Abstract 5881: Influence Of Cardiac Inflammation And Extracellular Matrix Regulation On Diastolic Dysfunction In Patients With Heart Failure With Normal Ejection Fraction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Dirk Westermann ◽  
Mario Kasner ◽  
Olga Lettau ◽  
Micheal Noutsias ◽  
Heinz-Peter Schultheiss ◽  
...  
Keyword(s):  
Heart Failure ◽  
Extracellular Matrix ◽  
Left Ventricular ◽  
Collagen Content ◽  
Exercise Intolerance ◽  
Atrial Pacing ◽  
Mrna Levels ◽  
Titin Isoforms ◽  
Cardiac Inflammation ◽  
Diastolic Stiffness

Aims: One of the hemodynamic mechanisms underlying heart failure with normal EF (HFNEF) is increased LV stiffness. In order to clarify the pathological changes leading to increased stiffness we investigated the left ventricular (LV) function using pressure-volume loops under basal conditions and during atrial pacing and investigated endomyocardial biopsies of patients with HFNEF. Methods: In 36 patients with HFNEF and 8 controls pressure volume loops were measured under basal conditions and during atrial pacing. Furthermore, endomyocardial biopsies were analyzed for changes in the extracellular matrix regulation, cardiac inflammation and changes in the titin isoforms. Results: Patients with HFNEF had an increased LV diastolic stiffness (+350%) compared to controls. During atrial pacing, stroke volume decreased (−35%) due to a leftward shift of the PV loops. This was associated with increased collagen content in cardiac biopsies (+380%), which blunted their cardiac output response to enhanced cardiac demand. This may explain the exercise intolerance in HFNEF patients. The total collagen correlated with cardiac stiffness in the HFNEF group (r2=0.69). This was associated with increased mRNA levels of the pro fibrotic TGF-b. Furthermore, the collagenase matrix metalloproteinases (MMP) 1 was not changed while TIMP-1 was increased (+150%), which supposes a decrease in collagen degradation in HFNEF. Nevertheless, MMP 2 was increased (+160%). This MMP is also associated with inflammation, and coherently, we investigated cardiac inflammation. We documented increased cardiac inflammation by an increment of adhesion molecules (ICAM +55%) and invading cells (CD11b cells +250%) in the cardiac tissue of HFNEF patients compared to controls. Interestingly, there was no change in titin isoforms between both groups. Conclusion: Patients with HFNEF have increased diastolic stiffness leading to an impairment of the Frank-Starling mechanism during atrial pacing. Since increased stiffness correlated with the cardiac collagen content, changes in the ECM regulation might be important for the development of HFNEF and invading cells triggering cardiac inflammation might further participate in this pathophysiology.

scholarly journals Heart Rate–Induced Myocardial Ca 2+ Retention and Left Ventricular Volume Loss in Patients With Heart Failure With Preserved Ejection Fraction

2020 ◽  
Vol 9 (17) ◽  
Author(s):  
Daniel N. Silverman ◽  
Mehdi Rambod ◽  
Daniel L. Lustgarten ◽  
Robert Lobel ◽  
Martin M. LeWinter ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Sinus Rhythm ◽  
Left Ventricular ◽  
Atrial Pacing ◽  
Preserved Ejection Fraction ◽  
Volume Loss ◽  
Heart Rates ◽  
Patients With Heart Failure

