Psychosocial stress and well-being in patients presenting with acute myocardial infarction in a tertiary care center.

BACKGROUND: Psychosocial factors such as stress have been previously implicated as a risk factor for cardiovascular diseases (CVDs). There is little evidence regarding the prevalence of stress among patients with acute myocardial infarction (AMI). METHODS: A total of 903 patients with AMI enrolled in the North Indian ST-Segment Elevation Myocardial Infarction (NORIN-STEMI) registry were included in this study. Perceived stress in these subjects was evaluated using the Perceived Stress Scale-10 questionnaire while the World health Organization (WHO-5) Well-being Index was used to evaluate psychological well-being. All these patients were followed up for one month and major adverse cardiac events (MACE) were determined. RESULTS: A majority of patients with AMI had either severe (478 [52.9%]) or moderate stress (347 [38.4%]) while low stress levels were observed in 78 [8.6%] patients. Additionally, most of the patients with AMI (478 [53%]) had WHO-5 well-being index <50%. Subjects with severe stress were younger (50.86 ± 13.31; P < 0.0001), more likely to be males (403 [84.30%]; P = 0.027), were less likely to have optimal level of physical activity (P < 0.0001) and had lower WHO-5 well-being score (45.54 ± 1.94%; P < 0.0001) as compared to those with low and moderate stress levels. On 30-days follow-up, subjects with moderate/severe stress had higher MACE however, the difference was non-significant (2.1% vs 1.04%; P = 0.42). CONCLUSION: A high prevalence of perceived stress and low well-being index was observed in patients presenting with AMI in India.

Matrix metalloproteinases and their gene polymorphism in young ST-segment elevation myocardial infarction.

BACKGROUND: Genetic polymorphism in MMPs are associated with multiple adverse CV events. There is little evidence regarding role of MMPs and their genetic polymorphisms in young (<50 years) ST-segment elevation myocardial infarction (STEMI) patients. METHODS: This study included 100 young (18-50 years) STEMI patients and 100 healthy controls. Serum levels of MMP-3, MMP-9 and TIMP were estimated for both patients as well as controls. Additionally, genetic polymorphisms in the MMP-9 gene (-1562 C/T and R279Q) & MMP-3 gene (5A/6A-1612) was evaluated. All these patients were followed up for one year and major adverse cardiac events (MACE) were determined. RESULTS: Serum levels of MMP-3 (128.16 ± 115.81 vs 102.3 ± 57.28 ng/mL; P = 0.04), MMP-9 (469.63 ± 238.4 vs 188.88 ± 94.08 pg/mL; P < 0.0001) and TIMP (5.84 ± 1.93 vs 2.28 ± 1.42 ng/mL; P < 0.0001) were significantly higher in patients as compared to controls. Additionally, patients with genetic polymorphisms in the MMP genes (5A/5A, 6A/6A and the AG genotypes) had an increased risk of STEMI. Patients with MACE had significantly higher levels of MMP-9 (581.73 ± 260.93 vs 438.01 ± 223.38 pg/mL; P = 0.012). A cutoff value of 375.5 pg/mL of MMP-9 was best able to discriminate patients with STEMI and MACE with sensitivity of 77.3% and specificity of 57%. CONCLUSION: Novel biomarkers such as MMP-3, MMP-9 and TIMP and their genetic polymorphism are associated with the susceptibility for STEMI in young individuals. Higher MMP-9 levels in STEMI patients with MACE suggests its potential role in predicting cardiac remodeling and left ventricular dysfunction.

Paraparesis in adult aortic coarctation: Reversal by stent supported angioplasty.

Aortic coarctation presenting with neurological complications as compressive myelopathy is rare. We report a case of a 43-year-old, hypertensive, female who presented with gradually progressive paraparesis over 4 years. She was diagnosed to be having coarctation of the aorta with intra-spinal collaterals causing compressive myelopathy. She underwent successful percutaneous endovascular implantation of a balloon-expandable aortic stent to relieve her aortic coarctation. This led to regression of her intra-spinal collaterals relieving her cord compression. This nonsurgical modality treatment proved to be safe and effective in relieving her hypertension and neurological complication of paraparesis. Learning objectives: •To recognize that paraparesis can be a rare manifestation of coarctation of the aorta.•To highlight the importance of treating the primary pathology of coarctation of the aorta in such critically ill therapeutically challenging patients.

