Background Cardiovascular disease is increasingly recognized as a leading nonobstetric cause of maternal morbidity and mortality worldwide, including low- and middle-income countries. Objectives This study evaluated fetomaternal outcomes in women with and without structural heart disease (SHD). Methods From a total of 25,000 patients enrolled in the Prospective Pakistan Registry of Echocardiographic Screening in Asymptomatic Pregnant Women registry between February 2023 and April 2025, 489 pregnancies with SHD were identified and compared with 510 pregnancies without SHD. Adverse fetomaternal outcomes were evaluated in both groups as a composite endpoint, comprising fetal outcomes (preterm delivery, fetal death, or low birth weight) and maternal outcomes (maternal death and pulmonary edema). Results The SHD cohort had a higher mean maternal age (27.3 ± 5.7 vs 26.1 ± 5.2 years; P = 0.011) compared to the non-SHD cohort. Composite adverse maternal outcomes (3.7% vs 0.4%; P < 0.001), fetal outcomes (29.9% vs 13.3%; P < 0.001), and overall fetomaternal outcomes (30.7% vs 13.3%; P < 0.001) were significantly higher in the SHD compared to the non-SHD cohort. SHD was independently associated with adverse fetomaternal outcomes (adjusted OR: 2.67; 95% CI: 1.93-3.70; P < 0.001). Conclusions Prospective Pakistan Registry of Echocardiographic Screening in Asymptomatic Pregnant Women is the first global study linking subclinical echocardiographic abnormalities in asymptomatic pregnant women to adverse fetomaternal outcomes. In a large cohort of asymptomatic pregnant women, an abnormal echocardiogram was found to be associated with 2- to 4 time as many adverse fetomaternal outcomes compared to a normal echocardiogram. Future studies are needed to evaluate optimal timing of screening, cost-effectiveness, and applicability of broad antenatal screening in higher-income countries.

Background: Frailty is a recognized predictor of adverse outcomes after percutaneous coronary intervention (PCI), but its long-term association with mortality and health-related quality of life (HRQoL) remains uncertain. This study evaluated the three-year association between discharge frailty and subsequent frailty, mortality, and HRQoL in post-PCI patients. Methods: This retrospective cohort study included patients with acute myocardial infarction (AMI) who underwent PCI, required ICU/CICU admission with mechanical ventilation and/or advanced life support, and remained alive at routine 6-month follow-up. Frailty was assessed at discharge and reassessed after three years. HRQoL was assessed using the EQ-5D-3 L descriptive system and summarised using a study-specific level-sum impairment score; this was not a preference-weighted EQ-5D utility index. Results: Among 164 patients, 131 (79.9%) were frail at discharge. During three-year follow-up, 51 patients (31.1%) died. Crude mortality did not differ significantly between frail and non-frail patients (32.1%vs. 27.3%; p = 0.595). In adjusted logistic regression, moderate-to-severe discharge frailty was independently associated with death during the follow-up interval (adjusted OR 2.55; 95% CI 1.06–6.11; p = 0.036). Among survivors, 43 (38.1%) remained frail at follow-up. Moderate-to-severe discharge frailty was associated with moderate-to-severe frailty at three-year follow-up (adjusted OR 12.75; 95% CI 1.84–88.35; p = 0.010), although the wide confidence interval indicates limited precision and supports an exploratory interpretation. Poor HRQoL, defined as an EQ-5D-3 L level-sum score ≥8, was present in 33 survivors. Neither age >60 years (adjusted OR 1.56; 95% CI 0.44–5.53; p = 0.492) nor discharge frailty was independently associated with poor HRQoL. Conclusion: Among mechanically ventilated AMI patients undergoing PCI who survived to routine 6-month follow-up, moderate-to-severe frailty at hospital discharge was independently associated with death during the three-year follow-up interval. It was also associated with moderate-to-severe frailty at follow-up, although this estimate was imprecise and should be interpreted as hypothesis-generating. Discharge frailty was not independently associated with poor long-term HRQoL.

