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BACKGROUND Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain. METHODS In this double-blind trial, we randomly assigned 5988 patients with class II--IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. RESULTS Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; PcO.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin. CONCLUSIONS Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure or death from cardiovascular causes among patients with stable heart failure. However, the safety and efficacy of SGLT2 inhibitors when initiated soon after an episode of decompensated heart failure are unknown.Methods: We performed a multicenter, double-blind trial in which patients with type 2 diabetes mellitus who were recently hospitalized for worsening heart failure were randomly assigned to receive sotagliflozin or placebo. The primary end point was the total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure (first and subsequent events). The trial ended early because of loss of funding from the sponsor.Results: A total of 1222 patients underwent randomization (608 to the sotagliflozin group and 614 to the placebo group) and were followed for a median of 9.0 months; the first dose of sotagliflozin or placebo was administered before discharge in 48.8% and a median of 2 days after discharge in 51.2%. Among these patients, 600 primary end-point events occurred (245 in the sotagliflozin group and 355 in the placebo group). The rate (the number of events per 100 patient-years) of primary end-point events was lower in the sotagliflozin group than in the placebo group (51.0 vs. 76.3; hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.85; P<0.001). The rate of death from cardiovascular causes was 10.6 in the sotagliflozin group and 12.5 in the placebo group (hazard ratio, 0.84; 95% CI, 0.58 to 1.22); the rate of death from any cause was 13.5 in the sotagliflozin group and 16.3 in the placebo group (hazard ratio, 0.82; 95% CI, 0.59 to 1.14). Diarrhea was more common with sotagliflozin than with placebo (6.1% vs. 3.4%), as was severe hypoglycemia (1.5% vs. 0.3%). The percentage of patients with hypotension was similar in the sotagliflozin group and the placebo group (6.0% and 4.6%, respectively), as was the percentage with acute kidney injury (4.1% and 4.4%, respectively). The benefits of sotagliflozin were consistent in the prespecified subgroups of patients stratified according to the timing of the first dose.Conclusions: In patients with diabetes and recent worsening heart failure, sotagliflozin therapy, initiated before or shortly after discharge, resulted in a significantly lower total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure than placebo. (Funded by Sanofi and Lexicon Pharmaceuticals; SOLOIST-WHF ClinicalTrials.gov number, NCT03521934.). [ABSTRACT FROM AUTHOR]

Autonomic imbalance, including depleted parasympathetic drive, is a fundamental pathophysiological feature of heart failure (HF). In clinical studies, parasympathetic withdrawal is assessed using arterial baroreflex sensitivity (BRS). Parasympathetic activity can also be tracked based on the assessment of molecular elements of cholinergic signaling in target cells. Hence, we investigated whether BRS is associated with the mRNA expression of nicotinic cholinergic receptors (α7nAChR) in peripheral blood mononuclear cells (PBMCs) in subjects with and without HF. We examined 39 patients with stable systolic HF (35 men, 4 women, age 56 ± 13 years, left ventricular ejection fraction, LVEF, 30 ± 9%) and 17 healthy subjects (6 men, 11 women, age 60 ± 11 years, LVEF 64 ± 9%). BRS was assessed using a phenylephrine test. Relative transcript levels of α7nAChRs in PBMCs were analyzed using a real-time PCR. Patients with HF, as compared to healthy subjects, demonstrated much higher expression of α7nAChR mRNA in PBMCs (4.4 ± 2.2 vs. 1.4 ± 2.2 AU; P < 0.01) without a difference in BRS (P > 0.2). In a combined sampling including subjects with and without HF, BRS negatively correlated with the content of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r = -0.43, P < 0.05). In such sampling, α7nAChR expression in PBMCs also negatively correlated with LVEF (r = -0.39, P < 0.05) and was positively associated with plasma NT-proBNP (r = 0.38, P < 0.01), but without associations with other clinical and laboratory measures. Expression of α7nAChRs in PMBCs is inversely correlated with BRS (r = -0.50, P < 0.01). Thus, autonomic imbalance confirmed by physiological tests is accompanied by increased expression of α7 nicotinic receptors on circulating immune cells. [ABSTRACT FROM AUTHOR]