Machine learning based model for risk prediction after ST-Elevation myocardial infarction: Insights from the North India ST elevation myocardial infarction (NORIN-STEMI) registry.

BACKGROUND: Risk prediction following ST-Elevation Myocardial Infarction (STEMI) in resource limited countries is critical to identify patients at an increased risk of mortality who might benefit from intensive management. METHODS: North India ST-Elevation Myocardial Infarction (NORIN-STEMI) is an ongoing registry that has prospectively enrolled 3,635 STEMI patients. Of these, 3191 patients with first STEMI were included. Patients were divided into two groups: development (n=2668) and validation (unseen) dataset (n=523). Various ML strategies were used to train and tune the model based on validation dataset results that included 31 clinical characteristics. These models were compared in sensitivity, specificity, F1-score, receiver operating characteristic area under the curve (AUC), and overall accuracy to predict mortality at 30 days. ML model decision making was analyzed using the Shapley Additive exPlanations (ShAP) summary plot. RESULTS: At 30 days, the mortality was 7.7%. On the validation dataset, Extra Tree ML model had the best predictive ability with sensitivity: 85%, AUC: 79.7%, and Accuracy: 75%. ShAP interpretable summary plot determined delay in time to revascularization, baseline cardiogenic shock, left ventricular ejection fraction <30%, age, serum creatinine, heart failure on presentation, female sex, and moderate-severe mitral regurgitation to be major predictors of all-cause mortality at 30 days (P<0.001 for all). CONCLUSION: ML models lead to an improved mortality prediction following STEMI. ShAP summary plot for the interpretability of the AI model helps to understand the model's decision in identifying high-risk individuals who may benefit from intensified follow-up and close monitoring.

Left ventricular function assessment after aortic and renal intervention in Takayasu arteritis by speckle tracking echocardiography: A pilot study.

BACKGROUND: Overt left ventricular (LV) dysfunction and congestive heart failure are known entities in Takayasu arteritis (TA). Subclinical LV dysfunction may develop in these patients despite normal LV ejection fraction (LVEF). Moreover, effect of treatment of aortic or renal artery narrowing in such patients is unknown. METHODS: This study included 15 angiographically confirmed TA patients undergoing aortic and/or renal intervention. A comprehensive clinical, biochemical and echocardiographic (2-dimensional, speckle tracking and tissue doppler imaging) evaluation were done at baseline, 72 h, and six months post intervention. RESULTS: Six patients (40%) had reduced LVEF (<50%) at baseline while rest 9 (60%) patients had reduced global longitudinal strain (GLS) but normal EF. Diastolic filling pattern was abnormal in all the patients. In patients with baseline reduced EF, mean EF improved from 24.62 ± 12.14% to 45.6 ± 9.45% (p = 0.001), E/e' ratio decreased from 15.15 ± 3.19 to 10.8 ± 2.56 (p = 0.005) and median NT pro BNP decreased from 1673 pg/ml (970-2401 pg/ml) to 80 pg/ml (40-354 pg/ml) (p = 0.001) at 6 months after interventional procedure. In patients with baseline normal EF, median NT pro BNP decreased from 512 pg/ml (80-898.5 pg/ml) to 34 pg/ml (29-70.8 pg/ml) (p < 0.01), mean GLS improved from -8.80 ± 0.77% to -16.3 ± 0.78% (p < 0.001) and mean E/e' decreased from 12.93 ± 2.63 to 7.8 ± 2.73 (p = 0.005) at 6 months follow up. CONCLUSION: LV dysfunction is common in patients with TA and obstructive lesions in aorta or renal arteries. GLS can be used to assess subclinical systolic dysfunction in these patients. Timely intervention can improve LV dysfunction and can even reverse the subclinical changes.

Guideline based eligibility for primary prevention statin therapy - Insights from the North India ST-elevation myocardial infarction registry (NORIN-STEMI).

