Heart Failure Research Articles

EGFR slope as predictor of mortality in heart failure patients.

Heart failure (HF) leads to an imbalance between heart and kidney function, resulting in poor outcomes. However, the prognostic significance of the estimated glomerular filtration rate (eGFR) trajectory in HF patients remains unclear. We analysed electronic health records (EHRs) of real-world HF patients, assessing eGFR trajectories and their impact on mortality. Retrospective clinical data of HF patients were processed using natural language processing. Chronic kidney disease (CKD) was evaluated, and eGFR trajectories were analysed using linear mixed-effects models. Cox proportional hazard models were used to evaluate the relationship between baseline variables and mortality, while joint modelling combined eGFR trends and mortality. The dataset comprised 1986 patients, with a mean age of 74.8years (SD±11.7) and 58% male. At the time of HF diagnosis, 58% of patients were diagnosed with CKD, and 39% presented with heart failure with preserved ejection fraction (HFpEF). The median follow-up duration was 3.16years, during which 399 patients (20%) died. Patients with CKD were significantly older and exhibited a higher prevalence of myocardial infarction (P=0.048), coronary revascularization (P=0.004), stroke (P<0.001), atrial fibrillation (P<0.001) and type 2 diabetes (P<0.001). Mortality rates at 1 and 2years were nearly twice as high in CKD patients compared with those without (P<0.001). Notably, CKD was significantly less prevalent among survivors (55% vs. 71%, P<0.001). Key predictors of mortality included older age, beta-blocker use, prior stroke, lower serum haemoglobin levels, and elevated potassium and NT-proBNP levels. Each 10mL/min/1.73m2 decrease in eGFR was associated with a 1.22 (95% CI: 1.10-1.35, P<0.001) increase in mortality hazard. Additionally, a 1-year decline of 10mL/min/1.73m2 in eGFR resulted in a mortality hazard of 1.97 (95% CI: 1.45-2.69, P<0.001). CKD is prevalent in a real-world HF population and is an independent predictor of mortality. The current eGFR value and the eGFR slope from the previous year have the potential to be used for assessing individual mortality risk in the clinical follow-up of HF patients.

Enhanced Parkin-mediated mitophagy mitigates adverse left ventricular remodelling after myocardial infarction: role of PR-364.

Almost 30% of survivors of myocardial infarction (MI) develop heart failure (HF), in part due to damage caused by the accumulation of dysfunctional mitochondria. Organelle quality control through Parkin-mediated mitochondrial autophagy (mitophagy) is known to play a role in mediating protection against HF damage post-ischaemic injury and remodelling of the subsequent deteriorated myocardium. This study has shown that a single i.p. dose (2 h post-MI) of the selective small molecule Parkin activator PR-364 reduced mortality, preserved cardiac ejection fraction, and mitigated the progression of HF. To reveal the mechanism of PR-364, a multi-omic strategy was deployed in combination with classical functional assays using in vivo MI and in vitro cardiomyocyte models. In vitro cell data indicated that Parkin activation by PR-364 increased mitophagy and mitochondrial biogenesis, enhanced adenosine triphosphate production via improved citric acid cycle, altered accumulation of calcium localization to the mitochondria, and initiated translational reprogramming with increased expression of mitochondrial translational proteins. In mice, PR-364 administered post-MI resulted in widespread proteome changes, indicating an up-regulation of mitochondrial metabolism and mitochondrial translation in the surviving myocardium. This study demonstrates the therapeutic potential of targeting Parkin-mediated mitophagy using PR-364 to protect surviving cardiac tissue post-MI from progression to HF.