We investigated whether indices of the reflex regulation of the cardiovascular system, i.e., muscle ergoreflex activity (ERGO) and characteristics of the autonomic balance, differ from each other while measured in the vertical vs. horizontal positions in healthy humans. Ten young healthy men (mean age 28 ± 1 years; BMI 23.6 ± 0.8 kg/m) were examined. In each subject, the ERGO (ventilatory response to a control handgrip exercise, with repetitive isometric contractions at 50% of the maximal strength), baroreflex sensitivity (BRS, the sequence method), heart rate variability (HRV), and a few hemodynamic parameters were measured in two positions, horizontal and vertical. In the latter position, the heart rate, and diastolic and mean blood pressures (BP) were higher, while the stroke volume was smaller (all P < 0.05) with no differences in the systolic BP, cardiac output, and systemic vascular resistance (all P > 0.2). The HRV time domains, as well as BRS, decreased, whereas HRV-LF increased (all P < 0.05) in the vertical position as compared to the horizontal one. There were no differences between other HRV parameters (all P > 0.2) in the two examined positions. Minute ventilation during the exercise increased, while ERGO was reduced in the vertical position (all P < 0.05). Thus, the body position noticeably affects both reflex regulation of the cardiovascular system and autonomic balance. This observation has to be taken into account during physiological testing. [ABSTRACT FROM AUTHOR]

Background: In patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients' long-term prognosis.Methods: In this double-blind trial, we randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. Treatment was initiated a median of 6 hours after the initial clinical evaluation. The coprimary outcomes were death from cardiovascular causes during a median follow-up of 15 months and a hierarchical composite end point that evaluated the initial 48-hour clinical course.Results: Death from cardiovascular causes occurred in 236 patients in the ularitide group and 225 patients in the placebo group (21.7% vs. 21.0%; hazard ratio, 1.03; 96% confidence interval, 0.85 to 1.25; P=0.75). In the intention-to-treat analysis, there was no significant between-group difference with respect to the hierarchical composite outcome. The ularitide group had greater reductions in systolic blood pressure and in levels of N-terminal pro-brain natriuretic peptide than the placebo group. However, changes in cardiac troponin T levels during the infusion did not differ between the two groups in the 55% of patients with paired data.Conclusions: In patients with acute heart failure, ularitide exerted favorable physiological effects (without affecting cardiac troponin levels), but short-term treatment did not affect a clinical composite end point or reduce long-term cardiovascular mortality. (Funded by Cardiorentis; TRUE-AHF ClinicalTrials.gov number, NCT01661634 .). [ABSTRACT FROM AUTHOR]

Background The interpretation and clinical usefulness of elevated levels of cardiac troponins in acute heart failure (AHF) remain controversial. We aimed to characterize the relationship between changes in cardiac troponin I (measured using a new high-sensitive immunoassay by single-molecule counting technology, Singulex, Alameda, USA; hs-TnI) during first 48 h of hospital stay and patients' characteristics and the outcomes. Methods and results We measured hs-TnI at baseline, after 24 and 48 h in 130 AHF patients (mean age: 65 ± 13 years, 77% men). The percentage of patients with elevated hs-TnI (i.e., above the upper reference limit [URL] > 10.19 pg/mL) were: on admission – 59%, after 24 h – 61%, and after 48 h – 58%. Elevated baseline level of hs-TnI was associated with more severe dyspnoea on admission but neither peak level nor changes in hs-TnI during first 48 h were related to the dyspnoea severity or magnitude of dyspnoea relief. During 1-year follow-up there were 32 (25%) cardiovascular deaths. Neither absolute baseline nor peak values of hs-TnI predicted cardiovascular mortality. Only changes in hs-TnI were independently associated with cardiovascular mortality with the strongest relationship seen in peak change in hs-TnI: patients with an increase vs. remaining patients - hazard ratio (95% confidence interval): 3.22 (1.52–6.82) p = 0.002. Conclusions Using the new assay (proved to be more sensitive that the other available troponin assays) we observed that approximately 60% of patients with AHF presented elevated hs-TnI above URL during first 48 h of hospital stay. Only significant increase in hs-TnI predicted cardiovascular mortality. [ABSTRACT FROM AUTHOR]

