Comparison of the efficacy, safety, and tolerability of the new FDC telmisartan + bisoprolol with comparator telmisartan + metoprolol succinate ER combination therapy for stage 1 and stage 2 hypertension: The double-blind, multicentric, phase-III clinical study.

AIM: The present study compared the safety, efficacy, and tolerability of the new fixed-dose combination (FDC) telmisartan 40 mg + bisoprolol 5 mg (TBP) tablets with the existing comparator FDC telmisartan 40 mg + metoprolol succinate ER 50 mg (TMS) tablets in patients with stage 1 and stage 2 hypertension. METHODOLOGY: The multicentric, double-blind, parallel-group, comparative, prospective, phase-III clinical study involved 264 subjects with stage 1 and stage 2 hypertension from 10 centres across India. The selected subjects were randomized into two groups: group A received the TMS and group B received the new FDC TBP. The primary endpoint was the mean change in seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) from baseline to week 12 in both the control and study arms. The secondary endpoint was achieving the target of SeSBP <140 mmHg and SeDBP <90 mmHg from baseline to week 12 in both groups. Safety and tolerability parameters were evaluated in both groups based on adverse effects (AEs) reported by the patients and the physician. RESULTS: Both treatment groups exhibited a reduction in BP after 2 weeks of treatment, which was sustained until 12 weeks. The mean change in SeSBP and SeDBP at weeks 2, 6, and 12 compared to the previous visit showed statistical significance (P <0.001) in all cases for both groups A and B. The mean changes in SeSBP and SeDBP from baseline to study end were numerically higher in group B than in group A. The mean difference in SeSBP from baseline to study end was significantly higher in group B compared to group A (P=0.029). By week 12, 88.28% and 89.84% of subjects in group B achieved SeSBP <140 mmHg and SeDBP <90 mmHg respectively, while 86.71% and 91.40% of subjects in group A achieved the same targets. Reported AEs were mostly mild to moderate in both treatment groups, and no serious AEs or deaths were reported. Tolerability was rated as 'excellent' by 93.75% of subjects in group B and 91.40% of subjects in group A. CONCLUSION: Both the new FDC TBP and the existing comparator TMS combination therapy have comparable efficacy, tolerability, and safety for the management of stage 1 and stage 2 hypertension. TRIAL REGISTRY NAME: The Clinical Trials Registry- India (CTRI), TRIAL REGISTRATION NO: CTRI/2021/11/037926 PROTOCOL NO: MLBTL/05/2021 PROTOCOL URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62069&EncHid=&userName=bisoprolol.

The Promise of Cilnidipine in Hypertension with Comorbidities: National Consensus Statement: National Consensus Group Comprises Cardiologists, Nephrologists, and Diabetologists from India in a National Meet at New Delhi held on 22nd May 2022.

The rapidly increasing burden of hypertension is responsible for premature deaths from cardiovascular disease (CVD), renal disease, and stroke, with a tremendous public health and financial burden. Hypertension detection, treatment, and control vary worldwide; it is still low, particularly in low- and middle-income countries (LMICs). High blood pressure (BP) and CVD risk have a strong, linear, and independent association. They contribute to alarming numbers of all-cause and CVD deaths. A major culprit for increased hypertension is sympathetic activity, and further complications of hypertension are heart failure, ischemic heart disease (IHD), stroke, and renal failure. Now, antihypertensive interventions have emerged as a global public health priority to reduce BP-related morbidity and mortality. Calcium channel blockers (CCB) are highly effective vasodilators. and the most common drugs used for managing hypertension and CVD. Cilnidipine, with both L- and N-type calcium channel blocking activity, is a promising 4th generation CCB. It causes vasodilation via L-type calcium channel blockade and inhibits the sympathetic nervous system (SNS) via N-type calcium channel blockade. Cilnidipine, which acts as a dual L/N-type CCB, is linked to a reduced occurrence of pedal edema compared to amlodipine, which solely blocks L-type calcium channels. The antihypertensive properties of cilnidipine are very substantial, with low BP variability and long-acting properties. It is beneficial for hypertensive patients to deal with morning hypertension and for patients with abnormal nocturnal BP due to exaggerated sympathetic nerve activation. Besides its BP-lowering effect, it also exhibits organ protection via sympathetic nerve inhibition and renin-angiotensin-aldosterone system inhibition; it controls heart rate and proteinuria. Reno-protective, neuroprotective, and cardioprotective effects of cilnidipine have been well-documented and demonstrated.

