Neuregulin-1 attenuates mitochondrial dysfunction in a rat model of heart failure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mitochondrial dysfunction plays a pivotal role in the progression of left ventricular (LV) remodeling and heart failure (HF). Recombinant human neuregulin-1 (rhNRG-1) improves cardiac function in models of experimental HF and in clinical trials; however, its impact on mitochondrial function during chronic HF remains largely unknown. The purpose of this study was to investigate whether rhNRG-1 could attenuate the functional and structural changes that occur in cardiac mitochondria in a rat model of HF induced by myocardial infarction.</p><p><b>METHODS</b>Sixty adult rats underwent sham or coronary ligation to induce HF. Four weeks after ligation, 29 animals with LV ejective fraction ≤ 50% were randomized to receive either vehicle or rhNRG-1 (10 µg×kg(-1)×d(-1), I.V.) for 10 days, another 12 sham-operated animals were given no treatment. Echocardiography was used to determine physiological changes. Mitochondrial membrane potential (MMP), respiratory function and tissue adenosine triphosphate (ATP) production were analyzed. Cytochrome c expression and cardiomyocyte apoptosis were determined. Oxidative stress was evaluated by reactive oxygen species production using fluorescence assays and gene expression of glutathione peroxidase measured by real-time quantitative PCR.</p><p><b>RESULTS</b>Compared with sham-operated animals, vehicle treated HF rats exhibited severe LV remodeling and dysfunction, significant mitochondrial dysfunction, increased mitochondrial cytochrome c release, increased myocyte apoptosis and enhanced oxidative stress. Short-term treatment with rhNRG-1 significantly attenuated LV remodeling and cardiac function. Concomitant with this change, mitochondrial dysfunction was significantly attenuated; with ATP production, MMP and respiratory function restored, cytochrome c release and apoptosis inhibited, and oxidative stress reduced.</p><p><b>CONCLUSION</b>The present study demonstrated that rhNRG-1 can significantly improve LV remodeling and cardiac function in the failing heart, this beneficial effect is related to reducing mitochondrial dysfunction, myocyte apoptosis and oxidative stress.</p>

Optimal pharmacotherapy according to guideline improved prognosis of outpatients with chronic heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of optimal pharmacotherapy according to guideline on treating chronic heart failure(CHF) in real world clinical practice.</p><p><b>METHODS</b>A total of 231 consecutive outpatients with reduced left ventricular ejection fraction (LVEF ≤ 40%) and enlarged left ventricular end diastolic diameter (male > 55 mm, female > 60 mm) were recruited from January 2001 to June 2009. All patients were treated with optimal pharmacotherapy according to guideline recommendations and followed up to December 31, 2009. Mortality, rehospitalization and changes of heart size and cardiac function at baseline and at the end of follow-up period were analyzed.</p><p><b>RESULTS</b>(1) 14 patients were lost during follow-up (6.1%), and follow-up was complete in 217 patients (93.9%). 97.2% and 98.2% patients were prescribed angiotensin converting enzyme (ACE) inhibitors and β-blockers (βB). Combined of ACE inhibitors and BB use was applied in 95.3% patients. The target dose of ACE inhibitors and βB were reached in 50.7% and 37.3% patients. (2) Lower mortality and re-hospitalization rates were observed in this cohort: all-cause morality, average annual mortality was 11.5% and 3.9% respectively. Re-hospitalization rate was 27.6%. (3) Left ventricular end-diastolic diameter (LVEDD) decreased from (68.2 ± 7.2) mm to (62.2 ± 9.6) mm. LVEDD value was normal or near normal (male ≤ 60 mm, female ≤ 55 mm) in 43.2% patients. LVEF improved form (29.8 ± 7.5)% to (43.3 ± 11.8)%, LVEF was > 40% in 60.4% patients, LVEF was ≤ 40% but increased ≥ 10% after treatment in 22.9% patients.</p><p><b>CONCLUSION</b>Optimal pharmacotherapy according to guideline can improve prognosis of outpatients with CHF.</p>

Factors influencing recovery of left ventricular structure in patients with chronic heart failure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Angiotensin converting enzyme (ACE) inhibitors and β-blockers (βB) have beneficial effects on left ventricular (LV) remodeling, alleviate symptoms and reduce morbidity and mortality in patients with chronic heart failure (CHF). However the correlation between the d osages of ACE inhibitors, βB, and recovery of LV structure remains controversial. Clinical factors associated with recovery of normal ventricular structure in CHF patients receiving medical therapy are poorly defined. Here we aimed to identify variables associated with recovery of normal or near-normal structure in patients with CHF.</p><p><b>METHODS</b>We recruited 231 consecutive CHF outpatients, left ventricular ejection fraction (LVEF) ≤ 40% and left ventricular end diastolic diameter (LVEDD) > 55/50 mm (male/female), who were receiving optimal pharmacotherapy between January 2001 and June 2009, and followed them until December 31, 2009. They were divided into three groups according to LVEDD and whether they were still alive at final follow-up: group A, LVEDD ≤ 60/55 mm (male/female); group B, LVEDD > 60/55 mm (male/female); and group C, those who died before final follow-up. Apart from group C, univariate analysis was performed followed by Logistic multivariate analysis to determine the predictors of recovery of LV structure.</p><p><b>RESULTS</b>A total of 217 patients completed follow-up, and median follow-up time was 35 months (range 6 - 108). Twenty-five patients died during that period; the all-cause mortality rate was 11.5%. Group A showed clinical characteristics as follows: the shortest duration of disease and shortest QRS width, the lowest N-terminal brain natriuretic peptide (NT-proBNP) at baseline, the highest dose of βB usage, the highest systolic blood pressure (SBP), diastolic blood pressure (DBP) and the lowest New York Heart Association (NYHA) classification, serum creatinine, uric acid, total bilirubin and NT-proBNP after treatment. Logistic multivariate analysis was performed according to recovery or no recovery of LV structure. Data showed that LVEF at follow-up (P = 0.013), mitral regurgitation at baseline (P = 0.020), LVEDD at baseline (P = 0.031), and βB dosage (P = 0.041) were independently associated with recovery of LV diameter.</p><p><b>CONCLUSION</b>Our study suggests that four clinical variables may predict recovery of LV structure to normal or near-normal values with optimal drug therapy alone, and may be used to discriminate between patients who should receive optimal pharmacotherapy and those who require more aggressive therapeutic interventions.</p>