Low central venous oxygen saturation on critical care unit admission is associated with higher in-hospital mortality in critically ill patients with acute myocardial infarction

Introduction

Acute myocardial infarction (AMI), characterized by myocardial necrosis primarily attributed to persistent ischemia and hypoxia following atherosclerotic plaque rupture or erosion, continues to impose a substantial burden on global public health systems (1). A nationwide cohort study revealed that nearly 50% of AMI patients in the United States required intensive care unit admission, and the mortality remained in the range of 14–50% over the past two decades (2-4). Despite advancements in percutaneous coronary interventions and pharmacological therapies, epidemiological data reveal a paradoxical increase in AMI hospitalizations without corresponding reductions in in-hospital mortality over the past decade (5,6). Particularly, AMI patients requiring mechanical ventilation in the intensive care unit represent an extremely high-risk phenotype. They face a markedly elevated risk of mortality, often due to cardiogenic shock or severe systemic complications, underscoring the urgent need for reliable prognostic tools specific to this vulnerable subgroup (7,8).

Pathophysiological disturbances in tissue oxygenation underlie many shock-related systemic derangements. Sustained global tissue hypoxia induces mitochondrial dysfunction and impaired oxygen utilization, which may progress irreversibly to multiorgan failure and fatal outcomes if uncorrected (9). Central venous oxygen saturation (ScvO₂) is quantified through superior vena cava or right atrial blood sampling and serves as an integrative measure of systemic oxygen delivery-demand balance (10). Extensive clinical evidence supports ScvO₂ as a sensitive indicator of global tissue hypoxia, with prognostic implications across critical care settings (11). In the context of cardiac disease, ScvO₂ holds specific diagnostic and prognostic significance that may complement existing risk assessment tools. Coronary occlusion in AMI induces anaerobic metabolism, lactate accumulation, and intracellular acidosis, progressing to mitochondrial dysfunction and cardiomyocyte death. Left ventricular mass loss exceeding 40% culminates in cardiogenic shock with a vicious cycle of hypoperfusion (12). Established risk scores such as the Global Registry of Acute Coronary Events score and the Thrombolysis in Myocardial Infarction (TIMI) score incorporate clinical variables, electrocardiographic findings, and conventional biomarkers but do not directly capture the dynamic balance between systemic oxygen delivery and consumption (13). This limitation is particularly relevant in mechanically ventilated AMI patients, who frequently operate at the margin of hemodynamic compensation. Similarly, conventional biomarkers such as serum lactate, although widely used as a marker of anaerobic metabolism, exhibit a delayed response to resuscitative efforts and are significantly influenced by hepatic function, whereas B-type natriuretic peptide primarily reflects ventricular wall stress rather than global tissue oxygen balance (14,15). In contrast, ScvO₂ provides a real-time, integrative assessment of systemic oxygen supply-demand equilibrium, offering information that is complementary to, and potentially independent of, these established markers. ScvO₂ levels are notably reduced in states of cardiogenic shock or left ventricular failure, reflecting an inadequate cardiac output response to increased metabolic demand and compensatory increases in oxygen extraction (16,17). A decline in ScvO₂, which sensitively marks cardiac deterioration, portends impending hemodynamic compromise (18,19).

However, significant knowledge gaps remain regarding its precise utility in AMI. Substantial controversy exists regarding optimal ScvO₂ thresholds across different critical illness phenotypes. Previous sepsis guidelines advocated for maintaining ScvO₂ >70% based on evidence from early goal-directed therapy (20). Based on evidence from current clinical practice, a target of ScvO₂ ≥60% for hemodynamic optimization is advocated for cardiothoracic surgical populations (21,22). Given that compensatory increases in oxygen extraction are limited by impaired cardiac output and microcirculatory dysfunction in certain pathophysiological states, a lower threshold may be more appropriate in these populations. Preliminary studies suggest an inverse relationship between ScvO₂ and mortality in general intensive care populations (23,24). However, whether the same thresholds apply to mechanically ventilated AMI patients, a population characterized by mixed shock phenotypes, remains unclear, as robust evidence specifically validating its prognostic role in this high-risk subgroup is scarce. This knowledge deficit highlights the necessity for targeted investigations into ScvO₂’s prognostic utility in AMI-related critical illness. To address this evidence gap, we performed a secondary analysis of data from a prospective audit conducted at a tertiary cardiovascular center to evaluate the association between ScvO₂ levels at the critical care unit (CCU) admission and in-hospital mortality among adult AMI patients, with a specific focus on those receiving mechanical ventilation. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0864/rc).

