An architecturally rational hemostat for rapid stopping of massive bleeding on anticoagulation therapy.

Hemostatic devices are critical for managing emergent severe bleeding. With the increased use of anticoagulant therapy, there is a need for next-generation hemostats. We rationalized that a hemostat with an architecture designed to increase contact with blood, and engineered from a material that activates a distinct and undrugged coagulation pathway can address the emerging need. Inspired by lung alveolar architecture, here, we describe the engineering of a next-generation single-phase chitosan hemostat with a tortuous spherical microporous design that enables rapid blood absorption and concentrated platelets and fibrin microthrombi in localized regions, a phenomenon less observed with other classical hemostats without structural optimization. The interaction between blood components and the porous hemostat was further amplified based on the charged surface of chitosan. Contrary to the dogma that chitosan does not directly affect physiological clotting mechanism, the hemostat induced coagulation via a direct activation of platelet Toll-like receptor 2. Our engineered porous hemostat effectively stopped the bleeding from murine liver wounds, swine liver and carotid artery injuries, and the human radial artery puncture site within a few minutes with significantly reduced blood loss, even under the anticoagulant treatment. The integration of engineering design principles with an understanding of the molecular mechanisms can lead to hemostats with improved functions to address emerging medical needs.

Unique Aspects of Coronary Artery Disease in Indian Women.

PURPOSE: Epidemiologic and clinical research suggests important gender-related differences in the prevalence, presentation, associated conventional and non-conventional risk factors, management and outcomes of coronary heart disease (CHD) patients. Adequate data is not available for Indian population where prevalence of CHD and depression is high. METHOD: We conducted an observational, single-center, study from January 2010 to December 2011 on 10450 consecutive patients visiting a tertiary care center, Ahmedabad, Gujarat, India who presented with complaints related to CHD. RESULTS: Of these, 6867 patients had coronary artery disease (CAD) as confirmed by angiographic investigation; 5678 were males, and 1189 were females with similar mean age. As compared to males, females had higher prevalence of hypertension, diabetes and obesity while males had higher prevalence of smoking. Invasive treatment options like Coronary Artery Bypass Grafting (p < 0.001) and Percutaneous Coronary Intervention (p = 0.001) were used less often to treat females, and medical therapy (p < 0.001) was the preferred treatment option irrespective of the contributing risk factors/extent of CAD. Depression was observed in 39.8% of acute coronary syndrome patients (n = 1648) as assessed by MARDS scale. It was higher in female patients and in low socioeconomic strata (p < 0.001).At 12 and 36 months, rates of revascularization (p < 0.001) and mortality (p < 0.005) were higher with poor quality of life (QoL) (P < 0.001) in depressed CAD patients. CONCLUSION: In India, women appear to have a higher prevalence of hypertension, diabetes, obesity, and family history of CHD. Yet women get invasive treatments less often than men. Depression is also more common in women and is associated with poor QoL and early mortality than men.

Endeavour zotarolimus-eluting stent reduces stent thrombosis and improves clinical outcomes compared with cypher sirolimus-eluting stent: 4-year results of the PROTECT randomized trial.

AIMS: To compare the long-term clinical safety between two drug-eluting stents with different healing characteristics in the Patient Related Outcomes with Endeavour (E-ZES) vs. Cypher (C-SES) Stenting Trial (PROTECT). At 3 years, there was no difference in the primary outcome of definite or probable stent thrombosis or in the other main secondary clinical outcomes consisting of the composite of death or myocardial infarction (MI). Prespecified 4-year clinical follow-up was analysed. METHODS AND RESULTS: Patient Related OuTcomes with Endeavour vs. Cypher Stenting Trial was a prospective, open-label randomized-controlled superiority trial powered to look at differences in long-term clinical safety, including stent thrombosis. Dual antiplatelet therapy (DAPT) was prescribed for ≥ 3 months and up to 12 months based on current guidelines. Patient Related OuTcomes with Endeavour vs. Cypher Stenting Trial enrolled 8791 patients undergoing elective or emergency PCI to E-ZES or C-SES. There was no difference in DAPT usage between the two groups up to 4 years. At 4-year follow-up, the primary outcome occurred in 1.6% of E-ZES vs. 2.6% of C-SES patients [HR 0.63 (95% CI 0.46-0.85), P = 0.003]. The composite of all-cause death or large MI occurred in 6.7% of E-ZES vs. 8.0% of C-SES-treated patients [HR 0.84 (95% CI 0.71-0.98), P = 0.024]. CONCLUSIONS: Drug-eluting coronary stents with different healing characteristics demonstrated different late safety profiles: after 4 years, compared with C-SES, E-ZES reduced the risk of stent thrombosis and the risk of the composite endpoints of death or MI. Appropriately powered large-scale trials with long-term follow-up are critical to determine clinical safety and efficacy of permanently implanted coronary stents. This trial is registered with ClinicalTrials.gov, number NCT00476957.

Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive, fatal disease with no cure. Parenteral and inhaled prostacyclin analogue therapies are effective for the treatment of PAH, but complicated administration requirements can limit the use of these therapies in patients with less severe disease. This study was designed to evaluate the safety and efficacy of the oral prostacyclin analogue treprostinil diolamine as initial treatment for de novo PAH. METHODS AND RESULTS: Three hundred forty-nine patients (intent-to-treat population) not receiving endothelin receptor antagonist or phosphodiesterase type-5 inhibitor background therapy were randomized (treprostinil, n=233; placebo, n=116). The primary analysis population (modified intent-to-treat) included 228 patients (treprostinil, n=151; placebo, n=77) with access to 0.25-mg treprostinil tablets at randomization. The primary end point was change from baseline in 6-minute walk distance at week 12. Secondary end points included Borg dyspnea index, clinical worsening, and symptoms of PAH. The week 12 treatment effect for 6-minute walk distance (modified intent-to-treat population) was 23.0 m (P=0.0125). For the intent-to-treat population, 6-minute walk distance improvements were observed at peak (26.0 m; P=0.0001) and trough (17.0 m; P=0.0025) plasma study drug concentrations. Other than an improvement in the combined 6-minute walk distance/Borg dyspnea score, there were no significant changes in secondary end points. Oral treprostinil therapy was generally well tolerated; the most common adverse events (intent-to-treat) were headache (69%), nausea (39%), diarrhea (37%), and pain in jaw (25%). CONCLUSIONS: Oral treprostinil improves exercise capacity in PAH patients not receiving other treatment. Oral treprostinil could provide a convenient, first-line prostacyclin treatment option for PAH patients not requiring more intensive therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00325403.

Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial.

BACKGROUND: We sought to compare the long-term safety of two devices with different antiproliferative properties: the Endeavor zotarolimus-eluting stent (E-ZES; Medtronic, Inc) and the Cypher sirolimus-eluting stent (C-SES; Cordis, Johnson & Johnson) in a broad group of patients and lesions. METHODS: Between May 21, 2007 and Dec 22, 2008, we recruited 8791 patients from 36 recruiting countries to participate in this open-label, multicentre, randomised, superiority trial. Eligible patients were those aged 18 years or older undergoing elective, unplanned, or emergency procedures in native coronary arteries. Patients were randomly assigned to either receive E-ZES and C-SES (ratio 1:1). Randomisation was stratified per centre with varying block sizes of four, six, or eight patients, and concealed with a central telephone-based or web-based allocation service. The primary outcome was definite or probable stent thrombosis at 3 years and was analysed by intention to treat. Patients and investigators were aware of treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT00476957. FINDINGS: PROTECT randomised 8791 patients, of whom 8709 provided consent to participate and were eligible: 4357 were allocated to the E-ZES group and 4352 patients to the C-SES group. At 3 years, rates of definite or probable stent thrombosis did not differ between groups (1·4% for E-ZES [predicted: 1·5%] vs 1·8% [predicted: 2·5%] for C-SES; hazard ratio [HR] 0·81, 95% CI 0·58-1·14, p=0·22). Dual antiplatelet therapy was used in 8402 (96%) patients at discharge, 7456 (88%) at 1 year, 3041 (37%) at 2 years, and 2364 (30%) at 3 years. INTERPRETATION: No evidence of superiority of E-ZES compared with C-SES in definite or probable stent thrombosis rates was noted at 3 years. Time analysis suggests a difference in definite or probable stent thrombosis between groups is emerging over time, and a longer follow-up is therefore needed given the clinical relevance of stent thrombosis. FUNDING: Medtronic, Inc.

