Ticagrelor versus prasugrel in acute coronary syndrome: sex-specific analysis from the RENAMI Registry.

BACKGROUND: The use of potent P2Y12 inhibitors (ticagrelor & prasugrel) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions (PCI) is a class I recommendation. We performed a sex-specific analysis comparing the difference in efficacy and safety outcomes between ticagrelor and prasugrel in a real-world ACS population. METHODS: Data from the multicenter REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) for 4424 ACS patients who underwent PCI and were treated with ticagrelor or prasugrel between 2012 to 2016 were analyzed. Mean follow-up was 17±9 months. RESULTS: After propensity score matching, there was no significant difference in the occurrence of primary endpoint of net adverse cardiac events between ticagrelor and prasugrel in men (HR: 0.94; 95% CI: 0.69-1.29; P=0.71), or women (HR: 1.17; 95% CI: 0.63-2.20; P=0.62; P interaction [sex] = 0.40). Similarly, no differences were found in the occurrence of any of the secondary endpoints (MACE, all cause death, re-infarction, stent thrombosis, BARC major bleeding and BARC any bleeding) between the two P2Y12 groups between men and women. CONCLUSIONS: In this real-world ACS population, no relative difference in efficacy or safety outcomes were found between ticagrelor and prasugrel between sexes.

The impact of coronary perforation in percutaneous interventions involving the left main stem coronary artery in the United Kingdom 2007-2014: Insights from the British Cardiovascular Intervention Society database.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly utilized for treatment of coronary disease involving the unprotected left main stem (ULMS). However, no studies to date have examined the outcomes of such interventions when complicated by coronary perforation (CP). METHODS: Using the British Cardiovascular Intervention society (BCIS) database, data were analyzed on all ULMS-PCI procedures complicated by CP in England and Wales between 2007 and 2014. Multivariate logistic regressions were used to identify predictors of ULMS CP and to evaluate the association between this complication and outcomes. RESULTS: During 10,373 ULMS-PCI procedures, CP occurred more frequently than in non-ULMS-PCI (0.9 vs. 0.4%, p < .001) with a stable annual incidence. Covariates associated with CP included number of stents used, female gender, use of rotational atherectomy and chronic total occlusion (CTO) intervention. Adjusted odds of adverse outcomes for ULMS-PCI complicated by CP were higher for peri-procedural complications including cardiogenic shock, tamponade, side-branch loss, DC cardioversion, in-hospital major bleeding, transfusion requirement, and peri-procedural myocardial infarction. There were also significantly increased odds for in-hospital major adverse cardiac events (MACCE, OR 8.961, 95% CI [4.902-16.383]) and 30-day mortality (OR 5.301, 95% CI [2.741-10.251]). CONCLUSIONS: CP is an infrequent event during ULMS-PCI and is predicted by female gender, rotational atherectomy, CTO interventions or number of stents used. CP was associated with significantly higher odds of mortality and morbidity, but at rates similar to previously published all-comer PCI complicated by CP.

Excimer laser coronary atherectomy during complex PCI: An analysis of 1,471 laser cases from the British Cardiovascular Intervention Society database.

