The Role of GDF-15 in Heart Failure Patients With Chronic Kidney Disease.

BACKGROUND: Growth differentiation factor-15 (GDF-15) is a stress-inducible cytokine and member of the transforming growth factor-ß cytokine superfamily that refines prognostic assessment in subgroups of patients with heart failure (HF). We evaluated its role in HF patients with chronic kidney disease (CKD, estimated glomerular filtration rate <60 mL/min/1.73 m2). METHODS: A total of 358 patients with stable systolic HF were followed for a median of 1121 (interquartile range, 379-2600) days. Comprehensive evaluation including B-type natriuretic peptide (BNP) and GDF-15 testing was performed at study entry; the analysis was stratified according to kidney function. RESULTS: Patients with CKD (33.8%) were older, had more often diabetes, and were less often treated with angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB). GDF-15 was associated with estimated glomerular filtration rate, whereas BNP was associated with left ventricular-end diastolic diameter and ejection fraction (P < 0.01). During follow-up, 244 patients (68.2%) experienced an adverse outcome (death, urgent transplantation, implantation of mechanical circulatory support). In patients with HF and CKD, the Cox proportional hazard model identified BNP, GDF-15, sex, systolic blood pressure, sodium, total cholesterol, and ACEi/ARB treatment as significant variables associated with an adverse outcome (P < 0.05). In multivariable analysis, BNP was replaced by GDF-15. Net reclassification improvement confirmed prognostic superiority of the model encompassing GDF-15 (GDF-15, sodium, total cholesterol, ACEi/ARB treatment) compared with the model without GDF-15 (BNP, sex, sodium, ACEi/ARB treatment), net reclassification improvement 0.62, P = 0.005. In contrast, in patients with HF and normal kidney function, BNP remained superior to GDF-15 in a multivariable model. CONCLUSIONS: In patients with systolic HF and CKD, GDF-15 is more strongly associated with adverse outcomes than the conventionally used BNP.

Novel predictors of left ventricular reverse remodeling in individuals with recent-onset dilated cardiomyopathy.

OBJECTIVES: This study aimed to evaluate the performance of cardiac magnetic resonance (CMR), cardiac biomarkers, and endomyocardial biopsy (EMB) results to predict left ventricular reverse remodeling (LVRR) in individuals with recent-onset dilated cardiomyopathy (DCM). BACKGROUND: LVRR is a marker of a favorable prognosis in individuals with recent-onset DCM. We used the aforementioned novel methods of prognostication to predict this event. METHODS: A total of 44 consecutive patients with recent-onset DCM underwent at baseline CMR, measurement of biomarkers and EMB together with conventional methods, including cardiopulmonary exercise testing and echocardiography. Measurement of B-type natriuretic peptide (BNP) and the cardiological examination were repeated at 3, 6, and 12 months. CMR was repeated at 12 months. LVRR was defined as an absolute increase in left ventricular ejection fraction from ≥10% to a final value of >35% accompanied by a decrease in left ventricular end-diastolic dimension ≥10% at 12 months of follow-up. RESULTS: LVRR was observed in 20 individuals (45%) at 12 months. At baseline, a lower extent of late gadolinium enhancement (odds ratio [OR]: 0.67 [95% confidence interval (CI): 0.50 to 0.90]; p = 0.008) and a higher myocardial edema ratio (OR: 1.45 [95% CI: 1.04 to 2.02]; p = 0.027) measured by CMR were independent predictors of LVRR. At 3 months, the latest BNP plasma level (OR: 0.14 [95% CI: 0.02 to 0.94] per log BNP; p = 0.047) was the strongest predictor of LVRR. CONCLUSIONS: Both CMR and serial BNP testing provide a better prediction of LVRR in recent-onset DCM than EMB results, other biomarkers, and the conventional methods of follow-up.

The hemodynamic effect of right ventricle (RV), RT3DE targeted left ventricle (LV) and biventricular (BIV) pacing in the early postoperative period after cardiac surgery.

BACKGROUND: Congestive heart failure negatively impacts the prognosis in patients after cardiac surgery. The aim of our study was to assess the value of targeted cardiac resynchronization therapy (CRT) within 72 hours after cardiac surgery in patients with mechanical dyssynchrony, who had an ejection fraction ≤ 35%, QRS ≥150 ms or between 120 and 150 ms. METHODS: A prospective randomized trial based on three-dimensional echocardiography (RT3DE) and optimized sequential dual-chamber (DDD ) pacing in patients after cardiac surgery. DDD epicardial pacing (Medtronic coaxial epicardial leads 6495) was provided by a modified Medtronic INSYNC III Pacemaker (Medtronic Inc., Minneapolis, MN, USA). SUMMARY OF RESULTS: The study included 21 patients with ischemic heart disease (HD) or valvular HD (16 men, 5 women, average age 69 years) with left ventricle (LV) dysfunction after cardiac surgery . Patients with biventricular (BIV) (CO 6.7 ± 1.7 L/min, CI 3.5 ± 0.8 L/min/m(2) ) and LV (CO 6.2 ± 1.5 L/min, CI 3.2 ± 0.7 L/min/m(2) ) pacing had statistically significantly higher CO and CI than patients with right ventricular (RV) (CO 5.4 ± 1.4 L/min, CI 2.8 ± 0.6 L/min/m(2) ) pacing (BIV vs RV P ≤ 0.001; LV vs RV P ≤ 0.05; BIV vs LV P ≤ 0.05). CONCLUSIONS: RT3DE targeted and optimized CRT in the early postperative period after cardiac surgery provided better hemodynamic results than RV pacing.

Assessment of left ventricular function in non-dilated and dilated hearts: comparison of contrast-enhanced 2-dimensional echocardiography with multi-detector row CT angiography.

OBJECTIVE: Multidetector-row CT (MDCT) and contrast-enhanced echocardiography (CEE) are being increasingly used for assessment of left ventricular (LV) function. Excellent spatial and contrast resolution of MDCT allows this evaluation along with coronary angiography. CEE improves the accuracy of 2D echocardiography. Data on side-by-side comparison of both techniques for assessment of LV size and function in subjects with a non-dilated or dilated left ventricle are limited. METHODS AND RESULTS: Our study population included 64 patients. Group I included 31 patients with an implanted pacemaker who had a non-dilated left ventricle with preserved systolic function. Group II comprised 33 patients with dilated cardiomyopathy and severe systolic LV dysfunction. LV end-diastolic and end-systolic volumes (LVEDV, LVESV) and ejection fraction (LVEF) were assessed using both CEE and short-axis MDCT. The results obtained by both techniques were compared by linear regression and Bland-Altman analysis. Additionally, intra- and interobserver reproducibility was assessed. Both CEE and MDCT measurements highly correlated (r = 0.61-0.94). However, CEE significantly underestimated LVEDV and LVESV, and this bias was higher with enlarged LV volumes. LVEF was overestimated by CEE in both groups with a higher bias in the group with preserved systolic function. Both intra- and interobserver reproducibility was significantly better for MDCT, the worst reproducibility was observed for CEE in group I. CONCLUSION: Despite a high correlation between MDCT and CEE measurements, CEE provides consistently lower volumes and higher LVEF. This suggests that both methods are not completely interchangeable. Reproducibility of CEE is inferior to reproducibility of MDCT, especially in non-dilated left ventricles with preserved function.

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.