Franco Cobelli

Short-Term Heart Rate Variability Strongly Predicts Sudden Cardiac Death in Chronic Heart Failure Patients

Background—The predictive value of heart rate variability (HRV) in chronic heart failure (CHF) has never been tested in a comprehensive multivariate model using short-term laboratory recordings designed to avoid the confounding effects of respiration and behavioral factors. Methods and Results—A multivariate survival model for the identification of sudden (presumably arrhythmic) death was developed with data from 202 consecutive patients referred between 1991 and 1995 with moderate to severe CHF (age 52±9 years, left ventricular ejection fraction 24±7%, New York Heart Association class 2.3±0.7; the derivation sample). Time- and frequency-domain HRV parameters obtained from an 8′ recording of ECG at baseline and during controlled breathing (12 to 15 breaths/min) were challenged against clinical and functional parameters. This model was then validated in 242 consecutive patients referred between 1996 and 2001 (validation sample). In the derivation sample, sudden death was independently predicted by a model that included low-frequency power (LFP) of HRV during controlled breathing ≤13 ms2 and left ventricular end-diastolic diameter ≥77 mm (relative risk [RR] 3.7, 95% CI 1.5 to 9.3, and RR 2.6, 95% CI 1.0 to 6.3, respectively). The derivation model was also a significant predictor in the validation sample (P =0.04). In the validation sample, LFP ≤11 ms2 during controlled breathing and ≥83 ventricular premature contractions per hour on Holter monitoring were both independent predictors of sudden death (RR 3.0, 95% CI 1.2 to 7.6, and RR 3.7, 95% CI 1.5 to 9.0, respectively). Conclusions—Reduced short-term LFP during controlled breathing is a powerful predictor of sudden death in patients with CHF that is independent of many other variables. These results refine the identification of patients who may benefit from prophylactic implantation of a cardiac defibrillator.

Predictors of primary atrial fibrillation and concomitant clinical and hemodynamic changes in patients with chronic heart failure: A prospective study in 344 patients with baseline sinus rhythm

OBJECTIVES This study investigated the incidence, predisposing factors and significance of the onset of atrial fibrillation (AF) in patients with chronic congestive heart failure (CHF). BACKGROUND The association between CHF and AF is well documented, but the factors that predispose to the onset of the arrhythmia and its impact remain controversial. Methods. We prospectively followed up 344 patients with CHF and sinus rhythm (SR). Over a period of 19 +/- 12 months (mean +/- SD), 28 patients developed atrial fibrillation (AF), which became chronic in 18. RESULTS At baseline, no differences were found in any clinical and hemodynamic variables between patients who developed chronic AF and those who did not. Reversible AF occurring during follow-up and lower mitral flow velocity at atrial contraction as detected at the last evaluation in SR were independent predictors of the subsequent development of chronic AF. When AF occurred, New York Heart Association functional class worsened (from 2.4 +/- 0.5 to 2.9 +/- 0.6, p = 0.0001), peak exercise oxygen consumption declined (from 16 +/- 5 to 11 +/- 5 ml/kg per min, p = 0.002), cardiac index decreased (from 2.2 +/- 0.4 to 1.8 +/- 0.4, p = 0.0008), and mitral and tricuspid regurgitation increased (from grade 1.8 +/- 1.1 to grade 2.4 +/- 1.4, p = 0.0001 and from grade 1.0 +/- 1.2 to grade 1.8 +/- 1.2, p = 0.001, respectively). Systemic thromboembolism occurred in 3 of the 18 patients with AF. Nine of 18 patients died after AF, and the occurrence of AF was a predictor of major cardiac events. CONCLUSIONS In patients with CHF, reversible AF and reduction of left atrial contribution to left ventricular filling predict the subsequent development of chronic AF. The onset of AF is associated with clinical and hemodynamic deterioration and may predispose to systemic thromboembolism and poorer prognosis.

β-Blockade therapy in chronic heart failure: Diastolic function and mitral regurgitation improvement by carvedilol

