Rationale and design of the TUXEDO-2 India study: Ultra-Thin strUt Supraflex Cruz versus XiencE in a Diabetic pOpulation with multi-vessel disease-2.

BACKGROUND: The role of percutaneous coronary interventions (PCI) in patients with diabetes mellitus and multi-vessel disease has been questioned by the results of the FREEDOM trial, which showed superiority of coronary artery bypass graft(CABG) over first generation drug-eluting stents (DES) including a reduction in mortality. In the light of safer and more efficacious stents and significantly better medical management, those results that date back to 2012 need to be revisited. TUXEDO-2 is a study designed to compare two contemporary stents in Indian diabetic patients with multi-vessel disease. AIMS: The primary objective of the TUXEDO-2 study is to compare the clinical outcomes of PCI with ultra-thin Supraflex Cruz vs Xience when combined with contemporary optimal medical therapy (OMT) in diabetic patients with multi-vessel disease. The secondary objective is to compare clinical outcomes between a pooled cohort from both arms of the study (Supraflex Cruz + Xience; PCI arm) vs CABG based on a performance goal derived from the CABG arm of the FREEDOM trial (historical cohort). The tertiary objective is a randomized comparison of ticagrelor vs prasugrel in addition to aspirin for the composite of ischemic and bleeding events. METHODS: In this prospective, open-label, multi-centre, 2 × 2 factorial, randomized, controlled study, 1,800 patients with diabetes mellitus and multi-vessel disease (inclusion criteria similar to FREEDOM trial) with indication for coronary revascularization will be randomly assigned to Supraflex Cruz or Xience stents and also to ticagrelor- or prasugrel- based antiplatelet strategies. All patients will receive guideline directed OMT and optimal PCI including image- and physiology-guided complete revascularization where feasible. The patients will be followed through five years to assess their clinical status and major clinical events. The primary endpoint is a non-inferiority comparison of target lesion failure at one-year for Supraflex Cruz vs Xience (primary objective) with an expected event rate of 11% and a non-inferiority margin of 4.5%. For PCI vs CABG (secondary objective), the primary endpoint is major adverse cardiac events (MACE), defined as a composite of all cause death, nonfatal myocardial infarction, or stroke at one-year and yearly up to five years, with a performance goal of 21.6%. For ticagrelor vs prasugrel (tertiary objective), the primary endpoint is composite of death, myocardial infarction, stroke, and major bleeding as per the Bleeding Academic Research Consortium (BARC) at one-year with expected event rate of 15% and a non-inferiority margin of 5%. CONCLUSIONS: The TUXEDO-2 study is a contemporary study involving state-of-the-art PCI combined with guideline directed OMT in a complex subset of patients with diabetes mellitus and multi-vessel disease. The trial will answer the question as to whether a biodegradable polymer coated ultra-thin Supraflex Cruz stent is an attractive option for PCI in diabetic patients with multi-vessel disease. It will also help address the question whether the results of FREEDOM trial would have been different in the current era of safer and more efficacious stents and modern medical therapy. In addition, the comparative efficacy and safety of ticagrelor vs prasugrel in addition to aspirin will be evaluated. (CTRI/2019/11/022088).

Impact of Medication Nonadherence in a Clinical Trial of Dual Antiplatelet Therapy.

BACKGROUND: Nonadherence to antiplatelet therapy after percutaneous coronary intervention (PCI) is common, even in clinical trials. OBJECTIVES: The purpose of this study was to investigate the impact of nonadherence to study protocol regimens in the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen) trial. METHODS: At 1-month after PCI, 4,579 high bleeding risk patients were randomized to single antiplatelet therapy (SAPT) for 11 months (or 5 months in patients on oral anticoagulation [OAC]) or dual antiplatelet therapy (DAPT) for ≥2 months followed by SAPT. Coprimary outcomes included net adverse clinical events (NACE), major adverse cardiac and cerebral events (MACE), and major or clinically relevant nonmajor bleeding (MCB) at 335 days. Inverse probability-of-censoring weights were used to correct for nonadherence Academic Research Consortium type 2 or 3. RESULTS: In total, 464 (20.2%) patients in the abbreviated-treatment and 214 (9.4%) in the standard-treatment groups incurred nonadherence Academic Research Consortium type 2 or 3. At inverse probability-of-censoring weights analyses, NACE (HR: 1.01; 95% CI: 0.88-1.27) or MACE (HR: 1.07; 95% CI: 0.83-1.40) did not differ, and MCB was lower with abbreviated compared with standard treatment (HR: 0.51; 95% CI: 0.60-0.73) consistently across OAC subgroups; among OAC patients, SAPT discontinuation 6 months after PCI was associated with similar MACE and lower MCB (HR: 0.47; 95% CI: 0.22-0.99) compared with SAPT continuation. CONCLUSIONS: In the MASTER DAPT adherent population, 1-month compared with ≥3-month DAPT was associated with similar NACE or MACE and lower MCB. Among OAC patients, SAPT discontinuation after 6 months was associated with similar MACE and lower MCB than SAPT continuation (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).

