Atrial fibrillation incidence, prevalence, predictors, and adverse outcomes in acute coronary syndromes: A pooled analysis of data from 8 million patients.

OBJECTIVE: To summarize data on the prevalence/incidence, risk factors and prognosis of atrial fibrillation (AF) in patients with acute coronary syndromes (ACS). METHODS: MEDLINE, Embase, and Web of Science were searched to identify all published studies providing relevant data through August 23, 2020. Random-effects meta-analysis method was used to pool estimates. RESULTS: We included 109 studies reporting data from a pooled population of 8 239 364 patients. The prevalence rates were 5.8% for pre-existing AF, 7.3% for newly diagnosed AF, and 11.3% for prevalent (total) AF, in patients with ACS. Predictors of newly diagnosed AF included age (per year increase) (adjusted odds ratio [aOR]: 1.05), C-reactive protein (aOR: 1.49), left atrial (LA) diameter (aOR: 1.08), LA dilatation (aOR: 2.32), left ventricular ejection fraction <40% (aOR: 1.82), hypertension (aOR: 1.87), and Killip ˃ 1 (aOR: 1.85), p < .01 in all analyzes. Newly diagnosed AF was associated with an increased risk of acute heart failure (adjusted hazard ratio [aHR]: 3.20), acute kidney injury (aHR: 3.09), re-infarction (aHR: 1.96), stroke (aHR: 2.15), major bleeding (aHR: 2.93), and mortality (aHR: 1.80) in the short term; and with an increased risk of heart failure (aHR: 2.21), stroke (aHR: 1.75), mortality (aHR: 1.67), CV mortality (aHR: 2.09), sudden cardiac death (aHR: 1.53), and a composite of major adverse cardiovascular events (aHR: 1.54) in the long term (beyond 1 month), p < .05 in all analyzes. CONCLUSION: One in nine patients with ACS has AF, with a high proportion of newly diagnosed AF. AF, in particular newly diagnosed AF, is associated with poor short-term and long-term outcomes in patients with ACS.

Effects of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients.

BACKGROUND: Cardiovascular morbidity and mortality remain high in recipients of a kidney transplant. The persistence of a patent arteriovenous fistula (AVF) after transplantation may contribute to ongoing maladaptive cardiovascular remodeling. The ability to reverse this maladaptive remodeling by ligation of this AVF is unknown. We conducted the first randomized controlled trial to evaluate the effect of AVF ligation on cardiac structure and function in stable kidney transplant recipients. METHODS: In this randomized controlled trial, kidney transplant recipients (>12 months after transplantation with stable graft function) were randomized to AVF ligation or no intervention. All participants underwent cardiac magnetic resonance imaging at baseline and at 6 months. The primary outcome was the change in left ventricular (LV) mass. Secondary outcomes included changes in LV volumes, left and right atrial areas, LV ejection fraction, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, cardiac output/index, brachial flows (ipsilateral to AVF), and pulmonary artery velocity. RESULTS: A total of 93 patients were screened, of whom 64 met the inclusion criteria and were randomized to the AVF ligation (n=33) or control (n=31) group. Fifty-four participants completed the study: 27 in the AVF ligation group and 27 in the control group. On the second cardiac magnetic resonance scan, a mean decrease of 22.1 g (95% CI, 15.0-29.1) was observed in LV mass in the AVF ligation group compared with a small increase of 1.2 g (95% CI, -4.8 to 7.2) in the control group ( P<0.001). Significant decreases in LV end-diastolic volumes, LV end-systolic volumes, cardiac output, cardiac index, atrial volumes, and NT-proBNP were also seen in the AVF closure group ( P<0.01). No significant changes were observed in LV ejection fraction ( P=0.93) and pulmonary artery velocity ( P=0.07). No significant complications were noted after AVF ligation. No changes in estimated glomerular filtration rate or systolic and diastolic blood pressures were observed between cardiac magnetic resonance scans. CONCLUSIONS: Elective ligation of patent AVF in adults with stable kidney transplant function resulted in clinically significant reduction of LV myocardial mass. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry URL: https://www.anzctr.org.au . Unique Identifier: ACTRN12613001302741.

Aortic distensibility is associated with both resting and hyperemic coronary blood flow.

