Therapeutic Advances in Cardiovascular Disease最新文献

Cardiac amyloidosis (CA) is a condition caused by extracellular deposition of amyloid fibrils in the heart. It is an underdiagnosed disease entity which can present with a variety of cardiac and non-cardiac manifestations. Diagnosis usually follows an initial suspicion based on clinical evaluation or imaging findings before confirmation with subsequent imaging (echocardiography, cardiac magnetic resonance imaging, 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy) in combination with biochemical screening for monoclonal dyscrasia (serum free light chains and serum and urine electrophoresis) and/or histology (bone marrow trephine, fat or endomyocardial biopsy). More than 95% of CA can be classified as either amyloid light-chain (AL) CA or amyloid transthyretin (ATTR) CA; these two conditions have very different management strategies. AL-CA, which may be associated with multiple myeloma, can be managed with chemotherapy agents, autologous stem cell transplantation, cardiac transplant and supportive therapies. For ATTR-CA, there is increasing importance in making an early diagnosis because of novel treatments in development, which have transformed this once incurable disease to a potentially treatable disease. Timely diagnosis is crucial as there may only be a small window of opportunity where patients can benefit from treatment beyond which therapies may be less effective. Reviewing the existing patient pathway provides a basis to better understand the complexities of real-world activities which may be important to help reduce missed opportunities related to diagnosis and treatment for patients with CA. With healthcare provider interest in improving the care of patients with CA, the development of an optimal care pathway for the condition may help reduce delays in diagnosis and treatment and thus enhance patient outcomes.

Introduction: Diuretic efficiency (DE) is an independent predictor of all-cause mortality in acute heart failure (HF) at long-term follow-up. The performance of DE in advanced HF and the outpatient scenario is unclear.

Methods: Survival function analysis on a retrospective cohort of patients with advanced HF followed at the outpatient clinic of Hospital Universitario San Ignacio (Bogotá, Colombia) between 2017 and 2021. DE was calculated as the average of total diuresis in milliliters divided by the dose of IV furosemide in milligrams for each 6-h session, considering all the sessions in which the patient received levosimendan and IV furosemide. We stratified DE in high or low using the median value of the cohort as the cutoff value. The primary outcome was a composite of all-cause mortality and HF hospitalizations during a 12-month follow-up. Kaplan-Meier curves and log-rank test were used to compare patients with high and low DE.

Results: In all, 41 patients (66.5 ± 13.2 years old, 75.6% men) were included in the study, with a median DE of 24.5 mL/mg. In total, 20 patients were categorized as low and 21 as high DE. The composite outcome occurred more often in the high DE group (13 versus 5, log-rank test p = 0.0385); the all-cause mortality rate was 29.2% and was more frequent in the high DE group (11 versus 1, log-rank test p = 0.0026).

Conclusion: In patients with advanced HF on intermittent inotropic therapy, a high DE efficiency is associated with a higher risk of mortality or HF hospitalization in a 12-month follow-up period.

Background: Secundum atrial septal defect (ASD) is treated following trans-catheter closure in alternative to surgical treatment. Per-intervention selection of device size with balloon occlusive diameter (BOD) often cause tearing or enlarging, causing arrhythmias and hypotension. We assessed the suitability of percutaneous device closure for ASD using 3-dimensional transthoracic echocardiography (3DTTE).

Objectives: This study was conducted to investigate if 3DTTE could be an alternative of balloon sizing for selection of device size in atrial septal defect device closure.

Design: It was a cross-sectional comparative study.

Methods: This study was conducted at the department of Pediatric Cardiology, Bangabandhu Sheikh Mujib Medical University for a period of 2 years. Thirty-three purposively selected secundum ASD patients suitable for device closure were included in the study. Ethical permission was taken from the Institutional Review Board and written consent was taken from each patient's guardian. In this study, 3DTTE derived ASD diameter and BOD were compared with that of deployed device size using correlation analysis.

Results: Out of 33 patients, 63.6% were female and 36.4% were males had a mean age of 18.07 ± 14.58 years (range 2-55 years). Mean diameter of ASD measured by 2-dimensional (2D) and 3-dimensional (3D) echocardiography were 17.09 ± 6.08 mm and 21.30 ± 6.56 mm, respectively, yielding a significant difference (p < 0.001). 3D echocardiography derived ASDs diameter were highly correlated with device size than BOD and 2D echocardiography derived diameter (2D echocardiography: r = 0.796, p = <0.001, 3D echocardiography: r = 0.960, p = <0.001, BOD: r = 0.840, p = <0.001).

Conclusion: 3DTTE can accurately measure ASD diameter and can be used as an alternate, effective, and safe method to select device size.

Background: Despite the use of safe and effective conventional drugs, drug therapy problems (DTPs) pose a threat to the successful management of hypertension. DTPs are of a great concern in health care because of their serious consequences such as poor quality of life, increased health care costs, morbidity and mortality. However, there is no published information regarding the prevalence of DTPs and associated factors among hypertensive patients in Uganda.

