Pulmonary hypertension (PH) due to left heart disease (group 2 PH) is associated with a worse prognosis than isolated heart failure. Both pulmonary arterial hypertension (group 1 PH) and group 2 PH are involved in pulmonary artery (PA) remodeling, which is potentially driven by shared molecular mechanisms. The aim of this study was to investigate the underlying processes contributing to PA remodeling in group 2 PH. To mimic the response to a left-sided pressure load, pulmonary arterial smooth muscle cells (PASMCs) were subjected to mechanical stretch. RNA sequencing of PAs from patients with group 2 PH was performed using the Gene Expression Omnibus database. Mice with transverse aortic constriction and spontaneously hypertensive rats were used as group 2 PH models, and they were treated with adeno-associated virus via intratracheal instillation. RNA sequencing of PASMCs after the stretch stress identified 1585 genes specifically upregulated in PASMCs from patients with group 1 PH. Further PA and plasma analyses from patients with group 2 PH, integrated with group 1 PH findings, identified enhancement of TGF-β (transforming growth factor-beta) signaling by the INHBA (inhibin subunit beta A) as a key feature. Metabolomics revealed that stretch-induced mitochondrial dysfunction in PASMCs caused lactic acidosis via enhancement of PDK1 (pyruvate dehydrogenase kinase 1) and c-MYC, leading to increased INHBA expression. Mice with transverse aortic constriction exhibited increased INHBA expression, decreased PDH (pyruvate dehydrogenase) expression, and acidic alterations in PAs. Targeted silencing of INHBA or PDK1 using adeno-associated virus in mice with transverse aortic constriction attenuated PA remodeling, improved right ventricular function, and reduced PH. Integrated RNA sequencing and metabolomics with stretched PASMCs and animal models identified mitochondrial dysfunction and subsequent acidic alterations as stimulators of increased INHBA expression and TGF-β signaling. These mechanisms contributed to PA remodeling in group 2 PH and provided potential therapeutic strategies.

This investigation aims to elucidate the impact of echocardiography in assessing the association between the watershed region of the lower abdominal aorta and renal function impairment during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy. In this retrospective cohort study, patients who underwent VA-ECMO treatment for left heart failure at one hospital from March 2014 to November 2021 were included. Based on the position of the watershed in the lower abdominal aorta during ECMO therapy, according to echocardiography, subjects were categorized into 2 cohorts: the upper watershed group and the lower watershed group. The primary endpoint was an elevation in serum creatinine levels exceeding 133 μmol/L within 24 hours following the discontinuation of VA-ECMO. The cohort comprised 657 participants, with 437 allocated to the lower watershed group and 220 to the upper watershed group. No significant disparities were observed between the groups in terms of age (P = .078), gender (P = .638), and the underlying cause for VA-ECMO deployment (P = .865). The likelihood of successful weaning from VA-ECMO was notably higher in the lower watershed group compared to the upper watershed group (97.0% vs 88.2%, P < .001). Conversely, the upper watershed group exhibited elevated mortality (8.2% vs 2.3%, P < .001) and renal failure (16.4% vs 4.1%, P < .001) rates. A significant difference in serum creatinine levels was recorded between the groups (β = 64.176, P < .001), with the upper watershed group demonstrating a higher association with serum creatinine levels exceeding 133 μmol/L within 24 hours post-VA-ECMO weaning (compared to the lower group, odds ratio = 15.206, 95% confidence interval: 9.791-23.616, P < .001). The echocardiographically determined position of the watershed above the lower abdominal aorta was found to be independently associated with an increased risk of serum creatinine levels exceeding 133 μmol/L within 24 hours after weaning from VA-ECMO. Additional multicenter, prospective validation studies are necessary to determine the exact causality between watershed position and ECMO weaning outcomes.

Hepatopulmonary fusion is a rare defect describing the physical connection of liver and lung. A neonate with hypoplastic left heart syndrome arrived at the hospital with concern for congenital diaphragmatic hernia, later found to have hepatopulmonary fusion. In the coming months, he underwent a series of operations, including ligation of the hepatopulmonary fusion and the first two stages of surgical palliation of hypoplastic left heart syndrome. He ultimately died of septic shock at 15 months of age.

