Profile of serum microRNAs in heart failure with reduced and preserved ejection fraction: Correlation with myocardial remodeling.

Background and aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%) and its association with myocardial remodeling. Methods: Prospectively enrolled symptomatic HF patients (HFpEF:n = 36; HFrEF:n = 31) and controls (n = 23) underwent cardiac magnetic resonance imaging with T1-mapping and circulating miRNA expression (OpenArray system). Results: 13 of 188 miRNAs were differentially expressed between HF groups (11 downregulated in HFpEF). Myocardial extracellular volume (ECV) was increased in both HF groups (HFpEF 30 ± 5%; HFrEF 30 ± 3%; controls 26 ± 2%, p < 0.001). miR-128a-3p, linked to cardiac hypertrophy, fibrosis, and dysfunction, correlated positively with ECV in HFpEF (r = 0.60, p = 0.01) and negatively in HFrEF (r = -0.51, p = 0.04). miR-423-5p overexpression, previously associated HF mortality, was inversely associated with LVEF (r = - 0.29, p = 0.04) and intracellular water lifetime (τic) (r = -0.45, p < 0.05) in both HF groups, and with NT-proBNP in HFpEF (r = -0.63, p < 0.01). Conclusions: miRNA expression profiles differed between HF phenotypes. The differential expression and association of miR-128a-3p with ECV may reflect the distinct vascular, interstitial, and cellular etiologies of HF phenotypes.

Strength training improves heart function, collagen and strength in rats with heart failure.

BACKGROUND/OBJECTIVES: Myocardial infarction (MI) frequently leads to cardiac remodeling and failure with impaired life quality, playing an important role in cardiovascular deaths. Although physical exercise is a well-recognized effective non-pharmacological therapy for cardiovascular diseases, the effects of strength training (ST) on the structural and functional aspects of cardiac remodeling need to be further documented. In this study, we aimed to investigate the role of a linear block ST protocol in the rat model of MI. METHODS AND RESULTS: After 6 weeks of MI induction or sham surgery, male adult rats performed ST for the following 12 weeks. The ladder-based ST program was organized in three mesocycles of 4 weeks, with one load increment for each block according to the maximal carrying load test. After 12 weeks, the infarcted-trained rats exhibited an increase in performance, associated with reduced cardiac hypertrophy and pulmonary congestion compared with the untrained group. Despite not changing MI size, the ST program partially prevented cardiac dilatation and ventricular dysfunction assessed by echocardiography and hemodynamics, and interstitial fibrosis evaluated by histology. In addition, isolated cardiac muscles from infarcted-trained rats had improved contractility parameters in a steady state, and in response to calcium or stimuli pauses. CONCLUSIONS: The ST in infarcted rats increased the capacity to carry mass, associated with attenuation of cardiac remodeling and pulmonary congestion with improving cardiac function that could be attributed, at least in part, to the improvement of myocardial contractility.

Identifying Patients With a Higher Potential for Recovery Post Left Ventricular Assist Device: A Single-Center Experience.

Background: Few patients with a left ventricular assist device (LVAD) achieve functional myocardial recovery to the point of LVAD explantation. The aim of this study was to highlight some of the hemodynamic and echocardiographic parameters we observed in patients who recovered. Methods: We conducted a retrospective analysis of 7 patients who received the HeartMate II LVAD (Abbott) at Temple Heart and Vascular Institute and subsequently underwent successful explantation following myocardial recovery. We compared baseline characteristics, echocardiographic data, and hemodynamic data. Results: Baseline characteristics of the cohort were as follows: age 51.6 ± 12.0 years, 57.1% male, 42.9% with nonischemic cardiomyopathy, and mean duration of LVAD support of 10.6 months. Comparison of echocardiographic and hemodynamic data (preimplant vs preexplant) revealed the following: left ventricular ejection fraction (%) was 12.8 ± 6.9 vs 52.8 ± 8.1 (P=0.0001), right atrial pressure (mmHg) was 12.3 ± 3.4 vs 5.0 ± 4.0 (P=0.022), mean pulmonary artery pressure (mmHg) was 36.0 ± 7.8 vs 15.4 ± 7.1 (P=0.01), cardiac output (L/min) was 3.6 ± 1.3 vs 5.5 ± 1.8 (P=0.004), and cardiac index (L/min/m2) was 1.8 ± 0.5 vs 2.7 ± 0.7 (P=0.008). Mean LVAD-free survival was 49.1 months. Results were consistent in both ischemic and nonischemic LVAD explants. Conclusion: A potential for LVAD explantation exists in patients with both ischemic and nonischemic cardiomyopathy. Myocardial recovery may be more likely among young patients with nonischemic cardiomyopathy and patients with recently diagnosed ischemic cardiomyopathy. Future prospective studies are needed.

Assessment of Cardiotoxicity of Cancer Chemotherapy: The Value of Cardiac MR Imaging.

