Cardiac involvement in systemic inflammatory erythematosus (SLE) is a complex condition that encompasses aspects yet to be elucidated. Besides those well recognized cardiovascular manifestations of ...SLE including coronary artery disease, pulmonary hypertension and valvular disease, the ultimate clinical consequence of these pathologies will be heart failure 1. ...cardiovascular risk factors modifications, physical exercise and perhaps revascularization of significant coronary artery disease may potentially reduce clinical heart failure. S1050-1738(17)30144-5 3 K.H. Yiu, M.Y. Mok, S. Wang, Prognostic role of coronary calcification in patients with rheumatoid arthritis and systemic lupus erythematosus, Clin Exp Rheumatol, Vol. 30, 2012, 345-350 4 E. Hachulla, X. Jais, G. Cinquetti, Pulmonary arterial hypertension associated with systemic lupus erythematosus: results from the French Pulmonary Hypertension Registry, Chest, 2017, Epub ahead of print 5 C. Huang, M. Li, Y. Liu, Baseline characteristics and risk factors of pulmonary arterial hypertension in systemic lupus erythematosus patients, Medicine (Baltimore), Vol. 95, 2016, e2761 6 G.N. Leal, K.F. Silva, C.M. França, Subclinical right ventricle systolic dysfunction in childhood-onset systemic lupus erythematosus: insights from two-dimensional speckle-tracking echocardiography, Lupus, Vol. 24, 2015, 613-620 7 O. Karadag, M. Calguneri, B. Yavuz, Clin Rheumatol, Vol. 26, 2007, 1701-1704 8 M.Y. Mok, F.P. Huang, W.K. Ip, Serum levels of IL-33 and soluble ST2 and their association with disease activity in systemic lupus erythematosus, Rheumatology (Oxford), Vol. 43, 2016, 520-527 9 B. Parker, A. Al-Husain, P. Pemberton, Suppression of inflammation reduces endothelial microparticles in active systemic lupus erythematosus, Ann Rheum Dis, Vol. 73, 2014, 1144-1150 10 P.M. Ridker, B.M. Everett, T. Thuren, CANTOS Trial Group, Antiinflammatory therapy with canakinumab for atherosclerotic disease, N Engl J Med, Vol. 377, 2017, 1119-1131
The organ protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors may be beneficial against infectious complications. This real-world study aims to compare the risk of pneumonia and ...sepsis between SGLT2 inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors in patients with type 2 diabetes.
Using a territory-wide clinical registry in Hong Kong (Clinical Data Analysis and Reporting System CDARS), we included patients initiated on SGLT2 inhibitors or DPP-4 inhibitors between January 01, 2015 and December 31, 2019 through 1:2 propensity score matching. The primary outcomes were incident events of pneumonia, sepsis and the related mortality. Cox proportional hazards analysis was used to compare the risk of incident pneumonia and sepsis for SGLT2 inhibitors versus DPP-4 inhibitors.
After propensity score matching, 10,706 new users of SGLT2 inhibitors and 18,281 new users of DPP-4 inhibitors were included. The mean age of all eligible subjects were 60 years (SD 11.07) and 61.1% were male. There were 309 pneumonia events incidence rate per 1000 person-years (IR) = 11.38 among SGLT2 inhibitors users and 961 events (IR = 20.45) among DPP-4 inhibitors users, with lower risk of pneumonia among SGLT2 inhibitors users (adjusted HR 0.63 95%CI 0.55–0.72, p<0.001). Similarly, SGLT2 inhibitors users had lower incidence of sepsis 164 (IR=6.00) vs. 610 (IR=12.88) events as well as associated risk of incident sepsis (HR 0.52 95% CI 0.44–0.62, p<0.001), compared to DPP-4 inhibitors users. Outcome analyses showed that SGLT2 inhibitors were associated with lower risk of pneumonia-related death (HR 0.41 95%CI 0.29–0.58, p<0.001), sepsis-related death (HR 0.39 95%CI 0.18–0.84, p<0.05), and infection-related death (HR 0.43 95%CI 0.32–0.57, p<0.001), compared to DPP-4 inhibitors users. Results were consistent when stratified by age, sex, pre-existing cardiovascular disease, and type of SGLT2 inhibitors.
We provide real-world evidence that irrespective of age, sex, prior-existing cardiovascular disease, or type of SGLT2 inhibitors used, patients with type 2 diabetes initiated on SGLT2 inhibitors have lower incidence of pneumonia and sepsis as well as mortality risk associated with pneumonia, sepsis, and infectious diseases, compared with those initiated on DPP-4 inhibitors.
