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British Journal of Pharmacology Jul 2024Pulmonary hypertension (PH) results from pulmonary vasculopathy, initially leading to a compensatory right ventricular (RV) hypertrophy, and eventually to RV failure....
BACKGROUND AND PURPOSE
Pulmonary hypertension (PH) results from pulmonary vasculopathy, initially leading to a compensatory right ventricular (RV) hypertrophy, and eventually to RV failure. Hypoxia can trigger both pulmonary vasculopathy and RV failure. Therefore, we tested if myo-inositol trispyrophosphate (ITPP), which facilitates oxygen dissociation from haemoglobin, can relieve pulmonary vasculopathy and RV hypoxia, and eventually prevent RV failure and mortality in the rat model of monocrotaline-induced PH.
EXPERIMENTAL APPROACH
Rats were injected with monocrotaline (PH) or saline (control) and received ITPP or placebo for 5 weeks. Serial echocardiograms were obtained to monitor the disease, pressure-volume loops were recorded and evaluated, myocardial pO was measured using a fluorescent probe, and histological and molecular analyses were conducted at the conclusion of the experiment.
KEY RESULTS AND CONCLUSIONS
ITPP reduced PH-related mortality. It had no effect on progressive increase in pulmonary vascular resistance, yet significantly relieved intramyocardial RV hypoxia, which was associated with improvement of RV function and reduction of RV wall stress. ITPP also tended to prevent increased hypoxia inducible factor-1α expression in RV cardiac myocytes but did not affect RV capillary density.
IMPLICATIONS
Our study suggests that strategies aimed at increasing oxygen delivery to hypoxic RV in PH could potentially be used as adjuncts to other therapies that target pulmonary vessels, thus increasing the ability of the RV to withstand increased afterload and reducing mortality. ITPP may be one such potential therapy.
PubMed: 38952183
DOI: 10.1111/bph.16482 -
Cardiology Jul 2024The prevalence of atrial fibrillation (AF) increases with age. Although most AF cases are caused by irregular electrical impulses near the pulmonary vein, not all...
INTRODUCTION
The prevalence of atrial fibrillation (AF) increases with age. Although most AF cases are caused by irregular electrical impulses near the pulmonary vein, not all elderly individuals develop AF. Moreover, risk factors such as hypertension and diabetes do not always lead to AF, even in severe conditions such as pneumonia. We aimed to examine iron kinetics, including ferritin, in patients with AF and individuals in normal sinus rhythm (NSR) using peripheral blood samples.
METHODS
This case-control study included 178atients who visited the outpatient clinic of a cardiovascular and arrhythmia specialist at the National Center for Geriatrics and Gerontology between August and October 2023. Patients with missing iron-related blood tests and those with pacemaker implantation were excluded. Iron parameters (ferritin, free iron, transferrin saturation) were compared between AF (n = 53) and NSR (n = 125) groups.
RESULTS
The AF group had higher Log brain natriuretic peptide (BNP) levels, indicating increased cardiac load (AF 2.18 vs NSR 1.53). However, there were no significant differences in iron parameters between the AF and NSR groups. After matching for age, sex, and coronary artery disease, the AF group showed an increasing trend in ferritin and a decreasing trend in free iron with BNP elevation, suggesting chronic inflammation. In contrast, the NSR group showed no significant changes in iron parameters with BNP elevation.
CONCLUSION
Patients with AF are more likely to have elevated ferritin levels and decreased free iron levels during cardiac overload. Thus, they are more likely to present with chronic inflammation associated with cardiac overload in AF. Future studies should investigate the mechanisms underlying this phenomenon and its implications for AF treatment.
PubMed: 38952114
DOI: 10.1159/000540095 -
Diabetes, Obesity & Metabolism Jul 2024Prospective studies suggest that sleep-disordered breathing enhances the risk of diabetes. However, it remains unclear whether diabetes could worsen sleep-disordered...
AIM
Prospective studies suggest that sleep-disordered breathing enhances the risk of diabetes. However, it remains unclear whether diabetes could worsen sleep-disordered breathing.
METHODS
The participants from Sleep Heart Health Study underwent two polysomnograms at a 5-year interval. The relationship of baseline diabetes to change in the apnoea-hypopnoea index (AHI) was examined based on general linear models, adjusting for demographics, lifestyles, history of hypertension, pulmonary function, length of follow-up and baseline AHI.
RESULTS
In total, 161 of the 2603 participants were diagnosed with diabetes at the first polysomnograms. Compared with participants without diabetes, those with diabetes had a higher baseline and larger increases in follow-up AHI and obstructive apnoea index (oAI). Diabetes increased 2.52 events per hour (95% confidence interval 0.45-4.59; p = .017) for AHI change and 1.13 events per hour (95% confidence interval 0.04-2.23; p = .042) for oAI change, respectively. In addition, subgroup analysis suggested that the association was consistent across baseline obstructive sleep apnoea severity and body mass index groups.
