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Background. Galectin-3 plasma levels (gal-3) were shown to correlate with the scar burden in chronic heart failure (CHF) setting. As scar burden predicts response to stem cell therapy, we sought to explore a correlation between gal-3 and response to CD34+ cell transplantation in patients with CHF. Methods. We performed a post hoc analysis of patients, enrolled in 2 prospective trials investigating the clinical effects of CD34+ cell therapy in patients with ischemic cardiomyopathy (ICMP) and nonischemic dilated cardiomyopathy (DCMP). CD34+ cells were mobilized by G-CSF, collected via apheresis, and injected transendocardially using NOGA system. Patients were followed for 3 months and demographic, echocardiographic, and biochemical parameters and gal-3 were analyzed at baseline and at follow-up. Response to cell therapy was defined as an LVEF increase of ≥5%. Results. 61 patients were included in the analysis. The mean age of patients was 52 years and 83% were male. DCMP and ICMP were present in 69% and 31% of patients, respectively. The average serum creatinine was 86±23 μmol/L, NT-proBNP 1132 (IQR 350-2279) pg/mL, and LVEF 30±6%. Gal-3 at baseline and at 3 months did not differ significantly (13.4±5.5 ng/mL vs. 13.1±5.8 ng/mL; p=0.72), and there were no differences in baseline gal-3 with respect to heart failure etiology (15.1±7.2 ng/mL in ICMP vs. 12.7±4.3 ng/mL in DCMP; p=0.12). Comparing responders (N=49) to nonresponders (N=18), we found no differences in baseline gal-3 (13.6±5.7 ng/mL vs. 13.2±4.9 ng/mL; p=0.80). However, responders had significantly lower gal-3 at 3-month follow-up (12.1±4.0 ng/mL vs. 15.7±8.4 ng/mL; p<0.05). Also, responders demonstrated a significant decrease in gal-3 over 3 months, while in nonresponders, an increase in gal-3 occurred (−1.5±5.4 ng/mL vs. +2.7±4.3 ng/mL; p=0.01). Conclusions. In patients with chronic heart failure undergoing CD34+ cell therapy, a decrease in galectin-3 plasma levels is associated with beneficial response to this treatment modality. Further prospective data is warranted to confirm our findings and to deepen our understanding of the role of gal-3 in the field of stem cell therapy. [ABSTRACT FROM AUTHOR]

In patients with heart failure, sacubitril/valsartan therapy was associated with a decrease in NT-proBNP and improved echocardiographic parameters, which suggests a potential effect on cardiac reverse remodeling.1,2 Despite optimization of medical management, a significant proportion of heart failure patients progress to an advanced stage of the disease and require implantation of a left ventricular assist device (LVAD). CASE SERIES We analyzed clinical, echocardiographic, and laboratory data in six LVAD patients receiving sacubitril/valsartan therapy. Sacubitril/valsartan therapy was introduced instead of ACE inhibitors at 1 year after LVAD implantation; patients were followed for 6 months. [Extracted from the article]

Background. We sought to evaluate the long-term effects of angiotensin receptor blocker–neprilysin inhibitor (ARNI) therapy on reverse remodeling of the failing myocardium in HFrEF patients. Methods. We performed a prospective non-randomized longitudinal study on 228 HFrEF patients treated with ARNI at our center. Prior to ARNI introduction all patients received stable doses of ACEI/ARB for at least six months. Clinical, biochemical and echocardiography data were obtained at ARNI introduction and 12-month follow-up. Results At follow-up, we found significant improvements in LVEF (29.7% ± 8% vs. 36.5% ± 9%; p < 0.001), LVOT-VTI (14.8 ± 4.2 cm vs. 17.2 ± 4.2 cm; p < 0.001), TAPSE (1.7 ± 0.5 cm vs. 2.1 ± 0.6 cm; p < 0.001) and LV-EDD (6.5 ± 0.8 cm vs. 6.3 ± 0.9 cm; p = 0.001). NT-proBNP serum levels also decreased significantly (1324 (605, 3281) pg/mL vs. 792 (329, 2022) pg/mL; p = 0.001). A total of 102 (45%) of patients responded favorably to ARNI (ΔLVEF < +5%; Group A) and 126 (55%) patients achieved ΔLVEF ≥ +5% (Group B). The two groups differed significantly in age, heart failure etiology, baseline LVEF and baseline NT-proBNP. On multivariable analysis, nonischemic heart failure, LVEF < 30% and NT-proBNP < 1500 pg/mL emerged as independent correlates of favorable response to ARNI therapy. Conclusion. ARNI therapy appears to improve echocardiographic parameters of left and right ventricular function in HFrEF patients above the effect of pre-existing optimal medical management. These effects may be particularly pronounced in patients with nonischemic heart failure, LVEF < 30% and lower degree of neurohumoral activation. [ABSTRACT FROM AUTHOR]