BACKGROUND:Despite advances in primary percutaneous coronary intervention (PCI), patients with ST-elevation myocardial infarction (STEMI) continue to experience major adverse cardiovascular events (MACE) in the contemporary era. Existing risk scores (TIMI, GRACE, PAMI, CADILLAC) are outdated, mortality-focused, and largely derived in the fibrinolytic era from high-income settings, limiting their global relevance. AIMS:This prospective study aimed to develop a novel model to predict short-term (approximately 8 months) MACE after primary PCI. METHODS:STEMI patients presenting at the largest cardiac care center in Pakistan were prospectively enrolled to develop a model for predicting short-term (approximately 8 months) MACE. The predictive performance of the newly developed model was compared with the existing scores in the 20% testing cohort. RESULTS:The complete cohort comprised 2839 patients, of whom 2250 (79.3%) were men, with a mean age of 55.6 ± 11.2 years. A total of 580 patients (20.4%) were randomly assigned to the testing cohort. At a median follow-up of 244 [175-393] days, MACE was documented in 521 patients (18.4%), with 97 (16.7%) in the testing cohort and 424 (18.8%) in the training cohort. The new additive model yielded an AUC of 0.772 [95% CI: 0.72-0.83] with the NRI (net reclassification improvement) of 0.239 (p = 0.003), 0.268 (p = 0.001), 0.086 (p = 0.322), and 0.061 (p = 0.445) against TIMI, PAMI, CADILLAC, and GRACE scores, respectively. CONCLUSIONS:The NICVD predictive instrument outperformed the existing TIMI and PAMI scores and showed accuracy comparable to that of the GRACE and CADILLAC scores in predicting short-term MACE after primary PCI. And the model's enhanced predictive accuracy makes it a valuable tool for clinicians, enabling more enhanced risk stratification of STEMI patients.

BACKGROUND:Incomplete microvascular reperfusion during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) remains a major challenge. OBJECTIVES:This study sought to determine whether the pressure optimization protocol (POP) improves reperfusion outcomes compared with conventional rapid inflation-deflation stenting in patients undergoing primary PCI for STEMI. METHODS:In this multicenter randomized trial with blinded endpoint assessment, patients undergoing primary PCI were assigned 1:1 to POP (stent inflation to ≥14 atm maintained until pressure stability, defined as no pressure drop ≥0.3 atm over 30 seconds) or conventional rapid inflation-deflation stenting. The primary endpoint was hierarchical reperfusion success, analyzed using the Finkelstein-Schoenfeld unmatched WIN ratio: ST-segment resolution ≥70% at 90 minutes, final TIMI grade 3, and absence of slow-flow/no-reflow. RESULTS:Between September 30, 2024, and November 11, 2025, 607 patients underwent randomization (POP arm, n = 307; conventional arm, n = 300). POP improved the primary hierarchical reperfusion endpoint (WIN ratio: 1.42; 95% CI: 1.11-1.79; P = 0.004). The net WIN difference was +12.64% (95% CI: 3.69-20.98), driven mainly by the first 2 hierarchical components, ST-segment resolution ≥70% (+5.70%; 95% CI: -1.89 to 12.56) and final TIMI grade 3 flow (+5.95%; 95% CI: 1.80-10.00). Postdilation was less frequent with POP (213 of 326 stents [65.3%] vs 294 of 323 [91.0%]; P < 0.001). At median follow-up of 30 days (IQR: 29-32), major adverse cardiovascular events (death, myocardial infarction, stent thrombosis, or stroke) occurred in 6 of 307 vs 12 of 300 patients; Kaplan-Meier estimated event rates were 2.0% (95% CI: 0.4-3.5) and 4.1% (95% CI: 1.8-6.3), respectively (HR: 0.49; 95% CI: 0.18-1.31; P = 0.15). CONCLUSIONS:Among patients with STEMI undergoing primary PCI, pressure-optimized stent inflation resulted in significantly higher rates of successful reperfusion than conventional stenting and reduced need for post dilation. A trend toward fewer 30-day major adverse cardiovascular events was observed. Larger trials are warranted to assess effects on longer-term clinical outcomes. (RAPID-POP: A Randomized Controlled Trial; NCT06430892).

