Pharmacogenetic guided versus standard warfarin dosing for routine clinical care with its pharmacoeconomic impact: a randomized controlled clinical trial.

BACKGROUND: Empirical use of pharmacogenetic test(PGT) is advocated for many drugs, and resource-rich setting hospitals are using the same commonly. The clinical translation of pharmacogenetic tests in terms of cost and clinical utility is yet to be examined in hospitals of low middle income countries (LMICs). AIM: The present study assessed the clinical utility of PGT by comparing the pharmacogenetically(PGT) guided- versus standard of care(SOC)- warfarin therapy, including the health economics of the two warfarin therapies. METHODS: An open-label, randomized, controlled clinical trial recruited warfarin-receiving patients in pharmacogenetically(PGT) guided- versus standard of care(SOC)- study arms. Pharmacogenetic analysis of CYP2C9*2(rs1799853), CYP2C9*3(rs1057910) and VKORC1(rs9923231) was performed for patients recruited to the PGT-guided arm. PT(Prothrombin Time)-INR(international normalized ratio) testing and dose titrations were allowed as per routine clinical practice. The primary endpoint was the percent time spent in the therapeutic INR range(TTR) during the 90-day observation period. Secondary endpoints were time to reach therapeutic INR(TRT), the proportion of adverse events, and economic comparison between two modes of therapy in a Markov model built for the commonest warfarin indication- atrial fibrillation. RESULTS: The study enrolled 168 patients, 84 in each arm. Per-protocol analysis showed a significantly high median time spent in therapeutic INR in the genotype-guided arm(42.85%; CI 21.4-66.75) as compared to the SOC arm(8.8%; CI 0-27.2)(p < 0.00001). The TRT was less in the PG-guided warfarin dosing group than the standard-of-care dosing warfarin group (17.85 vs. 33.92 days) (p = 0.002). Bleeding and thromboembolic events were similar in the two study groups. Lifetime expenditure was ₹1,26,830 in the PGT arm compared to ₹1,17,907 in the SOC arm. The QALY gain did not differ in the two groups(3.9 vs. 3.65). Compared to SOC, the incremental cost-utility ratio was ₹35,962 per QALY gain with PGT test opting. In deterministic and probabilistic sensitivity analysis, the base case results were found to be insensitive to the variation in model parameters. In the cost-effectiveness-acceptability curve analysis, a 90% probability of cost-effectiveness was reached at a willingness-to-pay(WTP) of ₹ 71,630 well below one time GDP threshold of WTP used. CONCLUSION: Clinical efficacy and the cost-effectiveness of the warfarin pharmacogenetic test suggest its routine use as a point of care investigation for patient care in LMICs.

Optical Coherence Tomography Predictors of SIde Branch REstenosis after unprotected Left Main bifurcation angioplasty using double kissing crush technique (OP-SIBRE LM Study).

BACKGROUND: Among the two stent strategies, contemporary evidence favors double kissing crush technique (DKC) for complex unprotected distal left main bifurcation (UdLMB) lesions. However one of the major challenges to these lesions is side branch (SB) restenosis. AIMS: Our aim was to identify optical coherence tomographic (OCT) characteristics that may predict SB restenosis (SBR) after UdLMB angioplasty using DKC technique. METHODS: This was a single-center, retrospective study that included 60 patients with complex UdLMB disease, who underwent OCT-guided angioplasty using DKC technique. Angiographic follow-up was performed in all patients at 1 year to identify patients with SBR. Patients with SBR group were compared with patients without SBR (NSBR group) for OCT parameters during index procedure. RESULTS: Twelve (20%) patients developed SBR at 1-year follow-up. The SBR group had longer SB lesion (18.8 ± 3.2 vs. 15.3 ± 3.7 mm, p = 0.004) and neo-metallic carinal length (2.1 vs. 0.1 mm, p < 0.001) when compared to the NSBR group. Longer neo-metallic carinal length was associated with the absence of the dumbbell sign, presence of hanging stent struts across the SB ostium on OCT of final MB pullback. On multivariate regression analysis, SB distal reference diameter (DRD) and SB stent expansion were identified as independent predictors of SBR with SB-DRD of ≤2.8 mm (area under curve-0.73, sensitivity-83.3%, and specificity-62.5%) and SB stent expansion of ≤89% (area under curve-0.88, sensitivity-83.3%, and specificity- 81.2%) as the best cut off values to predict SBR. CONCLUSIONS: SB DRD and SB stent expansion are the OCT predictors of future SBR after UdLMB angioplasty using DKC technique.