CONCLUSIONS
Baseline diabetes was associated with worsening sleep-disordered breathing over 5 years, which mainly increased the change in AHI and oAI.
PubMed: 38951866
DOI: 10.1111/dom.15742 -
Zhonghua Nei Ke Za Zhi Jul 2024
Review
Topics: Humans; Early Diagnosis; Neoplasms; Vascular Diseases; Hypertension, Pulmonary
PubMed: 38951098
DOI: 10.3760/cma.j.cn112138-20231031-00266 -
The Journal of Rheumatology Jul 2024Systemic sclerosis sine scleroderma (ssSSc), formally described in 1962, is a subset of SSc which, unlike limited (lcSSc) and diffuse cutaneous (dcSSc) forms, lacks skin...
OBJECTIVE
Systemic sclerosis sine scleroderma (ssSSc), formally described in 1962, is a subset of SSc which, unlike limited (lcSSc) and diffuse cutaneous (dcSSc) forms, lacks skin fibrosis. According to the 2013 ACR/EULAR criteria, SSc can be diagnosed in the absence of skin thickening, even if this is expected to develop later in disease course. Driven by a fatal case of ssSSc with cardiac involvement, we analysed published data on ssSSc prevalence and severity.
METHODS
A systematic literature review and qualitative synthesis of SSc cohorts with data on ssSSc was performed.
RESULTS
Thirty-five studies on a total of 25,455 SSc patients published between 1976 and 2023 were identified. The mean prevalence of ssSSc, albeit using different definitions, was almost 10% (range 0-23%), with the largest study reporting a cross-sectional prevalence of 13%. In 5 studies with a follow-up period of up to 9 years, reclassification of ssSSc into lcSSc or dcSSc ranged from 0% to 28%. Interstitial lung disease, pulmonary arterial hypertension, scleroderma renal crisis, and cardiac diastolic dysfunction were present in 46% (range 9.3-59.1%), 15% (range 5.9-24.6%), 5% (range 1.6-24.6%), and 26.5% (range 1.8-40.7%) of ssSSc patients, respectively. Survival across studies was comparable to lcSSc and better than dcSSc.
CONCLUSION
Published data on ssSSc vary widely regarding prevalence, clinical expression and prognosis partly due to underdiagnosis and misclassification. Although classification criteria should not impact appropriate management of patients, updated ssSSc subclassification criteria, which will take into account time from disease onset, should be considered.
PubMed: 38950948
DOI: 10.3899/jrheum.2023-1113 -
PLoS Medicine Jul 2024Preclinical animal studies have suggested that myeloid cell-synthesized coagulation factor X dampens antitumor immunity and that rivaroxaban, a direct factor Xa...
BACKGROUND
Preclinical animal studies have suggested that myeloid cell-synthesized coagulation factor X dampens antitumor immunity and that rivaroxaban, a direct factor Xa inhibitor, can be used to promote tumor immunity. This study was aimed at assessing whether patients with atrial fibrillation taking direct factor Xa inhibitors have lower risk of cancer and cancer-related mortality than patients taking the direct thrombin inhibitor dabigatran.
METHODS AND FINDINGS
This nationwide population-based cohort study in Denmark included adult patients with atrial fibrillation and without a history of cancer, who started taking a factor Xa inhibitor or dabigatran between 2011 and 2015. Data on medical history, outcomes, and drug use were acquired through Danish healthcare registries. The primary outcome was any cancer. Secondary outcomes were cancer-related mortality and all-cause mortality. Outcome events were assessed during 5 years of follow-up in an intention-to-treat analysis. The propensity score-based inverse probability of treatment weighting was used to compute cumulative incidence and subdistribution hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs), with death as a competing event. Propensity scores were estimated using logistic regression and including in the model sex, age group at index date, comorbidities, and use of comedications. A total of 11,742 patients with atrial fibrillation starting a factor Xa inhibitor and 11,970 patients starting dabigatran were included. Mean age was 75.2 years (standard deviation [SD] 11.2) in the factor Xa cohort and 71.7 years (SD 11.1) in the dabigatran cohort. On the basis of the propensity score-weighted models, after 5 years of follow-up, no substantial difference in the cumulative incidence of cancer was observed between the factor Xa inhibitor (2,157/23,711; 9.11%, 95% CI [8.61%,9.63%]) and dabigatran (2,294/23,715; 9.68%, 95% CI [9.14%,10.25%]) groups (SHR 0.94, 95% CI [0.89,1.00], P value 0.0357). We observed no difference in cancer-related mortality (factor Xa inhibitors cohort 1,028/23,711; 4.33%, 95% CI [4.02%,4.68%]. Dabigatran cohort 1,001/23,715; 4.22%, 95% CI [3.83%,4.66%]; SHR 1.03, 95% CI [0.94,1.12]), but all-cause mortality was higher in the factor Xa inhibitor cohort (factor Xa inhibitors cohort 7,416/23,711; 31.31%, 95% CI [30.37%,32.29%]. Dabigatran cohort 6,531/23,715; 27.56%, 95% CI [26.69%,28.45%]; HR 1.17, 95% CI [1.13,1.21]). The main limitations of the study were the possibility of residual confounding and the short follow-up period.