A large body of evidence demonstrates an independent association between arterial stiffness and prospective risk of cardiovascular events. A reduction in coronary perfusion is presumed to underscore this association; however, studies confirming this are lacking. This study compared invasive measures of coronary blood flow (CBF) with cardiac magnetic resonance (CMR)-derived aortic distensibility (AD). Following coronary angiography, a Doppler FloWire and infusion microcatheter were advanced into the study vessel. Average peak velocity (APV) was acquired at baseline and following intracoronary adenosine to derive coronary flow velocity reserve (CFVR = hyperemic APV/resting APV) and CBF [π × (diameter)2 × APV × 0.125]. Following angiography, patients underwent CMR to evaluate distensibility at the ascending aorta (AA), proximal descending aorta (PDA) and distal descending aorta (DDA). Fifteen participants (53 ± 13 yr) with minor epicardial disease (maximum stenosis <30%) were enrolled. Resting CBF was 44.1 ± 11.9 mL/min, hyperemic CBF was 143.8 ± 37.4 mL/min, and CFVR was 3.15 ± 0.48. AD was 3.89 ± 1.72·10-3mmHg-1 at the AA, 4.08 ± 1.80·10-3mmHg-1 at the PDA, and 4.42 ± 1.67·10-3mmHg-1 at the DDA. All levels of distensibility correlated with resting CBF (R2 = 0.350-0.373, P < 0.05), hyperemic CBF (R2 = 0.453-0.464, P < 0.01), and CFVR (R2 = 0.442-0.511, P < 0.01). This study demonstrates that hyperemic and, to a lesser extent resting CBF, are significantly associated with measures of aortic stiffness in patients with only minor angiographic disease. These findings provide further in vivo support for the observed prognostic capacity of large artery function in cardiovascular event prediction.NEW & NOTEWORTHY Cardiac magnetic resonance-derived aortic distensibility is associated with invasive measures of coronary blood flow. Large artery function is more strongly correlated with hyperemic than resting blood flow. Increased stiffness may represent a potential target for novel antianginal medications.

Do arteriovenous fistulas increase cardiac risk?

An effectively functioning arteriovenous fistula is the life line for patients on long-term hemodialysis, and for most an upper limb, native vessel fistula has significant short- and long-term advantages. There are, however, situations where a fistula has deleterious effects, including the relatively uncommon problem of severe heart failure exacerbated in particular by high-flow fistulas. There is also increasing evidence that a fistula can add to the already high burden of cardiovascular risk in patients with advanced kidney disease, including by promoting water and salt retention, and by inducing or worsening left ventricular hypertrophy. While cases periodically arise where a fistula needs to be ligated with some urgency, such as severe heart failure, an increasingly persuasive case can be made for electively ligating fistulas that are not being used. The most common example of this is in stable renal transplant recipients, where the risks of ligation are outweighed by the potential risks of maintaining an unused fistula. Surgically reducing the blood flow in large (usually upper arm) fistulas is also a legitimate maneuver in specific high-risk situations.

Ascending aortic blood flow velocity is increased in children with primary snoring/mild sleep-disordered breathing and associated with an increase in CD8 + T cells expressing TNFα and IFNγ.