BACKGROUND: Current risk scores to estimate atherosclerotic cardiovascular disease (ASCVD) risk and allocate statins in at-risk persons have largely been developed in Western populations; their applicability in India is uncertain. OBJECTIVE: To assess eligibility for primary prevention statin therapy using the 2018 U.S Multisociety Guideline and other contemporary cholesterol guidelines in patients presenting with ST-elevation myocardial infarction (STEMI) in the North India STEMI (NORIN-STEMI) registry. METHODS: NORIN-STEMI registry prospectively enrolled 3,635 patients at 2 tertiary care centers in Delhi, India from January 2019 to February 2020. Pooled cohort risk equations were used to estimate ASCVD risk at presentation. Patients were evaluated for statin eligibility using the 2018 U.S Multisociety Guideline, United States Preventive Services Task Force (USPSTF), and National Cholesterol Education Program (NCEP) III cholesterol guidelines. RESULTS: A total of 2,551 met the inclusion criteria. The median age was 54 years; 17% were women. The median ASCVD risk was 7.0%. At the time of MI, 54% of patients were eligible for primary prevention statin therapy by Multisociety Guideline, 46% by USPSTF, and 30% by NCEP III guidelines. These findings were applicable in both women and men. Compared with patients aged ≥50 years, those <50 years were less likely to be recommended statin therapy by all the three guidelines. CONCLUSION: A significant proportion of patients with STEMI in India did not meet the current guideline-based threshold for statin therapy for primary prevention. Novel risk stratification tools are needed to identify patients for primary prevention statin therapy in this population.

Prevalence and patterns of coronary artery anomalies in 28,800 adult patients undergoing angiography in a large tertiary care centre in India.

Coronary artery anomalies (CAAs) are a diverse group of disorders with varied clinical presentation and pathophysiological mechanisms. A majority of these anomalies are asymptomatic and often an incidental finding on coronary angiogram or autopsy. This retrospective study included 28,800 patients who underwent coronary angiography from 2016 to 2020. The coronary angiograms were reviewed by two independent reviewers and CAAs were documented. CAAs were classified into i) anomalies of coronary artery connection, ii) anomalies of intrinsic coronary arterial anatomy and iii) anomalies of myocardial/coronary artery interaction as proposed by the European Society of Cardiology. Of the 28,800 coronary angiograms, CAAs were present in 4.12% with anomalies in the left coronary artery (LCA) being most common. Anomalies of coronary artery connection were most common (48.48%) followed by anomalies of myocardial/coronary artery interaction (34.49%) and anomalies of intrinsic coronary artery anatomy (17.03%). Among anomalies of coronary artery connection, absent left main trunk or split LCA with separate origins of left anterior descending coronary artery and left circumflex coronary artery from the left coronary sinus of Valsalva (22.59%) was most common. An intramural course or "myocardial bridge" had an incidence of 1.16%  while incidence of coronary artery fistulae (CAF) was 0.115%.

COVID 19-related burnout among healthcare workers in India and ECG based predictive machine learning model: Insights from the BRUCEE- Li study.

OBJECTIVES: COVID-19 pandemic has led to unprecedented increase in rates of stress and burn out among healthcare workers (HCWs). Heart rate variability (HRV) has been shown to be reflective of stress and burnout. The present study evaluated the prevalence of burnout and attempted to develop a HRV based predictive machine learning (ML) model to detect burnout among HCWs during COVID-19 pandemic. METHODS: Mini-Z 1.0 survey was collected from 1615 HCWs, of whom 664, 512 and 439 were frontline, second-line and non-COVID HCWs respectively. Burnout was defined as score ≥3 on Mini-Z-burnout-item. A 12-lead digitized ECG recording was performed and ECG features of HRV were obtained using feature extraction. A ML model comprising demographic and HRV features was developed to detect burnout. RESULTS: Burnout rates were higher among second-line workers 20.5% than frontline 14.9% and non-COVID 13.2% workers. In multivariable analyses, features associated with higher likelihood of burnout were feeling stressed (OR = 6.02), feeling dissatisfied with current job (OR = 5.15), working in a chaotic, hectic environment (OR = 2.09) and feeling that COVID has significantly impacted the mental wellbeing (OR = 6.02). HCWs with burnout had a significantly lower HRV parameters like root mean square of successive RR intervals differences (RMSSD) [p < 0.0001] and standard deviation of the time interval between successive RR intervals (SDNN) [p < 0.001]) as compared to normal subjects. Extra tree classifier was the best performing ML model (sensitivity: 84%) CONCLUSION: In this study of HCWs from India, burnout prevalence was lower than reports from developed nations, and was higher among second-line versus frontline workers. Incorporation of HRV based ML model predicted burnout among HCWs with a good accuracy.