Background Increases in heart rate are thought to result in incomplete left ventricular (LV) relaxation and elevated filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). Experimental studies in isolated human myocardium have suggested that incomplete relaxation is a result of cellular Ca 2+ overload caused by increased myocardial Na + levels. We tested these heart rate paradigms in patients with HFpEF and referent controls without hypertension. Methods and Results In 22 fully sedated and instrumented patients (12 controls and 10 patients with HFpEF) in sinus rhythm with a preserved ejection fraction (≥50%) we assessed left‐sided filling pressures and volumes in sinus rhythm and with atrial pacing (95 beats per minute and 125 beats per minute) before atrial fibrillation ablation. Coronary sinus blood samples and flow measurements were also obtained. Seven women and 15 men were studied (aged 59±10 years, ejection fraction 61%±4%). Patients with HFpEF had a history of hypertension, dyspnea on exertion, concentric LV remodeling and a dilated left atrium, whereas controls did not. Pacing at 125 beats per minute lowered the mean LV end‐diastolic pressure in both groups (controls −4.3±4.1 mm Hg versus patients with HFpEF −8.5±6.0 mm Hg, P =0.08). Pacing also reduced LV end‐diastolic volumes. The volume loss was about twice as much in the HFpEF group (controls −15%±14% versus patients with HFpEF −32%±11%, P =0.009). Coronary venous [Ca 2+ ] increased after pacing at 125 beats per minute in patients with HFpEF but not in controls. [Na + ] did not change. Conclusions Higher resting heart rates are associated with lower filling pressures in patients with and without HFpEF. Incomplete relaxation and LV filling at high heart rates lead to a reduction in LV volumes that is more pronounced in patients with HFpEF and may be associated with myocardial Ca 2+ retention.

Abstract P352: An Antiplatelet Agent Sarpogrelate Suppresses Pressure Overload-induced Development Of Heart Failure In A 5-ht 2a Receptor-independent Manner

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Kana Shimizu ◽  
Masafumi Funamoto ◽  
Yoichi Sunagawa ◽  
Yasufumi Katanasaka ◽  
Yusuke Miyazaki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Western Blotting ◽  
Drug Repositioning ◽  
Antiplatelet Agent ◽  
Left Ventricular ◽  
Antiplatelet Drug ◽  
Cardiomyocyte Hypertrophy ◽  
Sham Operation ◽  
Mrna Levels ◽  
Independent Manner

Purpose: The cost of new drug development is increasing year by year, and drug repositioning is being used as a strategy to develop new treatments at low-cost. We used a library of approved drugs to screen for compounds that suppress cardiomyocyte hypertrophy, and identified as a candidate the antiplatelet drug sarpogrelate, a selective serotonin-2A (5-HT 2A ) receptor antagonist. In this study, we examined the effect of sarpogrelate on cultured cardiomyocyte hypertrophy and development of heart failure. Methods & Results: First, primary cultured cardiomyocytes were treated with 1 μM sarpogrelate and then stimulated with various hypertrophic stimuli (30 μM phenylephrine (PE), 0.1 μM angiotensin II and 0.1 μM endothelin 1). The results of immunofluorescence staining with anti-MHC antibody showed that sarpogrelate significantly suppressed cardiomyocyte hypertrophy induced by each stimulus. Western blotting and qPCR analysis showed that the mRNA and protein levels of 5-HT 2A receptor did not change by PE, and sarpogrelate significantly suppressed PE-induced phosphorylation of ERK1/2 and GATA4. Next, C57BL/6j male mice were subjected to a transverse aortic constriction (TAC) and sham operation. One day after the operation, the mice were randomly divided into 3 groups: sarpogrelate at 1 mg/kg or 5 mg/kg, and vehicle as a control. Daily oral administration was repeated for 8 weeks. Echocardiographic analysis showed that 5 mg/kg sarpogrelate significantly prevented a TAC-induced increase in posterior left ventricular wall thickness and a decrease in fractional shortening at 8 weeks after the operation. Five mg/kg sarpogrelate also suppressed TAC-induced increase in HW/BW ratio, cross-sectional areas, perivascular fibrosis, and mRNA levels of ANF and BNP. Moreover, the western blotting analysis showed that 5 mg/kg sarpogrelate significantly suppressed TAC-induced phosphorylation of ERK1/2. Conclusions: These results indicate that sarpogrelate significantly suppresses cardiomyocyte hypertrophy and the development of heart failure via at least, in part, by inhibition of ERK1/2-GATA4 pathway. These findings suggest that sarpogrelate may be an effective agent for heart failure therapy.

