Role of biomarkers of cardiac remodeling, myofibrosis, and inflammation in assessment of disease severity in euvolemic patients with chronic stable heart failure.

OBJECTIVE: This study aimed to determine the importance of biomarkers of chronic heart failure (CHF) for assessing disease severity in euvolemic stable patients. PATIENTS AND METHODS: N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, galectin-3, cystatin-C, soluble suppression of tumorigenicity 2 (sST2), tissue type inhibitor of matrix metalloproteinase (TIMP)-1, and ceruloplasmin levels were measured in euvolemic patients with stable CHF. Severity of CHF was defined by echocardiographic and biochemical parameters. RESULTS: In 160 patients (123 men and 37 women, mean age: 65.8±12.2 years), we found strong associations between NT-proBNP and bilirubin levels (r = 0.434) and the estimated glomerular filtration rate (r = -0.321). GDF-15 and cystatin-C levels were significantly correlated with parameters of kidney function. In multivariable regression analysis, NT-proBNP levels were associated with the left ventricular ejection fraction and left ventricular end-systolic volume (coefficient of determination R2 = 0.777). Additionally, GDF-15 levels were correlated with urea levels (R2 = 0.742), and cystatin C levels were correlated with urea and bilirubin levels (R2 = 0.732). CONCLUSION: Besides NT-proBNP, GDF-15 and cystatin C are promising biomarkers for establishing the severity of disease in euvolemic patients with stable CHF.

Hyperuricemia treatment in acute heart failure patients does not improve their long-term prognosis: A propensity score matched analysis from the AHEAD registry.

BACKGROUND: Hyperuricemia is associated with a poorer prognosis in heart failure (HF) patients. Benefits of hyperuricemia treatment with allopurinol have not yet been confirmed in clinical practice. The aim of our work was to assess the benefit of allopurinol treatment in a large cohort of HF patients. METHODS: The prospective acute heart failure registry (AHEAD) was used to select 3160 hospitalized patients with a known level of uric acid (UA) who were discharged in a stable condition. Hyperuricemia was defined as UA ≥500 µmoL/L and/or allopurinol treatment at admission. The patients were classified into three groups: without hyperuricemia, with treated hyperuricemia, and with untreated hyperuricemia at discharge. Two- and five-year all-cause mortality were defined as endpoints. Patients without hyperuricemia, unlike those with hyperuricemia, had a higher left ventricular ejection fraction, a better renal function, and higher hemoglobin levels, had less frequently diabetes mellitus and atrial fibrillation, and showed better tolerance to treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or beta-blockers. RESULTS: In a primary analysis, the patients without hyperuricemia had the highest survival rate. After using the propensity score to set up comparable groups, the patients without hyperuricemia had a similar 5-year survival rate as those with untreated hyperuricemia (42.0% vs 39.7%, P = 0.362) whereas those with treated hyperuricemia had a poorer prognosis (32.4% survival rate, P = 0.006 vs non-hyperuricemia group and P = 0.073 vs untreated group). CONCLUSION: Hyperuricemia was associated with an unfavorable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients.

Extra corporeal membrane oxygenation in the therapy of cardiogenic shock (ECMO-CS): rationale and design of the multicenter randomized trial.

AIMS: Extracorporeal membrane oxygenation (ECMO) in veno-arterial configuration represents an increasingly used method for circulatory support. ECMO in cardiogenic shock offers rapid improvement of circulatory status and significant increase in tissue perfusion. Current evidence on the use of ECMO in cardiogenic shock remains insufficient. The aim of the ECMO-CS trial is to compare two recognized therapeutic approaches in the management of severe cardiogenic shock: early conservative therapy and early implantation of veno-arterial ECMO on the background of standard care. METHODS: Eligible patients have either rapidly deteriorating or severe cardiogenic shock, defined using echocardiography, hemodynamic and metabolic criteria. Patients are randomized to the one of two arms: immediate veno-arterial ECMO therapy or early conservative therapy. All other diagnostic and therapeutic procedures are performed as per current standard of care, including other cardiovascular interventions (i.e. percutaneous coronary intervention or cardiac surgery). Follow-up includes visits at 30 days, 6 months and 12 months. Primary endpoint is a composite of death from any cause, resuscitated circulatory arrest, and implantation of another mechanical circulatory support device at 30 days. The sample size of 120 individuals (60 in each arm) provides 80% power to detect 50% reduction of primary endpoint, at alpha = 0.05. Patient recruitment started in October 2014. CONCLUSION: The results of the ECMO-CS trial may significantly influence current practice in the management of patients with severe and rapidly deteriorating cardiogenic shock. ECMO-CS trial registration number is NCT02301819.

Ischemic Postconditioning and Nitric Oxide Administration Failed to Confer Protective Effects in a Porcine Model of Extracorporeal Cardiopulmonary Resuscitation.