Methods

Study design and novelty

This study was a retrospective secondary analysis of a pre-existing dataset derived from a prospective observational cohort study (25). While the original study primarily investigated outcomes related to mechanical ventilation in AMI patients, focusing on predictors of prolonged ventilation (>24 hours) and 180-day mortality, our analysis addresses a distinct research question. It is specifically designed to evaluate the prognostic value of ScvO₂ at admission for in-hospital mortality. To this end, we employed novel analytical approaches including tertile-based stratification of ScvO₂, multivariable logistic regression modeling for in-hospital death, subgroup analyses, and curve fitting. The dataset for this analysis was sourced from the publicly available file (https://doi.org/10.1371/journal.pone.0290399.s001), originating from the parent study which was conducted at the CCU of the National Institute of Cardiovascular Diseases (NICVD), Karachi, Pakistan, from August 2021 to January 2022. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Ethical approval for the parent study was granted by the Ethical Review Committee of the National Institute of Cardiovascular Diseases, Pakistan (No. ERC-74/2021); written informed consent was obtained from the patients’ designated caregivers or immediate family members. The present secondary analysis of the de-identified public dataset required no further approval.

Study population

This study was a secondary analysis of an existing clinical database. The critically ill patients were defined according to the original study’s objective inclusion criteria: consecutively recruited adults (>18 years) diagnosed with AMI requiring invasive mechanical ventilation for respiratory failure within 24 hours following the onset of symptoms. Exclusion criteria comprised: (I) failure to undergo revascularization therapy during hospitalization; (II) Manifestations of severe hypoxic encephalopathy (Glasgow Coma Scale 3–8) during initial clinical evaluation; (III) absence of documented ScvO₂ measurements upon CCU admission. All patients received standardized intensive care unit care according to institutional guidelines, implemented through a multidisciplinary team led by board-certified intensivists and cardiology specialists.

Data collection and preprocessing

The following variables were included in the analytical cohort: sex, age, time to reperfusion, anterior wall myocardial infarction, percutaneous coronary intervention, angiographic findings (TIMI flow, culprit vessel, or other diseased vessels), comorbidities, left ventricular ejection fraction, tricuspid annular plane systolic excursion, right ventricular dimension, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, Sequential Organ Failure Assessment (SOFA) score, frailty score, intra-aortic balloon pump, use of vasopressors or inotropes, arterial blood gas, venous blood gas and laboratory markers. ScvO₂ measurements were obtained upon CCU admission via superior vena cava catheterization using calibrated blood gas analyzers. Data cleaning and preprocessing were performed as follows: First, the cohort was defined based on ScvO₂ data availability as described above. Second, variables with >20% missing data were excluded from multivariable modeling. For remaining variables with missing values (<20%), multiple imputation was performed using the Random Forest algorithm (R package missForest) (26). Third, the primary exposure, ScvO₂, was analyzed both as a continuous variable and categorized into tertiles (tertile 1: 25–54%; tertile 2: 55–64%; tertile 3: 65–86%) for logistic regression.

Grouping and outcome definitions

Participants were stratified into tertiles based on ScvO₂ measurements: tertile 1 (n=58): ScvO₂ 25–54%, tertile 2 (n=59): ScvO₂ 55–64%, tertile 3 (n=62): ScvO₂ 65–86%. The primary endpoint was defined as in-hospital mortality.

