Abstract
Chronic kidney disease (CKD) is highly prevalent in patients with chronic heart failure (CHF) and increases the risk of overall and cardiovascular (CV) mortality. Despite evidence supporting ...the effectiveness of angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers, and mineralocorticoid receptor antagonists in decreasing mortality in patients with CHF, CKD hampers the optimization of standard pharmacologic therapy for heart failure. Therefore, other treatment options are needed to optimize treatment outcomes in CHF patients with CKD. The first-in-class angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, has a complementary activity that counteracts the potential unwanted long-term effects of over-activation of the renin–angiotensin–aldosterone system. Sacubitril/valsartan reduced the risk of CV mortality compared to standard therapy with an ACE-I in patients with heart failure with reduced ejection fraction (HFrEF) in the PARADIGM-HF trial and has been shown to be safe and effective in a broad range of HFrEF patients. However, data on the efficacy and tolerability of sacubitril/valsartan in patients with more advanced CKD are limited. This review discusses the evidence for the role of sacubitril/valsartan in providing additional renal benefit in patients with HFrEF. Data from clinical trials and real-world experience in patients with HFrEF and advanced CKD support the benefits of dual angiotensin/neprilysin inhibition across the breadth of kidney disease stages, including patients with significant renal impairment that was not reported in the pivotal PARADIGM-HF trial, and suggests a central role for the cardiac benefits of sacubitril/valsartan in nephroprotection.
Sodium-glucose cotransporter-2 inhibitors (SGLT-2i), initially studied and approved for the treatment of diabetes, are now becoming a promising class of agents to treat heart failure (HF) and chronic ...kidney disease (CKD), even in patients without diabetes. While the potential benefits in several diseases (usually treated by different medical specialties) is amplifying the interest in these drugs, their use in frail patients with multiple pathologies and on polypharmacy can be complex, requiring a composite multidisciplinary approach. Following a brief overview of the evidence supporting the benefits of SGLT-2i in patients with HF or CKD, we herein provide guidance for prescribing SGLT-2i in daily practice using a multidisciplinary approach. A shared treatment algorithm is presented for initiating an SGLT-2i in patients already being treated for diabetes and HF. Tools to prevent hypoglycemia, blood pressure drop, genital infections, euglycemic diabetic ketoacidosis and eGFR dip are also provided. It is hoped that this practical, multidisciplinary guidance for initiating SGLT-2i in patients with HF and/or CKD, whatever therapy they are currently on, can help to offer SGLT-2i to the largest population of patients possible to provide the most therapeutic benefit.
•SGLT-2i are a promising class of agents for heart failure and chronic kidney disease.•An algorithm is provided for prescribing SGLT-2i using a multidisciplinary approach.•Tips to prevent common adverse effects with SGLT2i are given.•Multidisciplinary guidance can help to offer SGLT-2i to more patients.
We are observing a resurgence of major diabetic vascular complications after a period of dramatic decrease during the period 1990 to 2010. The classical division of cardiovascular prevention into ...primary (with an event) and secondary (without an event) is largely used to describe cardiovascular risk in type 2 diabetes (T2D); however, there is evidence that the cardiovascular risk in diabetes may range from highest in patients who experienced a previous cardiovascular event to mild in patients with the main risk factors at target. Herein, we present details of the 14 cardiovascular outcome trials (CVOTs) published to date, including the total population investigated, and their separation into primary (T2D + multiple risk factors) and secondary prevention (T2D + established cardiovascular disease CVD) populations as detailed within the trials. We also summarize evidence for the effects of dipeptidyl peptidase‐4 inhibitors (DPP‐4i), glucagon‐like peptide‐1 receptor agonists (GLP1‐RA) and sodium glucose co‐transporter‐2 inhibitors (SGLT‐2i) versus placebo on the risk of major cardiovascular events (MACE), heart failure (HF) and diabetic kidney disease (DKD). In primary prevention, SGLT‐2i reduce both the risk of hospitalization for HF and progression of DKD; in secondary prevention, SGLT‐2i are effective on the three endpoints, DPP‐4i are neutral, while GLP1‐RA show mixed results.