CONCLUSIONS
In this population based cohort study, factor Xa inhibitor use was not associated with an overall lower incidence of cancer or cancer-related mortality when compared to dabigatran. We did observe an increase in all-cause mortality in the factor Xa inhibitor cohort.
PubMed: 38950074
DOI: 10.1371/journal.pmed.1004400 -
Journal of Family Medicine and Primary... May 2024Evaluations have shown that the severity of pulmonary involvement is very important in the mortality rate of patients with coronavirus disease 2019 (COVID-19). The...
BACKGROUND
Evaluations have shown that the severity of pulmonary involvement is very important in the mortality rate of patients with coronavirus disease 2019 (COVID-19). The purpose of this study was to evaluate the value of chest CT severity score in assessment of COVID-19 severity and short-term prognosis.
MATERIALS AND METHODS
This study was a cross-sectional study with a sample size of 197 patients, including all patients admitted to Rasoul Akram Hospital, with positive polymerase chain reaction, to investigate the relationship between computed tomography (CT) severity score and mortality. The demographic data and CT scan findings (including the pattern, side, and distribution of involvement), co-morbidities, and lab data were collected. Finally, gathered data were analyzed by SPSS-26.
RESULTS
119 (60.4%) patients were male, and 78 (39.6%) were female. The mean age was 58.58 ± 17.3 years. Totally, 61 patients died; of those, 41 (67.2%) were admitted to the intensive care unit (ICU), so there was a significant relation between death and ICU admission ( value = 0.000). Diabetes was the most common co-morbidity, followed by hypertension and IHD. There was no significant relation between co-morbidities and death ( value = 0.13). The most common patterns of CTs were interlobular septal thickening and ground glass opacities, and a higher CT severity score was in the second week from the onset of symptoms, which was associated with more mortality ( value < 0.05).
CONCLUSION
Our study showed that a patient with a higher CT severity score of the second week had a higher risk of mortality. Also, association of the CT severity score, laboratory data, and symptoms could be applicable in predicting the patient's condition.
PubMed: 38948629
DOI: 10.4103/jfmpc.jfmpc_414_23 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Atrial fibrillation (AF) is a disease of high heterogeneity, and the association between AF phenotypes and the outcome of different catheter ablation strategies remains...
OBJECTIVE
Atrial fibrillation (AF) is a disease of high heterogeneity, and the association between AF phenotypes and the outcome of different catheter ablation strategies remains unclear. Conventional classification of AF (e.g. according to duration, atrial size, and thromboembolism risk) fails to provide reference for the optimal stratification of the prognostic risks or to guide individualized treatment plan. In recent years, research on machine learning has found that cluster analysis, an unsupervised data-driven approach, can uncover the intrinsic structure of data and identify clusters of patients with pathophysiological similarity. It has been demonstrated that cluster analysis helps improve the characterization of AF phenotypes and provide valuable prognostic information. In our cohort of AF inpatients undergoing radiofrequency catheter ablation, we used unsupervised cluster analysis to identify patient subgroups, to compare them with previous studies, and to evaluate their association with different suitable ablation patterns and outcomes.
METHODS
The participants were AF patients undergoing radiofrequency catheter ablation at West China Hospital between October 2015 and December 2017. All participants were aged 18 years or older. They underwent radiofrequency catheter ablation during their hospitalization. They completed the follow-up process under explicit informed consent. Patients with AF of a reversible cause, severe mitral stenosis or prosthetic heart valve, congenital heart disease, new-onset acute coronary syndrome within three months prior to the surgery, or a life expectancy less than 12 months were excluded according to the exclusion criteria. The cohort consisted of 1102 participants with paroxysmal or persistent/long-standing persistent AF. Data on 59 variables representing demographics, AF type, comorbidities, therapeutic history, vital signs, electrocardiographic and echocardiographic findings, and laboratory findings were collected. Overall, data for the variables were rarely missing (<5%), and multiple imputation was used for correction of missing data. Follow-up surveys were conducted through outpatient clinic visits or by telephone. Patients were scheduled for follow-up with 12-lead resting electrocardiography and 24-hours Holter monitoring at 3 months and 6 months after the ablation procedure. Early ablation success was defined as the absence of documented AF, atrial flutter, or atrial tachycardia >30 seconds at 6-month follow-up. Hierarchical clustering was performed on the 59 baseline variables. All characteristic variables were standardized to have a mean of zero and a standard deviation of one. Initially, each patient was regarded as a separate cluster, and the distance between these clusters was calculated. Then, the Ward minimum variance method of clustering was used to merge the pair of clusters with the minimum total variance. This process continued until all patients formed one whole cluster. The "NbClust" package in R software, capable of calculating various statistical indices, including pseudo t index, cubic clustering criterion, silhouette index etc, was applied to determine the optimal number of clusters. The most frequently chosen number of clusters by these indices was selected. A heatmap was generated to illustrate the clinical features of clusters, while a tree diagram was used to depict the clustering process and the heterogeneity among clusters. Ablation strategies were compared within each cluster regarding ablation efficacy.