BACKGROUND: In patients with chronic heart failure, the use of carvedilol therapy induces clinical and hemodynamic improvement. However, although the benefits of this beta-blocker have been established in patients with chronic heart failure, the mechanisms underlying them and the changes in left ventricular systolic function, diastolic function, and mitral regurgitation during long-term therapy remain unclear. OBJECTIVE: To identify the clinical and functional effects of carvedilol, focusing on diastolic function and mitral regurgitation variations. METHODS: Forty-five consecutive patients with chronic heart failure (ejection fraction 24% +/- 7%), 17 with dilated ischemic and 28 with nonischemic cardiomyopathy, were treated with carvedilol (mean dose 44 +/- 30 mg) and matched for clinical (New York Heart Association functional class and heart failure duration) and hemodynamic (cardiac index and pulmonary wedge pressure) characteristics to a control group. Clinical and echocardiographic variables were measured in the 2 groups at baseline and after 6 months and the results compared. RESULTS: After 6 months of treatment with carvedilol, left ventricular ejection fraction had increased from 24% +/- 7% to 29% +/- 9% (P <.0001); this change was caused by a reduction in end-systolic volume index (106 +/- 41 vs 93 +/- 37 mL/m(2); P <. 0001). Deceleration time of early diastolic filling increased (134 +/- 74 vs 196 +/- 63 ms; P <.0001). Seventeen of the 27 patients with demonstrated improvement of left ventricular diastolic filling moved from having a restrictive filling pattern to having a normal or pseudonormal left ventricular filling pattern. In the control group, no significant changes in deceleration time of early diastolic filling were found (139 +/- 74 vs 132 +/- 45 ms; P = not significant). The effective regurgitant orifice area decreased significantly in the carvedilol group but not in the control group. These changes were associated with a significant reduction of the mitral regurgitant stroke volume in the carvedilol group (50 +/- 25 vs 16 +/- 13 mL; P <.0001) but not in the control group (57 +/- 29 vs 47 +/- 24 mL; P = not significant). These changes of mitral regurgitation were closely associated with significant improvement of forward aortic stroke volume (r = -.57, P <.0001). These findings were not observed in patients in the control group. CONCLUSIONS: The results of this study show that long-term carvedilol therapy in patients with chronic heart failure was able to prevent or partially reverse progressive left ventricular dilatation. The effects on left ventricular remodeling were associated with a concomitant recovery of diastolic reserve and a decrease of mitral regurgitation, which have been demonstrated to be powerful prognostic predictors in such patients. Overall these findings provide important insights into the pathophysiologic mechanisms by which carvedilol improves the clinical course of patients with chronic heart failure.

Cost/utility ratio in chronic heart failure: comparison between heart failure management program delivered by day-hospital and usual care

OBJECTIVES This study compared the effectiveness and cost/utility ratio between a heart failure (HF) management program delivered by day-hospital (DH) and usual care in chronic heart failure (CHF) outpatients. BACKGROUND Previous studies showed that about 50% of readmissions for CHF can be prevented by a multidisciplinary approach However, the performance, effectiveness, and cost/utility ratio of a process of HF outpatient management related to evidence-based medicine have not been considered. METHODS A total of 234 prospective patients discharged by a HF Unit were randomized to two management strategies: 122 patients to usual community care and 112 patients to a HF management program delivered by the DH. Management (rate of readmissions, therapeutic interventions), functional parameters (New York Heart Association [NYHA] functional class, left ventricular diameters, and ejection fraction, deceleration time of early diastolic mitral flow, peak oxygen uptake, and mitral regurgitation) and hard outcomes (cardiac death and urgent cardiac transplantation) were evaluated. The cost/utility ratios of the two strategies were compared. RESULTS After 12 3 months of follow-up, the individual rate access in DH was 5.5 3.8 days. The DH subjects were readmitted to the hospital less frequently than were the usual-care group patients (13 vs. 78, p 0.00001). Patients allocated to usual-care management showed heterogeneous changes in NYHA functional class (13% improved and 16% worsened p NS); In contrast, the DH group showed significant changes in NYHA functional class (23% improved and 11% worsened, p 0.009). Hard cardiac events in the one-year follow-up occurred in 25/234 (10.6%) patients; cardiac death occurred in 21/122 (17.2%) of the community group and in 3/112 (2.7%) in the DH group (p 0.0007). One DH patient underwent urgent transplantation. Comparison of the two managerial models by Cox regression analysis showed that DH management significantly protected against the appearance of hard events (relative risk [RR] 0.17; confidence interval [CI] 0.06 to 0.66). The cost/utility ratio of the two management strategies was similar (usual care

Doppler echocardiography reliably predicts pulmonary artery wedge pressure in patients with chronic heart failure with and without mitral regurgitation

2,409 vs. DH

Nonselective beta-adrenergic blocking agent, carvedilol, improves arterial baroflex gain and heart rate variability in patients with stable chronic heart failure

2,244). The incremental analysis revealed a cost savings of

Dobutamine and nitroprusside infusion in patients with severe congestive heart failure: Hemodynamic improvement by discordant effects on mitral regurgitation, left atrial function, and ventricular function

1,068 for each quality-adjusted life year gained. The cost/utility ratio for the integration of DH management of CHF was

Association between hemodynamic impairment and cheyne-stokes respiration and periodic breathing in chronic stable congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

19,462 (CI

Invasive and non-invasive determinants of pulmonary hypertension in patients with chronic heart failure

13,904 to

Doppler evaluations of left ventricular diastolic filling and pulmonary wedge pressure provide similar prognostic information in patients with systolic dysfunction after myocardial infarction.

34,048). CONCLUSIONS A heart failure outpatient management program delivered by a DH can reduce mortality and morbidity of CHF patients. This management strategy is cost-effective and has an equitable value from a societal point of view. (J Am Coll Cardiol 2002;40:1259 ‐ 66)