B-type natriuretic peptide: powerful predictor of end-stage chronic heart failure in individuals with systolic dysfunction of the systemic right ventricle.

AIM: To assess whether B-type natriuretic peptide (BNP) can serve as a predictor of end-stage chronic heart failure (CHF) in patients with severe systolic dysfunction of the systemic right ventricle (SRV). METHODS: We performed a retrospective analysis in 28 patients with severe systolic dysfunction of the SRV (ejection fraction 23 ± 6%) who were evaluated as heart transplant (HTx) candidates between May 2007 and October 2014. The primary endpoints of the study (end-stage CHF) were progressive CHF, urgent HTx, and ventricular assist device (VAD) implantation. Plasma BNP levels were measured using a chemiluminescent immunoassay. RESULTS: During median follow-up of 29 months (interquartile range, 9-50), 3 patients died of progressive CHF, 5 patients required an urgent HTx, and 6 patients underwent VAD implantation. BNP was a strong predictor of end-stage CHF (hazard ratio per 100 ng/L: 1.079, 95% confidence interval, 1.042-1.117, P<0.001). The following variables with corresponding areas under the curve (AUC) were identified as the most significant predictors of end-stage CHF: BNP (AUC 1.00), New York Heart Association functional class class III or IV (AUC 0.98), decompensated CHF in the last year (AUC 0.96), and systolic dysfunction of the subpulmonal ventricle (AUC 0.96). CONCLUSION: BNP is a powerful predictor of end-stage CHF in individuals with systolic dysfunction of the SRV.

[30 years heart transplantation program in Institute for Clinical and Experimental Medicine in Prague]. / 30 let programu transplantace srdce v Institutu klinické a experimentální medicíny v Praze.

Heart transplantation has become in recent decades an established method for the treatment of advanced heart failure. Precisely, it was in January 2014 when 30 years have passed since the start of clinical heart transplantation program at the Institute for Clinical and Experimental Medicine. 936 heart transplants were performed by the end of 2013. The transplant program has reached considerable development since its beginnings. The knowledge of whole issue has deepened, indication criteria have been extended, new immunosuppressives are available and many of them are still in research. Life expectancy of patients has been prolonged and quality of life has improved. Nevertheless, the care of transplant patient is very complicated task for medical professionals and brings a lot of problems to solve.

Metformin treatment is associated with improved outcome in patients with diabetes and advanced heart failure (HFrEF).

The role of metformin (MET) in the treatment of patients with advanced HFrEF and type 2 diabetes mellitus (DM) is not firmly established. We studied the impact of MET on metabolic profile, quality of life (QoL) and survival in these patients. A total of 847 stable patients with advanced HFrEF (57.4 ± 11.3 years, 67.7% NYHA III/IV, LVEF 23.6 ± 5.8%) underwent clinical and laboratory evaluation and were prospectively followed for a median of 1126 (IQRs 410; 1781) days for occurrence of death, urgent heart transplantation or mechanical circulatory support implantation. A subgroup of 380 patients (44.9%) had DM, 87 of DM patients (22.9%) were treated with MET. Despite worse insulin sensitivity and more severe DM (higher BMI, HbA1c, worse insulin resistance), MET-treated patients exhibited more stable HF marked by lower BNP level (400 vs. 642 ng/l), better LV and RV function, lower mitral and tricuspid regurgitation severity, were using smaller doses of diuretics (all p < 0.05). Further, they had higher eGFR (69.23 vs. 63.34 ml/min/1.73 m2) and better QoL (MLHFQ: 36 vs. 48 points, p = 0.002). Compared to diabetics treated with other glucose-lowering agents, MET-treated patients had better event-free survival even after adjustment for BNP, BMI and eGFR (p = 0.035). Propensity score-matched analysis with 17 covariates yielded 81 pairs of patients and showed a significantly better survival for MET-treated subgroup (p = 0.01). MET treatment in patients with advanced HFrEF and DM is associated with improved outcome by mechanisms beyond the improvement of blood glucose control.

The effect of three major co-morbidities on quality of life and outcome of patients with heart failure with reduced ejection fraction.

