Cristina Opasich

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.

Tumor Necrosis Factor Soluble Receptors in Patients With Various Degrees of Congestive Heart Failure

BACKGROUND Tumor necrosis factor alpha (TNF-alpha) increases in patients with severe congestive heart failure (CHF) and cachexia. Two naturally occurring modulators of TNF-alpha activity have been identified in human serum. These two soluble proteins are the extracellular domains of the TNF receptors (sTNF-RI and sTNF-RII, respectively). The determination of circulating sTNF-Rs could provide us with some additional information about the activation of this cytokine in CHF. METHODS AND RESULTS This study was undertaken to examine the concentration of sTNF-Rs and of bioactive and antigenic TNF-alpha in 37 consecutive patients with various degrees of CHF compared with that of 26 age-matched healthy subjects. Antigenic TNF-alpha increased (from 14.3 +/- 7.08 to 33.5 +/- 13.1 pg/mL, P < .001) in preterminal patients with severe CHF (New York Heart Association [NYHA] class IV). In these patients, sTNF-Rs were also increased (sTNF-RI from 1.17 +/- 0.43 to 4.43 +/- 2.14 ng/mL and sTNF-RII from 2.2 +/- 0.44 to 7.55 +/- 2.28 ng/mL, P < .001). When measured by cytolytic bioassay, TNF-alpha was undetectable (< 100 pg/mL). Addition of 625 pg/mL recombinant human TNF-alpha (rhTNF-alpha), corresponding in the bioassay to 60% of the lethal dose, to the serum of healthy subjects resulted in a significant increase of the expected cytotoxicity (from 625 to 1290 +/- 411 pg/mL, P < .001). Addition of the same dose of rhTNF-alpha to the serum of patients with mild to moderate CHF (NYHA classes II and III) increased the cytotoxicity from 625 to 877 +/- 132 pg/mL, P < .001. In 4 patients with severe CHF (class IV), the expected cytotoxicity was completely inhibited, whereas it was reduced from 625 to 263 +/- 198 pg/mL, P < .001, in the remaining 8 patients. Ten patients died within 1 month of entry into the study. They had the highest level of sTNF-RII (8.18 +/- 1.92 ng/mL). sTNF-RII was a more powerful independent indicator of mortality than TNF-alpha, sTNF-RI, NYHA class, norepinephrine, and atrial natriuretic peptide. CONCLUSIONS Measurement of sTNF-Rs, in addition to antigenic and bioactive TNF-alpha, is essential for evaluation of the activation of this cytokine in CHF. Both sTNF-Rs increase in preterminal patients with severe CHF and might inhibit the in vitro cytotoxicity of TNF-alpha. Antigenic TNF-alpha also increases in severe CHF. The increased levels of sTNF-RII independently correlate with poor short-term prognosis.

Arterial Baroreflex Modulation of Heart Rate in Chronic Heart Failure: Clinical and Hemodynamic Correlates and Prognostic Implications

BACKGROUND In chronic heart failure (CHF), arterial baroreflex regulation of cardiac function is impaired, leading to a reduction in the tonic restraining influence on the sympathetic nervous system. Because baroreflex sensitivity (BRS), as assessed by the phenylephrine technique, significantly contributes to postinfarction risk stratification, the aim of the present study was to evaluate whether in CHF patients a depressed BRS is associated with a worse clinical hemodynamic status and unfavorable outcome. METHODS AND RESULTS BRS was assessed in 282 CHF patients in sinus rhythm receiving stable medical therapy (age, 52+/-9 years; New York Heart Association [NYHA] class, 2.4+/-0.6; left ventricular ejection fraction [LVEF], 23+/-6%). The BRS of the entire population averaged 3.9+/-4.0 ms/mm Hg (mean+/-SD) and was significantly related to LVEF and hemodynamic parameters (LVEF, P<.005; cardiac index and pulmonary wedge pressure, P<.001 by regression analysis). Patients in NYHA classes III or IV and those with severe mitral regurgitation had markedly depressed vagal reflexes. The association of BRS with survival was described after its categorization in three groups: below the lowest quartile (<1.3 ms/mm Hg), between the lowest quartile and the median (1.3 to 3 ms/mm Hg), and above the median (>3 ms/mm Hg). During a mean follow-up of 15+/-12 months, 78 primary events (cardiac death, nonfatal cardiac arrest, and status 1 priority transplantation) occurred (27.6%). BRS was significantly related to outcome (log rank, 9.1; P<.01), with a relative risk of 2.7 (95% confidence interval, 1.6 to 4.7) for patients with the major derangement in BRS (<1.3 ms/mm Hg). At multivariate analysis, BRS was an independent predictor of death after adjustment for noninvasive known risk factors but not when hemodynamic indexes were also considered. In CHF patients with severe mitral regurgitation, however, BRS remained a strong prognostic marker independent of hemodynamic function. CONCLUSIONS In moderate to severe CHF, a depressed sensitivity of vagal reflexes parallels the deterioration of clinical and hemodynamic status and is significantly associated with poor survival. Particularly in patients with severe mitral regurgitation the baroreceptor modulation of heart rate provides prognostic information of incremental value to hemodynamic parameters.

