Relation between Mid-Regional Pro-Adrenomedullin in Patients with Chronic Heart Failure and the Dose of Diuretics in 2-Year Follow-Up-Data from FAR NHL Registry.

Background and Objectives: The aim of this paper is to evaluate the impact of humoral substance mid-regional pro-adrenomedullin (MR-proADM) on the two-year survival of patients with chronic heart failure and relate it to the dosage of furosemide. Materials and Methods: The data is taken from the stable systolic heart failure (EF < 50%) FAR NHL registry (FARmacology and NeuroHumoraL activation). The primary endpoint at two-year follow-up was death, heart transplantation, or LVAD implantation. Results: A total of 1088 patients were enrolled in the FAR NHL registry; MR-proADM levels were available for 569 of them. The mean age was 65 years, and 81% were male. The aetiology of HF was ischemic heart disease in 53% and dilated cardiomyopathy in 41% of patients. The mean EF was 31 ± 9%. Statistically significant differences (p < 0.001) were obtained in several parameters: patients with higher MR-proADM levels were older, rated higher in NYHA class, suffered more often from lower limb oedema, and had more comorbidities such as hypertension, atrial fibrillation, diabetes, and renal impairment. MR-proADM level was related to furosemide dose. Patients taking higher doses of diuretics had higher MR-proADM levels. The mean MR-proADM level without furosemide (n = 122) was 0.62 (±0.55) nmol/L, with low dose (n = 113) 1−39 mg/day was 0.67 (±0.30) nmol/L, with mid dose (n = 202) 40−79 mg/day was 0.72 (±0.34) nmol/L, with high dose (n = 58) 80−119 mg/day was 0.85 (±0.40) nmol/L, and with maximum dose (n = 74) ≥120 mg/day was 1.07 (±0.76) nmol/L, p < 0.001. Patients with higher MR-proADM levels were more likely to achieve the primary endpoint at a two-year follow-up (p < 0.001) according to multivariant analysis. Conclusions: Elevated plasma MR-proADM levels in patients with chronic heart failure are associated with an increased risk of death and hospitalization. Higher MR-proADM levels in combination with increased use of loop diuretics reflect residual congestion and are associated with a higher risk of severe disease progression.

Prescription and dosage of RAAS inhibitors in patients with chronic heart failure in the FAR NHL registry.

BACKGROUND: Congestive heart failure with reduced ejection fraction is a common clinical condition with a serious prognosis. Treatment focuses on improving the symptoms and preventing the progression of the disease. First-line therapy include angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs). METHODS: These data come from the FAR NHL registry (FARmacology and NeuroHumoraL activation). This is a multicenter database of patients with stable systolic heart failure (EF < 50 %) collected between November 2014 and November 2015. RESULTS: A population of 1 100 patients was evaluated, the mean age was 65 years, 80.8 % were male. The etiology of heart failure was ischemic heart disease (49.7 %), dilated cardiomyopathy (41.7 %) and other (8.6 %). The total prescription of ACEI/ARB was 88.4 %, the most commonly prescribed ACEI were ramipril and perindopril, ARB was losartan. The prescription of ACEI/ARBs decreased with the severity of the disease according to NYHA classification (all 88.4 %, NYHA I 95.2 %, NYHA II 89.0 %, NYHA III-IV 83.5 %, p < 0.001). 129 subjects (11.6 %) were not treated by ACEI/ARBs at all. The target dose of ACEI/ARB, as it is recommended in the ESC Guidelines, was admissioned to only 13.5 % of patients. The dose was decreasing with the severity of disease evaluated by NYHA, NT-proBNP value, systolic blood pressure and renal functions. CONCLUSIONS: These data show the tendency of pharmacological prescription of RAAS blockers (including doses), which reflects not only the severity of heart failure but also renal functions and blood pressure and points to possible reserves in up-titration of the target dose. Key words: angiotensin-converting enzyme inhibitors - angiotensin receptor blockers - FAR NHL - heart failure - pharmacotherapy - registry - target dose.

Renal Functions and Prognosis Stratification in Chronic Heart Failure Patients and the Importance of Neutrophil Gelatinase-Associated Lipocalin.

