Functional electrical stimulation of peripheral muscles improves endothelial function and clinical and emotional status in heart failure patients with preserved left ventricular ejection fraction.

BACKGROUND: Functional electrical stimulation (FES) improves exercise capacity, quality of life, emotional stress, and endothelial function in chronic heart failure with impaired systolic function. We sought to investigate the effects of FES on the above parameters in patients with preserved ejection fraction (HFpEF). METHODS: Thirty HFpEF patients, 18 female and 12 male, aged 69 ± 8 years, in New York Heart Association class II or III and with mean ejection fraction 63% ± 6%, were randomly (1:1) assigned to a 6-week FES program or placebo. Assessment was performed at baseline and after completion of training protocol and included 6-minute walked distance, quality of life (Kansas City Cardiomyopathy Questionnaire and Minnesota Living with Heart Failure Questionnaire), depressive symptoms (Beck Depression Inventory and Zung self-rated depression scores), B-type natriuretic peptide, endothelial function (flow-mediated dilatation), and left ventricular diastolic function. RESULTS: A significant improvement in 6-minute walked distance (F = 21.61, P = .001), Kansas City Cardiomyopathy Questionnaire summary (F = 8.68, P = .006), Minnesota Living with Heart Failure Questionnaire (F = 6.43, P = .017), Beck Depression Inventory (F = 6.66, P = .015), Zung (F = 6.25, P = .019), and flow-mediated dilatation diameter (F = 11.98, P = .002) was observed in the FES group compared with placebo group; B-type natriuretic peptide also declined but not significantly (F = 0.249, P = .622), and there was a tendency toward lower mitral E/e' wave ratio (F = 3.066, P = .091). CONCLUSION: As in heart failure and reduced left ventricular ejection fraction, FES also improves exercise capacity, quality of life, emotional status, and endothelial function in HFpEF. Given the lack of effective evidence-based therapies in these patients, FES warrants further investigation.

Colchicine treatment for the prevention of bare-metal stent restenosis in diabetic patients.

OBJECTIVES: This study sought to test the hypothesis that colchicine treatment after percutaneous coronary intervention (PCI) can lead to a decrease in in-stent restenosis (ISR). BACKGROUND: ISR rates are particularly high in certain patient subsets, including diabetic patients, especially when a bare-metal stent (BMS) is used. Pharmacological interventions to decrease ISR could be of clinical relevance. METHODS: Diabetic patients with contraindication to a drug-eluting stent, undergoing PCI with a BMS, were randomized to receive colchicine 0.5 mg twice daily or placebo for 6 months. Restenosis and neointima formation were studied with angiography and intravascular ultrasound 6 months after the index PCI. RESULTS: A total of 196 patients (63.6 ± 7.0 years of age, 128 male) were available for analysis. The angiographic ISR rate was 16% in the colchicine group and 33% in the control group (p = 0.007; odds ratio: 0.38, 95% confidence interval: 0.18 to 0.79). The number needed to treat to avoid 1 case of angiographic ISR was 6 (95% confidence interval: 3.4 to 18.7). The results were similar for IVUS-defined ISR (odds ratio: 0.42; 95% confidence interval: 0.22 to 0.81; number needed to treat = 5). Lumen area loss was 1.6 mm(2) (interquartile range: 1.0 to 2.9 mm(2)) in colchicine-treated patients and 2.9 mm(2) (interquartile range: 1.4 to 4.8 mm(2)) in the control group (p = 0.002). Treatment-related adverse events were largely limited to gastrointestinal symptoms. CONCLUSIONS: Colchicine is associated with less neointimal hyperplasia and a decreased ISR rate when administered to diabetic patients after PCI with a BMS. This observation may prove useful in patients undergoing PCI in whom implantation of a drug-eluting stent is contraindicated or undesirable.

Colchicine for prevention of early atrial fibrillation recurrence after pulmonary vein isolation: a randomized controlled study.

