scholarly journals Protection against Doxorubicin-Induced Cardiac Dysfunction Is Not Maintained Following Prolonged Autophagy Inhibition

2020 ◽  
Vol 21 (21) ◽  
pp. 8105
Author(s):  
Ryan N. Montalvo ◽  
Vivian Doerr ◽  
Oh Sung Kwon ◽  
Erin E. Talbert ◽  
Jeung-Ki Yoo ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Cardiac Dysfunction ◽  
Redox Balance ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Dominant Negative ◽  
Sprague Dawley ◽  
Autophagosome Formation ◽  
Underlying Mechanisms ◽  
Autophagy Inhibition

Doxorubicin (DOX) is a highly effective chemotherapeutic agent used in the treatment of various cancer types. Nevertheless, it is well known that DOX promotes the development of severe cardiovascular complications. Therefore, investigation into the underlying mechanisms that drive DOX-induced cardiotoxicity is necessary to develop therapeutic countermeasures. In this regard, autophagy is a complex catabolic process that is increased in the heart following DOX exposure. However, conflicting evidence exists regarding the role of autophagy dysregulation in the etiology of DOX-induced cardiac dysfunction. This study aimed to clarify the contribution of autophagy to DOX-induced cardiotoxicity by specifically inhibiting autophagosome formation using a dominant negative autophagy gene 5 (ATG5) adeno-associated virus construct (rAAV-dnATG5). Acute (2-day) and delayed (9-day) effects of DOX (20 mg/kg intraperitoneal injection (i.p.)) on the hearts of female Sprague–Dawley rats were assessed. Our data confirm established detrimental effects of DOX on left ventricular function, redox balance and mitochondrial function. Interestingly, targeted inhibition of autophagy in the heart via rAAV-dnATG5 in DOX-treated rats ameliorated the increase in mitochondrial reactive oxygen species emission and the attenuation of cardiac and mitochondrial function, but only at the acute timepoint. Deviation in the effects of autophagy inhibition at the 2- and 9-day timepoints appeared related to differences in ATG5–ATG12 conjugation, as this marker of autophagosome formation was significantly elevated 2 days following DOX exposure but returned to baseline at day 9. DOX exposure may transiently upregulate autophagy signaling in the rat heart; thus, long-term inhibition of autophagy may result in pathological consequences.

scholarly journals Autophagy inhibition enables Nrf2 to exaggerate the progression of diabetic cardiomyopathy in mice

2020 ◽  
Author(s):  
Ada Admin ◽  
Huimei Zang ◽  
Weiwei Wu ◽  
Lei Qi ◽  
Wenbin Tan ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Antioxidant Defense ◽  
Myocardial Damage ◽  
Related Factor ◽  
Nrf2 Knockout ◽  
Underlying Mechanisms ◽  
Autophagy Inhibition ◽  
And Oxidative Stress

Nuclear factor-erythroid factor 2-related factor 2 (Nrf2) may either ameliorate or worsen diabetic cardiomyopathy. However, the underlying mechanisms are poorly understood. Herein we report a novel mechanism of Nrf2-mediated myocardial damage in type 1 diabetes (T1D). Global Nrf2 knockout (Nrf2KO) hardly affected the onset of cardiac dysfunction induced by T1D but slowed down its progression in mice independent of sex. In addition, Nrf2KO inhibited cardiac pathological remodeling, apoptosis and oxidative stress associated with both onset and advancement of cardiac dysfunction in T1D. Such Nrf2-mediated progression of diabetic cardiomyopathy was confirmed by cardiomyocyte-restricted (CR) Nrf2 transgenic (Tg) approach in mice. Moreover, cardiac autophagy inhibition via CR KO of autophagy related 5 gene (CR-Atg5KO) led to early onset and accelerated development of cardiomyopathy in T1D, and CR-Atg5KO-induced adverse phenotypes were rescued by additional Nrf2KO. Mechanistically, chronic T1D leads to glucolipotoxicity inhibiting autolysosome efflux, which in turn intensifies Nrf2-driven transcription to fuel lipid peroxidation while inactivating Nrf2-mediated antioxidant defense and impairing Nrf2-coordinated iron metabolism, thereby leading to ferroptosis in cardiomyocytes. These results demonstrate that diabetes over time causes autophagy deficiency, which turns off Nrf2-mediated defense while switching on Nrf2-operated pathological program toward ferroptosis in cardiomyocytes, thereby worsening the progression of diabetic cardiomyopathy.