Objective: The aim of the study was to determine the prevalence and factors associated with DTPs among hypertensive patients at the hypertension clinic of Mbarara Regional Referral Hospital (MRRH).

Method: A cross-sectional study was conducted at the hypertension clinic, MRRH, Uganda among 228 hypertensive patients. Data were collected from medical records using a data abstraction tool and patients were interviewed using a structured questionnaire. Data analysis was done using Statistical Package for Social Sciences (SPSS) version 22.0. Descriptive analysis was used to determine the prevalence of DTPs. Logistic regression was used to determine the association between the independent and dependent variables. Variables were considered statistically significant at p-value <0.05.

Results: A total of 178 DTPs were identified among 141 hypertensive patients. The prevalence of antihypertensive-related DTPs was 61.8% (95% confidence interval [CI]: 55.3-67.5) with an average of 1.26 ± 0.52 DTPs per patient. Out of 141 participants with DTPs, 109 (77.3%) had one DTP, 27 (19.1%) had 2 DTPs, and 5 (3.5%) had 3 DTPs. The most common types of antihypertensive-related DTPs were 'dosage too low' which accounted for 53 (29.8%), followed by 'adverse drug reactions' which accounted for 48 (27%). Uncontrolled blood pressure (BP; adjusted odds ratio [AOR]: 4.17; 95% CI: 2.33-7.45, p < 0.001) and routine laboratory test results (AOR: 1.87; 95% CI: 1.04-3.36, p = 0.036) were significantly associated with antihypertensive-related DTPs among hypertensive patients.

Conclusion: Almost two-thirds of study participants had antihypertensive-related DTPs. The most common DTPs were 'dosage too low' and 'adverse drug reactions' which both accounted for almost a third of the total DTPs each. Uncontrolled BP and routine laboratory test results were significantly associated with antihypertensive-related DTPs among the study participants. Our study emphasizes the need for improved patient care by clinical pharmacists to identify and prevent DTPs among hypertensive patients.

Background: Heart failure (HF) is the most common cardiovascular diseases and the leading cause of cardiovascular diseases related deaths. Increasing molecular targets have been discovered for HF prognosis and therapy. However, there is still an urgent need to identify novel biomarkers. Therefore, we evaluated biomarkers that might aid the diagnosis and treatment of HF.

Methods: We searched next-generation sequencing (NGS) dataset (GSE161472) and identified differentially expressed genes (DEGs) by comparing 47 HF samples and 37 normal control samples using limma in R package. Gene ontology (GO) and pathway enrichment analyses of the DEGs were performed using the g: Profiler database. The protein-protein interaction (PPI) network was plotted with Human Integrated Protein-Protein Interaction rEference (HiPPIE) and visualized using Cytoscape. Module analysis of the PPI network was done using PEWCC1. Then, miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed by Cytoscape software. Finally, we performed receiver operating characteristic (ROC) curve analysis to predict the diagnostic effectiveness of the hub genes.

Results: A total of 930 DEGs, 464 upregulated genes and 466 downregulated genes, were identified in HF. GO and REACTOME pathway enrichment results showed that DEGs mainly enriched in localization, small molecule metabolic process, SARS-CoV infections, and the citric acid tricarboxylic acid (TCA) cycle and respiratory electron transport. After combining the results of the PPI network miRNA-hub gene regulatory network and TF-hub gene regulatory network, 10 hub genes were selected, including heat shock protein 90 alpha family class A member 1 (HSP90AA1), arrestin beta 2 (ARRB2), myosin heavy chain 9 (MYH9), heat shock protein 90 alpha family class B member 1 (HSP90AB1), filamin A (FLNA), epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), cullin 4A (CUL4A), YEATS domain containing 4 (YEATS4), and lysine acetyltransferase 2B (KAT2B).

Conclusions: This discovery-driven study might be useful to provide a novel insight into the diagnosis and treatment of HF. However, more experiments are needed in the future to investigate the functional roles of these genes in HF.

Cardio-metabolic diseases are the leading causes of premature death worldwide. The conditions are together some of the most prevalent and severe multimorbidities and include conditions such as diabetes, hypertension, coronary heart disease and stroke. People with these conditions are at a higher risk of all-cause death and have a reduction in life expectancy when compared to patients without cardio-metabolic disorders. As a result of the increasing prevalence and impact of cardio-metabolic multimorbidity on disability, no healthcare system can 'treat' its way out of this pandemic. 'Treating our way out' requires the use of multiple medications which can lead to improper prescribing, insufficient compliance, overdosing or underdosing, improper drug choice, insufficient monitoring, unfavourable drug effects, and drug interactions and inappropriate wastes and costs. Therefore, individuals living with these conditions should be empowered to adopt lifestyle changes that foster independent living with their conditions. Adopting these healthy lifestyles such as smoking cessation, improving dietary habits, sleep hygiene and physical activity is a suitable adjunctive measure if not an alternative to polypharmacy in cardio-metabolic multimorbidity.