Hypoxia/reoxygenation(H/R)-induced apoptosis of cardiomyocytes plays an important role in myocardial injury. Lycopene is a potent antioxidant carotenoid that has been shown to have protective ...properties on cardiovascular system. The aim of the present study is to investigate the potential for lycopene to protect the cardiomyocytes exposed to H/R. Moreover, the effect on mitochondrial function upon lycopene exposure was assessed.
Primary cardiomyocytes were isolated from neonatal mouse and established an in vitro model of H/R which resembles ischemia/reperfusion in vivo. The pretreatment of cardiomyocytes with 5 µM lycopene significantly reduced the extent of apoptosis detected by TUNEL assays. To further study the mechanism underlying the benefits of lycopene, interactions between lycopene and the process of mitochondria-mediated apoptosis were examined. Lycopene pretreatment of cardiomyocytes suppressed the activation of the mitochondrial permeability transition pore (mPTP) by reducing the intracellular reactive oxygen species (ROS) levels and inhibiting the increase of malondialdehyde (MDA) levels caused by H/R. Moreover, the loss of mitochondrial membrane potential, a decline in cellular ATP levels, a reduction in the amount of cytochrome c translocated to the cytoplasm and caspase-3 activation were observed in lycopene-treated cultures.
The present results suggested that lycopene possesses great pharmacological potential in protecting against H/R-induced apoptosis. Importantly, the protective effects of lycopene may be attributed to its roles in improving mitochondrial function in H/R-treated cardiomyocytes.
Abstract Background Cirrhosis has been shown to be associated with left ventricular (LV) myocardial dysfunction, but studies of right ventricular (RV) function in cirrhotic patients compared with ...controls are scarce. Limited studies have prospectively evaluated the progression of myocardial function in patients with cirrhosis and assessed changes in cardiac function following liver transplantation (LTx). So the aim of the study was to evaluate biventricular myocardial function in cirrhotic patients and its alteration with or without liver transplantation. Methods A total of 103 patients with cirrhosis (age 55 ± 7 years, male 75%) were recruited. Conventional and 2-dimensional speckle tracking echocardiography was performed to determine the presence of LV and RV (biventricular) dysfunction. For comparison, 48 matched control subjects were included. Follow-up echocardiography was performed in 41 patients following LTx and in 26 patients who did not undergo LTx. Results Patients with cirrhosis had biventricular dilatation, increased LV mass, impaired LV diastolic function, and biventricular systolic strain compared with controls. Following LTx, cirrhotic patients had reduced biventricular dilatation, a smaller LV mass, and improved biventricular systolic strain after a mean duration of 18.2 ± 6.6 months. Patients who did not undergo LTx had a further increase in LV mass but no significant change in biventricular dimensions or systolic strain (mean duration of 20.4 ± 8.3 months). Conclusions The present study demonstrates that patients with cirrhosis had biventricular dilatation and impaired biventricular systolic strain compared with controls. Following LTx, biventricular dilatation reduced and biventricular systolic strain improved. In contrast, patients who did not undergo LTx experienced a further increase in LV mass.
Background Strategies to improve long-term prediction of heart failure and death in valvular surgery are urgently needed because of an increasing number of procedures globally. This study sought to ...report the prevalence, changes, and prognostic implications of concomitant hepatorenal dysfunction and malnutrition in valvular surgery. Methods and Results In 909 patients undergoing valvular surgery, 3 groups were defined based on hepatorenal function (the modified model for end-stage liver disease excluding international normalized ratio score) and nutritional status (Controlling Nutritional Status score): normal hepatorenal function and nutrition (normal), hepatorenal dysfunction or malnutrition alone (mild), and concomitant hepatorenal dysfunction and malnutrition (severe). Overall, 32%, 46%, and 19% of patients were classified into normal, mild, and severe groups, respectively. Over a 4.1-year median follow-up, mild and severe groups incurred a higher risk of mortality (hazard ratio HR, 3.17 95% CI, 1.40-7.17 and HR, 9.30 95% CI, 4.09-21.16, respectively), cardiovascular death (subdistribution HR, 3.29 95% CI, 1.14-9.52 and subdistribution HR, 9.29 95% CI, 3.09-27.99), heart failure hospitalization (subdistribution HR, 2.11 95% CI, 1.25-3.55 and subdistribution HR, 3.55 95% CI, 2.04-6.16), and adverse outcomes (HR, 2.11 95% CI, 1.25-3.55 and HR, 3.55 95% CI, 2.04-6.16). Modified model for end-stage liver disease excluding international normalized ratio and controlling nutritional status scores improved the predictive ability of European System for Cardiac Operative Risk Evaluation (area under the curve: 0.80 versus 0.73,
<0.001) and Society of Thoracic Surgeons score (area under the curve: 0.79 versus 0.72,
=0.004) for all-cause mortality. One year following surgery (n=707), patients with persistent concomitant hepatorenal dysfunction and malnutrition (severe) experienced worse outcomes than those without. Conclusions Concomitant hepatorenal dysfunction and malnutrition was frequent and strongly linked to heart failure and mortality in valvular surgery.