Sleep-disordered breathing (SDB) is associated with cardiovascular disease and systemic inflammation in adults but this remains to be explored in children, especially in children with the most common form of SDB, i.e. primary snoring/mild SDB. This pilot study investigated the relationship between the cardiovascular function and inflammation in children with mild SDB. Nineteen participants aged 5-14 years underwent overnight polysomnography, cardiac magnetic resonance imaging (aortic blood flow velocity and left and right ventricular systolic function) and assessment for inflammatory markers (intracellular cytokine analysis of T cells by flow cytometry). Parents also completed the Sleep Disturbances Scale for Children (SDSC). Children with mild SDB exhibited increased ascending aortic peak systolic velocity compared to controls (SDB 119.95 m/s vs. control 101.49 m/s, p < 0.05). No significant group differences were observed for left and right ventricular ejection fraction or mean aortic blood flow velocity from either the ascending aorta or pulmonary artery. Children with mild SDB had increased inflammatory markers as demonstrated by elevated T cell interferon gamma (IFNγ) (SDB 52 ± 4% vs. control 25 ± 3% positive cells, p < 0.005) and tumour necrosis factor alpha (TNFα) (SDB 39 ± 4% vs. control 20 ± 2% positive cells, p < 0.005) expression from CD8+ cells. A strong positive correlation was observed between ascending aorta peak blood flow velocity and both TNFα and IFNγ (TNFα, r = 0.54, p < 0.03; IFNγ, r = 0.63, p < 0.005, respectively). Polysomnography revealed that oxygen saturation (SaO2) nadir was significantly lower in children with mild SDB compared to controls (SDB 92.3 ± 2.7% vs. control 94.4 ± 1.6%, p < 0.05). A lower SaO2 nadir was associated with an increased ascending aorta peak systolic velocity (r = - 0.48, p < 0.05). As well, both a lower SaO2 nadir and an increased ascending aorta peak systolic velocity were associated with higher SDSC Sleep-Disordered Breathing and Disorder of Initiating and Maintaining Sleep subscale scores but not the polysomnographic-derived Obstructive Apnea-Hypopnea Index. The finding of elevated ascending aortic peak systolic blood flow velocity and its association with increased inflammatory markers suggests that the profile of cardiovascular changes noted in adult SDB may also occur in children with mild SDB.

The predictive capabilities of a novel cardiovascular magnetic resonance derived marker of cardiopulmonary reserve on established prognostic surrogate markers in patients with pulmonary vascular disease: results of a longitudinal pilot study.

BACKGROUND: No unified method exists to effectively predict and monitor progression of pulmonary arterial hypertension (PAH). We assessed the longitudinal relationship between a novel marker of cardiopulmonary reserve and established prognostic surrogate markers in patients with pulmonary vascular disease. METHODS AND RESULTS: Twenty participants with confirmed (n = 14) or at high risk (n = 6) for PAH underwent cardiovascular magnetic resonance (CMR) at baseline and after ~6 months of guideline-appropriate management. Ten PAH participants underwent RHC within 48 h of each CMR. RHC (mean pulmonary arterial pressure, mPAP; pulmonary vascular resistance index, PVRI; cardiac index, CI) and phase-contrast CMR (mean pulmonary arterial blood flow velocity, meanPAvel) measurements were taken at rest and during continuous adenosine infusion (70/140/210 mcg/kg/min). Initial meanPAvel's (rest and hyperemic) were correlated with validated surrogate prognostic parameters (CMR: RV ejection fraction, RVEF; RV end systolic volume indexed, RVESVI; RHC: PVRI, CI; biomarker: NT-pro brain natriuretic peptide, NTpBNP; clinical: 6-min walk distance, 6MWD), a measure of pulmonary arterial stiffness (elastic modulus) and volumetric estimation of RV ventriculoarterial (VA) coupling. Changes in meanPAvel's were correlated with changes in comparator parameters over time. At initial assessment, meanPAvel at rest correlated significantly with PVRI (inversely), CI (positively) and elastic modulus (inversely) (R 2 > 0.37,P < 0.05 for all), whereas meanPAvel at peak hyperemia correlated significantly with PVRI, RVEF, RVESVI, 6MWD, elastic modulus and VA coupling (R 2 > 0.30,P < 0.05 for all). Neither resting or hyperemia-derived meanPAvel correlated with NTpBNP levels. Initial meanPAvel at rest correlated significantly with RVEF, RVESVI, CI and VA coupling at follow up assessment (R 2 > 0.2,P < 0.05 for all) and initial meanPAvel at peak hyperemia correlated with RVEF, RVESVI, PVRI and VA coupling (R 2 > 0.37,P < 0.05 for all). Change in meanPAvel at rest over time did not show statistically significant correlation with change in prognostic parameters, while change in meanPAvel at peak hyperemia did show a significant relationship with ΔRVEF, ΔRVESVI, ΔNTpBNP and ΔCI (R 2 > 0.24,P < 0.05 for all). CONCLUSION: MeanPAvel during peak hyperemia correlated with invasive, non-invasive and clinical prognostic parameters at different time points. Further studies with predefined clinical endpoints are required to evaluated if this novel tool is a marker of disease progression in patients with pulmonary vascular disease.

