Does fusion contribute to the improvement of LV systolic function of heart failure patients when pacing the LV with varying AV delays?

Background: Mitochondria (MITO) of failed human hearts and hearts of dogs with experimental heart failure (HF) manifest structural and functional abnormalities characterized by hyperplasia and reduced organelle size and reduced respiration. These abnormalities lead to reduced ATP synthesis that adversely impacts LV function. We previously showed that chronic therapy (3 months) with Bendavia (MTP-131), a novel mitochondria-targeting peptide, improves LV systolic function in dogs with heart failure (HF), reverses MITO abnormalities and normalizes mitochondria ATP synthesis in myocardium from Bendavia-treated HF dogs. In the present study we examined the direct effects of Bendavia on mitochondria ADP-stimulated state 3 respiration in freshly isolated cardiomyocytes from dogs with advanced chronic HF. Methods: Cardiomyocytes were isolated from LV free wall of 3 untreated dogs with HF produced by intracoronary microembolizations (LV ejection fraction <30%). A standard collagenase-based enzymatic process was used for isolation that yielded ~70% viable rod-shaped cardiomyocytes that excluded trypan blue. Equal aliquotes of cardiomyocytes were incubated in 0, 0.01, 0.10, 1.0 and 10 μM concentration of Bendavia for one hour at 37°C. At the end of incubation, ADP-stimulated state-3 respiration was measured using a Clark electrode system and quatified in nAtom Oxygen/min/mg protein. Results: State-3 respiration in the absence of Bendavia (Vehicle-Control) was 248±9 nAtom Oxygen/min/mg protein. Compared to vehicle-control, incubation of failing cardiomyocytes with Bendavia significantly increased state-3 respiration to 303±33 at 0.01 μM, p<0.05; 405±39 at 0.10 μM, p<0.05; 371±28 at 1.0 μM, p<0.05; and 346±29 at 10.0 μM, p<0.05. Conclusions: Results of this study indicate that the effects of Bendavia on mitochondrial respiration in cardiomyocytes is direct and not a consequence of improved global LV structure or function. Furthermore, the results indicate that the improvement in mitochondrial respiration after treatment with Bendavia can occur early after initiation of therapy (within one hour) and is dose-dependent up to concentrations of 0.10 μM.

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394 The influence of cardiac resynchronization therapy on right ventricular systolic function in heart failure patients with right ventricular impairment

European Journal of Echocardiography ◽

10.1016/s1525-2167(06)60184-4 ◽

2006 ◽

Vol 7 ◽

pp. S51-S51

Author(s):

M SZULIK ◽

W STREB ◽

R LENARCZYK ◽

P PRUSZKOWSKASKRZEP ◽

O KOWALSKI ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Resynchronization Therapy ◽

Right Ventricular ◽

Systolic Function ◽

Cardiac Resynchronization ◽

Resynchronization Therapy ◽

Ventricular Systolic Function ◽

Heart Failure Patients ◽

Right Ventricular Systolic Function

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Systolic Function and Intraventricular Mechanical Dyssynchrony Assessed by Advanced Speckle Tracking Imaging with N-terminal Prohormone of Brain Natriuretic Peptide for Outcome Prediction in Chronic Heart Failure Patients

Sultan Qaboos University Medical Journal [SQUMJ] ◽

10.12816/0003315 ◽

2013 ◽

Vol 13 (4) ◽

pp. 551-559 ◽

Cited By ~ 1

Author(s):

Faida A. Obaid ◽

Oteh Maskon ◽

Fadillah Abdolwahid

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Speckle Tracking ◽

Outcome Prediction ◽

Systolic Function ◽

Mechanical Dyssynchrony ◽

Speckle Tracking Imaging ◽

Heart Failure Patients

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Abstract 2936: Obesity and Mortality in Patients with Heart Failure and Preserved Systolic Function

Circulation ◽

10.1161/circ.118.suppl_18.s_795-b ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

John R Kapoor ◽

Paul A Heidenreich

Keyword(s):

Heart Failure ◽

Proportional Hazards ◽

Systolic Function ◽

Total Mortality ◽

Obesity Paradox ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Heart Failure Patients ◽

Objective Evidence

Several large cohort studies document better survival in heart failure patients with decreased left ventricular ejection fraction (EF) and higher body mass index (BMI) compared to those with a lower BMI. It is unclear, though, if this “obesity paradox” applies to heart failure patients with preserved EF or if it extends to the very obese (BMI>35). We followed 1,235 consecutive patients with a prior diagnosis of heart failure and a preserved EF (≥50%) documented on echocardiography at one of three laboratories. We determined adjusted mortality and readmission rates at 1 year following the echocardiogram. Obesity (BMI>30) was noted in 542 patients (44%). The mean age of the cohort was 71 years, but this varied depending on BMI (73 years for BMI<25, 64 years for BMI> 35, p< 0.001). In a subset of patients with complete diastolic indices and LV mass measurements (n=405), 95% had objective evidence of diastolic dysfunction. Age-adjusted all-cause mortality (Figure ) at one year decreased with increasing BMI (31% if BMI < 25, 22% if BMI 25–29, 20% if BMI 30–35 and 19% if BMI>35, p=0.003). In a proportional hazards analysis that adjusted for patient history, demographics and laboratory values, the hazard ratios for total mortality (relative to a normal BMI) were 1.47 (95% CI, 1.06–2.05) for BMI<25, 0.95 (95% CI, 0.64 –1.42) for BMI 30 –35, and 0.83 (95% CI, 0.52–1.31), for BMI >35, p=0.046). Similar findings were noted for the composite endpoint of survival free from heart failure hospitalization. These data suggest that the obesity paradox applies to heart failure patients with preserved systolic function and extends to very obese patients (BMI>35).

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