Vitamin D: A Bridge between Kidney and Heart.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factors, such as hypertension, diabetes, obesity, and smoking, among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

The Changing Role of Loop Diuretics in Heart Failure Management across the Last Century.

Congestion is the main therapeutic target of acute heart failure (HF) treatment, and loop diuretics (LDs) are widely used drugs for this purpose. Despite their extensive use, these agents remain largely understudied in terms of modality administration, treatment duration, and escalation dose for subjects responding poorly to therapy. LDs were initially investigated in several edematous statuses such as cirrhosis, nephrotic syndrome, and congestive HF and initially approved for the treatment of cardiogenic congestion in 1966. Despite the long history and the undoubted role in congestion management, the use of LDs in the acute phase is mostly based on the physician's experience, the oral amount chronically administered, and clinical decongestion response. Recent literature suggests monitoring diuretic activity by the evaluation of daily diuresis, weight loss, and sample urinary sodium assessment after early intravenous LD administration. More recently, the measurement of urinary sodium integrated with urinary and blood creatinine values and fluid status has been suggested as optimal marker to predict whole diuretic efficiency and to target the optimal dose. However, this method is not easily available in the chronic setting or in patients with recurrent hospitalization taking a high loop diuretic amount. Since high loop diuretic dose is related to diuretic resistance (DR) and poorer outcome, additional diuretics acting in different nephron sites are often required. Current sequential nephron blockade can stimulate diuresis by synergic mechanisms. This strategy is attempted in patients with poor response, revealing good results in the early period, but the effects of neuro-endocrine stimulation and electrolyte balance across long-term follow-up are still questioned. This paper reviews the historical course of loop diuretics and highlights the need for a universal approach based on clinical conditions, cardio-renal interactions, and HF phenotypes.

Left Atrial Functional Remodeling in Patients with Chronic Heart Failure Treated with Sacubitril/Valsartan.

(1) Background: Previous studies showed left ventricular (LV) and left atrial (LA) improvement and reverse remodeling after therapy with Sacubitril/Valsartan (S/V) in patients affected by heart failure with reduced ejection fraction (HFrEF). Therefore, we sought to investigate predictors of LA structural and functional reverse remodeling (LARR) in this setting of patients after therapy with S/V, focusing on left atrial strain parameters, such as peak atrial longitudinal strain (PALS). (2) Methods: Patients with HFrEF underwent clinical and echocardiographic evaluation at baseline and after six months of therapy with S/V. Measures of LA structure (LA volume index, LAVi) and function (LA emptying fraction (LAEF), PALS, LA conduit strain and peak atrial contraction strain (PACS) were also analyzed. Patients were divided in two groups, those with a LARR (relative reduction in LAVi > 15%, LARR+) and those without (LARR-). (3) Results: A total of 47 consecutive patients (66 ± 8 years, 85% male, mean LVEF 28 ± 6%) were enrolled in the study and followed up. A significant increase of LAEF (46 ± 13 vs. 37 ± 11%, p < 0.001) and a significant reduction of LAVi (42 ± 15 vs. 45 ± 15 mL/m2, p = 0.008) were found after 6 months of S/V therapy; 47% of the population showed LA reverse remodeling. LA strain parameters, PALS (19 ± 8 vs. 15 ± 7 %, p < 0.001) and LA conduit (-9.7 ± 5.2% vs. -7.6 ± 4.1%, p = 0.007) significantly improved after 6 months of S/V therapy. At multivariable stepwise regression analysis, changes in LV End Diastolic Volume (LVEDV) and PALS were significantly proportional to changes in LAVi values. (4) Conclusions: Six months of treatment with S/V in patients with HFrEF was associated with an improvement in LA functional reverse remodeling in a real-world scenario. LARR was not significantly correlated to baseline echocardiographic variables, but was proportional to changes in LV volumes and LA strain parameters. Finally, after S/V therapy, a strict connection between LA and LV reverse remodeling and between LA anatomical and functional reverse remodeling seems to be outlined.

The Evolving Phenotypes of Cardiovascular Disease during COVID-19 Pandemic.

