Background: Bicuspid aortic valve (BAV) affects approximately 1.5% of the general population and ... more 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...
Supplemental material, sj-pdf-1-pul-10.1177_2045894019866335 for Long-term study of oral treprost... more Supplemental material, sj-pdf-1-pul-10.1177_2045894019866335 for Long-term study of oral treprostinil to treat pulmonary arterial hypertension: dosing, tolerability, and pharmacokinetics by R. James White, Keyur Parikh, Roblee Allen, Jeremy Feldman, Carlos Jerjez-Sanchez, Lei Pan, Anne Keogh, C. Dario Vizza, Shelley Shapiro, Kathryn Gordon, Meredith Broderick and Sonja Bartolome in Pulmonary Circulation
Oral treprostinil may be an option for low- and intermediate-risk patients with pulmonary arteria... more Oral treprostinil may be an option for low- and intermediate-risk patients with pulmonary arterial hypertension, a rare lung vascular disease. This open-label extension study collected data on participants who completed previously reported, placebo-controlled oral treprostinil studies. Eligible participants had completed the prospective parent studies and took increasing doses of oral treprostinil twice daily; some later transitioned to three times daily dosing. Investigators measured 6-minute walk distance at Month 12 as the sole efficacy measure but collected adverse events throughout the study. A single center measured pharmacokinetics in 13 subjects who changed dosing from twice daily to three times daily. Eight hundred and ninety-four participants enrolled and 71% completed one year of therapy, with a median total daily dose of 7 mg and a median 6-minute walk distance increase of 22 m (interquartile range, −14 to 67 m). Subjects achieving higher doses had larger increases in 6-...
Introduction: Limited data is available on outcomes with renal denervation (RDN) in an Indian pat... more Introduction: Limited data is available on outcomes with renal denervation (RDN) in an Indian patient population. The Single-arm Study of Symplicity TM Renal Denervation System in Patients With Uncontrolled HyperTensioN in India (HTN-India) study prospectively evaluated the safety and efficacy of renal denervation therapy in an Indian population with uncontrolled hypertension using the Symplicity Flex TM catheter (Medtronic, Inc.). Material: The primary effectiveness endpoint is 6-month change in office systolic blood pressure (SBP). Home BP was also recorded at baseline and 6 months. Observations and conclusions: A total of 28 subjects at 7 sites were consented and 14 subjects were treated with RDN in HTN-India when the study was stopped following the announcement of results of the SYMPLICITY HTN-3 trial. Baseline office and home SBP was 177 AE 17 and 160 AE 11 mmHg; average age was 51 AE 11 years, 57% were male, 21% had type II diabetes, and average body mass index was 28 AE 5 kg/m 2. Subjects were prescribed 4.1 AE 1.2 and 4.5 AE 1.1 antihypertensive medications at baseline and 6 months. Both office and home SBP decreased significantly at 6 months (À28.5 AE 23.8 mmHg, and À19.6 AE 13.6 mmHg, respectively, p ≤ 0.01 for both). No procedure-related adverse events were reported, although there was one non-cardiovascular death (severe burn unrelated to RDN) at 5 months. We conclude that RDN was safe and effective in this Indian population with treatment resistant hypertension. Confirmatory prospective sham controlled trials are warranted.
Background: Identifying adverse cardiac events and reducing readmissions improves patient surviva... more Background: Identifying adverse cardiac events and reducing readmissions improves patient survival, enhances quality of care, and lowers health care expenditure. Objective of the Hospital to Home (H2H) follow up visit, a first of its kind program was initiated to improve transition from inpatient to outpatient status for individuals hospitalized for coronary artery bypass graft (CABG) surgery. Methods: Since July 2012, trained healthcare personnel of CIMS Hospital, Ahmedabad, India, initiated H2H visits on a total of 437 patients following discharge after CABG surgery. Based on distance the visits were categorized as A (n=198, less than 70 km); B (n=137, 70-600 km);C (n=82, 600-1000km) and D (n=20, >1000km). Results: At 5 days early follow up, H2H visits depicted medical complications (36.56%) like wound infection (1.6%); poor dressing conditions (2.58%); inappropriate chest belts (8.46%) and poor hygiene (3.9%). Adverse Drug Reactions were reported in 10 patients of which 8 were...
Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor there... more Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor thereby attenuating the differential effect by race. Attenuation likely occurs in both race-groups but may be more pronounced in the less-represented race-group. Therefore, we evaluated whether the effect of clinical (age, body surface area [BSA], chronic kidney disease [CKD], and amiodarone use) and genetic factors (CYP2C9 *2, *3, *5, *6, *11, rs12777823, VKORC1, and CYP4F2) on warfarin dose differs by race using regression analyses among 1357 patients enrolled in a prospective cohort study, and compared predictive ability of race-combined versus race-stratified models. Differential effect of predictors by race was assessed using predictor-race interactions in race-combined analyses. Warfarin dose was influenced by age, BSA, CKD, amiodarone use, CYP2C9*3 and VKORC1 variants in both races, by CYP2C9*2 and CYP4F2 variants in European Americans, and rs12777823 in African Americans. CYP2C9*2 was...
To compare the long-term clinical safety between two drug-eluting stents with different healing c... more 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. 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 u...
To find out whether the addition of fenofibrate to statin monotherapy produced any synergistic or... more To find out whether the addition of fenofibrate to statin monotherapy produced any synergistic or additive beneficial effects in reducing risk factors, especially plasma fibrinogen, in patients with acute coronary syndrome (ACS) requiring percutaneous coronary interventions. A randomized, non-blinded, prospective study with parallel group design. One hundred two ACS patients who underwent angioplasty were randomly assigned to atorvastatin (20 mg/day, n=25), simvastatin (40 mg/day, n=27), atorvastatin-fenofibrate (10 mg/day-200 mg/day) combination (n=25) or simvastatin-fenofibrate (20 mg/day-200 mg/day) combination (n=25). The serum lipid profile and plasma fibrinogen were recorded before initiation of therapy and after three months of the respective treatments. All patients already had desirable lipid levels as per the National Cholesterol Education Program - Adult Treatment Panel III guidelines. The addition of fenofibrate to statin monotherapy produced further benefits to the redu...
We evaluated the impact of Metoprolol CR/XL on the diurnal and exercise induced variation on Pulm... more 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. 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. 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 upti...
Background We sought to compare the long-term safety of two devices with diff erent antiprolifera... more Background We sought to compare the long-term safety of two devices with diff erent 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 stratifi ed 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 defi nite 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 defi nite or probable stent thrombosis did not diff er 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 defi nite or probable stent thrombosis rates was noted at 3 years. Time analysis suggests a diff erence in defi nite 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.
Journal of the American College of Cardiology, 2012
Background: The Global Burden of Disease (GBD) study estimates that 52% of cardiovascular disease... more Background: The Global Burden of Disease (GBD) study estimates that 52% of cardiovascular disease (CVD) deaths occur below the age of 70 years in India as compared to 23% in established market economies. Despite the biological differences influencing the pathogenesis of CVD and the response to medical therapies, women access to medical therapy and cardiac procedures is inappropriately restricted elusive of the contributing factors. Methods: Patients with CVD visiting Care Institute of Medical Sciences (CIMS), Ahmedabad, India from January 2008 to September 2011 were enrolled in the study. Gender-based differences in age, habitat, risk factors, clinical presentation, angiography procedure approach and treatment options were analyzed. Subjects were categorized based on interventions like coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), and medical therapy respectively for analyzing treatment options. Results: A total of 10,450 consecutive patients were enrolled in the present study. Of these, 8744 (83.67%) were males and 1706 (16.33%) were females. Prevalence of CVD was higher in urban female subjects (p<0.0001)whereas it was higher in males in rural areas (p<0.0001). As compared to males, female population had an increased prevalence of hypertension (p<0.0001), diabetes (p=0.01) and family history (p<0.0001); while male population had smoking (p<0.0001) as a contributable risk factor. Obesity contributed equally as a risk factor to both male and female subjects. Number of patients who underwent angiography procedure was significantly higher in male population (p<0.0001) as compared to female population irrespective of radial or femoral approach. Treatment options like CABG (18.45% vs. 12.42%, p<0.0001) and PCI (45.04% vs. 40.73%, p=0.001) were higher in males as compared to female subjects where medical therapy was the preferred option (46.83% vs. 36.49%, p<0.0001) irrespective of the contributing/confounding factors. Conclusion: Gender related wide differences to testing, prevention and availed treatment options prevail in Indian CVD patients.