Safety and feasibility of orbital atherectomy for the treatment of calcified coronary lesions: the ORBIT I trial.

OBJECTIVE: The ORBIT I trial evaluated the safety and performance of an orbital atherectomy system (OAS) for the treatment of de novo calcified coronary lesions. BACKGROUND: Severely calcified coronary arteries pose an ongoing treatment challenge. Stent placement in calcified lesions can result in stent under expansion, malapposition, and procedural complications. OAS treatment may change calcified lesion compliance to reduce procedural complications and facilitate stent placement. METHODS: The ORBIT I trial, a prospective, nonrandomized study, was conducted in two centers in India. Fifty patients with de novo calcified coronary lesions were enrolled. Patients were treated with the OAS followed by stent placement. RESULTS: The average age of the patients was 57.4 years and 90% were male. Mean lesion length was 13.4 mm. The average number of OAS devices used per patient was 1.3. Device success was 98%, and procedural success was 94%. The cumulative major adverse cardiac event rate was 4% in-hospital (two non-Q-wave myocardial infarctions), 6% at 30 days (one additional non-Q-wave myocardial infarction leading to target lesion revascularization), and 8% at 6 months (one additional event of cardiac death). Angiographic complications were observed in seven patients (six dissections and one perforation). CONCLUSION: The ORBIT I trial suggests that the OAS may offer an effective method to change compliance of calcified coronary lesions to facilitate optimal stent placement in these difficult to treat patients. A larger trial is required to establish safety and overall effectiveness of the OAS in treating calcified coronary lesions.

One-Year Outcomes after Myval Implantation in Patients with Bicuspid Aortic Valve Stenosis-A Multicentre Real-World Experience.

BACKGROUND: Bicuspid aortic valve (BAV) affects approximately 1.5% of the general population and is seen in nearly 50% of candidates for aortic valve replacement (AVR). Despite increasingly utilised transcatheter aortic valve implantation (TAVI) in aortic stenosis (AS) patients, its use among patients with severe bicuspid AS is limited as BAV is a heterogeneous disease associated with multiple and complex anatomical challenges. AIM: To investigate the one-year outcomes of TAVI using the balloon-expandable Myval transcatheter heart valve (THV) (Meril Life Sciences Pvt. Ltd., Vapi, India) in patients with severe bicuspid AS. METHODS AND RESULTS: We collected data from consecutive patients with bicuspid AS who underwent TAVI with the Myval THV and had at least one-year follow-up. Baseline characteristics, procedural, and 30-day echocardiographic and clinical outcomes were collected. Sixty-two patients were included in the study. The median age was 72 [66.3, 77.0] years, 45 (72.6%) were males, and the mean STS PROM score was 3.2 ± 2.2%. All TAVI procedures were performed via the transfemoral route. The median follow-up duration was 13.5 [12.2, 18.3] months; all-cause mortality was reported in 7 (11.3%) patients and cardiovascular hospitalisation in 6 (10.6%) patients. All-stroke was reported in 2 (3.2%), permanent pacemaker implantation 5 (8.3%), and myocardial infarction 1 (1.6%) patients. The echocardiographic assessment revealed a mean pressure gradient of 10 [8, 16.5] mmHg, effective orifice area 1.7 [1.4, 1.9] cm2, moderate AR in 1 (2%), mild AR in 14 (27%), and none/trace AR in 37 (71%). In total, 1 patient was diagnosed with valve thrombosis (2.1%), Stage II (moderate) haemodynamic deterioration was seen in 3 (6.4%), and stage III (severe) haemodynamic deterioration in 1 (2.1%) patient. CONCLUSIONS: TAVI with the Myval THV in selected BAV anatomy is associated with favourable one-year hemodynamic and clinical outcomes.

