Research Article | Volume 20 Issue 1 (Jan-Dec, 2015) | Pages 1 - 5
Heart Failure: Trial Results, Guidelines, and more
1
Author affiliations: Department of Internal Medicine, Belgrade University School of Medicine, Belgrade, Serbia; Heart Failure Centre, Belgrade University Medical Centre, Belgrade, Serbia Address for correspondence: Petar M. Seferovic, Department of Cardiology, Clinical Centre of Serbia, 26 Visegradska, 11000 Belgrade, Serbia
Under a Creative Commons license
Open Access
Received
Jan. 1, 2017
Revised
May 5, 2017
Accepted
July 8, 2017
Published
Dec. 31, 2017
Abstract

The 2017 Heart Failure Congress and the 4th World Congress on Acute Heart Failure took place in Paris, France. The congress was a unique forum where heart failure professionals from around the world met and exchanged ideas and information. The congress was attended by 5024 participants from 121 countries, with a large faculty of 287 international experts. The record number of abstracts (1704; up by 151 from the previous year) and case study submissions (253; up by 36 from the previous year) has established the 2017 Heart Failure Congress as the largest and most influential heart failure meeting in the world. Besides its attractive core program, this year's congress had several distinct and attractive features, including three late-breaking trial sessions, guidelines into practice track, HFA championships, HFA grand debates, and off-the-record sessions.

INAUGURAL SESSION

Two named lectures, the HFA Eugene Braunwald lecture, and the HFA Philip Poole Wilson lecture, were delivered by the world-leading scientists Michel Komajda (FR) and Faiez Zannad (FR), respectively. Komajda addressed the common and underestimated relationship between heart failure and diabetes, stressing that diabetes is a major risk factor for heart failure and the combination is associated with poor outcomes. He emphasized the importance of selecting the appropriate antidiabetic drugs, highlighting the clinical advantages of the SGLT2 inhibitor em- pagliflozin. Zannad discussed MRAs in the treatment of heart failure. MRAs have demonstrated a reverse translational track, showing how clinical science can influence basic research. The discovery of aldosterone and MRAs almost 40 years ago. ago had little influence on heart failure treatment until the positive findings of the RALES trial, revived the basic science interest in the topic. He stated that MRAS is at the beginning of its evolution and that the development of newer drugs that are tolerated better is needed.

LATE-BREAKING TRIALS

Among the late-breaking trials, the results of RELAX-AHF-2, and TRUE-AHF, were eagerly anticipated. RELAX-AHF-2 was an event-driven, phase 3 trial involving 6 600 patients hospitalized for acute heart failure, who received the relaxin receptor- antagonist, serelaxin. Although the use of serelaxin was safe, the study did not meet the primary end points, with no difference in cardiovascular mortality at 180 days and a reduction in worsening heart failure. The secondary end points (all-cause mortality at 180 days, length of initial hospital stay, or the combined endpoint of cardiovascular death or rehospitalizations) were also not met. TRUE-AHF demonstrated that a 48-hour infusion of ularitide, given an average of 6 hours after heart failure presentation, did not reduce cardiovascular mortality at 36 months, nor did it improve the symptoms at 6, 24, or 48 hours; however, it was shown to be safe, im- prove hemodynamics, and decrease blood pressure and cardiac wall stress.

 

EDIFY, another late-breaking trial, investigated the use of ivabradine in patients with HFPEF. The results demonstrated that ivabradine significantly reduced heart rate compared with placebo, but had no effect on diastolic function, exercise- capacity, or NTproBNP levels.

 

Another study, a multicenter, proof-of-concept study, investigated the short- or long-term use of low vs high-dose bromocriptine for the treatment of peripartum cardiomyopathy. This therapy was safe for both short and long-term use and it was associated with a significant improvement in LVEF, with no between-group differences. The results show that short-term, low-dose bromocriptine is sufficient in most cases and that critically ill patients may benefit from prolonged treatment with high-dose bromocriptine. 

GUIDELINES IN DAILY PRACTICE

The 2016 ESC/HFA guidelines for the diagnosis and treatment of acute and chronic heart failure were reviewed in the new "guidelines in daily practice" session. The session was focused on the patient; it was based on the analysis of two cases and presented by the top experts involved in developing the guidelines. They described the optimal treatment related to the case and explained where the relevant information, tables, and algorithms can be found in the guidelines. This session was highly interactive because the delegates were given the opportunity to send questions via the Heart Failure 2017 app.