Journal of Molecular and Cellular Cardiology, 2006
demonstrated that diabetic cardiomyopathy in diabetic rats is associated with NADPH oxidase upreg... more demonstrated that diabetic cardiomyopathy in diabetic rats is associated with NADPH oxidase upregulation. The antihypertrophic actions of atrial natriuretic peptide (ANP) in vitro are mediated at least in part by NADPH oxidase suppression. Our objective was to test the hypothesis that ANP limits the functional and structural components of diabetic cardiomyopathy in type 1 diabetes, and elucidate whether antioxidant actions contribute to this protection. ANP treatment (10 pmol/ kg/min sc, n = 13) over the last 4 weeks of eight weeks streptozotocin diabetes significantly improved left ventricular (LV) diastolic dysfunction, by 22 T 6% on early/late diastolic filling (echocardiography-derived E/A ratio, p < 0.05 vs untreated STZ) and tended to improve LVdP/dt min by 15 T 9% (cardiac catheterization, p = 0.1). Aortic flow velocity and velocity of circumferential fibre shortening were also improved by ANP, by 19 T 7% (p < 0.05) and 14 T 6% (p = 0.07). No changes in LV systolic pressure or LVdP/dt max were observed. ANP significantly and potently attenuated LVexpression of the hypertrophic gene h-myosin heavy chain (by 69 T 5%, p < 0.001) and of NADPH oxidase (by 79 T 7%, p < 0.05). Aortic NADPH-driven superoxide generation was also decreased by ANP, by 69 T 5% (p < 0.01). Both the ACE inhibitor ramipril (1 mg/kg/day, n = 12) and the antioxidant tempol (1.5 mmol/kg/day sc, n = 11) improved diastolic, but not systolic, function. Tempol was the only treatment that attenuated cardiac fibrosis. In conclusion, our results demonstrate that ANP ameliorates diabetes-induced disturbances in myocardial function. These studies may lead to new therapies, based on natriuretic peptide and/or antioxidant approaches, for diabetic cardiomyopathy.
Background— Pulmonary arterial hypertension (PAH) is a progressive, fatal disease with no cure. P... more 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 inclu...
Canadian Journal of Physiology and Pharmacology, 2007
No or slow reflow following percutaneous coronary intervention (PCI), despite the presence of a p... more No or slow reflow following percutaneous coronary intervention (PCI), despite the presence of a patent epicardial vessel, is a serious complication resulting in increased morbidity and mortality. In the present study, we have evaluated the combination therapy of adenosine and sodium nitroprusside administered as sequential intracoronary (IC) boluses on no-reflow during PCI. Seventy-five high risk acute coronary syndrome patients who underwent PCI with evidence of initial less than TIMI (thrombolysis in myocardial infarction) III flow or developed deterioration in TIMI flow during the procedure were randomized to prophylactic administration of multiple boluses of IC saline solution, adenosine (12 µg/bolus) or the combination of adenosine (12 µg/bolus) and sodium nitroprusside (50 µg/bolus), sequentially. Assessment of TIMI and the TMP (tissue myocardial perfusion) grade was done and major adverse cardiac events (MACE) were assessed at the end of 6 months. Slow or no-reflow was persis...
Many studies have demonstrated a strong association between elevated plasma total homocyst(e)ine ... more Many studies have demonstrated a strong association between elevated plasma total homocyst(e)ine levels and vascular diseases. Consequently, hyperhomocyst(e)inemia is now generally accepted as an independent risk factor for coronary artery disease. We critically reviewed the results of 35 human studies in which the levels of plasma total homocysteine were measured in patients with atherosclerotic diseases (n = 4338) and in controls (n = 22,593). Total homocysteine levels were consistently higher in patients than in controls. The average of this increment among 23 case-control studies was 26%. New insights into the biochemical pathways of total homocysteine metabolism, the factors that influence total homocysteine levels, genetic contributions to hyperhomocyst(e)inemia, the pathogenesis of homocyst(e)ine-induced vascular damage, and current recommendations for treatment of hyperhomocyst(e)inemia were also reviewed. Various lines of evidence now link hyperhomocyst(e)inemia with vascular diseases. Although there are no data from double-blind, placebo-controlled clinical trials of treatment for hyperhomocyst(e)inemia, the strong epidemiologic and experimental evidence argues for treatment of hyperhomocyst(e)inemia; in fact, its treatment with low doses of vitamins is thought to be safe and is inexpensive.