BACKGROUND:Vitamin K antagonists, such as warfarin, are the standard treatment for left ventricular thrombus (LVT). However, direct oral anticoagulants, such as rivaroxaban, are increasingly being considered due to their fixed dosing and lack of routine monitoring requirements. OBJECTIVES:This study aimed to compare the effectiveness of rivaroxaban vs warfarin in treating post-myocardial infarction (MI) acute LVT at 12 weeks. METHODS:We conducted an open-label, noninferiority, randomized controlled trial involving patients with acute LVT diagnosed during initial MI hospitalization. Participants were randomized 2:1 to receive either rivaroxaban (20 mg daily) or warfarin (target international normalized ratio 2-3) for 12 weeks. The primary endpoint, LVT resolution, was assessed by echocardiography at 4 and 12 weeks. RESULTS:A total of 261 patients were randomized, with 171 in the rivaroxaban group and 90 in the warfarin group. The groups were similar in sex, age, and MI subtype, with most having ST-segment elevation MI and severe LV dysfunction. At 4 weeks, LVT resolution was higher in the rivaroxaban group (20% vs 8%; P = 0.017), with similar resolution at 12 weeks (95.8% vs 96.6%; P = 0.759). The cumulative all-cause mortality was comparable (3.5% vs 3.3%; P = 0.921). Major bleeding occurred in 2.3% of rivaroxaban patients vs 1.1% of the warfarin group (P = 0.491). CONCLUSIONS:Rivaroxaban demonstrated similar efficacy to warfarin in treating post-MI LVT, with >95% resolution in both groups. Future multicenter trials with longer follow-up are needed to validate these findings (Rivaroxaban in Left Ventricular Thrombus; NCT04970576).

BACKGROUND:Hypertension (HTN) affects over a billion people worldwide, with most cases in low- and middle-income countries (LMICs) where awareness and control remain low. In Pakistan, general practitioners (GPs) are usually the initial contact for hypertensive patients. Through the Train the Trainer (TTT) initiative, a group of consultant cardiologists were trained as master trainers to conduct training for GPs across Pakistan. This study aimed to assess the effectiveness of the TTT initiative regarding knowledge of GPs about the diagnosis and management of HTN. METHODS:This study included 540 GPs from all over Pakistan. Participants attended HTN training workshops run by Master Trainers under the TTT model and completed a structured online questionnaire in relation to knowledge of HTN before and 1-3 months after training. Knowledge scores were derived from correct responses for 19 items. RESULTS:Pre-training GPs demonstrated low HTN knowledge scores with a median of 26.3 [IQR: 15.8-36.8] and 92% scoring less than 50. In contrast, post-training medians increased significantly to 42.1 [IQR: 31.6-63.2], with 38.5% of GPs achieving moderate or high knowledge scores ≥50 (p < 0.001). Overall, gains were observed across all demographic groups; significant improvement was observed among female and younger GPs. CONCLUSIONS:The TTT initiative effectively improved knowledge in both the diagnosis and management of hypertension among GPs, thus standing to potentially improve the current gaps in HTN care in many LMICs through similar models. Further studies are warranted to document the long-term clinical impact of this kind of training on patient outcomes and hypertension control.

OBJECTIVES:Accurately predicting short-term MACE (major adverse cardiac events) following primary percutaneous coronary intervention (PCI) remains a clinical challenge. This study aims to assess the effectiveness of four established risk scores in predicting short-term MACE after primary PCI. DESIGN:Prospective observational study. SETTING:The National Institute of Cardiovascular Diseases, Karachi, Pakistan. PARTICIPANTS:We enrolled a cohort of consecutive adult patients diagnosed with ST-elevation myocardial infarction undergoing primary PCI over a 6-month period, from 1 January 2022 to 30 June 2022. OUTCOME MEASURES:All the patients were followed at intervals of 3 months up to 12 months, and MACE events were recorded. Thrombolysis in Myocardial Infarction (TIMI), Primary Angioplasty in Myocardial Infarction (PAMI), Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) and Global Registry of Acute Coronary Events (GRACE) scores were obtained. RESULTS:A total of 2839 patients (79.3% male, mean age 55.6±11.2 years) were included. Over a median follow-up of 244 days, the composite MACE rate was 18.4% (521). All-cause mortality was 13.5% (384), reinfarction requiring revascularisation was 4.3% (121), heart failure-related rehospitalisation was 2.7% (76), stent thrombosis occurred in 5.6% (160) and cerebrovascular accident events were documented in 1% (28). The area under the curve for TIMI, PAMI, CADILLAC and GRACE scores was 0.682 (95% CI 0.655 to 0.709), 0.688 (95% CI 0.663 to 0.713), 0.686 (95% CI 0.66 to 0.711) and 0.695 (95% CI 0.669 to 0.72), respectively, for the prediction of MACE. On multivariable Cox regression, high-risk categories based on GRACE score were independent predictors of MACE with adjusted HR of 1.88 (95% CI 1.28 to 2.77; p=0.001). CONCLUSIONS:A significant proportion of patients experienced short-term MACE after primary PCI. While none of the assessed scores demonstrated significant predictive power, the GRACE score exhibited comparatively better predictive ability than the TIMI, PAMI and CADILLAC scores.