Chemotherapy is associated with cardiovascular injury, including the development of a cardiomyopathy and vascular remodeling. Cardiac magnetic resonance (CMR) is sensitive to detect not only established morphologic and functional abnormalities but also early, potentially reversible, signs of myocardial injury. It robustly detects and quantifies myocardial edema, inflammation, and focal fibrosis, as well as interstitial fibrosis and vascular remodeling. These capabilities support the role of CMR as an excellent tool for evaluating cardiotoxicity. Novel CMR markers may even enhance patient management by facilitating the early detection of reversible myocardial tissue remodeling before classic morphologic and functional changes appear.

Myocardial expression of transforming growth factor beta family and endothelin-1 in the progression from heart failure to ascites in broilers with cold-induced pulmonary hypertension.

We determined mRNA expression of genes of endothelin-1 (ET-1), and of the transforming growth factor beta ligands (TGFß1, TGFß2 and TGFß3), their receptors (TßRI and TßRII) and their pseudoreceptor BAMBI in the heart of broilers raised under cold temperature conditions and affected by pulmonary hypertension. Gene expression was determined by RT-qPCR in right myocardial ventricle samples from 4-week-old chickens (n = 48) raised either under normal (control) or cold temperature conditions (22 °C versus 14 °C). We do not find differences among healthy birds, birds with cardiac failure and ascitic birds in the mRNA levels of TGFß2, TGFß3 and BAMBI. In the control group, ET-1 mRNA level was increased in the ascitic birds as compared with healthy birds and birds with cardiac failure (p < 0.05) whereas in the cold treated group, no increase was observed (p > 0.05); yet, ascitic birds in the cold group showed lower mean than ascitic birds in the control group (p < 0.05). TßRII mRNA expression was higher in ascitic than in healthy birds (p < 0.05) in both control and cold treated groups; however, in the ascitic birds of the cold treated group TßRII expression was lower than in ascitic birds from the control group (p < 0.05). Thus, the higher ET-1 and TßRII levels observed in ascitic birds seem to be attenuated by cold.

The effect of beta-blockade on myocardial remodelling in Chagas' cardiomyopathy

OBJECTIVE: Chagas' disease has spread throughout Latin America because of the high rate of migration among these countries. Approximately 30% of Chagas' patients will develop cardiomyopathy, and 10% of these will develop severe cardiac damage leading to heart failure. Beta-blockade improves symptoms and survival in heart failure patients; however, its efficacy has not been well established in Chagas' disease. We evaluated the role of carvedilol in cardiac remodeling and mortality in a Chagas' cardiomyopathy animal model. METHODS: We studied Trypanosoma cruzi infection in 55 Syrian hamsters that were divided into three groups: control (15), infected (20), and infected + carvedilol (20). Animals underwent echocardiography, electrocardiography, and morphometry for collagen evaluation in ventricles stained with picrosirius red. RESULTS: The left ventricular diastolic diameter did not change between groups, although it was slightly larger in infected groups, as was left ventricular systolic diameter. Fractional shortening also did not change between groups, although it was slightly lower in infected groups. Collagen accumulation in the interstitial myocardial space was significantly higher in infected groups and was not attenuated by carvedilol. The same response was observed in the perivascular space. The survival curve showed significantly better survival in the control group compared with the infected groups; but no benefit of carvedilol was observed during the study. However, in the acute phase (up to 100 days of infection), carvedilol did reduce mortality. CONCLUSION: Carvedilol did not attenuate cardiac remodeling or mortality in this model of Chagas' cardiomyopathy. The treatment did improve survival in the acute phase of the disease.

Effect of felodipine on myocardial and renal injury induced by aldosterone-high salt hypertension in uninephrectomized rats

It has been recently shown that calcium channel blockers might have a protective effect on cardiac fibrogenesis induced by aldosterone. The objective of this study was to evaluate the protective effect of felodipine, a dihydropyridine calcium channel blocker, against heart and kidney damage caused by aldosterone-high sodium intake in uninephrectomized rats. Wistar rats were divided into three groups: CNEP (uninephrectomized + 1 percent NaCl in the drinking water, N = 9); ALDO (same as CNEP group plus continuous infusion of 0.75 µg/h aldosterone, N = 12); ALDOF (same as ALDO group plus 30 mg·kg-1·day-1 felodipine in the drinking water, N = 10). All results were compared with those of age-matched, untreated rats (CTL group, N = 10). After 6 weeks, tail cuff blood pressure was recorded and the rats were killed for histological analysis. Blood pressure (mmHg) was significantly elevated (P < 0.05) in ALDO (180 ± 20) and ALDOF (168 ± 13) compared to CTL (123 ± 12) and CNEP (134 ± 13). Heart damage (lesion scores - median and interquartile range) was 7.0 (5.5-8.0) in ALDO and was fully prevented in ALDOF (1.5; 1.0-2.0). Also, left ventricular collagen volume fraction ( percent) in ALDOF (2.9 ± 0.5) was similar to CTL (2.9 ± 0.5) and CNEP (3.4 ± 0.4) and decreased compared to ALDO (5.1 ± 1.6). Felodipine partially prevented kidney injury since the damage score for ALDOF (2.0; 2.0-3.0) was significantly decreased compared to ALDO (7.5; 4.0-10.5), although higher than CTL (null score). Felodipine has a protective effect on the myocardium and kidney as evidenced by decreased perivascular inflammation, myocardial necrosis and fibrosis.