Drug-eluting stents (DES) reduce restenosis rates compared to bare-metal stents. Most trials usin... more 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.
Journal of the American College of Cardiology, 2017
parameters, functional class, quality of life and clinical endpoints including death, hospitaliza... more parameters, functional class, quality of life and clinical endpoints including death, hospitalization and acute kidney injury. RESULTS The results presented in this abstract are based on preliminary results of 34/70 patients who completed 6 months follow-up. A total of 6 females and 28 males were included, with a mean age of 60 AE 9yr. At baseline, 73.5% of the patients presented in NYHA class II and 26.5% in NYHA class III. Mean LVEF was 32 AE 9% and mean estimated glomerular filtration rate (eGFR) was 71 AE 25 mL/min at baseline. Mean change in late HMR at 6months was-0.06 AE 0.15 in the RDN group and-0.06 AE 0.25 in the OMT group (p¼NS for both comparisons of the change from baseline). NYHA class significantly improved in the RDN group at 6months (p <0.01) and remained unchanged in the OMT group. At 6 months blood pressure and eGFR remained unchanged in both cohorts. The mean (AESD) change in LVEF at 6 months was þ2 AE 7% in the RDN group as compared with þ0.5 AE 4% in the control group. Left ventricular end-diastolic diameter (LVEDD) significantly decreased in the RDN group-3 AE 4mm (p¼0.02) and remained unchanged in the OMT group (0.4 AE 3mm; p¼0.52). During follow-up, 1 patient died in the OMT group, rehospitalization for heart failure occurred in 3 patients (1 in the RDN group, 2 in the OMT). CONCLUSION The preliminary results of this randomized controlled study suggest that RDN in patients with HFrEF was safe with a potential positive effect on signs and symptoms of heart failure. No significant change was observed in cardiac sympathetic nerve activity at 6 months in patients in both arms.
Background: Bicuspid aortic valve (BAV) affects approximately 1.5% of the general population and ... more 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...
Supplemental material, sj-pdf-1-pul-10.1177_2045894019866335 for Long-term study of oral treprost... more Supplemental material, sj-pdf-1-pul-10.1177_2045894019866335 for Long-term study of oral treprostinil to treat pulmonary arterial hypertension: dosing, tolerability, and pharmacokinetics by R. James White, Keyur Parikh, Roblee Allen, Jeremy Feldman, Carlos Jerjez-Sanchez, Lei Pan, Anne Keogh, C. Dario Vizza, Shelley Shapiro, Kathryn Gordon, Meredith Broderick and Sonja Bartolome in Pulmonary Circulation
Oral treprostinil may be an option for low- and intermediate-risk patients with pulmonary arteria... more Oral treprostinil may be an option for low- and intermediate-risk patients with pulmonary arterial hypertension, a rare lung vascular disease. This open-label extension study collected data on participants who completed previously reported, placebo-controlled oral treprostinil studies. Eligible participants had completed the prospective parent studies and took increasing doses of oral treprostinil twice daily; some later transitioned to three times daily dosing. Investigators measured 6-minute walk distance at Month 12 as the sole efficacy measure but collected adverse events throughout the study. A single center measured pharmacokinetics in 13 subjects who changed dosing from twice daily to three times daily. Eight hundred and ninety-four participants enrolled and 71% completed one year of therapy, with a median total daily dose of 7 mg and a median 6-minute walk distance increase of 22 m (interquartile range, −14 to 67 m). Subjects achieving higher doses had larger increases in 6-...