Abstract 14664: Reduced Activin Like Kinase 1 Activity Promotes Cardiac Fibrosis in Heart Failure

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kevin Morine ◽  
Vikram Paruchuri ◽  
Xiaoying Qiao ◽  
Emily Mackey ◽  
Mark Aronovitz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Left Ventricular ◽  
Lv Function ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels

Introduction: Activin receptor like kinase 1 (ALK1) mediates signaling via transforming growth factor beta-1 (TGFb1), a pro-fibrogenic cytokine. No studies have defined a role for ALK1 in heart failure. We tested the hypothesis that reduced ALK1 expression promotes maladaptive cardiac remodeling in heart failure. Methods and Results: ALK1 mRNA expression was quantified by RT-PCR in left ventricular (LV) tissue from patients with end-stage heart failure and compared to control LV tissue obtained from the National Disease Research Interchange (n=8/group). Compared to controls, LV ALK1 mRNA levels were reduced by 85% in patients with heart failure. Next, using an siRNA approach, we tested whether reduced ALK1 levels promote TGFb1-mediated collagen production in human cardiac fibroblasts. Treatment with an ALK1 siRNA reduced ALK1 mRNA levels by 75%. Compared to control, TGFb1-mediated Type I collagen and pSmad-3 protein levels were 2.5-fold and 1.7-fold higher, respectively, after ALK1 depletion. To explore a role for ALK1 in heart failure, ALK1 haploinsufficient (ALK1) and wild-type mice (WT; n=8/group) were studied 2 weeks after thoracic aortic constriction (TAC). Compared to WT, baseline LV ALK1 mRNA levels were 50% lower in ALK1 mice. Both LV and lung weights were higher in ALK1 mice after TAC. Cardiomyocyte area and LV mRNA levels of BNP, RCAN, and b-MHC were increased similarly, while SERCa levels were reduced in both ALK1 and WT mice after TAC. Compared to WT, LV fibrosis (Figure) and Type 1 Collagen mRNA and protein levels were higher among ALK1 mice. Compared to WT, LV fractional shortening (48±12 vs 26±10%, p=0.01) and survival (Figure) were lower in ALK1 mice after TAC. Conclusions: Reduced LV expression of ALK1 is associated with advanced heart failure in humans and promotes early mortality, impaired LV function, and cardiac fibrosis in a murine model of heart failure. Further studies examining the role of ALK1 and ALK1 inhibitors on cardiac remodeling are required.

Abstract 337: Activation of Myocardial AMP-activated Protein Kinase by Metformin Prevents Progression of Heart Failure in Dogs; Involvement of eNOS Activation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hideyuki Sasaki ◽  
Hiroshi Asanuma ◽  
Masashi Fujita ◽  
Hiroyuki Takahama ◽  
Masanori Asakura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Heart Failure ◽  
Cell Death ◽  
Protein Kinase ◽  
Left Ventricular ◽  
Vehicle Group ◽  
Mrna Levels ◽  
Compound C ◽  
Amp Activated Protein Kinase

Background; Several studies have shown that metformin activates AMP-activated protein kinase (AMPK), which mediates potent cardioprotection against ischemia-reperfusion injury. AMPK is also activated in experimental failing myocardium, suggesting that activation of AMPK is beneficial for the pathophysiology of heart failure. We investigated whether metformin prevents oxidative stress-induced cell death in rat cardiomyocytes and attenuates the progression of heart failure in dogs. Methods and Results; The treatment with metformin (10 μmol/L) protected the rat cultured cardiomyocytes against cell death due to H 2 O 2 exposure (50 μmol/L) as indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), TUNEL staining, and flow cytometry. These effects were blunted by an AMPK inhibitor, compound-C (20 μmol/L), suggesting that the activation of AMPK decreased the extent of apoptosis-induced cell death due to H 2 O 2 exposure. Continuous rapid ventricular pacing (230/min for 4 weeks) in dogs caused heart failure and the treatment with metformin (100 mg/kg/day PO, n=8) decreased left ventricular (LV) end-diastolic dimension (32.8±0.4 vs. 36.5±1.0 mm, p< 0.01) and pressure (11.8±1.1 vs. 22±0.9 mmHg, p< 0.01), and increased LV fractional shortening (18.6±1.8 vs. 9.6±0.7 %, p< 0.01) along with enhanced phosphorylation of AMPK and the decreased the number of TUNEL-positive cells of the LV myocardium compared with the vehicle group (n=8). Interestingly, metformin increased the protein and mRNA levels of endothelial nitric oxide synthase of the LV myocardium and plasma nitric oxide levels. Metformin improved the plasma insulin resistance without increased myocardial GLUT-4 translocation. Furthermore, the subcutaneous administration of AICAR (50 mg/kg/every other day), another AMPK activator mediated the equivalent effects to metformin, strengthening the pivotal role of AMPK in reduction of apoptosis and prevention of heart failure. Conclusions; Activation of myocardial AMPK attenuated the oxidative stress-induced cardiomyocyte apoptosis and prevented the progression of heart failure in dogs, along with eNOS activation. Thus, metformin or AICAR may be applicable as a novel therapy for heart failure.