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.

Is nutritional intake adequate in chronic heart failure patients

OBJECTIVES The goal of this study was to investigate the nutrition adequacy and energy availability for physical activity in free-living, clinically stable patients with chronic heart failure (CHF). BACKGROUND Little information exists regarding the nutrition adequacy and alimentary habits of patients with clinically stable CHF. We hypothesized that CHF patients have an inadequate intake of calories and protein, leading to a negative calorie and nitrogen balance, an expression of increased tissue breakdown. METHODS In 57 non-obese patients with CHF (52 males and 5 females; 52 +/- 3 years; body mass index <25 kg/m(2)) and in 49 healthy subjects (39 males and 10 females) matched for age, body mass index, and sedentary life style we evaluated total energy expenditure (TEE), calorie intake (kcal(I)), and nitrogen intake (N(I)) from a seven-day food diary, total nitrogen excretion (TNE), and energy availability (EA = kcal(I) - resting energy expenditure). A zero calorie balance (CB) occurred when kcal(I) = TEE; a nitrogen balance (NB) in equilibrium was set at NB (= N(I) - TNE) 0 +/- 1 g/day. RESULTS In patients and controls kcal(I) and N(I) were similar. However, in CHF patients the kcal(I) was <TEE with a consequent negative CB (-186 +/- 305 kcal/day vs. + 104.2 +/- 273 kcal/day of controls; p < 0.01). Nitrogen balance resulted negative in CHF (-1.7 +/- 3.2 g/24 h vs. + 2.2 +/- 3.6 g/24 h in controls; p < 0.01). Energy availability in CHF patients was 41% lower than in controls (p < 0.05). CONCLUSIONS Non-obese, free-living patients with clinically stable CHF have an inadequate intake of calories and protein and reduced energy availability for physical activity.

Current presentation and management of heart failure in cardiology and internal medicine hospital units: a tale of two worlds--the TEMISTOCLE study.

BACKGROUND The purpose pf the current article is to describe the clinical profile, use of resources, management and outcome in a population of real-world inpatients with heart failure. METHODS AND RESULTS With a prospective, cross-sectional survey on acute hospital admissions, we evaluated the overall and provider-related differences in patient characteristics, diagnostic work-up, treatment and inhospital outcome of 2127 patients with heart failure admitted to 167 cardiology departments and 250 internal medicine departments between February 14 and 25, 2000. Patients admitted to cardiology units were younger (56.3% >70 years vs 76.2%, P <.0001), had more severe symptoms (NYHA IV 35% vs 29%, P =.00014), and more often underwent evaluation of ventricular function (89.3% vs 54.8%, P <.0001) and coronary angiography (7.5% vs 0.9%, P <.0001) than those admitted to medical units. Moreover, they were more often prescribed beta-blockers (17.8% vs 8.7%, P <.0001). However, prescription of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (78.7% vs 81.5%, P = not significant [NS]) and inhospital mortality (5.2% vs 5.9%, P = NS) were similar. A 6-month follow-up visit was performed in 56.4% of cases (68.2% of cardiology vs 49.4% of medicine patients, P <.0001); 6-month readmission (43.7% vs 45.4%, P = NS) and mortality (13.9% vs 16.7%, P = NS) rates were similar. CONCLUSIONS Patients with heart failure admitted to cardiology and internal medicine units represent 2 clearly different populations. In both groups, diagnostic procedures and evidence-based treatments, such as beta-blockers, appeared to be underused, and there was a lack of structured follow-up, as well as a poor 6-month prognosis.