Introduction: Limited data is available on outcomes with renal denervation (RDN) in an Indian pat... more Introduction: Limited data is available on outcomes with renal denervation (RDN) in an Indian patient population. The Single-arm Study of Symplicity TM Renal Denervation System in Patients With Uncontrolled HyperTensioN in India (HTN-India) study prospectively evaluated the safety and efficacy of renal denervation therapy in an Indian population with uncontrolled hypertension using the Symplicity Flex TM catheter (Medtronic, Inc.). Material: The primary effectiveness endpoint is 6-month change in office systolic blood pressure (SBP). Home BP was also recorded at baseline and 6 months. Observations and conclusions: A total of 28 subjects at 7 sites were consented and 14 subjects were treated with RDN in HTN-India when the study was stopped following the announcement of results of the SYMPLICITY HTN-3 trial. Baseline office and home SBP was 177 AE 17 and 160 AE 11 mmHg; average age was 51 AE 11 years, 57% were male, 21% had type II diabetes, and average body mass index was 28 AE 5 kg/m 2. Subjects were prescribed 4.1 AE 1.2 and 4.5 AE 1.1 antihypertensive medications at baseline and 6 months. Both office and home SBP decreased significantly at 6 months (À28.5 AE 23.8 mmHg, and À19.6 AE 13.6 mmHg, respectively, p ≤ 0.01 for both). No procedure-related adverse events were reported, although there was one non-cardiovascular death (severe burn unrelated to RDN) at 5 months. We conclude that RDN was safe and effective in this Indian population with treatment resistant hypertension. Confirmatory prospective sham controlled trials are warranted.
Background: Identifying adverse cardiac events and reducing readmissions improves patient surviva... more Background: Identifying adverse cardiac events and reducing readmissions improves patient survival, enhances quality of care, and lowers health care expenditure. Objective of the Hospital to Home (H2H) follow up visit, a first of its kind program was initiated to improve transition from inpatient to outpatient status for individuals hospitalized for coronary artery bypass graft (CABG) surgery. Methods: Since July 2012, trained healthcare personnel of CIMS Hospital, Ahmedabad, India, initiated H2H visits on a total of 437 patients following discharge after CABG surgery. Based on distance the visits were categorized as A (n=198, less than 70 km); B (n=137, 70-600 km);C (n=82, 600-1000km) and D (n=20, >1000km). Results: At 5 days early follow up, H2H visits depicted medical complications (36.56%) like wound infection (1.6%); poor dressing conditions (2.58%); inappropriate chest belts (8.46%) and poor hygiene (3.9%). Adverse Drug Reactions were reported in 10 patients of which 8 were...
Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor there... more Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor thereby attenuating the differential effect by race. Attenuation likely occurs in both race-groups but may be more pronounced in the less-represented race-group. Therefore, we evaluated whether the effect of clinical (age, body surface area [BSA], chronic kidney disease [CKD], and amiodarone use) and genetic factors (CYP2C9 *2, *3, *5, *6, *11, rs12777823, VKORC1, and CYP4F2) on warfarin dose differs by race using regression analyses among 1357 patients enrolled in a prospective cohort study, and compared predictive ability of race-combined versus race-stratified models. Differential effect of predictors by race was assessed using predictor-race interactions in race-combined analyses. Warfarin dose was influenced by age, BSA, CKD, amiodarone use, CYP2C9*3 and VKORC1 variants in both races, by CYP2C9*2 and CYP4F2 variants in European Americans, and rs12777823 in African Americans. CYP2C9*2 was...
To compare the long-term clinical safety between two drug-eluting stents with different healing c... more 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. 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 u...
To find out whether the addition of fenofibrate to statin monotherapy produced any synergistic or... more To find out whether the addition of fenofibrate to statin monotherapy produced any synergistic or additive beneficial effects in reducing risk factors, especially plasma fibrinogen, in patients with acute coronary syndrome (ACS) requiring percutaneous coronary interventions. A randomized, non-blinded, prospective study with parallel group design. One hundred two ACS patients who underwent angioplasty were randomly assigned to atorvastatin (20 mg/day, n=25), simvastatin (40 mg/day, n=27), atorvastatin-fenofibrate (10 mg/day-200 mg/day) combination (n=25) or simvastatin-fenofibrate (20 mg/day-200 mg/day) combination (n=25). The serum lipid profile and plasma fibrinogen were recorded before initiation of therapy and after three months of the respective treatments. All patients already had desirable lipid levels as per the National Cholesterol Education Program - Adult Treatment Panel III guidelines. The addition of fenofibrate to statin monotherapy produced further benefits to the redu...
We evaluated the impact of Metoprolol CR/XL on the diurnal and exercise induced variation on Pulm... more 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. 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. 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 upti...