Pregnancy in Eisenmenger syndrome: a case series from a tertiary care hospital of Northern India.

BACKGROUND: Despite advances in medical care, we still come across pregnancy in Eisenmenger syndrome. Eisenmenger syndrome represents the severe end of the spectrum for disease in pulmonary artery hypertension associated with CHD. Due to very high maternal and perinatal morbidity and mortality, pregnancy is contraindicated among these women. Current guidelines also recommend that the women who become pregnant should opt for early termination of pregnancy. Here, we present a case series of 11 women of Eisenmenger syndrome and their pregnancy outcome. METHODS: It was a retrospective analysis of 12 pregnancies among 11 women with Eisenmenger syndrome who were managed in a tertiary care referral centre of Northern India. RESULTS: The mean age of these women was 28 ± 4 years (range 22 to 36 years). Almost 80% of them (9/11) were diagnosed with Eisenmenger syndrome during pregnancy. The commonest cardiac lesion was Ventricular Septal defect (54.5%) followed by Atrial Septal defect (27.3%) and Patent Ductus arteriosus (9.1%). Only three women opted for medical termination of pregnancy, rest eight continued the pregnancy or presented late. Pregnancy complications found include pre-eclampsia (50%), abruption (22%), and fetal growth retardation (62.5%). There were three maternal deaths (mortality rate 27%) in postpartum period. CONCLUSION: This case series highlights the delay in diagnosis and treatment of CHD despite improvement in medical care. Women with Eisenmenger syndrome require effective contraception, preconceptional counselling, early termination of pregnancy, and multidisciplinary care.

Calcification Detection in Intravascular Ultrasound (IVUS) Images Using Transfer Learning Based MultiSVM model.

Cardiovascular disease serves as the leading cause of death worldwide. Calcification detection is considered an important factor in cardiovascular diseases. Currently, medical practitioners visually inspect the presence of calcification using intravascular ultrasound (IVUS) images. The study aims to detect the extent of calcification as belonging to class I, II as mild calcification, and class III, IV as dense calcification from IVUS images acquired at 40 MHz. To detect calcification, the features were extracted using improved AlexNet architecture and then were fed into machine learning classifiers. The experiments were carried out using 14 real IVUS pullbacks of 10 patients. Experimental results show that the combination of traditional machine learning with deep learning approaches significantly improves accuracy. The results show that support vector machines outperform all other classifiers. The proposed model is compared with two other pre-trained models GoogLeNet (98.8%), SqueezeNet (99.2%), and exhibits considerable improvement in classification accuracy (99.8%). In the future other models such as Vision Transformers could be explored with additional feature selection methods such as ReliefF, PSO, ACO, etc. to improve the overall accuracy of diagnosis.

Clinical presentation and treatment outcomes of arterial involvement in Behçet's disease: a single-centre experience.