The Impact of Arteriovenous Fistulae for Hemodialysis on the Cardiovascular System.

An arteriovenous fistula (AVF) is critical for the provision of optimal chronic hemodialysis. Its creation causes significant hemodynamic alterations in cardiovascular parameters, and can result in progressive left and right heart failure. Despite successful kidney transplantation, many patients retain a functional AVF indefinitely, which may contribute to ongoing adverse cardiovascular outcomes. A similar high risk:benefit ratio may exist in peritoneal dialysis patients with "backup" AVF.

Characterisation of Myocardial Injury via T1 Mapping in Early Reperfused Myocardial Infarction and its Relationship with Global and Regional Diastolic Dysfunction.

BACKGROUND: Cardiovascular magnetic resonance (CMR) advances in imaging techniques, permits the ability to accurately characterise tissue injury post myocardial infarction. Pre-contrast T1 mapping enables this through measurement of pre-contrast T1 relaxation times. We investigate the relationship between T1 characterisation of myocardial injury with global and regional diastolic function. METHODS: Revascularised acute myocardial infarction patients with normal left ventricular (LV) systolic function on TTE were assessed by 1.5T CMR. Acute regional diastolic wall motion abnormalities, global diastolic function measurements, acute segmental damage fraction with LGE and mean segmental pre-contrast T1 values were assessed on matching short axis slices. RESULTS: Forty-four patients were analysed. Mean LVEF was 62.1±9.4%. No difference between NSTEMI (22/44) and STEMI in mean pre-contrast T1 values of infarcted (1025.0±109.2 vs 1011.0±81.6ms, p=0.70), adjacent (948.3±45.3 vs 941.1±46.6ms, p=0.70) and remote (888.8±52.8 vs 881.2±54.5ms, p=0.66) segments was detected. There was no correlation between pre-contrast T1 of infarcted segments with global diastolic dysfunction (E/A, r2=0.216, p=0.06; S/D, r2=0.243, p=0.053; E/E', r2=0.240, p=0.072), but there was significantly positive, moderate correlation with circumferential diastolic strain rate, (r2=0.579, p<0.01) with excellent agreement and reproducibility. CONCLUSION: Cardiac magnetic resonance evaluation of pre-contrast T1 values revealed no difference between NSTEMI and STEMI patients in terms of tissue characterisation post-myocardial infarction. However, pre-contrast T1 of infarcted tissue is significantly correlated with regional diastolic circumferential strain rate.

Radial versus femoral access for elderly patients with acute coronary syndrome undergoing coronary angiography and intervention: insights from the RIVAL trial.

BACKGROUND: Radial access for percutaneous coronary intervention is associated with lower rates of access site complications and bleeding. However, elderly patients have more complex vascular anatomy and radial access may be more challenging in this population. There remains uncertainty regarding the role of radial access in elderly patients undergoing cardiac catheterization. METHODS AND RESULTS: The RIVAL trial randomized patients with acute coronary syndromes undergoing cardiac catheterization to radial versus femoral access. In this analysis, the rates of access site complications and access site cross-over were compared across different age groups. Among the 7,021 patients, 1035 (15%) were ≥75 years of age. Across all age categories, radial access was consistently associated with higher rates of access site cross over and lower rates of major access site complications, with no significant interaction between age and access site. Radial access was associated with lower rates of major vascular access site complications in patients ≥75 years of age (3.6% vs 6.6%; P = .03) and in patients <75 years of age (1.0% vs 3.2%; P < .001; P value for interaction = .2). The rates of access site crossover were higher with radial access among patients ≥75 (12.5% vs 2.6%; P < .001) and <75 (6.7% vs 1.9%; P < .001; P value for interaction = .9). There were no significant differences in the primary composite outcome (death, myocardial infarction, stroke or non coronary artery bypass graft major bleeding) or its individual components in either age group. In patients ≥75 years of age undergoing primary percutaneous coronary intervention, there was no significant difference in procedure time (120 vs 115 minutes; P = .3). CONCLUSIONS: Consistent with the overall RIVAL trial population, elderly patients undergoing cardiac catheterization have lower rates of major bleeding or access site complications and higher rates of access site crossover with radial access compared to femoral access.