Polygenic Risk Score Assessment for Coronary Artery Disease in Asian Indians.

We evaluated the performance of various polygenic risk score (PRS) models derived from European (EU), South Asian (SA), and Punjabi Asian Indians (AI) studies on 13,974 subjects from AI ancestry. While all models successfully predicted Coronary artery disease (CAD) risk, the AI, SA, and EU + AI were superior predictors and more transportable than the EU model; the predictive performance in training and test sets was 18% and 22% higher in AI and EU + AI models, respectively than in EU. Comparing individuals with extreme PRS quartiles, the AI and EU + AI captured individuals with high CAD risk showed 2.6 to 4.6 times higher efficiency than the EU. Interestingly, including the clinical risk score did not significantly change the performance of any genetic model. The enrichment of diversity variants in EU PRS improves risk prediction and transportability. Establishing population-specific normative and risk factors and inclusion into genetic models would refine the risk stratification and improve the clinical utility of CAD PRS.

Assessing the prediction of type 2 diabetes risk using polygenic and clinical risk scores in South Asian study populations.

Background: Genome-wide polygenic risk scores (PRS) have shown high specificity and sensitivity in predicting type 2 diabetes (T2D) risk in Europeans. However, the PRS-driven information and its clinical significance in non-Europeans are underrepresented. We examined the predictive efficacy and transferability of PRS models using variant information derived from genome-wide studies of Asian Indians (AIs) (PRSAI) and Europeans (PRSEU) using 13,974 AI individuals. Methods: Weighted PRS models were constructed and analyzed on 4602 individuals from the Asian Indian Diabetes Heart Study/Sikh Diabetes Study (AIDHS/SDS) as discovery/training and test/validation datasets. The results were further replicated in 9372 South Asian individuals from UK Biobank (UKBB). We also assessed the performance of each PRS model by combining data of the clinical risk score (CRS). Results: Both genetic models (PRSAI and PRSEU) successfully predicted the T2D risk. However, the PRSAI revealed 13.2% odds ratio (OR) 1.80 [95% confidence interval (CI) 1.63-1.97; p = 1.6 × 10-152] and 12.2% OR 1.38 (95% CI 1.30-1.46; p = 7.1 × 10-237) superior performance in AIDHS/SDS and UKBB validation sets, respectively. Comparing individuals of extreme PRS (ninth decile) with the average PRS (fifth decile), PRSAI showed about two-fold OR 20.73 (95% CI 10.27-41.83; p = 2.7 × 10-17) and 1.4-fold OR 3.19 (95% CI 2.51-4.06; p = 4.8 × 10-21) higher predictability to identify subgroups with higher genetic risk than the PRSEU. Combining PRS and CRS improved the area under the curve from 0.74 to 0.79 in PRSAI and 0.72 to 0.75 in PRSEU. Conclusion: Our data suggest the need for extending genetic and clinical studies in varied ethnic groups to exploit the full clinical potential of PRS as a risk prediction tool in diverse study populations.

Patient-Reported Status and Heart Failure Outcomes in Asia by Sex, Ethnicity, and Socioeconomic Status.