Arterial involvement, although rare, accounts for significant mortality and morbidity in patients of Behçet's disease (BD). There is paucity of data on arterial BD. The objective of this 5-year retrospective cohort study was to examine the clinical presentation, pattern of arterial involvement, and treatment outcome in Indian arterial BD patients. Data on demography, clinical presentation, radiology, instituted therapy, vascular interventions and treatment outcomes were recorded and analyzed. Ten (16.9%) out of 59 patients with BD had arterial involvement in 13 vascular territories [mean age 30 (8) years, 9 (90%) males]. Pulmonary artery was most commonly involved (46%), followed by abdominal aorta (15%), femoral artery (15%), descending thoracic aorta (8%), common iliac (8%), and dorsalis pedis artery (8%). Two patients had multi-territory involvement. The median interval between disease onset and development of arterial aneurysms was 3 years (3 months-12 years). Concomitant deep vein thrombosis was seen in 60% cases. Prednisolone and cyclophosphamide were the most common immunosuppressive therapy used; one patient who relapsed on cyclophosphamide responded to infliximab. Five surgical or endovascular interventions were performed. Four patients (40%) died due to aneurysm rupture-all had a delayed diagnosis, and three had pulmonary artery involvement, with death due to massive hemoptysis. Based on the present study, we concluded that arterial involvement in BD is seen predominantly in males and has a high mortality. Early detection and aggressive treatment with immunosuppression and surgical or endovascular interventions are essential for good outcomes.

Intravascular ultrasound-supported percutaneous angioplasty of post-kidney transplant renal artery bifurcation stenosis.

BACKGROUND: Transplant renal artery stenosis (TRAS) is an uncommon complication following renal transplantation. Its usual clinical presentation includes worsening hypertension and/or renal function, without any evidence of graft rejection. Bifurcation renal artery stenosis of the transplanted renal artery is rarely encountered. METHODS: Percutaneous transluminal renal angioplasty (PTRA) with or without stenting is the procedure of choice to treat TRAS. We hereby describe a patient, who presented with impaired renal functions, four months following the renal transplantation. He underwent intravascular ultrasound-guided PTRA of the bifurcation lesion of TRAS.Results and conclusion: Superior renal artery had coronary drug-eluting stent implantation, while inferior renal artery and side branch of the superior renal artery had balloon angioplasty, alone. Post-intervention, the raised serum creatinine level decreased from 2.9 mg% to 1.7 mg%. The index case described the successful PTRA and stenting of the bifurcation lesion of TRAS, the technical results of which was optimized with the use of intravascular ultrasound.

Objective-structured clinical examination in cardiovascular system for the assessment of internal medicine postgraduates amidst the Covid-19 pandemic.

Background The Covid-19 pandemic has posed a challenge to organizing a safe clinical assessment for postgraduate degree candidates completing the residency programmes in various specialties. Although minimizing the risk of Covid-19 transmission is a priority, fulfilling the objectives of the assessment is equally important. Methods We conducted this study in the Department of Internal Medicine at our institute. Instead of physically examining patients, case scenarios that included history, clinical and investigational data of the cardiovascular system (CVS) were presented to the candidates. Performance was scored by both the conventional and the CVS objective-structured clinical examination (CVS-OSCE) method and compared. Results Clinical assessment examination of 27 candidates for the degree of Doctor of Medicine showed that the median cumulative score gained in narrating and analysing various differential diagnoses was lower compared to the mean cumulative score gained in arriving at a single correct diagnosis (50% [interquartile range-IQR 39%-64%] v. 79% [IQR 64%-100%], p<0.01). Most of the candidates agreed that case scenarios were good alternatives to the conventional physical examination amidst the pandemic. Conclusion CVS-OSCE-based assessment using structured case scenarios is a feasible and effective alternative for clinical skill assessment in high-stake examinations.

Simultaneous endovascular revascularization of external iliac artery dissection and transplant renal artery stenosis in a recent renal allograft recipient.

Various vascular complications following renal transplantation include renal artery and vein thrombosis, renal artery stenosis, pseudoaneurysm, and iliac artery dissection. Transplant renal artery stenosis (TRAS) is the most common, while iliac artery dissection is the rarest of these various vascular complications. We describe an elderly male, who had both external iliac artery dissection and TRAS at 2 months following renal transplantation. He underwent successful percutaneous endovascular intervention of both complications. The post-intervention course was uneventful, with improvement in graft renal functions and left lower limb perfusion.