COVID-19 pandemic has negatively impacted the management of patients with acute and chronic cardiovascular disease: acute coronary syndrome patients were often not timely reperfused, heart failure patients not adequately followed up and titrated, atrial arrhythmias not efficaciously treated and became chronic. New phenotypes of cardiovascular patients were more and more frequent during COVID-19 pandemic and are expected to be even more frequent in the next future in the new world shaped by the pandemic. We therefore aimed to briefly summarize the main changes in the phenotype of cardiovascular patients in the COVID-19 era, focusing on new clinical challenges and possible therapeutic options.

Right heart failure in left heart disease: imaging, functional, and biochemical aspects of right ventricular dysfunction.

For decades, cardiologists have largely underestimated the role of the right heart in heart failure due to left heart disease. Nowadays, the importance of evaluating right ventricular (RV) structure and function in left heart failure is well documented and this concept has been emphasized in the most recent heart failure guidelines. However, several relevant questions remain unanswered such as the following: (a) which imaging technique (standard or 3D echocardiography or strain imaging or cardiac magnetic resonance) and, more, which parameters should be used to grade the severity of RV dysfunction? (b) do less widespread and less applied diagnostic tools such as cardiopulmonary stress testing and bioelectrical impedance analysis play a role in this field? (c) are there specific biochemical aspects of RV failure? (d) why notion of pathophysiology of heart and lung interaction are so well appreciated at an academic level but are not applied in the clinical setting? The present review has been prepared by the Heart Failure (HF) working group of the Italian Society of Cardiology and its main objective is to improve our understanding on RV dysfunction in heart failure.

Pharmacological Anti-Remodelling Effects of Disease-Modifying Drugs in Heart Failure with Reduced Ejection Fraction.

Cardiac remodelling is an adverse phenomenon linked to heart failure progression and an important contributor to heart failure severity. Cardiac remodelling could represent the real therapeutic goal in the treatment of patients with heart failure with reduced ejection fraction, being potentially reversed through different pharmacotherapies. Currently, there are well-established drugs such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and ß-blockers with anti-remodelling effects; recently, angiotensin receptor neprilysin inhibitor effects on inhibiting cardiac remodelling (improving N-terminal pro-B-type natriuretic peptide levels, echocardiographic parameters of reverse cardiac remodelling and right ventricular function in patients with heart failure with reduced ejection fraction) were demonstrated. More recently, hemodynamic consequences of gliflozins, reduced cardiac hydrostatic pressure as a possible cause of ventricular remodelling and hypertrophy were proposed to explain potential anti-remodelling effects of gliflozins. Gliflozins exert their cardioprotective effects by attenuating myofibroblast activity and collagen-mediated remodelling. Another postulated mechanism is represented by the reduction in sympathetic activity, through the reduction in renal afferent nervous activity and the suppression of central reflex mechanisms. Benefits of gliflozins on left ventricular hypertrophy, dilation, and systolic and diastolic function were also described. In this review, we aimed to provide a wide overview on cardiac remodelling with a particular focus on possible anti-remodelling effects of angiotensin receptor neprilysin inhibitors and gliflozins.

Switch to SGLT2 Inhibitors and Improved Endothelial Function in Diabetic Patients with Chronic Heart Failure.

PURPOSE: The use of sodium-glucose-cotransporter-type-2 inhibitors (SGLT2i) was associated in previous studies with an improved vascular function in non-human experimental models. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with chronic heart failure (CHF) and type-2 diabetes mellitus (T2DM), switching from other oral hypoglycemic agents to SGLT2i in an observational study. METHODS: Twenty-two consecutive outpatients with CHF and T2DM were enrolled after switching to SGLT2i therapy, and compared with 23 consecutive controls from the same registry comparable for principal clinical characteristics. In all patients, endothelial function was assessed by FMD at baseline and after 3 months of follow-up. RESULTS: Three months of therapy with SGLT2i were associated with a statistically significant improvement in endothelial function (19.0 ± 5.7% vs 8.5 ± 4.1%, p < 0.0001); baseline levels of FMD were comparable between groups (p n.s.). Therapy with SGLT2i was significantly associated to improved FMD levels even at multivariable stepwise regression analysis (p < 0.001). CONCLUSIONS: Switch to SGLT2i in patients with CHF and T2DM was associated in an observational non-randomized study with an improved endothelial function.