Obesity and hemoglobin content impact peak oxygen uptake in human heart failure

2018 ◽  
Vol 25 (18) ◽  
pp. 1937-1946 ◽  
Author(s):  
Erik H Van Iterson ◽  
Chul-Ho Kim ◽  
Katelyn Uithoven ◽  
Thomas P Olson
Keyword(s):  
Heart Failure ◽  
Body Mass Index ◽  
Oxygen Uptake ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Left Ventricular Ejection ◽  
Peak Exercise ◽  
Ventricular Ejection Fraction ◽  
Group 4 ◽  
Group 1

Background Exercise intolerance, obesity, and low hemoglobin (hemoglobin<13 and <12 g/dl, men/women, respectively) are common features of heart failure. Despite serving as potent contributors to metabolic dysfunction, the impact of obesity and low hemoglobin on exercise intolerance is unknown. This study tested the hypotheses, compared with non-obese (NO) heart failure with normal hemoglobin, (a) counterparts with low hemoglobin and obesity or non-obesity will demonstrate reduced peak exercise oxygen uptake; (b) obese with normal hemoglobin will demonstrate decreased peak exercise oxygen uptake; (c) compared across stratifications, obese with low hemoglobin will demonstrate the sharpest decrement in peak exercise oxygen uptake. Methods Adults with heart failure ( n = 315; left ventricular ejection fraction≤40%; 77% men) (Group 1: normal hemoglobin and non-obese, n = 137; Group 2: low hemoglobin and non-obese, n = 51; Group 3: normal hemoglobin+obesity, n = 89; Group 4, n = 38: low hemoglobin+obesity; body mass index = 26 ± 3, 26 ± 2, 34 ± 4, 34 ± 4 kg/m2, respectively) completed treadmill cardiopulmonary exercise testing as part of routine clinical management. Peak exercise oxygen uptake was measured via standard metabolic system. Results There were no group-wise differences for heart failure class, gender, left ventricular ejection fraction, and resting cardiopulmonary function. Group 1 demonstrated increased peak exercise oxygen uptake versus Groups 2–4 (20 ± 6 versus 17 ± 6, 17 ± 5, 13 ± 4 ml/kg/min, respectively; all p < 0.001); whereas Group 4 peak exercise oxygen uptake was reduced versus all groups ( p < 0.001). Additionally, both body mass index (R2 = 0.10) and hemoglobin (R2 = 0.12) were significant predictors of peak exercise oxygen uptake in Group 1; which were relationships not mirrored for Groups 2–4. Conclusion These data suggest obesity together with low hemoglobin are potent contributors to impaired peak exercise oxygen uptake and, hence, oxidative metabolic capacity. In diverse populations of heart failure where obesity and/or low hemoglobin are present, it is important to consider these features together when interpreting peak exercise oxygen uptake and underlying exercise limitations.

Abstract 19346: Peak Oxygen Consumption Predicts Outcome in Hypertrophic Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Carla Contaldi ◽  
Raffaella Lombardi ◽  
Alessandra Giamundo ◽  
Sandro Betocchi
Keyword(s):  
Heart Failure ◽  
Oxygen Consumption ◽  
Hypertrophic Cardiomyopathy ◽  
Nyha Class ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Peak Oxygen Consumption ◽  
Class Iii ◽  
Asymptomatic Patients

