The association of long-term outcome and biological sex in patients with acute heart failure from different geographic regions

Aims: Recent data from national registries suggest that acute heart failure (AHF) outcomes might vary in men and women, however, it is not known whether this observation is universal. The aim of this study was to evaluate the association of biological sex and 1-year all-cause mortality in patients with AHF in various regions of the world. Methods and results: We analysed several AHF cohorts including GREAT registry (22 523 patients, mostly from Europe and Asia) and OPTIMIZE-HF (26 376 patients from the USA). Clinical characteristics and medication use at discharge were collected. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model with adjustment for baseline characteristics (e.g. age, comorbidities, clinical and laboratory parameters at admission, left ventricular ejection fraction). In the GREAT registry, women had a lower risk of death in the year following AHF [HR 0.86 (0.79-0.94), P < 0.001 after adjustment]. This was mostly driven by northeast Asia [n = 9135, HR 0.76 (0.67-0.87), P < 0.001], while no significant differences were seen in other countries. In the OPTIMIZE-HF registry, women also had a lower risk of 1-year death [HR 0.93 (0.89-0.97), P < 0.001]. In the GREAT registry, women were less often prescribed with a combination of angiotensin-converting enzyme inhibitors and beta-blockers at discharge (50% vs. 57%, P = 0.001). Conclusion: Globally women with AHF have a lower 1-year mortality and less evidenced-based treatment than men. Differences among countries need further investigation. Our findings merit consideration when designing future global clinical trials in AHF

Associations between fluid removal and number of B-lines, peak early mitral inflow wave velocity, and inferior vena cava dimensions in hemodialysis patients

Abstract Background The inferior vena cava (IVC) dimensions represent the right ventricular preload, whereas the peak early mitral inflow wave velocity (peak E-velocity) represents the left ventricular preload. On the other hand, B-lines represent extravascular lung water. The aim of this study was to evaluate possible acute changes in the IVC dimensions, peak E-velocity, and number of B-lines during hemodialysis therapy. Methods A total of 55 consecutive patients receiving maintenance hemodialysis were enrolled in this study. We performed echo-graphic examinations at three time points (just after the start, during the middle, and just before the end of the hemodialysis therapy). We then investigated the changes in the IVC dimensions, peak E-velocity, and number of B-lines. Results The peak E-velocity decreased from 80 ± 26 cm/s at the start of the therapy to 58 ± 22 cm/s during the middle and 51 ± 21 cm/s at the end of the therapy. The IVC dimensions also decreased from 15 ± 4 mm at the start of the therapy to 12 ± 3 mm during the middle and 11 ± 3 mm at the end of the therapy. The number of B-lines also decreased from 12 ± 5 at the start of the therapy to 9 ± 4 during the middle and 5 ± 3 at the end of the therapy. The changes in the peak E-velocity and IVC dimensions were significantly greater during the first half of the dialysis period than during the second half of the dialysis period (P < 0.0001 and P < 0.0001, respectively). On the other hand, the changes in the number of B-lines during these periods were significantly smaller during the first half of the dialysis period than during the second half of the dialysis period (P = 0.0016). Conclusions We showed that the peak E-velocity and the IVC dimensions were reduced mainly during the first half of the dialysis period, while the number of B-lines showed a significant decrease mainly during the last half of the dialysis period. Even if the IVC dimensions are reduced sufficiently, caution is needed as lung congestion may still exist

Association between B-lines detected during lung ultrasound and various factors in hemodialysis patients

Abstract Background In recent years, the use of chest ultrasonography to detect lung water has received growing attention in clinical research. Estimation of the number of B-lines using lung ultrasound is now a standard method for the evaluation of pulmonary congestion. In the present study, we examined the relation between the number of B-lines and clinical parameters in hemodialysis patients. Methods A total of 49 consecutive patients receiving maintenance hemodialysis were enrolled in this study. Lung ultrasound was performed using Vscan® (GE Healthcare, Japan). Bilateral scanning of the anterior and lateral chest walls was performed with the patient in a supine position just after the start of the hemodialysis therapy. The total number of B-lines was estimated. We investigated the relationships between the number of B-lines and other clinical parameters. Results Patient heart rate and the serum log [NT-proBNP] level were positively correlated (P = 0.009 and 0.003, respectively), and body weight and the serum albumin and creatinine level were negatively correlated with the number of B-lines (P = 0.023, 0.001, and 0.011, respectively). Conclusions The number of B-lines was positively correlated with the serum N-terminal pro-brain natriuretic peptide level. Lung ultrasound can quantify lung edema. Body weight and the serum albumin and creatinine level were negatively correlated with the number of B-lines. Careful attention to the presence of pulmonary edema is needed in patients with a low body weight and a low serum albumin and creatinine level

