Pharmacological Treatment Of Chronic Heart Failure Research Articles

Sodium-glucose co-transporter 2 inhibitors for the treatment of cardio-renal syndrome.

The 2021 guidelines of the European Society of Cardiology on the diagnosis and therapy of heart failure (HF) introduced relevant changes in the pharmacological treatment of chronic HF. Among these, certainly the most significant was the introduction in the therapeutic flow-chart (with the highest recommendation level) of the sodium glucose co-transporter 2 (SGLT2) inhibitors. In fact, SGLT2 inhibitors are responsible for major paradigm shifts in the care of patients with or at high risk for HF, progression of chronic kidney disease, or both. SGLT2 inhibition demonstrated to improve cardiovascular outcomes in patients with HF over a wide range of ejection fractions, regardless of diabetic status, and have a strong nephroprotective effect. There are several important interactions between heart disease and kidneys disease. Indeed, acute or chronic dysfunction of the heart or kidneys can induce acute or chronic dysfunction in the other organ. The term 'cardiorenal syndrome' has been applied to these interactions. Since kidneys dysfunction in the setting of HF has a strong prognostic relevance, drugs that can slow down the decline of renal function are of utmost importance. Here, we discuss about the beneficial effects of SGLT2 inhibitors on the kidneys function in patients with HF and how these effects can improve both renal and cardiovascular outcomes.

Donepezil, Therapeutic Acetylcholinesterase Inhibitor, Prevents the Progression of Ventricular Dysfunction by Promoting Myocardial Glucose Utilization in Rat Model of Chronic Heart Failure Following Myocardial Infarction

Background: Donepezil, an acetylcholinesterase inhibitor, is reported to prevent cardiac pumping dysfunction in rats with chronic heart failure (CHF). Because energy substrate switching is a potential therapeutic target for the pharmacological treatment of CHF, we investigated the effect of donepezil on cardiac energy metabolism. Methods and Results: After induction of myocardial infarction (MI), rats were assigned to untreated and donepezil-treated (DPZ) groups. At the chronic phase of MI, resting heart rate was comparable between the untreated and DPZ groups. Nevertheless, left ventricular contractility evaluated in Langendorff-perfused hearts was significantly improved by donepezil treatment. At the same time point, the expression level of cardiac glucose transporter (GLUT) was significantly higher in the DPZ group than in the untreated group. In vitro studies showed that cultured cardiomyocytes treated with donepezil expressed high levels of GLUT and also exhibited accelerated cellular glucose uptake. Moreover, the beating rate of DPZ cardiomyocytes was approximately 2-fold higher than that of untreated control cells. Fasentin, a glucose transporter inhibitor, nullified the effects of donepezil, indicating that donepezil increases cellular activity by promoting glucose utilization in cardiomyocytes. Conclusion: The present study suggests that donepezil exhibits cardioprotective action by chronically modulating glucose metabolism in the failing heart.

Microvascular oxygen delivery-to-utilization mismatch at the onset of heavy-intensity exercise in optimally treated patients with CHF

Impaired muscle blood flow at the onset of heavy-intensity exercise may transiently reduce microvascular O(2) pressure and decrease the rate of O(2) transfer from capillary to mitochondria in chronic heart failure (CHF). However, advances in the pharmacological treatment of CHF (e.g., angiotensin-converting enzyme inhibitors and third-generation beta-blockers) may have improved microvascular O(2) delivery to an extent that intramyocyte metabolic inertia might become the main locus of limitation of O(2) uptake (Vo(2)) kinetics. We assessed the rate of change of pulmonary Vo(2) (Vo(2)(p)), (estimated) fractional O(2) extraction in the vastus lateralis (approximately Delta[deoxy-Hb+Mb] by near-infrared spectroscopy), and cardiac output (Qt) during high-intensity exercise performed to the limit of tolerance (Tlim) in 10 optimally treated sedentary patients (ejection fraction = 29 + or - 8%) and 11 controls. Sluggish Vo(2)(p) and Qt kinetics in patients were significantly related to lower Tlim values (P < 0.05). The dynamics of Delta[deoxy-Hb+Mb], however, were faster in patients than controls [mean response time (MRT) = 15.9 + or - 2.0 s vs. 19.0 + or - 2.9 s; P < 0.05] with a subsequent response "overshoot" being found only in patients (7/10). Moreover, tauVo(2)/MRT-[deoxy-Hb+Mb] ratio was greater in patients (4.69 + or - 1.42 s vs. 2.25 + or - 0.77 s; P < 0.05) and related to Qt kinetics and Tlim (R = 0.89 and -0.78, respectively; P < 0.01). We conclude that despite the advances in the pharmacological treatment of CHF, disturbances in "central" and "peripheral" circulatory adjustments still play a prominent role in limiting Vo(2)(p) kinetics and tolerance to heavy-intensity exercise in nontrained patients.