Outcomes and regional differences in practice in a worldwide coronary stent registry.

OBJECTIVE: The primary objective was to assess the performance of a new generation thin-strut sirolimus-eluting coronary stent with abluminal biodegradable polymer in an all comer population. The secondary objective was to detail differences in contemporary percutaneous coronary intervention (PCI) practice worldwide. METHODS: e-Ultimaster was an all-comer, prospective, global registry (NCT02188355) with independent event adjudication enrolling patients undergoing PCI with the study stent. The primary outcome measure was target lesion failure (TLF) at 1 year, defined as the composite of cardiac death, target vessel myocardial infarction and clinically driven target lesion revascularisation. Data were stratified according to 4 geographical regions. RESULTS: A total of 37 198 patients were enrolled (Europe 69.2%, Asia 17.8%, Africa/Middle East 6.6% and South America/Mexico 6.5%) and 1-year follow-up was available for 35 389 patients (95.1%). One-year TLF occurred in 3.2% of the patients, ranging from 2% (Africa/Middle East) to 4.1% (South America/Mexico). In patients with acute coronary syndrome, potent P2Y12 inhibitors were prescribed in 48% of patients at discharge, while at 1 year 72% were on any dual antiplatelet therapy. Lipid-lowering treatment was administered in 80.9% and 75.5% of patients at discharge and 1 year, respectively. Regional differences in the profile of the treated patients as well as in PCI practice were reported. CONCLUSIONS: In this investigation with worldwide representation, contemporary PCI using a new generation thin-strut sirolimus-eluting coronary stent with abluminal biodegradable polymer was associated with low 1-year TLF across clinical presentations and continents. Suboptimal adherence to current recommendations around antiplatelet and lipid lowering treatments was detected.

Serial evaluation of vascular responses after implantation of everolimus-eluting coronary stent by optical coherence tomography.

AIM: To evaluate healing response at strut-level and cross-section level after implanting an ultra-thin strut, everolimus-eluting stent with biodegradable polymer (Tetrilimus) using optical coherence tomography (OCT) at 3 and 6 months. METHODS: This was prospective, multi-centre, single-arm, and investigator-initiated study performed at seven Indian sites between January, 2017 and September, 2018. OCT evaluations were performed in 57 patients who underwent Tetrilimus stent implantation. Follow-up OCT was scheduled at 3 months for first 16 patients and at 6 months for 41 patients. Primary outcomes included degree of strut coverage, malapposition and thickness of neointimal hyperplasia (NIH) over covered struts. RESULTS: Sixty one Tetrilimus stents were implanted to treat 59 lesions in 57 patients. Paired (baseline and follow-up) OCT data was available for 12 patients and 30 patients at 3 and 6 months, respectively. At 3 months, rapid early healing was indicated by 95.48% covered struts per lesion with very low (0.11 ± 0.06 mm) NIH. At 6 months, NIH accumulation was greater (0.21 ± 0.07 mm) as compared to 3 months. 99.77% of struts per lesion were covered at 6 months. There was a very symmetrical healing as shown by very low eccentricity index. There was no difference in vascular healing between stents with small to moderate size vessels (≤3.00 mm) and large size vessels (>3.00 mm). CONCLUSION: Present study demonstrated nearly complete endothelization and low NIH accumulation at 3 and 6 months following implantation of ultra-thin strut everolimus-eluting biodegradable polymer-coated Tetrilimus stent. Moreover, though being an ultra-thin strut stent, there was no difference in vascular healing and eccentricity after implantation of the Tetrilimus stents with smaller and larger diameters.