Background Doxorubicin (DX)-induced cardiotoxicity involves dose- and time-dependent myocardial injury driven by oxidative stress, mitochondrial dysfunction, and disrupted topoisomerase IIβ signaling, leading to progressive left ventricular dysfunction and heart failure risk. Despite the growing literature in this field, no comprehensive bibliometric investigation has yet mapped the intellectual structure, research frontiers, and thematic evolution of this domain, creating a gap in synthesizing the knowledge landscape of DX-induced cardiotoxicity research (DCTR). Purpose The objective of this study was to fill this gap by exploring research frontiers, co-word analysis, theme integration, and thematic developments related to DCTR using a bibliometric network examination from 1974 to 2024. Materials and Methods The analyzes were executed in four sequential stages: (a) collection of data-driven studies from the Scopus database, (b) preprocessing and refining of the dataset, (c) construction and visualization of networks, and (d) analysis and elucidation of the dataset using Visualization of Similarities Viewer (bibliometric network mapping software) (VOSviewer) and Bibliometrix applications. An investigation was conducted using descriptive analysis, bibliometric network analysis, and full quantitative analysis. Results The 6,135 keywords extracted from 4,782 abstracts were used to determine the intellectual and thematic framework of the studies on DCTR. Prominent frontiers were identified, along with their corresponding effect measures. Three themes were identified to characterize the evolution of keywords in the structure over a period of 50 years: “Chemotherapy Theme,” “Breast Cancer Theme,” and “DX Theme.” Current emerging topics in this field include pyroptosis, ferroptosis, molecular docking, network pharmacology, and the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Conclusion The findings of this study offer significant perspectives for studies pertaining to the DCTR. These data may assist physicians in summarizing future research in this field.

This study aims to compare cerebral and splanchnic regional oxygen saturation(rSO2) in premature infants with duct-dependent congenital heart disease (CHD) using near-infrared spectroscopy (NIRS) with that of case-control premature infants without CHD.Premature infants with duct-dependent CHD requiring prostaglandin E1 (PGE1) for more than 10 days and control preterm infants (without CHD) were monitored for 36 hours using NIRS to assess cerebral and splanchnic rSO2. Both groups received gavage enteral feeding. Multiple measurements were taken around feeding at three different times (30 minutes before, during, and 30 minutes after feeding).A total of 16 cases were included in the study (8 CHD and 8 controls). The CHD infants had the following diagnoses: four with aortic coarctation, two with interrupted aortic arch, one with hypoplastic left heart syndrome, and one with D-transposition of the great arteries. The median gestational age (35 weeks in duct-dependent CHD vs. 34 weeks in controls) and birth weight (1850 g vs. 1800 g, respectively) were similar between the two groups (p>0.05). The median cerebral NIRS measurements in the controls were 12 points higher than in the cases (P=0.03), and the splanchnic NIRS measurements were 20 points higher (P=0.01). The median cerebral NIRS measurements in the cases were 60%, 64%, and 62% at baseline, during feeding, and post-feeding, respectively, while the controls had values of 72%, 74%, and 71% at the same times. The median splanchnic NIRS measurements in the cases were 30%, 35%, and 38% at baseline, during feeding, and post-feeding, respectively, while the controls had values of 50%, 52%, and 54%. Similar changes in cerebral and splanchnic NIRS values were observed during feeding in both the cases and controls (p>0.05).Premature neonates with duct-dependent CHD have a reduction in both cerebral and splanchnic rSO2 values when compared to age-matched controls. NIRS monitoring demonstrated lower regional oxygen saturation levels in duct-dependent CHD infants compared with controls, suggesting reduced tissue oxygenation during feeding. Further studies with larger sample sizes are needed in this area.

Perinatal transition is uniquely complex in newborns with critical congenital heart disease (CCHD), whose cardiopulmonary physiology often diverges from the standard neonatal resuscitation framework. We developed lesion-specific clinical practice guidelines (CPGs) for delivery room (DR) management of six high-risk CCHD diagnoses - hypoplastic left heart syndrome, dextro- transposition of the great arteries, Ebstein anomaly, congenital complete heart block, total anomalous pulmonary venous return, and tetralogy of Fallot with absent pulmonary valve. Developed collaboratively between neonatologists, cardiologists, and cardiac intensivists, these guidelines standardize DR stabilization for high-risk, low frequency events, promote a shared mental model among multidisciplinary teams, and provide structured escalation thresholds for oxygen, respiratory support, intubation, and medication use. Beyond clinical standardization, these CPGs enhance provider education, team preparedness, and family counseling. They offer a scalable framework adaptable to centers with or without on-site cardiac care, bridging physiologic principles with practical implementation.

Primary Biventricular Repair in Neonates with Borderline Left Ventricle.