AIMS: Diabetes mellitus, chronic obstructive pulmonary disease, and chronic kidney disease are prevalent in patients with heart failure with reduced ejection fraction (HFrEF). We have analysed the impact of co-morbidities on quality of life (QoL) and outcome. METHODS AND RESULTS: A total of 397 patients (58.8 ± 11.0 years, 73.6% with New York Heart Association functional class ≥3) with stable advanced HFrEF were followed for a median of 1106 (inter-quartile range 379-2606) days, and 68% of patients (270 patients) experienced an adverse outcome (death, urgent heart transplantation, and implantation of mechanical circulatory support). Chronic obstructive pulmonary disease was present in 16.4%, diabetes mellitus in 44.3%, and chronic kidney disease in 34.5% of patients; 33.5% of patients had none, 40.0% had one, 21.9% had two, and 3.8% of patient had three co-morbidities. Patients with more co-morbidities reported similar QoL (assessed by Minnesota Living with Heart Failure Questionnaire, 45.46 ± 22.21/49.07 ± 21.69/47.52 ± 23.54/46.77 ± 23.60 in patients with zero to three co-morbidities, P for trend = 0.51). Multivariable regression analysis revealed that furosemide daily dose, systolic blood pressure, New York Heart Association functional class, and body mass index, but not the number of co-morbidities, were significantly (P < 0.05) associated with QoL. Increasing co-morbidity burden was associated with worse survival (P < 0.0001), lower degree of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment (P = 0.001), and increasing levels of BNP (mean of 685, 912, 1053, and 985 ng/L for patients with zero to three co-morbidities, P for trend = 0.008) and cardiac troponin (sm-cTnI, P for trend = 0.0496), which remained significant (P < 0.05) after the adjustment for left ventricular ejection fraction, left ventricular end-diastolic diameter, right ventricular dysfunction grade, body mass index, and estimated glomerular filtration rate. CONCLUSIONS: In stable advanced HFrEF patients, co-morbidities are not associated with impaired QoL, but negatively affect the prognosis both directly and indirectly through lower level of HF pharmacotherapy and increased myocardial stress and injury.

Clinical correlates of B-type natriuretic peptide monitoring in outpatients with left ventricular assist device.

BACKGROUND: B-type natriuretic peptide (BNP) is a strong predictor of prognosis in chronic heart failure. We aimed to evaluate the clinical correlates and interpretation of BNP monitoring in LVAD out-patient recipients. METHODS: We performed a prospective study in 136 individuals after HeartMate II LVAD implantation. During follow-up they were divided into group A (severe adverse events requiring hospitalisation), group B (mild to moderate adverse events) and group C (an uneventful course). BNP was measured pre-implant, at the first out-patient visit, and then every 2 months. We identified the lowest level, and the level at the clinical event and/or the highest value in patients without clinical events (BNP peak). RESULTS: During a median follow-up of 298 days, 8 patients (6%) died, 21 patients (15%) experienced a severe adverse event (group A) and 38 patients (28%) had other adverse event (group B). Both the absolute value of BNP peak and its percentage values relative to pre-implant, first visit and minimum BNP had similar areas under the curve (AUC) to identify individuals with adverse events (group A and B) from group C. The performance of BNP peak rose from detection of infection to diagnosis of heart failure and culminated in individuals with pump thrombosis (AUC 0.68 vs. 0.75 vs. 0.93). CONCLUSIONS: Serial measurement of BNP in outpatients with LVAD correlates with the occurrence of adverse events. Assessment of absolute values of BNP peak seems to have a similar accuracy to analysis of intra-individual variation of BNP and it is more practical.

Non-Fontan Adult Congenital Heart Disease Transplantation Survival Is Equivalent to Acquired Heart Disease Transplantation Survival.

BACKGROUND: As a result of improved diagnostic methods, medical treatment, surgical correction, and palliation in childhood, there is a growing number of adult patients with congenital heart disease (CHD) who may experience heart failure and subsequently require heart transplantation (HT). Because of complex anatomy, previous operations, and frequently increased pulmonary vascular resistance (PVR), these patients represent a group with a higher risk of early mortality after transplantation. METHODS: From May 1999 to December 2014, our institution performed 25 HTs in adult patients with end-stage CHD. We present our data and outcomes of transplantation in this group. RESULTS: The median age at transplantation was 38 years (range, 18.4-53.7 years). Survival was 88% at 30 days, 88% at 1 year, and 77% at 5 years. We identified long donor heart ischemic time (>4 hours) as an important risk factor for early mortality. There was no significant difference in the survival of patients undergoing transplantation for CHD and patients undergoing transplantation for other diagnoses. CONCLUSIONS: With careful donor and recipient selection, adults with end-stage CHD undergoing HT can achieve excellent early and midterm survival, comparable to the survival of patients who undergo transplantation for other diagnoses.

Biphasic response in number of stem cells and endothelial progenitor cells after left ventricular assist device implantation: A 6month follow-up.