Evaluation of diagnostic performances of Pro-neurotensin and Heart-type fatty acid binding protein as reliable biomarkers for cardiovascular diseases

ABSTRACT Aim In 2019, cardiovascular diseases accounted for 32% of global deaths. So, early detection of cardiac disorders is crucial. The study aimed to examine the suitability of Pro-neurotensin and Heart-type fatty acid binding protein as dependable biomarkers for cardiac patients with Heart failure as a primary diagnosis. Methodology The prospective study involved 204 Egyptian volunteers (100 cardiac patients and 104 controls) enrolled from El-Sahel Teaching Hospital in Cairo, Egypt, between October 2022 and May 2023. Inclusion criteria included a high risk of cardiovascular events with symptoms like a fast or irregular pulse, shortness of breath, and fatigue. Exclusion criteria included asymptomatic individuals, cognitive disorders, and psychiatric conditions. The Research Ethics Committee approved the protocol. The consultant conducted a clinical examination of all patients and assessed their heart state. Serum ProNT and H-FABP were detected using a kit for the sandwich ELISA technique. Results ProNT and H-FABP were significantly elevated in patients compared to controls with p < 0.001. Demonstrated sensitivity of 81% and 84%, with a specificity of 89% and 91%, respectively. Conclusion Elevated ProNT and H-FABP levels are associated with severe CVDs, suggesting their potential as diagnostic biomarkers for patients, specifically those with heart failure, as a primary characteristic.

The Implication of NT-proBNP in the Assessment of the Clinical Phenotype of Patients with Type 2 Diabetes Mellitus, Without Established Cardiovascular Disease

Background: Natriuretic peptide (NP) levels have been proposed for characterization and risk stratification of heart failure (HF) among patients with cardiovascular disease (CVD). However, their role in patients with diabetes mellitus type 2 (T2DM) has not been well studied and understood. The aim of this study was to assess phenotypical, functional characteristics and imaging parameters in relation to N-terminal pro b-type natriuretic peptide (NT-proBNP) values in T2DM patients without known CVD that may predispose to overt HF. Methods: This was a cross-sectional study of 100 consecutive T2DM patients (mean overall age of 67 ± 9 years, 40% women and 60% men) who were enrolled from the outpatient diabetic clinic. Patients underwent a cardiopulmonary exercise test (CPET), and echocardiographic and cardiac magnetic resonance imaging (CMR); serum NT-proBNP was also measured. Results: The mean (standard deviation) NT-proBNP was 149 (±186) pg/mL. Patients in the highest tertile of NT-proBNP values (&gt;107 pg/mL) had lower values of predicted maximum oxygen consumption compared to the lowest quartile (&lt;55 pg/mL) (84% vs. 92%, p = 0.018) in the CPET and higher ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e′) (9.0 vs. 7.2, p = 0.05) in echocardiography. Finally, there was a negative correlation between right ventricle end diastolic volume in CMR and predicted maximum oxygen consumption (b = −0.225 ± 0.11, p = 0.046). Conclusions: NT-proBNP levels seemed to be a useful marker in people with T2DM, as elevated levels reflected ongoing appearance of HF with preserved ejection fraction and were related to CPET and echocardiographic indices of impaired left ventricular diastolic and right ventricular systolic function.

To investigate the correlation of serum NLRP3 level with endothelial function, severity of disease and prognosis in elderly patients with chronic heart failure.

To investigate the correlation of serum NLRP3 level with endothelial function, severity of disease and prognosis in elderly patients with chronic heart failure.

Sleep-Disordered Breathing in Patients with Chronic Heart Failure and Its Implications on Real-Time Hemodynamic Regulation, Baroreceptor Reflex Sensitivity, and Survival

