Synergistic impact of endurance training and intermittent hypobaric hypoxia on cardiac function and mitochondrial energetic and signaling

Background

Intermittent hypobaric-hypoxia (IHH) and endurance-training (ET) are cardioprotective strategies against stress-stimuli. Mitochondrial modulation appears to be an important step of the process. This study aimed to analyze whether a combination of these approaches provides additive or synergistic effects improving heart-mitochondrial and cardiac-function.

Methods

Two-sets of rats were divided into normoxic-sedentary (NS), normoxic-exercised (NE, 1 h/day/5 weeks treadmill-running), hypoxic-sedentary (HS, 6000 m, 5 h/day/5 weeks) and hypoxic-exercised (HE) to study overall cardiac and mitochondrial function. In vitro cardiac mitochondrial oxygen consumption and transmembrane potential were evaluated. OXPHOS subunits and ANT protein content were semi-quantified by Western blotting. HIF-1α, VEGF, VEGF-R1 VEGF-R2, BNP, SERCA2a and PLB expressions were measured by qRT-PCR and cardiac function was characterized by echocardiography and hemodynamic parameters.

Results

Respiratory control ratio (RCR) increased in NE, HS and HE vs. NS. Susceptibility to anoxia/reoxygenation-induced dysfunction decreased in NE, HS and HE vs. NS. HS decreased mitochondrial complex-I and -II subunits; however HE completely reverted the decreased content in complex-II subunits. ANT increased in HE. HE presented normalized ventricular–arterial coupling (Ea) and BNP myocardial levels and significantly improved myocardial performance as evaluated by increased cardiac output and normalization of the Tei index vs. HS.

Conclusion

Data demonstrates that IHH and ET confer cardiac mitochondria with a more resistant phenotype although without visible addictive effects at least under basal conditions. It is suggested that the combination of both strategies, although not additive, results into improved cardiac function.     

Cardiac autonomic function in adolescents operated by arterial switch surgery

Background

Children with transposition of the great arteries, in whom an arterial switch operation (ASO) is performed, have been shown to have an increased incidence of sudden death, which may be due to cardiac autonomic imbalance and repolarisation instability. We hypothesised that i) cardiac norepinephrine (NE) kinetics and ii) arterial baroreflex sensitivity (BRS), reflecting sympathetic activity and vagal function respectively, are altered in this group.

Methods and results

17 children (15.8 ± 1.5 years of age) with ASO-surgery in the neonatal period were studied. 17 had cardiac BRS assessed by spontaneous fluctuations of systolic blood pressure and RR-interval, and repolarisation was measured as QT variability index. Matched healthy subjects were controls. Cardiac vagal function and repolarisation pattern were unchanged following ASO-surgery. At cardiac catheterisation, we infused tritiated NE in 8 of these children to examine total body and cardiac sympathetic function at baseline and following 5 min of adenosine infusion to induce reflex sympathetic activation. Blood was sampled simultaneously from the aorta and coronary sinus. Cardiac fractional extraction of ^[3H]NE was substantially lower in operated children, being 56 ± 10 vs. 82 ± 9% (p = 0.0001). Following i.v. adenosine in the operated group, NE total body spillover doubled vs. baseline (p < 0.002) and the coronary venous-arterial concentration gradient of ^[3H]dihydroxyphenylglycol increased 4-fold (p = 0.04).

Conclusions

Arterial switch operation performed neonatally appears to leave cardiac vagal function intact and, although cardiac sympathetic activation in response to adenosine occurs, cardiac neuronal NE reuptake is impaired. This may be pro-arrhythmic by reducing removal capacity of NE from the cardiac synaptic cleft.     

Changes of plasma norepinephrine and serum N-terminal pro-brain natriuretic peptide after exercise training predict survival in patients with heart failure

Background

Short-term changes of neurohormones can give important prognostic information in heart failure (HF) patients. In this study, we evaluate whether changes in plasma Norepinephrine (NE) and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) after exercise training predict cardiac mortality in HF patients.