First-in-human evaluation of a novel balloon-expandable transcatheter heart valve in patients with severe symptomatic native aortic stenosis: the MyVal-1 study.

AIMS: The aim of this study was to demonstrate the safety and efficacy of the next-generation balloon-expandable Myval transcatheter heart valve (THV) in an intermediate- or high-risk patient population with severe symptomatic native aortic stenosis. METHODS AND RESULTS: MyVal-1 was a first-in-human, prospective, multicentre, single-arm, open-label study. Between June 2017 and February 2018, a total of 30 patients were enrolled at 14 sites across India. Mean age was 75.5±6.7 years; 43.3% had coronary artery disease. The mean Society of Thoracic Surgeons score was 6.4±1.8% and 100% of the patients were in New York Heart Association (NYHA) functional Class II/III/IV pre-procedure. The six-minute walk test and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores were recorded. After successful implantation of the Myval THV, 96.6% and 100% were in NYHA functional Class I/II at 30-day and 12-month follow-up, respectively. Outcomes of the six-minute walk test (148.0±87.4 vs 336.0±202.9 m) and KCCQ score (36.6±11.0 vs 65.9±11.4) improved from baseline to 12-month follow-up. The effective orifice area (0.6±0.2 vs 1.8±0.3 cm2, p<0.0001), mean aortic valve gradient (47.4±8.8 vs 12.0±3.3 mmHg, p<0.0001), peak aortic valve gradient (71.7±13.0 vs 20.3±5.9 mmHg, p<0.0001) and transaortic velocity (4.5±0.4 vs 2.2±0.4 m/s, p<0.0001) improved substantially from baseline to 12 months post procedure. Four all-cause mortality cases were reported up to 12 months. Moreover, there was no other moderate/severe paravalvular leak, aortic regurgitation or need for new permanent pacemaker (PPM) up to 12-month follow-up. CONCLUSIONS: The MyVal-1 study demonstrated the primary safety and efficacy of the Myval THV with no new PPM requirement up to 12-month follow-up. However, future trials with a larger number of patients and long-term follow-up are warranted to establish the safety and efficacy of the device.

Everolimus Eluting Stents in Patients with Diabetes Mellitus and Chronic Kidney Disease: Insights from the TUXEDO Trial.

BACKGROUND: Patients with diabetes and those with chronic kidney disease (CKD) are at increased risk of cardiovascular events. Everolimus eluting stents (EES) have been shown to be superior to paclitaxel eluting stents (PES) in patients with diabetes. However, it is not known if EES is as beneficial in diabetic patients with CKD compared with those without CKD. METHODS AND RESULTS: Patients enrolled in the TUXEDO-India trial, which is a clinical trial of patients with diabetes and coronary artery disease (CAD) randomly assigned to EES vs. thin-strut PES (Taxus Element), with data on baseline renal function were selected. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 using the Cockcroft-Gault formula. Primary outcome was target vessel failure (TVF-defined as cardiac death, TV myocardial infarction (MI) or ischemia driven TV revascularization) at 1 year. Various secondary outcomes including stent thrombosis were evaluated. Among the 1821 patients with diabetes included in this analysis, 344 (19%) had CKD. In a propensity score adjusted analysis, patients with CKD had a significant increase in MACE (HR = 2.02; 95% CI 1.17-3.50; P = 0.01); death/MI/TVR (HR = 1.99; 95% CI 1.18-3.34; P = 0.009); death/MI (HR = 2.31; 95% CI 1.30-4.08; P = 0.004); cardiac death/MI (HR = 2.40; 95% CI 1.31-4.42; P = 0.005); death (HR = 2.88; 95% CI 1.35-6.13; P = 0.006) driven by an increase in cardiac death (HR = 3.33; 95% CI 1.42-7.83; P = 0.006) when compared with those without CKD. However, stent related events (TV-MI, TVR, TLR and stent thrombosis) were not different between CKD and non CKD groups. A significant interaction between CKD status and stent type (EES vs. PES) was noted for the outcomes of TVF (Pinteraction = 0.046), MACE (Pinteraction = 0.02), cardiac death or MI (Pinteraction = 0.05), non-target vessel related MI (Pinteraction = 0.04), non-Q-wave MI (Pinteraction = 0.03) and deaths/MI/TVR (Pinteraction = 0.04) such that EES was superior to PES in the non-CKD cohort but not in the CKD cohort. CONCLUSIONS: In subjects with diabetes, CKD is an independent predictor of adverse cardiovascular outcomes including increased risk of death driven largely by non-stent related events. While EES was superior to PES in patients without CKD, this was not the case in those with CKD (Clinical Trials Registry-India number, CTRI/2011/06/001830).