BACKGROUND: Continuous blood flow could have deleterious effects on endothelium and vascular health. This could have serious consequences in patients with heart failure treated with continuous flow left ventricular assist devices (LVAD). Therefore, we studied effect of LVAD on three circulating vascular biomarkers: stem cells (SC), endothelial progenitor cells (EPC) and microparticles (MP). METHODS: In 23 patients (5 women) with end-stage heart failure, SC, EPC and MP were measured before, and 3 and 6months after implantation of LVAD (HeartMate II). SC were defined using determination of surface antigen expression as mononuclear CD34+/CD45low+ cells and EPC as mononuclear CD34+/CD45low+/KDR+ cells. MP concentrations were determined by ELISA method. RESULTS: Three months after LVAD implantation numbers of SC and EPC significantly decreased (p=0.01 and p=0.001, respectively). On the contrary, between 3rd and 6th month after implantation they significantly increased (p=0.006 and p=0.003, respectively).MP did not change significantly during the study despite exerting similar trend as SC and EPC. CONCLUSIONS: Observed biphasic changes of SC and EPC might reflect two processes. First, shortly after LVAD implantation, improved tissue perfusion could lead to decrease in ischemic stimuli and ensuing decrease of SC and EPC. Second, continuous flow between 3rd and 6th month produced by LVAD could lead to increase of SC and EPC through activation of endothelium. This explanation could be supported also by similar trend in the changes of concentrations of MP.

The value of B-type natriuretic peptide and big endothelin-1 for detection of severe pulmonary hypertension in heart transplant candidates.

BACKGROUND: Severe pulmonary hypertension (PH) and increased pulmonary vascular resistance (PVR) are important risk factors that predict early postoperative mortality after orthotopic heart transplantation. The aim of our study was to determine the value of B-type natriuretic peptide (BNP) and big endothelin-1 (big ET1) for prediction of severe PH in heart transplant candidates. METHODS: The study population included 43 potential heart transplant candidates (38 males, mean age 52 +/- 7 years). All underwent repeated right-heart catheterizations (2-5 studies) at an interval of 3-4 months, giving a total of 124 examinations, associated with blood sampling for BNP and big ET1 analysis. Severe PH was defined as the mean pulmonary artery pressure (MPAP) > 40 mmHg. RESULTS: Significantly high PVR (PVR > 3.0 Wood units and TPG > 15 mmHg) was noted on 12 occasions in 10 patients; always in the presence of severe PH. Low BNP levels (<67 pg/ml) ruled out the presence of severe PH with a 100% sensitivity, however, with a low specificity (34%). An increase in plasma BNP > 30 pg/ml (>40% of initial value) in subjects with a previous MPAP< or =40 mmHg detected development of severe PH with a 100% sensitivity and an 80-88% specificity. As a total of 58% of patients presented repeatedly with MPAP< or =40 mmHg, serial BNP testing could reduce the need for hemodynamic studies in this subgroup down to 12-20%. CONCLUSIONS: Serial BNP testing in hemodynamically stable heart transplant candidates with MPAP< or =40 mmHg allows reliable detection of development of severe PH, and may significantly reduce the need for repeated right-heart catheterizations in these patients.

Ischaemic heart disease is a risk factor for renal failure after heart transplantation.

BACKGROUND: The improvement of a long-term outcomes of heart transplantation (HTx) has resulted in a new phenomenon; specifically, the development of renal dysfunction secondary to calcineurin inhibitor toxicity. This study was designed to assess the participation of risk factors in the development of renal dysfunction in HTx. METHODS: Data from 310 patients undergoing HTx in our center between 1988-1998 with a post-operation survival period for minimum 5 years (n=155) were analyzed retrospectively. Study cohort was divided into two groups according to renal function estimated by serum creatinine in the fifth year (Group I n=72; serum creatinine > or = 150 micromol/l, Group II: n=83, serum creatinine < 150 micromol/l). RESULTS: We noted that patients with serum creatinine > or = 150 micromol/l at 5 years post-HTx had renal function significantly worse as early as 1 month (p<0.01), and 1 year post-HTx (p<0.001). The risk for developing renal dysfunction after HTx was doubled in patients with a history of coronary artery disease (CAD), and 2.5 times higher in those with small body weight gain. End stage renal disease developed in 16 patients (10.3%) and renal transplantation was performed in 13 (8.4%) of them. CONCLUSION: Our data documented that a history of CAD and limited weight gain is a major risk factor for development of renal dysfunction after HTx. Aggressive modification of risk factors for CAD may reduce the occurrence of this complication.