Methods and results

We enrolled 221 HF patients (mean age 72.5 ± 10.2 year) followed-up for a mean period of 27.64 ± 10.7 months. All pts underwent a 3-month exercise training. Before training, clinical examination, echocardiography, peak VO2 determination, and blood draw for NT-proBNP and NE measurements were performed. Primary end-point was cardiac related mortality. Eighty-six-nine percent of patients were in NYHA class III, mean left ventricular ejection fraction (LVEF) was 32.5 ± 10.4%, and mean peak VO2 was 12.36 ± 1.45 ml/kg/min. At baseline, mean NT-proBNP was 2111.4 ± 1145.6 pg/ml and mean NE was 641.8 ± 215.3 pg/ml. One hundred-one subjects died for cardiac causes. Training was associated with a significant increase of peak VO2 and LVEF, whereas NE, NT-proBNP, and heart rate decreased. Multiple Cox proportional hazards regression analysis was performed using delta% values (post vs pre-training) of LVEF, heart rate, NE, and NT-proBNP along with baseline covariates, revealing delta value of NE as the strongest predictor of cardiac mortality. Noteworthy, training reduced NT-proBNP in both survivor and non-survivor patients, while a lack of reduction of NE was observed in non survivors.

Conclusions

In our HF population, short-term changes of NE after exercise training independently predicted long-term cardiac mortality.     

Regular exercise training reduces coronary restenosis after percutaneous coronary intervention in patients with acute myocardial infarction

Background

It is well known that cardiac rehabilitation (CR) including regular exercise training (ET) is cardioprotective with respect to clinical events in patients with acute myocardial infarction (AMI). However, it is not known whether the regular ET may affect coronary restenosis after percutaneous coronary intervention (PCI) with stenting in AMI. The aim of this study was to evaluate the effect of regular ET on a stented coronary segment and its association with inflammatory markers in AMI.

Methods

Consecutively 74 AMI patients who underwent PCI with implantation of a drug-eluting stent and 9 month follow-up angiography were included. Thirty seven patients who received CR with ET were assigned to the ET group. Another 37 patients who did not participate in ET, of similar age to those of participants, were assigned to the control group. At 9 months, angiographic restenosis measured as in-segment late luminal loss of the stented coronary artery was analyzed via quantitative coronary angiography using CAAS 5.9.

Results

There were no significant differences in baseline characteristics including age, sex, body mass index, smoking, DM, hypertension, lipid profile, use of statin, and complete blood cell between two groups. On 9 month follow-up angiography, late luminal loss per stent was significantly smaller in the ET group compared to the control group (0.14 ± 0.57 vs. 0.54 ± 0.88 mm, p = 0.02). Maximal oxygen consumption (VO₂max) significantly improved in the ET group after 9 months (27.9 ± 6.4 vs. 30.8 ± 5.2 mL/kg/min, p < 0.001). Increment in high density lipoprotein-cholesterol (HDL-C) was significantly larger in the ET group at 9 months (0.15 ± 0.12 vs. 0.04 ± 0.24 mg/dL, p = 0.03).

Conclusion

Regular ET contributes to a significant reduction in late luminal loss in the stented coronary segment in AMI patients. This effect was associated with increased exercise capacity and increased HDL-C.     

Thyroid hormone improves the mechanical performance of the post-infarcted diabetic myocardium: A response associated with up-regulation of Akt/mTOR and AMPK activation

Objective

Thyroid hormone (TH) is shown to be protective against cardiac and pancreatic injury. Thus, this study explored the potential effects of TH treatment on the functional status of the postinfarcted diabetic myocardium. Diabetic patients have worse prognosis after acute myocardial infarction (AMI).

Materials/Methods

AMI was induced by left coronary ligation in rats previously treated with 35 mg/kg streptozotocin (STZ), (DM-AMI). TH treatment was initiated at 2 weeks after AMI and continued for 6 weeks (DM-AMI + TH), while sham-operated animals served as control (DM-SHAM).