scholarly journals XPO1 Gene Therapy Attenuates Cardiac Dysfunction in Rats with Chronic Induced Myocardial Infarction

2019 ◽  
Vol 13 (4) ◽  
pp. 593-600
Author(s):  
María García-Manzanares ◽  
Estefanía Tarazón ◽  
Ana Ortega ◽  
Carolina Gil-Cayuela ◽  
Luis Martínez-Dolz ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Dysfunction ◽  
Cardiac Tissue ◽  
Left Ventricular ◽  
Partial Recovery ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Coronary Ligation ◽  
Transcriptomic Signature ◽  
Echocardiographic Assessment

AbstractTranscriptomic signature of XPO1 was highly expressed and inversely related to left ventricular function in ischemic cardiomyopathy patients. We hypothesized that treatment with AAV9-shXPO1 attenuates left ventricular dysfunction and remodeling in a myocardial infarction rat model. We induced myocardial infarction by coronary ligation in Sprague-Dawley rats (n = 10), which received AAV9-shXPO1 (n = 5) or placebo AAV9-scramble (n = 5) treatment. Serial echocardiographic assessment was performed throughout the study. After myocardial infarction, AAV9-shXPO1-treated rats showed partial recovery of left ventricular fractional shortening (16.8 ± 2.8 vs 24.6 ± 4.1%, P < 0.05) and a maintained left ventricular dimension (6.17 ± 0.95 vs 4.70 ± 0.93 mm, P < 0.05), which was not observed in non-treated rats. Furthermore, lower levels of EXP-1 (P < 0.05) and lower collagen fibers and fibrosis in cardiac tissue were observed. However, no differences were found in the IL-6 or TNFR1 plasma levels of the myocardium of AAV9-shXPO1 rats. AAV9-shXPO1 administration attenuates cardiac dysfunction and remodeling in rats after myocardial infarction, producing the gene silencing of XPO1.

scholarly journals Testosterone deprivation accelerates cardiac dysfunction in obese male rats

2016 ◽  
Vol 229 (3) ◽  
pp. 209-220 ◽  
Author(s):  
Wanpitak Pongkan ◽  
Hiranya Pintana ◽  
Sivaporn Sivasinprasasn ◽  
Thidarat Jaiwongkam ◽  
Siriporn C Chattipakorn ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Function ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Normal Diet ◽  
Metabolic Parameters ◽  
Male Rats ◽  
Lv Function ◽  
Insulin Resistant ◽  
Aging Men

Low testosterone level is associated with increased risks of cardiovascular diseases. As obese-insulin-resistant condition could impair cardiac function and that the incidence of obesity is increased in aging men, a condition of testosterone deprivation could aggravate the cardiac dysfunction in obese-insulin-resistant subjects. However, the mechanism underlying this adverse effect is unclear. This study investigated the effects of obesity on metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function in testosterone-deprived rats. Orchiectomized or sham-operated male Wistar rats (n=36per group) were randomly divided into groups and were given either a normal diet (ND, 19.77% of energy fat) or a high-fat diet (HFD, 57.60% of energy fat) for 12weeks. Metabolic parameters, HRV, LV function, and cardiac mitochondrial function were determined at 4, 8, and 12weeks after starting each feeding program. We found that insulin resistance was observed after 8weeks of the consumption of a HFD in both sham (HFS) and orchiectomized (HFO) rats. Neither the ND sham (NDS) group nor ND orchiectomized (NDO) rats developed insulin resistance. The development of depressed HRV, LV contractile dysfunction, and increased cardiac mitochondrial reactive oxygen species production was observed earlier in orchiectomized (NDO and HFO) rats at week 4, whereas HFS rats exhibited these impairments later at week 8. These findings suggest that testosterone deprivation accelerates the impairment of cardiac autonomic regulation and LV function via increased oxidative stress and impaired cardiac mitochondrial function in obese-orchiectomized male rats.