Background: In heart failure (HF), symptoms and health-related quality of life (HRQoL) are known to vary among different HF subgroups, but evidence on the association between changing HRQoL and outcomes has not been evaluated. Objectives: The authors sought to investigate the relationship between changing symptoms, signs, and HRQoL and outcomes by sex, ethnicity, and socioeconomic status (SES). Methods: Using the ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) Registry, we investigated associations between the 6-month change in a "global" symptoms and signs score (GSSS), Kansas City Cardiomyopathy Questionnaire overall score (KCCQ-OS), and visual analogue scale (VAS) and 1-year mortality or HF hospitalization. Results: In 6,549 patients (mean age: 62 ± 13 years], 29% female, 27% HF with preserved ejection fraction), women and those in low SES groups had higher symptom burden but lower signs and similar KCCQ-OS to their respective counterparts. Malay patients had the highest GSSS (3.9) and lowest KCCQ-OS (58.5), and Thai/Filipino/others (2.6) and Chinese patients (2.7) had the lowest GSSS scores and the highest KCCQ-OS (73.1 and 74.6, respectively). Compared to no change, worsening of GSSS (>1-point increase), KCCQ-OS (≥10-point decrease) and VAS (>1-point decrease) were associated with higher risk of HF admission/death (adjusted HR: 2.95 [95% CI: 2.14-4.06], 1.93 [95% CI: 1.26-2.94], and 2.30 [95% CI: 1.51-3.52], respectively). Conversely, the same degrees of improvement in GSSS, KCCQ-OS, and VAS were associated with reduced rates (HR: 0.35 [95% CI: 0.25-0.49], 0.25 [95% CI: 0.16-0.40], and 0.64 [95% CI: 0.40-1.00], respectively). Results were consistent across all sex, ethnicity, and SES groups (interaction P > 0.05). Conclusions: Serial measures of patient-reported symptoms and HRQoL are significant and consistent predictors of outcomes among different groups with HF and provide the potential for a patient-centered and pragmatic approach to risk stratification.

Clinical profile of patients with cardiac amyloidosis in India.

Limited data exists on patients with cardiac amyloidosis (CA) in India, due to underdiagnosis and late presentation. We present single centre data from 13 patients over a 4 year period with a median age of 65 years. A majority presented with symptomatic heart failure (69%) and eight patients had confirmed AL amyloidosis. At the end of the follow up period, 46% patients died, with 30% of the overall cohort dead within six months. Among the survivors, 71% continue to have NYHA grade III/IV symptoms. A suggested algorithm for earlier diagnosis in resource constrained settings is also presented.

Clinical relevance of double-arm blood pressure measurement and prevalence of clinically important inter-arm blood pressure differences in Indian Primary Care.

Hypertension guidelines recommend measuring blood pressure (BP) in both arms at least once. However, this is seldom done due to uncertainties regarding measurement procedure and the implications of finding a clinically important inter-arm BP difference (IAD). This study aimed to provide insight into the prevalence of clinically important IADs in a large Indian primary care cohort. A number of 134678 (37% female) unselected Indian primary care participants, mean age 45.2 (SD 11.9) years, had BP measured in both arms using a standardized, triplicate, automated simultaneous measurement method (Microlife WatchBP Office Afib). On average, there were clinically minor differences in right and left arm BP values: systolic BP 134.4 vs. 134.2 mmHg (p<0.01) and diastolic BP 82.7 vs. 82.6 mmHg (p<0.01), respectively. Prevalence of significant mean systolic IAD between 10 and 15 mmHg was 7813 (5.8%). Systolic IAD ≥ 15 mmHg 2980 (2.2%) and diastolic IAD ≥ 10 mmHg 7151 (5.3%). In total, there were 7595 (5.6%) and 8548 (6.3%) participants with BP above the 140/90 mmHg threshold in only the left or right arm, respectively. Prevalence of participants with elevated BP on one arm only was highest in patients with a systolic IAD ≥ 15 mmHg; 19.1% and 13.7%, for left and right arm, respectively. This study shows that a substantial prevalence of IAD exist in Indian primary care patients. BP is above the diagnostic threshold for hypertension in one arm only for 6% of participants. These findings emphasise the importance of undertaking bilateral BP measurement in routine clinical practice. This article is protected by copyright. All rights reserved.

Effect of environment and season on acute decompensated heart failure: Data from low-to middle-income country.

OBJECTIVES: The environmental effect in heart failure (HF) patients is well established. However, the data is limited from low-to middle-income countries like India. This study determined the impact of environment on acute decompensated HF (ADHF) admissions and mortality in India. METHODS: Retrospectively, the data of all HF patients admitted between April 2017 and March 2019 was accessed through electronic hospital records. Simultaneously, the environmental-related data was collected from the central pollution control board. RESULTS: The study included 4561 patients of ADHF. The peak of monthly ADHF events (admission and mortality) was observed during the chilly month (January) while the lowest rates were observed in summer months (May-June). The most significant factor correlating inversely with the monthly ADHF admission (r = -0.78, p = 0.003) and mortality (r = -0.65, p = 0.004) was the maximum air temperature, and it was found to be the independent predictor for both ADHF mortality [t = -2.78, ß = -0.84; 95%CI(-6.0 to -0.6), p = 0.021] and admission [t = -4.83, ß = -0.91; 95%CI(-19.8 to -6.9), p = 0.001]. The above correlation was better seen in the elderly subset and male gender. Humidity and the air pollution attributes did not have a significant correlation with ADHF admission or mortality. CONCLUSION: In conclusion, even in low-to middle-income country like India, a periodic effect of season was demonstrated for ADHF mortality and admission, with a peak in ADHF events noted during winter months especially in the regions having extremes of seasons. Air pollution could not affect the ADHF outcome for which further studies are needed.