Background: Impairment in autonomic activity is a prognostic marker in patients with heart failure (HF), and its involvement has been suggested in cardiovascular complications of obstructive sleep apnea syndrome (OSAS) and Cheyne–Stokes respiration (CSR). This prospective observational study aims to investigate the implications of sleep-disordered breathing (SDB) on hemodynamic regulation and autonomic activity in chronic HF patients. Methods: Chronic HF patients, providing confirmation of reduced ejection fraction (≤35%), underwent polysomnography, real-time hemodynamic, heart rate variability (HRV), and baroreceptor reflex sensitivity (BRS) assessments using the Task Force Monitor. BRS was assessed using the sequencing method during resting conditions and stress testing. Results: Our study population (n = 58) was predominantly male (41 vs. 17), with a median age of 61 (±11) yrs and a median BMI of 30 (±5) kg/m2. Patients diagnosed with CSR were 13.8% (8/58) and 50.0% (29/58) with OSAS. No differences in the real-time assessment of hemodynamic regulation, heart rate variability, or baroreceptor reflex function were found between patients with OSAS, CSR, and patients without SDB. A subgroup analysis of BRS and HRV in patients with severe SDB (AHI &gt; 30/h) and without SDB (AHI &lt; 5) revealed numerically reduced BRS and increased LF/HF-RRI values under resting conditions, as well as during mental testing in patients with severe SDB. Patients with moderate-to-severe SDB had a shorter overall survival, which was, however, dependent upon age. Conclusions: Chronic HF patients with severe SDB may exhibit lower baroreceptor function and impaired cardiovascular autonomic function in comparison with HF patients without SDB.

High-Sensitivity Cardiac Troponin Assays in Acute Heart Failure, Moving Beyond Myocardial Infarction.

Cardiac troponins are essential structural proteins found in the contractile apparatus of cardiac myocytes. During myocardial damage, such as in myocardial infarction (MI), these troponins are released into the bloodstream. As a result, they play a central role in the diagnosis of MI, serving as sensitive and specific markers for cardiac injury. Earlier assays that were used for measuring troponin levels were considered as a dichotomous test, categorizing patients as being positive or negative for MI. The recent introduction of high-sensitivity cardiac troponin assays has revolutionized cardiac troponin detection. These assays can detect troponin levels that are 100 times lower than what traditional methods can detect. Hence it is now considered a quantitative measure of cardiac myocyte injury not only in the setting of MI but also in subjects without MI such as heart failure, in whom it can be regarded as a marker for myocardial stress. This review aims to establish the relationship between high-sensitivity cardiac troponin levels and the prognosis of patients suffering from acute heart failure. Additionally, this seeks to identify other applications where the release of troponin from the cardiomyocyte can provide prognostic information. This information can be vital in determining the appropriate treatment options for patients, ultimately improving their quality of life and positively impacting health economics.

Impeding Nucleotide-Binding Oligomerization Domain-Like Receptor 3 Inflammasome Ameliorates Cardiac Remodeling and Dysfunction in Obesity-Associated Cardiomyopathy.

Inflammation and metabolic disturbances are key culprits in the pathogenesis of obesity-associated cardiomyopathy. The NLRP3 (nucleotide-binding oligomerization domain-like receptor 3) inflammasome mediates the release of the proinflammatory cytokines IL-1β (interleukin-1β) and IL-18 by activating caspase-1, which is strongly implicated in metabolic disturbances. We here sought to determine whether NLRP3 inflammasome inhibition could ameliorate obesity cardiomyopathy and if so, to further explore its underlying mechanisms. Male mice were fed a high-fat diet for 24 weeks to induce obesity cardiomyopathy. MCC950 was used to inhibit NLRP3 inflammasome activation. Recombinant adeno-associated virus serotype 9 encoding TXNIP (thioredoxin-interacting protein) under cTnT (cardiac troponin T) promoter and the mitochondrial-targeted antioxidant MitoTEMPO were injected into obese mice to investigate the specific mechanism. To mimic obesity cardiomyopathy invitro, neonatal rat ventricular myocytes transfected with the small interfering RNA against TXNIP were incubated with 400 μmol palmitic acid for 24 hours. NLRP3 inflammasome was significantly increased in obese hearts. NLRP3 inflammasome inhibition by NLRP3 deletion or MCC950 prevented obesity-induced cardiac systolic and diastolic dysfunction, myocardial hypertrophy and fibrosis, and excessive lipid accumulation in male mice. Conversely, TXNIP overexpression worsened obesity-associated cardiomyopathy. Similarly, MCC950 treatment or TXNIP knockdown reduced palmitic acid-induced NLRP3 inflammasome activation and lipid storage. Mechanistically, abnormal NF-κB (nuclear factor kappa B) pathway activation, increased mitochondrial reactive oxygen species, and elevated TXNIP levels led to excessive NLRP3 inflammasome activation. Our study confirms that aberrant NLRP3 inflammasome activation in cardiomyocytes worsens obesity-associated cardiomyopathy and implicates inhibition of NLRP3 inflammasome as a potent therapeutic approach for obesity cardiomyopathy.