BACKGROUND:Ticagrelor has been proven superior to clopidogrel in reducing adverse cardiovascular events in patients with acute coronary syndrome (ACS), yet economic factors often favor clopidogrel in real-world clinical practice. Although double dose clopidogrel has shown potential benefits over once-daily regimens, its direct comparison with ticagrelor in ST-elevation myocardial infarction (STEMI) patients remains unexplored. METHODS AND DESIGN:Twice a Day Clopidogrel vs. Ticagrelor in Reducing Major Cardiac Events in Patients with Acute STEMI Undergoing Primary PCI (TADCLOT) trial is a double-blind, randomized controlled trial conducted at the National Institute of Cardiovascular Diseases (NICVD), Karachi, Pakistan. It is designed as a superiority trial to evaluate the efficacy and safety of ticagrelor over twice-daily clopidogrel in reducing major adverse cardiac events (MACE) in STEMI patients undergoing primary percutaneous coronary intervention (PCI). Following successful PCI for STEMI, and when the patient is deemed suitable for discharge, patients are randomized 1:1 to receive either ticagrelor (180 mg loading dose followed by 90 mg BID for 30 days) or clopidogrel (600 mg loading dose followed by 75 mg BID for 30 days). The primary endpoint is the rate of major adverse cardiac events (MACE), a composite of death, myocardial infarction, stent thrombosis, target lesion revascularization, or stroke at 30 days following randomization. Secondary endpoints include the individual components of MACE, bleeding complications, and drug discontinuation due to adverse events. Enrollment has reached 88%, with 2,200 patients planned to complete the trial. IMPLICATIONS:The TADCLOT trial will provide crucial insights into the comparative efficacy of ticagrelor versus twice-daily clopidogrel in reducing early stent thrombosis and improving outcomes in STEMI patients undergoing primary PCI. The trial will particularly contribute valuable insights for post-PCI care, considering both the economic and genetic context of the high risk South Asian population. TRIAL REGISTRATION:ClinicalTrials.gov NCT06318481.