Introduction: Peak oxygen consumption (VO 2 ) has a strong and independent prognostic value in systolic heart failure; in contrast no data support its prognostic role in hypertrophic cardiomyopathy (HCM). Hypothesis: We assess if peak VO 2 is a long-term predictor of outcome in HCM. Methods: We studied 92 HCM patients (40±15 years). Peak VO 2 was expressed as percentage (%) of the predicted value. Follow up was 76±57 months. The primary composite endpoint (CE) was atrial fibrillation, progression to NYHA class III or IV, myotomy-myectomy (MM), heart transplantation (HT) and cardiac death. An ancillary endpoint (HFE) included markers of heart failure (progression to NYHA class III or IV, MM and HT). Results: At baseline, 62% of patients were asymptomatic, 35% NYHA class II and 3% NYHA class III; 26% had left ventricular outflow tract obstruction. During follow up, 30 patients met CE with 43 events. By multivariate Cox survival analysis, we analyzed 2 models, using the CE, and in turn HFE. For CE, maximal left atrial diameter (LAD) (HR: 1.12; 95% CI: 1.04 to 1.22), maximal wall thickness (MWT) (HR: 0.14; 95% CI: 1.04 to 1.23) and % predicted peak VO 2 (HR: -0.03; 95% CI: 0.95 to 0.99) independently predicted outcome (overall, p<0.0001). For HFE, maximal LAD (HR:0.31; 95% CI: 1.09 to 1.70), MWT (HR: 0.35; 95% CI: 1.08 to 1.84) and % predicted peak VO 2 (HR: -0.06; 95% CI: 0.89 to 0.98) independently predicted outcome (overall, p<0.0001). Only 19% of mildly symptomatic or asymptomatic patients with % predicted peak VO 2 >80% had events, as opposed to 53% of them with % predicted peak VO 2 < 55% (p= 0.04). Event-free survival for both endpoints was significantly lower in patients with % predicted peak VO 2 < 55% as compared to those with it between 55 and 80 and >80% , Figure. Conclusion: In mildly or asymptomatic patients severe exercise intolerance may precede clinical deterioration. In HCM, peak VO 2 provides excellent risk stratification with a high event rate in patients with % predicted value <55%.

Abstract P410: A Novel Curcumin Formulation, ASD-cur Suppressed Heart Failure After Myocardial Infarction In Rats

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Hidemichi Takai ◽  
Tatsuya Morimoto
Keyword(s):  
Heart Failure ◽  
Plasma Concentration ◽  
Cardiac Fibrosis ◽  
Myocardial Cell ◽  
Left Ventricular ◽  
Cell Diameter ◽  
Maximum Plasma ◽  
Mrna Levels ◽  
Time Curve ◽  
Sd Rats

Introduction: Curcumin prevents the development of heart failure and is a potential treatment for heart failure. Although curcumin is known to be safe, its therapeutic efficiency is limited due to its low bioavailability. To overcome this problem, we developed ASD-Cur, an amorphous formulation of curcumin. In this study, we investigated the effect of ASD-Cur and compared it with Theracurmin ® , a colloidal submicron dispersion of curcumin. Methods: Male SD rats were orally administrated with ASD-Cur or Theracurmin ® (10 mg/kg curcumin). The plasma levels of curcumin were measured at 0.25, 0.5, 1, 2, 4 and 6 hours after administration. Twelve healthy volunteers, who had provided written informed consent, were administrated with ASD-Cur and Theracurmin ® containing 30 mg curcumin, and plasma curcumin concentrations were determined at 0.5, 1, 2, 4, and 8 hours. Next, male SD rats were subjected to MI or sham surgery. One week after surgery, the MI rats were randomly assigned to 4 groups: vehicle, ASD-Cur (0.2 mg/kg curcumin) or Theracurmin ® (0.2 or 0.5 mg/kg curcumin). Oral administration of these compounds was repeated for 6 weeks. After echocardiographic examinations, myocardial cell diameter, perivascular fibrosis, mRNA levels, and the acetylation of histone H3K9 were measured. Results: After administration in rats, the area under the plasma concentration-time curve ( AUC 0-6h ) and the maximum plasma concentration ( C max ) of ASD-Cur were 3.7-fold and 9.6-fold higher than those of Theracurmin ® , respectively. The AUC 0-8h and C max of ASD-Cur in humans were 3.4-fold and 5.4-fold higher than those of Theracurmin ® , respectively. Echocardiographic analysis showed that 0.2 mg/kg ASD-Cur and 0.5 mg/kg Theracurmin ® significantly improved the MI-induced deterioration of FS and left ventricular hypertrophy to the same extent. Both treatments significantly suppressed MI-induced increases in myocardial cell diameter, perivascular fibrosis, mRNA levels of hypertrophic markers and cardiac fibrosis, and acetylation of histone H3K9 to the same extent. Conclusion: These findings indicated that ASD-Cur has greater bioavailability than Theracurmin ® , and could exhibit greater therapeutic potency towards for MI-induced heart failure at a lower dose.