Statistical analysis

Continuous variables were reported as median [interquartile range (IQR)] and compared with Mann-Whitney U test or Kruskal-Wallis test. Categorical data were presented as frequencies and percentages, with between-group differences assessed using Pearson’s χ² test. All analyses were based on the preprocessed dataset. Based on clinical plausibility and previously published literature, we used DAGitty (https://www.dagitty.net/) to construct the directed acyclic graph (DAG) to identify minimally sufficient adjustment sets of covariates (MSAs) that would estimate the unconfounded effect of ScvO₂ indices on in-hospital mortality (Figure S1) (27). The MSAs for estimating the total effect of ScvO₂ on mortality included six covariates: time to reperfusion, left ventricular ejection fraction, tricuspid annular plane systolic excursion, arterial oxygen saturation (SaO₂), C-reactive protein, and albumin. For estimating the direct effect, the MSAs expanded to 11 covariates, adding anterior wall myocardial infarction, frailty score at admission, SOFA score at admission, intra-aortic balloon pump and use of vasopressors or inotropes. The variance inflation factor (VIF) was used to detect whether potential collinearity might exist in selected confounders (Table S1). A VIF value greater than 10 typically indicates significant multicollinearity; however, in this study, all VIF values were below 5, suggesting that multicollinearity was not a major issue (28). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using univariate and multivariable logistic regressions to evaluate associations between ScvO₂ and in-hospital mortality. In multivariate logistic regression for further investigation, we adjusted for multiple potential confounders in following three models: Model 1: unadjusted; Model 2: adjusted for time to reperfusion, left ventricular ejection fraction, tricuspid annular plane systolic excursion, SaO₂, C-reactive protein and albumin; Model 3: adjusted for Model 2 plus anterior wall myocardial infarction, frailty score at admission, SOFA score at admission, intra-aortic balloon pump and use of vasopressors or inotropes. ScvO₂ levels were categorized into tertiles for analysis. We examined the relationship between ScvO₂ and in-hospital mortality using restricted cubic splines (RCS) after adjustment for potential confounders. Stratified analytical methods were employed to ensure the consistency of associations between ScvO₂ levels and the study endpoints. To evaluate selection bias due to missing ScvO₂ data, we compared baseline characteristics and in-hospital mortality between the included (n=179) and excluded (n=133) groups (Table S2). As a sensitivity analysis, we compared the results from the complete-case analysis with those derived from the imputed dataset. Consistency between the two approaches was assessed based on the direction, magnitude, and statistical significance of effect estimates (Table S3). All statistical analyses were conducted using R statistical software (version 4.2, https://www.r-project.org) and EmpowerStats (http://www.empowerstats.com, X&Y Solutions, Inc., Boston, MA, USA). Two-sided P<0.05 was considered statistically significant.

Results

Baseline characteristics

Figure 1 illustrates the participant flow diagram. A total of 179 critically ill patients with AMI were enrolled in the study. The baseline characteristics of the study population are presented in Table 1. Patients were stratified into tertiles based on ScvO₂ levels (tertile 1, 25–54%, n=58; tertile 2, 55–64%, n=59; tertile 3, 65–86%, n=62). The levels of ScvO₂ of the three groups were 48.50% (42.25–52.75%), 60.00% (58.50–61.00%), and 70.00% (68.00–72.00%) (P<0.001), respectively. Totally 47 patients (26.26%) experienced in-hospital death, with the highest mortality in tertile 1 (n=20, 34.48%). Meanwhile, in-hospital mortality (P=0.03) decreased with increasing ScvO₂. We found that the incidence of diabetes was higher in tertile 2 than in the other groups. Interestingly, the levels of SaO₂ at admission had no difference between the three groups. There was no significant difference in the other variables between the groups (P>0.05).

Figure 1 Flowchart of patient selection. ScvO₂, central venous oxygen saturation.

Univariate analysis of characteristics associated with in-hospital mortality

Univariate logistic analysis was performed to evaluate the association between variables and in-hospital mortality. As shown in Table 2, a higher level of C-reactive protein, frailty score at admission, SOFA score at admission; a lower level of ScvO₂, left ventricular ejection fraction; and the presence of TIMI flow < III, diabetes, and intra-aortic balloon pump use were significantly associated with in-hospital mortality (P<0.05). Additional variables demonstrated no significant association with in-hospital mortality among critically ill patients with AMI following CCU admission.

Association between ScvO₂ and in-hospital mortality in different models

A multivariable logistic regression model was implemented to quantify the independent association between ScvO₂ levels and in-hospital mortality. Table 3 displays the OR (95% CI) for in-hospital mortality associated with ScvO₂ in different models. ScvO₂ levels demonstrated a significant inverse correlation with survival outcomes, with lower values being associated with an elevated mortality risk. When analyzed continuously, per 1% increase in ScvO₂ was associated with a lower mortality rate, showing OR of 0.95 (95% CI: 0.91–0.98, P=0.004) in the fully adjusted model (model 3). When ScvO₂ was stratified into tertiles, compared with tertile 1, the in-hospital mortality risk demonstrated a graded decrease, with tertile 2 showing no statistically significant difference (OR =1.02, 95% CI: 0.41–2.25, P=0.97) and tertile 3 exhibiting significantly lower odds (OR =0.18, 95% CI: 0.06–0.55, P=0.003), alongside a statistically significant linear trend across tertiles (P for trend =0.004). A sensitivity analysis comparing complete-case analysis with missForest-imputed data confirmed the robustness of these findings, as the two approaches yielded consistent effect estimates with no material differences (Table S3).