Incremental benefits of repeated mesenchymal stromal cell administration compared with solitary intervention after myocardial infarction.

BACKGROUND AIMS: Traditionally, stem cell therapy for myocardial infarction (MI) has been administered as a single treatment in the acute or subacute period after MI. These time intervals coincide with marked differences in the post-infarct myocardial environment, raising the prospect that repeat cell dosing could provide incremental benefit beyond a solitary intervention. This prospect was evaluated with the use of mesenchymal stromal cells (MSCs). METHODS: Three groups of rats were studied. Single-therapy and dual-therapy groups received allogeneic, prospectively isolated MSCs (1 × 10(6) cells) by trans-epicardial injection immediately after MI, with additional dosing 1 week later in the dual-therapy cohort. Control animals received cryopreservant solution only. Left ventricular (LV) dimensions and ejection fraction (EF) were assessed by cardiac magnetic resonance immediately before MI and at 1, 2 and 4 weeks after MI. RESULTS: Immediate MSC treatment attenuated early myocardial damage with EF of 35.3 ± 3.1% (dual group, n = 12) and 35.2 ± 2.2% (single group, n = 15) at 1 week after MI compared with 22.1 ± 1.9% in controls (n = 17, P < 0.01). In animals receiving a second dose of MSCs, EF increased to 40.7 ± 3.1% by week 4, which was significantly higher than in the single-therapy group (EF 35.9 ± 1.8%, P < 0.05). Dual MSC treatment was also associated with greater myocardial mass and arteriolar density, with trends toward reduced myocardial fibrosis. These incremental benefits were especially observed in remote (non-infarct) segments of LV myocardium. CONCLUSIONS: Repeated stem cell intervention in both the acute and the sub-acute period after MI provides additional improvement in ventricular function beyond solitary cell dosing, largely owing to beneficial changes remote to the area of infarction.

Magnetic resonance-derived circumferential strain provides a superior and incremental assessment of improvement in contractile function in patients early after ST-segment elevation myocardial infarction.

BACKGROUND: We evaluate whether circumferential strain derived from grid-tagged CMR is a better method for assessing improvement in segmental contractile function after STEMI compared to late gadolinium enhancement (LGE). METHODS: STEMI patients post primary PCI underwent baseline CMR (day 3) and follow-up (day 90). Cine, grid-tagged and LGE images were acquired. Baseline LGE infarct hyperenhancement was categorised as ≤25 %, 26-50 %, 51-75 % and >75 % hyperenhancement. The segmental baseline circumferential strain (CS) and circumferential strain rate (CSR) were calculated from grid-tagged images. Segments demonstrating an improvement in wall motion of ≥1 grade compared to baseline were regarded as having improved segmental contractile-function. RESULTS: Forty-five patients (aged 58 ± 12 years) and 179 infarct segments were analysed. A baseline CS cutoff of -5 % had sensitivity of 89 % and specificity of 70 % for detection of improvement in segmental-contractile-function. On receiver-operating characteristic analysis for predicting improvement in contractile function, AUC for baseline CS (0.82) compared favourably to LGE hyperenhancement (0.68), MVO (0.67) and baseline-CSR (0.74). On comparison of AUCs, baseline CS was superior to LGE hyperenhancement and MVO in predicting improvement in contractile function (P < 0.001). On multivariate-analysis, baseline CS was the independent predictor of improvement in segmental contractile function (P < 0.001). CONCLUSION: Grid-tagged CMR-derived baseline CS is a superior predictor of improvement in segmental contractile function, providing incremental value when added to LGE hyperenhancement and MVO following STEMI. KEY POINTS: Baseline CS predicts contractile function recovery better than LGE and MVO following STEMI. Baseline CS predicts contractile function recovery better than baseline CSR following STEMI. Baseline CS provides incremental value to LGE and MVO following STEMI.

Beneficial cardiovascular remodeling following arterio-venous fistula ligation post-renal transplantation: a longitudinal magnetic resonance imaging study.

