The ASCEND-NHQ randomized trial found positive effects of daprodustat on hemoglobin and quality of life in patients with non-dialysis chronic kidney disease.

The ASCEND-NHQ trial evaluated the effects of daprodustat on hemoglobin and the Medical Outcomes Study 36-item Short Form Survey (SF-36) Vitality score (fatigue) in a multicenter, randomized, double-blind, placebo-controlled trial. Adults with chronic kidney disease (CKD) stages 3-5, hemoglobin 8.5-10.0 g/dl, transferrin saturation 15% or more, and ferritin 50 ng/ml or more without recent erythropoiesis-stimulating agent use were randomized (1:1) to oral daprodustat or placebo to achieve and maintain target hemoglobin of 11-12 g/dl over 28 weeks. The primary endpoint was the mean change in hemoglobin between baseline and the evaluation period (Weeks 24-28). Principal secondary endpoints were proportion of participants with a 1 g/dl or more increase in hemoglobin and mean change in the Vitality score between baseline and Week 28. Outcome superiority was tested (1-sided alpha level of 0.025). Overall, 614 participants with non-dialysis-dependent CKD were randomized. The adjusted mean change in hemoglobin from baseline to the evaluation period was greater with daprodustat (1.58 vs 0.19 g/dl). The adjusted mean treatment difference (AMD) was significant at 1.40 g/dl (95% confidence interval 1.23, 1.56). A significantly greater proportion of participants receiving daprodustat showed a 1 g/dl or greater increase in hemoglobin from baseline (77% vs 18%). The mean SF-36 Vitality score increased by 7.3 and 1.9 points with daprodustat and placebo, respectively; a clinically and statistically significant 5.4 point Week 28 AMD increase. Adverse event rates were similar (69% vs 71%); relative risk 0.98, (95% confidence interval 0.88, 1.09). Thus, in participants with CKD stages 3-5, daprodustat resulted in a significant increase in hemoglobin and improvement in fatigue without an increase in the overall frequency of adverse events.

Use of a safe procedure checklist in the cardiac catheterisation laboratory.

BACKGROUND: The use of the WHO safe surgery checklist has been shown to reduce morbidity and mortality from surgical procedures. However, whether a WHO-style safe procedure checklist can improve safety in the cardiac catheterisation laboratory (CCL) has not previously been investigated. OBJECTIVES: The authors sought to design and implement a safe procedure checklist suitable for all CCL procedures, and to assess its impact over the course of 1 year. METHODS: In the first 3 months, weekly PDSA cycles (Plan-Do-Study-Act) were used to optimise the design of the checklist through testing and staff feedback, and team briefing sessions were introduced before each procedure list. The impact of the checklist and team briefs was assessed by analysing in-house procedural data subsequently submitted to national audit databases. Staff and patient questionnaires were performed throughout the year. RESULTS: Introduction of the checklist was associated with a significant reduction of 3 min in average turnaround time (95% CI 25 s to 6 min, p=0.027). Similarly, an initial reduction in patient radiation exposure was recorded (dose area product reduction of 641.5 cGy/cm2; 95% CI 255.9 to 1027.1, p=0.002). The rate of reported complications from all procedures fell significantly from 2.0% in 2012/2013 (95% CI 1.6% to 2.4%) to 0.8% in 2013/2014 (95% CI 0.6% to 1.1%, p≤0.001). Staff climate questionnaires showed that technicians and radiographers gave more positive responses at the end of the study period compared with the beginning (p=0.001). CONCLUSIONS: The use of a team brief and WHO-derived safe procedure checklist in the CCL was associated with decreased radiation exposure, fewer procedural complications, faster turnarounds and improved staff experience.

Transcatheter Mitral Valve Implantation: 30-day Outcome of First-in-Man Experience With an Apically Tethered Device.