 

An exciting new initiative was the HFA Championships, the competition for the best clinical case among the teams from Japan, Poland, and France. The teams were composed of four health care professionals who presented a case, followed by discussion and questions from the chairpersons. This session was also based on the ESC guidelines, and the teams had the opportunity to ask "trick" questions and to use two "jokers," which increased the tension and expectations of the competition. After a fierce, but fair, battle, Fausto Pinto, the president of the ESC, awarded the trophy to the French team.

GRAND DEBATES

The Grand Debate sessions attracted a lot of attention. In one session, the first debate focused on the use of sacubitril/valsartan as a first-line therapy in chronic heart failure, while the second discussed the role of vasodilators in acute heart failure. The arguments for the use of sacubitril/valsartan as a first-line therapy in chronic heart failure are based on the PARADIGM-HF trial, and it included the reduction in mortality and rehospitalization as well as the improvement in the biomarker profile, renal function, and symptoms/quality of life. However, it can be disputed that all of these beneficial findings are based on only one trial, which was done on the stable, outpatient population who were already taking ACE inhibitors or ARBs. In addition, due to the run-in design of the PARADIGM trial, the use of sacubitril/valsartan as a first-line therapy was not really tested. The second decade, which highlighted the role of vasodilators in acute heart failure in the years to come, concluded that, after the failure of two major clinical trials on promising drugs, a future strategy needs to be determined. It was felt that the targets in acute heart failure trials should be redefined and that joint efforts from both sides of the Atlantic Ocean are needed for innovative study designs.

 

In another Grand Debate session, the first debate focused on the benefit of treating nonischemic heart failure with an ICD. In light of the Danish study, which demonstrated that only nonischemic heart failure patients under the age of 68, but not older, benefited from ICD implantation, the discussion focused on the best indications. It was felt that the expense and uncertainty of the response to ICD therapy require a more individualized strategy to avoid unnecessary procedures. The second debate during the session discussed surgical revascularization in heart failure patients based on the long-term results from the STICH trial, which demonstrated a 10-year improvement with CABG in comparison with optimal medical therapy. The 2014 ESC/EACTS guidelines on myocardial revascularization recommend CABG for a subgroup of patients with significant left main and proximal left anterior descending coronary artery stenosis, a group that was excluded from STICH. Since improved blood flow and viable myocardium after revascularization are the most important factors for long-term benefit, it was felt that the treatment should be individualized. 

BEST HEART FAILURE PAPERS IN 2016

A special session featured the best heart failure papers of 2016, which was extremely well received. Marco Metra (IT), editor-in-chief of the European Journal of Heart Failure, acknowledged that the best paper published in this journal was the paper on the 2016 ESC/HFA guidelines for the diagnosis and treatment of acute and chronic heart failure, which was the most downloaded article in 2016, with the highest number of citations. Thomas Luscher (CH), editor-in-chief of the European Heart Journal, considered the paper on the results of the EMPA-REG OUTCOME trial, to be the best, since it is the most cited paper in this journal. The EMPA-REG OUTCOME trial demonstrated that empagliflozin reduced heart failure hospitalization and cardiovascular death in both patients with and without heart failure and type 2 diabetes. Stephan von Haehling (DE), the deputy editor of the ESC Heart Failure, an open-access journal, believed that the best paper was the article on the use of the CHAD,DS, VASC score to predict the mortality of heart failure patients with or without atrial fibrillation. This manuscript concluded that the CHAD DS, VASC score was a predictor of all-cause mortality in both groups, and may help identify high-risk heart failure patients.

THE GOLDEN ANNIVERSARY OF THE FIRST HUMAN HEART TRANSPLANT

One session of the congress was dedicated to the golden anniversary of the world's first human heart transplant. Heart transplantation is considered the breakthrough treatment for end-stage heart failure; it is the most successful therapeutic modality for these patients, with a mean life expectancy of 6 to 12 years. The progress in organ preservation and immunosuppression are important advancements, while the limited number of organs available remains a major obstacle. A total artificial heart needs further improvement, but it will be a viable option in the future.

CHART-1 TRIAL

The session on endomyocardial injection of cardiopoietic stem cells used for the treatment of ischemic heart failure reviewed the results of the CHART-1 clinical trial., In this investigation, the patient's own mesenchymal stem cells were used as a basis for the reparatory response. The results revealed that a stem cell injection. was associated with benefits in left ventricular remodeling, including an improvement in left ventricular end-systolic and end-diastolic volume after 52 weeks. The patients receiving fewer injections (<16) had a greater improvement in left ventricular dimensions than did patients receiving more injections.

CONCLUSION

The 2017 Heart Failure Congress was an extraordinary scientific event, that confirmed heart failure as a new, emerging specialty in cardiology, and it gave the latest updates on the recent developments in the field, reflecting the continuing success and leading place of the Heart Failure Association.

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