Association between ScvO₂ and in-hospital mortality in subgroups

Subgroup analyses were performed to assess the consistency of the primary association across key clinical subsets. We performed subgroup analyses stratified by age, sex, hypertension, diabetes, smoker, chronic kidney disease, ischemic heart diseases, anterior wall myocardial infarction, TIMI flow < III, culprit left main, culprit left anterior descending artery, culprit right coronary artery and culprit left circumflex artery, assessing differential ScvO₂-mortality relationships (Table 4). There were interactions of culprit right coronary artery (P=0.03) with the association between ScvO₂ and in-hospital mortality. In participants without culprit right coronary artery, higher ScvO₂ levels were independently associated with a lower risk of in-hospital death (OR =0.89, 95% CI: 0.81–0.97, P=0.006). However, the strength of this inverse association appeared attenuated and lost statistical significance in the subgroup with culprit right coronary artery (OR =0.98, 95% CI: 0.94–1.01, P=0.14), suggesting that the prognostic value of admission ScvO₂ might be modified by the infarct location. In the other subgroupings, no significant interactions were identified (P for interaction >0.05).

Relationships between ScvO₂ and in-hospital mortality explored by curve fitting analysis

In the present study, we discovered that the higher the ScvO₂ level, the lower the in-hospital mortality rate of patients with AMI after CCU admission, as shown in the curve fitting analysis. An RCS analysis revealed a predominantly linear inverse association between ScvO₂ and mortality risk (P for non-linearity =0.052) (Figure 2).

Figure 2 Association of the ScvO₂ level with in-hospital mortality. A linear relationship was observed between the ScvO₂ level and in-hospital mortality. The solid blue line represents the smooth curve fit between variables, and the blue shaded area represents the 95% confidence interval of the fit. All estimates were adjusted for time to reperfusion, left ventricular ejection fraction, tricuspid annular plane systolic excursion, SaO₂, C-reactive protein, albumin, anterior wall myocardial infarction, frailty score at admission, SOFA score at admission, intra-aortic balloon pump, and use of vasopressors or inotropes. SaO₂, arterial oxygen saturation; ScvO₂, central venous oxygen saturation; SOFA, Sequential Organ Failure Assessment.

Discussion

This study provides the first systematic evaluation of the association between ScvO₂ at admission and in-hospital mortality in critically ill AMI patients requiring mechanical ventilation. The central finding is that a higher initial ScvO₂ was independently associated with a significantly lower risk of in-hospital mortality, exhibiting a clear dose-response relationship. This association remained robust after adjusting for cardiac-specific factors and interventions, and was consistent across all predefined subgroups. This suggests that within the intensive monitoring framework of the CCU, ScvO₂ serves not only as a dynamic parameter for guiding therapy but also as an early and independent prognostic marker in this specific high-risk phenotype.

The balance between oxygen consumption and oxygen delivery is commonly assessed by measuring the oxygen saturation in pulmonary arterial blood, referred to as mixed venous oxygen saturation (SvO₂) (29). ScvO₂ is measured as a surrogate for SvO₂ using a central venous catheter, with reliable measurement requiring placement of the catheter tip near the right atrium. Even when correctly positioned, ScvO₂ may not perfectly match SvO₂ due to mixing of blood from the distal superior vena cava with blood returning from the coronary sinus and the inferior vena cava (30,31). Nevertheless, ScvO₂ is widely regarded as a reasonable clinical substitute for SvO₂; studies comparing serial measurements in the same patients have shown that trends in ScvO₂ and SvO₂ generally correlate well (32-34). In critically ill patients, ScvO₂ is typically 3–11% higher than SvO₂ (35). ScvO₂ serves as a clinically valuable hemodynamic parameter that reflects the dynamic balance between systemic oxygen delivery and consumption (36-38). In physiologically stable individuals, ScvO₂ normally ranges from 70% to 75% (39,40). Clinical evidence indicates that ScvO₂ levels below 60–65% are associated with adverse outcomes in patients after cardiac surgery and in sepsis populations (10,22). This pathophysiological relationship also extends to the management of AMI.