INTRODUCTION: Excimer laser coronary atherectomy (ELCA) is a recognized adjunctive therapy utilized in the percutaneous management of complex coronary lesions. Studies examining its safety and utility have been limited by small sample sizes. Our study examines the determinants and outcomes of ELCA. METHODS: Using the British Cardiac Intervention Society database, data were analyzed on all PCI procedures in the UK between 2006-2016. Descriptive statistics and multivariate logistic regressions were used to examine baseline, procedural and outcome associations with ELCA. RESULTS: We identified 1,471 (0.21%) ELCA cases out of 686,358 PCI procedures. Baseline covariates associated with ELCA use were age, BMI, number of lesions, CTO or restenosis attempted and history of prior MI, CABG or PCI. Procedural co-variates associated with ELCA were the use of glycoprotein inhibitors, intravascular imaging, rotational atherectomy, cutting balloons, microcatheters and intra-aortic balloon pumps. Adjusted rates of in-hospital major adverse cardiac/cerebrovascular events (MACCE) or its individual components (death, peri-procedural MI, stroke and major bleed) were not significantly altered by the use of ELCA. However, there were higher odds of dissection (OR 1.52, 95% CI 1.17-1.98), perforation (OR 2.18, 95% CI 1.44-3.30), slow flow (OR: 1.67, 95% CI 1.18-2.36), reintervention (OR: 2.12, 95% CI 1.14-3.93) and arterial complications (OR: 1.63, 95% CI 1.21-2.21). CONCLUSIONS: ELCA use during complex PCI is associated with higher risk baseline and procedural characteristics. Although increased rates of acute procedural complications were observed, ELCA does not increase likelihood of in-hospital MACCE or its individual components.

Rotational Atherectomy Complicated by Coronary Perforation Is Associated With Poor Outcomes: Analysis of 10,980 Cases From the British Cardiovascular Intervention Society Database.

BACKGROUND: Rotational atherectomy (RA) during PCI is linked to a higher likelihood coronary perforations (CP). However, the evidence base on incidence, predictors and outcomes of this complication in RA-PCI remains limited. METHODS: Using the British Cardiac Intervention Society database, data were analysed on all RA-PCI procedures in UK 2007-2014. Descriptive statistics and multivariate logistic regressions were used to examine baseline, procedural and outcome associations. RESULTS: During 10,980 RA-PCI procedures, 167 CPs were recorded (1.52%) with a stable annual incidence. Baseline and procedural covariates associated with higher rates of RA perforation were number of stents used, female gender, smoking, and left-main stenosis. CP was significantly associated with shock, DC cardioversion, heart block, transfusion, emergency surgery, periprocedural MI, in-hospital major bleed, acute kidney injury, dissection, side branch loss and in-hospital death. CP was also associated with higher rates of in-hospital MACCE (OR 12.22, 95% CI 7.67-19.47), 30-day mortality (OR 10.02, 95% CI 5.87-17.09) and 12-month mortality (OR 3.90, 95% CI 2.53-6.02). CONCLUSIONS: CP is more frequent in RA-PCI than all-comer PCI and is associated with a significant burden of morbidity and mortality. There are a limited number of baseline and procedural co-variates associated with CP in RA-PCI, making it difficult to predict.

Renal Artery Branch Denervation: Evaluation of Lesion Characteristics Using a Thermochromic Liquid Crystal Phantom Model.

BACKGROUND: Lately, combined main vessel and branch ablation has been recommended during radiofrequency (RF) renal artery denervation. Utilising a validated renal artery phantom model, we aimed (1) to determine thermal injury extent (lesion depth, width and circumferential coverage) and electrode-tissue interface temperature for branch renal artery ablation, and (2) to compare the extent of thermal injury for branch versus main vessel ablation using the same RF System. METHODS: We employed a gel based renal artery phantom model simulating variable vessel diameter and flow, which incorporated a temperature sensitive thermochromic-liquid-crystal (TLC) film for assessing RF ablation thermodynamics. Ablations in a branch renal artery model (n = 32) were performed using Symplicity Spyral (Medtronic, Minneapolis, MN, USA). Lesion dimensions defined by the 51 °C isotherm, circumferential injury coverage, and electrode-tissue interface temperature were measured for all ablations at 60 seconds. RESULTS: Lesion dimensions were 2.13 ± 0.13 mm and 4.13 ± 0.18 mm for depth and width, respectively, involving 23% of the vessel circumference. Maximum electrode-tissue interface temperature was 68.31 ± 2.29 °C. No significant difference in lesion depth between branch and main vessel ablations was found (Δ = 0.02 mm, p = 0.60). However, lesions were wider in the branch (Δ=0.49 mm, p < 0.001) with a larger circumferential coverage compared to main vessel (arc angle of 82.02±3.27° versus 54.90±4.36°, respectively). CONCLUSIONS: In the phantom model, branch ablations were of similar depth but had larger width and circumferential coverage compared to main vessel ablations. Concerning safety, no overheating at the electrode-tissue interface was observed.