OBJECTIVES: The purpose of the present study was to test the potential of colchicine, an agent with potent anti-inflammatory action, to reduce atrial fibrillation (AF) recurrence after pulmonary vein isolation in patients with paroxysmal AF. BACKGROUND: Proinflammatory processes induced by AF ablation therapy have been implicated in postablation arrhythmia recurrence. METHODS: Patients with paroxysmal AF who received radiofrequency ablation treatment were randomized to a 3-month course of colchicine 0.5 mg twice daily or placebo. C-reactive protein (CRP) and interleukin (IL)-6 levels were measured on day 1 and on day 4 of treatment. RESULTS: In the 3-month follow-up, recurrence of AF was observed in 27 (33.5%) of 80 patients of the placebo group versus 13 (16%) of 81 patients who received colchicine (odds ratio: 0.38, 95% confidence interval: 0.18 to 0.80). Gastrointestinal side-effects were the most common symptom among patients receiving active treatment. Diarrhea was reported in 7 patients in the colchicine group (8.6%) versus 1 in the placebo group (1.3%, p = 0.03). Colchicine led to higher reductions in CRP and IL-6 levels: the median difference of CRP and IL-6 levels between days 4 and 1 was -0.46 mg/l (interquartile range: -0.78 to 0.08 mg/l) and -0.10 mg/l (-0.30 to 0.10 pg/ml), respectively, in the placebo group versus -1.18 mg/l (-2.35 to -0.46 mg/l) and -0.50 pg/ml (-1.15 to -0.10 pg/ml) in the colchicine group (p < 0.01 for both comparisons). CONCLUSIONS: Colchicine is an effective and safe treatment for prevention of early AF recurrences after pulmonary vein isolation in the absence of antiarrhythmic drug treatment. This effect seems to be associated strongly with a significant decrease in inflammatory mediators, including IL-6 and CRP.

Association of soluble tumour necrosis factor-related apoptosis-inducing ligand levels with coronary plaque burden and composition.

BACKGROUND: Evidence shows that the soluble tumour necrosis factor-related apoptosis-inducing ligand (sTRAIL) may play a protective role against atherosclerosis. This study sought to investigate the potential association of sTRAIL levels with intravascular ultrasound (IVUS) and virtual histology characteristics of coronary plaques. METHODS: Patients with stable angina or positive for ischaemia non-invasive test were submitted to left cardiac catheterisation. Coronary blood samples were collected and sTRAIL was measured. Coronary arteries with at least one 50% or greater stenosis were studied with IVUS. RESULTS: 56 coronary arteries were studied with significant coronary artery disease. Plaque volume per unit of arterial length was 63 ± 5 mm(3)/cm in arteries at the lower quartile of sTRAIL concentration versus 30 ± 4 mm(3)/cm at the upper quartile (p<0.001; 95% CI of the difference 19.7 to 46.3 mm(3)/cm). The necrotic core and fibrofatty content of atheromatous plaques were inversely associated with sTRAIL (p<0.001). Thin-cap fibroatheromas (TCFA) were discovered in 16 of the 56 arterial segments. The mean sTRAIL concentration in these segments was 56.8 ± 7.5 pg/ml versus 99.9 ± 5.7 pg/ml in those without TCFA (p<0.001; 95% CI of the difference 22.7 to 63.5 pg/ml). The association of sTRAIL with the presence of TCFA remained significant in the logistic multivariate analysis (p=0.009). CONCLUSION: According to the findings of the present study, in addition to coronary artery disease burden, the sTRAIL concentration is also related to the composition of atheromatous plaques. A significant association is demonstrated between low sTRAIL levels and the presence of TCFA, the IVUS-virtual histology prototype of the vulnerable plaque.

Estimation of atrial fibrillation recency of onset and safety of cardioversion using NTproBNP levels in patients with unknown time of onset.

