Ephraim B. Winzer

High-Intensity Interval Training in Patients with Heart Failure with Reduced Ejection Fraction

Background: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE). Methods: Two hundred sixty-one patients with left ventricular ejection fraction ⩽35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks. Results: Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT (P=0.45); left ventricular end-diastolic diameter changes compared with RRE were −2.8 mm (−5.2 to −0.4 mm; P=0.02) in HIIT and −1.2 mm (−3.6 to 1.2 mm; P=0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake (P=0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P=0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT. Conclusions: HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.

High Intensity Interval Training in Heart Failure Patients with Reduced Ejection Fraction

Background: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE). Methods: Two hundred sixty-one patients with left ventricular ejection fraction ⩽35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks. Results: Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT (P=0.45); left ventricular end-diastolic diameter changes compared with RRE were −2.8 mm (−5.2 to −0.4 mm; P=0.02) in HIIT and −1.2 mm (−3.6 to 1.2 mm; P=0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake (P=0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P=0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT. Conclusions: HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.

Exercise Training in Patients with Chronic Heart Failure Promotes Restoration of High-Density Lipoprotein Functional Properties

Rationale: High-density lipoprotein (HDL) exerts endothelial-protective effects via stimulation of endothelial cell (EC) nitric oxide (NO) production. This function is impaired in patients with cardiovascular disease. Protective effects of exercise training (ET) on endothelial function have been demonstrated. Objective: This study was performed to evaluate the impact of ET on HDL-mediated protective effects and the respective molecular pathways in patients with chronic heart failure (CHF). Methods and Results: HDL was isolated from 16 healthy controls (HDLhealthy) and 16 patients with CHF-NYHA-III (HDLNYHA-IIIb) before and after ET, as well as from 8 patients with CHF-NYHA-II (HDLNYHA-II). ECs were incubated with HDL, and phosphorylation of eNOS-Ser1177, eNOS-Thr495, PKC-&bgr;II-Ser660, and p70S6K-Ser411 was evaluated. HDL-bound malondialdehyde and HDL-induced NO production by EC were quantified. Endothelial function was assessed by flow-mediated dilatation. The proteome of HDL particles was profiled by shotgun LC-MS/MS. Incubation of EC with HDLNYHA-IIIb triggered a lower stimulation of phosphorylation at eNOS-Ser1177 and a higher phosphorylation at eNOS-Thr495 when compared with HDLhealthy. This was associated with lower NO production of EC. In addition, an elevated activation of p70S6K, PKC-&bgr;II by HDLNYHA-IIIb, and a higher amount of malondialdehyde bound to HDLNYHA-IIIb compared with HDLhealthy was measured. In healthy individuals, ET had no effect on HDL function, whereas ET of CHF-NYHA-IIIb significantly improved HDL function. A correlation between changes in HDL-induced NO production and flow-mediated dilatation improvement by ET was evident. Conclusions: These results demonstrate that HDL function is impaired in CHF and that ET improved the HDL-mediated vascular effects. This may be one mechanism how ET exerts beneficial effects in CHF.

Exercise Training in Patients with Chronic Heart Failure Promotes Restoration of HDL Functional Properties

Rationale: High-density lipoprotein (HDL) exerts endothelial-protective effects via stimulation of endothelial cell (EC) nitric oxide (NO) production. This function is impaired in patients with cardiovascular disease. Protective effects of exercise training (ET) on endothelial function have been demonstrated. Objective: This study was performed to evaluate the impact of ET on HDL-mediated protective effects and the respective molecular pathways in patients with chronic heart failure (CHF). Methods and Results: HDL was isolated from 16 healthy controls (HDLhealthy) and 16 patients with CHF-NYHA-III (HDLNYHA-IIIb) before and after ET, as well as from 8 patients with CHF-NYHA-II (HDLNYHA-II). ECs were incubated with HDL, and phosphorylation of eNOS-Ser1177, eNOS-Thr495, PKC-&bgr;II-Ser660, and p70S6K-Ser411 was evaluated. HDL-bound malondialdehyde and HDL-induced NO production by EC were quantified. Endothelial function was assessed by flow-mediated dilatation. The proteome of HDL particles was profiled by shotgun LC-MS/MS. Incubation of EC with HDLNYHA-IIIb triggered a lower stimulation of phosphorylation at eNOS-Ser1177 and a higher phosphorylation at eNOS-Thr495 when compared with HDLhealthy. This was associated with lower NO production of EC. In addition, an elevated activation of p70S6K, PKC-&bgr;II by HDLNYHA-IIIb, and a higher amount of malondialdehyde bound to HDLNYHA-IIIb compared with HDLhealthy was measured. In healthy individuals, ET had no effect on HDL function, whereas ET of CHF-NYHA-IIIb significantly improved HDL function. A correlation between changes in HDL-induced NO production and flow-mediated dilatation improvement by ET was evident. Conclusions: These results demonstrate that HDL function is impaired in CHF and that ET improved the HDL-mediated vascular effects. This may be one mechanism how ET exerts beneficial effects in CHF.

