-
Clinical Benefit of the Transthyretin Stabiliser Tafamidis in Hereditary Transthyretin Amyloid Cardiomyopathy: A Case Report.1 week agoThis case report aims to illustrate the critical importance of a standardized diagnostic approach and genotype-specific therapy in hereditary transthyretin amyloid cardiomyopathy (ATTR-CM). It highlights the clinical challenge of diagnosing ATTR-CM amidst complex comorbidities and addresses the evidence gap regarding the long-term efficacy of tafamidis for the rare and aggressive p.Val40Ile (protein-level substitution of valine to isoleucine at codon 40) mutation.
A 72-year-old East Asian man with multiple comorbidities presented with refractory heart failure. Key clinical clues included the classic "red flag" of electrocardiogram (ECG)-echocardiogram discordance (low voltage with ventricular hypertrophy). Genetic testing identified the pathogenic p.Val40Ile transthyretin (TTR) mutation.
The diagnosis was confirmed non-invasively via cardiac magnetic resonance (CMR) and technetium-99m pyrophosphate scintigraphy. Following the initiation of tafamidis, the patient's symptoms significantly improved. Over a two-year follow-up period, he sustained clinical stability with a marked reduction in heart failure-related hospitalizations.
This report provides detailed case-based evidence supporting the long-term efficacy of tafamidis in stabilizing disease and improving prognosis for patients with ATTR-CM harboring the p.Val40Ile mutation. It underscores the value of timely diagnosis, genetic subtyping, and access to targeted therapy in altering the clinical course of this aggressive genotype.Cardiovascular diseasesAccessCare/Management -
Reverse Cascade Genetic Screening for Revealing New Cases of Familial Hypercholesterolemia in Russia: Pilot Project.1 week agoReverse cascade genetic screening, following initial lipid testing, is an effective strategy for the early diagnosis of familial hypercholesterolemia (FH) and related hereditary dyslipidemias. In this study, we present the results of a pilot project in Russia.
This was a hybrid retrospective-prospective cross-sectional study. Analysis of 1897 lipid screenings of children referred to the main pediatric centers in St. Petersburg, Russia, demonstrated that 60 (3.2%) met the Simon Broome criteria for FH, defined as total cholesterol (TC) ≥6.5 mmol/L or low-density lipoprotein cholesterol (LDL-C) ≥4 mmol/L. All families were invited to undergo genetic testing, regardless of their history, with 35 (58%) families participating in the second stage of the study. Targeted sequencing was performed for children, and Sanger sequencing was performed for variant validation in children and their family members.
Sixteen children were shown to have causal variants in dyslipidemia-associated genes, including fourteen (40% of 35 tested children) with hereditary dyslipidemias: twelve FH cases (linked to LDLR and APOB genetic variants), one dysbetalipoproteinemia case (APOE), and one sitosterolemia case (ABCG8). Two children were heterozygous for sitosterolemia variants (one case with ABCG5, one case with ABCG8). Family history of FH or atherosclerotic cardiovascular disease (ASCVD) was reported in only 50% of cases, regardless of whether a causal variant was present. TC and LDL-C were higher in the causal variant-positive subgroup. Receiver operating characteristic curve analysis revealed that LDL-C >4.8 mmol/L acted as a diagnostic indicator of disease causing variant with 84% accuracy, 93% sensitivity, and 73% specificity.
Reverse cascade genetic screening following selective lipid testing in children is an effective strategy to reveal new FH and other hereditary dyslipidemia cases, helping to mitigate future ASCVD risks and early mortality.Cardiovascular diseasesAccessCare/ManagementAdvocacy -
Factors Influencing Health Behavior Adherence in Young and Middle-Aged Stroke Patients.1 week agoHealth behavior adherence (HBA) is important for effective rehabilitation and secondary prevention after stroke. Young and middle-aged patients may face particular challenges in maintaining recommended health behaviors during hospitalization because of functional impairment, cognitive deficits, pain, and competing social or occupational responsibilities. However, factors associated with HBA in this population remain insufficiently characterized, and practical tools for the early identification of patients at risk of suboptimal adherence are limited. To identify factors associated with HBA in young and middle-aged patients with stroke during hospitalization and to develop a combined predictive model for the early identification of patients with non-high adherence.