RESULTS
Five statistically driven clusters were identified: 1) the younger age cluster (=404), characterized by the lowest prevalence of cardiovascular and cerebrovascular comorbidities but the highest prevalence of obstructive sleep apnea syndrome (14.4%); 2) a cluster of elderly adults with chronic diseases (=438), the largest cluster, showing relatively higher rates of hypertension, diabetes, stroke, and chronic obstructive pulmonary disease; 3) a cluster with high prevalence of sinus node dysfunction (=160), with patients showing the highest prevalence of sick sinus syndrome and pacemaker implantation; 4) the heart failure cluster (=80), with the highest prevalence of heart failure (58.8%) and persistent/long-standing persistent AF (73.7%); 5) prior coronary artery revascularization cluster (=20), with patients of the most advanced age (median: 69.0 years old) and predominantly male patients, all of whom had prior myocardial infarction and coronary artery revascularization. Patients in cluster 2 achieved higher early ablation success with pulmonary veins isolation alone compared to extensive ablation strategies (79.6% vs. 66.5%; odds ratio [OR]=1.97, 95% confidence interval [CI]: 1.28-3.03). Although extensive ablation strategies had a slightly higher success rate in the heart failure group, the difference was not statistically significant.
CONCLUSIONS
This study provided a unique classification of AF patients undergoing catheter ablation by cluster analysis. Age, chronic disease, sinus node dysfunction, heart failure and history of coronary artery revascularization contributed to the formation of the five clinically relevant subtypes. These subtypes showed differences in ablation success rates, highlighting the potential of cluster analysis in guiding individualized risk stratification and treatment decisions for AF patients.
Topics: Humans; Atrial Fibrillation; Catheter Ablation; Female; Male; Cluster Analysis; Treatment Outcome; Middle Aged; China; Aged
PubMed: 38948279
DOI: 10.12182/20240560101 -
Cancer Innovation Jun 2024Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular... (Review)
Review
Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular disease. Recent studies have focused on the crucial role of HDAC6 in regulating cardiovascular diseases such as atherosclerosis, myocardial infarction, myocardial hypertrophy, myocardial fibrosis, hypertension, pulmonary hypertension, and arrhythmia. Here, we review the association between HDAC6 and cardiovascular disease, the research progress of HDAC6 inhibitors in the treatment of cardiovascular disease, and discuss the feasibility of combining HDAC6 inhibitors with other therapeutic agents to treat cardiovascular disease.
PubMed: 38947757
DOI: 10.1002/cai2.114 -
Cureus May 2024Carcinoid syndrome is a rare condition resulting from neuroendocrine tumors (NETs) that secrete vasoactive substances like serotonin. This report describes the case of a...
Carcinoid syndrome is a rare condition resulting from neuroendocrine tumors (NETs) that secrete vasoactive substances like serotonin. This report describes the case of a 61-year-old man with a history of chronic obstructive pulmonary disease (COPD) and hypertension who presented with new-onset angioedema, loss of consciousness, and a fall. He had been treated for COPD exacerbations during ER visits without improvement and was unaware of a prior mesenteric carcinoid tumor diagnosis from 2012. The next emergency evaluation revealed significant airway and facial edema necessitating intubation. Imaging and biopsy identified a well-differentiated grade 1 NET with extensive liver metastases. Laboratory tests showed elevated levels of serum serotonin, chromogranin A, and 24-hour urine 5-hydroxyindoleacetic acid (5-HIAA). Post-discharge, a PET scan confirmed metastatic lesions primarily in the liver and small bowel, with an unresectable mesenteric mass. The patient was treated with lanreotide and became symptom-free. This case underscores the need to consider carcinoid syndrome in patients with COPD presenting with unexplained respiratory symptoms, as timely diagnosis and treatment can significantly enhance patient outcomes.
PubMed: 38947683
DOI: 10.7759/cureus.61321