Exercise-induced Reduction in Left Ventricular Ejection Fraction in the Absence of Coronary Artery Disease: Clinical Characteristics and Outcomes

During exercise stress echocardiography (ESE) there are patients with normal left ventricular ejection fraction (LVEF) who paradoxically develop reduced LVEF during exercise despite absence of coronary artery disease (CAD) and a significant hypertensive response. This study sought to describe the clinical features and outcomes of this population. Among ESE performed between 2003 and 2022, patients without CAD by angiogram within 90 days of ESE, resting LVEF ≥50% with a ≥5% LVEF decrease during ESE were included. Outcomes assessed were all-cause mortality, heart failure (HF) hospitalization, and atrial fibrillation (AF). Kaplan-Meier and Cox regression methods were used to analyze time-to-event outcomes. Among 213,643 ESE, 134 patients met eligibility criteria. The mean age of the population was 66±10 years, 76% were women, and 16% had AF at baseline. Mean LVEF was 58±4% at rest and 43±4% at peak stress. Stress ECG met criteria for ischemia in 14% of these patients. The 10-year estimated incidence of HF hospitalization was 17.6% (95% CI 9.0-26.2). Among the subgroup without AF at baseline, the 10-year estimated incidence of developing AF was 23.4% (95% CI 13.4-33.4). The 10-year estimated incidence of all-cause mortality was 12.9% (95% CI 5.5-20.3), with 89% of deaths occurring due to non-cardiovascular causes. Patients with exercise-induced reduction in LVEF in the absence of obstructive CAD have a high incidence of HF hospitalizations and AF. The underlying pathophysiology of this disease process needs to be further investigated.

Benefits from Implementing Low- to High-Intensity Inspiratory Muscle Training in Patients Undergoing Cardiac Surgery: A Systematic Review

Cardiac surgery procedures are among the main treatments for people with cardiovascular disease, with physiotherapy playing a vital part. Respiratory complications are common and associated with prolonged Intensive Care Unit (ICU) and hospital stay, as well as increased mortality. Inspiratory muscle training has been found to be beneficial in improving respiratory muscle function in critically ill patients and patients with heart failure. The purpose of this review is to present the results of implementing inspiratory muscle training (IMT) programs in patients before and/or after cardiac surgery. The PubMed, Embase and Science Direct databases were searched from January 2012 to August 2023. In the present review, randomized controlled clinical trials (RCTs), clinical trials and quasi-experimental studies conducted in adult patients pre and/or post cardiac surgery were included. Fifteen studies were considered eligible for inclusion in the review. The results revealed that the IMT programs varied in intensity, repetitions, and duration in all included studies. Most studies implemented the IMT after the surgery. Statistical significance between groups was noted in Maximal Inspiratory Pressure and the 6-Minute Walk Distance Test. Preoperative and postoperative programs could improve inspiratory muscle strength, pulmonary function, and functional capacity as well as decrease the length of hospital stay in patients undergoing cardiac surgery. No clear evidence emerged favoring low or higher IMT intensities. The combination of IMT with other forms of exercise might be beneficial in patients undergoing cardiac surgery. However, further RCTs are required to provide confirming evidence.