Clinical relevance of double-arm blood pressure measurement and prevalence of clinically important inter-arm blood pressure differences in Indian primary care.

Hypertension guidelines recommend measuring blood pressure (BP) in both arms at least once. However, this is seldom done due to uncertainties regarding measurement procedure and the implications of finding a clinically important inter-arm BP difference (IAD). This study aimed to provide insight into the prevalence of clinically important IADs in a large Indian primary care cohort. A number of 134 678 (37% female) unselected Indian primary care participants, mean age 45.2 (SD 11.9) years, had BP measured in both arms using a standardized, triplicate, automated simultaneous measurement method (Microlife WatchBP Office Afib). On average, there were clinically minor differences in right and left arm BP values: systolic BP 134.4 vs 134.2 mmHg (p < .01) and diastolic BP 82.7 vs 82.6 mmHg (p < .01), respectively. Prevalence of significant mean systolic IAD between 10 and 15 mmHg was 7,813 (5.8%). Systolic IAD ≥ 15 mmHg 2,980 (2.2%) and diastolic IAD ≥ 10 mmHg 7,151 (5.3%). In total, there were 7,595 (5.6%) and 8,548 (6.3%) participants with BP above the 140/90 mmHg threshold in only the left or right arm, respectively. Prevalence of participants with elevated BP on one arm only was highest in patients with a systolic IAD ≥ 15 mmHg; 19.1% and 13.7%, for left and right arm, respectively. This study shows that a substantial prevalence of IAD exists in Indian primary care patients. BP is above the diagnostic threshold for hypertension in one arm only for 6% of participants. These findings emphasize the importance of undertaking bilateral BP measurement in routine clinical practice.

Various Factors that are Causing Difference in Prevalence of Coronary Risk Factors among Siblings.

BACKGROUND AND AIM: Coronary artery disease (CAD) is one of the predominant types of cardiovascular disease (CVD). The aim of present study was to study various factors that are causing difference in prevalence of coronary risk factors among siblings. MATERIALS AND METHODS: This cross-sectional study was conducted in Dayanand Medical College and Hospital, among the healthy individuals (not known CAD) attending regular health care outpatient department (OPD) and their siblings over a period of 1½ years. All individuals coming for regular health checkup (not known CAD) of age more than 30 years or above and their siblings (with or without known CAD). RESULTS: This was a cross-sectional study, conducted among 100 pairs of healthy siblings (not known cases of CAD) who came for health checkup at health center of Dayanand Medical College and Hospital, a tertiary care hospital in North India. Prevalence of obesity was more in siblings living in urban area than their counter siblings living in rural area, but it was statistically insignificant. Six had impaired fasting blood sugar (FBS) and two were diabetic. Among their siblings living in urban area, 21 were nondiabetic, 10 had impaired FBS, and seven were diabetic. This correlation was statistically significant with p-value of 0.02. Among the CAD negative, out of 23 subjects, two subjects (9.0%) had heavy stress level, while remaining four subjects (17.0%) and 17 subjects (74.0%) had light and moderate stress levels, respectively. Among the CAD negative, out of 23 subjects, 10 subjects (43.0%) had high stress level, while remaining zero subject (0%) and 13 subjects (57.0%) had light and moderate stress levels, respectively. Significant results were obtained while comparing the CAD findings of subjects divided on the basis of stress level. CONCLUSION: In our study, among siblings (CAD positive and CAD negative), significant results were obtained for residence, socioeconomic class, physical activity, stress levels, smoking, waist-to-hip ratio (WHR), and diabetes, that is, all these factors have correlation in increasing CAD among siblings.