Transradial access for coronary diagnostic and interventional procedures: Consensus statement and recommendations for India: Advancing Complex CoronariES Sciences through TransRADIAL intervention in India - ACCESS RADIAL™: Clinical consensus recommendations in collaboration with Cardiological Society of India (CSI).

Radial access for cardiac catheterization and intervention in India has been growing steadily over the last decade with favorable clinical outcomes. However, its usage by interventional cardiologists varies greatly among Indian operators and hospitals due to large geographic disparities in health care delivery systems and practice patterns. It also remains unclear whether the advantages, as well as limitations of transradial (TR) intervention (as reported in the western literature), are applicable to developing countries like India or not. An evidence-based review involving various facets of radial procedure for cardiac catheterization, including practical, patient-related and technical issues was conducted by an expert committee that formed a part of Advancing Complex CoronariES Sciences through TransRADIAL intervention (ACCESS RADIAL™) Advisory Board. Emerging challenges in redefining TR management based on evidence supporting practices were discussed to formulate these final recommendations through consensus.

Paclitaxel-Eluting versus Everolimus-Eluting Coronary Stents in Diabetes.

BACKGROUND: The choice of drug-eluting stent in the treatment of patients with diabetes mellitus and coronary artery disease who are undergoing percutaneous coronary intervention (PCI) has been debated. Previous studies comparing paclitaxel-eluting stents with stents eluting rapamycin (now called sirolimus) or its analogues (everolimus or zotarolimus) have produced contradictory results, ranging from equivalence between stent types to superiority of everolimus-eluting stents. METHODS: We randomly assigned 1830 patients with diabetes mellitus and coronary artery disease who were undergoing PCI to receive either a paclitaxel-eluting stent or an everolimus-eluting stent. We used a noninferiority trial design with a noninferiority margin of 4 percentage points for the upper boundary of the 95% confidence interval of the risk difference. The primary end point was target-vessel failure, which was defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization at the 1-year follow-up. RESULTS: At 1 year, paclitaxel-eluting stents did not meet the criterion for noninferiority to everolimus-eluting stents with respect to the primary end point (rate of target-vessel failure, 5.6% vs. 2.9%; risk difference, 2.7 percentage points [95% confidence interval, 0.8 to 4.5]; relative risk, 1.89 [95% confidence interval, 1.20 to 2.99]; P=0.38 for noninferiority). There was a significantly higher 1-year rate in the paclitaxel-eluting stent group than in the everolimus-eluting stent group of target-vessel failure (P=0.005), spontaneous myocardial infarction (3.2% vs. 1.2%, P=0.004), stent thrombosis (2.1% vs. 0.4%, P=0.002), target-vessel revascularization (3.4% vs. 1.2%, P=0.002), and target-lesion revascularization (3.4% vs. 1.2%, P=0.002). CONCLUSIONS: In patients with diabetes mellitus and coronary artery disease undergoing PCI, paclitaxel-eluting stents were not shown to be noninferior to everolimus-eluting stents, and they resulted in higher rates of target-vessel failure, myocardial infarction, stent thrombosis, and target-vessel revascularization at 1 year. (Funded by Boston Scientific; TUXEDO-India Clinical Trials Registry-India number, CTRI/2011/06/001830).

Left ventricular pseudoaneurysm following balloon mitral valvuloplasty.

Balloon mitral valvotomy is a commonly performed procedure for mitral stenosis. This procedure can lead to complications such as left ventricular perforation with tamponade, mitral regurgitation and stroke. Here we report a case of left ventricular pseudoaneurysm following balloon mitral valvotomy. It was a consequence of adherent pericardium secondary to open mitral valvotomy performed earlier. It was surgically corrected by pseudoaneurysm repair and mitral valve replacement. We believe that this is the first such reported case.

Clinical outcomes with Biolimus (A9)™ eluting stent, 'BioMatrix' in diabetic patients--interim results from multicenter post market surveillance registry in India.

