Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR. Part II.

In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose­response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.

Heart transplantation in a low-organ-donation environment: a single center experience.

OBJECTIVE: Heart transplantation is the "gold standard" for treating patients in end-stage heart failure who satisfy strict selection criteria. However, infrequent transplant performance, eg, less than nine per year, may be associated with suboptimal results. METHODS: We reviewed our 13-year clinical experience (1996-2008) with 73 orthotopic heart transplants performed under strict selection criteria and followed closely thereafter at the only accredited center in Greece, a country with an annual rate of only seven donors per million population. RESULTS: Low perioperative (5.47%) and long-term (7.5%) mortality rates were responsible for a 94% survival rate in the first year, 92% at five years, and 70% at ten years-similar to those reported worldwide-along with excellent functional recovery. CONCLUSION: Strict recipient and donor selection criteria, combined with a rigorous multidisciplinary follow-up, yield excellent results despite the existing shortage of available grafts.

Clinical and prognostic implications of self-rating depression scales and plasma B-type natriuretic peptide in hospitalised patients with chronic heart failure.

BACKGROUND: Depression is common among patients with chronic heart failure (CHF) and has been independently associated with a poorer prognosis. PURPOSE: This study evaluated the clinical and prognostic value of depression scales (Beck Depression Inventory (BDI), Zung Self-rating Depression Scale (Zung SDS)) along with plasma B-type natriuretic peptide (BNP) in CHF. METHODS: 155 hospitalised CHF patients (ejection fraction 26.9% (SD 6.4%)) were studied by depression (BDI, Zung SDS) and functional questionnaires (Kansas City Cardiomyopathy Questionnaire (KCCQ), Duke Activity Status Index (DASI)), BNP and 6-minute walk test (6MWT). Patients were followed for 6 months for cardiovascular events, including death from any cause or rehospitalisation for CHF decompensation. RESULTS: Seventy-six (49%) patients with depressive symptoms, as estimated by both scales, had significantly lower DASI and KCCQ scores (13.2 (SD 9.9) vs 23.6 (SD 13.0) and 26.6 (SD 15.0) vs 45.0 (SD 17.0), respectively; p<0.001), higher BNP (921 (SD 889) vs 439 (SD 267) pg/ml, p = 0.001) and reduced 6MWT (270 (SD 130) vs 337 (SD 133); p<0.001). According to logistic regression analysis, Zung SDS and BNP were independently associated with adverse clinical outcomes; values of Zung SDS >or=40 and of BNP >or=290 pg/ml predicted future events with a sensitivity of 82% and 94% and a specificity of 45% and 46%, respectively. The combination of Zung SDS plus BNP had an additive prognostic value, predicting events with a sensitivity of 77% and a specificity of 70% (event-free survival: Zung <40 and BNP <290 pg/ml; 170 (SD 9) days; Zung >or=40 and BNP <290 pg/ml, 159 (SD 14) days; Zung <40 and BNP >or=290 pg/ml, 118 (SD 15) days; Zung >or=40 and BNP >or=290 pg/ml, 73 (SD 8) days, p<0.001). CONCLUSIONS: CHF patients with depressive symptoms have impaired physical activity, associated with excessive neurohormonal activation. Among the studied scales, Zung SDS seemed to independently predict clinical outcome, especially in patients with increased plasma BNP concentration. Hence, the combination of those two modalities provides a practical means for risk stratification in CHF.

Effects of serial levosimendan infusions on left ventricular performance and plasma biomarkers of myocardial injury and neurohormonal and immune activation in patients with advanced heart failure.

