Ashfaq Ahmad

Background: Sodium−glucose cotransporter−2 inhibitors (SGLT2 inhibitors) confer broad cardiovascular benefits, but their role in pulmonary arterial hypertension (PAH) remains unclear. Objective: To investigate the potential therapeutic role of SGLT2 inhibitors in PAH by evaluating their longitudinal association, including improvement in risk profile, functional status, and ventricular coupling. Design: Multicenter retrospective longitudinal pilot study. Methods: Adults with Group 1 PAH confirmed by right heart catheterization were followed and categorized by exposure to SGLT2 inhibitors. Time-to-clinical improvement was assessed using Cox proportional hazard models adjusted for age, gender, PAH etiology, pulmonary vascular resistance, and baseline risk profile. Two predefined endpoints were evaluated: (1) improvement by ≥ 1 category in a four-level risk stratification, and (2) achievement of a low-risk profile. Longitudinal changes in functional, biomarkers, and echocardiographic measures were analyzed using linear mixed-effects models adjusting for relevant covariates. Results: Among 83 patients with PAH, 43 received SGLT2 inhibitors. SGLT2 inhibitor use was independently associated with a higher rate of improvement by ≥ 1 risk category (hazard ratio [HR] 2.21, 95%CI 1.06−4.63; p = 0.034) and a higher likelihood of achieving a low risk profile (HR 2.62, 95% CI 1.02−6.76; p = 0.045). Longitudinal improvement was observed across the cohort in six-minute walk distance, Borg dyspnea score, B-type natriuretic peptide (BNP) levels, and composite risk score (all p <0.001), with SGLT2 inhibitor use associated with greater improvement in persistently lower log-BNP levels during follow-up (p = 0.007). Echocardiographic demonstrated reductions in pulmonary artery systolic pressure and improvement in RV-pulmonary artery coupling over time. Conclusion: In this real-world cohort, SGLT2 inhibitor use was associated with a higher likelihood of clinical improvement and achieving a low-risk profile in PAH, alongside favorable longitudinal changes in biomarkers and hemodynamics. Prospective randomized trials are warranted.

Aim: To evaluate arterio‐venous gas parameters—P(ca–v)CO ₂ or ΔPCO ₂ , Ca–vO ₂ , and P(v–a) CO ₂ /Ca–vO ₂ ratio, and to develop a novel Heart–Lung Coupling (HLC) index defined as (ΔPCO ₂ /Ca–vO ₂ )/Cardiac Index to quantify the interaction between ventilatory efficiency and circulatory performance in pulmonary arterial hypertension (PAH). Methods: In this single‐center retrospective study, patients with PAH who underwent right heart catheterization between September 2019 and May 2024 were evaluated. After exclusions, 115 patients were included (35 idiopathic PAH [IPAH] and 80 congenital heart disease–associated PAH [CHD‐PAH]). Hemodynamics, arteriovenous gas parameters, and functional indices, including 6‐min walk distance (6MWD) and NT‐proBNP, were analyzed. The HLC was calculated and compared between groups. Association with functional parameters was assessed using Spearman correlation and multivariate linear regression after LASSO selection. Receiver operating characteristic analysis evaluated the ability of HLC to identify impaired exercise capacity (6MWD < 350 m). Results: ΔPCO ₂ , Ca–vO ₂ and P(v–a) CO ₂ /Ca–vO ₂ ratio were significantly higher in IPAH than CHD‐PAH (8.3 vs. 3.5 mmHg, p < 0.001; 4.8 vs. 3.4 mL/dL, p = 0.005; 1.84 vs. 1.11, p < 0.001, respectively). The HLC index was also higher in IPAH (median 0.82 vs. 0.40, p = 0.001). HLC showed modest correlation with 6MWD ( r = 0.27, p = 0.04) and NT‐proBNP ( r = 0.24, p = 0.021). In multivariate regression, HLC remained independently associated with 6MWD ( β = 32.86, 95% CI: 5.15–60.57, p = 0.021). Discrimination of impaired exercise capacity was limited (AUC of 0.55). Conclusion: The HLC index integrates gas exchange and cardiac output to characterize heart–lung interaction in PAH. This novel physiological metric may provide complementary insights into cardiopulmonary coupling and functional limitation.

