Publications

Background Paravalvular regurgitation (PVR) is a common complication after transcatheter aortic valve replacement, posing an increased risk of heart failure and mortality. Accurate intraprocedural quantification of PVR is challenging. Both hemodynamic indices and videodensitometry can be used for intraprocedural assessment of PVR. We compared the predictive value of the isolated versus combined use of the hemodynamic index diastolic delta (DD) and videodensitometry for the incidence of relevant PVR 1 month after transcatheter aortic valve replacement. Methods and Results In this prospective cohort study, patients underwent periprocedural PVR assessment by DD and videodensitometry (using left ventricular outflow tract—aortic regurgitation [LVOT‐AR]). Cardiac magnetic resonance served as reference modality for PVR assessment. Relevant PVR was defined as cardiac magnetic resonance–regurgitant fraction >20%. Fifty‐one patients were enrolled in this study. Mean age was 80.6±5.2 years and 45.1% of patients were men. Mean LVOT‐AR and cardiac magnetic resonance–regurgitant fraction were 8.2%±7.8% and 11.7%±9.6%, respectively. The correlation between DD and LVOT‐AR was weak ( r =−0.36). DD and LVOT‐AR showed a comparable accuracy to predict relevant PVR (area under the curve 0.82, 95% CI: 0.69–0.95 versus area area under the time–density curve 0.80, 95% CI: 0.62–0.99). The combination of DD and LVOT‐AR improved the prediction of relevant PVR (area under the time–density curve, 0.90, 95% CI: 0.81–0.99), and resulted in an increased concordance (86.3%) and positive predictive value (75%) compared with DD alone (76.5% and 40%, respectively), or LVOT‐AR alone (82.3% and 50%, respectively). Conclusions DD and videodensitometry are both accurate and feasible modalities for the assessment of PVR after transcatheter aortic valve replacement. The synergistic use of both techniques increases the predictive value for relevant PVR after transcatheter aortic valve replacement. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04281771.

Despite having been recognized for a long time as a cheap and effective therapy for the treatment of asthma and chronic obstructive pulmonary disease (COPD), theophylline is relegated to third-line therapy in the treatment of airway diseases due to the drug's frequent side effects and relatively low efficacy. However, regardless of the current situation, there are reasons for thinking that the use of theophylline, in addition to inhaled steroids, may come back into fashion for the treatment of chronic asthma, as it may have an anti-inflammatory and immunomodulatory effect when given in low doses. At these low doses, the drug is easier to use, side effects are uncommon and the problems of drug interaction are less of an issue, thus making the clinical use of theophylline less complicated. In COPD, low-dose theophylline is the first drug to demonstrate clear anti-inflammatory effects, and thus it may even have a role in preventing progression of the disease. Furthermore, the reversal of the steroid resistance induced by oxidative stress suggests that theophylline may increase responsiveness to corticosteroids.

Objectives This study sought to analyze stroke rates in the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial's randomized and registry cohorts of patients being treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) for treatment of complex coronary artery disease. Background The SYNTAX trial compared PCI to CABG in patients with de novo 3-vessel and/or left main coronary disease. Methods The SYNTAX randomized trial was conducted at 85 U.S. and European sites (n = 1,800). All strokes (up to 4 years) were independently adjudicated by a clinical events committee that included a neurologist. An additional 1,077 (of which 644 were followed for 5 years) and 198 patients were included in the CABG and PCI registries, respectively. Results In the randomized cohort, 31 CABG and 19 PCI patients experienced 33 and 20 strokes post-randomization at 4-year follow-up, respectively (p = 0.062). Three strokes occurred pre-procedurally but following randomization in CABG-treated patients. After CABG, a large proportion of strokes occurred acutely (0 to 30 days: 9 of 33), whereas in the PCI arm, most strokes occurred >30 days after the procedure (18 of 20). Stroke resulted in death in 3 patients in both the PCI and CABG groups. Of the patients who developed stroke, 68% (21 of 31) in the CABG group had residual deficits at discharge; in the PCI group, 47% (9 of 19) had residual deficits. In a multivariate analysis, treatment with CABG was not significantly associated with increased stroke rates (odds ratio: 1.67, 95% confidence interval: 0.93 to 3.01, p = 0.089). The incidence and outcomes of stroke were similar in the randomized trial and registries. Conclusions There is a higher risk of periprocedural stroke in patients undergoing CABG versus PCI; however, the risk converges over the first 4 years of follow-up. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972)