BACKGROUND: Levosimendan is a novel inodilator that improves central haemodynamics and symptoms of patients with decompensated chronic heart failure. The role, however, of repeated levosimendan infusions in the management of these patients has not yet been properly assessed. PURPOSE: This randomised placebo-controlled trial investigated the effects of serial levosimendan infusions on cardiac geometry and function, and on biomarkers of myocardial injury and neurohormonal and immune activation (troponin T, N-terminal B-type natriuretic pro-peptide (NT-proBNP), C reactive protein (CRP) and interleukin (IL) 6) in patients with advanced heart failure. METHODS: 25 patients with decompensated chronic heart failure were randomised (2:1) to receive five serial 24-h infusions (every 3 weeks) of either levosimendan (n = 17) or placebo (n = 8), and were evaluated echocardiographically and biochemically before and after each drug infusion and 30 days after the final infusion. RESULTS: Following treatment, cardiac end-systolic and end-diastolic dimension and volume indices were significantly reduced only in the levosimendan-treated patients (p<0.01). A significant decrease in NT-proBNP (p<0.01), high-sensitivity CRP (p<0.01) and plasma IL6 (p = 0.05) was also observed in the levosimendan group, whereas these markers remained unchanged in the placebo group; similar changes were observed after each drug infusion. Although the number of patients with a positive troponin T (>or=0.01 ng/ml) was not different between the two groups at baseline, it was significantly higher in the placebo-treated group during the final evaluation (p<0.05). CONCLUSION: Serial levosimendan treatments improved left ventricular performance and modulated neurohormonal and immune activation beneficially in patients with advanced heart failure, without increasing myocardial injury.

Increased C reactive protein and cardiac enzyme levels after coronary stent implantation. Is there protection by remote ischaemic preconditioning?

AIM: To investigate whether remote ischaemic preconditioning (RIPC) can attenuate the inflammatory response and enzyme leakage that can occur after uncomplicated routine percutaneous coronary intervention (PCI). METHODS: 41 consecutive normotensive patients with stable angina and single-vessel disease were assigned to be exposed to RIPC (n = 20) or not (control group; n = 21) before elective PCI with stent implantation. RIPC was induced by three cycles of 5-min ischaemia-reperfusion of both upper limbs (inflation/deflation of blood pressure cuff). C reactive protein (CRP), creatine phosphokinase (CK), CK cardiac isoenzyme (CK-MB) and troponin I (TNI) were serially measured for 48 h. RESULTS: No difference in baseline values was observed between the groups. The CRP rose significantly (p<0.001) and at 48 h was similarly increased (>fourfold) in both groups (15.7 (2.6) v 14.0 (3.3) mg/l, RIPC v control; p = NS). However, sub-group analysis on the basis of statin use showed that the highest rise was in the group of patients with RIPC not taking statins and was significantly greater than in patients with RIPC taking statins (23.8 (3.71) v 11.4 (3.0) mg/l, respectively, p<0.01). Both CK-MB and TNI leakage were raised (slightly but significantly) after PCI in controls at 24 h compared with baseline values. However, this small rise was significantly worse after RIPC (CK-MB, 1.33 (0.27) v 3.57 (0.97) ng/ml, p<0.01; TNI, 0.255 (0.059) v 0.804 (0.232) ng/ml, p<0.05, respectively at 24 h). The increase was more marked in the RIPC subgroup not taking statins. CONCLUSIONS: RIPC does not reduce, but exacerbates, the enzyme and TNI release from the heart after single-vessel angioplasty with stent. Furthermore, the increased circulating CRP remains raised. It seems that there is an enhanced inflammatory response after RIPC in the absence of statin treatment.

A glossary of circulating cytokines in chronic heart failure.

Recent studies have emphasized the importance of biologically active molecules, termed cytokines, in the development and progression of the syndrome of chronic heart failure. This article summarizes a glossary of major cytokines and other cytokine-related inflammatory factors implicated in the pathophysiology of chronic heart failure, describing the source of their synthesis and factors regulating their secretion and analyzing their biologic effects on the cardiovascular system.

Dobutamine echocardiographic study in patients with nonischemic dilated cardiomyopathy and prognostically borderline values of peak exercise oxygen consumption: 18-month follow-up study.