Results

TH treatment increased cardiac mass, improved wall stress and favorably changed cardiac geometry. TH significantly increased echocardiographic left ventricular ejection fraction (LVEF%): [54.2 (6.5) for DM-AMI + TH vs 37 (2.0) for DM-AMI, p < 0.05]. TH treatment resulted in significantly increased insulin and decreased glucose levels in serum. The ratios of phosphorylated (p)-Akt/total Akt and p-mTOR/total mTOR were increased 2.0 fold and 2.7 fold in DM-AMI + TH vs DM-AMI respectively, p < 0.05. Furthermore, the ratio of p-AMPK/total AMPK was found to be increased 1.6 fold in DM-AMI + TH vs DM-AMI, p < 0.05.

Conclusion

TH treatment improved the mechanical performance of the post-infarcted myocardium in rats with STZ-induced diabetes, an effect which was associated with Akt/mTOR and AMPK activation.     

Tandospirone reduces wasting and improves cardiac function in experimental cancer cachexia

Background

Cancer cachexia is thought to be the cause of > 20% of cancer related deaths. Symptoms of cancer cachexia patients include depression and anorexia significantly worsening their quality of life. Moreover, in rodent models of cancer cachexia atrophy of the heart has been shown to impair cardiac function. Here, we characterize the effects of the antidepressant and anxiolytic drug tandospirone on wasting, cardiac function and survival in experimental cancer cachexia.

Methods

The well-established Yoshida hepatoma rat model was used and tumor-bearing rats were treated with 1 mg/kg/d (LD), 10 mg/kg/d (HD) tandospirone or placebo. Weight, body composition (NMR), cardiac function (echocardiography), activity and food intake were assessed. Noradrenalin and cortisol were measured in plasma and caspase activity in skeletal muscle.

Results

Ten mg/kg/d tandospirone decreased the loss of body weight (p = 0.0003) compared to placebo animals, mainly due to preservation of muscle mass (p < 0.001), while 1 mg/kg/d tandospirone was not effective. Locomotor activity (p = 0.0007) and food intake (p = 0.0001) were increased by HD tandospirone. The weight (p = 0.0277) and function of heart (left ventricular mass, fractional shortening, stroke volume, ejection fraction, all p < 0.05) were significantly improved. In the HD tandospirone group, plasma levels of noradrenalin and cortisol were significantly reduced by 49% and 52%, respectively, which may have contributed to the lower caspase activity in the gastrocnemius muscle. Most importantly, HD tandospirone significantly improved survival compared to placebo rats (HR: 0.34; 95% CI: 0.13–0.86; p = 0.0495).

Conclusion

Tandospirone showed significant beneficial effects in the Yoshida hepatoma cancer cachexia model and should be further examined as a prospective drug for this syndrome.     

The frequency and severity of cardiac involvement in myotonic dystrophy type 2 (DM2): Long-term outcomes

Background

Frequency and severity of cardiac involvement in DM2 are still controversial. The aims of our study were to determine the frequency and progression of cardiac and muscle involvement in a relatively large cohort of patients with DM2 throughout Italy and Germany and to provide long-term outcomes in this disorder.

Methods

104 DM2 and 117 DM1 patients underwent baseline and follow-up assessments of, ECG, 24 h Holter monitoring, 2D echocardiography and electrophysiological study (EPS) when appropriate, and manual muscle strength testing (mean follow-up: 7.4 ± 4.1 for DM2 and 5.7 ± 4 years for DM1).

Results

Overall, 10% of DM2 patients vs 31% of DM1 patients had PR ≥ 200 ms and 17% of DM2 patients vs 48% of DM1 patients had QRSD ≥ 100 ms. Six patients with DM2 vs 28 patients with DM1 required PM/ICD implantations. DM2 patients were stronger than DM1 patients at baseline, but muscle strength worsened significantly over time (p < 0.0001), just as in DM1, although at a slower annual rate.

Conclusion

Our data demonstrate that the frequency and severity of cardiac involvement and of muscle weakness are reduced in DM2 compared to DM1 and that progression is slower and less severe. Nonetheless, careful cardiac evaluation is recommended in this patient population to identify patients at risk for potential major cardiac arrhythmias.     

Predictive value of brachial–ankle pulse wave velocity for long-term clinical outcomes after percutaneous coronary intervention in a Korean cohort

Objective

The aim of this study was to determine the associations of brachial–ankle pulse wave velocity (baPWV), high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP) with the development of adverse outcomes after percutaneous coronary intervention (PCI).

