and heart failure parameters, and may represent a safe, effective, and cost-saving method compared to conventional in-office follow-up. Objective We hypothesized that remote device monitoring represents a cost-effective approach. This paper summarizes the economic evaluation of the Evolution of Management Strategies of Heart Failure Patients With Implantable Defibrillators (EVOLVO) study, a multicenter clinical trial aimed at measuring the benefits of remote monitoring for heart failure patients with implantable defibrillators. Methods Two hundred patients implanted with a wireless transmission–enabled implantable defibrillator were randomized to receive either remote monitoring or the conventional method of in-person evaluations. Patients were followed for 16 months with a protocol of scheduled in-office and remote follow-ups. The economic evaluation of the intervention was conducted from the perspectives of the health care system and the patient. A cost-utility analysis was performed to measure whether the intervention was cost-effective in terms of cost per quality-adjusted life year (QALY) gained. Results Overall, remote monitoring did not show significant annual cost savings for the health care system (€1962.78 versus €2130.01; P=.80). There was a significant reduction of the annual cost for the patients in the remote arm in comparison to the standard arm (€291.36 versus €381.34; P=.01). Cost-utility analysis was performed for 180 patients for whom QALYs were available. The patients in the remote arm gained 0.065 QALYs more than those in the standard arm over 16 months, with a cost savings of €888.10 per patient. Results from the cost-utility analysis of the EVOLVO study show that remote monitoring is a cost-effective and dominant solution. Conclusions Remote management of heart failure patients with implantable defibrillators appears to be cost-effective compared to the conventional method of in-person evaluations. Trial Registration ClinicalTrials.gov NCT00873899; http://clinicaltrials.gov/show/NCT00873899 (Archived by WebCite at http://www.webcitation.org/6H0BOA29f).

Oxygen Transport to Muscle During Exercise in Chronic Congestive Heart Failure Secondary to Idiopathic Dilated Cardiomyopathy

In chronic heart failure, oxygen delivery during exercise is impaired mainly because of failure of cardiac output to increase normally. Compensatory mechanisms are hemoglobin concentration increase, right-ward shift in the oxyhemoglobin dissociation curve, and blood flow redistribution from the nonexercising organs to the exercising muscles.

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.

Thrombin activation and late restenosis after percutaneous transluminal coronary angioplasty

BACKGROUND Mechanisms of restenosis after percutaneous transluminal coronary angioplasty (PTCA) have not been defined yet. Experimental studies have shown that thrombin, by stimulating platelet growth factor secretion and smooth muscle cell proliferation, can play a major role. METHODS AND RESULTS In 34 patients with single-vessel coronary disease undergoing PTCA, thrombin activity was evaluated through serial fibrinopeptide A (FPA) plasma determinations. Samples were performed before PTCA, immediately after and 24 hours, 72 hours, and 6 months later. Patients were grouped according to the development (group 1, n = 13) or nondevelopment (group 2, n = 21 ) of restenosis at a 6-month angiographic control. No difference in the two groups was found concerning baseline FPA values. In patients in group 1, soon after PTCA higher FPA levels (27.3 +/- 13.7 ng/ml) than those in group 2 (9.2 +/- 5.6 ng/ml; p < 0.05 vs pre-PTCA, and p < 0.01 between the two groups) were observed. No differences in FPA levels were detected at the other steps between the two groups. CONCLUSION Our data suggest that thrombin plays a role in the process of restenosis after PTCA; acute FPA response to the procedure seems to have a predictive value.

Effectiveness of subcutaneous implantable cardioverter-defibrillator testing in patients with hypertrophic cardiomyopathy