OBJECTIVES: We sought to study the prognostic value of dobutamine echocardiography in patients with nonischemic dilated cardiomyopathy (DCM) and prognostically borderline values of peak oxygen consumption (VO2max) during exercise. BACKGROUND: Changes in echocardiographic variables assessed by dobutamine echocardiography can be used to evaluate the functional status of patients with chronic heart failure (CHF) and DCM. METHODS: In 27 consecutive patients (mean age 55 +/- 15 years) with VO2max values between 10 and 14 ml/kg body weight per min, a low infusion rate (10 microg/kg per min) dobutamine echocardiographic test was performed. The induced changes in echocardiographic variables were measured, and an 18-month follow-up study was done. RESULTS: At the end of the protocol, 9 patients (group I) had died from cardiac reasons, whereas the remaining 18 patients (group II) survived. After dobutamine infusion, the left ventricular end-systolic diameter (LVESD) was smaller in group II (6.22 +/- 0.94 cm) than in group I (6.99 +/- 0.76 cm; p < 0.05), whereas end-systolic wall stress (ESWS) was higher in group I (1030.66 +/- 193.98 g/cm2) than in group II (691.57 +/- 297.06 g/cm2; p < 0.05). The changes in LVESD and ESWS were greater in group I (0.75 +/- 0.36 cm and 463.11 +/- 159.87 g/cm2, respectively) than in group II (-0.04 +/- 0.36 cm and 83.16 +/- 291.74 g/cm2, respectively; p < 0.01 for both). CONCLUSIONS: In the "gray" zone of VO2max, dobutamine echocardiography seems to be a valuable prognostic indicator in patients with CHF and DCM.

Physical training reduces peripheral markers of inflammation in patients with chronic heart failure.

AIMS: Previous studies have shown an abnormal expression of cellular adhesion molecules and cytokines in chronic heart failure, which may be related to endothelial dysfunction characterizing this syndrome. Our study investigates the effects of physical training on serum activity of some peripheral inflammatory markers associated with endothelial dysfunction, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with chronic heart failure. METHODS AND RESULTS: Serum levels of GM-CSF, MCP-1, sICAM-1 and sVCAM-1 were determined in 12 patients with stable chronic heart failure (ischaemic heart failure: 6/12, dilated cardiomyopathy: 6/12, New York Heart Association: II-III, ejection fraction: 24+/-2%) before and after a 12-week programme of physical training in a randomized crossover design. In addition, the functional status of chronic heart failure patients was evaluated by using a cardiorespiratory exercise stress test to measure peak oxygen consumption. Physical training produced a significant reduction in serum GM-CSF (28+/-2 vs 21+/-2 pg. ml(-1), P<0.001), MCP-1 (192+/-5 vs 174+/-6 pg. ml(-1), P<0.001), sICAM-1 (367+/-31 vs 314+/-29 ng. ml(-1), P<0.01) and sVCAM-1 (1247+/-103 vs 1095+/-100 ng. ml(-1), P<0.01) as well as a significant increase in peak oxygen consumption (14.6+/-0.5 vs 16.5+/-0.5 ml. kg(-1)min(-1), P<0.005). A significant correlation was found between the training-induced improvement in peak oxygen consumption and percentage reduction in soluble adhesion molecules sICAM-1 (r=-0.72, P<0.01) and sVCAM-1 (r=-0.67, P<0.02). CONCLUSION: Physical training affects beneficially peripheral inflammatory markers reflecting monocyte/macrophage-endothelial cell interaction. Training-induced improvement in exercise tolerance is correlated with the attenuation of the inflammatory process, indicating that inflammation may contribute significantly to the impaired exercise capacity seen in chronic heart failure.

Clinical and neurohormonal correlates of circulating granulocyte-macrophage colony-stimulating factor in severe heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

In this report, we showed for the first time that granulocyte-macrophage colony-stimulating factor plasma levels are elevated in patients with severe heart failure, and these levels are correlated well with neurohormonal activation and hemodynamic deterioration characterizing this syndrome.