OBJECTIVE: As shown previously in patients with new-onset atrial fibrillation (AF) without symptoms or signs of heart failure, N-terminal pro-brain natriuretic peptide (NTproBNP) increases rapidly, reaching a maximum within 24-36 h, and then decreases even if AF persists. A study was undertaken to use NTproBNP measurements in patients with AF of unknown time of onset to identify patients with presumed recent onset of the arrhythmia. DESIGN: Two-group open cross-sectional study. SETTING: Hospitalised patients in cardiology departments of four hospitals. PATIENTS: Patients presenting with AF of unknown onset and no signs or symptoms of heart failure were separated into two groups: group A with NTproBNP above the cut-off level and group B with a low NTproBNP level. INTERVENTIONS: No therapeutic intervention. All patients underwent transoesophageal echocardiography (TEE). MAIN OUTCOME MEASURES: Presence of left atrial thrombus on TEE. RESULTS: In group A (N=43) only two patients (4.7%) were found to have an atrial thrombus on TEE (negative predictive value of raised NTproBNP levels 95.3%) compared with 13 of 43 patients in group B (30.2%; p=0.002). Patients with a higher CHA(2)DS(2)VASc score (p=0.002) and a larger left atrium (p<0.001) were more likely to have an atrial thrombus. In the multivariate analysis, NTproBNP below the cut-off level was the most powerful predictor of the presence of thrombus (OR 25.0; p=0.016). CONCLUSION: The reported strong correlation between raised NTproBNP levels and the absence of atrial thrombi on TEE suggests that the short-term increase in NTproBNP levels after AF onset might be used to assess the age of the arrhythmia and thus the safety of cardioversion in patients with AF of unknown onset and no heart failure.

Radial artery flow-mediated dilation predicts arterial spasm during transradial coronary interventions.

BACKGROUND: Transradial coronary catheterization has emerged over the last years as a favorable catheterization practice, based on evidence that it is associated with less vascular complications and shorter hospital stays. However, access site crossover appears to be more frequent when the initial route is the transradial one, one of the main reasons being arterial spasm. We hypothesized that radial flow-mediated dilation (FMD) measurements could be used as a preprocedural method to assess the likelihood of arterial spasm. METHODS: The study population consisted of patients scheduled for transradial diagnostic catheterization in whom ad hoc percutaneous coronary intervention (PCI) was performed. FMD was measured 1-2 days before PCI. The primary endpoint of the study was operator-defined (operators were blinded as to the FMD results) radial artery spasm. RESULTS: A total of 172 patients (110 male, age 65.3 ± 9) were included. Radial artery spasm was recorded in 13 patients (7.6%). FMD showed a very significant univariate association with the occurrence of spasm (P < 0.001) and was the most important predictor of spasm in the multivariate logistic regression analysis (beta -3.15; P < 0.001), followed by baseline radial artery diameter (P = 0.04), the number of catheters used (P = 0.049) and the administered volume of contrast medium (P = 0.017). CONCLUSION: Preprocedural FMD is a significant predictor of arterial spasm before elective transradial PCI. It is a low cost, safe, and feasible noninvasive modality, whose results might be taken into account when deciding on the vascular access route for an elective procedure, the size of sheaths or catheters to be used or the intensity of antispasm medication.

Comparison of muscle functional electrical stimulation to conventional bicycle exercise on endothelium and functional status indices in patients with heart failure.

The aim of this prospective, open-label, cohort study was to compare the effect of muscle functional electrical stimulation (FES) on endothelial function to that of conventional bicycle training. Eligible patients were those with New York Heart Association class II or III heart failure symptoms and ejection fractions ≤ 0.35. Two physical conditioning programs were delivered: FES of the muscles of the lower limbs and bicycle training, each lasting for 6 weeks, with a 6-week washout period between them. Brachial artery flow-mediated dilation (FMD) and other parameters were assessed before and after FES and the bicycle training program. FES resulted in a significant improvement in FMD, which increased from 5.9 ± 0.5% to 7.7 ± 0.5% (95% confidence interval for the difference 1.5% to 2.3%, p < 0.001). Bicycle training also resulted in a substantial improvement of endothelial function. FMD increased from 6.2 ± 0.4% to 9.2 ± 0.4% (95% confidence interval for the difference 2.5% to 3.5%, p < 0.001). FES was associated with a 41% relative increase in FMD, compared to 57% with bicycle exercise (95% confidence interval for the difference between the relative changes 1.2% to 30.5%, p = 0.034). This resulted in attaining a significantly higher FMD value after bicycle training compared to FES (9.2 ± 0.4% vs 7.7 ± 0.5%, p < 0.001). In conclusion, the effect of muscle FES in patients with heart failure on endothelial function, although not equivalent to that of conventional exercise, is substantial. Muscle FES protocols may prove very useful in the treatment of patients with heart failure who cannot or will not adhere to conventional exercise programs.