OBJECTIVE: A small number of transcatheter mitral valve implants (TMVIs) have been reported using devices designed to treat secondary mitral regurgitation (MR). However, MR has many etiologies, and patients have a broad spectrum of annular size, geometry, and lesions. There are a number of technical challenges for TMVI including left ventricular outflow tract obstruction and paravalvular MR. Thirty days' outcome of first-in-man implants with a novel TMVI device is reported. METHODS: The Tendyne TMVI system consists of a porcine pericardial valve in a tethered nitinol frame. An apical tether fixed to an epicardial pad stabilizes the device. The device is fully repositionable and retrievable even after complete deployment. Preoperative assessment was performed with 3-dimensional (3D) transesophageal echocardiogram and multislice computed tomography to define annular dimensions, geometry, and guide surgical access. Three patients were deemed not to be candidates for conventional surgery or for treatment with any Conformitè Européenne-marked device by Heart Team Evaluation. They were a 68-year-old woman with prior coronary artery bypass grafts and severe functional MR; a 75-year-old man with prior coronary bypass grafts, significant renal dysfunction, and severe degenerative MR; and a frail 86-year-old man with severe degenerative MR. Each had a TMVI via a transapical approach through a left minithoracotomy. Apical tether tension was adjusted to optimize device position. RESULTS: Implantation was guided by 2D and 3D transesophageal echocardiogram. The apical pad facilitated LV apical closure. There were no procedural complications. No patient had hemodynamically significant residual MR or left ventricular outflow tract obstruction, and there was no significant mitral gradient. All patients were discharged to their own home (the third on the fifth postoperative day), all with significant improvement in their symptoms. All were alive and well 30 days after implant. Two patients with existing conduction abnormalities had cardiac resynchronisation therapy after the procedure, and one patient had para valvular leak (PVL) with evidence of hemolysis at 30 days, which reduced in severity with conservative treatment. CONCLUSIONS: The first-in-man experience with the Tendyne TMVI system is promising. Valve stabilization by an apical tether is a novel way to address some of the challenges of TMVI. The unique Tendyne design features may offer potential for its use across a wide range of mitral valve pathologies.

A low-dose, dual-phase cardiovascular CT protocol to assess left atrial appendage anatomy and exclude thrombus prior to left atrial intervention.

Assessment of the left atrial appendage (LAA) for thrombus and anatomy is important prior to atrial fibrillation (AF) ablation and LAA exclusion. The use of cardiovascular CT (CCT) to detect LAA thrombus has been limited by the high incidence of pseudothrombus on single-pass studies. We evaluated the diagnostic accuracy of a two-phase protocol incorporating a limited low-dose delayed contrast-enhanced examination of the LAA, compared with a single-pass study for LAA morphological assessment, and transesophageal echocardiography (TEE) for the exclusion of thrombus. Consecutive patients (n = 122) undergoing left atrial interventions for AF were assessed. All had a two-phase CCT protocol (first-past scan plus a limited, 60-s delayed scan of the LAA) and TEE. Sensitivity, specificity, diagnostic accuracy, positive (PPV) and negative predictive values (NPV) were calculated for the detection of true thrombus on first-pass and delayed scans, using TEE as the gold standard. Overall, 20/122 (16.4 %) patients had filling defects on the first-pass study. All affected the full delineation of the LAA morphology; 17/20 (85 %) were confirmed as pseudo-filling defects. Three (15 %) were seen on late-pass and confirmed as true thrombi on TEE; a significant improvement in diagnostic performance relative to a single-pass scan (McNemar Chi-square 17, p < 0.001). The sensitivity, specificity, diagnostic accuracy, PPV and NPV was 100, 85.7, 86.1, 15.0 and 100 % respectively for first-pass scans, and 100 % for all parameters for the delayed scans. The median (range) additional radiation dose for the delayed scan was 0.4 (0.2-0.6) mSv. A low-dose delayed scan significantly improves the identification of true LAA anatomy and thrombus in patients undergoing LA intervention.