Design and rationale of an intelligent algorithm to detect BuRnoUt in HeaLthcare workers in COVID era using ECG and artificiaL intelligence: The BRUCEE-LI study.

BACKGROUND: There is no large contemporary data from India to see the prevalence of burnout in HCWs in covid era. Burnout and mental stress is associated with electrocardiographic changes detectable by artificial intelligence (AI). OBJECTIVE: The present study aims to estimate the prevalence of burnout in HCWs in COVID-19 era using Mini Z-scale and to develop predictive AI model to detect burnout in HCWs in COVID-19 era. METHODS: This is an observational and cross-sectional study to evaluate the presence of burnout in HCWs in academic tertiary care centres of North India in the COVID-19 era. At least 900 participants will be enrolled in this study from four leading premier government-funded/public-private centres of North India. Each study centre will be asked to recruit HCWs by approaching them through various listed ways for participation in the study. Interested participants after initial screening and meeting the eligibility criteria, will be asked to fill the questionnaire (having demographic and work related with Mini Z questionnaire) to assess burnout. The healthcare workers will include physicians at all levels of training, nursing staff and paramedical staff who are involved directly or indirectly in COVID-19 care. The analysis of the raw electrocardiogram (ECG) data and development of algorithm using convolutional neural networks (CNN) will be done by experts. CONCLUSIONS: In Summary, we propose that ECG data generated from the people with burnout can be utilized to develop AI-enabled model to predict the presence of stress and burnout in HCWs in COVID-19 era.

Molecular Evaluation of Exon 8 Cystathionine rs5742905T T>C Gene Polymorphism and Determination of its Frequency, Distribution Pattern, and Association with Susceptibility to Coronary Artery Disease in the North Indian Population.

BACKGROUND: The protein coded by the cystathionine ß synthase (CBS) gene acts as a catalyzer and converts homocysteine to cystathionine. Impairment of the CBS gene leads to homocystinuria by cystathionine ß synthase deficiency which is linked to Coronary Artery Disease. A number of polymorphisms studies have been performed on the cystathionine ß synthase gene. In the current study, we planned to analyze the influence of CBS T833C gene polymorphism(exon 8 cystathionine rs5742905T T>C), its association with Coronary Artery Disease development, and its progression in the north Indian population. MATERIALS AND METHODS: The present study comprises 100 angiographically confirmed CAD patients and 100 age and sex-matched healthy controls. A total of 50% or more luminal stenosis at one major coronary artery was considered for the inclusion criteria of the cases. The investigation of T833C polymorphism in the CBS gene was performed by PCR- RFLP technique. RESULTS: As a result, we found that homozygous mutant (CC) and heterozygous (TC) genotypes of CBS T833C gene polymorphism were significantly higher in CAD patients than in healthy subjects. We also observed a substantially increased CAD risk in dominant, codominant inheritance, and allele-specific models for the CBS T833C gene polymorphism. We analyzed the differential distribution with respect to disease severity, but there was no significant association (p=0.96). CONCLUSION: In conclusion, this study demonstrates that CBS T833C gene polymorphism plays a key role in developing coronary artery disease and its progression.

Telomere length in young patients with acute myocardial infarction without conventional risk factors: A pilot study from a South Asian population.