Despite improvements in survival following renal transplantation, high rates of cardiovascular morbidity and mortality remain. Persistence of arterio-venous fistulae (AVF) may contribute to maladaptive cardiovascular remodeling and poor health outcomes in this cohort. Utilizing recent advances in cardiovascular magnetic resonance imaging (CMR), we prospectively evaluated alterations in cardiac and vascular structure and function six months after elective ligation of AVF, following stable, successful renal transplantation. Eighteen subjects underwent CMR evaluation of cardiac structure and function, aortic distensibility and endothelial function prior to AVF ligation and at six months. At follow-up, while left ventricular ejection fraction was unchanged, mean cardiac output decreased by 15.6% (9.6 ± 2.9 L/min vs. 8.1 ± 2.3 L/min, p = 0.004) and left ventricular mass had regressed by 10% (166 ± 56 g vs. 149 ± 51 g, p = 0.0001). Significant improvements were also noted in right ventricular and biatrial structure and function. Aortic distensibility was unchanged at follow-up, but endothelial dependent vasodilatation had improved (2.5 ± 6.5% vs. 8.0 ± 5.9%, p = 0.04). Elective AVF ligation following successful renal transplantation is associated with improvements in left ventricular mass, right ventricular, and biatrial structure and function. Further randomized studies are warranted to determine the potential clinical improvement following AVF ligation in this cohort.

Dramatic improvement in decompensated right heart failure due to severe tricuspid regurgitation following ligation of arteriovenous fistula in a renal transplant recipient.

Arteriovenous (AV) fistulas with high blood flow rate are necessary for adequate hemodialysis, but they can also cause significant hemodynamic changes, including raised cardiac output, left ventricular hypertrophy and occasionally overt cardiac failure (Basile et al., Nephrol Dial Transplant, 23, 2008, 282; Unger et al., Am J Transplant, 4, 2004, 2038). We now report a case of rapid and dramatic improvement in symptomatic right heart failure due to severe tricuspid regurgitation following ligation of an arteriovenous fistula. Cardiac magnetic resonance imaging (MRI) performed before and after the ligation of fistula showed striking improvement in both the tricuspid regurgitation and right ventricular dimensions, with minimal impact on left ventricular mass, size, and function.

Characterization of thrombogenic, endothelial and inflammatory markers in supraventricular tachycardia: a study in patients with structurally normal hearts.

Patients with atrial fibrillation (AF) are at an increased risk of thromboembolism and stroke primarily from the development of thrombi within the left atrium. Pathological changes in blood constituents and atrial endothelial damage promote left atrial thrombus formation. It is not known whether factors predisposing to left atrial thrombus formation in AF are disease specific or also evident within the normal heart. The present study examined whether there are differences in platelet reactivity, endothelial function and inflammation in blood samples obtained from intracardiac and peripheral sites in subjects within structurally normal hearts. Sixteen patients with diagnosed left-sided supraventricular tachycardia (SVT) undergoing a routine elective electrophysiological study and ablation were investigated. Blood samples were taken simultaneously from the femoral vein, right atrium and left atrium, immediately following trans-septal puncture and prior to heparin bolus administration. Between peripheral and atrial sample sites, patients with SVT showed no change in platelet reactivity or aggregation (P-selectin (CD62P) P = 0.91; platelet-derived soluble CD40 ligand P = 0.9), thrombus formation (thrombin-antithrombin complex; P = 0.55), endothelial function (von Willebrand factor P = 0.75; asymmetric dimethylarginine (ADMA) P = 0.97; nitric oxide P = 0.61), or inflammation (vascular cell adhesion molecule-1 P = 0.59; intercellular adhesion molecule-1 (ICAM-1) P = 0.69). However, SVT patients had lower ADMA and ICAM-1 levels than AF patients. The present study demonstrates, for the first time, that SVT subjects with structurally normal hearts have consistent haemostatic function between atrial and peripheral sites. These results suggest that the atria of SVT patients do not contain predisposing thrombogenic, endothelial or inflammatory factors that promote and/or initiate thrombus formation.

Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnligHTN I trial.