Clinical and economic consequences of non-cardiac incidental findings detected on cardiovascular computed tomography performed prior to transcatheter aortic valve implantation (TAVI).

Transcatheter aortic valve implantation (TAVI) is an effective treatment option for patients with severe degenerative aortic valve stenosis who are high risk for conventional surgery. Computed tomography (CT) performed prior to TAVI can detect pathologies that could influence outcomes following the procedure, however the incidence, cost, and clinical impact of incidental findings has not previously been investigated. 279 patients underwent CT; 188 subsequently had TAVI and 91 were declined. Incidental findings were classified as clinically significant (requiring treatment), indeterminate (requiring further assessment), or clinically insignificant. The primary outcome measure was all-cause mortality up to 3 years. Costs incurred by additional investigations resultant to incidental findings were estimated using the UK Department of Health Payment Tariff. Incidental findings were common in both the TAVI and medical therapy cohorts (54.8 vs. 70.3%; P = 0.014). Subsequently, 45 extra investigations were recommended for the TAVI cohort, at an overall average cost of £32.69 per TAVI patient. In a univariate model, survival was significantly associated with the presence of a clinically significant or indeterminate finding (HR 1.61; P = 0.021). However, on multivariate analysis outcomes after TAVI were not influenced by any category of incidental finding. Incidental findings are common on CT scans performed prior to TAVI. However, the total cost involved in investigating these findings is low, and incidental findings do not independently identify patients with poorer outcomes after TAVI. The discovery of an incidental finding on CT should not necessarily influence or delay the decision to perform TAVI.

Subintimal TRAnscatheter Withdrawal (STRAW) of hematomas compressing the distal true lumen: a novel technique to facilitate distal reentry during recanalization of chronic total occlusion (CTO).

The development of a large hematoma impairing visualization of the distal true lumen is a recognized complication of antegrade recanalization of chronic total occlusions, often forcing the operator to abort the procedure or switch to a retrograde approach. We describe a novel technique utilizing an over-the-wire balloon inflated in the proximal occluded vessel to block inflow and allow aspiration of the blood from the subintimal space. This decompressed the true lumen, restored distal visualization, and allowed successful reentry using a dedicated technology. Utilization of this novel technique may rescue antegrade recanalization attempts complicated by large subintimal hematomas.

Intracoronary optical coherence tomography: a review of clinical applications.

Optical coherence tomography (OCT) is a light-based technology that provides very high spatial resolution images. OCT has been initially employed as a research tool to investigate plaque morphology and stent strut coverage. The introduction of frequency domain OCT allowing fast image acquisition during a prolonged contrast injection via the guiding catheter has made OCT applicable for guidance of coronary interventions. In this manuscript, the various applications of OCT are reviewed, from assessment of plaque vulnerability and severity to characteristics of unstable lesions and thrombus burden to stent optimization and evaluation of late results.

Non-invasive imaging of carotid arterial restenosis using 3T cardiovascular magnetic resonance.