BACKGROUND: There is need to identify novel markers that lead to an early occurrence of myocardial infarction (MI) in young South Asian population. This population has different risk profile as compared with others. Telomere length is known to be a marker of aging, and shorter telomeres have been reported in cardiovascular diseases (CVDs). We aimed to identify the association of telomere length in young nonsmokers and non-diabetic MI patients. METHODS: In a case-control study of 154 subjects (n = 77 cases (ages 18-45 years, non-diabetic, non-smoker patients with MI) and n = 77, age and sex matched healthy controls), DNA extraction from peripheral blood leukocytes was carried out and the relative telomere length was estimated by quantitative PCR. The results were adjusted with various demographic parameters like age, gender and body mass index (BMI). The correlation studies were carried out between telomere length, sex and type of MI. RESULTS: The relative telomere length was significantly shorter in young MI patients (31-45 years) compared with matched healthy controls (p < 0.0001). Interestingly, in a gender-based comparison, the female patients had shorter telomere length (p < 0.01). CONCLUSION: In this pilot study, we found that the telomere length was shorter among young, non-diabetic, non-smoker MI patients as compared with similar young controls without MI in a South Asian cohort. Thus, telomere length may be a potential screening tool for young patients who don't have conventional risk factors. Larger studies are needed to confirm these findings.

Evaluation of systemic inflammatory and thrombotic markers of cardiovascular risk among young Indian oral tobacco users.

BACKGROUND: While the pro-inflammatory and pro-coagulant effects of cigarette smoking have been well described, the effect of smokeless tobacco (ST) on inflammatory and coagulation markers is still not clear. The study aimed to evaluate impact of smokeless tobacco use on systemic markers of inflammation [(TLC), neutrophil-lymphocyte ratio (NLR) (ESR), interleukin (IL) IL-1ß, IL-6 and tumor necrosis factor alpha (TNFα)] and hypercoagulable state [fibrinogen and d-dimer] leading to increased cardiovascular risk in ST users as compared to non-users. METHODS: 150 healthy young adults using oral tobacco products for at least 1 year were included in the case group and 50 age-matched non-consumers as controls. Subjects with any known chronic illness or comorbidity were excluded from the study. Blood samples were tested for TLC, NLR, ESR, IL-1ß, IL-6, TNFα, fibrinogen and d-dimer. Statistical analysis was done using SPSS 17.0 software. RESULTS: The baseline clinical and cardio-metabolic characteristics were comparable between the two groups. ST users had significantly elevated serum IL-6 [59.29 ± 124.69 pg/mL (n = 149) vs 8.21 ± 27.27 pg/mL (n = 47), p-value = 0.005], TNFα [77.18 ± 236.10 pg/mL (n = 149) vs 8.32 ± 9.36 pg/mL (n = 47), p-value = 0.041], fibrinogen [310.53 ± 129.05 mg/dL (n = 143) vs 282.82 ± 65.23 mg/dL (n = 42), p-value = 0.045] and d-dimer [0.28 ± 0.42 mg/L (n = 144) vs 0.17 ± 0.09 mg/L (n = 45), p-value = 0.043] levels as compared to non-users. Serum TLC, NLR, ESR and IL-1ß remained unchanged in ST users and were similar to that of controls. CONCLUSIONS: Chronic use of ST is associated with systemic inflammation and coagulation, which may increase the risk of athero-thrombotic cardiovascular events among ST users.

Prevalence of hypertension among Indian adults: Results from the great India blood pressure survey.

OBJECTIVE: Hypertension is the most important risk factor for cardiovascular morbidity and mortality. There is limited data on hypertension prevalence in India. This study was conducted to estimate the prevalence of hypertension among Indian adults. METHODS: A national level survey was conducted with fixed one-day blood pressure measurement camps across 24 states and union territories of India. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg or a diastolic BP ≥90 mmHg or on treatment for hypertension. The prevalence was age- and gender-standardized according to the 2011 census population of India. RESULTS: Blood pressure was recorded for 180,335 participants (33.2% women; mean age 40.6 ± 14.9 years). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%), and 2,878 (1.6%) participants were of the age group 18-19, 20-44, 45-54, 55-64, 65-74, and ≥ 75 years, respectively. Overall prevalence of hypertension was 30.7% (95% confidence interval [CI]: 30.5, 30.9) and the prevalence among women was 23.7% (95% CI: 23.3, 24). Prevalence adjusted for 2011 census population and the WHO reference population was 29.7% and 32.8%, respectively. CONCLUSION: There is a high prevalence of hypertension, with almost one in every three Indian adult affected.