As diversas complicações vasculares possíveis após um transplante renal incluem trombose da veia e artéria renais, estenose da artéria renal, pseudoaneurisma e dissecção da artéria ilíaca. Entre essas diversas complicações, a estenose da artéria renal transplantada é a mais comum, enquanto a dissecção da artéria ilíaca é a mais rara. Relatamos o caso de um homem idoso que desenvolveu tanto dissecção da artéria ilíaca quanto estenose da artéria renal transplantada 2 meses após transplante renal. As intervenções endovasculares percutâneas foram bem-sucedidas em ambas as complicações. O período pós-intervenção cursou sem complicações, com melhora na função renal do enxerto e na perfusão do membro inferior esquerdo.

Endovascular stenting with a drug-eluting stent of transplanted renal artery stenosis in a dual kidney transplanted patient.

Renal transplant remains the preferred therapy for end-stage renal disease (ESRD). Given the shortage of suitable donor kidneys, use of an expanded criteria donor (ECD) allows marginal kidneys to be transplanted; albeit at risk of increased graft failure due to lower nephron mass. To reduce the risk of graft failure, double kidney transplant (DKT) is advocated, with favorable outcomes. Transplant renal artery stenosis (TRAS) is one of the most common vascular complications following renal transplant. Unlike single kidney transplants, where TRAS usually presents with fluid overload, uncontrolled hypertension, and worsening kidney functions; it may be clinically silent in DKT patients since they have two functional transplanted kidneys. We hereby report a case of TRAS in a DKT patient who had 2 years of favorable clinical outcomes following successful endovascular stenting. He however recently died of COVID-19 associated pneumonitis.

O transplante renal continua sendo a terapia preferida para doenças renais em fase terminal. Dada a escassez de rins de doadores adequados, o doador com critérios expandidos permite que rins marginais sejam transplantados, embora haja um maior risco de falha do enxerto devido à diminuição da massa nefrótica. Para diminuir o risco de falha do enxerto, recomenda-se o transplante renal duplo (TRD), com resultados favoráveis. A estenose de artéria renal transplantada (EART) é uma das complicações vasculares mais comuns após o transplante renal. Ao contrário dos transplantes de rim simples, nos quais a EART geralmente se manifesta como sobrecarga de fluido, hipertensão descontrolada e piora das funções renais, ela pode ser clinicamente silenciosa em pacientes com TRD, pois eles têm dois rins funcionais transplantados. Relatamos aqui um caso de EART em um paciente com TRD que teve resultados clínicos favoráveis por dois anos após o sucesso do implante de stent endovascular. No entanto, ele morreu recentemente de pneumonite associada à covid-19.

Retroperitoneal iliac conduits as an alternative access site for endovascular aortic repair: a tertiary care center experience.

Background: Retroperitoneal open iliac conduits (ROIC) are used in patients with hostile iliac anatomy undergoing endovascular aortic repair (EVAR). Objectives: We hereby report our experience of ROIC in patients subjected to EVAR. Methods: This was a retrospective evaluation of 8 patients out of a total of 75 patients (11%) who underwent EVAR in the last 10 years. Pre-procedure computed tomography angiography was used to assess the dimensions of iliac and femoral arteries. Patients who had small arterial dimensions (i.e. smaller than the recommended access size for the aortic endograft device) were subjected to ROIC. Results: The mean age of the 3 males and 5 females studied was 45.7 ± 15.2 years. The indication for ROIC was the small caliber ilio-femoral access site in 7 patients and atherosclerotic disease in 1 patient. All external grafts were anastomosed to the right common iliac artery except one which was anastomosed to the aortic bifurcation site because of a small common iliac artery. The procedural success rate was 100%. Local access site complications included infection (n=1), retroperitoneal hematoma (n=1), and need for blood transfusion (n=3). The median post-intervention hospital stay was 10 days. All patients had favorable long-term outcomes at a median follow-up of 18 months. Conclusions: Female patients require ROIC during EVAR more frequently. Adjunctive use of iliac conduit for EVAR was associated with favorable perioperative and short-term outcomes.