The time course of haemodynamic, autonomic and skeletal muscle metabolic abnormalities following first extensive myocardial infarction in man.

We investigated the time course of genesis of skeletal muscle dysfunction and sympatho-vagal imbalance after myocardial infarction. We studied 22 normal controls, 22 patients with >6 months stable chronic heart failure and 10 patients after a first massive myocardial infarction at 1-3 weeks (the "early" period), 6-8 weeks ("mid") and 6-9 months ("late") following their infarct. Four patients developed overt heart failure. Forearm muscle metabolism was studied using (31)P magnetic resonance spectroscopy (MRS). Sympatho-vagal balance was assessed by heart rate variability and radiolabelled norepinephrine kinetics. Increased norepinephrine spillover (0.55+/-0.02 v 0.27+/-0.04 mg/min/m(2); P<0.01) and decreased heart rate variability were confined to those post-myocardial infarction patients who subsequently developed heart failure. Resting cardiac output was normal in all the post-myocardial infarction patients, although the response of cardiac output to supine bicycle exercise at the "mid" study point was less in the group who subsequently developed heart failure (9+/-1 v 41+/-8 %; P<0.005). In the MRS studies, there were no detectable differences between those who did or did not develop heart failure. The initial rate of ATP turnover, calculated from initial-exercise changes in pH and phosphocreatine (PCr), was increased in established chronic heart failure, but in the post-myocardial infarction patients a numerically similar increase reached statistical significance only in the early group (19+/-3 v 11+/-1 mM/min; P<0.005). The apparent maximum rate of oxidative ATP synthesis, calculated from post-exercise PCr recovery kinetics, was lower than control in the late post-myocardial infarction and established chronic heart failure groups 34+/-5 v 55+/-4 mM/min; P<0.03 and 38+/-3 v 55+/-4 mM/min; P<0.003, respectively). Skeletal muscle metabolism and autonomic function become abnormal after an extensive myocardial infarction. While skeletal muscle abnormalities are relatively slow to develop and unrelated to the degree of failure, excessive neurohormonal activation and impaired cardiac output response to exercise seem from an early stage to characterize patients who subsequently develop chronic heart failure.

Assessment of the functional status of heart failure in non ischemic dilated cardiomyopathy: an echo-dobutamine study.

BACKGROUND: The functional status of heart failure (HF) is conventionally evaluated by peak exercise oxygen consumption (VO2 max). Dobutamine echocardiography can be used to evaluate myocardial reserve. The aim of this study was to estimate the functional status of chronic HF in patients with dilated cardiomyopathy, by investigating the changes in echo-variables, as assessed by echo-dobutamine, in relation with VO2 max. METHODS AND RESULTS: A low infusion rate echo-dobutamine test (10 micrograms/kg/min) was performed in 30 patients with dilated cardiomyopathy and 1 h later VO2 max was measured. VO2 max (ranging from 7.6 to 23 ml/kg/min, mean 14.06 +/- 0.64 ml/kg/min) was correlated with the changes (values obtained after inotropic stimulation minus those obtained at baseline) in left ventricular end-systolic diameter (r:0.80, p:0.001), in left ventricular end-systolic posterior wall thickness (r:0.73, p:0.001) and in left ventricular heart-rate corrected mean velocity of circumferential fiber shortening (Vcfc)/end-systolic meridional wall stress ratio (r:0.64, p:0.0001). A negative correlation was found between VO2 max and the changes in end-systolic meridional wall stress (r: -0.76, p:0.001). After dobutamine infusion Vcfc/systolic meridional wall stress ratio increased in patients with VO2 max > 14 ml/kg/min but decreased in patients with VO2 max < 14 ml/kg/min (0.0001 +/- 0.0001 vs -0.0002 +/- 0.0003 circ x cm2/g x s, p:0.0001). End-systolic meridional wall stress was decreased in patients with VO2 max > 14 ml/kg/min but increased in patients with VO2 max < 14 ml/kg/min (-126.97 +/- 34.24 vs 205.77 +/- 56.71 g/cm2, p:0.0001). CONCLUSION: The changes in echo-variables assessed by echo-dobutamine are well correlated with VO2 max and seem to be accurate for evaluating the functional status of chronic HF in patients with dilated cardiomyopathy.

