Heart failure risk and major cardiovascular events in diabetes: an overview of within-group differences in non-insulin antidiabetic treatment.

Recently, great attention is paid to cardiovascular impact of non-insulin glucose-lowering drugs, particularly in terms of major cardiovascular events and risk of heart failure. In this regard, a surprising diversity among different molecules within the same pharmacological class has been noticed, yielding to an intra-class discrepancy which has no analogous in other cardiovascular fields. The aim of this paper is to review the literature, giving an insight of the heterogeneous effects among groups and within group shown by oral antidiabetic drugs, with a special concern to fragile patients, such as those with or at risk of heart failure.

Heart Failure and Kidney Disease.

Kidney disease is commonly found in heart failure (HF) patients. They share many risk factors and common pathophysiological pathways which often lead to mutual dysfunction. Both haemodynamic and non-haemodynamic mechanisms are involved in the development of renal impairment in heart failure patients. Moreover, the presence of a chronic kidney disease is a significant independent predictor of worse outcome in chronic as well as in acute decompensated HF. As a consequence, an accurate evaluation of renal function plays a key role in the management of HF patients. Serum creatinine levels and glomerular filtration rate (GFR) estimates are the corner stones of renal function evaluation in clinical practice. However, to overcome their limits, several emerging glomerular and tubular biomarkers have been proposed over the last years. Alongside the renal biomarkers, imaging techniques could complement the laboratory data exploring different pathophysiological pathways. In particular, Doppler evaluation of renal circulation is a highly feasible technique that can effectively identify HF patients prone to develop renal dysfunction and with a worse outcome. Finally, some classes of drugs currently used in heart failure treatment can affect renal function and their use can be influenced by the presence of chronic kidney disease.

TSH Variations in Chronic Heart Failure Outpatients: Clinical Correlates and Outcomes.

BACKGROUND: Hypothyroidism is a frequently observed comorbidity in patients with chronic heart failure (CHF), possibly giving rise to unfavorable outcomes. AIM: The aim of the study was to evaluate the impact of TSH changes over time on cardiac function and prognosis of outpatients with CHF. METHODS: Patients underwent clinical, electrocardiographic, and echocardiographic evaluations at baseline and after 12 months. Moreover, blood chemistry tests were performed to evaluate renal function, cardiac biomarkers, fT3, fT4, and TSH levels. Based on TSH serum levels, patients were retrospectively classified into four categories: Group 1, patients with improved thyroid function at one-year follow up vs. baseline; Group 2, patients with stable and mildly high TSH values (3.74 - 10 mUI/L); Group 3, patients with worsening thyroid function; Euthyroid patients Group, TSH levels within the normal range of reference at baseline as well as at 12 months follow-up. We considered as end-points: one-year changes of laboratory and echocardiographic parameters; hospitalizations due to worsening of HF (acute decompensated heart failure - ADHF); death for all causes. RESULTS: Among 257 patients, 174 (67.7%) were euthyroid at baseline and after 12 months. Group 1 patients (n. 22, 8.6%) showed a significant improvement in systolic and diastolic function, filling pressures, NT-proBNP and Galectin-3. Group 2 patients (n. 34, 13.2%) did not exhibit significant modifications in studied parameters. Group 3 patients (n. 27, 10.5%) showed worsening of diastolic function and NT-proBNP and a greater risk of ADHF (HR: 2.12; 95%CI: 1.20-3.74; p: 0.009) and death (HR: 4.05; 95%CI: 2.01-8.15; p<0.001). CONCLUSION: In patients with CHF, changes in thyroid function over time influenced echocardiographic parameters and biomarkers reflecting modifications of cardiac function and prognosis, thus suggesting the clinical relevance of thyroid deficiency screening and correction.

New Frontiers in the Therapeutic Approach of Patients with Cardiovascular and Endocrine Diseases.

BACKGROUND AND OBJECTIVE: Cardiovascular disease is the most important cause of morbidity and mortality worldwide, with a significant economic burden, which is expected to increase in the next years. Alongside the management of cardiac manifestations and major risk factors for atherosclerosis, great attention has been paid to the role of comorbidities in initiating and worsening cardiac conditions. DISCUSSION: The cardiovascular impact of a broad spectrum of endocrine disorders has been evaluated, with particular regard to their effects on cardiac function and cardiovascular prognosis in affected patients. Among the different endocrine conditions considered, the association between subclinical hypothyroidism and cardiovascular events is still uncertain. A number of observational studies have linked subclinical hypothyroidism (in particular severe elevation of TSH levels) with incident cardiovascular disease and poor prognosis, however thyroid replacement therapy is still controversial, especially in the elderly, due to the lack of evidence coming from randomized controlled trials. With regards to testosterone deficiency, even though it has been associated with metabolic abnormalities and poor prognosis in patients affected by cardiovascular diseases, the cardiac safety of replacement therapy has still to be completely clarified. Similarly, growth hormone deficiency showed detrimental effects on cardiovascular events and risk factors which seem to be reverted by replacement therapy, even if unequivocal evidence from randomized clinical trials is still lacking Another relevant chapter in cardiovascular disease management is about the cardiovascular outcomes of diabetes medical treatments. In recent years, a growing interest has been developed around the cardiovascular safety of antidiabetic medications which has led to a great number of publications addressing this issue for the different classes of antidiabetic drugs. Interestingly, the recently approved classes, i.e. incretins and SGLT-2 inhibitors, have additionally demonstrated a protective effect against major cardiovascular events, shedding new light on the management of diabetes in patients affected by cardiovascular disease. CONCLUSION: Important controversies still exist regarding the cardiac implications of the therapies adopted in endocrine diseases. Owing the large prevalence of these conditions, particularly in the cardiovascular population, further research is awaited in order to clarify the potential advantage and the possible cardiac risk related to treatment of the endocrine comorbidities.

