In patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, ...thereby favorably affecting patients' long-term prognosis.
In this double-blind trial, we randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. Treatment was initiated a median of 6 hours after the initial clinical evaluation. The coprimary outcomes were death from cardiovascular causes during a median follow-up of 15 months and a hierarchical composite end point that evaluated the initial 48-hour clinical course.
Death from cardiovascular causes occurred in 236 patients in the ularitide group and 225 patients in the placebo group (21.7% vs. 21.0%; hazard ratio, 1.03; 96% confidence interval, 0.85 to 1.25; P=0.75). In the intention-to-treat analysis, there was no significant between-group difference with respect to the hierarchical composite outcome. The ularitide group had greater reductions in systolic blood pressure and in levels of N-terminal pro-brain natriuretic peptide than the placebo group. However, changes in cardiac troponin T levels during the infusion did not differ between the two groups in the 55% of patients with paired data.
In patients with acute heart failure, ularitide exerted favorable physiological effects (without affecting cardiac troponin levels), but short-term treatment did not affect a clinical composite end point or reduce long-term cardiovascular mortality. (Funded by Cardiorentis; TRUE-AHF ClinicalTrials.gov number, NCT01661634 .).
Ventricular–arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent ...diagnostic and prognostic value and may be used to refine riskstratification and monitor therapeutic interventions. Traditionally, VAC is assessed by the non‐invasive measurement of the ratio of arterial (Ea) to ventricular end‐systolic elastance (Ees). With disease progression, both Ea and Ees may become abnormal and the Ea/Ees ratio may approximate its normal values. Therefore, the measurement of each component of this ratio or of novel more sensitive markers of myocardial (e.g. global longitudinal strain) and arterial function (e.g. pulse wave velocity) may better characterize VAC. In valvular heart disease, systemic arterial compliance and valvulo–arterial impedance have an established diagnostic and prognostic value and may monitor the effects of valve replacement on vascular and cardiac function. Treatment guided to improve VAC through improvement of both or each one of its components may delay incidence of heart failure and possibly improve prognosis in heart failure. In this consensus document, we describe the pathophysiology, the methods of assessment as well as the clinical implications of VAC in cardiac diseases and heart failure. Finally, we focus on interventions that may improve VAC and thus modify prognosis.
Fibrosis is a pivotal player in heart failure development and progression. Measurements of (markers of) fibrosis in tissue and blood may help to diagnose and risk stratify patients with heart ...failure, and its treatment may be effective in preventing heart failure and its progression. A lack of pathophysiological insights and uniform definitions has hampered the research in fibrosis and heart failure. The Translational Research Committee of the Heart Failure Association discussed several aspects of fibrosis in their workshop. Early insidious perturbations such as subclinical hypertension or inflammation may trigger first fibrotic events, while more dramatic triggers such as myocardial infarction
and myocarditis give rise to full blown scar formation and ongoing fibrosis in diseased hearts. Aging itself is also associated with a cardiac phenotype that includes fibrosis. Fibrosis is an extremely heterogeneous phenomenon, as several stages of the fibrotic process exist, each with different fibrosis subtypes and a different composition of various cells and proteins — resulting in a very complex pathophysiology. As a result, detection of fibrosis, e.g. using current cardiac imaging modalities or plasma biomarkers, will detect only specific subforms of fibrosis, but cannot capture all aspects of the complex fibrotic process. Furthermore, several anti‐fibrotic therapies are under investigation, but such therapies generally target aspecific aspects of the fibrotic process and suffer from a lack of precision. This review discusses the mechanisms and the caveats and proposes a roadmap for future research.
Acute right ventricular (RV) failure is a complex clinical syndrome that results from many causes. Research efforts have disproportionately focused on the failing left ventricle, but recently the ...need has been recognized to achieve a more comprehensive understanding of RV anatomy, physiology, and pathophysiology, and of management approaches. Right ventricular mechanics and function are altered in the setting of either pressure overload or volume overload. Failure may also result from a primary reduction of myocardial contractility owing to ischaemia, cardiomyopathy, or arrhythmia. Dysfunction leads to impaired RV filling and increased right atrial pressures. As dysfunction progresses to overt RV failure, the RV chamber becomes more spherical and tricuspid regurgitation is aggravated, a cascade leading to increasing venous congestion. Ventricular interdependence results in impaired left ventricular filling, a decrease in left ventricular stroke volume, and ultimately low cardiac output and cardiogenic shock. Identification and treatment of the underlying cause of RV failure, such as acute pulmonary embolism, acute respiratory distress syndrome, acute decompensation of chronic pulmonary hypertension, RV infarction, or arrhythmia, is the primary management strategy. Judicious fluid management, use of inotropes and vasopressors, assist devices, and a strategy focusing on RV protection for mechanical ventilation if required all play a role in the clinical care of these patients. Future research should aim to address the remaining areas of uncertainty which result from the complexity of RV haemodynamics and lack of conclusive evidence regarding RV‐specific treatment approaches.
Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the ...predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post‐discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient‐centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field.
Acute heart failure is a fatal syndrome. Emergency physicians, cardiologists, intensivists, nurses and other health care providers have to cooperate to provide optimal benefit. However, many ...treatment decisions are opinion‐based and few are evidenced‐based. This consensus paper provides guidance to practicing physicians and nurses to manage acute heart failure in the pre‐hospital and hospital setting. Criteria of hospitalization and of discharge are described. Gaps in knowledge and perspectives in the management of acute heart failure are also detailed. This consensus paper on acute heart failure might help enable contiguous practice.
Abstract
In acute heart failure (AHF) syndromes significant respiratory failure (RF) is essentially seen in patients with acute cardiogenic pulmonary oedema (ACPE) or cardiogenic shock (CS). ...Non-invasive ventilation (NIV), the application of positive intrathoracic pressure through an interface, has shown to be useful in the treatment of moderate to severe RF in several scenarios. There are two main modalities of NIV: continuous positive airway pressure (CPAP) and pressure support ventilation (NIPSV) with positive end expiratory pressure. Appropriate equipment and experience is needed for NIPSV, whereas CPAP may be administered without a ventilator, not requiring special training. Both modalities have shown to be effective in ACPE, by a reduction of respiratory distress and the endotracheal intubation rate compared to conventional oxygen therapy, but the impact on mortality is less conclusive. Non-invasive ventilation is also indicated in patients with AHF associated to pulmonary disease and may be considered, after haemodynamic stabilization, in some patients with CS. There are no differences in the outcomes in the studies comparing both techniques, but CPAP is a simpler technique that may be preferred in low-equipped areas like the pre-hospital setting, while NIPSV may be preferable in patients with significant hypercapnia. The new modality ‘high-flow nasal cannula’ seems promising in cases of AHF with less severe RF. The correct selection of patients and interfaces, early application of the technique, the achievement of a good synchrony between patients and the ventilator avoiding excessive leakage, close monitoring, proactive management, and in some cases mild sedation, may warrant the success of the technique.
Background
Cardiac resynchronisation therapy (CRT) reduces morbidity and mortality in appropriately selected patients with heart failure and is strongly recommended for such patients by guidelines. A ...European Society of Cardiology (ESC) CRT survey conducted in 2008–2009 showed considerable variation in guideline adherence and large individual, national and regional differences in patient selection, implantation practice and follow‐up. Accordingly, two ESC associations, the European Heart Rhythm Association and the Heart Failure Association, designed a second prospective survey to describe contemporary clinical practice regarding CRT.
Methods and results
A survey of the clinical practice of CRT‐P and CRT‐D implantation was conducted from October 2015 to December 2016 in 42 ESC member countries. Implanting centres provided information about their hospital and CRT service and were asked to complete a web‐based case report form collecting information on patient characteristics, investigations, implantation procedures and complications during the index hospitalisation. The 11 088 patients enrolled represented 11% of the total number of expected implantations in participating countries during the survey period; 32% of patients were aged ≥75 years, 28% of procedures were upgrades from a permanent pacemaker or implantable cardioverter‐defibrillator and 30% were CRT‐P rather than CRT‐D. Most patients (88%) had a QRS duration ≥130 ms, 73% had left bundle branch block and 26% were in atrial fibrillation at the time of implantation. Large geographical variations in clinical practice were observed.
Conclusion
CRT Survey II provides a valuable source of information on contemporary clinical practice with respect to CRT implantation in a large sample of ESC member states. The survey permits assessment of guideline adherence and demonstrates variations in patient selection, management, implantation procedure and follow‐up strategy.
Aims
Decisive evidence on the optimal diuretic agent, dosing schedule, and administration route is lacking in acute heart failure (AHF) with congestion. The Acetazolamide in Decompensated heart ...failure with Volume OveRload (ADVOR) trial is designed to test the hypothesis that the carbonic anhydrase inhibitor acetazolamide, a potent inhibitor of proximal tubular sodium reabsorption, improves decongestion when combined with loop diuretic therapy in AHF, potentially leading to better clinical outcomes.
Methods
The ADVOR trial is set up as a multicentre, randomized, double‐blind, placebo‐controlled study, aiming to recruit 519 patients with AHF and clinically evident volume overload. All study participants receive high‐dose intravenous loop diuretics as background therapy and are randomized towards intravenous acetazolamide at a dose of 500 mg once daily vs. placebo, stratified according to including study centre and ejection fraction (< 40% vs. ≥ 40%). The primary endpoint is successful decongestion with no more than trace oedema assessed on the third morning after hospital admission, with good diuretic efficacy defined as a urine output > 3.5 L during the first 30–48 h of decongestive treatment. Secondary endpoints include all‐cause mortality or heart failure readmission after 3 months, length of hospital stay for the index admission, and longitudinal changes in the EuroQol‐5 dimensions questionnaire.
Conclusion
ADVOR will investigate if acetazolamide combined with loop diuretic therapy improves decongestion in AHF with volume overload.
PDF