Objectives The goal of the study was to assess the effects of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) on the composite of cardiovascular (CV) death, ...myocardial infarction (MI), and stroke, and on all-cause death, new-onset heart failure (HF), and new-onset diabetes mellitus (DM) in high-risk patients without HF. Background ACE-Is reduce CV events in high-risk patients without HF whereas the effects of ARBs are less certain. Methods Twenty-six randomized trials comparing ARBs or ACE-Is versus placebo in 108,212 patients without HF were collected in a meta-analysis and analyzed for the risk of the composite outcome, all-cause death, new-onset HF, and new-onset DM. Results ACE-Is significantly reduced the risk of the composite outcome (odds ratio OR: 0.830 95% confidence interval (CI): 0.744 to 0.927; p = 0.001), MI (OR: 0.811 95% CI: 0.748 to 0.879; p < 0.001), stroke (OR: 0.796 95% CI: 0.682 to 0.928; p < 0.004), all-cause death (OR: 0.908 95% CI: 0.845 to 0.975; p = 0.008), new-onset HF (OR: 0.789 95% CI: 0.686 to 0.908; p = 0.001), and new-onset DM (OR: 0.851 95% CI: 0.749 to 0.965; p < 0.012). ARBs significantly reduced the risk of the composite outcome (OR: 0.920 95% CI: 0.869 to 0.975, p = 0.005), stroke (OR: 0.900 95% CI: 0.830 to 0.977, p = 0.011), and new-onset DM (OR: 0.855 95% CI: 0.798 to 0.915; p < 0.001). Conclusions In patients at high CV risk without HF, ACE-Is and ARBs reduced the risk of the composite outcome of CV death, MI, and stroke. ACE-Is also reduced the risk of all-cause death, new-onset HF, and new-onset DM. Thus, ARBs represent a valuable option to reduce CV mortality and morbidity in patients in whom ACE-Is cannot be used.
Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide, placing a major economic and resource burden on public health systems. During hospitalization, all AMI ...patients should be evaluated with transthoracic echocardiography, a noninvasive, low-cost, and easily available bedside imaging tool that allows the detection of myocardial walls involved in the ischemic process, damage extent, functional consequences, and mechanical complications. Moreover, and more importantly, transthoracic echocardiography can provide information on short- and long-term outcomes after AMI. The purpose of this review is to clarify the role of standard and advanced echocardiographic parameters for an early identification of patients at high risk for developing adverse events and mortality after AMI. Standard echocardiography (in particular left ventricular ejection fraction, wall motion score index, and diastolic measurements including E velocity deceleration time and E/e' ratio) proposes powerful parameters for risk stratification after AMI. Advanced echocardiographic technologies, in particular speckle-tracking-derived longitudinal strain, coronary flow velocity reserve, and myocardial contrast echocardiography (contrast defect index), can provide additional prognostic value beyond standard techniques. Therefore, echocardiography plays a fundamental role in predicting short- and long-term prognosis, and a more accurate risk stratification of patients may be useful to drive therapy and follow-up after AMI. Accordingly, a comprehensive echocardiography-based algorithm would be welcome for an early stratification of cardiovascular risk in patients experiencing AMI.
Introduction
In the risk stratification and selection of patients with heart failure (HF) eligible for implantable cardioverter‐defibrillator (ICD) therapy, 123I‐meta‐IodineBenzylGuanidine ...(123I‐mIBG) scintigraphy has emerged as an effective non‐invasive method to assess cardiac adrenergic innervation. Similarly, clinical risk scores have been proposed to identify patients with HF at risk of all‐cause mortality, for whom the net clinical benefit of device implantation would presumably be lower. Nevertheless, the association between the two classes of tools, one suggestive of arrhythmic risk, the other of all‐cause mortality, needs further investigation.
Objective
To test the relationship between the risk scores for predicting mortality and cardiac sympathetic innervation, assessed through myocardial 123I‐mIBG imaging, in a population of patients with HF.
Methods
In HF patients undergoing 123I‐mIBG scintigraphy, eight risk stratification models were assessed: AAACC, FADES, MADIT, MADIT‐ICD non‐arrhythmic mortality score, PACE, Parkash, SHOCKED and Sjoblom. Cardiac adrenergic impairment was assessed by late heart‐to‐mediastinum ratio (H/M) <1.6.
Results
Among 269 patients suffering from HF, late H/M showed significant negative correlation with all the predicting models, although generally weak, ranging from −0.15 (p = .013) for PACE to −0.32 (p < .001) for FADES. The scores showed poor discrimination for cardiac innervation, with areas under the curve (AUC) ranging from 0.546 for Parkash to 0.621 for FADES.