Impaired baroreflex sensitivity and sympathovagal balance in syndrome X.

Alterations of autonomic nervous control of cardiac function have been described in syndrome X. The characteristics, however, of the autonomic control of the cardiovascular system in patients with syndrome X have not been adequately studied; thus, the aim of the present study was to investigate the role of baroreceptor sensitivity and sympathovagal balance in syndrome X. The study group included 12 patients with syndrome X, 12 age- and sex-matched control patients with coronary artery disease, and 12 age- and sex-matched controls with no evidence of heart disease. Baroreceptor sensitivity was evaluated by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in the RR interval. Sympathovagal balance was assessed by using heart rate variability in the time and frequency domain and measuring plasma norepinephrine at rest and during incremental bicycle exercise. Baroreceptor sensitivity was significantly reduced in syndrome X compared with that in control normal subjects (7.4 +/- 1.2 vs 16.8 +/- 2.3 ms/mm Hg; p < 0.02). This was associated with a significantly lower percentage of adjacent normal RR intervals that differ by >50 ms, lower root-mean-square of the difference of adjacent RR intervals, and lower logarithmic value of the high-frequency component in patients with syndrome X compared with normal subjects. A nonsignificant trend toward lower baroreceptor sensitivity was found in patients with syndrome X compared with control ischemic patients (7.4 +/- 2 vs 12.2 +/- 1.3 ms/mm Hg). A nonsignificant trend toward a higher value of the low- to high-frequency ratio was also observed in patients with syndrome X than in both control groups. No difference was detected in norepinephrine levels either at rest or during exercise or in the exercise-induced norepinephrine increase between the 3 groups. No difference was also observed between ischemic patients and normal subjects in either baroreceptor sensitivity or heart rate variability measurements. A significant correlation (r = 0.80, p < 0.01) was found between baroreceptor sensitivity and the high-frequency component in normal controls but not for other measurements of autonomic function in the 3 groups. In conclusion, patients with syndrome X have an altered autonomic control of the cardiovascular system characterized by impaired baroreceptor sensitivity and reduced heart rate variability. Abnormal autonomic regulation of the cardiovascular system may be of pathophysiologic importance in syndrome X.

Depressed heart rate variability as an independent predictor of death in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