Inducible Camp Early Repressor (ICER) Is a Negative-Feedback Regulator of Cardiac Hypertrophy and an Important Mediator of Cardiac Myocyte Apoptosis in Response to Β-Adrenergic Receptor Stimulation

Although stimulation of the β-adrenergic receptor increases levels of cAMP and activation of the cAMP response element (CRE) in cardiac myocytes, the role of the signaling mechanism regulated by cAMP in hypertrophy and apoptosis is not well understood. In this study we show that protein expression of inducible cAMP early repressor (ICER), an endogenous inhibitor of CRE-mediated transcription, is induced by stimulation of isoproterenol (ISO), a β-adrenergic agonist with a peak at ≈12 hours and persisting for more than 24 hours in neonatal rat cardiac myocytes. ICER is also upregulated by phenylephrine but not by endothelin-1. Continuous infusion of ISO also increased ICER in the rat heart in vivo. Overexpression of ICER significantly attenuated ISO- and phenylephrine-induced cardiac hypertrophy but did not inhibit endothelin-1-induced cardiac hypertrophy. Overexpression of ICER also stimulated cardiac myocyte apoptosis. Antisense inhibition of ICER significantly enhanced β-adrenergic hypertrophy, whereas it significantly inhibited β-adrenergic cardiac myocyte apoptosis, suggesting that endogenous ICER works as an important regulator of cardiac hypertrophy and apoptosis. Inhibition of CRE-mediated transcription by dominant-negative CRE binding protein inhibited cardiac hypertrophy, whereas it stimulated cardiac myocyte apoptosis, thereby mimicking the effect of ICER. Both ISO and ICER reduced expression of Bcl-2, an antiapoptotic molecule, whereas antisense ICER prevented ISO-induced downregulation of Bcl-2. These results suggest that ICER is upregulated by cardiac hypertrophic stimuli increasing CRE-mediated transcription in cardiac myocytes and acts as a negative regulator of hypertrophy and a positive mediator of apoptosis, in part through both inhibition of CRE-mediated transcription and downregulation of Bcl-2

Prognostic Impact of Renal Dysfunction Does Not Differ According to the Clinical Profiles of Patients: Insight from the Acute Decompensated Heart Failure Syndromes (ATTEND) Registry

<div><p>Background</p><p>Renal dysfunction associated with acute decompensated heart failure (ADHF) is associated with impaired outcomes. Its mechanism is attributed to renal arterial hypoperfusion or venous congestion, but its prognostic impact based on each of these clinical profiles requires elucidation.</p><p>Methods and Results</p><p>ADHF syndromes registry subjects were evaluated (N = 4,321). Logistic regression modeling calculated adjusted odds ratios (OR) for in-hospital mortality for patients with and without renal dysfunction. Renal dysfunction risk was calculated for subgroups with hypoperfusion-dominant (eg. cold extremities, a low mean blood pressure or a low proportional pulse pressure) or congestion-dominant clinical profiles (eg. peripheral edema, jugular venous distension, or elevated brain natriuretic peptide) to evaluate renal dysfunction's prognostic impact in the context of the two underlying mechanisms. On admission, 2,150 (49.8%) patients aged 73.3±13.6 years had renal dysfunction. Compared with patients without renal dysfunction, those with renal dysfunction were older and had dominant ischemic etiology jugular venous distension, more frequent cold extremities, and higher brain natriuretic peptide levels. Renal dysfunction was associated with in-hospital mortality (OR 2.36; 95% confidence interval 1.75–3.18, p<0.001), and the prognostic impact of renal dysfunction was similar in subgroup of patients with hypoperfusion- or congestion-dominant clinical profiles (p-value for the interaction ranged from 0.104–0.924, and was always >0.05).</p><p>Conclusions</p><p>Baseline renal dysfunction was significantly associated with in-hospital mortality in ADHF patients. The prognostic impact of renal dysfunction was the same, regardless of its underlying etiologic mechanism.</p></div