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.

Ipsilateral Uterine Artery Access Through Unilateral Transfemoral Approach Using Simple-Curve Catheter.

Uterine artery embolization (UAE) is a technique for management of various obstetrical and gynecological problems. Transfemoral approach (TFA) is preferred which can be unilateral or bilateral; however, unilateral puncture is preferred due to lesser chances of puncture-related complications as compared to bilateral puncture. UAE through unilateral TFA is possible with use of reverse loop catheters (Roberts uterine catheter [RUC] or Gandras catheter) to access ipsilateral uterine artery. Other way of cannulating the ipsilateral uterine artery is by maneuvering catheters to form Waltman's loop/Simmon's reverse loop. With advent of RUC, unilateral TFA became standard of care. In the recent past, RUC was retracted from Indian market and its nonavailability had mandated use of either bilateral TFA or use of catheters and techniques used in the past for unilateral TFA. Herein, we describe a technique of doing UAE by unilateral TFA using simple gentle curve catheter (Picard) by making a reverse curve loop.

Development and validation wise assessment of genotype guided warfarin dosing algorithm in Indian population.

OBJECTIVES: A study was conducted to develop and validate the warfarin pharmacogenetic dose optimization algorithm considering the clinical pharmacogenetic implementation consortium (CPIC) recommendations for the Asian ethnicity population. METHODS: The present prospective observational study recruited warfarin-receiving patients. We collected a three ml blood sample for VKORC1, CYP2C9*2, CYP2C9*3, and CYP4F2 polymorphism assessment during the follow-up visits. Clinical history, sociodemographic and warfarin dose details were noted. RESULTS: The study recruited 300 patients (250 in derivation and 50 in validation timed cohort) receiving warfarin therapy. The baseline characteristics were similar in both cohorts. BMI, presence of comorbidity, VKORC1, CYP2C9*2, and CYP2C9*3 were identified as covariates significantly affecting the warfarin weekly maintenance dose (p<0.001 for all) and the same were included in warfarin pharmacogenetic dose optimization algorithm building. The algorithm built-in the present study showed a good correlation with Gage (r=0.57, p<0.0001), and IWPC (r=0.51, p<0.0001) algorithms, widely accepted in western side of the globe. The receiver operating characteristic curve analysis showed a sensitivity of 73 %, a positive predictive value of 96 %, and a specificity of 89 %. The algorithm correctly identified the validation cohort's warfarin-sensitive, intermediate reacting, and resistant patient populations. CONCLUSIONS: Validation and comparisons of the warfarin pharmacogenetic dose optimization algorithm have made it ready for the clinical trial assessment.

CADNet: an advanced architecture for automatic detection of coronary artery calcification and shadow border in intravascular ultrasound (IVUS) images.

Intravascular Ultrasound (IVUS) is a medical imaging modality widely used for the detection and treatment of coronary heart disease. The detection of vascular structures is extremely important for accurate treatment procedures. Manual detection of lumen and calcification is very time-consuming and requires technical experience. Ultrasound imaging suffers from the generation of artifacts which obstructs the clear delineation among structures. Considering, the need, to provide special attention to crucial areas, convolutional block attention modules (CBAM) is integrated into an encoder-decoder-based U-Net architecture along with Atrous Spatial Pyramid Pooling (ASPP) to detect vessel components: lumen, calcification and shadow borders. The attention modules prove effective in dealing with areas of special attention by assigning additional weights to crucial channels and preserving spatial features. The IVUS data of 12 patients undergoing the treatment is taken for this study. The novelty of the model design is such that it is able to detect the lumen area in the presence/absence of calcification and bifurcation artifacts too. Also, the model efficiently detects the calcification area even in case of severely complex lesions with shadows behind them. The main contribution of the work is that IVUS images of varying degrees of calcification till 360° are also considered in this work, which is usually neglected in previous studies. The experimental results of 1097 IVUS images of 12 patients resulted in meanIoU (0.7894 ± 0.011), Dice Coefficient (0.8763 ± 0.070), precision (0.8768 ± 0.069) and recall (0.8774 ± 0.071) of the proposed model CADNet which show the model's effectiveness relative to other state-of-the art methods.

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.

Percutaneous coronary intervention of anomalous right coronary arteries arising from the left sinus of Valsalva: a single-centre experience from Northern India.

Background: An anomalous right coronary artery (ARCA) arising from the left sinus of Valsalva is an uncommon congenital anomaly. The unusual location, take-off and intramural courses of ARCA pose a considerable technical challenge during percutaneous coronary intervention (PCI). Aims: We sought to report our experience of PCI of ARCA in 35 cases of atherosclerotic occlusion. Methods: The PCI database of 35 cases of ARCA was retrospectively analysed. The details about demography, clinical presentation, PCI procedure and clinical follow-up were noted. Results: The mean age was 56.7±13.5 years. The clinical presentation included stable angina in 45.7%, unstable angina in 20% and acute myocardial infarction in 34.3% of patients. Vascular access was transradial in 37.1% of cases, transfemoral in 60% of cases, and transbrachial in 1 case (2.9%). Judkins left and Amplatz left were commonly used guide catheters. Two patients with balloon-uncrossable, calcified lesions required rotablation-assisted PCI. Intravascular imaging was performed in 12 patients (34.3%). Optical coherence tomography demonstrated a proximal intramural course in 3 patients, and a slit-like orifice in 4 patients. The mean radiation dose and fluoroscopy time were 877±687.3 mGy and 18.8±11.6 minutes, respectively. Twenty-eight (80%) patients had an asymptomatic median follow-up of 49 (interquartile range: 29.0-97.5) months. Conclusions: We performed successful PCI in a cohort of 35 patients with ARCA, with favourable long-term clinical outcomes. The selection of an appropriate guide catheter and technical skills were important factors in achieving favourable results.