After acute myocardial infarction, depressed heart rate variability (HRV) has been proven to be a powerful independent predictor of a poor outcome. Although patients with chronic congestive heart failure (CHF) have also markedly impaired HRV, the prognostic value of HRV analysis in these patients remains unknown. The aim of this study was to investigate whether HRV parameters could predict survival in 102 consecutive patients with moderate to severe CHF (90 men, mean age 58 years, New York Heart Association [NYHA] class II to IV, CHF due to idiopathic dilated cardiomyopathy in 24 patients and ischemic heart disease in 78 patients, ejection fraction [EF], 26%; peak oxygen consumption, 16.9 ml/kg/min) after exclusion of patients in atrial fibrilation with diabetes or with chronic renal failure. In the prognostic analysis (Cox proportional-hazards model, Kaplan-Meier survival analysis), the following factors were investigated: age, CHF etiology, NYHA class, EF, peak oxygen consumption, presence of ventricular tachycardia on Holter monitoring, and HRV measures derived from 24-hour electrocardiography monitoring, calculated in the time (standard deviation of all normal RR intervals [SDNN], standard deviation of 5-minute RR intervals [SDANN], mean of all 5-minute standard deviations of RR intervals [SD], root-mean-square of difference of successive RR intervals [rMSSD], and percentage of adjacent RR intervals >50 ms different [pNN50]) and frequency domain (total power [TP], power within low-frequency band [LF], and power within high-frequency band [HF]). During follow-up of 584 +/- 405 days (365 days in all who survived), 19 patients (19%) died (mean time to death: 307 +/- 315 days, range 3 to 989). Cox's univariate analysis identified the following factors to be predictors of death: NYHA (p = 0.003), peak oxygen consumption (p = 0.01), EF (p = 0.02), ventricular tachycardia on Holter monitoring (p = 0.05), and among HRV measures: SDNN (p = 0.004), SDANN (p = 0.003), SD (p = 0.02), and LF (p = 0.003). In multivariate analysis, HRV parameters (SDNN, SDANN, LF) were found to predict survival independently of NYHA functional class, EF, peak oxygen consumption, and ventricular tachycardia on Holter monitoring. The Kaplan-Meier survival curves revealed SDNN < 100 ms to be a useful risk factor; 1-year survival in patients with SDNN < 100 ms was 78% when compared with 95% in those with SDNN > 100 ms (p = 0.008). The coexistence of SDNN < 100 ms and a peak oxygen consumption < 14 ml/kg/min allowed identification of a group of 18 patients with a particularly poor prognosis (1-year survival 63% vs 94% in the remaining patients, p <0.001). We conclude that depressed HRV on 24-hour ambulatory electrocardiography monitoring is an independent risk factor for a poor prognosis in patients with CHF. Whether analysis of HRV could be recommended in the risk stratification for better management of patients with CHF needs further investigation.

Heart rhythms, ventricular arrhythmias, and death in chronic heart failure.

BACKGROUND: The aim of this study was to evaluate whether abnormalities in heart rate variability (HRV) could act as markers of ventricular tachycardia and prognosis in patients with advanced, chronic heart failure. Fifty patients with chronic heart failure (45 men; mean age, 59 +/- 9 years; New York Heart Association [NYHA] class II-III; left ventricular ejection fraction [LVEF], 19 +/- 9% and peak oxygen consumption, 16.6 +/- 5.4 mL/kg/min) caused by idiopathic dilated cardiomyopathy (n = 12) and ischemic heart disease (n = 38) were included in the study. Heart rate variability measures derived from 24-hour electrocardiographic (ECG) monitoring (Marquette 8500 recorder, Marquette Electronics, Milwaukee, WI) were calculated in the time domain and frequency domain. METHODS AND RESULTS: Twenty-five patients (50%) revealed episodes of ventricular tachycardia on 24-hour ECG monitoring (1-143 episodes). The presence of ventricular tachycardia was associated with lower LVEF but there was no difference in NYHA class and peak oxygen consumption between patients with and without ventricular tachycardia (LVEF, 16 vs 22%, P = .01; NYHA class, 2.6 vs 2.4; peak oxygen consumption, 16.5 vs 16.8 mL/kg/min, not significant). Patients with ventricular tachycardia exhibited markedly lower HRV measures. Multiple regression analysis was used to test HRV parameters as potential predictors of ventricular tachycardia. Among them, high-frequency power was the only independent predictor of the presence of ventricular tachycardia, and this predictive correlation was independent of LVEF and mean R-R interval duration. During a follow-up period of 24 +/- 18 months, 12 patients (24%) died. No difference was found in age, etiology, NYHA class, peak oxygen consumption, or occurrence of ventricular tachycardia, but a lower LVEF (15 +/- 6 vs 21 +/- 9%, P = .046) was observed in those who died compared with those who survived. Certain estimates of HRV were in contrast, lower in those who subsequently died: standard deviation of all normal R-R intervals (61 +/- 30 vs 101 +/- 33 ms), standard deviation of 5-minute mean R-R intervals (55 +/- 27 vs 92 +/- 31 ms), mean of all 5-minute standard deviations of R-R intervals (22 +/- 12 vs 37 +/- 11 ms), and the low-frequency (3.2 +/- 1.8 vs 4.8 +/- 0.9 ln ms2) and high-frequency (3.0 +/- 1.1 vs 3.8 +/- 0.8 ln ms2) components of the HRV spectrum (all differences, P < .01). In univariate Cox analysis, all of these HRV measures were independent predictors of death. Kaplan-Meier survival analysis revealed that the standard deviations of all normal R-R intervals and of 5-minute mean R-R intervals dichotomized at median values (99 and 90.5 ms, respectively) were the best predictors of mortality. CONCLUSIONS: In patients with moderate to severe chronic heart failure, depressed indices of HRV on 24-hour ambulatory ECG monitoring could be related to higher risk of ventricular tachycardia and death, suggesting that analysis of HRV could be usefully applied to risk stratification in chronic heart failure patients.