Effectiveness and safety of optical coherence tomography-guided PCI in Indian patients with complex lesions: A multicenter, prospective registry.

BACKGROUND: Optical coherence tomography (OCT) is reported to be a feasible and safe imaging modality for the guidance of percutaneous coronary intervention (PCI) of complex lesions. METHODS: This multicenter, prospective registry assessed the minimum stent area (MSA) achieved under OCT guidance. A performance goal of 24% improvement in MSA over and above the recommendation set by the European Association of Percutaneous Cardiovascular Interventions Consensus 2018 (4.5 mm2 MSA for non-left main and 3.5 mm2 for small vessels). The incidence of contrast-induced nephropathy was also assessed. Core lab analysis was conducted. RESULTS: Five hundred patients (average age: 59.4 ± 10.1 years; 83% males) with unstable angina (36.8%), NSTEMI (26.4%), and STEMI (22%) were enrolled. The primary endpoint was achieved in 93% of lesions with stent diameter ≥2.75 mm (average MSA: 6.44 mm2) and 87% of lesions with stent diameter ≤2.5 mm (average MSA: 4.56 mm2). The average MSA (with expansion ≥80% cutoff) was 6.63 mm2 and 4.74 mm2 with a stent diameter ≥2.75 mm and ≤2.5 mm, respectively. According to the core lab analysis, the average MSA achieved with a stent diameter ≥2.75 mm and ≤2.5 mm was 6.23 mm2 and 3.95 mm2, respectively (with expansion ≥80% cutoff). Clinically significant serum creatinine was noted in two patients (0.45%). Major adverse cardiac events at 1 year were noted in 1.2% (n = 6) of the patients; all were cardiac deaths. CONCLUSION: PCI under OCT guidance improves procedural and long-term clinical outcomes in patients with complex lesions not just in a controlled trial environment but also in routine clinical practice.

Platelet inhibition with cangrelor in patients undergoing PCI.

BACKGROUND: Cangrelor, a nonthienopyridine adenosine triphosphate analogue, is an intravenous blocker of the adenosine diphosphate receptor P2Y(12). This agent might have a role in the treatment of patients who require rapid, predictable, and profound but reversible platelet inhibition. METHODS: We performed a large-scale international trial comparing cangrelor with 600 mg of oral clopidogrel administered before percutaneous coronary intervention (PCI) in patients with acute coronary syndromes. The primary efficacy end point was a composite of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours. RESULTS: We enrolled 8877 patients, and 8716 underwent PCI. At 48 hours, cangrelor was not superior to clopidogrel with respect to the primary composite end point, which occurred in 7.5% of patients in the cangrelor group and 7.1% of patients in the clopidogrel group (odds ratio, 1.05; 95% confidence interval [CI], 0.88 to 1.24; P=0.59). Likewise, cangrelor was not superior at 30 days. The rate of major bleeding (according to Acute Catheterization and Urgent Intervention Triage Strategy criteria) was higher with cangrelor, a difference that approached statistical significance (3.6% vs. 2.9%; odds ratio, 1.26; 95% CI, 0.99 to 1.60; P=0.06), but this was not the case with major bleeding (according to the Thrombolysis in Myocardial Infarction criteria) or severe or life-threatening bleeding (according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria). A secondary exploratory end point of death from any cause, Q-wave myocardial infarction, or ischemia-driven revascularization showed a trend toward a reduction with cangrelor, but it was not significant (0.6% vs. 0.9%; odds ratio, 0.67; 95% CI, 0.39 to 1.14; P=0.14). CONCLUSIONS: Cangrelor, when administered intravenously 30 minutes before PCI and continued for 2 hours after PCI, was not superior to an oral loading dose of 600 mg of clopidogrel, administered 30 minutes before PCI, in reducing the composite end point of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours. (ClinicalTrials.gov number, NCT00305162.)