BACKGROUND:The first month postprimary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is the highest risk period for major adverse cardiovascular events (MACEs), including stent thrombosis. Ticagrelor and double-dose clopidogrel are effective antiplatelet therapies, but no head-to-head comparison exists in this setting. OBJECTIVES:The authors sought to evaluate the efficacy of ticagrelor over twice-daily clopidogrel in reducing MACE events within the first 1 month postprimary PCI. METHODS:TADCLOT (Twice-A-Day CLOpidogrel vs Ticagrelor), a double-blind, randomized superiority trial at the National Institute of Cardiovascular Diseases, Karachi, Pakistan (February 19, 2024 to January 30, 2025), randomized 2,201 patients with STEMI within 24 hours of primary PCI 1:1 to ticagrelor (180-mg loading dose, 90 mg twice a day) or twice-daily clopidogrel (600-mg loading dose, 75 mg twice a day) for 1 month. The primary endpoint was MACEs (death, myocardial infarction, stent thrombosis, stroke, or target lesion revascularization) at 1 month, analyzed by intention to treat. Secondary endpoints were individual MACE components and clinically significant bleeding (Bleeding Academic Research Consortium [BARC] type 2, 3, or 5). RESULTS:Among 2,201 randomized patients, MACEs occurred in 24 (2.2%) ticagrelor patients vs 32 (2.9%) in twice-daily clopidogrel patients (HR: 0.75; 95% CI: 0.44-1.27; P = 0.28; absolute risk difference: -0.7%; 95% CI: -2.05 to 0.60). Cardiovascular death or definite stent thrombosis occurred in 21 (1.9%) vs 27 (2.5%) patients (HR: 0.77; 95% CI: 0.44-1.37). Clinically significant bleeding (BARC type 2, 3, or 5) occurred in 6 patients (0.5%) with ticagrelor vs 4 (0.4%) with clopidogrel (HR: 1.50; 95% CI: 0.42-5.31). Major bleeding (BARC type 3 or 5) was infrequent and similar between the groups: 3 patients (0.3%) in the ticagrelor arm and 2 (0.2%) in the clopidogrel arm (HR: 1.50; 95% CI: 0.25-8.97). At both 7 (HR: 0.15; 95% CI: 0.04-0.5; P = 0.002) and 14 days (HR: 0.46; 95% CI: 0.23-0.91; P = 0.02), MACEs were significantly lower with ticagrelor compared with twice-daily clopidogrel, although these differences were no longer statistically significant at 30 days. CONCLUSIONS:Ticagrelor was not superior to twice-daily clopidogrel in reducing MACEs at 1 month after primary PCI, and bleeding rates were similar. However, event rates were lower than anticipated, and ticagrelor significantly reduced MACEs within the first 2 weeks compared with twice-daily clopidogrel. (TADCLOT-a Double Blind Randomized Controlled Trial [TADCLOT]; NCT06318481).

Aims:The Prospective Pakistan Registry of Echocardiographic Screening in Asymptomatic Pregnant Women (PRESAP) is a registry designed for the echocardiographic screening of structural heart disease (SHD). It offers a unique opportunity to compare the effectiveness of point-of-care ultrasound (POCUS) vs. routine transthoracic echocardiography (TTE) in this population. This sub-study of the PRESAP registry aimed to compare the detection of SHD in asymptomatic pregnant women using POCUS vs. routine TTE. Methods and results:Between February 2023 and March 2024, pregnant women without known heart disease were enrolled in the PRESAP registry. Participants underwent a limited echocardiogram, using either POCUS or TTE. The primary outcome was the detection of abnormal findings, including left ventricular systolic dysfunction (LVSD), valvular heart disease (VHD), and congenital heart disease (CHD). Matching cohorts were created using propensity score matching, based on demographic factors, comorbid conditions, and gestational history. Among 18 401 patients, 9681 (52.6%) underwent POCUS. The 1:1 propensity-matched cohort included 4177 patients in each arm. Abnormal echocardiographic findings were detected in 4.4% (185) of the TTE group and 3% (124) of the POCUS group (P < 0.001). VHD (1.3% vs. 1.1%; P = 0.416) and CHD (0.4% vs. 0.6%; P = 0.093) were detected at similar rates by both methods, while LVSD was more frequently identified by TTE compared with POCUS (2.8% vs. 1.5%; P < 0.001). Conclusion:POCUS may be considered as an alternative to TTE for screening for SHD in asymptomatic pregnant women, particularly in resource-limited settings. TTE was superior for LVSD, and POCUS was equally effective in identifying valvular and congenital heart disease.

Cardiovascular disease (CVD) is understudied, underdiagnosed, and undertreated in women due to a lack of knowledge and understanding, particularly in the context of low-middle incomes countries (LMICs). Over a 20-month period from October 2022 to June 2024, we included 2003 patients from our valve registry, 11,894 patients from the Cath-PCI registry, and 542 patients from the structural intervention registry in Pakistan’s largest tertiary-care cardiac hospital. We discovered that females are more likely than males to suffer from valvular heart disease (VHD) and present at a considerably younger age. Females had a higher likelihood of mitral valve disease than males, who were more likely to have aortic valve disease. Rheumatic heart disease was the leading cause of all left-sided VHD. Amongst the acute coronary syndrome cohort, females had a significantly higher prevalence of diabetes and hypertension and significantly higher rate of death, longer door to balloon time and total ischemic time.