Clinical Importance of Estrogen Receptor 1 (ESR1) Gene Polymorphisms and Their Expression Patterns in Coronary Artery Disease Patients: A Study from India.

The influence of Estrogen Receptor 1 (ESR1) gene -397T>C (PvuII) and -351A>G (XbaI) polymorphisms on the risk of development of coronary artery disease (CAD) in the north Indian population was analysed. We hypothesized that ESR1 gene polymorphisms may influence the susceptibility to CAD through variation in Estrogen Receptor α (ERα) expression. To assess this concept, we evaluated ERα mRNA expression in blood plasma of CAD patients. The study included hundred CAD patients who showed presence of greater than 50% luminal stenosis in at least one major coronary artery in angiography along with hundred age and sex matched healthy controls. The ESR1 polymorphisms were investigated by PCR-RFLP. Quantitative Real Time PCR was carried out for the measurement of ERα mRNA expression. The results showed that genotypic frequencies of ESR1 -397T>C and -351A>G gene polymorphisms were significantly higher in CAD patients than control subjects (p < 0.0001). A significantly increased CAD risk was also found in dominant and codominant inheritance model for both of the SNPs. In gender based analysis these findings were replicated only in male subgroup. In case of -397T>C polymorphism, the ERα mRNA expression was highest in CAD patients with wild type homozygous TT genotype (2-∆ct = 0.28). A mutant 'C' allele, dose dependent, significant decrease in trend in ERα mRNA expression was observed, with lowest expression in mutant homozygous CC genotype (2-∆ct = 0.09), and intermediate expression level in heterozygous TC genotype (2-∆ct = 0.14) subgroups of CAD patients. In conclusion, this study demonstrates a significantly heightened risk of CAD associated with the inheritance of mutant genotypes of ESR1 -397T>C and -351A>G gene polymorphisms, in the north Indian population. This is the first report of a lowered ERα mRNA expression in conjunction with the presence of mutant 'C' allele of ESR1 -397T>C polymorphism with consequent increased CAD susceptibility.

Role of ApoE gene polymorphism and nonconventional biochemical risk factors among very young individuals (aged less than 35 years) presenting with acute myocardial infarction.

BACKGROUND: Incidence rate of acute myocardial infarction (MI) has increased in younger population over the years. The young patients have a different risk profile, presentation, and prognosis than the elderly. Hence, it is essential to understand the risk factors in young patients for proper treatment. METHODS: Apolipoprotein E (ApoE) polymorphism and biochemicals such as total cholesterol, serum triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein(a), insulin, interleukin-6, homocysteine, fibrinogen, and highly sensitive C-reactive protein were investigated in very young MI (yMI patients; age ≤ 35 years; n = 125), in old MI (oMI patients; age >35 and < 80 years; n = 111), and healthy controls (age ≤35 years; n = 103). RESULTS: HDL-C was significantly lower in yMI patients than in controls (p = 2.63E-04) and oMI patients (p = 1.29E-05). ApoA1 was also lowest in yMI patients, but significant only in comparison to controls (p = 2.62E.04). The yMI group had the highest ratios of total cholesterol:HDL-C (p = 0.027 in yMI patients versus controls and p = 0.018 in yMI patients versus oMI patients), LDL-C:HDL-C (p = 0.002 in yMI patients versus controls and p = 0.005 in yMI patients versus oMI patients), and ApoB:ApoA1 (p = 8.75E-05 in yMI patients versus controls and p > 0.05 in yMI patients versus oMI patients). No significant pattern of ApoE polymorphisms was observed. CONCLUSION: The lower level of HDL-C and ApoA1 and higher ratios of total cholesterol:HDL-C, LDL-C:HDL-C, and ApoB:ApoA1 are risk factors for MI in young patients.