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.

Risk of, and risk factors for, vasculopathy associated with acute herpes zoster.

OBJECTIVES: We aimed to summarize the known risk of vasculopathy (stroke, myocardial infarction [MI], and transient ischemic attack [TIA]) after herpes zoster (HZ) and the impact of antiviral treatment and vaccination against HZ on the risk of vasculopathy. MATERIALS AND METHODS: A narrative literature review was conducted in PubMed to identify evidence published in the past 15 years that was relevant to the scope of this article. RESULTS: Ten studies reported that HZ was associated with an increased risk of stroke and one UK study reported no association. Four studies reported that HZ was associated with an increased risk of MI, and four reported that HZ was associated with an increased risk of TIA. Two studies reported that antiviral treatment was associated with a reduced risk of stroke and an additional two studies reported no association between antiviral treatment and the risk of stroke. In addition, two studies reported that vaccination against HZ using the live zoster vaccine (ZVL) was associated with a reduced risk of stroke, and an additional two studies reported that the risk of stroke or MI after HZ was similar between ZVL vaccinated and unvaccinated individuals. CONCLUSIONS: HZ is associated with an increased risk of stroke, MI, or TIA (strongest association is between HZ and stroke). Further studies are needed to determine whether antiviral treatment or ZVL vaccination influence the risk of HZ-associated vasculopathy. In addition, the effect of the recombinant zoster vaccine on the risk of HZ-associated vasculopathy should be studied.

Pharmacokinetics of Daprodustat and Metabolites in Individuals with Normal and Impaired Hepatic Function.

Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor in development for treatment of anemia of chronic kidney disease. We evaluated the role of hepatic impairment on daprodustat pharmacokinetics, pharmacodynamics, and tolerability. Participants with mild (Child-Pugh Class A, score 5-6) and moderate (Child-Pugh Class B, score 7-9) hepatic impairment and matched healthy controls were administered single 6-mg doses of daprodustat. Exposure parameters were determined for daprodustat and its six metabolites. Comparisons resulted in 1.5- and 2.0-fold higher daprodustat Cmax and area under the curve (AUC) exposures in participants with mild and moderate hepatic impairment, respectively, versus controls; Cmax in mild hepatic impairment was comparable to controls. Similarly, aligned with parent drug, unbound daprodustat Cmax and AUC exposures increased 1.6- to 2.3-fold in hepatic-impaired participants versus controls, and metabolite exposures were 1.2- to 2.0-fold higher in participants with hepatic impairment. Erythropoeitin (EPO) baseline-corrected AUC exposures were between 0.3-fold lower and 2.2-fold higher in matched controls versus hepatic-impaired participants. No serious or study drug-related adverse events were reported. Daprodustat exposure was increased in participants with moderate and mild hepatic impairment compared with matched controls; however, no meaningful differences in EPO were observed and no new safety concerns were identified (ClinicalTrials.gov: NCT03223337).

Clinical Pharmacokinetics of Daprodustat: Results of an Absorption, Distribution, and Excretion Study With Intravenous Microtracer and Concomitant Oral Doses for Bioavailability Determination.

Daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being investigated for treatment of anemia in chronic kidney disease. This phase 1, nonrandomized, 2-period, crossover study in 6 healthy men characterized the absorption, distribution, and excretion of daprodustat when administered as oral and intravenous (IV) doses of unlabeled and radiolabeled daprodustat ([14 C]-GSK1278863). Tolerability and pharmacokinetic properties of daprodustat, and its 6 metabolites in the systemic circulation, were also evaluated. The mean recovery of radiolabeled daprodustat was ≈95% by day 5, with the majority in feces and minor renal elimination, indicating that daprodustat and metabolites are primarily eliminated via hepatobiliary and fecal routes. Approximately 40% of total circulating radioactivity in plasma following both IV and oral administration was daprodustat; thus, 60% was attributed to metabolites. It was estimated that ≈80% of daprodustat was absorbed across the gastrointestinal tract, and ≈18% cleared by hepatic extraction. Pharmacokinetics were essentially dose proportional, with moderate (≈66%) oral tablet bioavailability. Following IV administration, daprodustat plasma clearance (19.3 L/h) and volume of distribution (14.6 L) were low, suggesting low tissue distribution outside systemic circulation with likely low penetration into tissues. Daprodustat was generally well tolerated, with no deaths or serious or significant adverse events reported.

