Could SGLT2 Inhibitors Improve Exercise Intolerance in Chronic Heart Failure?

Despite the constant improvement of therapeutical options, heart failure (HF) remains associated with high mortality and morbidity. While new developments in guideline-recommended therapies can prolong survival and postpone HF hospitalizations, impaired exercise capacity remains one of the most debilitating symptoms of HF. Exercise intolerance in HF is multifactorial in origin, as the underlying cardiovascular pathology and reactive changes in skeletal muscle composition and metabolism both contribute. Recently, sodium-related glucose transporter 2 (SGLT2) inhibitors were found to improve cardiovascular outcomes significantly. Whilst much effort has been devoted to untangling the mechanisms responsible for these cardiovascular benefits of SGLT2 inhibitors, little is known about the effect of SGLT2 inhibitors on exercise performance in HF. This review provides an overview of the pathophysiological mechanisms that are responsible for exercise intolerance in HF, elaborates on the potential SGLT2-inhibitor-mediated effects on these phenomena, and provides an up-to-date overview of existing studies on the effect of SGLT2 inhibitors on clinical outcome parameters that are relevant to the assessment of exercise capacity. Finally, current gaps in the evidence and potential future perspectives on the effects of SGLT2 inhibitors on exercise intolerance in chronic HF are discussed

The value of echocardiographic measurement of epicardial adipose tissue in heart failure patients

AIMS: Epicardial adipose tissue (EAT) is increasingly recognized as an important factor in the pathophysiology of heart failure (HF). Cardiac magnetic resonance (CMR) imaging is the gold‐standard imaging modality to evaluate EAT size, but in contrast to echocardiography, CMR is costly and not widely available. We investigated EAT thickness on echocardiography in relation to EAT volume on CMR, and we assessed the agreement between observers for measuring echocardiographic EAT. METHODS AND RESULTS: Patients with HF and left ventricular ejection fraction >40% were enrolled. All patients underwent CMR imaging and transthoracic‐echocardiography. EAT volume was quantified on CMR short‐axis cine‐stacks. Echocardiographic EAT thickness was measured on parasternal long‐axis and short‐axis views. Linear regression analyses were used to assess the association between EAT volume on CMR and EAT thickness on echocardiography. Intraclass correlation coefficient (ICC) was used to assess the interobserver agreement as well as the intraobserver agreement. EAT on CMR and echocardiography was evaluated in 117 patients (mean age 71 ± 10 years, 49% women and mean left ventricular ejection fraction 54 ± 7%). Mean EAT volume on CMR was 202 ± 64 mL and ranged from 80 to 373 mL. Mean EAT thickness on echocardiography was 3.8 ± 1.5 mm and ranged from 1.7 to 10.2 mm. EAT volume on CMR and EAT thickness on echocardiography were significantly correlated (junior‐observer: r = 0.62, P < 0.001, senior‐observer: r = 0.33, P < 0.001), and up to one‐third of the variance in EAT volume was explained by EAT thickness (R (2) = 0.38, P < 0.001). The interobserver agreement between junior and senior observers for measuring echocardiographic EAT was modest [ICC, 0.65 (95% confidence interval (CI) 0.47–0.77], whereas the intraobserver agreement was good (ICC 0.98, 95% CI 0.84–0.99). CONCLUSIONS: There was a modest correlation between EAT volume on CMR and EAT thickness on echocardiography. Limited agreement between junior and senior observers for measuring echocardiographic EAT was observed. EAT thickness on echocardiography is limited in estimating EAT volume

SGLT2 Inhibitors and Ketone Metabolism in Heart Failure

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as powerful drugs that can be used to treat heart failure (HF) patients, both with preserved and reduced ejection fraction and in the presence or absence of type 2 diabetes. While the mechanisms underlying the salutary effects of SGLT2 inhibitors have not been fully elucidated, there is clear evidence for a beneficial metabolic effect of these drugs. In this review, we discuss the effects of SGLT2 inhibitors on cardiac energy provision secondary to ketone bodies, pathological ventricular remodeling, and inflammation in patients with HF. While the specific contribution of ketone bodies to the pleiotropic cardiovascular benefits of SGLT2 inhibitors requires further clarification, ketone bodies themselves may also be used as a therapy for HF