A single-center retrospective observational study was conducted, including 298 young and middle-aged stroke patients hospitalized between January 2021 and June 2024. Patients were categorized into a high-adherence group and a non-high-adherence group based on the HBA Index. Differences in demographic and functional characteristics between the groups were compared. Correlation analysis and multivariate logistic regression were performed to identify independent factors affecting HBA. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive performance of individual indicators and the combined model.
Among the 298 patients, 143 (48.0%) were classified as non-high-adherence. The high-adherence group had significantly better functional and cognitive scores, including the Barthel Index (BI), Mini-Mental State Examination (MMSE), Fugl-Meyer Assessment (FMA), and Berg Balance Scale (BBS), and experienced less pain (all p < 0.001). Adherence was positively correlated with BI, MMSE, FMA, and BBS scores, and negatively correlated with Numeric Rating Scale (NRS) pain scores. In multivariate logistic regression analysis, MMSE, NRS, educational level, and first stroke status were independently associated with non-high adherence. In the final parsimonious multivariable logistic regression model, MMSE score, NRS score, educational level, and first-stroke status were independently associated with non-high adherence. The final four-predictor model demonstrated good discrimination.
A multidimensional combined predictive model demonstrated good discrimination performance and may help to identify patients at higher risk of non-high adherence.Cardiovascular diseasesMental HealthAccessCare/ManagementAdvocacy -
Association of Short-Course Methylprednisolone Therapy With Early Composite Imaging Abnormalities in Patients With Early Neurological Deterioration After Endovascular Thrombectomy for Acute Ischemic Stroke.1 week agoEarly neurological deterioration (END) after endovascular thrombectomy (EVT) may be accompanied by heterogeneous postprocedural imaging abnormalities. We investigated the association between short-course methylprednisolone and a study-defined early composite imaging abnormality after EVT.
This single-center retrospective analysis included 297 patients with acute ischemic stroke who developed END within 72 hours after EVT (96 treated with methylprednisolone and 201 not treated). The index time was defined as completion of the post-END treatment decision, and the first intravenous methylprednisolone dose marked the onset of exposure. The first evaluable scan obtained after END confirmation but before completion of the treatment decision was designated the index scan. All evaluable scans obtained after the index time through 72 hours after EVT were reviewed. For patients who met the primary composite outcome, the endpoint scan was the first scan showing a new abnormality or progression of a preexisting abnormality that met the specified progression criteria; for patients who did not meet the primary outcome, it was the last evaluable scan within 72 hours after EVT. Multivariate logistic regression, propensity-score analyses, a restricted analysis among patients with modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b-3, and false discovery rate (FDR) correction were used.
The composite outcome occurred in 42 of 96 treated patients and 122 of 201 untreated patients (43.8% vs 60.7%; p = 0.006). After multivariate adjustment, short-course methylprednisolone was associated with lower odds of the composite outcome (adjusted odds ratio, 0.46; 95% confidence interval [CI], 0.27-0.80; p = 0.005). The results were directionally consistent among patients with mTICI grades 2b-3 (adjusted odds ratio, 0.48; 95% CI, 0.27-0.86; p = 0.013), whereas the estimate for mTICI grades 0-2a was imprecise (p = 0.699). The index-to-endpoint-scan interval, endpoint imaging modality, and post-index scan frequency were comparable between groups. After FDR correction across 17 exploratory outcomes, only new or worsening cerebral edema remained statistically significant (q = 0.034). Neither the 90-day 3-category modified Rankin Scale (mRS) distribution nor the comparison of mRS 0-2 remained statistically significant after correction. Safety estimates were imprecise.