The protective effects of ischemic postconditioning (IPC) and nitric oxide (NO) administration have been demonstrated in several ischemic scenarios. However, current evidence regarding the effect of IPC and NO in extracorporeal cardiopulmonary resuscitation remains lacking. Fifteen female swine (body weight 45 kg) underwent veno-arterial extracorporeal membrane oxygenation (ECMO) implantation; cardiac arrest-ventricular fibrillation was induced by rapid ventricular pacing. After 20 min of cardiac arrest, blood flow was restored by increasing the ECMO flow rate to 4.5 L/min. The animals (five per group) were then randomly assigned to receive IPC (three cycles of 3 min ischemia and reperfusion), NO (80 ppm via oxygenator), or mild hypothermia (HT; 33.0°C). Cerebral oximetry and aortic blood pressure were monitored continuously. After 90 min of reperfusion, blood samples were drawn for the measurement of troponin I, myoglobin, creatine-phosphokinase, alanine aminotransferase, neuron-specific enolase, cystatin C, and reactive oxygen metabolite (ROM) levels. Significantly higher blood pressure and cerebral oxygen saturation values were observed in the HT group compared with the IPC and NO groups (P < 0.05). The levels of troponin I, myoglobin, creatine phosphokinase, and alanine aminotransferase were significantly lower in the HT group (P < 0.05); levels of neuron-specific enolase, cystatin C, and ROM were not significantly different. IPC and NO were comparable in all monitored parameters. The results of the present study indicate that IPC and NO administration are not superior interventions to HT for the maintenance of blood pressure, cerebral oxygenation, organ protection, and suppression of oxidative stress following extracorporeal cardiopulmonary resuscitation.

Positive influence of being overweight/obese on long term survival in patients hospitalised due to acute heart failure.

BACKGROUND: Obesity is clearly associated with increased morbidity and mortality rates. However, in patients with acute heart failure (AHF), an increased BMI could represent a protective marker. Studies evaluating the "obesity paradox" on a large cohort with long-term follow-up are lacking. METHODS: Using the AHEAD database (a Czech multi-centre database of patients hospitalised due to AHF), 5057 patients were evaluated; patients with a BMI <18.5 kg/m2 were excluded. All-cause mortality was compared between groups with a BMI of 18.5-25 kg/m2 and with BMI >25 kg/m2. Data were adjusted by a propensity score for 11 parameters. RESULTS: In the balanced groups, the difference in 30-day mortality was not significant. The long-term mortality of patients with normal weight was higher than for those who were overweight/obese (HR, 1.36; 95% CI, 1.26-1.48; p<0.001)). In the balanced dataset, the pattern was similar (1.22; 1.09-1.39; p<0.001). A similar result was found in the balanced dataset of a subgroup of patients with de novo AHF (1.30; 1.11-1.52; p = 0.001), but only a trend in a balanced dataset of patients with acute decompensated heart failure. CONCLUSION: These data suggest significantly lower long-term mortality in overweight/obese patients with AHF. The results suggest that at present there is no evidence for weight reduction in overweight/obese patients with heart failure, and emphasize the importance of prevention of cardiac cachexia.

Uric acid, allopurinol therapy, and mortality in patients with acute heart failure--results of the Acute HEart FAilure Database registry.

STUDY OBJECTIVE: The aim of this study was to explore the prognostic role of serum uric acid (UA) measurement in the hospital and long-term mortality assessment in subjects with acute heart failure (AHF) from the Acute HEart FAilure Database registry (AHEAD). The AHEAD registry comprised 4153 patients with AHF syndromes hospitalized at the AHEAD participating centers. PATIENTS AND METHODS: The study included 1255 patients who were admitted to the AHEAD participating centers with acute decompensated chronic heart failure, de novo heart failure, or cardiogenic shock between September 2006 and October 2009 and who had information about serum UA concentration available at the time of hospital admission. The hospital and long-term mortality was followed using the centralized database of the Ministry of Health, Czech Republic. The mean age of the cohort was 73.4 years, the female population represented 43%, the median hospital stay was 8 days, and the mean hospital mortality was 7.6%. RESULTS: The median UA concentration of the patients with AHF was 432 µmol/L (7.26 mg/dL), the median estimated glomerular filtration rate (eGFR) was 49.0 mL/min, and N-terminal pro-brain natriuretic peptide level was 5510 pg/mL. Among other laboratory variables, UA concentration greater than 515 µmol/L (8.67 mg/dL) was associated with increased hospital mortality (P < .001), as well as eGFR less than 30 mL/min (P < .001), Na 135 mmol/L or less, and positive troponin. Uric acid concentration greater than 500 µmol/L (8.41 mg/dL) was associated with increased long-term mortality (P < .001), followed by eGFR less than 30 mL/min (P < .001), Na 135 mmol/L or less, and hemoglobin level lower than 130 g/L (P < .001). The 1-year survival rate of patients discharged from hospital (n = 1159) was 75.6%, and the 2-year rate was 66.8%. Survival of patients treated with allopurinol for hyperuricemia was significantly lower compared with untreated subjects (70.1 vs 77.2 for 1-year survival and 60.3 vs 68.5 for 2-year survival). CONCLUSION: In patients with AHF, increased UA levels and documented allopurinol therapy for hyperuricemia were associated with increased hospital and long-term mortality. Allopurinol therapy is not a cause but the identifier of the subjects at risk.