Safety and Efficacy of Myval Implantation in Patients with Severe Bicuspid Aortic Valve Stenosis-A Multicenter Real-World Experience.

Bicuspid aortic valve (BAV) is the most common valvular congenital anomaly and is apparent in nearly 50% of candidates for AV replacement. While transcatheter aortic valve implantation (TAVI) is a recommended treatment for patients with symptomatic severe aortic stenosis (AS) at all surgical risk levels, experience with TAVI in severe bicuspid AS is limited. TAVI in BAV is still a challenge due to its association with multiple and complex anatomical considerations. A retrospective study has been conducted to investigate TAVI's procedural and 30-day outcomes using the Myval transcatheter heart valve (THV) (Meril Life Sciences Pvt. Ltd. Vapi, Gujarat, India) in patients with severe bicuspid AS. Data were collected on 68 patients with severe bicuspid AS who underwent TAVI with the Myval THV. Baseline characteristics, procedural, 30-day echocardiographic and clinical outcomes were collected. The mean age and STS PROM score were 72.6 ± 9.4 and 3.54 ± 2.1. Procedures were performed via the transfemoral route in 98.5%. Major vascular complications (1.5%) and life-threatening bleeding (1.5%) occurred infrequently. No patient had coronary obstruction, second valve implantation or conversion to surgery. On 30-day echocardiography, the mean transvalvular gradient and effective orifice area were 9.8 ± 4.5 mmHg and 1.8 ± 0.4 cm2, respectively. None/trace aortic regurgitation occurred in 76.5%, mild AR in 20.5% and moderate AR in 3%. The permanent pacemaker implantation rate was 8.5% and 30-day all-cause death occurred in 3.0% of cases. TAVI with the Myval THV in selected BAV anatomy is associated with favorable short-term hemodynamic and clinical outcomes.

Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial.

BACKGROUND: Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates. METHODS AND RESULTS: Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n=3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that of patients with normal renal function (n=11 965): 7.9% versus 8.9% (HR, 0.90; 95% CI, 0.79 to 1.02). In patients with chronic kidney disease, ticagrelor reduced total mortality (10.0% versus 14.0%; HR, 0.72; 95% CI, 0.58 to 0.89). Major bleeding rates, fatal bleedings, and non-coronary bypass-related major bleedings were not significantly different between the 2 randomized groups (15.1% versus 14.3%; HR, 1.07; 95% CI, 0.88 to 1.30; 0.34% versus 0.77%; HR, 0.48; 95% CI, 0.15 to 1.54; and 8.5% versus 7.3%; HR, 1.28; 95% CI, 0.97 to 1.68). The interactions between creatinine clearance and randomized treatment on any of the outcome variables were nonsignificant. CONCLUSIONS: In acute coronary syndrome patients with chronic kidney disease, ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non-procedure-related bleeding. CLINICAL TRIAL REGISTRATION: URL:http://www.clinicatrials.gov. Unique identifier: NCT00391872.

Extended follow-up safety and effectiveness of the Endeavor zotarolimus-eluting stent in real-world clinical practice: two-year follow-up from the E-Five Registry.

OBJECTIVES: To present data from the cohort of patients in the all-comers Endeavor zotarolimus-eluting stent (ZES) registry (E-Five) who underwent 2-year follow-up. BACKGROUND: The Endeavor ZES has been shown to be safe and efficacious for treatment of single, de novo lesions in patients with stable coronary artery disease. E-Five evaluated the ZES in over 8,000 real-world patients, at 188 sites followed to 1 year. A subset of sites continued follow-up through 2 years to evaluate late-term safety and effectiveness of the ZES in this population with diverse clinical and lesion characteristics. METHODS: E-Five, a prospective, multicenter, nonrandomized global registry, collected 2-year outcomes for 2,116 patients from 26 centers. Sites were selected for participation based on patient accrual rates and the ability to continue follow-up activities for an additional year. Complete data was available for 2,054 patients. To observe whether or not a sustained benefit was achieved, data for all patients from the selected sites were included in the analysis. RESULTS: The outcomes in the 2-year cohort tracked with the results of randomized controlled trials using the Endeavor ZES. One year results were MACE 7.5%, TLR 4.5%, and ARC definite/probable stent thrombosis 0.6%. Outcomes at 2 years for MACE, TLR, and ARC definite/probable stent thrombosis were 8.5, 5.1, and 0.7%, respectively. CONCLUSIONS: Long-term efficacy and safety outcomes were maintained between 1 and 2 years for the 2-year patient cohort, with only a small number of additional MACE, TLR, and very late stent thrombosis events.