Conclusion
A weak association emerged among mortality risk scores and cardiac innervation, suggesting to integrate in clinical practice tools indicative of both arrhythmic and general mortality risks, when evaluating patients affected by HF eligible for device implantation.
Myriad advances in all fields of cardiac imaging have stimulated and reflected new understanding of cardiac performance, myocardial damage and the mechanisms of heart failure. In this paper, the ...Heart Failure Association assesses the potential usefulness of innovative imaging modalities in enabling more precise diagnostic and prognostic evaluation, as well as in guiding treatment strategies. Many new methods have gradually penetrated clinical practice and are on their way to becoming a part of routine evaluation. This paper focuses on myocardial deformation and three‐dimensional ultrasound imaging; stress tests for the evaluation of contractile and filling function; the progress of magnetic resonance techniques; molecular imaging and other sound innovations.
The Heart Failure Association aims to highlight the ways in which paradigms have shifted in several areas of cardiac assessment. These include reassessing of the simplified concept of ejection fraction and implementation of the new parameters of cardiac performance applicable to all heart failure phenotypes; switching from two‐dimensional to more accurate and reproducible three‐dimensional ultrasound volumetric evaluation; greater tissue characterization via recently developed magnetic resonance modalities; moving from assessing cardiac function and congestion at rest to assessing it during stress; from invasive to novel non‐invasive hybrid techniques depicting coronary anatomy and myocardial perfusion; as well as from morphometry to the imaging of pathophysiologic processes such as inflammation and apoptosis. This position paper examines the specific benefits of imaging innovations for practitioners dealing with heart failure aetiology, risk stratification and monitoring, and, in addition, for scientists involved in the development of future research.
β-blockers represent a mainstay in the pharmacological approach to patients affected by heart failure with reduced ejection fraction (HFrEF). However, underuse of this class of drugs is still ...reported, especially in the presence of cardiovascular and non-cardiovascular comorbidities, even if they are not contraindications for prescription of a β-blocker. The prognostic benefit of β-blockers is relevant in the presence of comorbidities, and achievement of the maximum tolerated dose is an important goal to increase their favorable prognostic role. The aim of the present review is to analyze the available evidence on the use of β-blockers in HFrEF patients with the most common comorbidities. In particular, we will discuss the role and most appropriate beta-blocker in patients with pulmonary disease (bisoprolol, metoprolol, nebivolol), diabetes (carvedilol and nebivolol), atrial fibrillation (all indicated for rate control, with metoprolol as the first choice followed by bisoprolol, nebivolol, and carvedilol), erectile dysfunction (bisoprolol and nebivolol), peripheral arterial disease (nebivolol), and other conditions, in order to clarify the correct use of this class of drugs in the clinical practice.
Epicardial adipose tissue (EAT) thickness and pro-inflammatory status has been shown to be associated with several cardiac diseases, including aortic stenosis (AS). Thus, cardiac visceral fat could ...represent a potential new target for drugs. In the present study we evaluate the effect of statin therapy on EAT accumulation and inflammation.
Echocardiographic EAT thickness was assessed in 193 AS patients taking (n.87) and not taking (n.106) statins, undergoing cardiac surgery. To explore the association between statin therapy and EAT inflammation, EAT biopsies were obtained for cytokines immunoassay determination in EAT secretomes. An in vitro study was also conducted and the modulation of EAT and subcutaneous adipose tissue (SCAT) secretomes by atorvastatin was assessed in paired biopsies.
Statin therapy was significantly associated with lower EAT thickness (p < 0.0001) and with lower levels of EAT-secreted inflammatory mediators (p < 0.0001). Of note, there was a significant correlation between EAT thickness and its pro-inflammatory status. In vitro, atorvastatin showed a direct anti-inflammatory effect on EAT which was significantly higher compared to the SCAT response to statin incubation (p < 0.0001).
The present study indicates a robust association between statin therapy and reduced EAT accumulation in patients with AS. The present data also suggest a direct relationship between EAT thickness and its inflammatory status, both modulated by statin therapy. The in vitro results support the hypothesis of a direct action of statins on EAT secretory profile. Overall our data suggest EAT as a potential new therapeutic target for statin therapy.
•Statin therapy is associated with a reduced EAT thickness.•The association between statins and EAT is paralleled by an attenuation of EAT inflammatory profile.•Statins have a direct and selective anti-inflammatory effect on EAT.
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