Restrictive Cardiomyopathy, Atrioventricular Block and Mild to Subclinical Myopathy in Patients With Desmin-Immunoreactive Material Deposits

OBJECTIVES We present clinical data and heart and skeletal muscle biopsy findings from a series of patients with ultrastructural accumulations of granulofilamentous material identified as desmin. BACKGROUND Desmin cardiomyopathy is a poorly understood disease characterized by abnormal desmin deposits in cardiac and skeletal muscle. METHODS Clinical evaluation, endomyocardial and skeletal muscle biopsy, light and electron microscopy and immunohistochemistry were used to establish the presence of desmin cardiomyopathy. RESULTS Six hundred thirty-one patients with primary cardiomyopathy underwent endomyocardial biopsy (EMB). Ultrastructural accumulations of granulofilamentous material were found in 5 of 12 biopsy samples from patients with idiopathic restrictive cardiomyopathy and demonstrated specific immunoreactivity with anti-desmin antibodies by immunoelectron microscopy. Immunohistochemical findings on light microscopy were nonspecific because of a diffuse intracellular distribution of desmin. All five patients had atrioventricular (AV) block and mild or subclinical myopathy. Granulofilamentous material was present in skeletal muscle biopsy samples in all five patients, and unlike the heart biopsy samples, light microscopic immunohistochemical analysis demonstrated characteristic subsarcolemmal desmin deposits. Two patients were first-degree relatives (mother and son); another son with first-degree AV block but without myopathy or cardiomyopathy demonstrated similar light and ultrastructural findings in skeletal muscle. Electrophoretic studies demonstrated two isoforms of desmin--one of normal and another of lower molecular weight--in cardiac and skeletal muscle of the familial cases. CONCLUSIONS Desmin cardiomyopathy must be considered in the differential diagnosis of restrictive cardiomyopathy, especially in patients with AV block and myopathy. Diagnosis depends on ultrastructural examination of EMB samples or light microscopic immunohistochemical studies of skeletal muscle biopsy samples. Familial desminopathy may manifest as subclinical disease and may be associated with abnormal isoforms of desmin.

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

OBJECTIVES In patients with severe heart failure additional therapeutic support with intravenous inotropic or vasodilator drugs is frequently used in the attempt to obtain hemodynamic control. The nature and extent to which diastolic filling, atrial function, and mitral regurgitation are modified by these drugs have not been fully explored. The aim of this study was to compare the acute adaptations of the left ventricular performance, left atrial function, and mitral regurgitation that accompanied hemodynamic improvement during intravenous dobutamine and nitroprusside infusions in patients with severe chronic heart failure. METHODS Forty consecutive patients with severe heart failure were evaluated by simultaneous echo-Doppler and hemodynamic investigations at baseline and during nitroprusside and dobutamine administration. Mitral flow velocity variables, left atrial and ventricular volumes, left atrial reservoir, conduit and pump volumes, and mitral regurgitation jet area were compared by analysis of variance for repeated measurements. RESULTS Nitroprusside increased cardiac output (2.1 +/- .5 vs 2.6 +/- .5 L/min/m2, p < 0.004), reduced left ventricular filling pressure (25 +/- 6 vs 14 +/- 4 mm Hg, p < 0.0001), and improved left atrial pump volume (19 +/- 3 vs 26 +/- 12 ml, p < 0.02) without variations in left atrial reservoir and conduit volume. The restoration of preload reserve and improvement of the atrial contribution to left ventricular diastolic filling were demonstrated by the Doppler mitral flow pattern, which moved from a restrictive to a normal pattern. Furthermore mitral regurgitation decreased in all patients (9 +/- 4.6 vs 4.6 +/- 3.4 cm2, p < 0.0001). Dobutamine increased cardiac output (2.1 +/- .5 vs 2.8 +/- .6 L/min/m2), but the effects on pulmonary wedge pressure and mitral regurgitation were variable and unpredictable. Left atrial reservoir and conduit volumes increased, whereas left atrial pump volume did not change (19 +/- 13 vs 22 +/- 14 ml, p = NS). Furthermore Doppler mitral flow showed a persistent restrictive pattern. CONCLUSIONS In patients with advanced congestive heart failure both nitroprusside and dobutamine improve cardiac output, with different adaptations of left ventricular performance and left atrial function. Nitroprusside seems to restore both atrial and ventricular pump function better. Careful echo-Doppler monitoring during drug infusion provides information relevant to the clinical treatment of individual patients.

Comparison of one-year outcome in women versus men with chronic congestive heart failure

Using information from the Italian Network on Congestive Heart Failure, we examined whether clinical epidemiologic characteristics, drug prescription patterns, and outcome of patients with congestive heart failure differed according to sex and whether gender was an independent risk factor for mortality and hospital admissions.

Adequate energy-protein intake is not enough to improve nutritional and metabolic status in muscle-depleted patients with chronic heart failure

An adequate energy‐protein intake (EPI) when combined with amino acid supplementation may have a positive impact nutritional and metabolic status in patients with chronic heart failure (CHF).