Contexto: Os condutos ilíacos abertos retroperitoneais são utilizados em pacientes submetidos a reparo endovascular de aneurisma (REVA) com anatomia ilíaca hostil. Objetivos: Relatamos a nossa experiência com os condutos ilíacos em pacientes submetidos a REVA. Métodos: Trata-se de uma avaliação retrospectiva de oito pacientes, de um total de 75 (11%), os quais foram submetidos a REVA nos últimos 10 anos. Foi realizada angiotomografia computadorizada antes do procedimento para avaliar as dimensões das artérias ilíaca e femoral. Os pacientes com dimensões arteriais menores, abaixo do tamanho de acesso recomendado para o dispositivo de endoprótese aórtica, foram submetidos a condutos ilíacos. Resultados: A média de idade dos participantes foi de 45,7±15,2 anos, sendo três do sexo masculino e cinco do sexo feminino. As indicações para condutos ilíacos foram local de acesso ilíaco femoral de pequeno calibre, para sete pacientes, e doença aterosclerótica, para um paciente. Todas as próteses externas foram anastomosadas na artéria ilíaca comum direita, com exceção de uma, que foi anastomosada no local da bifurcação aórtica por apresentar artéria ilíaca comum menor. A taxa de sucesso do procedimento foi de 100%. As complicações no local de acesso incluíram infecção (n = 1), hematoma retroperitoneal (n = 1) e necessidade de transfusão de sangue (n = 3). O tempo mediano de internação hospitalar pós-intervenção foi de 10 dias. Todos os pacientes apresentaram desfechos de longo prazo favoráveis no seguimento mediano de 18 meses. Conclusões: As pacientes do sexo feminino necessitaram de condutos ilíacos durante REVA com maior frequência. O uso adjuvante de condutos ilíacos com REVA foi associado a desfechos perioperatórios e de curto prazo favoráveis.

Non-bronchial causes of haemoptysis: imaging and interventions.

PURPOSE: To describe non-bronchial causes of haemoptysis on imaging and the role of interventional radiology in their management from cases of haemoptysis archived from our database at a tertiary care, federally funded institution. MATERIAL AND METHODS: Retrospective analysis of cases that presented with haemoptysis in our institution from 2008 to 2013 was done, and details of cases in which the bleeding was from a non-bronchial source were archived and details of imaging and treatment were recorded. RESULTS: Retrospective analysis of patients presenting with haemoptysis yielded 24 (n = 24) patients having haemoptysis from non-bronchial sources. Causes of haemoptysis were: Rasmussen aneurysms (n = 12/24), costocervical trunk pseudoaneurysm (n = 1/24), left internal mammillary artery pseudoaneurysm (n = 1/24), left ventricular aneurysms (n = 3/24), pulmonary arteriovenous malformations (AVMs) (n = 5/24), and proximal interruption of pulmonary artery (n = 2/24). Imaging and interventional radiology management are described in detail. CONCLUSIONS: Haemoptysis can be from non-bronchial sources, which may be either from systemic or pulmonary arteries or cardio-pulmonary fistulas. Bronchial computed tomography angiography (CTBA), if feasible, must always be considered before bronchial artery embolisation because it precisely identifies the source of haemorrhage and vascular anatomy that helps the interventional radiologist in pre-procedural planning. This circumvents chances of re-bleed if standard bronchial artery embolisation is done without CTBA.

Endovascular Treatment of an External Iliac Artery Dissection Causing Early Renal Graft Dysfunction.

Vascular complications such as renal artery or renal vein thrombosis and laceration and iliac artery dissection are rarely encountered after renal transplantation. Timely management of these vascular complications is important to prevent ischemic injury of a transplanted kidney. We hereby report a case of a 60-year-old male who had acute renal dysfunction due to iatrogenic left external iliac artery dissection after renal transplantation. An endovascular stenting of the dissected iliac artery resulted in a brisk flow across both iliac and transplanted renal arteries. The management issues related to this rare vascular complication is discussed in the article.

OUTCOME OF ENDOVASCULAR PROCEDURES ON OCULAR FINDINGS IN TAKAYASU ARTERITIS.