Evaluating efficiency and equity of prevention and control strategies for rheumatic fever and rheumatic heart disease in India: an extended cost-effectiveness analysis.

BACKGROUND: There is a dearth of evidence on the cost-effectiveness of a combination of population-based primary, secondary, and tertiary prevention and control strategies for rheumatic fever and rheumatic heart disease. The present analysis evaluated the cost-effectiveness and distributional effect of primary, secondary, and tertiary interventions and their combinations for the prevention and control of rheumatic fever and rheumatic heart disease in India. METHODS: A Markov model was constructed to estimate the lifetime costs and consequences among a hypothetical cohort of 5-year-old healthy children. Both health system costs and out-of-pocket expenditure (OOPE) were included. OOPE and health-related quality-of-life were assessed by interviewing 702 patients enrolled in a population-based rheumatic fever and rheumatic heart disease registry in India. Health consequences were measured in terms of life-years and quality-adjusted life-years (QALY) gained. Furthermore, an extended cost-effectiveness analysis was undertaken to assess the costs and outcomes across different wealth quartiles. All future costs and consequences were discounted at an annual rate of 3%. FINDINGS: A combination of secondary and tertiary prevention strategies, which had an incremental cost of ₹23 051 (US$30) per QALY gained, was the most cost-effective strategy for the prevention and control of rheumatic fever and rheumatic heart disease in India. The number of rheumatic heart disease cases prevented among the population belonging to the poorest quartile (four cases per 1000) was four times higher than the richest quartile (one per 1000). Similarly, the reduction in OOPE after the intervention was higher among the poorest income group (29·8%) than among the richest income group (27·0%). INTERPRETATION: The combined secondary and tertiary prevention and control strategy is the most cost-effective option for the management of rheumatic fever and rheumatic heart disease in India, and the benefits of public spending are likely to be accrued much more by those in the lowest income groups. The quantification of non-health gains provides strong evidence for informing policy decisions by efficient resource allocation on rheumatic fever and rheumatic heart disease prevention and control in India. FUNDING: Department of Health Research, Ministry of Health and Family Welfare, New Delhi.

Mitochondrial miRNA as epigenomic signatures: Visualizing aging-associated heart diseases through a new lens.

Aging bears many hard knocks, but heart disorders earn a particular allusion, being the most widespread. Cardiovascular diseases (CVDs) are becoming the biggest concern to mankind due to sundry health conditions directly or indirectly related to heart-linked abnormalities. Scientists know that mitochondria play a critical role in the pathophysiology of cardiac diseases. Both environment and genetics play an essential role in modulating and controlling mitochondrial functions. Even a minor abnormality may prove detrimental to heart function. Advanced age combined with an unhealthy lifestyle can cause most cardiomyocytes to be replaced by fibrotic tissue which upsets the conducting system and leads to arrhythmias. An aging heart encounters far more heart-associated comorbidities than a young heart. Many state-of-the-art technologies and procedures are already being used to prevent and treat heart attacks worldwide. However, it remains a mystery when this heart bomb would explode because it lacks an alarm. This calls for a novel and effective strategy for timely diagnosis and a sure-fire treatment. This review article provides a comprehensive overture of prospective potentials of mitochondrial miRNAs that predict complicated and interconnected pathways concerning heart ailments and signature compilations of relevant miRNAs as biomarkers to plot the role of miRNAs in epigenomics. This article suggests that analysis of DNA methylation patterns in age-associated heart diseases may determine age-impelled biomarkers of heart disease.

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.

Challenges and outcomes of pregnancy in an uncorrected Tetralogy of Fallot with pulmonary atresia and major aorta-pulmonary collateral arteries (MAPCA): a case report.

BACKGROUND: Tetralogy of Fallot is a severe type of congenital heart disease (CHD) and one of the leading indirect causes of mortality & morbidity among women with CHD. We came across a rare case of an uncorrected Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries in pregnancy. CASE PRESENTATION: We are reporting the challenges in managing a pregnancy of 25-years-old G3 P0110, previous one stillbirth and who was diagnosed to have congenital heart disease during pregnancy following spontaneous abortion. CONCLUSIONS: This case report highlights the role of multidisciplinary care in managing such a high risk case. It also emphasizes the role of cardiac examination of every woman before pregnancy so that definitive treatment or optimization can be done in time for a better outcome.