AIMS: Catheter-based renal artery sympathetic denervation has emerged as a novel therapy for treatment of patients with drug-resistant hypertension. Initial studies were performed using a single electrode radiofrequency catheter, but recent advances in catheter design have allowed the development of multi-electrode systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the EnligHTN(™) multi-electrode system. METHODS AND RESULTS: We conducted the first-in-human, prospective, multi-centre, non-randomized study in 46 patients (67% male, mean age 60 years, and mean baseline office blood pressure 176/96 mmHg) with drug-resistant hypertension. The primary efficacy objective was change in office blood pressure from baseline to 6 months. Safety measures included all adverse events with a focus on the renal artery and other vascular complications and changes in renal function. Renal artery denervation, using the EnligHTN system significantly reduced the office blood pressure from baseline to 1, 3, and 6 months by -28/10, -27/10 and -26/10 mmHg, respectively (P < 0.0001). No acute renal artery injury or other serious vascular complications occurred. Small, non-clinically relevant, changes in average estimated glomerular filtration rate were reported from baseline (87 ± 19 mL/min/1.73 m2) to 6 months post-procedure (82 ± 20 mL/min/1.73 m2). CONCLUSION: Renal sympathetic denervation, using the EnligHTN multi-electrode catheter results in a rapid and significant office blood pressure reduction that was sustained through 6 months. The EnligHTN system delivers a promising therapy for the treatment of drug-resistant hypertension.

Clopidogrel improves microvascular endothelial function in subjects with stable coronary artery disease.

BACKGROUND: Clopidogrel therapy has recently been shown to reduce cardiovascular events in patients with stable vascular disease. This benefit may be due to effects not exclusively related to platelet aggregation. The aim of this study was to evaluate the effect of clopidogrel therapy on microvascular endothelial function in subjects with stable coronary artery disease (CAD). METHODS AND RESULTS: Forty subjects with stable CAD were randomised to clopidogrel therapy (75mg/day) or control. Blood and endothelial function testing occurred at baseline, one week and three months following randomisation. Microvascular endothelial function was assessed via reactive hyperaemic index (RHI). Platelet function was assessed by adenosine diphosphate (ADP)-induced whole blood aggregation and the VerifyNow™ system. Plasma markers of endothelial function (asymmetric dimethylarginine, ADMA) and oxidative stress (myeloperoxidase, MPO) were also tested. The primary endpoint was endothelial function assessment (RHI) at three months. At one week RHI increased by 20±10% in the clopidogrel group; this effect was maintained at three months (21±9% increase from baseline; P<0.01). A significant decrease in ADP-induced platelet aggregation and P2Y12 reaction units was observed in the clopidogrel therapy group (P<0.01). There was no correlation between endothelial function and platelet function testing in the clopidogrel therapy group. CONCLUSION: Clopidogrel therapy is associated with improved microvascular endothelial function in patients with stable CAD. This effect is independent of its effects on ADP-induced platelet reactivity.

Anti-Anginal Efficacy of Zibotentan in the Coronary Slow-Flow Phenomenon.

BACKGROUND: Patients with coronary microvascular disorders often experience recurrent angina for which there are limited evidence-based therapies. These patients have been found to exhibit increased plasma levels of endothelin; thus, selective endothelin-A (Et-A) receptor blockers such as zibotentan may be an effective anti-anginal therapy in these patients. The study evaluated the impact of a 10 mg daily dose of zibotentan on spontaneous angina episodes in patients with the coronary slow-flow phenomenon who had refractory angina (i.e., experiencing angina at least three times/week despite current anti-anginal therapy). METHODS: Using a randomized, double-blind, placebo-controlled, crossover trial design with 4-week treatment periods, 18 patients (63.2 ± 9.9 years, 33% females) were recruited. The primary endpoint was angina frequency as measured by an angina diary, with secondary endpoints including nitrate consumption, angina duration/severity and the Seattle Angina Questionnaire (SAQ) domains. RESULTS: During the 4 weeks of therapy, angina frequency significantly improved with zibotentan therapy (placebo 41.4 (58.5) vs. zibotentan 29.2 (31.6), p < 0.05), and sublingual nitrate consumption significantly reduced (placebo 11.8 (15.2) vs. zibotentan 8.8 (12.9), p < 0.05. CONCLUSIONS: Zibotentan improved the frequency of spontaneous angina episodes and reduced sublingual nitrate consumption in patients unresponsive to standard anti-anginal therapy.