Absence of meal-induced insulin sensitization (AMIS) in aging rats is associated with cardiac dysfunction that is protected by antioxidants

2011 ◽  
Vol 111 (3) ◽  
pp. 704-714 ◽  
Author(s):  
Zhi Ming ◽  
Dallas J. Legare ◽  
W. Wayne Lautt
Keyword(s):  
Cardiac Dysfunction ◽  
Insulin Action ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Cardiac Performance ◽  
Sprague Dawley ◽  
Antioxidant Treatment ◽  
Aging Rats ◽  
Progressive Development

We have previously demonstrated that progressive development of absence of meal-induced insulin sensitization (AMIS) leads to postprandial hyperglycemia, compensatory hyperinsulinemia, resultant hyperlipidemia, increased oxidative stress, and obesity, progressing to syndrome X in aging rats. The present study tested the hypothesis that progressive development of AMIS in aging rats further resulted in deterioration in cardiac performance. Anesthetized male Sprague-Dawley rats were tested at 9, 26, and 52 wk to determine their dynamic response to insulin and cardiac function. Dynamic insulin sensitivity was determined before and after atropine to quantitate hepatic insulin sensitizing substance (HISS)-dependent and -independent insulin action. Cardiac performance was evaluated using a Millar pressure-volume conductance catheter system. AMIS developed with age, as demonstrated by significant decrease in HISS-dependent insulin action, and this syndrome was increased by sucrose supplementation and inhibited by the antioxidant treatment. Associated with progressive development of AMIS, aging rats showed impaired cardiac performance, including the reduction in cardiac index, heart rate, dP/d tmax, dP/d tmin, ejection fraction and decreased slope of left ventricular end-systolic pressure-volume relationship, and increased relaxation time constant of left ventricular pressure as well as increased left ventricular end-diastolic pressure. Total peripheral vascular resistance also increased with age. Sucrose supplementation and antioxidant treatment, respectively, potentiated and attenuated cardiac dysfunction associated with age. In addition, poor cardiac performance correlated closely with the development of AMIS. These results indicate that AMIS is the first metabolic defect that leads to homeostatic disturbances and dysfunctions, including cardiovascular diseases.

scholarly journals Autophagy inhibition enables Nrf2 to exaggerate the progression of diabetic cardiomyopathy in mice

2020 ◽  
Author(s):  
Ada Admin ◽  
Huimei Zang ◽  
Weiwei Wu ◽  
Lei Qi ◽  
Wenbin Tan ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Antioxidant Defense ◽  
Myocardial Damage ◽  
Related Factor ◽  
Nrf2 Knockout ◽  
Underlying Mechanisms ◽  
Autophagy Inhibition ◽  
And Oxidative Stress

Nuclear factor-erythroid factor 2-related factor 2 (Nrf2) may either ameliorate or worsen diabetic cardiomyopathy. However, the underlying mechanisms are poorly understood. Herein we report a novel mechanism of Nrf2-mediated myocardial damage in type 1 diabetes (T1D). Global Nrf2 knockout (Nrf2KO) hardly affected the onset of cardiac dysfunction induced by T1D but slowed down its progression in mice independent of sex. In addition, Nrf2KO inhibited cardiac pathological remodeling, apoptosis and oxidative stress associated with both onset and advancement of cardiac dysfunction in T1D. Such Nrf2-mediated progression of diabetic cardiomyopathy was confirmed by cardiomyocyte-restricted (CR) Nrf2 transgenic (Tg) approach in mice. Moreover, cardiac autophagy inhibition via CR KO of autophagy related 5 gene (CR-Atg5KO) led to early onset and accelerated development of cardiomyopathy in T1D, and CR-Atg5KO-induced adverse phenotypes were rescued by additional Nrf2KO. Mechanistically, chronic T1D leads to glucolipotoxicity inhibiting autolysosome efflux, which in turn intensifies Nrf2-driven transcription to fuel lipid peroxidation while inactivating Nrf2-mediated antioxidant defense and impairing Nrf2-coordinated iron metabolism, thereby leading to ferroptosis in cardiomyocytes. These results demonstrate that diabetes over time causes autophagy deficiency, which turns off Nrf2-mediated defense while switching on Nrf2-operated pathological program toward ferroptosis in cardiomyocytes, thereby worsening the progression of diabetic cardiomyopathy.