PURPOSE: To evaluate the outcome of endovascular procedures on ocular findings in patients with Takayasu arteritis. METHODS: Retrospective study of patients who underwent percutaneous endovascular stenting of aortic arch arteries for Takayasu arteritis (TA) and who had documented retinopathy findings before and after the procedure. Change in visual acuity, regression of retinopathy, and development of complications after endovascular procedure were studied over a follow-up of 6 months. RESULTS: Ten eyes of five patients were included. Eyes which had Stage II or less of retinopathy before the endovascular procedure had favorable outcome; however, those with advanced stage of retinopathy at presentation had poor outcomes. Patients who underwent revascularization of both-sided arteries within 1 month had better anatomical and functional outcomes as compared with those who underwent sequential endovascular procedures on their arteries after a gap of 3 months or more. CONCLUSION: Percutaneous endovascular stenting of aortic arch arteries, affected in TA, can lead to reversal of retinopathy changes and restoration of vision if done before neovascular complications set in.

Factors affecting the outcome of pregnancy with rheumatic heart disease: an experience from low-middle income country.

Studies on pregnancy with rheumatic heart disease (RHD), still common in the developing world, are relatively old and small. This retrospective study was conducted to study the outcome of pregnancy in women with RHD and factors associated with poor outcome. We studied 353 pregnancies in 273 women. In 35% of the patients, the diagnosis was first made during index pregnancy. Women with severe MS had lesser gestational age at delivery and birth weight than those with mild-to-moderate MS. Women with NYHA III-IV status delivered at lesser gestational age had lesser birth weight and had higher perinatal and maternal mortality than NYHA I-II status. Pregnancy outcome was better among women who underwent Balloon mitral valvotomy (BMV) when indicated than those who did not. Cardiac complications were higher in women with severe MS and poor NYHA status. Early booking is important for the optimal outcome. BMV is safe during pregnancy and should be done when necessary. Impact statement What is already known on this subject? Rheumatic heart disease continues to be the major cause of maternal morbidity and mortality in developing countries. Most of the recent studies discuss pregnancy with heart disease as a whole with RHD being a part. What do the results of this study add? A large number of women in developing countries conceive with unknown underlying heart disease. Late access to antenatal care is associated with poor outcome. Cardiac and obstetric complications are significantly higher in women with severe mitral stenosis and poor NYHA functional status. Balloon mitral valvotomy (BMV) during pregnancy is safe and technically feasible. BMV averts major complications that may occur due to severe disease. Patients with RHD can undergo labour and vaginal delivery under vigilant monitoring. What are the implications for clinical practice? Thorough clinical examination by the clinician at initial visit is important to detect unknown heart disease. Symptoms pointing towards underlying heart disease should prompt evaluation. This study provides evidence for population-based screening for heart disease in women. Optimal management of compensated mitral stenosis requires weighing the risks and benefits of pharmacological therapy versus BMV in the context of maternal condition. BMV should be performed when necessary.

Analysis of traditional and emerging risk factors in premenopausal women with coronary artery disease: A pilot-scale study from North India.

Premenopausal women are known to have less heart disease than their menopausal counterparts and men. However, there is a rising prevalence of coronary artery disease (CAD) in premenopausal females, which necessitates determination of risk factors that negate the effects of hormonal protection. There are few studies describing the prevalence of traditional and emerging risk factors in premenopausal women with CAD. Thus, our objective was to explore the prevalence of traditional and emerging risk factors and features of coronary lesions in premenopausal women with CAD in an Indian population. Forty premenopausal female patients with angiographically proven CAD and undergoing treatment with conventional therapies and 40 age-matched premenopausal females without any evidence of CAD were enrolled. Premenopausal females with CAD most commonly had the single-vessel CAD and the left anterior descending artery was most commonly involved. The prevalence of hypertension, diabetes, obesity, metabolic syndrome, family history of CAD and 10-year risk score was higher in premenopausal females with CAD than controls. Even after treatment with conventional therapies, premenopausal women with CAD had dyslipidemia and significantly elevated levels of emerging risk factors such as ApoB, ApoB/ApoA1 ratio, hsCRP, lipoprotein (a), uric acid, T4, fibrinogen, and total leukocyte count as compared to controls (p < 0.05). Further, they had significantly lower levels of HDL-C, and Apolipoprotein A1 and T3 which are protective markers for vascular risk. Multivariate regression analysis demonstrated that low levels of Apo A1 and high levels of fibrinogen, hsCRP and TG drive the vascular risk, and therefore these factors should be considered as candidates for better diagnosis, early detection, and intervention of CAD in premenopausal women.