In patients suffering from heart failure (HF), autonomic imbalance develops even at early stages along with derangements of cardiopulmonary reflex control and abnormalities in metabolism of several hormones. In 34 men with stable systolic HF, we investigated hypercapnic chemosensitivity (HCS, liter/min·mm Hg) measured using the rebreathing method and defined as the slope of the regression line relating minute ventilation (VE, liter/min) to end-tidal carbon dioxide concentration (PETCO, mm Hg). Serum levels of testosterone, dehydroepiandrosterone sulfate, type-1 insulin-like growth factor (IGF-1), sex hormone-binding globulin (SHBG), estradiol, and cortisol were measured using immunoassays. We found that there were no associations between HCS and clinical variables, applied therapy, and co-morbidities (all P > 0.2). Augmented HCS was accompanied by the significantly increased serum SHBG (when expressed in nM, r = 0.43, P < 0.05; when expressed as percentage of the age-matched reference values, r = 0.62, P < 0.001) and the reduced serum IGF-1 (when expressed in ng/ml and as percentage of the above-mentioned values, r = -0.49, P < 0.05, and r = = -0.47, P = 0.007, respectively). The HCS was not related considerably to serum levels of all the remaining analyzed hormones (all P > 0.2). Thus, it may be suggested that the hormone stimuli can noticeably modify the reflex mechanisms in cardiorespiratory control in the clinical setting of cardiovascular pathology. [ABSTRACT FROM AUTHOR]

Growing awareness that heart failure, renal impairment, and anaemia are frequent co-morbidities which can exacerbate one another in a vicious circle of clinical deterioration has led to the concept of the cardiorenal anaemia syndrome (CRAS). The role of iron deficiency within this complex interplay has been less well examined. Scrutiny of data from the recent FAIR-HF trial raises a new hypothesis: is it time for 'CRAS' to be supplemented with new acronyms such as CRIDS (cardiorenal-iron deficiency syndrome) or even CRAIDS (cardiorenal-anaemia-iron deficiency syndrome)? Iron deficiency occurs frequently in heart failure patients with or without anaemia. It not only impairs oxygen transport through reduced erythropoiesis, but adversely affects oxidative metabolism, cellular energetics, and immune mechanisms, and the synthesis and degradation of complex molecules such as DNA. One large observational study in patients with heart failure found iron deficiency to be an independent predictor of death or urgent heart transplantation (hazard ratio 1.58, 95% confidence interval 1.14-2.17, P = 0.005). In the FAIR-HF trial, i.v. iron therapy was associated with significant improvements in physical functioning in iron-deficient patients with heart failure, even in non-anaemic patients in whom haemoglobin levels did not change following i.v. iron administration. Key questions regarding the use of i.v. iron supplementation in the setting of heart failure merit exploration and could readily be answered by appropriately designed clinical trials. It is to be hoped that these important clinical trials are conducted, to permit a more subtle characterization of the patient's pathological condition and interventional requirements. [ABSTRACT FROM AUTHOR]