Meta-Analysis of 26 638 Individuals Identifies Two Genetic Loci Associated With Left Ventricular Ejection Fraction.

BACKGROUND: Left ventricular ejection fraction (EF) is an indicator of cardiac function, usually assessed in individuals with heart failure and other cardiac conditions. Although family studies indicate that EF has an important genetic component with heritability estimates up to 0.61, to date only 6 EF-associated loci have been reported. METHODS: Here, we conducted a genome-wide association study (GWAS) of EF in 26 638 adults from the Genetic Epidemiology Research on Adult Health and Aging and the UK Biobank cohorts. RESULTS: A meta-analysis combining results from Genetic Epidemiology Research on Adult Health and Aging and UK Biobank identified a novel locus: TMEM40 on chromosome 3p25 (rs11719526; ß=0.47 and P=3.10×10-8) that replicated in Biobank Japan and confirmed recent findings implicating the BAG3 locus on chromosome 10q26 in EF variation, with the strongest association observed for rs17617337 (ß=-0.83 and P=8.24×10-17). Although the minor allele frequencies of TMEM40 rs11719526 were generally common (between 0.13 and 0.44) in different ethnic groups, BAG3 rs17617337 was rare (minor allele frequencies<0.05) in Asian and African ancestry populations. These associations were slightly attenuated, after considering antecedent cardiac conditions (ie, heart failure/cardiomyopathy, hypertension, myocardial infarction, atrial fibrillation, valvular disease, and revascularization procedures). This suggests that the effects of the lead variants at TMEM40 or BAG3 on EF are largely independent of these conditions. CONCLUSIONS: In this large and multiethnic study, we identified 2 loci, TMEM40 and BAG3, associated with EF at a genome-wide significance level. Identifying and understanding the genetic determinants of EF is important to better understand the pathophysiology of this strong correlate of cardiac outcomes and to help target the development of future therapies.

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.

Prevalence and Prognostic Significance of Right Ventricular Systolic Dysfunction in Patients Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: Cardiovascular magnetic resonance (CMR) can provide important structural information in patients undergoing transcatheter aortic valve implantation. Although CMR is considered the standard of reference for measuring ventricular volumes and mass, the relationship between CMR findings of right ventricular (RV) function and outcomes after transcatheter aortic valve implantation has not previously been reported. METHODS AND RESULTS: A total of 190 patients underwent 1.5 Tesla CMR before transcatheter aortic valve implantation. Steady-state free precession sequences were used for aortic valve planimetry and to assess ventricular volumes and mass. Semiautomated image analysis was performed by 2 specialist reviewers blinded to patient treatment. Patient follow-up was obtained from the Office of National Statistics mortality database. The median age was 81.0 (interquartile range, 74.9-85.5) years; 50.0% were women. Impaired RV function (RV ejection fraction ≤50%) was present in 45 (23.7%) patients. Patients with RV dysfunction had poorer left ventricular ejection fractions (42% versus 69%), higher indexed left ventricular end-systolic volumes (96 versus 40 mL), and greater indexed left ventricular mass (101 versus 85 g/m(2); P<0.01 for all) than those with normal RV function. Median follow-up was 850 days; 21 of 45 (46.7%) patients with RV dysfunction died, compared with 43 of 145 (29.7%) patients with normal RV function (P=0.035). After adjustment for significant baseline variables, both RV ejection fraction ≤50% (hazard ratio, 2.12; P=0.017) and indexed aortic valve area (hazard ratio, 4.16; P=0.025) were independently associated with survival. CONCLUSIONS: RV function, measured on preprocedural CMR, is an independent predictor of mortality after transcatheter aortic valve implantation. CMR assessment of RV function may be important in the risk stratification of patients undergoing transcatheter aortic valve implantation.

Renal denervation in heart failure with preserved ejection fraction (RDT-PEF): a randomized controlled trial.

