Cardiorenal syndrome type 2 (CRS-2) is common in end-stage chronic heart failure (CHF). Peritoneal ultrafiltration (pUF) may entail clinical functional improvement and a reduction in hospitalizations.Thirty-nine consecutive end-stage CHF patients with stable CRS-2 were initiated on ambulatory pUF after interdisciplinary cardiological/nephrological evaluation and prospectively followed for 1 year. All-cause hospitalization was the primary end point. Secondary end points included mortality, treatment alteration and change in weight, NYHA functional class or quality of life (QoL). Outcomes were compared both within the pUF cohort (365 prior to initiation) and with 39 matched CHF patients receiving standard medical treatment.Compared with pretreatment, there was a trend to a reduction in 1-year hospitalization days in the pUF group (P = 0.07). One-year mortality was 33% in the pUF group and 23% in the matched control cohort. pUF was stopped in eight patients (18%) due to recurrent peritonitis (n = 3), insufficient ultrafiltration (n = 3) or cardiac recompensation (n = 1). Compared with standard medical treatment, pUF significantly improved volume overload (P < 0.05), NYHA functional class (P < 0.001) and mental health (P < 0.05). Moreover, hospitalization days for all causes as well as cardiovascular hospitalization days were significantly reduced during the interim periods in the pUF group (P < 0.05 and P < 0.001, respectively).pUF is effective in improving the clinical condition of end-stage CHF patients suffering from CRS-2. Randomized controlled trials are needed to clarify the effects of pUF on hospitalization and mortality in these patients.
We report the case of a 57-year-old woman suffering from congestive heart failure. Due to refractory congestions despite optimised medical treatment, the patient was listed for heart transplantation and peritoneal dialysis was initiated. Peritoneal dialysis led to a significant weight loss, reduction of hyperhydration and extracellular water obtained by bioimpedance measurement, and a significant improvement in clinical and echocardiographic examination. Furthermore, residual kidney function increased during the long-term followup, and subsequently peritoneal dialysis was ceased. Pulmonary artery pressure and left ventricular ejection fraction remained stable and the patient did well. This case demonstrates the possibility of treating hyperhydration due to congestive heart failure with peritoneal dialysis resulting in recompensation of both heart and kidney functions.
Background: Cardiac expression of the Ca-dependent inotropic protein S100A1 is decreased in human end-stage heart failure (HF) and cardiomyocyte-targeted viral-based S100A1 gene transfer rescued failing myocardium in small animal models in vivo and in vitro via improved systolic and diastolic sarcoplasmic reticulum Ca-handling. We therefore hypothesized that cardioselective AAV9-S100A1 gene therapy will improve cardiac performance in a large animal experimental HF model under clinical conditions. Methods and Results: Left ventricular (LV) posterolateral myocardial infarction (MI) was induced in pigs by occlusion of the left coronary circumflex artery and resulted in LV failure (HF) 2 weeks post-MI reflected by a 40% and 27% reduction in LV +dp/dt max. and EF, respectively, as assessed by LV catheterization and echocardiography. Post-MI HF pigs were then randomized for retroinfusion of AAV9-luciferase (luc; n=6, 1.5×10 13 total viral particles, tvp) and AAV9-S100A1 (S100A1; n=6, 1.5×10 13 tvp) driven by a cardioselective promoter via the anterior cardiac vein while the left anterior descending artery was temporarily occluded. 14 weeks after cardiac gene transfer, the S100A1-treated HF group showed significantly enhanced S100A1 protein expression (+46.7±17.9%, P<0.05 vs. control groups) in targeted remote LV myocardium and improved indices of cardiac function and remodeling (luc vs. S100A1: +dp/dtmax: 983±81 vs. 1526±83 mmHg/s, EF: 39±2.1 vs. 61±3.7 %, P<0.05 S100A1 vs. luc, LV endsystolic diameter: luc 4.45±0.1 vs. S100A1 3.43 ±0.1 cm, P<0.05 S100A1 vs. luc, HR: 72±4 vs. 69±2, beats/min, P=n.s. S100A1 vs. luc). Importantly, analyses of renal, hepatic and hematopoetic function showed no alteration as assessed by unchanged transaminases, retention values and white blood cell counts compared to sham pigs. Conclusions: Our translational study provides proof of concept that AAV9-S100A1 based HF gene therapy is feasible and restores cardiac function in a large animal HF model under clinical conditions. Next, certified toxicological analysis and different AAV9-S100A1 dosage protocols will be assessed to eventually advance to first phase I/II clinical studies determining therapeutic efficiency of cardiac S100A1 gene therapy in HF patients.
Background— Osteopontin, a glycoprotein that can be detected in plasma, was found to be upregulated in several animal models of cardiac failure and may thus represent a new biomarker that facilitates risk stratification in patients with heart failure. We therefore tested whether osteopontin plasma levels are elevated in patients with chronic heart failure and whether they provide independent prognostic information. Methods and Results— We analyzed osteopontin plasma levels in 420 patients with chronic heart failure due to significantly impaired left ventricular systolic function and correlated the results with disease stage and prognostic information (median follow-up of 43 months). We found that osteopontin plasma levels were significantly elevated in patients with heart failure as compared with healthy control subjects (532 versus 382 ng/mL, P =0.008), irrespective of heart failure origin (ischemic versus dilated cardiomyopathy). Furthermore, osteopontin levels were higher in patients with moderate to severe heart failure than in patients with no or mild symptoms (672 ng/mL for New York Heart Association class III/IV versus 479 ng/mL for class I/II, P <0.0001). Estimated 4-year death rates in patients with osteopontin levels above or below a cutoff value derived from receiver operating characteristic analyses were 56.5% and 28.4%, respectively (hazard ratio 3.4, 95% confidence interval 2.2 to 5.3, P <0.0001). In a multivariable model that included demographic, clinical, and biochemical parameters such as N-terminal prohormone brain natriuretic peptide, osteopontin emerged as an independent predictor of death (hazard ratio 2.3, 95% confidence interval 1.4 to 3.5, P <0.001). Conclusion— Our findings suggest that osteopontin might be useful as a novel prognostic biomarker in patients with chronic heart failure.