Background: Adenosine exerts actions in multiple organ systems, and adenosine receptors are a therapeutic target in many development programmes.Objective: The aim of this analysis was to evaluate the safety of rolofylline, an adenosine A(1)-receptor antagonist, in patients with acute heart failure.Methods: The effect of rolofylline was investigated in patients hospitalized for acute heart failure with impaired renal function. Intravenous rolofylline 30 mg or placebo was infused over 4 hours daily for up to 3 days. Adverse events (AEs) and serious AEs (SAEs) were recorded from baseline through 7 and 14 days, respectively, and clinical events were adjudicated through 60 days.Results: Of 2033 patients enrolled, 2002 received study drug randomized 2 : 1 to rolofylline or placebo. Rolofylline and placebo were associated with a similar risk of pre-specified groups of AEs or SAEs, other than selected neurological events. Investigator-reported seizures occurred in 11 (0.8%) rolofylline-treated patients and zero patients receiving placebo (p = 0.02). Stroke occurred in 21 (1.6%) patients assigned to rolofylline compared with 3 (0.5%) placebo-treated patients through 60 days with a greater risk for stroke in the rolofylline group (hazard ratio 3.49; 95% CI 1.04, 11.71; p = 0.043). There was no temporal relation to rolofylline administration and no specific stroke subtype or clinical characteristics that predicted stroke in the rolofylline group.Conclusions: Rolofylline treatment was associated with an increased seizure rate, an anticipated complication of A(1)-receptor antagonists. An unanticipated, disproportionate increase in strokes in the rolofylline-treated patients emerged, although no clear temporal relation, aetiology, stroke subtype or interacting factor suggestive of a causal mechanism was identified. Further research into stroke as a potential complication of adenosine-modulating therapies is required. Additionally, this study underscores the value of longer follow-up durations for AEs, even for agents with short treatment periods, such as in acute heart failure. [ABSTRACT FROM AUTHOR]

Many patients with heart failure have underlying renal dysfunction, and similarly, patients with kidney failure are prone to cardiac failure. This has led to the concept of cardio-renal syndromes, which can be an acute or chronic cardio-renal syndrome, when cardiac failure causes deterioration in renal function, or acute and/or chronic Reno-Cardiac syndrome, when renal dysfunction leads to cardiac failure. Patients who develop these syndromes have increased risk of hospital admission and mortality. Although there are clinical guidelines for managing both heart failure and chronic kidney disease, there are no agreed guidelines for managing patients with cardio-renal and/or Reno-Cardiac syndromes, as these patients have typically been excluded from clinical trials. We have therefore reviewed the currently available published literature to outline a consensus of current best clinical practice for these patients. [ABSTRACT FROM PUBLISHER]

Aims: Iron deficiency (ID) and anaemia are common in patients with chronic heart failure (CHF). The presence of anaemia is associated with increased morbidity and mortality in CHF, and ID is a major reason for the development of anaemia. Preliminary studies using intravenous (i.v.) iron supplementation alone in patients with CHF and ID have shown improvements in symptom status. FAIR-HF (Clinical Trials.gov NCT00520780) was designed to determine the effect of i.v. iron repletion therapy using ferric carboxymaltose on self-reported patient global assessment (PGA) and New York Heart Association (NYHA) in patients with CHF and ID.Methods and Results: This is a multi-centre, randomized, double-blind, placebo-controlled study recruiting ambulatory patients with symptomatic CHF with LVEF < or = 40% (NYHA II) or < or =45% (NYHA III), ID [ferritin <100 ng/mL or ferritin 100-300 ng/mL when transferrin saturation (TSAT) < 20%], and haemoglobin 9.5-13.5 g/dL. Patients were randomized in a 2:1 ratio to receive ferric carboxymaltose (Ferinject((R))) 200 mg iron i.v. or saline i.v. weekly until iron repletion (correction phase), then monthly until Week 24 (maintenance phase). Primary endpoints are (i) self-reported PGA at Week 24 and (ii) NYHA class at Week 24, adjusted for baseline NYHA class.Conclusion: This study will provide evidence on the efficacy and safety of iron repletion with ferric carboxymaltose in CHF patients with ID with and without anaemia. [ABSTRACT FROM AUTHOR]