Ablation therapy of type I atrial flutter may eradicate paroxysmal atrial fibrillation.

In patients with paroxysms of atrial fibrillation preceded by episodes of atrial flutter on Holter monitoring, eradication of the flutter circuit may also abolish the episodes of atrial fibrillation. At electrophysiology study, these patients are identified by documentation of simultaneous flutter of the right atrium and fibrillation of the left atrium.

Abnormalities in exercising skeletal muscle in congestive heart failure can be explained in terms of decreased mitochondrial ATP synthesis, reduced metabolic efficiency, and increased glycogenolysis.

OBJECTIVE: To distinguish between the effects of reduced oxidative capacity and reduced metabolic efficiency on skeletal muscle bioenergetics during exercise in patients with congestive heart failure. DESIGN AND PATIENTS: Patients were studied by 31P magnetic resonance spectroscopy during aerobic exercise and recovery, and results compared with controls. RESULTS: In flexor digitorum superficialis muscle (26 patients) there was a 30% decrease in oxidative capacity compared with control (mean (SE) 36 (2) v 51 (4) mM/min) and also a 40% decrease in "effective muscle mass" (5 (1) v 9 (1) arbitrary units), probably at least partly the result of reduced metabolic efficiency. Both contribute to increased phosphocreatine depletion and intracellular acidosis during exercise. However, an increased concentration of ADP (an important mitochondrial regulator) during exercise permitted near-normal rates of oxidative ATP synthesis. Results were similar in gastrocnemius muscle (20 patients), with a 30% decrease in maximum oxidative capacity (29 (4) v 39 (3) mM/min) and a 65% decrease in effective muscle mass (5 (1) v 13 (2) arbitrary units). Exercise training improved maximum oxidative capacity in both muscles, and in gastrocnemius effective muscle mass also. CONCLUSIONS: Skeletal muscle exercise abnormalities in patients with congestive heart failure results more from decreased metabolic efficiency than from the abnormalities in mitochondrial oxidation. Both decreased efficiency and defective mitochondrial oxidation result in an increased activation of glycogen phosphorylase, and may be improved by exercise training.

Contribution of muscle afferents to the hemodynamic, autonomic, and ventilatory responses to exercise in patients with chronic heart failure: effects of physical training.

BACKGROUND: A neural linkage between peripheral abnormalities and the exaggerated exercise responses in chronic heart failure (CHF) was postulated. We studied the ergoreceptors (afferents sensitive to skeletal muscle work) in CHF and whether training can affect their activity. METHODS AND RESULTS: In 12 stable CHF patients (ejection fraction [EF] = 26.4%) and 10 control subjects (EF = 55.3%), we compared the responses to dynamic handgrip and during a 3-minute period of posthandgrip regional circulatory occlusion (PH-RCO). The ergoreflex contribution was quantified as the percentage responses to exercise maintained by PH-RCO compared with recovery without PH-RCO. Patients showed ergoreflex overactivation compared with control subjects in terms of ventilation (86.5% versus 54.5%), diastolic pressure (97.8% versus 53.5%), and leg vascular resistance (108.1% versus 48.9%) (all P < .05). The contribution of the ergoreflex to vagal withdrawal (high frequency of RR variability) and sympathetic activation (low frequency of RR, pressure variability) was evident in both groups. Nine control subjects and nine CHF patients participated in 6 weeks of forearm training. Training reduced the ergoreflex contributions more in CHF than in control subjects: diastolic pressure (-33.2% versus -4.6%), ventilation (-57.6% versus -24.6%), and leg vascular resistance (-59.9% versus -8.0%) (all P < .05). CONCLUSIONS: (1) The ergoreflex role has a larger effect on the responses to exercise in CHF than in control subjects. (2) Training may reduce this exaggerated ergoreflex activity, thereby improving the responses to exercise.