Renal Artery Denervation in Resistant Hypertension: The Good, The Bad and The Future.

Early studies of renal artery denervation (RAD) demonstrated efficacy in treating resistant hypertension patients with significant reduction in office blood pressure (BP). This resulted in a growing enthusiasm in the field and a rapid evolution of technology with expanding procedural indications. However, the first randomised sham-controlled trial, Symplicity HTN-3, failed to demonstrate a significant difference in BP reduction between the RAD and the sham control arm, which subsequently led to a major reduction in the clinical application of this procedure. Additionally, the results generated further interest into understanding the mechanism and factors affecting procedural success and identifying the limitations within the field. Many lessons were learned from Symplicity HTN-3 trial, and with recent evidence emerging for RAD in hypertension treatment, the field continues to be refined.

Transcatheter microwave ablation can deliver deep and circumferential perivascular nerve injury without significant arterial injury to provide effective renal denervation.

BACKGROUND: Clinical studies of transcatheter radiofrequency renal denervation for treating hypertension have been hampered by the lack of consistent denervation efficacy. We aimed to demonstrate the short-term efficacy and safety of transcatheter microwave renal denervation. METHODS: A novel 7F microwave system was validated in a sheep model of unilateral renal denervation. Up to two microwave ablations were delivered to each artery with maximum power at 100-110 W for 480 s. RESULTS: Catheter deployment and ablation was successful in all 19 targeted vessel segments, and ablation produced substantial circumferential perivascular injury; median ablation lesion area greater than 395 [interquartile range (IQR) 251-437] mm, depth 17.1 (IQR 15.8-18.4) mm, length 16 (IQR 12-20) mm, without collateral visceral injury. Limiting power to 100 W minimized arterial injury, while maintaining a deep circumferential perivascular ablation. Microwave denervation reduced median functional sympathetic nerve surface area at the renal hilum on antityrosine hydroxylase staining by 100% (IQR 87-100%, P = 0.0039), and median renal cortical norepinephrine content by 83% (IQR 76-92%, P = 0.0078), compared to the paired control kidney at 2-3 weeks postprocedure. CONCLUSION: Transcatheter microwave ablation can produce deep circumferential perivascular ablations over a long segment of the renal artery without significant arterial or collateral visceral injury to provide effective renal denervation.

Comparison of two different radiofrequency ablation systems for renal artery denervation: Evaluation of short-term and long-term follow up.

OBJECTIVES: To assess the clinical efficacy of renal artery denervation (RAD) in our center and to compare the efficacy of two different radiofrequency (RF) systems. BACKGROUND: Several systems are available for RF renal denervation. Whether there is a difference in clinical efficacy among various systems remains unknown. METHODS: Renal artery denervation was performed on 43 patients with resistant hypertension using either the single electrode Symplicity Flex (n = 20) or the multi-electrode EnligHTN system (n = 23). Median post-procedural follow-up was 32.93 months. The primary outcome was post-procedural change in office blood pressure (BP) within 1 year (short-term follow-up). Secondary outcomes were change in office BP between 1 and 4 years (long-term follow-up) and the difference in office BP reduction between the two systems at each follow-up period. RESULTS: For the total cohort, mean baseline office BP (systolic/diastolic) was 174/94 mmHg. At follow-up, mean changes in office BP from baseline were -19.70/-11.86 mmHg (P < 0.001) and -21.90/-13.94 mmHg (P < 0.001) for short-term and long-term follow-up, respectively. The differences in office BP reduction between Symplicity and EnligHTN groups were 8.96/1.23 mmHg (P = 0.42 for systolic BP, P = 0.83 for diastolic BP) and 9.56/7.68 mmHg (P = 0.14 for systolic BP, P = 0.07 for diastolic BP) for short-term and long-term follow-up, respectively. CONCLUSIONS: In our cohort, there was a clinically significant office BP reduction after RAD, which persisted up to 4 years. No significant difference in office BP reduction between the two systems was found.

