Heart Failure

Experimental models of cardiac physiology and pathology Abstract Experimental models of cardiac disease play a key role in understanding the pathophysiology of the disease and developing new therapies. The features of the experimental models should reflect the clinical phenotype, which can have a wide spectrum of underlying mechanisms. We review characteristics of commonly used experimental models of cardiac physiology and pathophysiology in all translational steps including in vitro, small animal, and large animal models. Understanding their characteristics and relevance to clinical disease is the key for successful translation to effective therapies.

Cardiorenal syndrome in heart failure with preserved ejection fraction—an under-recognized clinical entity Abstract Cardiorenal syndrome (CRS) results from the complex and bidirectional interaction between the failing heart and the kidneys. Limited information exists about the pathophysiology and treatment options for worsening kidney function in the setting of heart failure with preserved ejection fraction (HFpEF). This review summarizes the salient pathophysiological pathways in CRS in patients with HFpEF, with emphasis on type 1 and type 2 phenotypes, and outlines diagnostic and therapeutic strategies that are applicable in this population. Elevated central venous and intra-abdominal pressure, left ventricular hypertrophy, LV strain, RAAS activation, oxidative injury, pulmonary hypertension, and RV dysfunction play key roles in the pathogenesis of CRS in the backdrop of HFpEF. The availability of biomarkers of renal and cardiac injury offer a new dimension in accurately diagnosing and quantifying end organ damage in CRS and will improve the accuracy of goal-directed therapies in this population. Novel targeted therapies such as the development of angiotensin/neprilysin inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors offer new territory in realizing potential benefits in reduction of cardio-renal adverse outcomes in this population. Future studies focusing exclusively on renal outcomes in patients with HFpEF are crucial in delivering optimal therapies in this subset of patients.

Valuing health-related quality of life in heart failure: a systematic review of methods to derive quality-adjusted life years (QALYs) in trial-based cost–utility analyses Abstract The accurate measurement of health-related quality of life (HRQoL) and the value of improving it for patients are essential for deriving quality-adjusted life years (QALYs) to inform treatment choice and resource allocation. The objective of this review was to identify and describe the approaches used to measure and value change in HRQoL in trial-based economic evaluations of heart failure interventions which derive QALYs as an outcome. Three databases (PubMed, CINAHL, Cochrane) were systematically searched. Twenty studies reporting economic evaluations based on 18 individual trials were identified. Most studies (n = 17) utilised generic preference-based measures to describe HRQoL and derive QALYs, commonly the EQ-5D-3L. Of these, three studies (from the same trial) also used mapping from a condition-specific to a generic measure. The remaining three studies used patients' direct valuation of their own health or physician-reported outcomes to derive QALYs. Only 7 of the 20 studies reported significant incremental QALY gains. Most interventions were reported as being likely to be cost-effective at specified willingness to pay thresholds. The substantial variation in the approach applied to derive QALYs in the measurement of and value attributed to HRQoL in heart failure requires further investigation.

Advances in the diagnosis and treatment of transthyretin amyloidosis with cardiac involvement Abstract Amyloidosis is caused by extracellular deposition of insoluble abnormal fibrils constituted by misfolded proteins, which can modify tissue anatomy and hinder the function of multiple organs including the heart. Amyloidosis that can affect the heart includes mostly systemic amyloidosis (amyloid light chain, AL) and transthyretin amyloidosis (ATTR). The latter can be acquired in elderly patients (ATTRwt), or be inherited in younger individuals (ATTRm). The diagnosis is demanding given the high phenotypic heterogeneity of the disease. Therefore, "red flags," which are suggestive features giving support to diagnostic suspicion, are extremely valuable. However, the lack of broad awareness among clinicians represents a major obstacle for early diagnosis and treatment of ATTR. Furthermore, recent implementation of noninvasive diagnostic techniques has revisited the need for endomyocardial biopsy (EMB). In fact, unlike AL amyloidosis, which requires tissue confirmation and typing for diagnosis, ATTR can now be diagnosed noninvasively with the combination of bone scintigraphy and the absence of a monoclonal protein. Securing the correct diagnosis is pivotal for the newly available therapeutic options targeting both ATTRm and ATTRwt, and are directed to either stabilization of the abnormal protein or the reduction of the production of transthyretin. The purpose of this article is to review the contemporary aspects of diagnosis and management of transthyretin amyloidosis with cardiac involvement, summarizing also the recent therapeutic advances with tafamidis, patisiran, and inotersen.