BACKGROUND/AIMS: The rate of incidence and prevalence of acute kidney injury is increasing due to an increased number of patients with heart failure. Therefore it is very pertinent to early detect the level of renal injuries and to make necessary heart failure predictions. Thus the aim of this study is to determine renal functions and prognosis stratification in chronic heart failure patients and importance of Neutrophil Gelatinase-Associated Lipocalin (NGAL), an early diagnostic marker of acute kidney injury, as well as stratification of cardiovascular risk in heart failure patients. METHODS: Data including age, gender, comorbidities and medical history of outpatients and hospitalized patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry comprising three Cardiological Centers in the Czech Republic were collected between 1st October 2014 and 30th November 2015. One-year follow-up data were collected in November 2016 in such a way that all patients had at least one-year data from the time of recruitment, but up to two years to the time of follow-up. One-year data were used for the whole set of patients while data up to 24 months were used with Kaplan-Meier's survival curves to analyse the patients' survival data. Blood samples were collected from the patients and basic parameters were evaluated in order to analyse Neutrophil gelatinase-associated lipocalin (NGAL) and plasma levels of N-terminal pro-brain natriuretic peptide (NT-ProBNP) using Lipocalin-2/NGAL Human ELISA kit (Bio Vendor, Czechia) and the Cobas E411 NT-proBNP Immunoassay kit (Roche Diagnostics, Indianapolis, IN, USA) respectively. Statistical analysis was further carried out to explain the level of significance of the evaluated parameters using Spearman Correlation, Mann Whitney or Kruskal-Wallis test and log-rank test. RESULTS: Out of 547 patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry with available data on hospitalizations, mortality, biomarkers and one-year follow-up that were recorded, there were 439 males (80.3%) with a median age of 66 years. At least one-month stable patients with left ventricle ejection fraction (LV EF) under 50% were recorded. The etiology of heart failure was ischemic heart disease in 54%, dilated cardiomyopathy in 40% and others in 6%. 69% patients were in New York Heart Association functional class II. There were 76 events (13.9%; all-cause mortality, acute heart failure hospitalization, left ventricle assist device implantation and orthotopic heart transplant) in the first 365 days of follow-up. The area under the receiver operating characteristic curve was higher for NT-proBNP (0.77) than the creatinine (0.57), NGAL (0.55) or creatinine clearance (0.54). In multivariable analyses, NT-proBNP (P= 0.001) and NGAL (P = 0.004) were significant predictors of events. Subjects with NT-proBNP and NGAL above the cut off value (NT-proBNP 1,121 pg/ml, NGAL 80 ng/ml) survived without any event in 55.7%, subjects with NT-proBNP and NGAL under the cut off value survived without any event in 90.5%, after two years (P = 0.001). CONCLUSION: The findings of the study showed that NGAL associated with NT-proBNP was a stronger predictor of the primary endpoint than NGAL or NT-proBNP alone. The level of NGAL was rising in hypertension, ischemia, anemia, hypoalbuminemia, diabetes or arrhythmias.

Prognostic value of high-sensitivity cardiac troponin I in heart failure patients with mid-range and reduced ejection fraction.

BACKGROUND: The identification of high-risk heart failure (HF) patients makes it possible to intensify their treatment. Our aim was to determine the prognostic value of a newly developed, high-sensitivity troponin I assay (Atellica®, Siemens Healthcare Diagnostics) for patients with HF with reduced ejection fraction (HFrEF; LVEF < 40%) and HF with mid-range EF (HFmrEF) (LVEF 40%-49%). METHODS AND RESULTS: A total of 520 patients with HFrEF and HFmrEF were enrolled in this study. Two-year all-cause mortality, heart transplantation, and/or left ventricular assist device implantation were defined as the primary endpoints (EP). A logistic regression analysis was used for the identification of predictors and development of multivariable models. The EP occurred in 14% of the patients, and these patients had higher NT-proBNP (1,950 vs. 518 ng/l; p < 0.001) and hs-cTnI (34 vs. 17 ng/l, p < 0.001) levels. C-statistics demonstrated that the optimal cut-off value for the hs-cTnI level was 17 ng/l (AUC 0.658, p < 0.001). Described by the AUC, the discriminatory power of the multivariable model (NYHA > II, NT-proBNP, hs-cTnI and urea) was 0.823 (p < 0.001). Including heart failure hospitalization as the component of the combined secondary endpoint leads to a diminished predictive power of increased hs-cTnI. CONCLUSION: hs-cTnI levels ≥ 17 ng/l represent an independent increased risk of an adverse prognosis for patients with HFrEF and HFmrEF. Determining a patient's hs-cTnI level adds prognostic value to NT-proBNP and clinical parameters.