Burden of Type 2 Diabetes and Associated Cardiometabolic Traits and Their Heritability Estimates in Endogamous Ethnic Groups of India: Findings From the INDIGENIUS Consortium.

To assess the burden of type 2 diabetes (T2D) and its genetic profile in endogamous populations of India given the paucity of data, we aimed to determine the prevalence of T2D and estimate its heritability using family-based cohorts from three distinct Endogamous Ethnic Groups (EEGs) representing Northern (Rajasthan [Agarwals: AG]) and Southern (Tamil Nadu [Chettiars: CH] and Andhra Pradesh [Reddys: RE]) states of India. For comparison, family-based data collected previously from another North Indian Punjabi Sikh (SI) EEG was used. In addition, we examined various T2D-related cardiometabolic traits and determined their heritabilities. These studies were conducted as part of the Indian Diabetes Genetic Studies in collaboration with US (INDIGENIUS) Consortium. The pedigree, demographic, phenotypic, covariate data and samples were collected from the CH, AG, and RE EEGs. The status of T2D was defined by ADA guidelines (fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5% and/or use of diabetes medication/history). The prevalence of T2D in CH (N = 517, families = 21, mean age = 47y, mean BMI = 27), AG (N = 530, Families = 25, mean age = 43y, mean BMI = 27), and RE (N = 500, Families = 22, mean age = 46y, mean BMI = 27) was found to be 33%, 37%, and 36%, respectively, Also, the study participants from these EEGs were found to be at increased cardiometabolic risk (e.g., obesity and prediabetes). Similar characteristics for the SI EEG (N = 1,260, Families = 324, Age = 51y, BMI = 27, T2D = 75%) were obtained previously. We used the variance components approach to carry out genetic analyses after adjusting for covariate effects. The heritability (h2) estimates of T2D in the CH, RE, SI, and AG were found to be 30%, 46%, 54%, and 82% respectively, and statistically significant (P ≤ 0.05). Other T2D related traits (e.g., BMI, lipids, blood pressure) in AG, CH, and RE EEGs exhibited strong additive genetic influences (h2 range: 17% [triglycerides/AG and hs-CRP/RE] - 86% [glucose/non-T2D/AG]). Our findings highlight the high burden of T2D in Indian EEGs with significant and differential additive genetic influences on T2D and related traits.

The incidence and clinical impact of thrombotic events in hospitalized COVID-2019 illness.

BACKGROUND: Coronavirus disease-2019 (COVID-19) infection and thrombosis are of great clinical importance as this association has shown to increase mortality. We intend to estimate the incidence of thrombotic events (TE) and their impact on clinical outcomes in hospitalized COVID-19 patients. METHODS: This was an analytical cross-sectional study. The study population comprised of hospitalized COVID-19 patients between 1st March 2021 and 31st May 2021. The clinico-demographic data, thrombotic events, and clinical outcomes were collected from electronic health records. RESULTS: A total of 1274 patients were analyzed. The median age of the study population was 56 years (IQR: 44-66 years). The estimated incidence of TE was 5.8% (N.=74); 60.8% of these TE occurred in patients having severe/critical COVID-19 illness and 70.3% of TE occurred in patients in the intensive care unit. Venous events (3.9%) were common compared to arterial events(1.9%). On multivariate logistic regression analysis, total leukocyte count, C-reactive protein, and D-dimer level were found to be the independent predictors of having TE. Receiver operator curve revealed a cut-off point of 872.5 DDU µg/L for D-dimer level (sensitivity: 67.6% and specificity: 72.1%; P<0.001, area under curve 0.78) for predicting TE. Patients with TE had significantly higher mortality compared to those without TE (58.1% vs. 22.2%; P<0.001); and the presence of TE (OR=2.94; 95% CI:1.7-5.1, P<0.001) was found to be the independent predictor of mortality. CONCLUSIONS: The incidence of TE is high for hospitalized COVID-19 patients and it is even higher in severe/critical COVID illness. Its presence has shown to double the mortality compared to those without it.

Prolapsing giant right atrial myxoma in a young male presenting as pulmonary embolism.