Midodrine and tolvaptan in patients with cirrhosis and refractory or recurrent ascites: a randomised pilot study.

BACKGROUND: Splanchnic arterial vasodilatation and subsequent sodium and water retention play an important role in cirrhotic ascites. Midodrine and tolvaptan have been used separately in these patients. However, there are no reports on the use of combination of midodrine and tolvaptan in the control of ascites. The aim of this study was to evaluate the safety and efficacy of midodrine, tolvaptan and their combination in control of refractory or recurrent ascites in cirrhotics. METHODS: Fifty cirrhotic patients with refractory or recurrent ascites were randomised to receive midodrine (n=13), tolvaptan (n=12) or both (n=13) plus standard medical therapy (SMT) or SMT alone (n=12). RESULTS: A significant increase in urinary volume and urinary sodium at 1 and 3 months (P<.05) was observed in all groups except SMT. There was no worsening of renal or hepatic function in any group. There was deterioration of model for end-stage liver disease (MELD) in SMT. Midodrine as well as combination of midodrine and tolvaptan but not tolvaptan alone was superior to SMT in control of ascites at 3 months (P<.05). The combination therapy was also superior to midodrine in the control of ascites at 1 month. The morbidity and mortality were similar in all the groups except SMT. CONCLUSIONS: The results of this pilot study suggest that midodrine and combination with tolvaptan better controls ascites without any renal or hepatic dysfunction. The combination therapy rapidly controls ascites as compared to midodrine or tolvaptan alone.

Midodrine and clonidine in patients with cirrhosis and refractory or recurrent ascites: a randomized pilot study.

OBJECTIVES: Splanchnic arterial vasodilatation and subsequent activation of anti-natriuretic and vasoconstrictive mechanisms have an important role in cirrhotic ascites. The aim of this study was to evaluate the effects of midodrine, clonidine, and their combination on systemic hemodynamics, renal function, and control of ascites in patients with cirrhosis and refractory or recurrent ascites. METHODS: Sixty cirrhotic patients with refractory or recurrent ascites were prospectively studied after long-term administration of clonidine (n=15) or midodrine (n=15), or both (n=15) plus standard medical therapy (SMT), or SMT alone (n=15), in a randomized controlled trial at a tertiary center. RESULTS: A significant increase in urinary volume, urinary sodium excretion, mean arterial pressure, and decrease in plasma renin activity (P<0.05) was noted after 1 month. There was also a significant decrease in cardiac output (P<0.05) and increase in systemic vascular resistance (P<0.05) in all groups, except clonidine. There was no change in glomerular filtration rate and model for end-stage liver disease score. Midodrine and a combination of midodrine and clonidine plus SMT were superior to SMT alone in the control of ascites (P=0.05), and there was a trend towards better control of ascites in the clonidine group (P=0.1). The mortality and frequency of various complications were similar in all groups. CONCLUSIONS: These results suggest that midodrine, clonidine, and their combination plus SMT improves the systemic hemodynamics without any renal or hepatic dysfunction, and is superior to SMT alone for the control of ascites. However, the combination therapy was not superior to midodrine or clonidine alone.