Background We sought to compare the long-term safety of two devices with diff erent antiprolifera... more Background We sought to compare the long-term safety of two devices with diff erent 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 stratifi ed 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 defi nite 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 defi nite or probable stent thrombosis did not diff er 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 defi nite or probable stent thrombosis rates was noted at 3 years. Time analysis suggests a diff erence in defi nite 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.
Journal of the American College of Cardiology, 2012
Background: The Global Burden of Disease (GBD) study estimates that 52% of cardiovascular disease... more Background: The Global Burden of Disease (GBD) study estimates that 52% of cardiovascular disease (CVD) deaths occur below the age of 70 years in India as compared to 23% in established market economies. Despite the biological differences influencing the pathogenesis of CVD and the response to medical therapies, women access to medical therapy and cardiac procedures is inappropriately restricted elusive of the contributing factors. Methods: Patients with CVD visiting Care Institute of Medical Sciences (CIMS), Ahmedabad, India from January 2008 to September 2011 were enrolled in the study. Gender-based differences in age, habitat, risk factors, clinical presentation, angiography procedure approach and treatment options were analyzed. Subjects were categorized based on interventions like coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), and medical therapy respectively for analyzing treatment options. Results: A total of 10,450 consecutive patients were enrolled in the present study. Of these, 8744 (83.67%) were males and 1706 (16.33%) were females. Prevalence of CVD was higher in urban female subjects (p<0.0001)whereas it was higher in males in rural areas (p<0.0001). As compared to males, female population had an increased prevalence of hypertension (p<0.0001), diabetes (p=0.01) and family history (p<0.0001); while male population had smoking (p<0.0001) as a contributable risk factor. Obesity contributed equally as a risk factor to both male and female subjects. Number of patients who underwent angiography procedure was significantly higher in male population (p<0.0001) as compared to female population irrespective of radial or femoral approach. Treatment options like CABG (18.45% vs. 12.42%, p<0.0001) and PCI (45.04% vs. 40.73%, p=0.001) were higher in males as compared to female subjects where medical therapy was the preferred option (46.83% vs. 36.49%, p<0.0001) irrespective of the contributing/confounding factors. Conclusion: Gender related wide differences to testing, prevention and availed treatment options prevail in Indian CVD patients.
Journal of Molecular and Cellular Cardiology, 2006
demonstrated that diabetic cardiomyopathy in diabetic rats is associated with NADPH oxidase upreg... more demonstrated that diabetic cardiomyopathy in diabetic rats is associated with NADPH oxidase upregulation. The antihypertrophic actions of atrial natriuretic peptide (ANP) in vitro are mediated at least in part by NADPH oxidase suppression. Our objective was to test the hypothesis that ANP limits the functional and structural components of diabetic cardiomyopathy in type 1 diabetes, and elucidate whether antioxidant actions contribute to this protection. ANP treatment (10 pmol/ kg/min sc, n = 13) over the last 4 weeks of eight weeks streptozotocin diabetes significantly improved left ventricular (LV) diastolic dysfunction, by 22 T 6% on early/late diastolic filling (echocardiography-derived E/A ratio, p < 0.05 vs untreated STZ) and tended to improve LVdP/dt min by 15 T 9% (cardiac catheterization, p = 0.1). Aortic flow velocity and velocity of circumferential fibre shortening were also improved by ANP, by 19 T 7% (p < 0.05) and 14 T 6% (p = 0.07). No changes in LV systolic pressure or LVdP/dt max were observed. ANP significantly and potently attenuated LVexpression of the hypertrophic gene h-myosin heavy chain (by 69 T 5%, p < 0.001) and of NADPH oxidase (by 79 T 7%, p < 0.05). Aortic NADPH-driven superoxide generation was also decreased by ANP, by 69 T 5% (p < 0.01). Both the ACE inhibitor ramipril (1 mg/kg/day, n = 12) and the antioxidant tempol (1.5 mmol/kg/day sc, n = 11) improved diastolic, but not systolic, function. Tempol was the only treatment that attenuated cardiac fibrosis. In conclusion, our results demonstrate that ANP ameliorates diabetes-induced disturbances in myocardial function. These studies may lead to new therapies, based on natriuretic peptide and/or antioxidant approaches, for diabetic cardiomyopathy.