Role of Diastole in Left Ventricular Function, II: Diagnosis and Treatment

2004 ◽  
Vol 13 (6) ◽  
pp. 453-466 ◽  
Author(s):  
Shannan K. Hamlin ◽  
Penelope S. Villars ◽  
Joseph T. Kanusky ◽  
Andrew D. Shaw
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Left Atrial ◽  
Diastolic Heart Failure ◽  
Systolic Heart Failure ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Radiographic Findings ◽  
Ventricular Compliance

Left ventricular diastolic dysfunction plays an important role in congestive heart failure. Although once thought to be lower, the mortality of diastolic heart failure may be as high as that of systolic heart failure. Diastolic heart failure is a clinical syndrome characterized by signs and symptoms of heart failure with preserved ejection fraction (0.50) and abnormal diastolic function. One of the earliest indications of diastolic heart failure is exercise intolerance followed by fatigue and, possibly, chest pain. Other clinical signs may include distended neck veins, atrial arrhythmias, and the presence of third and fourth heart sounds. Diastolic dysfunction is difficult to differentiate from systolic dysfunction on the basis of history, physical examination, and electrocardiographic and chest radiographic findings. Therefore, objective diagnostic testing with cardiac catheterization, Doppler echocardiography, and possibly measurement of serum levels of B-type natriuretic peptide is often required. Three stages of diastolic dysfunction are recognized. Stage I is characterized by reduced left ventricular filling in early diastole with normal left ventricular and left atrial pressures and normal compliance. Stage II or pseudonormalization is characterized by a normal Doppler echocardiographic transmitral flow pattern because of an opposing increase in left atrial pressures. This normalization pattern is a concern because marked diastolic dysfunction can easily be missed. Stage III, the final, most severe stage, is characterized by severe restrictive diastolic filling with a marked decrease in left ventricular compliance. Pharmacological therapy is tailored to the cause and type of diastolic dysfunction.

scholarly journals Clinical Response to Personalized Exercise Therapy in Heart Failure Patients with Reduced Ejection Fraction Is Accompanied by Skeletal Muscle Histological Alterations

2019 ◽  
Vol 20 (21) ◽  
pp. 5514 ◽  
Author(s):  
Tatiana Lelyavina ◽  
Victoria Galenko ◽  
Oksana Ivanova ◽  
Margarita Komarova ◽  
Elena Ignatieva ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Ejection Fraction ◽  
Clinical Response ◽  
Exercise Therapy ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Left Ventricular Ejection ◽  
Histological Alterations ◽  
Before And After

Heart failure (HF) is associated with skeletal muscle wasting and exercise intolerance. This study aimed to evaluate the exercise-induced clinical response and histological alterations. One hundred and forty-four HF patients were enrolled. The individual training program was determined as a workload at or close to the lactate threshold (LT1); clinical data were collected before and after 12 weeks/6 months of training. The muscle biopsies from eight patients were taken before and after 12 weeks of training: histology analysis was used to evaluate muscle morphology. Most of the patients demonstrated a positive response after 12 weeks of the physical rehabilitation program in one or several parameters tested, and 30% of those showed improvement in all four of the following parameters: oxygen uptake (VO2) peak, left ventricular ejection fraction (LVEF), exercise tolerance (ET), and quality of life (QOL); the walking speed at LT1 after six months of training showed a significant rise. Along with clinical response, the histological analysis detected a small but significant decrease in both fiber and endomysium thickness after the exercise training course indicating the stabilization of muscle mechanotransduction system. Together, our data show that the beneficial effect of personalized exercise therapy in HF patients depends, at least in part, on the improvement in skeletal muscle physiological and biochemical performance.

Sign in / Sign up

Export Citation Format

Share Document