AIM: Heart failure with preserved ejection fraction (HFpEF) is associated with increased sympathetic nervous system (SNS) tone. Attenuating the SNS with renal denervation (RDT) might be helpful and there are no data currently in humans with HFpEF. METHODS AND RESULTS: In this single-centre, randomized, open-controlled study we included 25 patients with HFpEF [preserved left ventricular (LV) ejection fraction, left atrial (LA) dilatation or LV hypertrophy and raised B-type natriuretic peptide (BNP) or echocardiographic assessment of filling pressures]. Patients were randomized (2:1) to RDT with the Symplicity™ catheter or continuing medical therapy. The primary success criterion was not met in that there were no differences between groups at 12 months for Minnesota Living with Heart Failure Questionnaire score, peak oxygen uptake (VO2 ) on exercise, BNP, E/e', LA volume index or LV mass index. A greater proportion of patients improved at 3 months in the RDT group with respect to VO2 peak (56% vs. 13%, P = 0.025) and E/e' (31% vs. 13%, P = 0.04). Change in estimated glomerular filtration rate was comparable between groups. Two patients required plain balloon angioplasty during the RDT procedure to treat renal artery wall oedema. CONCLUSION: This study was terminated early because of difficulties in recruitment and was underpowered to detect whether RD improved the endpoints of quality of life, exercise function, biomarkers, and left heart remodelling. The procedure was safe in patients with HFpEF, although two patients did require intraprocedure renal artery dilatation.

Technical feasibility and validation of a coronary artery calcium scoring system using CT coronary angiography images.

OBJECTIVES: We validate a novel CT coronary angiography (CCTA) coronary calcium scoring system. METHODS: Calcium was quantified on CCTA images using a new patient-specific attenuation threshold: mean + 2SD of intra-coronary contrast density (HU). Using 335 patient data sets a conversion factor (CF) for predicting CACS from CCTA scores (CCTAS) was derived and validated in a separate cohort (n = 168). Bland-Altman analysis and weighted kappa for MESA centiles and Agatston risk groupings were calculated. RESULTS: Multivariable linear regression yielded a CF: CACS = (1.185 × CCTAS) + (0.002 × CCTAS × attenuation threshold). When applied to CCTA data sets there was excellent correlation (r = 0.95; p < 0.0001) and agreement (mean difference -10.4 [95% limits of agreement -258.9 to 238.1]) with traditional calcium scores. Agreement was better for calcium scores below 500; however, MESA percentile agreement was better for high risk patients. Risk stratification was excellent (Agatston groups k = 0.88 and MESA centiles k = 0.91). Eliminating the dedicated CACS scan decreased patient radiation exposure by approximately one-third. CONCLUSION: CCTA calcium scores can accurately predict CACS using a simple, individualized, semiautomated approach reducing acquisition time and radiation exposure when evaluating patients for CAD. This method is not affected by the ROI location, imaging protocol, or tube voltage strengthening its clinical applicability. KEY POINTS: • Coronary calcium scores can be reliably determined on contrast-enhanced cardiac CT • This score can accurately risk stratify patients • Elimination of a dedicated calcium scan reduces patient radiation by a third.

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.

Extended use of the GuideLiner in complex coronary interventions.

AIMS: Challenging coronary anatomies including chronic total occlusions (CTO), extreme vessel tortuosity, diseased bypass grafts, and anomalous coronary arteries pose difficulties in coronary interventions. The GuideLiner is a monorail catheter originally developed to facilitate delivery of stents to target lesions in tortuous vessels. We conducted a study on the feasibility and safety of utilising this catheter in a wider array of complex coronary interventions. METHODS AND RESULTS: Consecutive patients undergoing coronary or peripheral interventions where a GuideLiner was used were recruited into this study. Patient demographics, lesion and vessel characteristics, procedural details and outcomes were prospectively entered into our database and analysed. From September 2009 to October 2011, 54 consecutive patients underwent coronary intervention in our institution using a GuideLiner; 21 out of 54 coronary applications were motivated by the need to increase support to cross CTOs, predominantly of the RCA. Anomalous or angulated take-off of the treatment vessels (31%), previously deployed proximal stents (15%), heavy proximal calcification (9%) and tortuosity (7%) accounted for the remaining reasons. One patient had successful renal denervation with the aid of a GuideLiner catheter. Procedural success was 98% in our series with no device-related periprocedural complications such as ostial dissection or myocardial necrosis. CONCLUSIONS: The use of a GuideLiner facilitates the approach to complex coronary interventions including chronic total occlusion and saphenous vein graft intervention by providing greater back-up support and easier engagement of coronary ostia.