Abstract
Context
Individuals with type 2 diabetes mellitus (DM) have an increased risk of pneumonia and septic shock. Traditional glucose-lowering drugs have recently been found to be associated with ...a higher risk of infections. It remains unclear whether sodium-glucose cotransporter 2 inhibitors (SGLT2is), which have pleiotropic/anti-inflammatory effects, may reduce the risk of pneumonia and septic shock in DM.
Methods
MEDLINE, Embase, and ClinicalTrials.gov were searched from inception up to May 19, 2022, for randomized, placebo-controlled trials of SGLT2i that included patients with DM and reported outcomes of interest (pneumonia and/or septic shock). Study selection, data extraction, and quality assessment (using the Cochrane Risk of Bias Assessment Tool) were conducted by independent authors. A fixed-effects model was used to pool the relative risk (RRs) and 95% CI across trials.
Results
Out of 4568 citations, 26 trials with a total of 59 264 patients (1.9% developed pneumonia and 0.2% developed septic shock) were included. Compared with placebo, SGLT2is significantly reduced the risk of pneumonia (pooled RR 0.87, 95% CI 0.78-0.98) and septic shock (pooled RR 0.65, 95% CI 0.44-0.95). There was no significant heterogeneity of effect size among trials. Subgroup analyses according to the type of SGLT2i used, baseline comorbidities, glycemic control, duration of DM, and trial follow-up showed consistent results without evidence of significant treatment-by-subgroup heterogeneity (all Pheterogeneity > .10).
Conclusion
Among DM patients, SGLT2is reduced the risk of pneumonia and septic shock compared with placebo. Our findings should be viewed as hypothesis generating, with concepts requiring validation in future studies.
To evaluate the association between prediabetes and heart failure (HF) and the association of HF with changes in glycemic status.
Patients newly diagnosed with atrial fibrillation (AF) between 2015 ...and 2018 were divided into three groups (normoglycemia, prediabetes, and type 2 diabetes) according to their baseline glycemic status. The primary outcome was incident HF. The Fine and Gray competing risks model was applied, with death defined as the competing event.
Among 17,943 patients with AF (mean age 75.5 years, 47% female), 3,711 (20.7%) had prediabetes, and 10,127 (56.4%) had diabetes at baseline. Over a median follow-up of 4.7 years, HF developed in 518 (14%) patients with normoglycemia, 646 (15.7%) with prediabetes, and 1,795 (17.7%) with diabetes. Prediabetes was associated with an increased risk of HF compared with normoglycemia (subdistribution hazard ratio SHR 1.12, 95% CI 1.03-1.22). In patients with prediabetes at baseline, 403 (11.1%) progressed to diabetes, and 311 (8.6%) reversed to normoglycemia at 2 years. Compared with remaining prediabetic, progression to diabetes was associated with an increased risk of HF (SHR 1.50, 95% CI 1.13-1.97), whereas reversion to normoglycemia was associated with a decreased risk (SHR 0.61, 95% CI 0.42-0.94).
Prediabetes was associated with an increased risk of HF in patients with AF. Compared with patients who remained prediabetic, those who progressed to diabetes at 2 years experienced an increased risk of HF, whereas those who reversed to normoglycemia incurred a lower risk of HF.
Vitamin D deficiency is common among patients with type 2 diabetes and is associated with endothelial dysfunction and depletion of circulating endothelial progenitor cells.
Context:
Vitamin D (Vit-D) ...deficiency is associated with type 2 diabetes mellitus (DM) and endothelial dysfunction. The relationship of Vit-D deficiency with circulating endothelial progenitor cells and endothelial dysfunction in type 2 DM patients nonetheless remains unclear.
Objective:
We aimed to investigate the cross-sectional association of Vit-D status with brachial flow-mediated dilation (FMD) and circulating endothelial progenitor cell (EPC) numbers in type 2 DM patients.
Design, Setting, and Participants:
We conducted a cross-sectional study of 280 patients (59% male, aged 68 ± 10 yr) with type 2 DM recruited in outpatient clinics during the winter period.