Left Atrial Appendage Closure With Catheter Ablation vs. Ablation Alone on Outcomes of Atrial Fibrillation in Heart Failure With Reduced Ejection Fraction: A Propensity Score-Matched Analysis

Left Atrial Appendage Closure With Catheter Ablation vs. Ablation Alone on Outcomes of Atrial Fibrillation in Heart Failure With Reduced Ejection Fraction: A Propensity Score-Matched Analysis

Vascular rescue–minimally invasive management of a post-spinal surgery fistulized ilio-iliac pseudoaneurysm: a case report

BackgroundAortoiliac injury after intervertebral disc surgery is an uncommon but potentially fatal complication. This case study emphasizes how crucial it is to identify this uncommon complication, which can manifest itself in a variety of ways, including leg oedema, heart failure, and deep vein thrombosis. This case is unique in that it presents with an uncommon post-spinal surgery complication of fistulized pseudoaneurysm of the common iliac artery and vein. This combination calls for an immediate diagnosis and careful care.Case presentationA 36-year-old female patient presented with progressively worsening orthopnea, accompanied by chest pain and palpitations. Her medical history revealed gradually increasing right lower limb swelling since three months, following a discectomy procedure for the management of lower back pain associated with a herniated lumbar disc at the L5-S1 level. Doppler ultrasonography demonstrated an arterialized flow within the right common iliac vein. Subsequent computed tomography angiography identified a pseudoaneurysm of the right common iliac artery, which had formed a fistulous connection to the right common iliac vein. This uncommon complication was likely attributable to prior disc surgery. The patient received endovascular intervention, which was executed in two primary stages: first, embolization of the right internal iliac artery was performed, followed by the exclusion of the arteriovenous fistula through the deployment of a covered stent graft within the right common iliac artery. The intervention successfully resolved both the pseudoaneurysm and the arteriovenous fistula.ConclusionsThis case report underscores the importance of considering vascular complications in patients presenting with unusual symptoms following intervertebral disc surgery, even after a significant time lapse. While both open surgical and endovascular approaches can yield good results in treating such complications, the endovascular method, as demonstrated in this case, is associated with minimal morbidity. This approach offers a less invasive alternative that can effectively manage complex vascular injuries resulting from disc surgery. Clinicians should be aware of this rare but serious complication to ensure timely diagnosis and appropriate management, potentially improving patient outcomes in similar cases.

Survey on blood glucose and electrolyte levels in patients with acute myocarditis treated at Bach Mai Hospital

Background and Objectives:Myocarditis is a condition characterized by inflammation of the heart muscle tissue due to various causes, with viruses being a common cause. During the progression of the disease, damage to the heart muscle can lead to acute heart failure, dangerous arrhythmias, cardiogenic shock, or even cardiac arrest, which can result in rapid death. Clinical markers such as chest pain, shortness of breath, and arrhythmias, along with diagnostic tools like electrocardiograms and cardiac ultrasounds, play a crucial role in diagnosing and predicting the disease. In addition to monitoring vital signs, tracking blood glucose and electrolyte levels is an important criterion for nurses in managing patients with acute myocarditis. This aids in making appropriate care and treatment decisions for each specific patient. The study aims to investigate blood glucose and electrolyte levels and their relationship with the severity of heart failure and ventricular arrhythmias in patients with acute myocarditis. Methods:A retrospective review was conducted on the records of 119 patients with acute myocarditis treated at Bach Mai Hospital from 2017 to 2021. Biochemical results were included in a regression model to assess their correlation with the occurrence of adverse clinical outcomes during hospitalization. Results:Among the 119 patients (66.4% male; average age 33.93 ± 15.87 years), significant electrolyte disturbances included severe hyponatremia (6.7%), severe hypokalemia (5.8%), hyperkalemia (8.1%), and blood glucose disorders (31.1%). Severe hyponatremia was found to be predictive of ventricular arrhythmias and in-hospital mortality. Severe hypokalemia was also predictive of ventricular arrhythmias and in-hospital mortality. Hyperkalemia was associated with a higher risk of ventricular arrhythmias. Patients with severe conditions requiring intensive care, such as intravenous feeding or intravenous insulin administration, demonstrated a higher risk of in-hospital mortality. Conclusion:Severe electrolyte disturbances, such as severe hyponatremia, severe hypokalemia, and hyperkalemia, have prognostic significance in patients with acute myocarditis.

Abdominal Compared With Coronary Artery Calcification and Incident Cardiovascular Events and Mortality in Black Adults.