BACKGROUND: Restenosis of the carotid artery is common following carotid endarterectomy, but analysis of lesion composition has mostly been based on histological study of explanted restenotic lesions. This study investigated the ability of 3T cardiovascular magnetic resonance (CMR) to determine the components of recurrent carotid artery disease and examined whether these differed from primary atherosclerotic plaque. METHODS: 50 patients underwent 3T CMR of both carotid arteries using a standard multicontrast protocol: time-of-flight (TOF), T1-weighted (T1W), T2-weighted (T2W), and PD-weighted (PDW) Turbo-Spin-Echo (TSE) sequences. 25 patients had previously undergone carotid endarterectomy (mean time since surgery 1580 days, range 45-6560 days), and 25 with primary asymptomatic atherosclerotic plaques served as controls. Two experienced reviewers analysed the multicontrast CMR images according to the presence or absence of major plaque features and assigned an overall classification type. RESULTS: In patients with recurrent carotid disease following endarterectomy, the mean degree of restenosis was 51% (range 30-90%). Three distinct types of restenosis were identified: 5 patients (20%) showed CMR characteristics of fibro-atheromatous tissue, 11 patients (44%) had plaque features consistent with possible myointimal (fibromuscular) hyperplasia, and 6 patients (24%) had recurrent plaque suggestive of further lipid accumulation. Three patients (12%) showed evidence of post-surgical dissection of the carotid intima. Compared to primary atherosclerotic plaques, restenotic plaques were more likely to contain fibro-atheromatous tissue (p = 0.05) and smooth muscle (p < 0.01), and less likely to contain lipid (p < 0.01). Composition did not differ significantly between patients with early and late restenosis. CONCLUSIONS: As defined by CMR, restenotic lesions of the carotid artery fall into three distinct types and differ in composition from primary atherosclerotic plaques. If validated by subsequent histological studies, these findings could suggest a role for CMR in detecting high-risk (i.e. lipid-rich) restenotic lesions.

The biophysics of renal sympathetic denervation using radiofrequency energy.

Renal sympathetic denervation is currently performed in the treatment of resistant hypertension by interventionists who otherwise do not typically use radiofrequency (RF) energy ablation in their clinical practice. Adequate RF lesion formation is dependent upon good electrode-tissue contact, power delivery, electrode-tissue interface temperature, target-tissue impedance and the size of the catheter's active electrode. There is significant interplay between these variables and hence an appreciation of the biophysical determinants of RF lesion formation is required to provide effective and safe clinical care to our patients. In this review article, we summarize the biophysics of RF ablation and explain why and how complications of renal sympathetic denervation may occur and discuss methods to minimise them.

Predictors of stent strut malapposition in calcified vessels using frequency-domain optical coherence tomography.

BACKGROUND AND AIMS: Malapposition of stent struts to the arterial wall and suboptimal stent expansion have been linked with poor outcomes following percutaneous coronary intervention (PCI). The purpose of this study was to use optical coherence tomography (OCT) to investigate stent strut malapposition in relation to calcium distribution. METHODS AND RESULTS: Twenty-three PCI patients underwent OCT before and after stent deployment. Patient and procedural details and lesion characteristics - including the extent and depth of calcification - were measured, and the number of malapposed struts following final postdilatation was quantified. Patient and lesion characteristics associated with malapposition were assessed using univariate and multivariate analyses. The mean lesion length was 25.2 ± 10.8 mm, with a minimal lumen area (MLA) of 2.2 ± 1.2 mm². Eight percent of all stent struts were malapposed, most commonly in the proximal part of the stent. By univariate analysis, the percentage of malapposed struts was found to correlate with the circumferential extent of calcification (P=.04); however, no correlation was seen with the depth of calcification. Using multivariate analysis, the circumferential extent of vessel wall calcification was the only plaque feature found to correlate with the percentage of malapposed struts (P=.01). CONCLUSIONS: Using OCT to assess vessel wall characteristics, the circumferential extent of superficial calcification seen, and not the depth, correlated well with the percentage of malapposed struts following PCI.

Systemic and vascular oxidation limits the efficacy of oral tetrahydrobiopterin treatment in patients with coronary artery disease.