READY: relative efficacy of loop diuretics in patients with chronic systolic heart failure—a systematic review and network meta-analysis of randomised trials Abstract The majority of patients with chronic heart failure (HF) receive long-term treatment with loop diuretics. The comparative effectiveness of different loop diuretics is unknown. We searched PubMed, clinicaltrials.gov, the Cochrane Central Register of Controlled Trials and the European Union Clinical Trials Register for randomised clinical trials exploring the efficacy of the loop diuretics azosemide, bumetanide, furosemide or torasemide in patients with HF. Comparators included placebo, standard medical care or any other active treatment. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular mortality, HF-related hospitalisation and any combined endpoint thereof. Hypokalaemia and acute renal failure were defined as additional safety endpoints. Evidence was synthesised using network meta-analysis (NMA). Thirty-four trials reporting on 2647 patients were included. The overall quality of evidence was rated as moderate. NMA demonstrated no significant differences between loop diuretics with respect to all-cause mortality, cardiovascular mortality or hypokalaemia. In contrast, torasemide ranked best in terms of HF hospitalisation, and there was a trend towards benefits with torasemide with regard to occurrence of acute renal failure. Sensitivity analyses excluding trials with a follow-up < 6 months, trials with a cross-over design and those including < 25 patients confirmed the main results. We found no significant superiority of either loop diuretic with respect to mortality and safety endpoints. However, clinicians may prefer torasemide, as it was associated with fewer HF-related hospitalisations.

Pathophysiology and imaging of heart failure in women with autoimmune rheumatic diseases Abstract Autoimmune rheumatic diseases (ARDs) affect 8% of the population, and approximately 78% of them are women. Cardiovascular disease (CVD) in ARDs encompasses different pathophysiologic processes, such as endothelial dysfunction, myocardial/vascular inflammation and accelerated atherosclerosis with silent clinical presentation, leading to heart failure (HF), usually with preserved ejection fraction. Echocardiography and cardiovascular magnetic resonance (CMR) are the two most commonly used noninvasive imaging modalities for the evaluation of HF in patients with ARDs. Echocardiography currently represents the main diagnostic tool for cardiac imaging in clinical practice. However, the demand for more efficient and prompt diagnostic and therapeutic approach in this specific population necessitates the implementation of modalities capable of providing a more detailed and quantified information from the point of tissue characterization. Furthermore, echocardiography is an operator and acoustic window depended modality, with relatively low reproducibility and unable to perform tissue characterization. CMR is a noninvasive modality without radiation that can give reproducible and operator-independent information about both myocardial function and tissue characterization. By providing quantification of oedema, stress perfusion defects and fibrosis, CMR can diagnose myocardial inflammation, micro–macro-vascular myocardial ischemia and replacement or diffuse fibrosis, respectively. Tissue characterization allows for moving beyond the cardiac function to the assessment of intra- and inter-cellular alterations and promotes the development of personalized cardiac and anti-rheumatic treatment in ARDs with HF. ARDs are mainly female diseases. Cardiac involvement leading in HF is not unusual in ARDs and remains the main cause of death. Noninvasive, nonradiating imaging modalities such as echocardiography and CMR represent the main diagnostic tools. Specifically, echocardiography represents the first diagnostic approach; however, it is CMR that gives information about the pathophysiologic background behind HF in ARDs.