We describe two cases of choroidal involvement in patients with Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis. Short case series. The first patient was a 25-year-old man with asymptomatic ECD at the level of bones, lung, and central nervous system. Fundus examination revealed bilateral yellowish choroidal infiltration in the superior macula and nasal midperiphery. After initial mild enlargement of the choroidal lesions, treatment with weekly subcutaneous pegylated interferon α2a was started inducing partial regression of the lesions. The second patient was a 45-year-old man with ECD involving the left orbit, maxillary sinus, heart, blood vessels, kidney, retroperitoneum, bones, and testes. Fundus examination of the left eye showed choroidal folds. Macular spectral-domain optical coherence tomography confirmed the folds and revealed underlying choroidal infiltration. Final ocular diagnosis was left choroidal, scleral, and orbital involvement. The patient was initially treated with pegylated interferon α2a, and later with cobimetinib, a Mitogen-activated protein kinase kinase inhibitor, with favorable results. Neither patient developed choroidal neovascularization during the follow-up. Erdheim-Chester disease is a rare multisystem disorder that can present with ocular involvement, including orbital masses, xanthelasma-like lesions, and, occasionally, choroidal infiltrates. Early recognition and prompt treatment can lead to improvement of ophthalmic and systemic symptoms and prevent further complications. We recommend treating patients with choroidal ECD, regardless of the presence of symptoms, considering these patients are at increased risk of developing choroidal neovascularization.

The study by Inam et al. published in this issue of the Pakistan Heart Journal gives valuable evidence linking cannabis use with heart failure, especially heart failure with reduced ejection fraction (HFrEF). Conducted at Hayatabad Medical Complex, Peshawar the cross sectional study of 380 patients found that HFrEF was more common in cannabis users (60%) than in non-users (50%) (p = 0.03) [1]. These findings are consistent with recent international studies showing that cannabis users have higher rates of arrhythmia, myocardial dysfunction, and hospital admission. Importantly, users in this Pakistani cohort were generally younger, suggesting that cannabis may contribute to early cardiovascular injury [2-9]. Cannabis can affect the heart through several mechanisms by sympathetic activation, oxidative stress, endothelial injury, and vascular inflammation. It can also worsen metabolic stress in patients with hypertension or diabetes. When combined these factors may accelerate left ventricular dysfunction and heart failure progression [2-9]. Clinicians should routinely ask patients with heart failure about cannabis use especially younger individuals with unexplained systolic dysfunction. Counselling to stop cannabis use should be integrated into cardiac rehabilitation and outpatient care programs [2-9]. From a public health perspective cannabis should be recognised as a modifiable cardiovascular risk factor, similar to smoking or alcohol. Public awareness efforts and heart failure registries can incorporate cannabis screening to guide education, prevention and early intervention [2-9]. Although this was a single centre study, it provides an important foundation for larger national and regional research to explore dose response relationships and the reversibility of cardiac injury after cessation. In summary Inam et al. remind clinicians and policymakers that cannabis is not harmless. It can harm the heart and should be regarded as a preventable cause of heart failure, particularly among younger people. AUTHORS' CONTRIBUTION AKN, BM, and MTM: Concept and design, data acquisition, interpretation, drafting, final approval, and agree to be accountable for all aspects of the work. Acknowledgment: None. Funding: No specific grant for this research from any public, commercial, or not-for-profit funding agency References Inam S, Saeed I, Khan QA, Aamir M, Din HNU, Khan O. Prevalence and Incidence of Heart Failure among Cannabis Users: A Cross-Sectional Study. Pak Heart J. 2025;58(04):414-420. DOI: 10.47144/phj.v58i4.2970 Chandy M, Jimenez-Tellez N, Wu JC. The relationship between cannabis and cardiovascular disease: clearing the haze. Nat Rev Cardiol. 2025; 22: 467-481. DOI: 10.1038/s41569-025-01121-6 Storck W, Elbaz M, Vindis C, Déguilhem A, Lapeyre-Mestre M, Jouanjus E. Cardiovascular risk associated with the use of cannabis and cannabinoids: a systematic review and meta-analysis. Heart. 2025;111(22):1047-1056. DOI: 10.1136/heartjnl-2024-325429 Kamel I, Mahmoud AK, Twayana AR, Younes AM, Horn B, Dietzius H. Myocardial infarction and cardiovascular risks associated with cannabis use. JACC Advances. 2025; DOI: 10.1016/j.jacadv.2025.101698. American College of Cardiology. Cannabis Users Face Substantially Higher Risk of Heart Attack. Press Release. March 17, 2025. Available at: https://www.acc.org British Medical Journal Group. Cannabis Use Linked to Doubling in Risk of Cardiovascular-Disease Death. BMJ News. June 2025. Dhillon BK, Sombans S, Verma R, et al. Cannabis use among young females admitted for heart failure in the United States. Circulation. 2023; 147(Suppl 1): AP580. Patel RS, Gonzalez MD, Ajibawo T, Baweja R. Cannabis use disorder and increased risk of arrhythmia-related hospitalization in young adults. Am J Addict. 2021; 30(6): 578-584. DOI: 10.1111/ajad.13215 Richards JR, Blohm E, Toles KA, Jarman AF, Ely DF, Elder JW. The association of cannabis use and cardiac dysrhythmias: a systematic review. Clin Toxicol (Phila). 2020 Sep;58(9):861-869. DOI: 10.1080/15563650.2020.1743847