Methods

The baPWV, hs-cTnT and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary endpoint was cardiac death.

Results

There were 21 events of cardiac death during a mean of 25.8 months of follow-up. When the baPWV cut-off level was set to 1672 cm/s using the receiver operating characteristic curve, the sensitivity was 85.7% and the specificity was 60.1% for differentiating between the group with cardiac death and the group without cardiac death. Kaplan–Meier analysis revealed that the higher baPWV group (≥ 1672 cm/s) had a significantly higher cardiac death rate than the lower baPWV group (< 1672 cm/s) (11.4% vs. 1.4%, log-rank: P < 0.0001). This value was more useful in patients with myocardial injury (hs-cTnT ≥ 0.1 ng/mL) or heart failure (NT-proBNP ≥ 450 pg/mL).

Conclusions

The results of this study show that high baPWV is a predictive marker for cardiac death after PCI.     

Cardiovascular magnetic resonance imaging in asymptomatic patients with connective tissue disease and recent onset left bundle branch block

Background–aim

Recent LBBB in connective tissue diseases (CTDs) is challenging, due to high incidence of underlying pathology that may remain undetected, due to limitations of imaging tests. We hypothesized that cardiovascular magnetic resonance (CMR) may be of diagnostic value in CTDs with recent LBBB and normal echocardiogram.

Patients–methods

26 CTDs, aged 32 ± 7 yrs (19 F) and 26 controls without CTDs, aged 60 ± 4 yrs (10 F) with recent LBBB and normal echo were evaluated by CMR. The CTDs included 6 sarcoidosis (SRC), 4 systemic sclerosis (SSc), 6 systemic lupus erythematosus (SLE), 6 rheumatoid arthritis (RA) and 4 inflammatory myopathies (IM). CMR was performed by 1.5 T. LVEF, T2 ratio (oedema imaging) and late gadolinium enhancement (LGE) (fibrosis imaging) were evaluated. Acute and chronic lesions were characterised by T2 > 2 and positive LGE and T2 < 2 and positive LGE, respectively. According to LGE, lesions were characterised as diffuse subendo-, subepicardial/intramural not following and subendocardial/transmural following the distribution of coronaries, indicative of vasculitis, myocarditis and myocardial infarction, respectively.

Results

CTDs were younger (p < 0.001), with higher incidence of abnormal CMR (42.31 vs 30.77%, p = NS), including dilated cardiomyopathy (11.54%), diffuse subendocardial fibrosis (11.54%), myocardial infarction (7.69%) and acute myocarditis (11.54%) vs dilated cardiomyopathy (19.23%), myocardial infarction (7.69%) and acute myocarditis (3.85%), detected in non-CTDs.

Conclusions

In CTDs with recent LBBB, CMR documented acute and chronic cardiac pathology, particularly myocarditis. CMR should be considered as an adjunct to conventional diagnostic workup in both patient groups, more so in CTDs.     

Cardiac cachexia is associated with right ventricular failure and liver dysfunction

Background

The mechanisms involved in cardiac cachexia remain poorly understood. We examined the association of right ventricular (RV) and hepatic dysfunction with cardiac cachexia.

Methods

We prospectively enrolled 118 patients with left ventricular ejection fraction (LVEF) ≤ 40%, which were subgrouped as follows: New York Heart Association (NYHA) class II (n = 59), NYHA class III without cachexia (n = 41) and NYHA class III with cachexia (n = 18). All patients underwent blood collection, echocardiography and exercise testing.

Results

Reduced systolic RV function (tricuspid annular plane systolic excursion [TAPSE] ≤ 15 mm), was present in 80% of cachectic patients. When comparing NYHA class II patients vs. non-cachectic and cachectic NYHA class III patients we found a stepwise decrease in systolic RV function (TAPSE 19 [16–23] vs. 16 [13–19] vs. 14 [9–15] mm, respectively; p < 0.001) and an increase in right atrial pressure (RAP; > 10 mm Hg: 6.8 vs. 27.5 vs. 75.0%, respectively; p < 0.001), indicating a higher degree of congestive right HF in cardiac cachexia. Systolic and diastolic function of the left ventricle did not differ between non-cachectic and cachectic patients in NYHA class III. Serum alkaline phosphatase and direct bilirubin correlated with TAPSE and RAP, and were highest in cachectic patients (all p ≤ 0.002), suggesting cholestatic dysfunction due to liver congestion. In multivariable regression analysis, RV dysfunction, cholestatic liver parameters and albumin were independently associated with the presence of cardiac cachexia.