Pulmonary hypertension (PH) is a common complication in patients with chronic kidney disease (CKD) and is associated with high mortality. Early detection and proper management may improve outcomes in high‐risk patients. This study aimed to develop a simple and effective model for screening PH risk in this population. We retrospectively screened 1082 CKD patients. Feature selection was performed using the least absolute shrinkage and selection operator, univariate and multivariate logistic regression (LR). Nomograms were developed for PH risk assessment. The discriminative ability was estimated by the area under the receiver operating characteristic curve (AUROC), and the accuracy was assessed with a Brier score. Models were validated externally by calculating their performance on a validation cohort. Eight machine learning models were developed, and their performance was evaluated. Decision curve analysis and clinical impact curve were used to assess the model's clinical usefulness. A total of 440 patients were included in the analysis, with 308 in the development cohort and 132 in the validation cohort. The final nomogram included five variables as follows: haemoglobin, gamma‐glutamyl transferase, triglycerides, coronary heart disease and NT‐proBNP. The AUROC of the model was 0.772 (95% CI: 0.731–0.806). External validation confirmed the model's good performance, with an AUROC of 0.782 (95% CI: 0.696–0.854). Among the eight machine learning models, LR showed the best performance. We developed a machine learning model based on clinical and biochemical features to assess PH risk in CKD patients. It enables early detection and risk stratification during follow‐up.

Objective: This study aimed to investigate the etiology, clinical consequences, and cardiovascular burden of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD), particularly in severe CKD and end-stage renal disease. In addition, potential diagnostic markers were identified. Methods: In this single-center cross-sectional study, CKD patients (stage 3b–5) from the First Affiliated Hospital of Xi’an Jiaotong University were randomly matched 1:1 based on age, sex, and CKD stage between January 2020 and December 2022. Clinical and laboratory data—including blood cell counting, blood lipids, liver and kidney function, blood coagulation, N-terminal pro B-type natriuretic peptide, and troponin T—were collected from the Unified Digital Medical Record system. Additionally, transthoracic echocardiography and electrocardiogram results were collected upon patient admission. PH severity was classified as mild, moderate, or severe based on echocardiographic findings, and subgroup analyses were performed according to this classification. Results: A total of 440 CKD patients were enrolled with 220 patients diagnosed with PH (PH group) and 220 without PH (non-PH group). PH patients exhibited significantly lower red blood cell counts (2.76 (2.39, 3.20) × 10 ¹² /L vs. 3.14 (2.67, 3.73)×10 ¹² /L, P < 0.001), hemoglobin levels (82 (71, 93) g/L vs. 95 (79, 109) g/L, P < 0.001), and higher D-dimer (1.31(0.74, 2.75) mg/L vs. 0.83 (0.50, 1.47) mg/L, P < 0.001). Cardiac biomarkers, including N-terminal pro B-type natriuretic peptide (23,705 (6,809, 35,000) ng/L vs. 2,644 (665, 10,818) ng/L, P < 0.001) and troponin T (0.070 (0.032, 0.134) μg/L vs. 0.031 (0.013, 0.066) μg/L, P < 0.001), were markedly elevated in the PH group. Echocardiographic findings revealed significant right ventricular enlargement (29 (26, 32) mm vs. 27 (25,29) mm, P < 0.001) and a higher prevalence of pericardial effusion (62.7% vs. 25.0%, P < 0.001) in PH patients. Cardiac conduction abnormalities were more prevalent in PH patients, with significantly higher rates of atrial fibrillation, supraventricular premature beats, and right bundle branch block (all P < 0.05). There are 109 patients with mild PH, 83 with moderate PH, and 28 with severe PH. Left ventricular remodeling and functional impairment were observed in moderate and severe PH patients. Conclusion: Progressive PH in CKD patients is associated with significant cardiovascular abnormalities. Routine echocardiographic surveillance and biomarker monitoring are crucial for early risk stratification and management. Further research is needed to explore targeted therapies to improve outcomes in this high-risk population.