A seminal 1991 prospective observational study by Sumimoto et al. (n=119 AMI patients) identified ScvO₂ as a significant survival predictor (F=66.1; P<0.001) (41). In our AMI cohort, the elevated mortality risk observed in patients with TIMI flow<III, reduced left ventricular ejection fraction, and intra-aortic balloon pump use likely reflects impaired cardiac output. According to the Fick principle, ScvO₂ and cardiac index dynamically interact with oxygen demand: preserved ScvO₂ may mask reduced cardiac output during low metabolic states, whereas inadequate cardiac output triggers compensatory increases in oxygen extraction. This is illustrated by a study of 24 patients with complicated myocardial infarction undergoing continuous SvO₂ monitoring, in which increases in SvO₂ correlated with rises in cardiac index in 75% to 78.5% of cases, while decreases in SvO₂ corresponded with reductions in cardiac index in 45.5% to 61% of cases (42). Furthermore, a prospective study of 385 critically ill cardiac patients identified an SvO₂ of <40% as a predictor of in-hospital mortality, with non-survivors showing significantly lower levels compared to survivors (43). Our findings corroborate this relationship, demonstrating an 8.46-fold higher mortality risk (adjusted OR =8.46; 95% CI: 1.57–45.48; P=0.01) in the lowest versus highest ScvO₂ tertiles, indicating impaired systemic oxygenation consistent with previous studies. These findings underscore ScvO₂’s clinical utility as a dynamic biomarker of oxygen homeostasis. Given its direct association with shock pathophysiology, systematic ScvO₂ monitoring in critically ill AMI patients enables timely detection of tissue hypoxia, potentially guiding therapeutic interventions to mitigate morbidity and mortality risks.

While our findings demonstrate an inverse association between ScvO₂ and in-hospital mortality, certain previous investigations have reported divergent outcomes. Textoris et al. identified elevated ScvO₂ levels as mortality predictors in septic shock patients (adjusted OR =1.06; 95% CI: 1.01–1.13) (44). This discrepancy may reflect population-specific pathophysiological mechanisms, particularly microcirculatory dysfunction in sepsis patients with paradoxically high ScvO₂. Chung et al. further observed no mortality association with post-resuscitation ScvO₂ levels in severe sepsis cohorts (n=124) (45). Low ScvO₂ may be due to decreased oxygen delivery with or without increased oxygen consumption. However, the clinical interpretation of ScvO₂ thresholds remains debated. While low ScvO₂ (<66.5%) predicted complications in trauma populations, sepsis studies identified both hypo- (<70%) and hyper-saturation (>90%) as mortality risks (46,47). Current evidence suggests critical thresholds may vary between 65.5–70% depending on clinical context, with individual hemodynamic compensation potentially mitigating hypoxia risk below these levels. While ScvO₂ provides direct and continuous data on cardiac function and tissue oxygen extraction, its reliability as a sole marker of cardiac output or tissue hypoxia may be limited. Therefore, in the multifaceted prognostic assessment of critically ill AMI patients, ScvO₂ should be viewed as an integrative—rather than a decisive—marker. Its primary value lies in complementing the evaluation of core cardiac pathology and interventions with a clinically accessible measure of systemic oxygen metabolism, underscoring the necessity of multimodal monitoring in this population.