Conclusion

Patients with cardiac cachexia display a more pronounced degree of right HF, cholestatic liver dysfunction and hypoalbuminemia compared to non-cachectic patients of similar LVEF and NYHA class.     

HMG-CoA reductase inhibition prior reperfusion improves reparative fibrosis post-myocardial infarction in a preclinical experimental model

Background

Studies in patients support a beneficial effect of statin treatment early after acute coronary syndrome and/or prior percutaneous coronary intervention. However, statin effect during total occlusion remains unknown.

Objectives

To investigate whether infusion of activated simvastatin during ischemia and prior reperfusion and oral administration thereafter confers cardioprotection and improves cardiac healing in a preclinical model of myocardial infarction.

Methods

Pigs (n = 24) fed a 10 day Western-type diet underwent a 90 min coronary-balloon occlusion (MI) being randomized to a single intravenous infusion of active β-hydroxy acid derivative of simvastatin (β-OH-S; 0.3 mg/kg) 15 min prior to reperfusion or vehicle. Animals were either sacrificed 2.5 h post-reperfusion or kept under the same regime ± simvastatin (p.o., 20 mg/day) for 3 weeks. Jeopardized and remote myocardium was obtained for molecular/histological studies. Echocardiography was assessed.

Results

β-OH-S infusion prior to reperfusion reduced coronary and cardiac oxidative DNA-damage, diminished neutrophil infiltration at the site of ischemia, preserved mitochondrial membrane potential and reduced apoptosis in the ischemic myocardium (lower mRNA levels of Fas, casp8, p53, and casp3 and mitochondrial-p-Bcl2; and reduced TUNEL and active caspase-3; p < 0.05 vs. vehicle/control). This treatment regime attenuated reperfusion-related arrhythmias and stunning leading to a 40% increased myocardial salvage (p < 0.05 vs. vehicle/control). 3 weeks post-MI simvastatin-treated animals showed P-PKCε increase, lower intramyocardial lipotoxicity, TβRII/Smad2/3 signaling restoration and subsequent myofibroblast differentiation and collagen-fibril formation in the evolving scar (p < 0.05 vs. control). Simvastatin suppressed cardiac RhoA mobilization and triggered Akt/eNOS signaling.

Conclusions

Acute HMG-CoA-reductase inhibition during total ischemia and prior reperfusion limits reperfusion injury and prolonged oral simvastatin treatment thereafter improves cardiac healing post-MI.     

Resistance training improves cardiac output,exercise capacity and tolerance to positive airway pressure in Fontan physiology

Background

Subjects with Fontan-type circulation have no sub-pulmonary ventricle and thus depend exquisitely on the respiratory bellows and peripheral muscle pump for cardiac filling. We hypothesised that resistance training to augment the peripheral muscle pump might improve cardiac filling, reduce inspiratory-dependence of IVC return to the heart and thus improve exercise capacity and cardiac output on constant positive airway pressure (CPAP).

Methods

Eleven Fontan subjects (32 +/− 2 years, mean +/− SEM) had cardiac magnetic resonance imaging (MRI) and exercise testing (CPET); six underwent 20 weeks of high-intensity resistance training; others were non-exercising controls. After training, CPET was repeated. Four trainers had MRI with real-time flow measurement at rest, exercise and on CPAP in the trained state and following a 12-month detrain.