OBJECTIVE: The objective of this registry is to establish safety and efficacy of BioMatrix, BioMatrix™-Biolimus A9™ eluting stent in diabetic population in India. BACKGROUND: Diabetes mellitus is a major predisposing factor for coronary artery disease. Prognosis for diabetic population patients presenting with coronary artery disease who undergo coronary revascularization is inferior to non diabetics and remains an independent risk factor of restenosis, need for revascularization, and overall mortality. Stent thrombosis is a potential complication of first generation, permanent polymer drug-eluting stents. Biodegradable polymer is a good relief in this era and its utility in diabetic patients will be a major advantage for them. METHODS: 334 patients with diabetes mellitus and requiring angioplasty, implanted with BioMatrix stent were followed at 1, 6, 12 and 24 months who entered in a multicenter registry in India. We analyzed the incidence of major adverse cardiac events (MACE) and stent thrombosis (ST) at 1, 6, 12 and 24 months. RESULTS: The mean age was 58.71 ± 9.2 years, 81% were males, comorbidity index was 1.6 ± 1.02, and 59.1% presented with acute coronary syndrome. The incidence of adverse event rates was: MACE 1.27%. There were no incidences of myocardial infarction (MI) and target vessel revascularization (TVR). Definite stent thrombosis occurred only in 2 patients. CONCLUSION: In this registry of diabetic population treated with BioMatrixTM-Biolimus A9TM eluting stent (BioMatrix), the reported incidence of MACE and ST were much lower than previously published results. The 1- and 2-year follow-up result supports favorable clinical outcomes of using BioMatrix stents as a suitable alternative to contemporary DES available during PCI in diabetic patients.

Coronary angiography and angioplasty using the aberrant radial artery as an access site.

OBJECTIVE: To study the suitability of the aberrant radial artery (ARA) as an access site for coronary angiography and angioplasty. BACKGROUND: In certain situations, the radial artery operator finds that the right radial artery in its usual location is unsuitable for a transradial procedure (TRP). In such cases, the ARA should be considered as an alternate access site. METHODS: Between January 2002 and December 2004, all patients considered suitable for a TRP with a clinically absent radial artery, or a small radial artery and a palpable ARA, underwent a TRP using this vessel as an access site. We describe the technical aspects and the differences that this approach entails, in comparison to the standard radial artery approach to TRPs. RESULTS: Of the 3,610 patients considered suitable for a TRP, 22 patients underwent 29 procedures using the ARA as an access site [22 angiograms and 7 percutaneous transluminal coronary angioplasty procedures (PTCAs)]. The median age of the patients was 55 years, with 19 males and 3 females. All procedures using the aberrant radial artery were successful. None of the patients developed spasm or an access site complication. The mean fluoroscopy time for angiography in the right radial artery group was 4.6 minutes, and 4.8 minutes for the ARA group. The procedure timed were 24 minutes and 32 minutes, respectively. CONCLUSION: The aberrant radial artery can be used as a safe alternate access site for coronary angiography and angioplasty when the right radial artery at the usual site is not suitable.

Stent supported angioplasty for coronary arterial stenosis following the arterial switch operation.

We present a case of a patient who underwent stent-supported angioplasty for left main bifurcation disease following the arterial switch operation. Prior to this procedure, the patient underwent surgical repair of the left coronary ostium and subsequently coronary artery bypass surgery with an arterial graft to the left anterior descending artery. We could not find a similar report in the literature.

Collateral coronary circulation in the absence of obstructive coronary artery disease.

The presence of collateral coronary circulation almost always accounts for significant obstructive coronary artery disease and its development remains unclear. We present two cases wherein there was a large collateral artery in a patient with angiographically normal coronary arteries. In both cases, the vessel ran in the atrioventricular groove, between the distal right coronary artery and the circumflex artery. We believe that this vessel is of congenital origin and after reviewing the literature we describe the angiographic features that distinguish such a vessel from collaterals that are secondary to coronary stenosis or hypoxia.

Definitive percutaneous treatment of Lutembacher's syndrome.

Definitive percutaneous treatment of a patient with Lutembacher's syndrome was successfully accomplished using the Amplatzer septal occluder to close a secundum atrial septal defect and the Joseph mitral balloon catheter to dilate rheumatic mitral valve stenosis. Transcatheter therapy is an effective alternative to surgery in selected patients with Lutembacher's syndrome. Cathet. Cardiovasc. Intervent. 48:199-204, 1999.