Tomography and Prognostic Indices in the State of the Art of Evaluation in Hospitalized Patients with COVID-19 Pneumonia

Evaluation in medical emergencies of COVID-19 patients represents a challenge to regulate preventive and timely management. There are key imaging and laboratory tools to classify the severity. The aim of the study was to evaluate the chest CT score performance and prognostic indices in COVID-19 patients to predict the progression to critical illness. This was a retrospective study between run between April and December 2020, in which 109 patients were included. Patients of any age and gender and who required hospitalization due to a confirmed COVID-19 diagnosis by RT-PCR and chest CT and laboratory were analyzed. In 75% of them, there was at least one comorbidity, and 30% developed critical illness, and the average mortality was 10%. In 49.5%, there was a CORADS-5 on admission, and in 50%, there was a peripheral distribution of the interstitial infiltrate in the left lower lobe. The risk factors were FiO2, CT score > 18, and the NRL index. The combination of the high-risk Quick COVID-19 Severity Index (qCSI) plus CT score > 18 indices was the best prediction index for the development of a critical condition. The combined use of indices in infected COVID-19 patients showed diagnostic accuracy and predicted severity. Imaging and the laboratory tests are key tools independent of the wave of recurrence

Hyperglycemia and Loss of Redox Homeostasis in COVID-19 Patients

The infection with SARS-CoV-2 impairs the glucose&ndash;insulin axis and this contributes to oxidative (OS) and nitrosative (NSS) stress. Here, we evaluated changes in glucose metabolism that could promote the loss of redox homeostasis in COVID-19 patients. This was comparative cohort and analytical study that compared COVID-19 patients and healthy subjects. The study population consisted of 61 COVID-19 patients with and without comorbidities and 25 healthy subjects (HS). In all subjects the plasma glucose, insulin, 8-isoprostane, Vitamin D, H2S and 3-nitrotyrosine were determined by ELISA. The nitrites (NO2&minus;), lipid-peroxidation (LPO), total-antioxidant-capacity (TAC), thiols, glutathione (GSH) and selenium (Se) were determined by spectrophotometry. The glucose, insulin and HOMA-IR (p &lt; 0.001), 8-isoprostanes, 3-nitrotyrosine (p &lt; 0.001) and LPO were increased (p = 0.02) while Vitamin D (p = 0.01), H2S, thiols, TAC, GSH and Se (p &lt; 0.001) decreased in COVID-19 patients in comparison to HS. The SARS-CoV-2 infection resulted in alterations in the glucose&ndash;insulin axis that led to hyperglycemia, hyperinsulinemia and IR in patients with and without comorbidities. These alterations increase OS and NSS reflected in increases or decreases in some oxidative markers in plasma with major impact or fatal consequences in patients that course with metabolic syndrome. Moreover, subjects without comorbidities could have long-term alterations in the redox homeostasis after infection

Bioprosthesis in aortic valve replacement: long-term inflammatory response and functionality

Background: The evaluation of long-term inflammatory response and function in postoperative patients with aortic valve replacement (AVR) deserves special analysis because it is important to try to prevent reoperation and improve durability and functionality of the prostheses. It is our objectiveMethodsIn this study, we included a cohort of patients with aortic valve damage treated by AVR with mechanical prosthesis, bio prosthesis and we included a control group.ResultsWe found that IL-4 and osteopontin levels were higher in patients with mechanical vs biological prostheses (p=0.01 and p=0.04, respectively), osteoprotegerin (OPG) levels were decreased (p=0.01), women had lower levels of ET-1 and IL-6, (p=0.02) (p=0.04), respectively. Patients older than 60 years had decreased levels of IL-1ß pThe findings provide us with the opportunity to effectively treat patients with AVR in the postoperative period, which could prolong the functionality of the bio prostheses. Trial registration number NCT04557345.</jats:p