Results

In the trained state, muscle strength increased by 43% (p = 0.002), as did total muscle mass (by 1.94 kg, p = 0.003) and peak VO₂ (by 183 ml/min, p = 0.02). After detraining, calf muscle mass and peak workload had fallen significantly (p < 0.03 for both) as did peak VO₂ (2.72 vs. 2.18 l/min, p < 0.001) and oxygen pulse, a surrogate for SV (16% lower, p = 0.005). Furthermore after detraining, SV on MRI decreased at rest (by 11 ml, p = 0.01) and during moderate-intensity exercise (by 16 ml, p = 0.04); inspiratory-dependent IVC blood return during exercise was 40% higher (p = 0.02). On CPAP, cardiac output was lower in the detrained state (101 vs. 77 ml/s, p = 0.03).

Conclusions

Resistance muscle training improves muscle mass, strength and is associated with improved cardiac filling, stroke volume, exercise capacity and cardiac output on CPAP, in adults with Fontan-type circulation.     

Abnormal heart rate recovery on exercise in ankylosing spondylitis

Objectives

This study evaluated the heart rate recovery response in ankylosing spondylitis (AS) patients and control subjects.

Background

Delayed heart rate recovery after exercise reflects AD and independently predicts adverse cardiac outcome.

Methods

Fifty-one patients with AS and 50 age- and matched controls received electrocardiography, echocardiography, and treadmill exercise testing. The heart rate recovery (HRR) index was calculated as the reduction in heart rate from the rate at peak exercise to the rate at the 1st (HRR₁), 2nd (HRR₂), 3rd (HRR₃) and 5th (HRR₅) minute after the cessation of exercise stress testing.

Results

There were significant differences in HRR₁ and HRR₂ indices between patients and controls (24.8 ± 12.1 vs 34.9 ± 11.0; p < 0.001 and 41.2 ± 14.2 vs 54.3 ± 11.8; p < 0.001, beats/min, respectively). Similarly, HRR₃ and HRR₅ indices were lower in patients than controls (51.3 ± 15.1 vs 65.2 ± 14.0; p < 0.001 and 61.0 ± 14.2 vs 76.1 ± 14.8; p < 0.001). In addition, exercise capacity was markedly lower (8.1 ± 2.0 vs 10.5 ± 2.5 METs; p < 0.001) in AS than controls.

Conclusion

The HRR index is impaired in AS patients, implying the occurrence of autonomic dysfunction even without active joint disease or frank cardiac involvement.     

Prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction and non-significant coronary artery disease

Background and purpose

We aimed to study the prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction (STEMI) and non-significant coronary artery disease (CAD).

Methods

From January to October 2012 we consecutively included patients admitted with suspected STEMI and non-significant CAD (coronary artery stenosis diameter < 50%). Patients were diagnosed with acute cardiac disorder in the presence of elevated cardiac biomarkers (troponin T > 50 ng/l or creatine kinase MB > 4 μg/l) or dynamic ECG changes (ST-segment changes or T-wave inversion).

Results

Of the 871 patients admitted with suspected STEMI, 11% (n = 95) had non-significant CAD. Of these, 67% (n = 64) had elevated cardiac biomarkers or dynamic ECG changes and were accordingly diagnosed with acute cardiac disorders. In the remaining 33% (n = 31) of patients, cardiac biomarkers were normal and ECG changes remained stationary.

Conclusions

Acute cardiac disorders were diagnosed in two thirds of patients with suspected STEMI and non-significant CAD.     

Adiponectin promotes the migration of circulating angiogenic cells through p38-mediated induction of the CXCR4 receptor

Aims

Adiponectin (adipo) and exercise training (ET) contribute to the maintenance of a normal vascular tone by influencing vascular NO bioavailability and concentration and function of circulating angiogenic cells (CAC). The molecular mechanisms are only partially understood. Aim of the present study was to elucidate the effects of adipo on CAC migration and the underlying signaling pathways. Furthermore, the impact of ET on adiponectin-mediated CAC migration was investigated.