Hysterectomy for uterine adenocarcinoma in the elderly: tumor characteristics, and long-term outcome.

OBJECTIVES: To evaluate the tumor recurrences and survival in elderly patients ≥75 years of age with uterine endometrioid carcinoma treated with surgical staging with/without adjuvant radiation therapy (RT). METHODS: We identified 675 surgically staged patients with FIGO stage I-II uterine endometrioid carcinoma who were treated between 1985 and 2009. Their medical records were retrospectively reviewed in this IRB-approved study. Patients were classified as ≥75 years vs. <75 years and compared regarding tumor recurrence and survival. Following a univariate analysis, multivariable modeling was done using Cox regression analysis. RESULTS: 121 patients (18%) were ≥75 years old at the time of hysterectomy. For this group of elderly patients, median age was 79. All patients were surgically staged and some received adjuvant RT. Older patients were found to have higher FIGO stages (p<0.001), higher grade tumors (p<0.001), more frequent deep myometrial involvement (p<0.001), and more frequent lower uterine segment involvement (p<0.001). There was no significant difference found between older and younger patients with respect to lymphovascular space involvement (LVSI) (p=0.415), number of lymph nodes dissected (p=0.440), or adjuvant RT received (p=0.089). Older patients had more tumor recurrence (15% vs 7%) (p=0.005) and lower five year relapse-free survival of 80% compared to 90% in younger patients (p=0.0016). Multivariate analysis confirmed the significance of LVSI, grade 3 tumors, and deep myometrial invasion as prognostic factors for recurrence. After adjusting for other poor prognostic factors, age was not found to be an independent prognostic factor for recurrence. CONCLUSION: Despite similar surgical staging and adjuvant radiation treatment, patients ≥75 years old diagnosed with FIGO stage I-II uterine endometrioid carcinoma were found to have more adverse pathologic features and worse relapse-free, disease-specific and overall survival than younger patients. Age ≥75 years alone may not be an independent significant prognostic factor affecting tumor recurrence.

Transitional cell carcinoma in urachal cyst.

A 33-year-old male patient with abdominal mass for a year was referred to our institute. CT scan with intravenous contrast was performed, which showed a cystic lesion at the infraumbilical region, beneath the anterior abdominal wall with the presence of solid enhancing mass apposed to the anterior wall of the cyst. We suggested a diagnosis of urachal cyst with possibility of malignancy. On surgical exploration, the cystic mass was found superior to and separate from the urinary bladder dome. Histopathology revealed transitional cell carcinoma in a urachal cyst.

Rationale and design of the Patient Related OuTcomes with Endeavor versus Cypher stenting Trial (PROTECT): randomized controlled trial comparing the incidence of stent thrombosis and clinical events after sirolimus or zotarolimus drug-eluting stent implantation.