A 22-year male presented with complaints of dyspnea. Multimodality imaging revealed a polypoidal right atrial mass with submassive pulmonary embolism. The patient underwent urgent surgery. The pathological examination confirmed it as cardiac myxoma. Cardiac myxoma, a most common primary cardiac tumor, is commonly found in the left atrium. The right atrium is an uncommon site and the usual mode of presentation is the tumor or thrombus embolization to the pulmonary circulation.

An Optimized Machine Learning Model Accurately Predicts In-Hospital Outcomes at Admission to a Cardiac Unit.

Risk stratification at the time of hospital admission is of paramount significance in triaging the patients and providing timely care. In the present study, we aim at predicting multiple clinical outcomes using the data recorded during admission to a cardiac care unit via an optimized machine learning method. This study involves a total of 11,498 patients admitted to a cardiac care unit over two years. Patient demographics, admission type (emergency or outpatient), patient history, lab tests, and comorbidities were used to predict various outcomes. We employed a fully connected neural network architecture and optimized the models for various subsets of input features. Using 10-fold cross-validation, our optimized machine learning model predicted mortality with a mean area under the receiver operating characteristic curve (AUC) of 0.967 (95% confidence interval (CI): 0.963-0.972), heart failure AUC of 0.838 (CI: 0.825-0.851), ST-segment elevation myocardial infarction AUC of 0.832 (CI: 0.821-0.842), pulmonary embolism AUC of 0.802 (CI: 0.764-0.84), and estimated the duration of stay (DOS) with a mean absolute error of 2.543 days (CI: 2.499-2.586) of data with a mean and median DOS of 6.35 and 5.0 days, respectively. Further, we objectively quantified the importance of each feature and its correlation with the clinical assessment of the corresponding outcome. The proposed method accurately predicts various cardiac outcomes and can be used as a clinical decision support system to provide timely care and optimize hospital resources.

Causes of cardiovascular and noncardiovascular death in the ISCHEMIA trial.

BACKGROUND: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial demonstrated no overall difference in the composite primary endpoint and the secondary endpoints of cardiovascular (CV) death/myocardial infarction or all-cause mortality between an initial invasive or conservative strategy among participants with chronic coronary disease and moderate or severe myocardial ischemia. Detailed cause-specific death analyses have not been reported. METHODS: We compared overall and cause-specific death rates by treatment group using Cox models with adjustment for pre-specified baseline covariates. Cause of death was adjudicated by an independent Clinical Events Committee as CV, non-CV, and undetermined. We evaluated the association of risk factors and treatment strategy with cause of death. RESULTS: Four-year cumulative incidence rates for CV death were similar between invasive and conservative strategies (2.6% vs 3.0%; hazard ratio [HR] 0.98; 95% CI [0.70-1.38]), but non-CV death rates were higher in the invasive strategy (3.3% vs 2.1%; HR 1.45 [1.00-2.09]). Overall, 13% of deaths were attributed to undetermined causes (38/289). Fewer undetermined deaths (0.6% vs 1.3%; HR 0.48 [0.24-0.95]) and more malignancy deaths (2.0% vs 0.8%; HR 2.11 [1.23-3.60]) occurred in the invasive strategy than in the conservative strategy. CONCLUSIONS: In International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, all-cause and CV death rates were similar between treatment strategies. The observation of fewer undetermined deaths and more malignancy deaths in the invasive strategy remains unexplained. These findings should be interpreted with caution in the context of prior studies and the overall trial results.

Predictors of Left Main Coronary Artery Disease in the ISCHEMIA Trial.

BACKGROUND: Detection of ≥50% diameter stenosis left main coronary artery disease (LMD) has prognostic and therapeutic implications. Noninvasive stress imaging or an exercise tolerance test (ETT) are the most common methods to detect obstructive coronary artery disease, though stress test markers of LMD remain ill-defined. OBJECTIVES: The authors sought to identify markers of LMD as detected on coronary computed tomography angiography (CTA), using clinical and stress testing parameters. METHODS: This was a post hoc analysis of ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on nonimaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CTA to exclude LMD. Stress tests were read by core laboratories. Prior coronary artery bypass grafting was an exclusion. In a stepped multivariate model, the authors identified predictors of LMD, first without and then with stress testing parameters. RESULTS: Among 5,146 participants (mean age 63 years, 74% male), 414 (8%) had LMD. Predictors of LMD were older age (P < 0.001), male sex (P < 0.01), absence of prior myocardial infarction (P < 0.009), transient ischemic dilation of the left ventricle on stress echocardiography (P = 0.05), magnitude of ST-segment depression on ETT (P = 0.004), and peak metabolic equivalents achieved on ETT (P = 0.001). The models were weakly predictive of LMD (C-index 0.643 and 0.684). CONCLUSIONS: In patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CTA. For most patients with moderate or severe ischemia, anatomical imaging is needed to rule out LMD. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Analysis of anticoagulation therapy related complications in patients with prosthetic valves: Our experience.