Short-course methylprednisolone was associated with lower odds of the study-defined early post-EVT composite imaging abnormality, primarily reflecting edema-related findings. This observational association did not establish functional benefit and requires prospective confirmation.Cardiovascular diseasesAccessCare/ManagementAdvocacy -
Heart Failure: Lipid Metabolism Disorders Driving Cellular Senescence Through a Vicious Cycle, and Possible Intervention Strategies.1 week agoHeart failure (HF) is major and growing global health challenge, with lipid metabolism dysregulation recognized as a significant contributing factor. This review focuses on the emerging concept of the "metabolism-senescence axis", which plays a central role in disease development progression. Excess lipid metabolites, especially ceramides and diacylglycerols, contribute to cardiomyocyte injury through multiple mechanisms, including mitochondria dysfunction, promoting oxidative stress, and interfering with normal metabolic signals. The senescence-associated secretory phenotype (SASP) promotes a pro-senescent tissue microenvironment, thereby disrupting the normal metabolic balance and creating a vicious cycle that seriously affects heart structure and function. This review examines the molecular events underlying this process, including cellular injury, impaired fatty acid oxidation, oxidative stress, activation of the p53/p21 and p16INK4a/Rb, signaling pathways, and SASP-mediated metabolic dysfunction. We further discuss the rationale for combinatorial strategies targeting both metabolic dysfunction and cellular senescence, proposing that simultaneous intervention in these interconnected pathways may represent a promising therapeutic approach to delay the progression of HF and improve patient outcomes.Cardiovascular diseasesAccessCare/Management
-
LRP1 in Ischemic Stroke: From CNS Homeostasis to Ischemic Injury and Repair.1 week agoIschemic stroke is a leading cause of mortality and long-term disability worldwide, with complex pathophysiological mechanisms and limited therapeutic options. The identification of key molecular targets that can effectively modulate the multifaceted pathological and reparative processes underlying ischemic stroke is urgently needed. Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor widely expressed in the central nervous system (CNS), where it regulates lipid and bioenergetic metabolism, preserves blood‒brain barrier (BBB) function, modulates synaptic signaling, and supports neural stem/progenitor cell homeostasis. During cerebral ischemia, LRP1 undergoes a stage-dependent functional shift. In the acute phase, LRP1 promotes BBB disruption, tissue-type plasminogen activator (tPA)-associated hemorrhagic transformation, and early neuroinflammation, while also conferring neuroprotection by restraining inflammasome-mediated inflammatory responses and facilitating astrocyte-to-neuron mitochondrial transfer. In the recovery phase, LRP1 is involved in white matter injury and remodeling, including demyelination, remyelination, and white matter restoration. These effects are highly cell type-specific, reflecting distinct functions of LRP1 in endothelial cells, astrocytes, microglia, neutrophils, and oligodendrocyte-lineage cells. This context-dependent complexity underscores the need for a systematic review of the role of LRP1 in stroke. Here, we summarize the structural features and physiological functions of LRP1 in the CNS, discuss its roles and underlying mechanisms in ischemic stroke, and highlight the therapeutic potential and challenges of LRP1-targeted strategies for stroke intervention.Cardiovascular diseasesAccess
-
Medical Personnel Understanding Regarding Cardiac Rehabilitation Among Cardiac Patients in Bangladesh Medical University.1 week agoIn Bangladesh, Cardiovascular diseases (CVDs) impose a significant healthcare and socioeconomic burden. Cardiac rehabilitation, a proven multidisciplinary approach, enhances the well-being of Cardiovascular disease (CVD) patients. However, there may be gaps in medical personnel's understanding of this vital intervention. This study, conducted at Bangladesh Medical University (BMU), Dhaka, Bangladesh a renowned cardiac care institution in Bangladesh, seeks to evaluate and improve medical professionals' knowledge, perceptions and attitudes regarding cardiac rehabilitation to enhance patient care and outcomes. The aim of this study was to identify the key factors influencing medical personnel's understanding of cardiac rehabilitation, including their training, experience and exposure to current guidelines. This cross-sectional observational study was conducted in the Department of Cardiology of Bangladesh Medical University (BMU), Dhaka, Bangladesh during the period from August 2022 to July 2023. In total 100 medical personnel included in the study. We found that the Mean±SD of age was 33.16±7.06 and the majority (80.0%) were female, followed by 20.0% who were male and 5.0% who were physicians. We also found that the majority of medical personnel have a positive understanding of cardiac rehabilitation. Cardiac rehabilitation (CR) is underutilized in Bangladesh, including among healthcare professionals. This study aims to enhance CR awareness and integration for better patient outcomes at Bangladesh Medical University, ultimately improving cardiovascular care in Bangladesh.Cardiovascular diseasesAccessCare/ManagementAdvocacy
-