Influence of Intramyocardial Adipose Tissue on the Accuracy of Endocardial Contact Mapping of the Chronic Myocardial Infarction Substrate.

BACKGROUND: Recent studies have demonstrated that intramyocardial adipose tissue (IMAT) may contribute to ventricular electrophysiological remodeling in patients with chronic myocardial infarction. Using an ovine model of myocardial infarction, we aimed to determine the influence of IMAT on scar tissue identification during endocardial contact mapping and optimal voltage-based mapping criteria for defining IMAT dense regions. METHOD AND RESULTS: In 7 sheep, left ventricular endocardial and transmural mapping was performed 84 weeks (15-111 weeks) post-myocardial infarction. Spearman rank correlation coefficient was used to assess the relationship between endocardial contact electrogram amplitude and histological composition of myocardium. Receiver operator characteristic curves were used to derive optimal electrogram thresholds for IMAT delineation during endocardial mapping and to describe the use of endocardial mapping for delineation of IMAT dense regions within scar. Endocardial electrogram amplitude correlated significantly with IMAT (unipolar r=-0.48±0.12, P<0.001; bipolar r=-0.45±0.22, P=0.04) but not collagen (unipolar r=-0.36±0.24, P=0.13; bipolar r=-0.43±0.31, P=0.16). IMAT dense regions of myocardium reliably identified using endocardial mapping with thresholds of <3.7 and <0.6 mV, respectively, for unipolar, bipolar, and combined modalities (single modality area under the curve=0.80, P<0.001; combined modality area under the curve=0.84, P<0.001). Unipolar mapping using optimal thresholding remained significantly reliable (area under the curve=0.76, P<0.001) during mapping of IMAT, confined to putative scar border zones (bipolar amplitude, 0.5-1.5 mV). CONCLUSIONS: These novel findings enhance our understanding of the confounding influence of IMAT on endocardial scar mapping. Combined bipolar and unipolar voltage mapping using optimal thresholds may be useful for delineating IMAT dense regions of myocardium, in postinfarct cardiomyopathy.

Comparison of new-generation renal artery denervation systems: assessing lesion size and thermodynamics using a thermochromic liquid crystal phantom model.

AIMS: The aim of this study was to evaluate and compare lesion dimensions and thermodynamics of the new-generation multi-electrode Symplicity Spyral and the new-generation multi-electrode EnligHTN renal artery denervation systems, using a thermochromic liquid crystal phantom model. METHODS AND RESULTS: A previously described renal artery phantom model was used as a platform for radiofrequency ablation. A total of 32 radiofrequency ablations were performed using the multi-electrode Symplicity Spyral (n=16) and the new-generation EnligHTN systems (n=16). Both systems were used as clinically recommended by their respective manufacturer. Lesion borders were defined by the 51°C isotherm. Lesion size (depth and width) was measured and compared between the two systems. Mean lesion depth was 2.15±0.02 mm for the Symplicity Spyral and 2.32±0.02 mm for the new-generation EnligHTN (p-value <0.001). Mean lesion width was 3.64±0.08 mm and 3.59±0.05 mm (p-value=0.61) for the Symplicity Spyral and the new-generation EnligHTN, respectively. CONCLUSIONS: The new-generation EnligHTN system produced lesions of greater depth compared to the Symplicity Spyral under the same experimental conditions. Lesion width was similar between both systems. Achieving greater lesion depth by use of the new-generation EnligHTN may result in better efficacy of renal artery denervation.

Slow Pathway Radiofrequency Ablation Using Magnetic Navigation: A Description of Technique and Retrospective Case Analysis.