ABSORB biodegradable stents versus second-generation metal stents: a comparison study of 100 complex lesions treated under OCT guidance.

OBJECTIVES: The aim of this study was to compare the acute performance of the PLLA ABSORB bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, California) with second-generation metal drug-eluting stents (DES) in complex coronary artery lesions. BACKGROUND: Thick polymer-based BVS have different mechanical properties than thin second-generation DES. Data on the acute performance of BVS are limited to simple coronary lesions treated in trials with strict inclusion criteria. METHODS: Fifty complex coronary lesions (all type American College of Cardiology/American Heart Association B2-C) treated with a BVS undergoing a final optical coherence tomography (OCT) examination were compared with an equal number of matched lesions treated with second-generation DES. The following stent performance indexes were assessed with OCT: mean and minimal area, residual area stenosis (RAS), incomplete strut apposition (ISA), tissue prolapse, eccentricity index, symmetry index, strut fracture, and edge dissection. RESULTS: One hundred lesions from 73 patients were analyzed. A higher balloon diameter/reference vessel diameter ratio was used for predilation in the BVS group (p < 0.01). Most of the BVS and DES were post-dilated with short noncompliant (NC) balloons of similar diameter. OCT showed in the BVS group a higher tissue prolapse area (p = 0.08) and greater incidence of ISA at the proximal edge (p = 0.04) with no difference in the overall ISA. The RAS was 20.2% in the BVS group and 21.7% in the DES group (p = 0.32). There was no difference in the eccentricity index. The minimal and mean lumen areas were similar in the 2 groups. Two cases of strut fractures occurred after the BVS, whereas none was observed in the DES. CONCLUSIONS: Based on OCT, the BVS showed similar post-procedure area stenosis, minimal lumen area, and eccentricity index as second-generation DES. The different approach for lesion preparation and routine use of OCT guidance during BVS expansion may have contributed to these results.

Deriving coronary artery calcium scores from CT coronary angiography: a proposed algorithm for evaluating stable chest pain.

We validate a method of calcium scoring on CT coronary angiography (CTCA) and propose an algorithm for the assessment of patients with stable chest pain. 503 consecutive patients undergoing coronary artery calcium score (CACS) and CTCA were included. A 0.1 cm2 region of interest was used to determine the mean contrast density on CTCA images either in the left main stem (LM) or right coronary artery. Axial 3 mm CTCA images were scored for calcium using conventional software with a modified threshold: mean LM contrast density (HU) + 2SD. A conversion factor (CF) for predicting CACS from raw CTCA scores (rCTCAS) was determined using a multivariable regression model adjusted for model over-optimism (1,000 bootstrap samples). Accuracy of this method was determined using weighted kappa for NICE recommended CACS groupings (0, 1-400, >400) and Bland-Altman analysis for absolute score. With the CF applied: CACS = (1.183 × rCTCAS) + (0.002 × rCTCAS × threshold), there was excellent agreement between methods for absolute score (mean difference 5.44 [95% limits of agreement -207.0 to 217.8]). The method discriminated between high (>400) and low risk (<400) calcium scores with a sensitivity and specificity of 85 and 99%, and a PPV and NPV of 92 and 98%, respectively, and led to a significant reduction in radiation exposure (6.9 [5.1-10.2] vs. 5.2 [6.3-8.7] mSv; p < 0.0001). Our proposed method allows a comprehensive assessment of coronary artery pathology through the use of an individualised, semi-automated approach. If incorporated into stable chest pain guidelines the need for further functional testing or invasive angiography could be determined from CTCA alone, supporting a change to the current guidelines.

Multidetector computed tomography of congenital aortic abnormalities.

For many years invasive angiographic techniques have been considered as the gold standard for the assessment of large arterial abnormalities. However, the complexities and complications inherent to invasive imaging have meant that more recently non-invasive techniques such as echocardiography, Magnetic Resonance Imaging (MRI) and multidetector CT (MDCT) have been increasingly used in congenital cardiovascular disorders. In particular, MDCT has emerged as a fundamental tool for the diagnosis and pre-surgical work-up of aortic abnormalities due to its high spatial resolution, large area of coverage, and short scan time, and therefore is now one of the most widely used modalities for the detection of congenital abnormalities of the aorta. The purpose of this pictorial review is to review the spectrum of abnormalities of the aorta than can be reliably detected by MDCT both in infants and in adulthood. Abnormalities of the aortic root, ascending aorta, aortic arch, and descending aorta will be described separately.