Background: Mild anaemia frequently occurs in patients with chronic heart failure (CHF), particularly in the advanced stages of the disease. The correction of anaemia with erythropoietin is a therapeutic possibility. The aim of this study was to assess prospectively the relationship between the prevalence of anaemia (haemoglobin level≤120 g/l) and prognosis in an unselected CHF population. Methods: All consecutive patients with a diagnosis of CHF admitted to our department between January 2000 and April 2000 were considered for the present study. Those with secondary causes of anaemia were excluded. Patients were followed up until November 2001 (>18 months in all survivors), and the end-point of the study was all-cause mortality. Results: A total of 176 patients were enrolled (mean age: 63 years, New York Heart Association (NYHA) classification I/II/III/IV: 15/81/51/29; left ventricular ejection fraction (LVEF): 42%, ischaemic aetiology in 62%). In the whole population the mean haemoglobin level was 140±15 g/l. Anaemia was found in 18 (10%) patients, and was significantly more common in women than in men (18 vs. 7%, respectively, P=0.02) and in those with most severe CHF symptoms (frequency in NYHA I/II/III/IV: 0/9/10/21%, respectively; NYHA IV vs. I–III, P=0.03), but not related to the other clinical indices. Univariate analysis revealed NYHA class III–IV (hazard ratio 3.8, 95% CI: 1.6–8.9, P=0.003), low LVEF <35% (hazard ratio 2.3, 95% CI: 1.0–4.9, P=0.04) and anaemia (hazard ratio 2.9, 95% CI: 1.2–7.2, P=0.02) as predictors of 18-month mortality. In multivariate analysis, anaemia remained an independent predictor of death when adjusted for NYHA class and LVEF (hazard ratio: 2.6, 95% CI: 1.0–6.5, P=0.04). In anaemic patients, 18-month survival was 67% (95% CI: 45–89%) compared to 87% (81–92%) in patients with a normal haemoglobin level (P=0.016). Conclusions: Mild anaemia is a significant and independent predictor of poor outcome in unselected patients with CHF. Correction of low haemoglobin level may become an interesting therapeutic option for CHF patients. [Copyright &y& Elsevier]

Reduced heart rate variability (HRV) and attenuated baroreflex sensitivity (BS) after myocardial infarction and in patients with chronic congestive heart failure (CHF) are associated with poor prognosis. Recent studies have shown that a large proportion of the prognostic power from HRV measurements is localized in heart rate turbulence immediately after ventricular premature complexes. The mechanism of heart rate turbulence remains unknown. In the present study, we explore its relation to BS. In 45 patients with CHF and > or =3 ectopic beats in a 30-minute period, measurements of RR interval and continuous, noninvasive blood pressure (BP) were studied at rest. In response to an ectopic beat, average heart rate turbulence was 9.4 ms/beat (SD 6.1). Mean BP turbulence was 0.72 mm Hg/beat (SD 0.56). Using the ratio of heart rate and BP turbulence slopes to estimate BS showed good agreement (r = 0.67, p < 0.0001) with the alpha-index method (BSalpha). This relation was attributable to a marked correlation between heart rate turbulence and BSalpha (r = 0.70, p <0.0001); there was no correlation between BP turbulence and the BSalpha (r = 0.1, p = NS). Twenty-nine percent of patients had postectopic pulsus alternans, with a mean decay time of 1.4 beats (SD 0.5). The presence of pulsus alternans was associated with a significantly lower heart rate turbulence slope (6.3 [SEM 1.0] vs 10.7 [SEM 1.2] ms/beat, p = 0.03). Thus, heart rate turbulence is an effective measure of the baroreflex, correlating strongly with a standard measure. This is because it is the heart rate, rather than the BP, response to an ectopic beat that conveys the information relevant to BS measurement. [ABSTRACT FROM AUTHOR]

This study sought to assess the prognostic significance of echocardiographic measurements of left and right ventricular dimensions and function in patients >67 years of age with chronic congestive heart failure (CHF). This is a retrospective follow-up of elderly patients who underwent an echocardiography in the tertiary cardiac center. A total of 185 patients (131 men) aged >/=68 years (mean +/- SD 75 +/- 5) with CHF were enrolled into the study. After undergoing a detailed echocardiographic examination, all patients were followed-up for a median of 20 months (interquartile range 9 to 36). During the follow-up period 54 patients (29%) died. Left ventricular (LV) M-mode isovolumic relaxation time (IVRT), end-diastolic and end-systolic diameters, fractional shortening and mass, transmitral E:A ratio, and left atrial dimension, as well as New York Heart Association class and the age were found by Cox proportional-hazards univariate analyses to predict the outcome in these patients (all p <0.05). In multivariate analyses including these measurements, LV IVRT (p <0.04), age (p <0.03), and New York Heart Association class (p <0.001) were found to be the independent predictors of outcome. In the Kaplan-Meier analysis, patients with LV IVRT >30 ms had a better prognosis at 3 years (cumulative survival 78% [95% confidence interval 65% to 91%]) than those with LV IVRT 67 years of age with CHF. LV M-mode IVRT is among the most important independent predictors of outcome in this population. [ABSTRACT FROM AUTHOR]