Main Outcome Measure:
We measured serum 25-hydroxyvitamin D 25(OH)D by an ELISA kit, circulating CD34+/kinase insert domain-containing receptor (KDR)+ and CD133+/KDR+ EPCs by flow cytometry and brachial artery FMD by vascular ultrasound, respectively.
Results:
The mean serum 25(OH)D concentration was 25.00 ± 9.17 ng/ml, and 34.3% of patients had Vit-D deficiency 25(OH)D < 20 ng/ml. Serum 25(OH)D concentration had a significant correlation with hemoglobin A1c level B = −0.018, 95% confidence interval (CI) −0.035 to −0.002, P = 0.032. Patients with Vit-D deficiency status had significantly lower brachial FMD (mean difference −1.43%, 95% CI −2.31 to −0.55, P = 0.001) and CD133+/KDR+EPC counts (mean difference −0.12%, 95% CI −0.21 to −0.019, P = 0.022) than those with sufficient Vit-D status after adjustment for age, sex, and cardiovascular risk factors, including hemoglobin A1c levels.
Conclusions:
Our results demonstrate that serum 25(OH)D status was significantly associated with brachial artery FMD and circulating CD133+/KDR+EPCs. This suggests that Vit-D deficiency might contribute to depletion of EPCs and endothelial dysfunction in patients with type 2 DM.
Introduction:
Emerging data have suggested that right ventricular (RV) apical pacing results in progressive left ventricular (LV) dysfunction and contributes to the development of heart failure (HF). ...This study aimed to investigate the prevalence and clinical predictors for the development of new‐onset HF after long‐term RV apical pacing in patients with acquired atrioventricular (AV) block who require permanent pacing.
Methods:
We studied the clinical outcomes after long‐term RV apical pacing for acquired AV block in 304 patients without a prior history of HF. All patients had >90% ventricular pacing as determined by device diagnostic data.
Results:
After a median follow‐up of 7.8 years, 79 patients (26.0%) developed new‐onset HF after RV apical pacing. Univariate Cox‐regression analysis revealed that older age at the time of pacemaker implantation (P < 0.001), the presence of coronary artery disease (CAD) (P < 0.001) or atrial fibrillation (P = 0.03), VVI pacemaker (P < 0.001), wider paced QRS duration (P < 0.001), and new‐onset myocardial infarction (P < 0.001) were predictors for HF. Multivariate analysis revealed that older age at implantation (Hazard ratio HR 1.06, 95% confidential interval CI 1.04–1.09, P < 0.001), CAD (HR 1.98, 95% CI 1.12–3.50, P < 0.05), and a wider paced QRS duration (HR 1.27 for each 10 ms increment, 95% CI 1.11–1.45, P = 0.001) were independent predictors of HF. Furthermore, cardiovascular mortality was significantly increased in those with HF (36.7% vs. 2.7%, P < 0.001).
Conclusions:
After a median follow‐up of 7.8 years, permanent RV apical pacing was associated with HF in 26% of patients. Elderly age at the time of implant, a wider paced QRS duration and the presence of CAD independently predicted new‐onset HF. More importantly, HF after RV apical pacing was associated with a higher cardiovascular mortality.
The characteristics of infective endocarditis (IE) in Asians are poorly understood. Therefore, we aim to describe the epidemiological trends and clinical features of IE in Hong Kong.
All patients ...with incident IE from 2002–2019 in a territory-wide clinical database in Hong Kong were identified. We studied the age- and sex-adjusted and one-year mortality of IE between 2002 and 2019 and identified significant contributors to 1-year all-cause death using the attributable fraction. We used propensity score and inverse propensity of treatment weighting to study the association of surgery with mortality.
A total of 5139 patients (60.4 ± 18.2years, 37% women) were included. The overall incidence of IE was 4.9 per 100,000 person-year, which did not change over time (P = 0.17). Patients in 2019 were older and more comorbid than those in 2002. The one-year crude mortality rate was 30% in 2002, which did not change significantly over time (P = 0.10). Between 2002 and 2019, the rate of surgery increased and was associated with a 51% risk reduction in 1-year all-cause mortality (Hazard Ratio 0.49 0.28–0.87, P = 0.015). Advanced age (attributable fraction 19%) and comorbidities (attributable fraction 15%) were significant contributors to death.
The incidence of IE in Hong Kong did not change between 2002 and 2019. Patients with IE in 2019 were older and had more comorbidities than those in 2002. Mortality of IE remains persistently high in Hong Kong. Together, these data can guide public health strategies to improve the outcomes of patients with IE.
This work was supported by Sanming Project of Medicine in Shenzhen, China No. SZSM201911020 and HKU-SZH Fund for Shenzhen Key Medical Discipline No. SZXK2020081.
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