Rate-adaptive pacing in right-sided heart failure with tricuspid regurgitation: A prospective pilot study.

CPT1A exacerbates trastuzumab-induced cardiotoxicity via promotion of mitochondrial dysfunction.

ObjectiveEarly detection of major cardiac defects is crucial for the management and prognosis of affected pregnancies. This study evaluated the effectiveness of routine first-trimester ultrasounds in detecting major cardiac defects in singleton pregnancies.MethodsThis retrospective study (2015–2023) at a tertiary center included 35,230 singleton pregnancies undergoing routine ultrasounds at 11–14, 20–24, 28–34, and 34–38 weeks. High-resolution equipment and standardized protocols were used to assess fetal nuchal translucency and cardiac structure.ResultsAmong the 35,230 pregnancies studied, 270 cases (0.8%) of major heart defects were identified. Hypoplastic left heart syndrome (HLHS) was detected in 31 cases with a 90% detection rate, while ventricular septal defects (VSD) were the most common, found in 128 cases with a lower detection rate of 16%. Pregnancy outcomes varied significantly with gestational age: 55.9% of early detections (11–13 weeks) led to termination, while 63.9% of mid-term detections (18–22 weeks) resulted in live births. The first-trimester ultrasound scans demonstrated 100% sensitivity and Negative Predictive Value (NPV), with a specificity of 93.85% and a Positive Predictive Value (PPV) of 90.27%. The Kappa value of 0.917 indicated moderate agreement between early and later scans. Notably, early diagnosis (11–13 weeks) was associated with a higher rate of pregnancy terminations, while later diagnoses corresponded to higher live birth rates.ConclusionRoutine first-trimester ultrasounds effectively detect major cardiac defects early. However, the high sensitivity but low specificity necessitates follow-up scans to confirm findings and reduce false positives, ultimately enhancing prenatal care.

Understanding the Pressure-Volume Loop in Valvular Heart Disease.

Does Pericardiotomy With Cardiac Surgery Relieve Pericardial Restraint And Elevated Left Heart Pressures In Pre Capillary Pulmonary Hypertension?

Thrombi mainly form in the left heart chambers, particularly in dilated atria and in the context of atrial fibrillation. The presence of thrombi in the right atrium is uncommon; they are more often the result of peripheral venous circulation emboli, and less frequently, they originate in situ. In Latin America, the incidence of deep vein thrombosis is approximately 1 case per 1,000 people per year, and that of pulmonary embolism is 0.5 cases per 1,000 people per year. This clinical case presents a 64-year-old male patient diagnosed with a serpentine thrombus in the right atrium and dilated right heart chambers, successfully treated with oral anticoagulation.

EBV is a rare cause of encephalitis which can present with a broad spectrum of focal and diffuse neurological symptoms. In immunocompetent patients, prompt diagnosis can be difficult, especially in the context of comorbid conditions with similar symptomatology.