Black adults show heightened cardiovascular risk compared with other groups despite comparable or lower coronary artery calcium (CAC) scores, indicating potential cardiovascular risk underestimation by CAC. Abdominal aortic calcification (AAC), preceding CAC, may predict cardiovascular events better in Black adults who are prone to early atherosclerotic cardiovascular disease and excess events at low CAC scores. We included 2551 participants from the JHS (Jackson Heart Study) visit 2 examination (2005-2008) without cardiovascular disease, followed through 2016. Cox regression estimated hazard ratios for incident cardiovascular events defined as a composite of myocardial infarction, stroke, heart failure, and all-cause mortality. The predictive value of CAC and AAC, when added to the American College of Cardiology/American Heart Association cardiovascular risk algorithm (pool cohort equation), was assessed. Mean age was 57±10 years; 66% were women. Over a follow-up period of 12.6 years, 287 (11.3%) cardiovascular events and 360 (14.1%) mortality cases were observed. Adjusting for demographic and clinical variables, each 2-fold increase in CAC and AAC was associated with cardiovascular events (CAC: hazard ratio, 1.10 [95% CI, 1.06-1.13]; AAC: hazard ratio, 1.10 [95% CI, 1.06-1.13]) and all-cause mortality CAC: hazard ratio, 1.04 [95% CI, 1.01-1.08]; AAC: hazard ratio, 1.05 [95% CI, 1.01-1.08]). The incremental value of CAC (0.17 [95% CI, 0.08-0.23]) and AAC (0.15 [95% CI, 0.07-0.29]) to the pool cohort equation by net reclassification index was comparable. Notably, 45% of participants with 0 CAC showed some degree of AAC. Each 2-fold increase in AAC was associated with an increased risk of cardiovascular events (hazard ratio, 1.07 [95% CI, 1.01-1.19]) but not all-cause mortality among participants with 0 CAC. AAC is comparable to CAC in predicting cardiovascular events and all-cause mortality among Black adults, potentially valuable when CAC is absent.

Integrated Assessment of Coronary Physiology Based on Coronary Angiography in Heart Transplant Patients.

Early detection of cardiac allograft vasculopathy after heart transplant (HTx) with invasive coronary angiography is challenging. The study aimed to determine if computational techniques able to assess epicardial lesions, by means of Murray's law-based quantitative flow ratio (μFR), and microvascular physiology, by means of angiography microvascular resistance (AMR), enhance risk stratification in HTx patients with nonsignificant coronary artery disease. The cohort consisted of 86 consecutive HTx patients (200 epicardial vessels) with stenosis < 50% at baseline. μFR ≤ 0.80 indicated coronary ischemia, while AMR ≥ 2.5 suggested microvascular dysfunction. Clinical events were assessed over a median follow-up of 43 months, focusing on the relationship between μFR and target vessel failure (TVF), and between AMR and heart failure (HF) hospitalizations. At baseline, mean μFR was 0.94 ± 0.08, with eight vessels (4.0%) disclosing flow-limiting lesions, while AMR was 2.4 ± 0.7, with 80 vessels/40 patients (40.0%/46.5%) having microvascular dysfunction. TVF-related segments were associated with lower mean μFR values (0.89 ± 0.14 vs. 0.95 ± 0.05; p < 0.007) compared TVF-free segments. At the receiver operating characteristic curve a μFR ≤ 0.93 demonstrated an area under the curve of 0.632 (95% CI: 0.562-0.699) in predicting TVF occurrence, showing an accuracy of 76.0%, a sensitivity of 46.9%, a specificity of 81.6%, a negative predictive value of 89.0%, and a positive predictive value of 32.6%. μFR ≤ 0.93 showed a significant interaction with TVF occurrence at 43 months (32.6% vs. 11.0%; HR: 2.96; 95% CI: 1.26-6.96; p = 0.013). Microvascular dysfunction showed a significant interaction with HF hospitalizations occurence (AMR: 2.8 ± 4.4 vs. 2.4 ± 4.5; p = 0.001; CMD: 27.5% vs. 4.3%; HR: 7.36; 95% CI: 2.45-22.07; p = 0.002). Angiography-derived epicardial and microvascular physiology computation may improve risk stratification of heart transplanted patients.