Drug-eluting stents (DES) reduce restenosis rates compared to bare-metal stents. Most trials using DES enrolled selected patient and lesion subtypes, and primary endpoint focused on angiographic metrics or relatively short-term outcomes. When DES are used in broader types of lesions and patients, important differences may emerge in long-term outcomes between stent types, particularly the incidence of late stent thrombosis. PROTECT is a randomized, open-label trial comparing the long-term safety of the zotarolimus-eluting stent and the sirolimus-eluting stent. The trial has enrolled 8,800 patients representative of those seen in routine clinical practice, undergoing elective, unplanned, or emergency procedures in native coronary arteries in 196 centers in 36 countries. Indications for the procedure and selection of target vessel and lesion characteristics were at the operator's discretion. Procedures could be staged, but no more than 4 target lesions could be treated per patient. Duration of dual antiplatelet therapy was prespecified to achieve similar lengths of treatment in both study arms. The shortest predefined duration was 3 months, as per the manufacturer's instructions. The primary outcome measure is the composite rate of definite and probable stent thrombosis at 3 years, centrally adjudicated using Academic Research Consortium definitions. The main secondary end points are 3-year all-cause mortality, cardiac death, large nonfatal myocardial infarction, and all myocardial infarctions. This large, international, randomized, controlled trial will provide important information on comparative rates of stent thrombosis between 2 different DES systems and safety as assessed by patient-relevant long-term clinical outcomes.

Effect of Metoprolol CR/XL on pulmonary artery pressure in chronic heart failure patients assessed by an implanted ultrasonic device with special emphasis on diurnal variation and exercise capacity.

OBJECTIVE: We evaluated the impact of Metoprolol CR/XL on the diurnal and exercise induced variation on Pulmonary Artery Pressure (PAP) in patients with Chronic Heart Failure (CHF) by implanted ultrasonic device. BACKGROUND: Metoprolol produces haemodynamic and clinical benefits in patients with chronic heart failure and improves survival rate. There is limited information about their effect on PAP, its diurnal and exercise induced variation in heart failure. This study evaluates the diurnal variation and effects of exercise capacity on PAP and impact of Metoprolol CR/XL (XL) on these variations on PAP in CHF patients. METHODS: In this first-in-man study, ten NYHA class III/IV patients were implanted with an ultrasonic pressure-monitoring device, followed a month later by loading with MXL 25 mg/day and uptitrated every two weeks to 200 mg/day. PAP was measured at each follow up. Diurnal variation was evaluated at baseline (no MXL), 100, and 200 mg/day MXL. Treadmill Test (TMT) was performed before and at each uptitration. Echocardiography was performed at one year. RESULTS: Uptitrating MXL caused a slight initial rise in PAP, followed by a subsequent decrease on reaching 200 mg/day dose. One patient showed repeated symptomatic rise in PAP indicating MXL intolerance and was discontinued from the uptitration. The nocturnal rise in PAP at baseline was reduced on reaching 200 mg/day MXL dose. Uptitrating MXL to 200mg7divide;day improved exercise time and metabolic equivalent tasks (METS) with no significant change in post TMT PAP. Ejection fraction also improved at one-year follow-up. CONCLUSIONS: PAP increases post exercise and diurnally in CHF patients. Slow and careful uptitration of MXL with simultaneous non-invasive monitoring of PAP may benefit in nocturnal rise and exercise capacity in CHF patients.

A novel nanocarrier sirolimus-coated balloon for coronary interventions: 12-Month data from the Nanoluté Registry.

BACKGROUND: The aim of the Nanoluté registry was to observe the clinical performance of a novel sirolimus coated balloon (SCB) (Concept Medical Research Private Limited, India) for the treatment of coronary de-novo and restenotic lesions. METHODS: All patients treated with SCB between July 2012 and September 2015 were enrolled at Indian centres and clinically followed for 1, 3, 6 and 12 months post-procedure. Primary endpoints were procedural success and device-oriented adverse cardiac events (DOCE) at 12 months. DOCE were defined as a composite of cardiac death, target lesion revascularization (TLR) and target vessel-myocardial infarction. RESULTS: A total of 394 SCB were used in 332 patients to treat 356 lesions. In-stent restenosis and small coronary vessel disease occurred in 46% and 43% of the patients respectively. Mean balloon length and diameter (average ±â€¯SD) were 21.83 ±â€¯6.70 mm and 2.69 ±â€¯0.45 mm respectively. All patients with 1 year follow-up were included. Overall DOCE rate was 4.2% (n = 14) which included death 0.3% (n = 1), TLR 3.6% (n = 12) and myocardial infarction 0.3% (n = 1). CONCLUSION: The Nanoluté prospective registry, is the first clinical evidence of the safety and feasibility of this type of SCB, both in patients with in-stent restenosis or de novo lesions.