Gestational diabetes mellitus (GDM) is a common complication observed during pregnancy, with its global prevalence increasing in recent years. GDM has been linked to adverse myocardial remodeling in the fetus and impaired fetal cardiac function. This study seeks to evaluate the impact of GDM on fetal global cardiac function using dual-gate Doppler ultrasound (DD) technology, and to investigate the potential benefits and advantages of DD technology in assessing fetal cardiac function. A cohort consisting of 56 pregnant women diagnosed with gestational diabetes mellitus between 24 and 28 weeks of gestation (GDM group) was selected, alongside a control group of 55 pregnant women with normal glucose levels at the same gestational age. Both the conventional pulsed combined method and the dual-gate (DD) method were utilized to evaluate the ultrasound parameters of fetal global cardiac function in both groups. These parameters included isovolumic contraction time (ICT), isovolumic relaxation time (IRT), and ejection time (ET), from which the Tei index was subsequently calculated. The ICT, IRT, and Tei index of the left heart in the GDM group were significantly elevated compared to the control group (P < .05). Although ET in the GDM group, as assessed by the combined method, demonstrated a decreasing trend, this difference did not achieve statistical significance (P > .05). Conversely, the ET determined by the DD method in the GDM group was significantly reduced compared to the control group (P < .05). Right ventricular Tei index measurements showed poor consistency, with intraobserver ICCs of 0.56 for the separated measurement and 0.58 for the DD method, and interobserver ICCs of 0.50 and 0.53. As a result, right ventricular Tei indices were excluded from the final analysis. Pregnant women with GDM will cause an increase in the Tei index of the fetal left global cardiac function, indicating that the intrauterine hyperglycemic environment can cause damage to the global fetal cardiac function. The global fetal cardiac function was impaired in both the well-controlled and poorly controlled GDM groups, suggesting that early detection of GDM and the fetal cardiac dysfunction caused by GDM are necessary. The measurement of the Tei index of the left heart in the fetus using dual-gate Doppler technology can help detect the fetal cardiac dysfunction caused by GDM at an early stage, while the application of dual-gate Doppler technology in the overall cardiac function of the right heart still faces significant challenges.

Echo-derived left atrial (LA) stiffness index improves prognostication in patients with heart failure preserved ejection fraction but has not been studied in adults with repaired coarctation of aorta (COA). We hypothesized that, among adults with COA, those with high LA stiffness index would have worse disease severity indices [peak VO2, NT-proBNP, and right ventricular to pulmonary artery (RV-PA) coupling], heart failure hospitalization, and all-cause mortality. LA stiffness index was estimated using the baseline echocardiogram as the quotient of septal E/e' and LA reservoir strain (E/e'/LARS). Using the median septal LA stiffness index as the cut-off, patients were divided into high LA stiffness index (LA stiffness index >0.28) vs. low LA stiffness index groups (LA suggests index ≤0.28). The study comprised of 729 patients [age 36 ± 16 years; males 437 (60%)]. LA stiffness index correlated with RV-PA coupling (r = -0.56, P < 0.001), NT-proBNP (r = 0.62, P < 0.001), and predicted peak VO2 (r = -0.51, P < 0.001). High LA stiffness index was associated with heart failure hospitalization (adjusted HR 3.17, 95% confidence interval (CI) 1.84-7.36, P = 0.007) and all-cause mortality (adjusted HR 2.81, 95% CI 1.28-12.32, P = 0.005). LA stiffness index had superior prognostic performance for predicting 5-year risk of heart failure hospitalization (AUC 0.803, 95% CI 0.756-0.849, P < 0.001) and all-cause mortality (AUC 0.786, 95% CI 0.742-08.30, P < 0.001) compared with conventional echocardiographic indices of left heart diastolic function. LA stiffness index improves prognostication in adults with COA and can potentially be used to guide timing of intervention or monitor response to therapy.

As staged palliative surgery for patients with hypoplastic left heart syndrome ages to greater than 50 years in practice, providers are increasingly faced with the challenges of managing patients with "failed Fontan" physiology. In this brief case report, we discuss different ways paediatric palliative care can support this population.

Objective: to evaluate the effectiveness of various pharmacological approaches for the primary prevention of left ventricular dysfunction and heart failure induced by anticancer therapy. Materials and methods: the review was based on an analysis of the PubMed, Embase, Scopus, and Web of Science databases. A systematic literature review was conducted to analyze data on the use of beta-blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, statins, SGLT-2 inhibitors, and mineralocorticoid receptor antagonists. Clinical cases, case series, systematic reviews, meta-analyses, and animal studies were excluded from the results. No time limits were set, and articles published during the lifetime of the databases were analyzed. Studies were included if they reported the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, sodium-glucose cotransporter 2 inhibitors, statins, and mineralocorticosteroid receptor antagonists as primary prevention of left ventricular dysfunction and heart failure in cancer patients. Results: data on the effectiveness of beta-blockers are contradictory. Angiotensin receptor blockers (in particular, candesartan), angiotensin-converting enzyme inhibitors demonstrate improvement in left ventricular ejection fraction. Statins (atorvastatin and rosuvastatin) have shown effectiveness in primary prevention of cardiotoxicity. SGLT-2 inhibitors have demonstrated promising results in reducing the risk of cardiotoxicity and adverse cardiovascular events. Data on mineralocorticoid receptor antagonists are limited. Conclusions: beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and SGLT-2 inhibitors may have a cardioprotective effect in the context of preventing cardiotoxicity caused by anticancer therapy. Additional research is needed to determine the optimal prevention and treatment strategies that take into account individual patient risk factors and the specific therapy being used.