Effects of exercise training on cardiac function, exercise capacity, and quality of life in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials Abstract Left ventricular (LV) diastolic dysfunction is associated with the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and contributes importantly to exercise intolerance that results in a reduced quality of life (QOL) in HFpEF patients. Although the effects of exercise training on LV diastolic function, exercise capacity, or QOL in HFpEF patients have been examined in randomized clinical trials (RCTs), results are inconsistent due partly to limited power with small sample sizes. We aimed to conduct a meta-analysis of RCTs examining the effects of exercise training on LV diastolic function and exercise capacity as well as QOL in HFpEF patients. The search of electronic databases identified 8 RCTs with 436 patients. The duration of exercise training ranged from 12 to 24 weeks. In the pooled analysis, exercise training improved peak exercise oxygen uptake (weighted mean difference [95% CI], 1.660 [0.973, 2.348] ml/min/kg), 6-min walk distance (33.883 [12.384 55.381] m), and Minnesota Living With Heart Failure Questionnaire total score (9.059 [3.083, 15.035] point) compared with control. In contrast, exercise training did not significantly change early diastolic mitral annular velocity (weighted mean difference [95% CI], 0.317 [− 0.952, 1.587] cm/s), the ratio of early diastolic mitral inflow to annular velocities (− 1.203 [− 4.065, 1.658]), or LV ejection fraction (0.850 [− 0.128, 1.828] %) compared with control. In conclusion, the present meta-analysis suggests that exercise training improves exercise capacity and QOL without significant change in LV systolic or diastolic function in HFpEF patients.

Nutrition intervention in heart failure: should consumption of the DASH eating pattern be recommended to improve outcomes? Abstract Heart failure (HF) is a chronic, systemic disorder that presents a serious and growing public health problem due to its high prevalence, mortality, and cost of care. Due to the aging of the population and medical advances that prolong the life of HF patients, more effective, widespread strategies for improved HF management in this rapidly growing patient population are needed. While the prevalence of malnutrition in HF patients has been well characterized, evidence is limited regarding the effects of specific macro- and micronutrient deficiencies on HF outcomes and their interaction with other aspects of HF management, including pharmacotherapy. There is a mounting appreciation for the effects of nutritional intervention on pathophysiology, treatment, and outcomes in patients with HF. Heart-healthy dietary patterns, such as the Dietary Approaches to Stop Hypertension (DASH), carry importance for the prevention and treatment of hypertension. While preliminary evidence looks promising regarding effects of DASH eating pattern consumption on ventricular function and 30-day hospitalizations in HF patients, more research is needed to confirm its effects on short-term and long-term HF outcomes while better understand underlying mechanisms in the context of HF pharmacotherapy.

Effects of European Society of Cardiology guidelines on medication profiles after hospitalization for heart failure in 22,476 Dutch patients: from 2001 until 2015 Abstract Prescriber adherence to guideline-recommended medication in patients with heart failure (HF) in clinical practice is suboptimal. We analyzed how evolving guideline recommendations influenced medication profiles after a first HF hospitalization. We extracted medication profiles from the Dutch PHARMO Database Network for 22,476 patients with a diagnosis of HF at hospital discharge between 2001 and 2015. The percentage of patients prescribed the combination of a beta-blocker (BB) and an angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) increased from 24 to approximately 45% within this 15-year period. The percentage of patients who also used a mineralocorticoid-receptor antagonist (MRA) reached approximately 20%. The probability of being prescribed these combinations decreased with increasing age. As a consequence of the policy change in the ESC guideline 2001, the use of BB increased from less than 40% in 2001 to about 70% by 2015. The percentage of patients prescribed an ACEI and/or an ARB, an MRA, or a diuretic was about stable, at respectively 63%, 37%, and 82%. Although the 2012 ESC guideline also advised MRA in the New York Heart Association (NYHA) class II, there was no increase in MRA prescriptions. Compliance with the ESC guidelines varied for the individual recommendations. Remarkably, there was no significant increase in MRA prescriptions. At the same time, developments were demonstrated, which were not instigated by the guidelines, like the shift from ACEI to ARB. Although the exact HF classification of our patients was unknown, given a relatively stable case mix, our data provide insight into "real-world" pharmacological management.

Personalized physiology-guided resuscitation in highly monitored patients with cardiac arrest—the PERSEUS resuscitation protocol Abstract Resuscitation guidelines remain uniform across all cardiac arrest patients, focusing on the delivery of chest compressions to a standardized rate and depth and algorithmic vasopressor dosing. However, individualizing resuscitation to the appropriate hemodynamic and ventilatory goals rather than a standard "one-size-fits-all" treatment seems a promising new therapeutic strategy. In this article, we present a new physiology-guided treatment strategy to titrate the resuscitation efforts to patient's physiologic response after cardiac arrest. This approach can be applied during resuscitation attempts in highly monitored patients, such as those in the operating room or the intensive care unit, and could serve as a method for improving tissue perfusion and oxygenation while decreasing post-resuscitation adverse effects.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com