A State-Of-The-Art Review on Coronary Artery Border Segmentation Algorithms for Intravascular Ultrasound (IVUS) Images.

Intravascular Ultrasound images (IVUS) is a useful guide for medical practitioners to identify the vascular status of coronary arteries in human beings. IVUS is a unique intracoronary imaging modality that is used as an adjunct to angioplasty to view vessel structures using a catheter with high resolutions. Segmentation of IVUS images has always remained a challenging task due to various impediments, for example, similar tissue components, vessel structures, and artifacts imposed during the acquisition process. Many researchers have applied various techniques to develop standard methods of image interpretation, however, the ultimate goal is still elusive to most researchers. This challenge was presented at the MICCAI- Computing and Visualization for (Intra)Vascular Imaging (CVII) workshop in 2011. This paper presents a major review of recently reported work in the field, with a detailed analysis of various segmentation techniques applied in IVUS, and highlights the directions for future research. The findings recommend a reference database with a larger number of samples acquired at varied transducer frequencies with special consideration towards complex lesions, suitable validation metrics, and ground-truth definition as a standard against which to compare new and current algorithms.

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.

Validity and correlation of quantitative flow ratio with fractional flow reserve for assessment of intermediate coronary lesions.

BACKGROUND: The angiographic percent diameter stenosis (%DS) do not assess the physiological significance of epicardial coronary stenosis. The currently practised physiological indices require pressure wires with or without adenosine-induced hyperaemia. Quantitative flow ratio (QFR) is an angiography-based method to determine the functional significance of coronary stenosis. The present study aimed to analyse the diagnostic performance of QFR in comparison to fractional flow reserve (FFR) in intermediate coronary lesions. MATERIALS AND METHODS: It was a single centre retrospective study to analyse the diagnostic performance of offline QFR with the previously performed FFR in the last six years. A total of 56 interrogated vessels were included for the analysis. Offline QFR analysis was performed and correlated with FFR values in the intermediate coronary stenoses. RESULTS: The mean age of the study population was 62.4 ± 9.1 years, including 81% men. The left anterior descending artery (50%) was the most common analysed vessel followed by left circumflex (27%) and right coronary (21%) arteries. The mean % DS and % area stenosis were 45.25 ± 11.22% and 57.45% ± 16.25%, respectively. The mean FFR and QFR values were 0.83 ± 0.06 and 0.82 ± 0.10, respectively. A strong positive correlation was found between FFR and QFR with a Spearman correlation coefficient of 0.56. Receiver operating curve analysis for QFR and %DS with a FFR cut off value <0.80 showed an area under the curve of 0.97 and 0.77, respectively. The sensitivity, specificity and diagnostic accuracy of QFR were 87.5%, 95% and 92.8%, respectively. There was a discordance in four vessels (7.1%) between QFR and FFR. CONCLUSION: QFR has a good diagnostic performance in comparison to the gold standard FFR for physiological assessment of intermediate lesions. Its performance is significantly better than the anatomical % DS (p < 0.001).

Treatment adherence and its determinants among the rheumatic fever/rheumatic heart disease patients during COVID 19 pandemic - A cross sectional study from Chandigarh, India.

Background: Rheumatic heart disease/Rheumatic fever is a non - communicable disease being a major neglected health problem. Recurrent attacks of rheumatic fever can have catastrophic outcomes, therefore regular administration of antibiotics is recommended. During COVID 19 pandemic, people were afraid to approach hospitals hence the compliance and follow up of patients were affected. This study had planned to assess the treatment adherence of patients diagnosed with rheumatic fever/rheumatic heart disease during COVID 19 pandemic and to describe the socio demographic factors, clinical characteristics. This study also determines the factors associated with the treatment adherence. Methods: A cross sectional study was conducted among Rheumatic Fever/Rheumatic Heart Disease patients, attending Outpatient department at tertiary care hospital during COVID 19 pandemic. Mean score with confidence interval was calculated for quantitative data. P value less than 0.05 is significant. Results: The Mean (SD) age of the study participants was 41 ± 14.17 years. Treatment adherence was found to be 94.5 percent among Rheumatic Fever/Rheumatic Heart Disease patients during COVID 19 pandemic. 89.5% of injection benzathine penicillin users had an adherence rate above 80 percent. It was found that the presence of comorbidities (Diabetes/Hypertension/both Diabetes and Hypertension) had a statistically significant association with treatment adherence. Conclusions: Rheumatic Heart Disease is a disease of young and middle -age population affecting predominantly females. The overall adherence rate among Rheumatic Fever/Rheumatic Heart Disease patients was high. High time to maintain hospital-based registry to have follow up of patients.

Percutaneous Intervention of Coarctation of Aorta in an Adult Man Presenting With Congestive Heart Failure.

It is unusual to detect coarctation of aorta (CoA) in an adult person during their 6th decade of life. We came across a 52-year-old male who presented with left ventricular failure with low ejection fraction and atrial fibrillation, who was incidentally detected to have critical CoA. It was successfully managed with balloon angioplasty and had a favorable 6 months of clinical follow-up.

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.