New evidence continues to accumulate regarding a significant association between excessive inflammation and dysregulated immunity (local and systemic) and the risk of cardiovascular events in different patient cohorts. Whilst research has sought to identify novel atheroprotective therapies targeting inflammation and immunity, several marketed drugs for rheumatological conditions may serve a similar purpose. One such drug, methotrexate, has been used since 1948 for treating cancer and, more recently, for a wide range of dysimmune conditions. Over the last 30 years, epidemiological and experimental studies have shown that methotrexate is independently associated with a reduced risk of cardiovascular disease, particularly in rheumatological patients, and exerts several beneficial effects on vascular homeostasis and blood pressure control. This review article discusses the current challenges with managing cardiovascular risk and the new frontiers offered by drug discovery and drug repurposing targeting inflammation and immunity with a focus on methotrexate. Specifically, the article critically appraises the results of observational, cross-sectional and intervention studies investigating the effects of methotrexate on overall cardiovascular risk and individual risk factors. It also discusses the putative molecular mechanisms underpinning the atheroprotective effects of methotrexate and the practical advantages of using methotrexate in cardiovascular prevention, and highlights future research directions in this area.

Background: Del Nido cardioplegia (DNC) is a single-dose, high potassium, low-volume cardioplegia solution that has grown in favor recently. However, the use of DNC in the Asian population may be associated with certain challenges.

Methods: Between January 2017 and April 2022, DNC was used for myocardial protection in this single-center retrospective study. In total, 5731 patients underwent open heart surgeries, where 310 patients received DNC for single or multiple procedures. A total of 307 pair of propensity-matched patients from DNC and cold blood St. Thomas cardioplegia (STC) were compared.

Results: In total, 5085 patients with STC and 310 patients with DNC from the cohort were matched, reflecting the initial group sizes before propensity matching. About 307 patient pairs were included in the final analysis after propensity matching with the interest variables. In the STC group, the requirement for an immediate postoperative intra-aortic balloon pump (IABP) was significantly higher [18 (5.9%) in DNC versus 28 (9.1%) in STC, p = 0.021]. A 30-day mortality was comparable between the DNC and STC groups (2.9% versus 3.3%, p = 1.00). Major adverse cardiac events (MACE) (2.6% versus 3.6%, p = 0.648) showed no difference between the groups. In both single and multiple procedure subgroups, there were no statistically significant differences in 30-day mortality and MACE incidences when comparing STC and DNC.

Conclusion: The use of DNC in adults is acceptable and adaptable. Comparable clinical outcomes between STC patients and DNC were revealed by our investigation. There were no appreciable differences in 30-day mortality or MACE despite the STC group having a much higher need for immediate postoperative IABP.

Background: The use of ultrasound-based methods for imaging of subclinical atherosclerosis, including measurement of carotid plaque burden (cPB), is a promising direction for further improvement of major adverse cardiac and cerebrovascular events (MACCE) prediction.

Objectives: The aim of the study was to research the prognostic values' significance of cPB indicators with regard to the short-term progression of polyvascular subclinical atherosclerosis and the long-term onset of MACCE.

Design: Single-center prospective cohort study.

Methods: The study included patients 40-64 years of age. All patients underwent duplex scanning (DS) of the carotid and lower limb arteries. The following cPB indicators were determined: carotid plaque score (cPS), maximum carotid plaque thickness (cPTmax), and carotid total plaque area (cTPA). The combined endpoint included the following components: cardiovascular death; nonfatal myocardial infarction; nonfatal stroke or transient ischemic attack (TIA); revascularization of the coronary and/or peripheral arteries.

Results: The study included 387 patients, among whom 142 (36.7%) patients underwent repeated DS after 12-24 months. The median follow-up time was 20.0 (13.0; 36.5) months. MACCE were recorded in 33 (8.52%) of patients. cTPA and cPTmax, but not cPS, were independently associated with the progression of subclinical polyvascular atherosclerosis over a period of 13.9 months of follow-up. cTPA, but not cPTmax and cPS, was independently associated with the development of MACCE over a period of 20.0 months of follow-up. Only a cTPA > 42.0 mm² proved to be an independent predictor of both the progression of subclinical polyvascular atherosclerosis and MACCE.

Conclusion: In patients from 40 to 64 years of age with various cardiovascular risks, among the indicators of the cPB, only an increase in cTPA > 42.0 mm² was shown to be independently associated with an increase in the relative risk (RR) of progression of subclinical polyvascular atherosclerosis by 2.38 (1.08-5.25) times, as well as with the development of MACCE by 3.10 (1.54-6.26) times.