BACKGROUND: The Magnetic Navigation System (MNS) catheter was shown to be stable in the presence of significant cardiac wall motion and delivered more effective lesions compared to manual control. This stability could potentially make AV junctional re-entrant tachycardia (AVNRT) ablation safer. The aim of this study is to describe the method of mapping and ablation of AVNRT with MNS and 3-D electro-anatomical mapping system (CARTO, Biosense Webster, Diamond bar, CA, USA) anatomical mapping, with a view to improve the safety of ablation. METHODS: The method of precise mapping and ablation with MNS is described. Consecutive AVNRT cases (n=30) from 2012 January to 2015 November, in which magnetic navigation was used, are analysed. RESULTS: Ablation was successful in 27 (90%) out of 30 patients. In three cases, ablation was abandoned due to the proximity of the three-dimensional His image to the potential ablation site. No complications, including AV nodal injury, occurred. The distance from the nearest His position to successful ablation site in both LAO and RAO projections of CARTO images was 26.4±8.8 and 27±7.7mm respectively. Only in two (9%) patients, ablation needed to be extended superior to the plane of coronary sinus ostium, towards the His bundle region, to achieve slow pathway modification. CONCLUSION: AVNRT ablation with MNS allows for accurate mapping of the AV node and stable ablation at a safe distance, which could help avoid AV nodal injury. We recommend this modality for younger patients with AVNRT.

Transcatheter non-contact microwave ablation may enable circumferential renal artery denervation while sparing the vessel intima and media.

AIMS: Trials of transcatheter renal artery denervation (RDN) have failed to show consistent antihypertensive efficacy. Procedural factors and limitations of radiofrequency ablation can lead to incomplete denervation. The aim of the study was to show that non-contact microwave catheter ablation could produce deep circumferential perivascular heating while avoiding injury to the renal artery intima and media. METHODS AND RESULTS: A novel microwave catheter was designed and tested in a renal artery model consisting of layers of phantom materials embedded with a thermochromic liquid crystal sheet, colour range 50-78°C. Ablations were performed at 140 W for 180 sec and 120 W for 210 sec, delivering 25,200 J with renal arterial flow at 0.5 L/min and 0.1 L/min. Transcatheter microwave ablations 100-160 W for 180 sec were then performed in the renal arteries of five sheep. In vitro, ablations at 140 W and 0.5 L/min flow produced circumferential lesions 5.9±0.2 mm deep and 19.2±1.5 mm long with subendothelial sparing depth of 1.0±0.1 mm. In vivo, transcatheter microwave ablation was feasible with no collateral visceral thermal injury. There was histological evidence of preferential outer media and adventitial ablation. CONCLUSIONS: Transcatheter microwave ablation for RDN appears feasible and provides a heating pattern that may enable more complete denervation while sparing the renal arterial intima and media.

Magnetic guidance versus manual control: comparison of radiofrequency lesion dimensions and evaluation of the effect of heart wall motion in a myocardial phantom.