Background— Pulmonary arterial hypertension (PAH) is a progressive, fatal disease with no cure. P... more 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 inclu...
Canadian Journal of Physiology and Pharmacology, 2007
No or slow reflow following percutaneous coronary intervention (PCI), despite the presence of a p... more No or slow reflow following percutaneous coronary intervention (PCI), despite the presence of a patent epicardial vessel, is a serious complication resulting in increased morbidity and mortality. In the present study, we have evaluated the combination therapy of adenosine and sodium nitroprusside administered as sequential intracoronary (IC) boluses on no-reflow during PCI. Seventy-five high risk acute coronary syndrome patients who underwent PCI with evidence of initial less than TIMI (thrombolysis in myocardial infarction) III flow or developed deterioration in TIMI flow during the procedure were randomized to prophylactic administration of multiple boluses of IC saline solution, adenosine (12 µg/bolus) or the combination of adenosine (12 µg/bolus) and sodium nitroprusside (50 µg/bolus), sequentially. Assessment of TIMI and the TMP (tissue myocardial perfusion) grade was done and major adverse cardiac events (MACE) were assessed at the end of 6 months. Slow or no-reflow was persis...
Many studies have demonstrated a strong association between elevated plasma total homocyst(e)ine ... more Many studies have demonstrated a strong association between elevated plasma total homocyst(e)ine levels and vascular diseases. Consequently, hyperhomocyst(e)inemia is now generally accepted as an independent risk factor for coronary artery disease. We critically reviewed the results of 35 human studies in which the levels of plasma total homocysteine were measured in patients with atherosclerotic diseases (n = 4338) and in controls (n = 22,593). Total homocysteine levels were consistently higher in patients than in controls. The average of this increment among 23 case-control studies was 26%. New insights into the biochemical pathways of total homocysteine metabolism, the factors that influence total homocysteine levels, genetic contributions to hyperhomocyst(e)inemia, the pathogenesis of homocyst(e)ine-induced vascular damage, and current recommendations for treatment of hyperhomocyst(e)inemia were also reviewed. Various lines of evidence now link hyperhomocyst(e)inemia with vascular diseases. Although there are no data from double-blind, placebo-controlled clinical trials of treatment for hyperhomocyst(e)inemia, the strong epidemiologic and experimental evidence argues for treatment of hyperhomocyst(e)inemia; in fact, its treatment with low doses of vitamins is thought to be safe and is inexpensive.
Drug-eluting stents (DES) reduce restenosis rates compared to bare-metal stents. Most trials usin... more 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.
Journal of the American College of Cardiology, 2017
parameters, functional class, quality of life and clinical endpoints including death, hospitaliza... more parameters, functional class, quality of life and clinical endpoints including death, hospitalization and acute kidney injury. RESULTS The results presented in this abstract are based on preliminary results of 34/70 patients who completed 6 months follow-up. A total of 6 females and 28 males were included, with a mean age of 60 AE 9yr. At baseline, 73.5% of the patients presented in NYHA class II and 26.5% in NYHA class III. Mean LVEF was 32 AE 9% and mean estimated glomerular filtration rate (eGFR) was 71 AE 25 mL/min at baseline. Mean change in late HMR at 6months was-0.06 AE 0.15 in the RDN group and-0.06 AE 0.25 in the OMT group (p¼NS for both comparisons of the change from baseline). NYHA class significantly improved in the RDN group at 6months (p <0.01) and remained unchanged in the OMT group. At 6 months blood pressure and eGFR remained unchanged in both cohorts. The mean (AESD) change in LVEF at 6 months was þ2 AE 7% in the RDN group as compared with þ0.5 AE 4% in the control group. Left ventricular end-diastolic diameter (LVEDD) significantly decreased in the RDN group-3 AE 4mm (p¼0.02) and remained unchanged in the OMT group (0.4 AE 3mm; p¼0.52). During follow-up, 1 patient died in the OMT group, rehospitalization for heart failure occurred in 3 patients (1 in the RDN group, 2 in the OMT). CONCLUSION The preliminary results of this randomized controlled study suggest that RDN in patients with HFrEF was safe with a potential positive effect on signs and symptoms of heart failure. No significant change was observed in cardiac sympathetic nerve activity at 6 months in patients in both arms.
Uploads
Papers by Keyur Parikh