Prognostic value of NT-proBNP added to clinical parameters to predict two-year prognosis of chronic heart failure patients with mid-range and reduced ejection fraction - A report from FAR NHL prospective registry.

BACKGROUND: According to guidelines, the prognosis of patients with chronic heart failure can be predicted by determining the levels of natriuretic peptides, the NYHA classification and comorbidities. The aim our work was to develop a prognostic score in chronic heart failure patients that would take account of patients' comorbidities, NYHA and NT-proBNP levels. METHODS AND RESULTS: A total of 1,088 patients with chronic heart failure with reduced ejection fraction (HFrEF) (LVEF<40%) and mid-range EF (HFmrEF) (LVEF 40-49%) were enrolled consecutively. Two-year all-cause mortality, heart transplantation and/or LVAD implantation were defined as the primary endpoint (EP). The occurrence of EP was 14.9% and grew with higher NYHA, namely 4.9% (NYHA I), 11.4% (NYHA II) and 27.8% (NYHA III-IV) (p<0.001). The occurrence of EP was 3%, 10% and 15-37% in patients with NT-proBNP levels ≤125 ng/L, 126-1000 ng/L and >1000 ng/L respectively. Discrimination abilities of NYHA and NT-proBNP were AUC 0.670 (p<0.001) and AUC 0.722 (p<0.001) respectively. The predictive value of the developed clinical model, which took account of older age, advanced heart failure (NYHA III+IV), anaemia, hyponatraemia, hyperuricaemia and being on a higher dose of furosemide (>40 mg daily) (AUC 0.773; p<0.001) was increased by adding the NT-proBNP level (AUC 0.790). CONCLUSION: The use of prediction models in patients with chronic heart failure, namely those taking account of natriuretic peptides, should become a standard in routine clinical practice. It might contribute to a better identification of a high-risk group of patients in which more intense treatment needs to be considered, such as heart transplantation or LVAD implantation.

New echocardiographic parameters in the diagnosis of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a serious clinical disease. The pathophysiology of HFpEF is complex, and specific diagnostic criteria have evolved over time. Limited data are available on the quantification of diastolic function using two-dimensional real-time echocardiography, and a simple parameter has not yet been established. The aim of this work is to evaluate new echocardiographic parameters-the diastolic wall strain of the posterior wall (DWS PW) and the vortex formation time (VFT). Echocardiographic data from 111 subjects with exertional dyspnea and normal left ejection fraction (Group A) and 20 healthy volunteers (Group B) were retrospectively evaluated. In addition to the standard parameters used in the diagnosis of HFpEF, DWS PW and VFT were assessed in all patients. HFpEF was diagnosed in 38 patients with dyspnea (Group A1). The remaining 73 patients did not meet the established criteria for a positive diagnosis of HFpEF (Group A2). We discovered that both observed parameters were significantly lower in patients with HFpEF than in other groups. Multivariate analysis revealed that both DWS PW and VFT independently predicted the presence of HFpEF. DWS PW and VFT are simple parameters in the evaluation of diastolic function and may play a potential role as a part of an integrated approach to the assessment of HFpEF.

Can we diagnose isolated, exercise-induced heart failure with normal ejection fraction?

BACKGROUND: A significant proportion of patients with exertional dyspnea require exercise to diagnose heart failure with normal ejection fraction (HFNEF). METHODS AND RESULTS: In this review article, we evaluate current data on the prevalence, clinical significance and specifically the establishment of a diagnosis of isolated, exercise-induced HFNEF. Despite the unquestioned clinical importance and high prevalence of exercise-induced HFNEF, there are limited and conflicting data on making a diagnosis of exercise-induced HFNEF. This mostly relies on the evidence of exercise-induced elevation in left ventricular filling pressure (LVFP). At present, there is no agreement on the ability of exercise echocardiographic parameteres to predict exercise-induced LVFP elevation. In addition, even invasively measured exercise LVFP faces the problem of defining normal exercise LVFP values. More data and probably new diagnostic approaches are necessary to reliably diagnose exercise HFNEF. CONCLUSIONS: There are conflicting results and significant problems associated with the diagnosis of exercise HFNEF. This review hopefully will encourage further research in this difficult but clinically important area of heart failure.