Evaluation of Modified Frailty Index for Predicting Postoperative Outcomes after Upper Extremity Replantation and Revascularization Procedures.

Upper extremity (UE) replantation and revascularization are challenging surgical procedures, with survival rates being 50 to 90%. Preoperative risk stratification is challenging yet crucial as patients with comorbid conditions face increased complications. This study assesses the predictive value of the modified 5-item frailty index (5-mFI) for postoperative complications in these procedures. A retrospective study was done using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2011-2021) for UE replantation/revascularization. The 5-mFI score assigned points for comorbidities including pulmonary disease, heart failure, diabetes, hypertension, and functional status (0-5 scale; 1 point to each). 5-mFI scores stratified patients into <2 (low-risk) or ≥2 (high-risk) categories. Of 2,305 patients, the mean age and body mass index (BMI) were 53.13 years and 28.53 kg/m2, respectively. The 5-mFI ≥2 cohort experienced higher rates of all-cause complications, systemic complications, unplanned readmissions, and return to the operating room on univariate analysis. There was no significant difference in wound complication rates. Multivariable logistic regression showed that a higher 5-mFI was significantly associated with increased risks of all-cause mild and severe systemic complications. Wound complications, length of stay over 30 days, unplanned readmission, and return to the operating room were higher in high-risk patients, however not statistically significant. 5-mFI is an effective tool for evaluating risk in UE replantation and revascularization, correlating high scores with significantly increased postoperative complications. High-risk patients with 5-mFI ≥2 also had more reoperations and readmissions. The use of 5-mFI in preoperative assessments can help personalize management, enhancing patient selection and care quality in these complex reconstructions.

Molecular Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Update from a Basic Research Perspective

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but severe condition characterized by persistent obstruction and vascular remodeling in the pulmonary arteries following an acute pulmonary embolism (APE). Although APE is a significant risk factor, up to 25% of CTEPH cases occur without a history of APE or deep vein thrombosis, complicating the understanding of its pathogenesis. Herein, we carried out a narrative review discussing the mechanisms involved in CTEPH development, including fibrotic thrombus formation, pulmonary vascular remodeling, and abnormal angiogenesis, leading to elevated pulmonary vascular resistance and right heart failure. We also outlined how the disease’s pathophysiology reveals both proximal and distal pulmonary artery obstruction, contributing to the development of pulmonary hypertension. We depicted the risk factors predicting CTEPH, including thrombotic history, hemostatic disorders, and certain medical conditions. We finally looked at the molecular mechanisms behind the role of endothelial dysfunction, gene expression alterations, and inflammatory processes in CTEPH progression and detection. Despite these insights, there is still a need for improved diagnostic tools, biomarkers, and therapeutic strategies to enhance early detection and management of CTEPH, ultimately aiming to reduce diagnostic delay and improve patient outcomes.

VDAC1-NF-κB/p65-mediated S100A16 contributes to myocardial ischemia/reperfusion injury by regulating oxidative stress and inflammatory response via Calmodulin/CaMKK2/AMPK pathway