Patients with congenital heart disease‐related pulmonary arterial hypertension (CHD‐PAH) often require regular follow‐up through invasive right heart catheterization (RHC) to assess disease progression and potential interventions. This study aims to evaluate the relationship between arteriovenous oxygen content difference (Ca−vO₂) and RHC parameters to identify blood gas parameters that can aid in a clue about preselecting patients with CHD‐PAH for follow‐up RHC and potential surgical or percutaneous shunt closure. In this study, a total of 137 adult CHD‐PAH patients were retrospectively enrolled between September 2019 and May 2024. The patients were divided into two groups based on their Qp/Qs ratio (< 1.5 or ≥ 1.5). Key parameters such as Ca−vO₂, 6‐min walk distance (6MWD), TAPSE, and IVC diameter were correlated with RHC parameters such as mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and pulmonary capillary wedge pressure (PCWP) and compared across groups with Qp/Qs < 1.5 and ≥ 1.5. Statistical analysis included Pearson's correlation, logistic regression analysis, and receiver operator characteristic (ROC) curve to determine the predictors for shunt severity. The study enrolled 80 patients with CHD‐related PAH in the final evaluation, with a mean age of 41 ± 15 years. Ca−vO₂ exhibits a significant positive correlation with RHC parameters, notably with mPAP (r = 0.524, p < 0.0001) and a negative correlation with Qp/Qs (r = −0.463, p = 0.04). Moreover, Ca−vO₂ emerged as a significant diagnostic predictor with an optimal cutoff value of < 4.3 mmol/L (AUC = 0.71, sensitivity 88.8%, specificity 53.4%). Other noninvasive parameters such as 6MWD, TAPSE, and IVC diameter with AUCs of 0.87, 0.83, and 0.85, respectively, also demonstrated a strong predictive value. Ca−vO₂ correlates well with CHD‐PAH severity and can serve as a preselecting marker for invasive follow‐up in CHD‐related PAH. Other noninvasive measures such as 6MWD, TAPSE, and IVC diameter show stronger predictive value for assessing shunt severity.

The role of right ventricular (RV) dysfunction in pulmonary hypertension (PH) has garnered increasing interest in terms of outcomes. This systematic review and meta-analysis evaluated the prognostic utility of three-dimensional echocardiography (3DE) derived right ventricular ejection fraction (RVEF) in PH. A systematic review and meta-analysis were performed using MEDLINE, Embase, and Scopus databases for publications reporting the hazard ratio (HR) of 3DE-derived RVEF in PH patients for the clinical end-points of composite outcome or all-cause mortality. Nine articles totaling 885 subjects were included, among which 67.23% had pulmonary arterial hypertension (PAH), with the remainder having a range of PH etiologies. The mean value of 3DE-derived RVEF was 35.5 ± 9.07% reflecting impaired RV function. The primary endpoint was all-cause mortality in three studies, while the rest of the studies reported composite outcomes. Follow-up duration ranges from 6 to 44 months. From seven publications, the pooled HR by 3DE-derived RVEF was 0.91 (95% CI: 0.85 to 0.97, p = 0.001; heterogeneity: I² = 62%, p = 0.004). In subgroup analysis, 3DE-derived RVEF was a significant prognostic factor for group 1 PH (HR: 0.90, CI: 0.86–0.94; heterogeneity I² = 43%, p < 0.0001). From meta-regression analysis, only follow-up duration was found statistically significant with the HR of RVEF in the population (estimate: 0.028, p = 0.026). 3DE-derived RVEF provides important prognostic value in a large population of PH patients, especially for group 1 PH. Further accumulation of evidence is needed to perform a detailed subgroup analysis in each type of PH. Graphical Abstract