BACKGROUND Subcutaneous ICD (S-ICD) is a promising option for Hypertrophic Cardiomyopathy (HCM) patients at risk of Sudden Cardiac Death (SCD). However, its effectiveness in terminating ventricular arrhythmias in HCM is yet unresolved. METHODS Consecutive HCM patients referred for S-ICD implantation were prospectively enrolled. Patients underwent one or two attempts of VF induction by the programmer. Successful conversion was defined as any 65J shock that terminated VF (not requiring rescue shocks). Clinical and instrumental parameters were analyzed to study predictors of conversion failure. RESULTS Fifty HCM patients (34 males, 40±16years) with a mean BMI of 25.2±4.4kg/m2 were evaluated. Mean ESC SCD risk of was 6.5±3.9% and maximal LV wall thickness (LVMWT) was 26±6mm. In 2/50 patients no arrhythmias were inducible, while in 7 (14%) only sustained ventricular tachycardia was induced and cardioverted. In the remaining 41 (82%) patients, 73 VF episodes were induced (1 episode in 14 and >1 in 27 patients). Of these, 4 (6%) spontaneously converted. In 68/69 (98%) the S-ICD successfully cardioverted, but failed in 1 (2%) patient, who needed rescue defibrillation. This patient was severely obese (BMI 36) and LVMWT of 25mm. VF was re-induced and successfully converted by the 80J reversed polarity S-ICD. CONCLUSIONS Acute DT at 65J at the implant showed the effectiveness of S-ICD in the recognition and termination of VT/VF in all HCM patients except one. Extreme LVH did not affect the performance of the device, whereas severe obesity was likely responsible for the single 65J failure.

β-Thromboglobulin plasma levels in the first week after myocardial infarction: Influence of thrombolytic therapy

In vitro and in vivo studies have shown both an inhibition and an activation of platelets after thrombolysis in acute myocardial infarction. Plasma beta-thromboglobulin, a marker of platelet activity, was evaluated daily during the first week after myocardial infarction in 24 patients who received intravenous streptokinase (group 1) and 26 who did not (group 2). On admission, levels of beta-thromboglobulin, as compared to those in healthy subjects (35 +/- 9 IU/ml), were similarly augmented in group 1 (105 +/- 27 IU/ml) and in group 2 (115 +/- 30 IU/ml); 3 hours later, values averaged 191 +/- 58 IU/ml in group 1 (p < 0.001 vs baseline) and 95 +/- 28 IU/ml in group 2 (not significant vs baseline; p < 0.001 between the two groups). From the second to the seventh day, beta-thromboglobulin augmented in those patients in both groups with postinfarction angina. From day 5 to day 7, patients of group 1 without angina had lower beta-thromboglobulin levels than patients of group 2 who had no symptoms. The lowest levels of platelet activity were observed in group 1 reperfused patients. These data indicate that in myocardial infarction an early platelet activation takes place that is enhanced by thrombolytic treatment; recurrence of angina is associated with persistent activation; in the absence of recurrent angina, thrombolysis can limit late platelet activation.

Control of pulmonary vasomotility in congestive heart failure

Although enhanced sympathetic tone is a well-known component of the autonomic imbalance of heart failure, its influence on pulmonary vasomotility is undefined. We investigated the pulmonary circulation in 12 patients with congestive heart failure in NYHA functional class III and in a control group of 10 normal subjects. Sympathetic influence on pulmonary vessels was studied through adrenergic activation by the arithmetic test and the cold pressor test. A rubber balloon was distended in the inferior vena cava to reduce transpulmonary flow and its influence on vascular tone. In normal individuals the arithmetic test caused pulmonary vasodilation, probably because of the mechanical effect of a largely enhanced flow: in fact, caval obstruction unmasked a neurogenic vasoconstrictor response to the arithmetic test by simply reducing the amount of cardiac output increase. In patients with heart failure, cardiac output and pulmonary arteriolar resistance remained steady during the arithmetic test, no matter what the condition of the venous return was. The cold pressor test was always a vasoconstrictor stimulus, but only in normal subjects was vasoconstriction potentiated by reducing, with caval obstruction, transpulmonary flow and its vasodilatory influence. From these data an attenuation of the sympathetic influence on pulmonary vessels in congestive heart failure seems to be likely. This might be explained as the result of modifications of pulmonary vessels rather than of reduced sympathetic excitability since circulating catecholamine levels varied to similar extents in the two groups during the tests. In congestive heart failure interstitial edema and vascular wall imbibition might increase pulmonary vessel tone and decrease vascular receptor availability. Lower reactivity to sympathetic stimuli, particularly to the vasoconstrictor ones, would ensue.