Myocardial injury triggers intense inflammatory reactions and oxidative stress responses. S100 calcium-binding protein A16 (S100A16), a multi-functional calcium (Ca2+)-binding protein, participates in inflammatory responses and contributes to ischemia/reperfusion (I/R) injury. Nevertheless, the precise mechanism by which S100A16 operates in myocardial I/R injury remains uncertain. Cardiac I/R injury was produced by ligation/release of the left anterior descending artery, and mouse cardiac cells were subjected to hypoxia/reoxygenation (H/R) to determine the biological effects in vitro. We demonstrated that S100A16 was upregulated in the ischemic hearts and cardiac cells after I/R and H/R injury. Adenovirus-mediated S100A16 inhibition led to a considerable improvement in cardiac function with a reduced infarct size, accompanied by a reduction in cardiomyocyte apoptosis. Similar effects of S100A16 inhibition on inflammation and reactive oxygen species (ROS) production were observed in cultured cardiomyocytes. Importantly, we showed that I/R and H/R treatment upregulated the expression of voltage-dependent anion channel 1 (VDAC1), which subsequently activated NF-κB/p65 to facilitate the binding of NF-κB/p65 to the S100A16 promoter, thereby activating the transcription and expression of S100A16. Mechanically, S100A16 responded to increasing Ca2+ and interacted with calmodulin (CaM) to regulate the activation of calcium/calmodulin-dependent protein kinase 2 (CAMKK2)/AMPK pathway. In conclusion, VDAC1 sustained the NF-κB p65 pathway activation to elicit increased S100A16 expression, contributing to myocardial damage and heart failure post-I/R via the CaM/CaMKK2/AMPK pathway. This study revealed a crucial role of the VDAC1-S100A16 axis in the process of myocardial I/R injury, providing novel molecular targets for the treatment of cardiac conditions associated with I/R injury.

The Potential Contribution of MyomiRs miR-133a-3p, -133b, and -206 Dysregulation in Cardiovascular Disease Risk

Cardiovascular disease (CVD) is a major global health concern. The number of people with CVD is expected to rise due to aging populations and increasing risk factors such as obesity and diabetes. Identifying new molecular markers is crucial for early diagnosis and treatment. Among these, plasma levels of some miRNAs, specifically expressed in cardiac and skeletal muscle, known as myomiRs, have gained attention for their roles in cardiovascular health. This study analyzed the plasma levels of miR-133a-3p, -133b, and -206 in the pathogenesis of cardiovascular diseases. Using a case–control study design with patients recruited from several nursing homes from Calabria (southern Italy) characterized by different types of CVD compared with non-CVD controls, we found downregulation of miR-133a-3p in heart failure and miR-133b in stroke, along with the overall decreased expression of miR-133b and miR-206 in CVD patients, although they showed low specificity as biomarkers of CVD (as based on ROC analysis). In silico functional characterization of their targets and signaling pathways revealed their involvement in critical cardiovascular processes. Although further research is necessary to fully elucidate their mechanisms and clinical utility, the findings reported here may provide insight into the potential contribution of myomiRs in the cardiovascular injury framework, also offering indications for new research directions.

Chronic disease diagnoses and health service use among people who died of illicit drug toxicity in British Columbia, Canada.

Illicit drug toxicity (i.e., overdose) is the leading cause of death in British Columbia (BC) for people aged 10-59. Stimulants are increasingly detected among drug toxicity deaths. As stimulant useand detection in deaths rises, it is important to understand how people who die of stimulant toxicity differ from people who die of opioid toxicity. BC Coroners Service records were retrieved for all people who died of unintentional illicit drug toxicity (accidental or undetermined) between January 1, 2015, and December 31, 2019, whose coroner investigation had concluded and who had an opioid and/or stimulant detected in post-mortem toxicology and identified by the coroner as relevant to the death (N = 3788). BC Chronic Disease Registry definitions were used to identify people with chronic disease. Multinomial regression models were used to examine the relationship between chronic disease diagnoses and drug toxicity death type. Of the 3788 deaths, 11.1% (N = 422) had stimulants but not opioids deemed relevant to the cause of death (stimulant group), 26.8% (N = 1014) had opioids but not stimulants deemed relevant (opioid group), and 62.1% (N = 2352) had both opioids and stimulants deemed relevant (opioid/stimulant group). People with ischemic heart disease (1.80 (1.14-2.85)) and people with heart failure (2.29 (1.25-4.20)) had approximately twice the odds of being in the stimulant group as compared to the opioid group. Findings suggest that people with heart disease who use illicit stimulants face an elevated risk of drug toxicity death. Future research should explore this association and should identify opportunities for targeted interventions to reduce drug toxicity deaths among people with medical comorbidities.