Methods and results

CACs were isolated from peripheral blood and exposed to different adipo concentrations. Adipo (5 μg/ml) enhanced the ability of CACs to migrate following an SDF-1 gradient by 345%. This was associated with a significant increase in CXCR4 expression on the surface of CACs as compared to control (10.1 ± 1.5 vs. 33.2 ± 4.5% CXCR4 positive cells, p < 0.05). Adiponectin-induced CAC migration and CXCR4-upregulation were mediated through adipo-receptor 1 (AdipoR1) and blocked by an inhibitor of PI3-kinase, p38MAP kinase and NFκb. Adipo-stimulated migration of CACs, CXCR4 expression and p38MAPK-activation is impaired in patients with coronary artery disease (CAD). ET over 4 weeks partially corrects adiponectin-stimulated CAC migration and CXCR4 expression in patients with CAD (n = 10). No change was observed in the control group (n = 10).

Conclusion

Adipo improves the migratory capacity of CACs in response to SDF1, partially through an upregulation of CXCR4. This is mediated through a pathway that involves binding of adipo to the AdipoR1 and subsequent PI3kinase/p38MAPK/ NFκb activation. In addition ET corrects the adiponectin responsiveness of CACs, and thereby might promote endogenous repair of damaged endothelium.     

Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: A 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens

Background

Selenium and coenzyme Q10 are essential for the cell. Low cardiac contents of selenium and coenzyme Q10 have been shown in patients with cardiomyopathy, but inconsistent results are published on the effect of supplementation of the two components separately. A vital relationship exists between the two substances to obtain optimal function of the cell. However, reports on combined supplements are lacking.

Methods

A 5-year prospective randomized double-blind placebo-controlled trial among Swedish citizens aged 70 to 88 was performed in 443 participants given combined supplementation of selenium and coenzyme Q10 or a placebo. Clinical examinations, echocardiography and biomarker measurements were performed. Participants were monitored every 6th month throughout the intervention.The cardiac biomarker N-terminal proBNP (NT-proBNP) and echocardiographic changes were monitored and mortalities were registered. End-points of mortality were evaluated by Kaplan–Meier plots and Cox proportional hazard ratios were adjusted for potential confounding factors. Intention-to-treat and per-protocol analyses were applied.

Results

During a follow up time of 5.2 years a significant reduction of cardiovascular mortality was found in the active treatment group vs. the placebo group (5.9% vs. 12.6%; P = 0.015). NT-proBNP levels were significantly lower in the active group compared with the placebo group (mean values: 214 ng/L vs. 302 ng/L at 48 months; P = 0.014). In echocardiography a significant better cardiac function score was found in the active supplementation compared to the placebo group (P = 0.03).

Conclusion

Long-term supplementation of selenium/coenzyme Q10 reduces cardiovascular mortality. The positive effects could also be seen in NT-proBNP levels and on echocardiography.     

Preoperative renal dysfunction and clinical outcomes of cardiac surgery in octogenarians

Background

The proportion of elderly individuals is growing and the prevalence of chronic kidney disease (CKD) among elderly people undergoing cardiac surgery is increasing constantly. The aim of this study was to determine the influence of different degrees of preoperative renal dysfunction on postoperative outcomes in patients older than 80 years of age.

Methods

This is an observational study that included adult patients undergoing cardiac surgery in which data were collected prospectively. Patients were divided into groups according to their preoperative plasma creatinine and eGFR levels.

Results

From February 1997 to January 2010, 318 octogenarians underwent cardiac surgery. Of these, 140 patients (44%) had abnormal preoperative creatinine levels. A significantly higher incidence of postoperative sepsis (4% vs. 17%, p 0.03), CVA (1% vs. 6%, p 0.03), and prolonged hospital stay (16 ± 13 vs. 20 ± 16 days, p 0.04) were detected in patients with preoperative kidney dysfunction. Subgroup analysis revealed that preoperative CKD stage IV (eGFR 15–30 ml/min/1.73 m²) but not CKD stage III (eGFR 30–60 ml/min/1.73 m²) and preoperative creatinine > 1.8 mg/dl were independently associated with increased incidence of postoperative CVA (OR 4; 95% CI 0.07–0. 8, p = 0.05 for eGFR, and OR 7.8; 95% CI 1.2–60, p = 0.003 for creatinine). However, no significant increment in postoperative mortality with decreasing eGFR or increasing preoperative creatinine was demonstrated.