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.

Concept of the central clip: when to use one or two MitraClips®.

AIMS: Percutaneous edge-to-edge mitral valve repair with the MitraClip(®) was shown to be a safe and feasible alternative compared to conventional surgical mitral valve repair. We analyse the concept of the central clip and the predictors for the need of more than one MitraClip(®) in our high-risk surgical population with severe mitral regurgitation (MR). METHODS AND RESULTS: Patients with severe MR (3 or 4+) and high operative risk (as defined by logistic EuroSCORE) refused for conventional mitral valve repair were considered for MitraClip(®). The procedure was performed under general anaesthesia with transoesophageal echocardiographic (TOE) guidance. Device success was defined as placement of one or more MitraClips(®) with a reduction of MR to ≤2+. Patients were followed up clinically and with TOE at one month and one year. From September 2009 to March 2012, 43 patients with severe MR with a mean age of 74.8±10.7 years (30 males, 13 females; mean logistic EuroSCORE 24.1±11, mean LVEF 47.5±18.5%; mean±SD) were treated. Median follow-up was 385 days (104-630; Q1-Q3). Device implantation success was 93%. All patients were treated following the central clip concept: 52.5% of MR was degenerative in aetiology and 47.5% was functional. The degree of MR was reduced from 3.6±0.4 to 1.4±0.6 (p<0.001); NYHA Class improved from 3.1±0.4 to 1.8±0.7 (p<0.001). Nineteen patients (47.5%) received two or more clips. Vena contracta (p<0.001) and the presence of two broad jets (p<0.001) were correlated with the need for a second clip. The presence of a restricted posterior mitral valve leaflet (PML) was inversely correlated with the need for more than one clip (p=0.02). A cut-off value of ≥7.5 mm for vena contracta predicted the need for a second clip (sensitivity 83%, specificity 90%, p=0.01). CONCLUSIONS: The central MitraClip(®) concept achieved a significant reduction in the degree of mitral regurgitation in the majority of patients treated. The presence of a broad jet (quantified by a vena contracta greater than 7.5 mm) significantly predicted the need for more than one clip.

Optical coherence tomography characteristics of in-stent restenosis are different between first and second generation drug eluting stents.

AIMS: Characterization of neointimal tissue is essential to understand the pathophysiology of in-stent restenosis (ISR) after drug eluting stent (DES) implantation. Using optical coherence tomography (OCT), we compared the morphologic characteristics of ISR between first and second generation DES. METHODS AND RESULTS: OCT was performed in 66 DES-ISR, defined as > 50% angiographic diameter stenosis within the stented segment. Patients with ISR of first generation sirolimus-eluting stents (SES), paclitaxel eluting stents (PES) and second generation zotarolimus-eluting stents (ZES), everolimus-eluting stents (EES) and biolimus-eluting stents (BES) were enrolled. Quantitative and qualitative ISR tissue analysis was performed at 1-mm intervals along the entire stent, and categorised as homogeneous, heterogeneous and neo-atherosclerosis. The presence of microvessels and peri-strut low intensity area (PSLIA) was determined in all ISR. Neoatherosclerosis was identified by lipid, calcium and thin-cap fibro-atheroma (TCFA) like lesions. We compared the two DES generations at both early (< 1 year) and late (> 1 year) follow-ups.In second generation DES a heterogeneous pattern was prevalent both before and after 1 year (57.1% and 58.6% respectively). Neo-atherosclerosis was more common in the early period in first generation DES (19.4% vs 11.7%, p < 0.01), but after one year was more prevalent in second generation DES (7.0% vs 19.3%, p < 0.01). Similar prevalence of TCFAs was observed in both groups in all comparisons. CONCLUSIONS: When ISR restenosis occurs in second generation DES, the current data suggest a different time course and different morphological characteristics from first generation. Future prospective studies should evaluate the relationship between ISR morphology, time course and clinical events.