Abstract 1651: Exercise Improves Aging-associated Myocardial Insulin Resistance by Enhancing Mitochondrial Function in an eNOS Dependent Mechanism

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Qiu X Li ◽  
Quan J Zhang ◽  
Hai F Zhang ◽  
Kun R Zhang ◽  
Jia Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Mitochondrial Function ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Enos Expression ◽  
Adult Heart ◽  
Aging Heart ◽  
Myocardial Insulin Resistance

Objective . This study sought to determine whether exercise reduces aging-associated myocardial insulin resistance, with a specific focus on the role of eNOS and its relation to mitochondria. Methods . Aging male Sprague-Dawley rats (24 months) were subjected to swim training (60 min/d, 5 d/wk, 9 wk) or assigned as sedentary control. The myocardial contraction, myocardial glucose uptake, mitochondrial function, and eNOS signaling were determined. Results. Aging rats had myocardial insulin resistance as shown by decreased insulin-induced glucose uptake (0.22±0.05 μmol/min/g in aging heart vs.1.29 ± 0.13 μmol/min/g in adult heart, n=8, P <0.01) and attenuated insulin’s positive inotropic role as evidenced by reduced left ventricular developed pressure (90±12 mmHg in aging heart vs. 155±14 mmHg in adult heart, P <0.01). Mitochondrial function was decreased in aging hearts as manifested by the attenuated maximum O 2 consumption by FCCP (1.85±0.39 μmol/min/g in aging hearts vs. 3.72±0.40 μmol/min/g in adult hearts, P <0.01). This was accompanied with the reduced insulin-induced O 2 consumption (1.37±0.31 μmol/min/g in aging heart vs. 2.35±0.31 μmol/min/g in adult heart, P <0.01). In addition, eNOS expression and its phosphorylation by insulin were reduced by 1.2- and 2.3-fold in aging heart, respectively ( P <0.01). Swim training upregulated eNOS expression by 72% ( P <0.01), facilitated eNOS phosphorylation by insulin ( P <0.01), and improved myocardial insulin sensitivity as shown by enhanced glucose uptake by insulin ( P <0.01). Moreover, mitochondrial function was facilitated as manifested by the enhanced O 2 consumption by insulin ( P <0.05), and maximum O 2 consumption ( P <0.01) following swim training. Pretreatment with Cavtratin, an eNOS inhibitor, abolished exercise-improved mitochondrial response to insulin, blocked exercise-improved myocardial insulin sensitivity and the positive inotropic response to insulin in aging heart. Conclusion . These results demonstrate that impaired eNOS signaling and subsequent mitochondrial depression is a major mechanism contributes to aging-associated myocardial insulin resistance, and that exercise improves insulin sensitivity by restoring eNOS signaling and enhancing mitochondrial function.

scholarly journals Vildagliptin and caloric restriction for cardioprotection in pre-diabetic rats

2017 ◽  
Vol 232 (2) ◽  
pp. 189-204 ◽  
Author(s):  
Pongpan Tanajak ◽  
Hiranya Pintana ◽  
Natthaphat Siri-Angkul ◽  
Juthamas Khamseekaew ◽  
Nattayaporn Apaijai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Cardiac Dysfunction ◽  
Metabolic Regulation ◽  
Left Ventricular ◽  
Lv Function ◽  
Insulin Resistant

Long-term high-fat diet (HFD) consumption causes cardiac dysfunction. Although calorie restriction (CR) has been shown to be useful in obesity, we hypothesized that combined CR with dipeptidyl peptidase-4 (DPP-4) inhibitor provides greater efficacy than monotherapy in attenuating cardiac dysfunction and metabolic impairment in HFD-induced obese-insulin resistant rats. Thirty male Wistar rats were divided into 2 groups to be fed on either a normal diet (ND, n = 6) or a HFD (n = 24) for 12 weeks. Then, HFD rats were divided into 4 subgroups (n = 6/subgroup) to receive just the vehicle, CR diet (60% of mean energy intake and changed to ND), vildagliptin (3 mg/kg/day) or combined CR and vildagliptin for 4 weeks. Metabolic parameters, heart rate variability (HRV), cardiac mitochondrial function, left ventricular (LV) and fibroblast growth factor (FGF) 21 signaling pathway were determined. Rats on a HFD developed insulin and FGF21 resistance, oxidative stress, cardiac mitochondrial dysfunction and impaired LV function. Rats on CR alone showed both decreased body weight and visceral fat accumulation, whereas vildagliptin did not alter these parameters. Rats in CR, vildagliptin and CR plus vildagliptin subgroups had improved insulin sensitivity and oxidative stress. However, vildagliptin improved heart rate variability (HRV), cardiac mitochondrial function and LV function better than the CR. Chronic HFD consumption leads to obese-insulin resistance and FGF21 resistance. Although CR is effective in improving metabolic regulation, vildagliptin provides greater efficacy in preventing cardiac dysfunction by improving anti-apoptosis and FGF21 signaling pathways and attenuating cardiac mitochondrial dysfunction in obese-insulin-resistant rats.