Role of imaging in the evaluation of renal dysfunction in heart failure patients.

Heart failure and kidney disease share common pathophysiological pathways which can lead to mutual dysfunction, known as cardiorenal syndrome. In heart failure patients, renal impairment is related to hemodynamic and non-hemodynamic factors. Both decreased renal blood flow and renal venous congestion due to heart failure could lead to impaired renal function. Kidney disease and worsening renal function are independently associated with poor prognosis in heart failure patients, both in acute and chronic clinical settings. The aim of this review is to assess the role of renal imaging modalities in the evaluation and management of heart failure patients. Renal imaging techniques could complete laboratory data, as estimated glomerular filtration rate, exploring different pathophysiological factors involved in kidney disease and adding valuable information about renal structure and function. In particular, Doppler examination of arterial and venous hemodynamics is a feasible and non invasive technique, which has proven to be a reliable method for prognostic stratification in patients with cardiorenal syndrome. The renal resistance index, a measure related to renal hemodynamics, can be calculated from the Doppler evaluation of arterial flow. Moreover, the analysis of Doppler venous flow patterns can integrate information from the arterial study and evaluate renal congestion. Other imaging modalities are promising, but still confined to research purposes.

Right ventriculo-arterial coupling assessed by two-dimensional strain: A new parameter of right ventricular function independently associated with prognosis in chronic heart failure patients.

AIM OF THE STUDY: To evaluate whether right ventriculo-arterial coupling obtained by the estimation of the two-dimensional right ventricular (RV) longitudinal strain and of the pulmonary arterial systolic pressure (PASP) could improve prognostic stratification of chronic heart failure (CHF) outpatients. METHODS: CHF outpatients in a stable clinical condition and in conventional therapy were enrolled. The global RV longitudinal strain (RV-GLS) and the strain of the RV free wall (RV-fwLS) were evaluated. PASP was estimated on the basis of tricuspid regurgitation velocity and the estimated central venous pressure. Both RV-GLS and RV-fwLS were then indexed for PASP. RESULTS: Of the 315 patients evaluated, 69 died during follow-up. Both RV-GLS/PASP and RV-fwLS/PASP were significantly associated with an increased risk of death at univariate (HR: 0.43; 95%CI: 0.34-0.56; p<0.001 and HR: 0.44; 95% CI: 0.34-0.57; p<0.001, respectively) and multivariate analysis (HR: 0.66; 95% CI: 0.49-0.89; p: 0.008 and HR: 0.65; 95% CI: 0.49-0.85; p: 0.002, respectively) after correction for age, NYHA class, mean arterial pressure, left ventricular ejection fraction, natremia, glomerular filtration rate and NT-proBNP. CONCLUSIONS: Indexing RV function, assessed by speckle-tracking analysis, with an estimation of pulmonary systolic arterial pressure provides a parameter of ventricular arterial coupling that is independently associated with an increased risk of mortality.

A Multiparametric Approach Based on NT-proBNP, ST2, and Galectin3 for Stratifying One Year Prognosis of Chronic Heart Failure Outpatients.

Galectin-3 and ST2 are emerging biomarkers involved in myocardial fibrosis. We evaluate the relevance of a multiparametric biomarker approach based on increased serum levels of NT-proBNP, galectin-3, and ST2 in stratifying the prognosis of chronic heart failure (CHF) outpatients. In 315 CHF outpatients in stable clinical condition clinical and echocardiographic evaluations were performed. Routine chemistry and serum levels of NT-proBNP, galectin-3, and ST2 were also assessed. During a 12 month follow-up, cardiovascular death, and/or heart failure (HF) occurred in 64 patients. The presence of NT-proBNP, galectin-3, and ST2 were higher than the recommended cutoffs and were all associated with events at univariate Cox regression analysis, as well as in a multivariate analysis including the three biomarkers. When a score based on the number of biomarkers above the recommended cut-offs was used (in a range of 0-3), it was associated with events both with respect to the univariate (HR 2.96, 95% CI 2.21-3.95, p < 0.001, C-index 0.78) and the multivariate (HR 1.52, 95% CI 1.06-2.17, p: 0.023, C-index 0.87) analyses, after correction for the variables of a reference model. Our results suggest that an easy prognostic approach based on the combination of three biomarkers, although with partially-overlapping pathophysiological mechanisms, is able to identify patients with the highest risk of heart failure progression.