BACKGROUND: The endothelial nitric oxide synthase cofactor tetrahydrobiopterin (BH4) plays a pivotal role in maintaining endothelial function in experimental vascular disease models and in humans. Augmentation of endogenous BH4 levels by oral BH4 treatment has been proposed as a potential therapeutic strategy in vascular disease states. We sought to determine the mechanisms relating exogenous BH4 to human vascular function and to determine oral BH4 pharmacokinetics in both plasma and vascular tissue in patients with coronary artery disease. METHODS AND RESULTS: Forty-nine patients with coronary artery disease were randomized to receive low-dose (400 mg/d) or high-dose (700 mg/d) BH4 or placebo for 2 to 6 weeks before coronary artery bypass surgery. Vascular function was quantified by magnetic resonance imaging before and after treatment, along with plasma BH4 levels. Vascular superoxide, endothelial function, and BH4 levels were determined in segments of saphenous vein and internal mammary artery. Oral BH4 treatment significantly augmented BH4 levels in plasma and in saphenous vein (but not internal mammary artery) but also increased levels of the oxidation product dihydrobiopterin (BH2), which lacks endothelial nitric oxide synthase cofactor activity. There was no effect of BH4 treatment on vascular function or superoxide production. Supplementation of human vessels and blood with BH4 ex vivo revealed rapid oxidation of BH4 to BH2 with predominant BH2 uptake by vascular tissue. CONCLUSIONS: Oral BH4 treatment augments total biopterin levels in patients with established coronary artery disease but has no net effect on vascular redox state or endothelial function owing to systemic and vascular oxidation of BH4. Alternative strategies are required to target BH4-dependent endothelial function in established vascular disease states.

Molecular imaging with optical coherence tomography using ligand-conjugated microparticles that detect activated endothelial cells: rational design through target quantification.

OBJECTIVES: Optical coherence tomography (OCT) is a high resolution imaging technique used to assess superficial atherosclerotic plaque morphology. Utility of OCT may be enhanced by contrast agents targeting molecular mediators of inflammation. METHODS AND RESULTS: Microparticles of iron oxide (MPIO; 1 and 4.5 µm diameter) in suspension were visualized and accurately quantified using a clinical optical coherence tomography system. Bound to PECAM-1 on a plane of cultured endothelial cells under static conditions, 1 µm MPIO were also readily detected by OCT. To design a molecular contrast probe that would bind activated endothelium under conditions of shear stress, we quantified the expression (basal vs. TNF-activated; molecules µm(-2)) of VCAM-1 (not detected vs. 16 ± 1); PECAM-1 (132 ± 6 vs. 198 ± 10) and E-selectin (not detected vs. 46 ± 0.6) using quantitative flow cytometry. We then compared the retention of antibody-conjugated MPIO targeting each of these molecules plus a combined VCAM-1 and E-selectin (E+V) probe across a range of physiologically relevant shear stresses. E+V MPIO were consistently retained with highest efficiency (P < 0.001) and at a density that provided conspicuous contrast effects on OCT pullback. CONCLUSION: Microparticles of iron oxide were detectable using a clinical OCT system. Assessment of binding under flow conditions recommended an approach that targeted both E-selectin and VCAM-1. Bound to HUVEC under conditions of flow, targeted 1 µm E+V MPIO were readily identified on OCT pullback. Molecular imaging with OCT may be feasible in vivo using antibody targeted MPIO.

Cannabis as a precipitant of cardiovascular emergencies.

Cannabis smoking is on the increase both in the United Kingdom and in the United States. For over three decades it has been known that cannabis has pathophysiological effects on the cardiovascular system, and previously an association with an increased risk of myocardial infarction has been reported. However, it is not yet known whether cannabis contributes directly to coronary artery disease. We describe two distinct cases; in the first cannabis use precipitated a malignant arrhythmia in a patient with critical ischaemia from longstanding coronary artery disease. In the second, a young patient presented with an acute myocardial infarction that had started whilst smoking marijuana; subsequently diffuse coronary artery disease was found at angiography despite the patient's low risk factor status. Patients who are known cannabis smokers and who have cardiovascular disease should be warned that it is likely to aggravate coronary ischaemia, and may even trigger myocardial infarction.

Stem cells as future therapy in cardiology.

This article focuses on the key studies relevant to the clinical application of stem-cell research in cardiovascular disease. The authors also discuss current and future directions in clinical cardiovascular stem-cell research, including the potential problems and pitfalls that must be addressed to ensure the safety, as well as the efficacy, of treatment regimens in this rapidly evolving therapeutic field.