Differential effect of biventricular and right ventricular DDD pacing on coronary flow reserve in patients with ischemic cardiomyopathy.

UNLABELLED: CRT and Coronary Flow Reserve. BACKGROUND: Cardiac resynchronization therapy (CRT) has become a mainstay in heart failure management. There are also indications that upgrading of existing pacemakers to CRT systems may be of benefit. The aim of this study was to assess the effect of biventricular (BiV), compared with right ventricular (RV), pacing, on coronary flow reserve (CFR), in patients with ischemic cardiomyopathy. METHODS AND RESULTS: From our database of heart failure patients implanted with BiV pacemakers, 20 patients (10 responders and 10 non-responders to CRT) were randomly selected. Left anterior descending artery coronary flow reserve was measured invasively, under BiV and RV pacing, using intracoronary adenosine to induce hyperemia. In all the 20 patients, there was a significant difference in the pairwise comparison between CFR recorded during BiV and RV pacing (mean difference 0.15, 95% confidence interval 0.07-0.23, P = 0.001). When comparing responders to non-responders, there was a significant difference as to the effect of BiV, compared with RV, pacing on CFR: mean difference (BiV minus RV CFR) was 0.26 ± 0.06 (95% confidence interval 0.13-0.39; P = 0.002), while in non-responders the difference was 0.04 ± 0.03 (95% confidence interval -0.02 to 0.10; P = 0.168). CONCLUSION: BiV pacing is overall associated to higher CFR, compared with RV DDD pacing. This difference is almost exclusively attributable to the beneficial effect of CRT on coronary flow reserve in CRT-responders. This effect may contribute to the beneficial action of resynchronization in the failing heart and can be viewed in the context of reports of the usefulness of upgrading RV pacemakers to CRT systems.

Cardioprotective role of remote ischemic periconditioning in primary percutaneous coronary intervention: enhancement by opioid action.

OBJECTIVES: We sought to determine the potential of remote ischemic periconditioning (RIPC), and its combination with morphine, to reduce reperfusion injury in primary percutaneous coronary interventions. BACKGROUND: Remote ischemic post-conditioning is implemented by applying cycles of ischemia and reperfusion on a remote organ, which result in release of circulating factors inducing the effects of post-conditioning on the myocardium. METHODS: A total of 96 patients (59 men) were enrolled. The patients were randomized to groups as follows: 33 to each treatment group (Group A: RIPC; Group B: RIPC and morphine) and 30 to the control group (Group C). Measures of efficacy were achievement of full ST-segment resolution (primary), and reduction of ST-segment deviation score and peak troponin I during hospitalization. RESULTS: A higher proportion of patients in Groups A (73%) and B (82%) achieved full ST-segment resolution after percutaneous coronary intervention, compared with control patients (53%) (p = 0.045). Peak troponin I was lowest in Group B, 103.3 +/- 13.3 ng/ml, in comparison to peak levels in Group A, 166.0 +/- 28.0 ng/ml, and the control group, 255.5 +/- 35.5 ng/ml (p = 0.0006). ST-segment deviation resolution was 87.3 +/- 2.7% in Group B, compared with 69.9 +/- 5.1% in Group A and 53.2 +/- 6.4% in the control group (p = 0.00002). In paired comparisons between groups, Group B did better than the control group in terms of both ST-segment reduction (p = 0.0001) and peak troponin I (p = 0.004), whereas Group A differences from the control group did not achieve statistical significance (p = 0.054 and p = 0.062, respectively). CONCLUSIONS: These findings demonstrate a cardioprotective effect of RIPC and morphine during primary percutaneous coronary intervention for the prevention of reperfusion injury. This is in agreement with observations that the beneficial effect of RIPC is inhibited by the opioid receptor blocker naloxone.