A comparative evaluation of prasugrel and clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

OBJECTIVE: Primary objective of this study was to compare the efficacy of Prasugrel vs. Clopidogrel in the patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) by measuring inhibition of platelet aggregation after loading and maintenance dose of both the drugs. The patients were also assessed for safety of the drugs. METHODS: This was a randomised, double-blind, double-dummy, comparative, multicentric clinical trial in patients with acute coronary syndrome (unstable angina, non-ST elevation MI and ST elevation MI) undergoing PCI. The patients were randomly assigned to receive prasugrel (loading dose of 60 mg followed by maintenance dose of 10-mg once daily) or clopidogrel (loading dose of 300 mg followed by maintenance dose of 75 mg once daily) for a period of 12 weeks. All the patients were co-prescribed aspirin 325 mg with both the drugs. The primary efficacy end point in this study was percentage inhibition of ADP induced platelet aggregation (IPA) at 4 +/- 1 hours after the loading dose and at 30 +/- 3 days during maintenance treatment. The platelet aggregation of both the drugs was measured by whole blood aggregometer using 10 mmol of ADP as an aggregant. Though this study was not powered to see the difference in clinical efficacy parameters, the patients were observed for the incidence of nonfatal MI, nonfatal stroke, re-hospitalization, death, or need for urgent revascularization due to a cardiac ischemic event at days 30 and 90 during the study. The safety of study drugs were evaluated by incidence of major bleeding, reported adverse drug reaction and alterations of any laboratory parameters. RESULT: A total of 220 patients were enrolled at 11 centres across India. Ten patients were given the loading dose of prasugrel or clopidogrel but did not underwent PCI due to change in investigator's decision to go for PCI. Out of 210 eligible patients, 21 patients were discontinued during the study. 157 patients were evaluated for platelet inhibition after loading dose at 4 hours and 150 patients at day 30 during maintenance phase of antiplalelet therapy. The investigators could not perform this test in remaining patients due to urgency and criticality of the patients. 189 patients were observed for the incidence of nonfatal MI, nonfatal stroke, rehospitalisation, urgent revascularisation or death due to a cardiac ischemic event. All eligible patients who received at least a loading dose were evalauted for safety. In prasugrel group, 85 and 77 patients were evaluated for IPA at 4 hours and day 30 respectively whereas in clopdogrel group 72 and 73 patients were tested for IPA at 4 hours and at 30 days. Patients in prasugrel group have demonstrated significantly higher inhibition of platelets as compared to clopidogrel group (82.5% vs 71.1%) at 4 hours and at 30 days (84.1% vs 67.4%). The difference in inhibition of platelets between prasugrel and clopidogrel after loading dose and maintenenace dose was statistically significant (p < or = 0.01). The patients were also evaluated for drug hyporesponsiveness to antiplatelet therapy if IPA was < 20% at day 30 from the baseline. More patients on prasugrel have shown response to antiplatlet therapy than on clopidogrel (97.4% vs 87.6%). The difference between the two groups was statistically significant (p < 0.05). There was no difference observed during the study in the incidence of nonfatal MI, nonfatal stroke, death, rehospitalisation or need for urgent revascularisation due to a cardiac event between prasugrel and clopidogrel. Both the drugs were found to be to be well tolerated and have comparable safety profile. CONCLUSION: This study suggests that prasugrel is more effective than clopidogrel as an anti platelet drug as evident by inhibition of platelet aggregation. More patients on clopidogrel are likely to have poor response to therapy as compared to prasugrel. Both the drugs were well tolerated and have comparable safety profile.

Spontaneous Recanalized Chronic Total Occlusion or Recanalized Thrombus-What Are the Differentials?

The authors comment on certain points of the Akhar article from the April 2022 issue of the JIC. In their letter, they differentiate between chronic total occlusions and functional occlusions and discuss spontaneous recanalizations and the appearance of multiple intraluminal channels.They question whether the thrombotic occlusion of the right coronary artery was because of atherothrombosis or thromboembolism of both the right coronary artery and pulmonary circulation. The authors also mention that the index case needs a detailed evaluation of the hypercoagulable state to explain thrombosis of both the pulmonary and coronary circulation.