BACKGROUND: Magnetic navigation system (MNS) ablation was suspected to be less effective and unstable in highly mobile cardiac regions compared to radiofrequency (RF) ablations with manual control (MC). The aim of the study was to compare the (1) lesion size and (2) stability of MNS versus MC during irrigated RF ablation with and without simulated mechanical heart wall motion. METHODS: In a previously validated myocardial phantom, the performance of Navistar RMT Thermocool catheter (Biosense Webster, CA, USA) guided with MNS was compared to manually controlled Navistar irrigated Thermocool catheter (Biosense Webster, CA, USA). The lesion dimensions were compared with the catheter in inferior and superior orientation, with and without 6-mm simulated wall motion. All ablations were performed with 40 W power and 30 ml/ min irrigation for 60 s. RESULTS: A total of 60 ablations were performed. The mean lesion volumes with MNS and MC were 57.5 ± 7.1 and 58.1 ± 7.1 mm(3), respectively, in the inferior catheter orientation (n = 23, p = 0.6), 62.8 ± 9.9 and 64.6 ± 7.6 mm(3), respectively, in the superior catheter orientation (n = 16, p = 0.9). With 6-mm simulated wall motion, the mean lesion volumes with MNS and MC were 60.2 ± 2.7 and 42.8 ± 8.4 mm(3), respectively, in the inferior catheter orientation (n = 11, p = <0.01*), 74.1 ± 5.8 and 54.2 ± 3.7 mm(3), respectively, in the superior catheter orientation (n = 10, p = <0.01*). During 6-mm simulated wall motion, the MC catheter and MNS catheter moved 5.2 ± 0.1 and 0 mm, respectively, in inferior orientation and 5.5 ± 0.1 and 0 mm, respectively, in the superior orientation on the ablation surface. CONCLUSIONS: The lesion dimensions were larger with MNS compared to MC in the presence of simulated wall motion, consistent with greater catheter stability. However, similar lesion dimensions were observed in the stationary model.

Evaluation of lesion and thermodynamic characteristics of Symplicity and EnligHTN renal denervation systems in a phantom renal artery model.

AIMS: Radiofrequency renal artery denervation has been used effectively to treat resistant hypertension. However, comparison of lesion and thermodynamic characteristics for different systems has not been previously described. We aimed to assess spatiotemporal lesion growth and ablation characteristics of Symplicity and EnligHTN systems. METHODS AND RESULTS: A total of 39 ablations were performed in a phantom renal artery model using Symplicity (n=17) and EnligHTN (n=22) systems. The phantom model consisted of a hollowed gel block surrounding a thermochromic liquid crystal (TLC) film, exhibiting temperature sensitivity of 50-78°C. Flow was simulated using 37°C normal saline with impedance equal to blood. Radiofrequency ablations with each system were delivered with direct electrode tip contact to the TLC. Lesion size was interpreted from the TLC as the maximum dimensions of the 51°C isotherm. Mean lesion depth was 3.82 mm±0.04 versus 3.44 mm±0.03 (p<0.001) for Symplicity and EnligHTN, respectively. Mean width was 7.17 mm±0.08 versus 6.23 mm±0.07 (p<0.001), respectively. With EnligHTN, steady state temperature was achieved 20 sec earlier, and was 15°C higher than Symplicity. CONCLUSIONS: In this phantom model, Symplicity formed larger lesions compared to EnligHTN with lower catheter-tip temperature. The clinical significance of our findings needs to be explored further.

Novel use of NavX three-dimensional mapping to guide renal artery denervation.

AIMS: Renal artery denervation (RAD) is an effective treatment for resistant hypertension. The Navigation and Visualisation Technology (NavX) system creates three-dimensional (3-D) anatomical maps to guide catheter position and identify ablation sites. This first-in-human study assessed the utility of NavX 3-D mapping for RAD. METHODS AND RESULTS: Consecutive patients who underwent RAD using fluoroscopy alone (control group, n=8) were compared to NavX-guided RAD (NavX group, n=10). Where NavX was utilised, orthogonally located skin patches were applied to the torso for acquisition of 3-D geometry of each renal artery. Baseline clinical characteristics and renal artery anatomy were similar between groups. Median contrast dose was significantly higher in the control versus NavX group (123 ml versus 78 ml, p=0.016). Median radiation dose was significantly higher in the control versus NavX group (166 Gy cm² versus 43 Gy cm², p=0.034). Mean changes in systolic and diastolic BP at three-month follow-up were -22/-9 mmHg and -23/-11 mmHg in the control and NavX group, respectively (p=0.99). CONCLUSIONS: Use of NavX mapping as compared to standard renal artery denervation was found to correlate with a significant reduction in contrast load and radiation exposure. This study demonstrates both the feasibility and potential benefits of NavX 3-D mapping to guide renal artery denervation.