We recognize several limitations to this study. First, this was a single-center, retrospective, observational cohort study. As a secondary analysis, the sample size was determined by data availability rather than by a priori power calculation. Specifically, nearly 43% (133/312) of the original cohort was excluded due to missing ScvO₂ measurements, our key exposure variable. While necessary, this exclusion could introduce selection bias if the reasons for missing data were systematically related to patient severity or outcomes. Furthermore, this study only included AMI patients who underwent ScvO₂ monitoring, a subgroup with significantly higher mortality than those without monitoring. Therefore, our findings are subject to selection bias and are only generalizable to AMI patients who receive ScvO₂ monitoring, not to the entire AMI population. Other important data, including cardiovascular risk factors such as biomarkers (e.g., lipids, HbA1c), detailed longitudinal hemodynamic data, specific shock markers, and serial kidney function measurements, and medication use were unavailable. This limitation introduces potential bias and underscores the need for cautious interpretation of the findings. Moreover, detailed information on ScvO₂ measurement procedures (e.g., catheter tip position confirmed by imaging, specific blood gas analyzer models, quality control protocols, and exact timing of sampling relative to mechanical ventilation) was not available in the original database, as this study is a secondary analysis of an existing clinical dataset. This lack of standardization may affect measurement accuracy and reproducibility. Second, most covariates, including ScvO₂, were measured only at baseline. The single-point assessment of ScvO₂ at admission reflects oxygen transport and metabolic status at the initiation of therapy but does not account for dynamic changes that may occur during the course of treatment due to interventions, disease progression, or recovery. This represents a critical limitation, as temporal fluctuations in ScvO₂ could provide additional prognostic insights, such as identifying critical thresholds or patterns predictive of clinical outcomes. Future studies should prioritize evaluating the temporal dynamics of ScvO₂ using advanced statistical methods, such as trajectory analysis or time-series models, to better understand how variability in ScvO₂ impacts patient prognosis. Third, this study focused on critically ill patients with AMI, a population with specific clinical characteristics that may limit the generalizability of our findings. While we observed an association between higher ScvO₂ and reduced mortality in this cohort, the interpretation of this relationship may be influenced by sample size, residual confounding, and variable selection. Although prior studies suggest that elevated ScvO₂ may correlate with adverse outcomes in other patient groups, the single-center design of our study further restricts the external validity of these results. Larger, multicenter studies are needed to validate these findings and determine optimal ScvO₂ thresholds for diverse patient populations to guide individualized hemodynamic management. Finally, this analysis was derived from a public database and focused on the association between ScvO₂ at CCU admission and outcomes in critically ill patients with AMI. While a correlation between initial ScvO₂ and prognosis was identified, data limitations preclude detailed mechanistic exploration of the biological pathways underlying this relationship. The original public dataset did not provide individual-level death times or survival durations, only binary in-hospital mortality status. The absence of time-to-event data is a significant limitation. Logistic regression treats mortality as a binary outcome without accounting for differential follow-up times or censoring, which may bias effect estimates under certain conditions. For example, if patients with low ScvO₂ tend to die earlier than those with normal ScvO₂, logistic regression may either overestimate or underestimate the true association depending on the underlying hazard patterns. Future prospective studies should collect survival time information to enable Cox regression analyses. Future research should incorporate prospective data collection and mechanistic studies to further validate the role of ScvO₂ in AMI management. Given the methodological limitations described above, our findings should be considered exploratory and hypothesis-generating, and external validation in independent cohorts is required before clinical application. Thereby providing more robust evidence to support clinical decision-making.

Conclusions

In summary, this study indicates that among critically ill AMI patients requiring mechanical ventilation who undergo ScvO₂ monitoring, lower ScvO₂ measured at CCU admission is associated with an increased risk of in-hospital mortality. As an available parameter obtained early in the critical care course, ScvO₂ could serve as a practical biomarker for early risk stratification in this population. These findings highlight the potential clinical utility of ScvO₂ in identifying high-risk patients; however, further prospective studies are warranted to validate its prognostic role and to elucidate the underlying mechanisms.

Acknowledgments

The authors thank Muhammad Imran Ansari and colleagues for making their dataset publicly available. This analysis utilized data from the clinical audit originally conducted at the Coronary Care Unit (CCU) of the National Institute of Cardiovascular Diseases (NICVD), Karachi, Pakistan (August 2021–January 2022). The dataset is accessible via figshare at https://figshare.com/articles/dataset/S1_Dataset_-/23990967 and is shared under the Creative Commons Attribution 4.0 International (CC BY 4.0) license. We also acknowledge the NICVD review board for ethical approval (ERC-74/2021) and the patients’ caregivers or immediate family members for providing written informed consent.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0864/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0864/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0864/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Ethical approval for the parent study was granted by the Ethical Review Committee of the National Institute of Cardiovascular Diseases, Pakistan (No. ERC-74/2021); written informed consent was obtained from the patients’ designated caregivers or immediate family members. The present secondary analysis of the de-identified public dataset required no further approval.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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