Safety and efficacy of indigenously developed and manufactured bivalirudin in moderate/high-risk Indian patients undergoing percutaneous coronary intervention: the Bivaflo Registry.

BACKGROUND: Current treatment strategies for percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS) include concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and antithrombotic therapy such as aspirin, clopidogrel, and unfractionated or low-molecular-weight heparin. The "direct thrombin inhibitor" bivalirudin has been associated with better efficacy and safety than heparin. OBJECTIVE: The present study is performed to evaluate the safety and efficacy of an indigenously developed and manufactured bivalirudin (Bivaflo; Sun Pharmaceutical Industries Ltd., Mumbai) as the primary anticoagulation strategy during PCI in moderate-high risk patients with only provisional use of GPI. METHODS: This prospective multicentered registry enrolled 439 patients in 11 tertiary care centers across India. Patients who had ACS or other clinical/angiographic characteristics, which increase risk during PCI, were enrolled in the registry. Bivaflo was administered as a bolus dose of 0.75 mg/kg, followed by infusion at a rate of 1.75 mg/kg/h during the procedure and optionally 0.25 mg/kg/h for 4 hours after the procedure at investigator's discretion. GPI use was discouraged except as bailout. The primary endpoints were composite and individual incidences of death, myocardial infarction (MI), urgent revascularization, subacute stent thrombosis (SAT), or bleeding at day 7/hospital discharge, whichever was earlier. The secondary endpoints were 30-day composite and individual incidences of death, MI, urgent revascularization, and SAT. RESULTS: The mean age of the group was 58 +/- 10 years and 83% were males. Bivaflo was administered for a mean duration of 102 +/- 79 minutes, and 65% patients received Bivaflo infusion post-PCI. ACT values measured at 10 minutes after bolus and at the end of the PCI were found to be 339 +/- 110 and 336 +/- 104 seconds, respectively. GPI was provisionally used in only 4% (16) patients mostly due to new or suspected thrombus and obstructive dissection with decreased flow. At day 7/hospital discharge, there were no incidences of major adverse cardiac events or major bleeding. Minor bleeding occurred in only 4 patients (0.9%). The 30-day composite major adverse cardiac event rate was 0.68%. One death and two subacute thrombosis occurred during the 30-day follow-up. CONCLUSION: Bivaflo is safe and effective sole anticoagulation strategy during PCI of moderate-high risk patients. Bivaflo administration was associated with no major bleeding events and extremely low in hospital and 30-day MACE rate. These rates were lower than expected MACE rates for such a subgroup of patients based on historical controls.

Efficacy of PercuSurge in acute myocardial infarction patients undergoing revascularization with a special emphasis on procedural time.

AIM: To evaluate the efficacy of the PercuSurge Guardwire(R) Plus Temporary Occlusion and Aspiration System, the actual procedural time involved and long-term follow-up in acute MI patients undergoing primary/rescue percutaneous coronary intervention (PCI). METHODS & RESULTS: It was a single centred, prospective study in 67 prospective AMI patients undergoing PCI. They were divided randomly into two groups depending on whether PercuSurge was used (n=30) or not used (control n=37) during PCI. Final TIMI flow, TMP grade and the time involved in or necessary for various steps of the PCI were recorded. PercuSurge showed significantly greater achievement of TIMI III flow and TMP III grade (p<0.01). Its use was associated with less total procedural time (p<0.05). The time required from guidewire crossing to stent placement; from guidewire crossing to TIMI III flow and from predilatation/stent placement to optimal TIMI flow was significantly reduced with its use (p<0.05 for all). Slow/no-reflow was significantly reduced (p<0.001), thus reducing intracoronary vasodilators and GP IIb/IIIa antagonists requirements. A 2 years' follow-up revealed four deaths in control and one death in PercuSurge group. CONCLUSION: PercuSurge reduced the total procedural time with better and faster optimal TIMI flow and TMP grade in primary/rescue PCI and was associated with less long term events.