Conclusions

A substantial increase in the risk of postoperative CVA and sepsis, but not mortality, was demonstrated in octogenarians with advanced but not mild degrees of preoperative CKD. Compared to younger patients, a high burden of comorbidities in octogenarians may have a greater influence on outcomes post cardiac surgery than impaired renal function. Our data may provide a rationale for modified risk stratification in octogenarian candidates for cardiac surgery.     

Long-term outcome of the unrestricted use of everolimus-eluting stents compared to sirolimus-eluting stents and paclitaxel-eluting stents in diabetic patients: The Bern–Rotterdam diabetes cohort study

Background

Newer generation everolimus-eluting stents (EES) improve clinical outcome compared to early generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). We investigated whether the advantage in safety and efficacy also holds among the high-risk population of diabetic patients during long-term follow-up.

Methods

Between 2002 and 2009, a total of 1963 consecutive diabetic patients treated with the unrestricted use of EES (n = 804), SES (n = 612) and PES (n = 547) were followed throughout three years for the occurrence of cardiac events at two academic institutions. The primary end point was the occurrence of definite stent thrombosis.

Results

The primary outcome occurred in 1.0% of EES, 3.7% of SES and 3.8% of PES treated patients ([EES vs. SES] adjusted HR = 0.58, 95% CI 0.39–0.88; [EES vs. PES] adjusted HR = 0.29, 95% CI 0.13–0.67). Similarly, patients treated with EES had a lower risk of target-lesion revascularization (TLR) compared to patients treated with SES and PES ([EES vs. SES], 5.6% vs. 11.5%, adjusted HR = 0.68, 95% CI: 0.55–0.83; [EES vs. PES], 5.6% vs. 11.3%, adjusted HR = 0.51, 95% CI: 0.33–0.77). There were no differences in other safety end points, such as all-cause mortality, cardiac mortality, myocardial infarction (MI) and MACE.

Conclusion

In diabetic patients, the unrestricted use of EES appears to be associated with improved outcomes, specifically a significant decrease in the need for TLR and ST compared to early generation SES and PES throughout 3-year follow-up.     

Long-term outcomes of patients receiving zotarolimus-eluting stents in ST elevation myocardial infarction,non-ST elevation acute coronary syndrome,and stable angina: Data from the Resolute program

Background

Outcome data are limited in patients with ST-segment elevation acute myocardial infarction (STEMI) or other acute coronary syndromes (ACSs) who receive a drug-eluting stent (DES). Data suggest that first generation DES is associated with an increased risk of stent thrombosis when used in STEMI. Whether this observation persists with newer generation DES is unknown. The study objective was to analyze the two-year safety and effectiveness of Resolute™ zotarolimus-eluting stents (R-ZESs) implanted for STEMI, ACS without ST segment elevation (non-STEACS), and stable angina (SA).

Methods

Data from the Resolute program (Resolute All Comers and Resolute International) were pooled and patients with R-ZES implantation were categorized by indication: STEMI (n = 335), non-STEACS (n = 1416), and SA (n = 1260).

Results

Mean age was 59.8 ± 11.3 years (STEMI), 63.8 ± 11.6 (non-STEACS), and 64.9 ± 10.1 (SA). Fewer STEMI patients had diabetes (19.1% vs. 28.5% vs. 29.2%; P < 0.001), prior MI (11.3% vs. 27.2% vs. 29.4%; P < 0.001), or previous revascularization (11.3% vs. 27.9% vs. 37.6%; P < 0.001). Two-year definite/probable stent thrombosis occurred in 2.4% (STEMI), 1.2% (non-STEACS) and 1.1% (SA) of patients with late/very late stent thrombosis (days 31–720) rates of 0.6% (STEMI and non-STEACS) and 0.4% (SA) (P = NS). The two-year mortality rate was 2.1% (STEMI), 4.8% (non-STEACS) and 3.7% (SA) (P = NS). Death or target vessel re-infarction occurred in 3.9% (STEMI), 8.7% (non-STEACS) and 7.3% (SA) (P = 0.012).

Conclusion

R-ZES in STEMI and in other clinical presentations is effective and safe. Long term outcomes are favorable with an extremely rare incidence of late and very late stent thrombosis following R-ZES implantation across indications.