Physical Activity in the Prevention and Treatment of Coronary Artery Disease

In primary prevention, regular physical activity decreases the incidence of cardiovascular disease. At the endothelial level, this decreased incidence was attributed to higher expression and phosphorylation of the endothelial isoform of NO synthase, which results in a more effective radical

Impact of Rosuvastatin Treatment on HDL-Induced PKC-βII and eNOS Phosphorylation in Endothelial Cells and Its Relation to Flow-Mediated Dilatation in Patients with Chronic Heart Failure

Background. Endothelial function is impaired in chronic heart failure (CHF). Statins upregulate endothelial NO synthase (eNOS) and improve endothelial function. Recent studies demonstrated that HDL stimulates NO production due to eNOS phosphorylation at Ser1177, dephosphorylation at Thr495, and diminished phosphorylation of PKC-βII at Ser660. The aim of this study was to elucidate the impact of rosuvastatin on HDL mediated eNOS and PKC-βII phosphorylation and its relation to endothelial function. Methods. 18 CHF patients were randomized to 12 weeks of rosuvastatin or placebo. At baseline, 12 weeks, and 4 weeks after treatment cessation we determined lipid levels and isolated HDL. Human aortic endothelial cells (HAEC) were incubated with isolated HDL and phosphorylation of eNOS and PKC-βII was evaluated. Flow-mediated dilatation (FMD) was measured at the radial artery. Results. Rosuvastatin improved FMD significantly. This effect was blunted after treatment cessation. LDL plasma levels were reduced after rosuvastatin treatment whereas drug withdrawal resulted in significant increase. HDL levels remained unaffected. Incubation of HAEC with HDL had no impact on phosphorylation of eNOS or PKC-βII. Conclusion. HDL mediated eNOS and PKC-βII phosphorylation levels in endothelial cells do not change with rosuvastatin in CHF patients and do not mediate the marked improvement in endothelial function.

Risikofaktormanagement bei KHK

Durch eine gezielte Behandlung von Risikofaktoren kann bei Patienten mit KHK der weitere Krankheitsverlauf maßgeblich beeinflusst werden. Eine Reduktion von Krankenhauseinweisungen, Verbesserung der Lebensqualität und Verlängerung der Lebenserwartung durch sekundärprophylaktische Maßnahmen ist gut belegt. Neben einer optimalen medikamentösen Therapie ist hierfür eine oft drastische Veränderung des Lebensstils mit den Schwerpunkten einer konsequenten Nikotinabstinenz, einer gesunden Ernährung und regelmäßiger körperlicher Aktivität notwendig. Daten aus der Versorgungsforschung zeigen, dass diese Ziele nur unzulänglich erreicht werden. Die Umsetzung der bestehenden Behandlungsleitlinien sollte daher mit Nachdruck verfolgt werden. Forschungsbedarf besteht insbesondere hinsichtlich der prognostischen Bedeutung einer Betablockertherapie bei Patienten mit stabiler KHK und erhaltener LV-Funktion, der prognostischen Bedeutung einer gezielten Gewichtsreduktion bei KHK-Patienten mit Übergewicht und Adipositas, der Effektivität psychosozialer Interventionen bei unterschiedlichen Patientengruppen und deren Implementierung in die Routineversorgung sowie hinsichtlich der Optimierung von strukturierten Rehabilitationsprogrammen und der Verbesserung der Patientencompliance.

Impact of Weight Reduction During Adolescence on Parameters of Cardiac Geometry and Function in Obese Children

Childhood obesity is associated with changes in myocardial geometry and function indicating early onset of unfavorable alterations of the myocardium [(1,2)][1]. The value of those studies is limited by a cross-sectional study design. We aimed to assess the impact of weight reduction on temporal