Aim: Patients with congenital heart disease-related pulmonary arterial hypertension (CHD-PAH) often require regular follow-up through invasive right heart catheterization (RHC) to assess disease progression and potential interventions. This study aims to evaluate the relationship between arteriovenous oxygen content difference (Ca−vO₂) and RHC parameters to identify blood gas parameters that can aid in a clue about pre-selecting patients with CHD-PAH for follow-up RHC and potential surgical or percutaneous shunt closure. Methods: In this study, a total of 137 adult CHD-PAH patients were retrospectively enrolled between September 2019 and May 2024. The patients were divided into two groups based on their Qp/Qs ratio (2, 6-minute walk distance (6MWD), TAPSE, and IVC diameter were correlated with RHC parameters such as mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and pulmonary capillary wedge pressure (PCWP) and compared across groups with Qp/Qs 2 exhibits a significant positive correlation with RHC parameters, notably with mPAP (r = 0.524, p < 0.0001) and a negative correlation with Qp/Qs (r = −0.463, p = 0.04). Moreover, Ca−vO₂ emerged as a significant diagnostic predictor with an optimal cutoff value of 2 correlates well with CHD-PAH severity and can serve as a pre-selecting marker for invasive follow-up in CHD-related PAH. Other non-invasive measures such as 6MWD, TAPSE, and IVC diameter show stronger predictive value for assessing shunt severity.

Background The role of right ventricular (RV) dysfunction in pulmonary hypertension (PH) has garnered increasing interest in terms of outcomes. This systematic review and meta-analysis evaluated the prognostic utility of three-dimensional echocardiography (3DE) derived right ventricular ejection fraction (RVEF) in PH. Methods A systematic review and meta-analysis were performed using MEDLINE, Embase, and Scopus databases for publication reporting the hazard ratio (HR) of 3DE-derived RVEF in PH patients for the clinical end-points of composite outcome or all-cause mortality. Results Nine articles totaling 885 subjects were included, among which 67.23% had pulmonary arterial hypertension (PAH), with the remainder having a range of PH etiologies. The mean value of 3DE-derived RVEF was 35.5 ± 9.07% reflecting impaired RV function. The primary endpoint was all-cause mortality in three studies while the rest of the studies reported composite outcomes. Follow-up duration ranges from 6 months to 44 months. From seven publications the pooled HR by 3DE-derived RVEF was 0.91 (95% CI: 0.85 to 0.97, p = 0.001; heterogeneity: I² = 62%, p = 0.004). In subgroup analysis, 3DE-derived RVEF was a significant prognostic factor for group 1 PH (HR: 0.90, CI: 0.86–0.94; heterogeneity I² = 43%, p < 0.0001). From meta-regression analysis, only follow-up duration was found statistically significant with the HR of RVEF in the population (estimate: 0.028, p = 0.026). Conclusion 3DE-derived RVEF provides important prognostic value in a large and mixed population of PH patients. Further accumulation of evidence is needed to perform a detailed subgroup analysis in each type of PH.

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease that eventually leads to heart failure (HF) and subsequent fatality if left untreated. Right ventricular (RV) function has proven prognostic values in patients with a variety of heart diseases including PAH. PAH is predominantly a right heart disease; however, given the nature of the continuous circulatory system and the presence of shared septum and pericardial constraints, the interdependence of the right and left ventricles is a factor that requires consideration. Accurate and timely assessment of ventricular function is very important in the management of patients with PAH for disease outcomes and prognosis. Non-invasive modalities such as cardiac magnetic resonance (CMR) and echocardiography (two-dimensional and three-dimensional), and nuclear medicine, positron emission tomography (PET) play a crucial role in the assessment of ventricular function and disease prognosis. Each modality has its own strengths and limitations, hence this review article sheds light on (i) ventricular dysfunction in patients with PAH and RV–LV interdependence in such patients, (ii) the strengths and limitations of all available modalities and parameters for the early assessment of ventricular function, as well as their prognostic value, and (iii) lastly, the challenges faced and the potential future advancement in these modalities for accurate and early diagnosis of ventricular function in PAH.