Endurance exercise attenuates cardiotoxicity induced by androgen deprivation and doxorubicin

2014 ◽  
Vol 92 (5) ◽  
pp. 356-362 ◽  
Author(s):  
Traci L. Parry ◽  
David S. Hydock ◽  
Brock T. Jensen ◽  
Chia-Ying Lien ◽  
Carole M. Schneider ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Endurance Exercise ◽  
Cardiac Dysfunction ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Androgen Deprivation ◽  
Maximal Rate ◽  
Sprague Dawley ◽  
Developed Pressure

Doxorubicin (DOX) is associated with cardiac dysfunction and irreversible testicular damage. Androgen deprivation therapy (ADT) is administered prior to DOX treatment to preserve testicular function. However, ADT may exacerbate DOX-induced cardiac dysfunction. Exercise is cardioprotective, but the effects of exercise on cardiac function during combined ADT and DOX treatment are currently unknown. In this study, male Sprague–Dawley rats were randomly assigned to experimental groups: control (CON), ADT, DOX, or ADT+DOX. Animals received ADT or control implants on days 1 and 29 of the 56-day protocol. Animals remained sedentary (SED) or engaged in treadmill endurance exercise (TM) beginning on day 1. On day 15, the animals received DOX at 1 mg·(kg body mass)–1·d–1 by intraperitoneal injection for 10 consecutive days, or an equivalent volume of saline. On day 57, cardiac function was assessed in vivo and ex vivo. Animals treated with DOX alone, or with combined ADT+DOX, showed significant (P < 0.05) reductions in left ventricular developed pressure (–21% and –27%), maximal rate of pressure development (–29% and –32%), and maximal rate of pressure decline (25% and 31%), respectively when compared with the sedentary control animals. Endurance exercise training attenuated (P > 0.05) cardiac dysfunction associated with combined ADT+DOX treatment, indicating that exercise during simultaneous ADT+DOX treatment is cardioprotective.

Abstract 284: Ovariectomy Exacerbates Mitochondrial Dysfunction, Oxidative Stress and Fibrosis to Cause Diastolic Dysfunction

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Dale J Hamilton ◽  
Shumin Li ◽  
Aijun Zhang ◽  
Indira Vedula ◽  
Jessie A Smith ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drinking Water ◽  
Diastolic Dysfunction ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Internal Diameter ◽  
Dd Mice ◽  
Underlying Mechanisms