Predictors of right ventricular function improvement with sacubitril/valsartan in a real-life population of patients with chronic heart failure.

BACKGROUND: Observational studies have demonstrated that treatment with sacubitril/valsartan may improve left ventricular (LV) systolic and diastolic function in subjects with reduced LV ejection fraction (LVEF) in real-world studies. Subjects with heart failure and reduced EF (HFrEF), however, are also characterized by an impaired right ventricular (RV) function. We therefore aimed to evaluate whether also RV function may improve after S/V therapy and possible predictors of RV improvement could be identified at echocardiography and tissue Doppler imaging. METHODS: Fifty consecutive patients (67 ± 8 years, LVEF 28 ± 6%, male 86%) with chronic HFrEF and NYHA class II-III were followed up for 6 months after therapy with S/V. LV&RV function was assessed at baseline and after 6 months of therapy. RESULTS: After 6-month therapy with S/V a significant improvement was shown in the following echocardiography parameters assessing RV function: PAsP (31 ± 11 vs. 35 ± 10 mmHg, p < 0.001), TAPSE (19 ± 3 vs. 18 ± 3 mm, p < 0.001), RV FAC (38 ± 7 vs. 34 ± 6 mm, p < 0.001), RV S' (12 ± 2 vs. 10 ± 2 cm/s, p < 0.001), RV-FW-LS (-20 ± 5 vs. -18 ± 5%, p < 0.001), RV-4Ch-LS (-16 ± 5 vs. -14 ± 5%, p < 0.001). At multivariable analysis improvement in RV-FW-LS was associated to baseline levels of RV S' (r 0.75, p < 0.01) and RAV (r -0.32, p < 0.05). CONCLUSIONS: In a real-world scenario, 6-month therapy with S/V was associated with an improved RV function in HFrEF. RV function improvement may be predicted by assessing baseline RV S' and right atrial volume values.

New Targets in Heart Failure Drug Therapy.

Despite recent advances in chronic heart failure management (either pharmacological or non-pharmacological), the prognosis of heart failure (HF) patients remains poor. This poor prognosis emphasizes the need for developing novel pathways for testing new HF drugs, beyond neurohumoral and hemodynamic modulation approaches. The development of new drugs for HF therapy must thus necessarily focus on novel approaches such as the direct effect on cardiomyocytes, coronary microcirculation, and myocardial interstitium. This review summarizes principal evidence on new possible pharmacological targets for the treatment of HF patients, mainly focusing on microcirculation, cardiomyocyte, and anti-inflammatory therapy.

Infection, atherothrombosis and thromboembolism beyond the COVID-19 disease: what similar in physiopathology and researches.

The recent Sars-Cov-2 pandemic (COVID-19) has led to growing research on the relationship between thromboembolism and Sars-Cov-2 infection. Nowadays, endothelial dysfunction, platelet activation, coagulation, and inflammatory host immune response are the subject of extensive researches in patients with COVID-19 disease. However, studies on the link between microorganisms or infections and thrombotic or thromboembolic events met fluctuating interest in the past. We, therefore, aimed to briefly summarize previous evidence on this topic, highlighting common points between previous data and what experienced today with SARS-COV2 infections.

Chronic thromboembolic pulmonary hypertension mimicking coronary artery disease.

We report the case of 63-year-old man, complaining of dyspnea and with abnormal systolic motion of the interventricular septum at echocardiography, referred for coronary angiography and suspect coronary artery disease. In the presence of normal coronary angio, a specific work-up showed chronic thromboembolic pulmonary hypertension requiring pulmonary endarterectomy. The case highlights the need for a global cardiovascular and imaging approach in presence of poorly specific symptoms and signs of coronary artery disease.