Changes in Serum Aspartate Aminotransferase in Patients with Acute Myocardial Infarction.1 week agoAcute myocardial infarction (AMI), more commonly known as heart attack is a medical emergency and the leading cause of death for both men and women all over the world. There is a correlation between changes in the serum aspartate aminotransferase with acute myocardial infarction. This study was undertaken to evaluate the changes in serum aspartate aminotransferase status in patients with acute myocardial infarction. This cross-sectional study was carried out in the Department of Biochemistry, Mymensingh Medical College, Bangladesh with the collaboration of the Department of Cardiology, Mymensingh Medical College Hospital, Mymensingh, during the period of July 2021 to June 2022. A total of 100 subjects were included in this study among them, 50 were diagnosed AMI patients denoted as case group and 50 were normal healthy individuals denoted as control group. Serum aspartate aminotransferase was determined by colorimetric method by using electrolyte analyzer for each sample. All statistical analysis was done by using SPSS (statistical package for social science) windows package version 26.0. P value <0.05 was considered significant. The mean±SD values of serum aspartate aminotransferase were 76.28±12.87 U/L and 22.58±6.24 U/L in case group and control group respectively. The analysis showed that there was highly significant increase in mean serum aspartate aminotransferase levels between two groups. This was a cross-sectional study. Analyzing the findings of the present study, highly significant increase in serum aspartate aminotransferase level was observed in AMI patients. A large-scale prospective study with the application of more sophisticated technology may be planned to find out the relationship of this biochemical variable with AMI.Cardiovascular diseasesAccessAdvocacy
-
Left Ventricular Hypertrophy and Proteinuria in Hypertensive Patient with Retinopathy in Tertiary Care Hospital.1 week agoHypertensive retinopathy almost always associated with other target organ damage. Relationship of hypertensive retinopathy with left ventricular hypertrophy (LVH) and proteinuria was inconclusive in previous studies. The objective of the study was to assess the relation of Left Ventricular Hypertrophy and Proteinuria in Hypertensive Patient with Retinopathy in Tertiary Care Hospital. This is a cross-sectional observational study and conducted at the Department of Medicine and Cardiology in Dhaka Medical College Hospital. Study period was 01 year started from July 2016 to June 2017. Total 100 hypertensive retinopathy patients were included in the study. Following informed written consent, physical examination, relevant investigations were done. In all cases, Ethical issues were maintained properly and collected data were analyzed by SPSS 20.0. Among 100 participants, mean ±SD age was 57.15±12.989 years (age range 29-85) and 61.0% were male and 39.0% were female. Mean ±SD value of systolic and diastolic blood pressure in Grade (G)-1, G-2 and G-3 hypertension were 150.8±5.4) and 94.0±2.6 mm Hg, 170.3±4.9 and 101.0±4.7 mm Hg and 188.0±7.0 and 102.6±6.5 mm Hg respectively and it is significantly associated with severity of LVH (p value <0.001 in both systolic blood pressure (SBP) and diastolic blood pressure (DBP). Proteinuria is also associated with severity of hypertension (p<0.001) but there were no association of Hypertensive retinopathy with LVH and proteinuria (p value 0.32 and 0.27 respectively). Hypertensive retinopathy is not associated with LVH and proteinuria, though further large cohort is recommended for final comment.Cardiovascular diseasesAccessAdvocacy
-
Post-Discharge Antiseizure Medication Use and Poststroke Survival: An Emulated Target Trial in Older Adults.1 week agoLevetiracetam is commonly prescribed for seizure prophylaxis after acute ischemic stroke (AIS) and often continued beyond discharge. While its short-term effectiveness for preventing poststroke seizures is established, it is unclear whether prolonged use improves survival, particularly in older adults. We estimated the effect of continued levetiracetam use on 90-day mortality among Medicare beneficiaries after AIS.
Using Traditional Medicare claims data (2008-2021), we identified beneficiaries aged ≥ 65 years hospitalized for AIS who initiated outpatient levetiracetam within 90 days of discharge. After 1 month of continued poststroke levetiracetam use (start of follow-up), we compared 90-day mortality between patients with a new levetiracetam dispensation within a 14-day grace period post-follow-up and those without one. We performed cloning, censoring, and weighting to address immortal-time bias and estimated standardized mortality risks, risk differences, and 95% confidence intervals (CIs).
Among 3212 eligible beneficiaries, 1779 (55.4%) received a new levetiracetam dispensation within the 14-day grace period. After adjustment for demographics, hospitalization characteristics, timing of initiation, and comorbidities, continued use was associated with lower 90-day mortality than discontinuation (53 vs. 62 deaths per 1000; risk difference -9 per 1000; 95% CI: -12, -5).
Among older Medicare beneficiaries who initiated levetiracetam after AIS, continued outpatient use was associated with lower short-term 90-day mortality, particularly among patients aged ≥ 75 years. These findings should not be interpreted as support for routine or indefinite continuation, because the claims-based design cannot assess seizure recurrence, functional outcomes, quality of life, treatment indication, or potential neuropsychiatric harms.Cardiovascular diseasesAccessCare/ManagementPolicyAdvocacy