Introduction: Noncompaction cardiomyopathy (NCC) is a congenital heart disease characterized by an arrest of the myocardial compaction process. Although NCC patients have impaired formation of microvasculature, the functional impact of these changes remains undefined. Hypothesis: We sought to analyze a potential correlation between myocardial ischemia and heart failure progression in patients with NCC. Methods: We enrolled 20 (12 male, 8 female) patients with NCC, diagnosed by cardiac MRI. The average age was 46±15.3 years. Echocardiography was performed to determine left ventricular end diastolic diameter and volume (EDD and EDV), ejection fraction (LVEF), with global longitudinal strain (GLS) postprocessing. At patient inclusion we also measured serum levels of NT-proBNP. Myocardial SPECT was performed at rest and on stress, determining summed difference score (SDS). Significant myocardial ischemia was defined as SDS≥2. Results: Of 20 patients enrolled, 9 patients (45%) had evidence of myocardial ischemia (Group A), 11 patients (55%) showed no significant ischemic changes (Group B). The two groups did not differ in sex (male 67% in Group A vs. 55% in Group B, P=0.58), age (45±14,6 years vs. 46±14,6 years, P=0.92), creatinine (79±14 μmol/L vs. 74±12 μmol/L, P=0.48) or bilirubin (12±7 μmol/L vs. 11±3 μmol/L, P=0.51). When compared to Group B, Group A had significantly higher EDD (6.3±0.9 cm vs. 5.3±0.6 cm, P=0.018), lower NTproBNP levels (1950±2004 pg/mL vs. 294±429 pg/mL in Group B, P=0.02) and a tendency toward lower LVEF (36.6±16.7% vs. 51.8±16.8% in Group B, P=0.06), higher EDV (179.2±53.9 mL vs. 138.7±47.4 mL, P=0.09), and lower GLS (-11.4±7% vs. -15.4±4%, P=0.12). Overall, higher SDS was associated with lower LVEF (r=-0.46, P=0.04), higher EDV (r=0.53, P=0.02), higher levels of NT-proBNP (r=0,82, P<0.001), and a tendency toward lower GLS (r=0.40, P=0.06). Conclusions: In patients with NCC, the presence of myocardial ischemia is associated with worse left ventricular function, dilation of left ventricle and more pronounced neurohumoral activation. Further studies are needed to investigate whether treatment approaches targeting myocardial ischemia, such as CD34+ cell therapy, may halt the progression of disease in this patient cohort. [ABSTRACT FROM AUTHOR]

Background: Data from preclinial models suggest that cell therapy may be associated with antiarrythmic effects due to improved cell-to-cell coupling. Hypothesis: We sought to investigate potential anti-arrhythmogenic effects of transendocardial CD34+ cell therapy in patients with chronic heart failure (CHF). Metods: We performed registry data analysis of 48 patients with CHF and implanted ICD/CRT devices treated with transendocardial CD 34+ cell therapy. Patients demonstrating ventricular arrhythmias (VA) in 12 months prior to cell therapy were included in the analysis. All patients were followed for 12 months after cell therapy. Demographic, echocardiographic and biochemical parameters were analysed. All patients uderwent electroanatomical mapping and myocardial scar was defined as unipolar voltage (UV)<8.3mV and linear local shortening (LLS)<6%. Areas of slow conduction were defined as areas with fragmented QRS signal. QRS fragmentation was defined as a multicomponent QRS signal and the cut-off value for normal QRS fragmentation was ≤ 4 positive peak deflections. Results: Of 20 patients included, 6 (30%, Group A) did not experience VA and 14 (70%, Group B) continued to have VA in 12 months after cell therapy. The two groups did not differ in gender (male; 67% in Group A vs. 93% in Group B; P=0.14), age (57±10 years vs. 53±8 years; P=0.31), chronic kidney disease (17% vs. 21%; P=0.82), NT-proBNP levels (1375±958 pg/mL vs. 1679±1629 pg/mL; P=0.69), left ventricular ejection fraction (31±6% vs. 29±8%; P=0.55), LV end-diastolic volume (221±126 mL vs. 229±85 mL; P=0.89) and amiodarone therapy (16% vs. 14%; P=0.89). In Group A significantly higher percentage of cell injections was performed in areas of slow conduction when compared to Group B (47±11% vs. 29±16%; P=0.03). Additionally, in Group B, the number ob ICD activations after cell therapy was reduced (3.6±2.7 ICD activations before cell therapy vs. 2.1±2.0 ICD activations after cell therapy; P=0.14). Conclusions: Transendocardial CD34+ cell therapy may reduce the VA burden in CHF when applied to the areas of slow conduction of the left ventricle. Prospective data are needed to confirm the anti-arrhythmic potential of cell therapy in chronic heart failure patients. [ABSTRACT FROM AUTHOR]