Heart failure with preserved ejection fraction, characterized by diastolic dysfunction (DD) is most common in post-menopausal women, suggesting a link with estrogen (E2). However, the underlying mechanisms are not well understood. In this study we tested how ovariectomy (OVX)-induced E2-deficiency exacerbates DD. Female C57BL6/J mice (12 weeks old) underwent a sham or OVX surgery, and were administered either normal drinking water or L-N G -Nitroarginine methyl ester (L-NAME, 0.3 mg/ml in 1% NaCl solution) in the drinking water and Angiotensin II (AngII, 1.2 mg/kg/day) via subcutaneous osmotic pumps for 5 weeks to induce DD. Subsets of the OVX-DD mice were treated with E2, E2-receptor (ER) α agonist PPT, ERβ agonist DPN or G-protein ER-1 agonist G1. Echocardiography revealed reduced left ventricular (LV) internal diameter, LV volume, cardiac output but increased LV posterior wall thickness in OVX-DD mice compared with sham-DD mice. However, ejection fractions and fractional shortening were normal in all groups. Doppler studies showed E/A ratios dramatically suppressed and E/e’ ratios increased in mice treated with L-NAME+AngII, with larger changes in OVX mice. Extensive fibrosis was seen in OVX-DD hearts than sham-DD hearts. ADP-supported cardiac mitochondrial function with pyruvate-malate was moderately reduced in OVX-DD mice along with greater production of reactive oxygen species. Ionoptix studies revealed delayed relaxation but maintained contraction in cardiomyocytes isolated from OVX-DD mice, similar to effects of low-dose oligomycin in control mice. These data suggest that E2 deficiency is associated with impaired mitochondrial function to cause small decreases in ATP formation, which impair diastolic relaxation but not contraction. Treatment with E2, PPT, DPN and G1 reduced E/e’ ratios in OVX-DD mice, with the greatest effects of G1. Treatment of mice with L-NAME in this model excludes the previously described action of G1 through nitric oxide. In conclusion, OVX exacerbates mitochondrial dysfunction, oxidative stress and fibrosis in non-ischemic HF, leading to exacerbated DD. These may be some of the mechanisms by which E2 protects the myocardium in females. Activation of GPER1 offers a novel therapeutic target for DD after menopause.

Abstract 15613: Evaluating the Heart Failure With Preserved Ejection Fraction (HFpEF) Phenotype Amongst Persons Living With HIV; a Miami Health System Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jelani Grant ◽  
Bertrand Ebner ◽  
Louis Vincent ◽  
Quentin Loyd ◽  
Alexis Powell ◽  
...  
Keyword(s):  
Heart Failure ◽  
System Analysis ◽  
Undetectable Viral Load ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Current Evidence ◽  
Increased Risk ◽  
Persons Living With Hiv ◽  
Underlying Mechanisms ◽  
Living With Hiv

Introduction: Current evidence suggests a 1 to 2-fold increased risk of heart failure among persons living with HIV (PWH), with possible underlying mechanisms including increased vascular stiffness, chronic inflammation and myocardial toxicity. This study evaluated the prevalence of HFpEF and differences in cardiovascular complications in PWH with and without HFpEF. Methods: Participants included 257 of 965 PWH at our Special Immunology Clinic at the Jackson Memorial and University of Miami Hospitals from 2017-19. Demographic, clinical, and laboratory information, were obtained from retrospective review of the electronic health records. HFpEF was confirmed by clinical and echocardiography findings, from which H2FpEF score was derived. Patients with an EF <50% were excluded. Results: The prevalence of HFpEF was 0.7%, while the mean H2FpEF score was 3.3±1.4. Thus, on average the cohort had an intermediate probability of HFpEF. When comparing persons with compared with those without HFpEF, mean age (56.4 vs. 52.0 years) and proportion of women (57.1 vs.45.0%) did not significantly differ. Similarly, groups did not differ on mean CD4 count (665 vs. 568 cells/uL, p=0.40), % with undetectable Viral Load (85.7% vs. 71.6%, p=0.41), or antiretroviral therapy use (100.0% vs. 92.8%, p=0.46). Of note, the prevalence of coronary artery disease (CAD) (14.3% vs. 1.6%, p=0.009), myocardial infarction (28.6 vs. 1.8%, p<0.001), abnormal stress testing (14.3% vs. 0.8%, p=0.001), PCI (14.3% vs. 0.9%, p=0.001), type II diabetes (57.1% vs. 16.0%, p=0.003), HbA1C (8.0±2.9% vs. 5.9±1.4%, p=0.004) and chronic kidney disease (57.1% vs. 10.2%, p<0.001) were higher in PWH with HFpEF. Of note, the groups had comparable mean EF (55.0 vs. 56.0%, p=0.66), diastolic dysfunction (33.3% vs. 41.9%, p=0.68), left ventricular (LV) hypertrophy (28.6% vs. 20.9%, p=0.62) and LV mass index (86.4±30.8 vs. 79.1±23.2 g/m2, p=0.34). Conclusions: The overall prevalence was similar to that reported in persons 45 years of age or more in the general population. Risk markers for atherosclerotic disease were significantly higher in PWH with HFpEF. HIV disease severity did not appear to be associated with HFpEF prevalence. Further studies evaluating the pathophysiology of HFpEF in PWH are needed.

Sign in / Sign up

Export Citation Format

Share Document