Effect of quinapril on in-stent restenosis and relation to plasma apoptosis signaling molecules.

Angiotensin-converting enzyme inhibitors have been reported to inhibit in-stent restenosis. To assess the effect of angiotensin-converting enzyme inhibition on in-stent restenosis and its relation to apoptosis, 86 patients with chronic coronary artery disease who required stent implantation in the left anterior descending coronary artery or a major diagonal branch were studied. Patients were randomized to receive quinapril 40 mg/day orally (n = 43) or a placebo (n = 43). Drug therapy was initiated 1 week before initial stenting and continued for 6 months. Plasma levels of the apoptotic signaling molecules soluble Fas and soluble Fas ligand obtained from blood drawn from the left anterior descending coronary artery were measured just before initial stenting and 6 months later, at the time of repeat coronary angiography. In-stent restenosis was present in 9.3% of patients in the quinapril group and 25.6% of patients in the placebo group (p = 0.047). Mean late luminal loss was 0.56 +/- 0.51 mm in the quinapril group and 0.95 +/- 0.95 mm in the placebo group (p = 0.003). There were no significant differences in plasma soluble Fas or soluble Fas ligand levels at baseline. At 6 months, the change in plasma soluble Fas level was significantly higher in the quinapril group (0.72 +/- 1.24 ng/ml) than in the placebo group (0.28 +/- 0.72 ng/ml) (p = 0.024). The change in plasma soluble Fas ligand levels at 6 months was significantly higher in the quinapril group (7.43 +/- 12.2 pg/ml) than in the placebo group (0.06 +/- 6.8 pg/ml) (p = 0.002). In conclusion, the angiotensin-converting enzyme inhibitor quinapril inhibits in-stent restenosis by stimulating apoptosis after percutaneous intervention.

Effect of radiographic contrast media on markers of complement activation and apoptosis in patients with chronic coronary artery disease undergoing coronary angiography.

The effects of radiographic contrast media on markers of complement activation and apoptosis in patients with chronic coronary artery disease (CAD) are unknown. The purpose of this study was to assess the comparative effects of ionic high-osmolar and non-ionic iso-osmolar radiographic contrast media on plasma markers of complement activation and apoptosis in patients with chronic CAD undergoing coronary angiography. Forty-four patients undergoing coronary angiography for chronic CAD were randomly assigned to receive the ionic high-osmolar radiographic contrast agent diatrizoate (Group A), or the non-ionic iso-osmolar contrast agent iodixanol (Group B) during angiography. Complement component 5 (C5a) and apoptotic markers sFas and sFasL were measured just prior to angiography and 1 hour after completion of angiography. Comparison of mean pre- and post-angiography plasma marker levels showed significantly greater increases in plasma levels in Group A than in Group B of C5a (29.30 +/- 5.45 ng/ml for Group A and 0.47 +/- 0.70 ng/ml for Group B (p < 0.00001), sFas (2.36 +/- 1.63 ng/ml for Group A and 0.23 +/- 0.90 ng/ml for Group B (p < 0.00001) and sFasL (14.00 +/- 5.41 pg/ml for Group A and 0.01 +/- 1.00 pg/ml for Group B (p < 0.00001). The results suggest that in patients with chronic CAD, the use of ionic high-osmolar radiographic contrast media during coronary angiography is associated with a more robust inflammatory and apoptotic milieu than that associated with the use of non-ionic iso-osmolar radiographic contrast media.