The effects of a 6-week treatment with amiodarone on the P-wave triggered signal-averaged electrocardiogram in patients with paroxysmal atrial fibrillation and coronary artery disease have been studied. Amiodarone favorably influences P-wave triggered signal-averaged electrocardiographic parameters, predominantly in patients in whom amiodarone is effective in preventing paroxysmal atrial fibrillation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In chronic congestive heart failure (CHF) an overactivity of muscle ergoreceptors and peripheral chemoreceptors may lead to an increased ventilatory response to exercise and contribute to the autonomic imbalance. The analysis of heart rate variability (HRV), which is a reliable method of studying autonomic regulations within the cardiovascular system, showed depressed HRV indexes in CHF, but predictors of abnormal HRV pattern in CHF remain controversial. Considering a common mechanism involved in generation of both abnormal ventilation and autonomic dysfunction in CHF, we hypothesized that impaired ventilation may be better than other variables of CHF severity in determining HRV parameters. Seventy-two patients with CHF (57+/-9 years, ejection fraction: 28+/-11%) underwent cardiopulmonary exercise testing; the relation between ventilation and carbon dioxide production (VE/VCO2) was used as an index of the ventilatory response to exercise. Time and frequency-domain measurements of HRV were derived from 24-hour electrocardiographic monitoring. Patients had reduced exercise tolerance with abnormal ventilatory response (peak oxygen consumption [VO2max]: 17.8+/-5.5 ml/kg/min, VE/VCO2: 36.0+/-9.8). Correlations were found between HRV measures and etiology, New York Heart Association (NYHA) functional class, and VO2max, but the strongest relation was observed for VE/VCO2 slope (r values from -0.33 to -0.65, p <0.01). In the multiple regression analysis only VE/VCO2 was found to correlate independently with all HRV measurements. To investigate the role of peripheral chemoreceptor overactivity as the mechanism of autonomic imbalance and the increased ventilatory response to exercise, we assessed peripheral chemosensitivity in 22 patients (mean value of peripheral chemosensitivity: 0.62+/-0.34 L/min/%SaO2, significantly higher than in normal controls, mean value: 0.29+/-0.20 L/min/%SaO2 in our laboratory). The activity of the peripheral chemoreflex inversely correlated with all parameters of HRV. Increased ventilatory response to exercise correlated with depressed HRV measures in patients with CHF better than other clinical variables. An important role of the increased peripheral chemosensitivity in this relation may be relevant, being also a potential link between functional severity and sympathovagal imbalance in CHF. [ABSTRACT FROM AUTHOR]

An abstract of the article "Effects of rolofylline, a new adenosine A1 receptor antagonist, on symptoms, renal function and outcomes in patients with acute heart failure. Results of the PROTECT pilot study," by C. O’Connor and colleagues is presented.

An abstract of the article "Combined testosterone and insulin-like growth factor deficiency impairs quadriceps strength in men with chronic heart failure," by E. A. Jankowska and colleagues is presented.

An abstract of the article "Association of physician-determined worsening heart failure with signs and symptoms, hospitalization duration, and 60-day outcomes in patients hospitalised for acute heart failure," by M. Metra and colleagues is presented.

An abstract of the study "Does Andropause Exist in Men With Chronic Heart Failure, and Is It Linked to Multiple Anabolic Deficiency," by E. A. Jankowska and colleagues is presented.

An abstract of the article "Prognostic Utility of Growth-Differentiation Factor-15 in Patients With Chronic Heart Failure," by T. Kempf and colleagues is presented.