Outcome after transcatheter aortic valve implantation (TAVI) depends on the patient risk profile, operator experience, progress in technology, and technique. We sought to compare the results of TAVI during the initiation phase and after certification to perform TAVI with the Medtronic CoreValve System without proctoring. A total of 165 consecutive patients was categorized into a first cohort of 33 patients treated before certification (November 2005 to December 2007) and a second cohort of 132 patients treated after certification (January 2008 to October 2010). The study end points were selected and defined according to the Valve Academic Research Consortium recommendations. Compared to cohort 2, the patients in cohort 1 more frequently had New York Heart Association class III–IV (100% vs 71%, p <0.001), hypertension (67% vs 39%, p = 0.004), and aortic regurgitation grade III–IV (46% vs 22%, p = 0.006) before TAVI. Over time, the patients in cohort 2 more frequently underwent a truly percutaneous approach (98% vs 82%, p = 0.002) without circulatory support (96% vs 67%, p <0.001) but with more concomitant percutaneous coronary intervention (11% vs 0%, p = 0.042) than the patients in cohort 1. They also more often received a 29-mm prosthesis (72% vs 24%, p <0.001), required less postimplantation balloon dilation (10% vs 27%, p = 0.008), and had less aortic regurgitation grade III–IV after TAVI (12% vs 30%, p = 0.010). The clinical outcome showed a nonsignificant reduction in the combined safety end point (30% to 17%) but a significant reduction in cerebrovascular events (21% to 7%, p = 0.020) and life-threatening bleeding (15% to 5%, p = 0.044) in cohort 2. However, the reduction in overall bleeding and vascular complications (25% and 14%, respectively) was not significant. In conclusion, TAVI became significantly less complex and was associated with better results over time but remained associated with a high frequency of periprocedural major cardiovascular complications.

No abstract is provided for this article.

1. The purine nucleoside adenosine relaxes smooth muscle in vitro and is a vasodilator in animals, but its effects on cardiac output and systemic vascular resistance have not been measured in normal conscious human subjects. 2. We have studied the effects of infused adenosine in doses of 0.005, 0.03 and 0.07 mg kg‐1 min‐1 on pulmonary blood flow and systemic vascular resistance in eight healthy volunteers, using a non‐ invasive, inert gas method and mass spectrometry. 3. At a dose of 0.07 mg kg‐1 min‐1, there was a rise in effective pulmonary blood flow (which is approximately equivalent to cardiac output) of 0.52 +/‐ 0.08 l min‐1 m‐2 (mean +/‐ s.e. mean) and a fall in estimated systemic vascular resistance of 357 +/‐ 44 dyn s cm‐5. Despite this marked systemic vasodilation, there was no significant change in mean heart rate. 4. The effects of this dose of adenosine were maximal 2 min after starting the infusion, and had disappeared within 5 min of stopping it. 5. Adenosine may be therapeutically useful in the reduction of left ventricular afterload, where the absence of reflex tachycardia may be advantageous. We suggest that adenosine in doses of 0.03 mg kg‐1 min‐1 should be evaluated as a selective pulmonary vasodilator.

EuroInterv.2007;3:149-153 Description Kaneka’s coronary stent, MAHOROBATM, is a new drug eluting stent (DES), which combines a thin, flexible cobalt-chromium (CoCr) metal stent platform coated with a biodegradable polymer including the pharmaceutical agent tacrolimus. The device has been designed and developed to inhibit the growth of neointimal hyperplasia and avoid interference with the vascular healing response.

Corticosteroid resistance is a major barrier to the effective treatment of chronic obstructive pulmonary disease (COPD). Oxidative stress from cigarette smoke and chronic inflammation is likely to induce this corticosteroid insensitivity. Quercetin is a polyphenol that has been reported to be an active oxygen scavenger as well as a functional adenosine monophosphate-activated protein kinase (AMPK) activator.The aim of this study was to investigate the effect of quercetin on corticosteroid responsiveness in COPD cells. Corticosteroid sensitivity was examined in human monocytic U937 cells exposed to cigarette smoke extract (CSE) and peripheral blood mononuclear cells (PBMC) collected from patients with COPD. Corticosteroid sensitivity was determined as the dexamethasone concentration causing 40% inhibition of tumor necrosis factor alpha-induced CXCL8 production (Dex-IC40) in the presence or absence of quercetin. In U937 cells, treatment with quercetin activated AMPK and induced expression of nuclear factor erythroid 2-related factor 2, and consequently reversed CSE-induced corticosteroid insensitivity. PBMC from patients with COPD showed corticosteroid insensitivity compared with those from healthy volunteers, and treatment with quercetin restored corticosteroid sensitivity.In conclusion, quercetin restores corticosteroid sensitivity, and has the potential to be a novel treatment in combination with corticosteroids in COPD.