Circadian pattern of heart rate variability in chronic heart failure patients. Effects of physical training.

The effect of physical training on the circadian pattern of heart rate variability (recorded over 24 h in relation to both time and frequency) was assessed in 12 chronic heart failure patients randomized, in a cross-over design, to 8 weeks training or detraining, and compared with 12 age-matched normals. Training improved heart rate variability indices: all R-R interval 5 min standard deviations increased by 17.6%, the root mean square of the differences of successive R-R intervals by 34.9%, the percentage difference between adjacent normal R-R intervals > 50 ms by 112.5%, total power by 58.3%, high frequency by 128.5% and low frequency by 65.0%. Compared with controls, circadian variations in autonomic parameters were maintained in chronic heart failure. Training-induced changes were observed at different time intervals throughout the day: the highest values were at 0100 h-0700 h (detraining: low frequency 361 +/- 83 ms2, high frequency 126 +/- 47 ms2; training: low frequency 535 +/- 202 ms2, high frequency 227 +/- 115 ms2, P < 0.01) and the lowest at 1300 h-1900 h (detraining: low frequency 91 +/- 23 ms2, high frequency 39 +/- 14 ms2; training: low frequency 154 +/- 42 ms2, high frequency 133 +/- 67 ms2, P < 0.05). In chronic heart failure, training maintains and improves circadian variations in heart rate variability measures.

Sympathetic stimulations by exercise-stress testing and by dobutamine infusion induce similar changes in heart rate variability in patients with chronic heart failure.

1. Heart rate variability can be used to evaluate autonomic balance, but it is unclear how inotropic therapy may affect the findings. The aim of the study was to assess whether heart rate variability can differentiate between sympathetic stimulation induced by inotrope infusion or by physical exercise. 2. Ten patients with chronic heart failure (64.3 +/- 5.4 years of age) underwent four dobutamine infusions (8-min steps of 5 micrograms min-1 kg-1) and four supine bicycle exercise tests (5-min steps of 25 W). Plasma noradrenaline was evaluated, as well as the SD of R-R intervals, together with low-frequency (0.03-0.14 Hz) and high-frequency (0.15-0.4 Hz) components of heart rate variability using autoregressive spectral analysis. 3. Exercise and inotrope infusion produced similar changes in heart rate variability. An exercise load of 50 W and a dobutamine infusion of 15 micrograms min-1 kg-1 gave the following results respectively: heart rate, 120.3 +/- 3.0 beats/min versus 110.2 +/- 3.0 beats/min; SD, 16.0 +/- 1.1 ms versus 16.3 +/- 2.5 ms; low-frequency component, 4.3 +/- 0.3 ln-ms2 versus 4.4 +/- 0.3 ln-ms2 and high-frequency component, 2.6 +/- 0.3 ln-ms2 versus 2.2 +/- 0.3 ln-ms2. All comparisons were nonsignificant. The variables of heart rate variability showed high reproducibility in the same subject during different conditions. Noradrenaline was elevated by exercise from 326.0 +/- 35.2 pg/ml to 860.1 +/- 180.4 pg/ml (P < 0.05), but was unchanged by dobutamine infusion. 4. Heart rate variability changes cannot differentiate between dobutamine infusions and physical exercise, indicating that we should be cautious in evaluating patients undergoing inotropic therapy. The degree of receptor stimulations, rather than the level of sympathetic drive, would appear to determine the changes in heart rate variability.