PURPOSE: The aim of this study is to analyze anticoagulation-related complications in patients following mechanical valve replacement and factors influencing the outcome. MATERIALS AND METHODS: A total of 250 patients were analyzed during OPD follow-up for anticoagulation-related complications and various factors influencing outcome. Patients received prosthetic valve at mitral and/or aortic or both. RESULTS: Out of 250 patients, 48% were male and 52% were female. The mean age was 41.9 ± 14.4. A total of 139 had mitral valve replacement (MVR), 70 had aortic valve replacement (AVR), 40 had double valve replacement (DVR), and 1 patient had triple valve replacement. Valves implanted were mechanical bileaflet valve. The mean international normalization ratio (INR) in the study was 2.4 ± 0.56. A total of 49 events occurred during follow-up, of which 4.5% per patient years were anticoagulation-related hemorrhagic events and 4.8% per patient years were thromboembolic events. Among thromboembolic events, valve thrombosis occurred in 10 patients and cerebrovascular accidents occurred in 11 patients. Mean INR for thromboembolic events was 1.46 ± 0.25 and anticoagulation-related hemorrhagic events was 4.4 ± 1.03. Mortality rate was 1.6% in AVR, 4% in MVR, and 0.4% in DVR groups; about 34% of patients needed dose modification of Acenocoumarol and reason for derangement of INR was associated with infectious process and poor compliance; 85% of cases showed good compliance for daily anticoagulation therapy. CONCLUSION: Anticoagulation for mechanical valve replacement can be managed with INR range of 2.0 to 2.5 in MVR and 1.5 to 2.0 in AVR with acceptable hemorrhagic and thromboembolic events. We must educate and counsel the patients during follow-up for better compliance to optimal anticoagulation.

Effects of initial invasive vs. initial conservative treatment strategies on recurrent and total cardiovascular events in the ISCHEMIA trial.

AIMS: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial prespecified an analysis to determine whether accounting for recurrent cardiovascular events in addition to first events modified understanding of the treatment effects. METHODS AND RESULTS: Patients with stable coronary artery disease (CAD) and moderate or severe ischaemia on stress testing were randomized to either initial invasive (INV) or initial conservative (CON) management. The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), and hospitalization for unstable angina, heart failure, or cardiac arrest. The Ghosh-Lin method was used to estimate mean cumulative incidence of total events with death as a competing risk. The 5179 ISCHEMIA patients experienced 670 index events (318 INV, 352 CON) and 203 recurrent events (102 INV, 101 CON). A single primary event was observed in 9.8% of INV and 10.8% of CON patients while ≥2 primary events were observed in 2.5% and 2.8%, respectively. Patients with recurrent events were older; had more frequent hypertension, diabetes, prior MI, or cerebrovascular disease; and had more multivessel CAD. The average number of primary endpoint events per 100 patients over 4 years was 18.2 in INV [95% confidence interval (CI) 15.8-20.9] and 19.7 in CON (95% CI 17.5-22.2), difference -1.5 (95% CI -5.0 to 2.0, P = 0.398). Comparable results were obtained when all-cause death was substituted for cardiovascular death and when stroke was added as an event. CONCLUSIONS: In stable CAD patients with moderate or severe myocardial ischaemia enrolled in ISCHEMIA, an initial INV treatment strategy did not prevent either net recurrent events or net total events more effectively than an initial CON strategy. CLINICAL TRIAL REGISTRATION: ISCHEMIA ClinicalTrials.gov number, NCT01471522, https://clinicaltrials.gov/ct2/show/NCT01471522.