In this study, we compared the incidence of short-term outcomes between two groups of patients based on the occurrence of intra-procedural slow-flow/no-reflow phenomenon (SF/NR) and identified predictors of short-term outcomes. This study enrolled a consecutive series of patients diagnosed with ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). The patients were divided into two groups based on the presence or absence of SF/NR, and the incidence of short-term major adverse cardiovascular events (MACE) was compared between the two groups. Furthermore, the study aimed to identify predictors of short-term mortality in these patients. A total of 2582 patients were included, of whom 79.1

Background: This cross-sectional study aimed to evaluate the correlation between Duke Treadmill Score (DTS) and SYNTAX score and assess the role of DTS in predicting the severity of coronary artery disease (CAD) in patients with stable ischemic heart diseases. Methods: Conducted at a tertiary care cardiac center, the study included patients presenting to the outpatient department for the first time with angina and a positive exercise tolerance test (ETT), who underwent coronary angiogram. Correlation analysis was performed between DTS and SYNTAX score, and receiver operating characteristic (ROC) curve analysis was conducted for DTS to detect the presence (SYNTAX score ≥0) and severity (SYNTAX score ≥33) of CAD. Results: Out of 303 patients, 72.6% (220) were male, with a mean age of 53.31±10.11 years. CAD was confirmed in 79.9% (242) of patients. The mean SYNTAX score was 18.77±14.18, with 46.5% (141) categorized as low-risk, 27.1% as intermediate-risk, and 26.4% as high-risk. The mean DTS score was -6.09±4.5, with 13.9% categorized as high risk and the remaining 86.1% as intermediate or low risk. The Pearson correlation coefficient between DTS and SYNTAX score was -0.806 (p<0.001). The area under the curve (AUC) for DTS score in detecting the presence and severity of CAD was 0.992 [0.985–0.998] and 0.895 [0.860–0.929], respectively. Conclusion: A strong negative correlation was observed between SYNTAX score and DTS, highlighting the predictive value of DTS for assessing CAD severity. The DTS score demonstrated very high diagnostic accuracy in detecting the presence and severity of CAD.

Background The aim of our research was to design and evaluate an Artificial Neural Network (ANN) model using a systemic grid search for the early prediction of major adverse cardiac events (MACE) among patients presenting to the triage of an emergency department. Methods This is a single-center, cross-sectional study using electronic health records from January 2017 to December 2020. The research population consists of adults coming to our emergency department triage at Aga Khan University Hospital. The MACE during hospitalization was the main outcome. To enhance the architecture of an ANN using triage data, we used a systematic grid search strategy. Four hidden ANN layers were used, followed by an output layer. Following each hidden layer was back normalization and a dropout layer. MACE was predicted using three binary classifiers: ANN, Random Forests (RF), and logistic regression (LR). The overall accuracy, sensitivity, specificity, precision, and recall of these models were examined. Each model was evaluated using the receiver operating characteristic curve (ROC) and an F1-score with a 95% confidence interval. Results A total of 97,333 emergency department visits were recorded during the study period, with 33% of patients having cardiovascular symptoms. The mean age was 54.08 (19.18) years old. The MACE was observed in 23,052 (23.7%) of the patients, in-hospital (up to 30 days) mortality in 10,888 (11.2%) patients, and cardiac arrest in 5483 (5.6%) patients. The data used for training and validation were 77,866 and 19,467 in an 80:20 ratio, respectively. The AUC score for MACE with ANN was 0.97, which was greater than RF (0.96) and LR (0.96). Similarly, the precision-recall curve for MACE utilizing ANN was greater (0.94 vs. 0.93 for RF and 0.93 for LR). The sensitivity for MACE prediction using ANN, RF, and LR classifiers was 99.3%, 99.4%, and 99.2%, respectively, with the specificities being 94.5%, 94.2%, and 94.2%, respectively. Conclusion When triage data is used to predict MACE, death, and cardiac arrest, ANN with systemic grid search gives precise and valid outcomes and will benefit in predicting MACE in emergency rooms with limited resources that have to deal with a substantial number of patients.