All cardiology roads led to Rome
The 2016 annual meeting of the European Society of Cardiology took place in Rome, Italy and convened more than 33 000 participants, reaching an unprecedented record of participation to confirm that this meeting is the largest cardiovascular forum worldwide. In addition, this meeting had the honor to welcome His Holiness Pope Francis who strongly encouraged the professionals to continue their efforts to reduce the burden of cardiovascular diseases in the world and heal the people who are affected by these diseases. In the area of heart failure, several important studies were presented.
TELEMONITORING IN HEART FAILURE: DISAPPOINTING RESULTS
Two implant-based telemonitoring studies were presented. Martin Cowie (UK) presented the results from the REM-HF trial,1 which included 1650 patients with mild-to-moderate heart failure from nine centers in the UK. The trial compared usual care with usual care plus weekly transmission of data through an implantable cardiac defibrillator or a pacemaker. The primary outcome (all-cause mortality or cardiovascular hospitalization) and its components were unchanged in the telemonitoring group although transmission of information led to action in ≈70% of the patients.
Similarly, the MORE-CARE trial,2 which was presented by Giuseppe Boriani (IT), enrolled just over 900 patients before recruitment was stopped due to a low enrollment rate. Patients were randomized to in-of fice follow-ups alone or remote monitoring plus in-of fice follow-ups. No significant dif ferences were found in the primar y end point (composite of death and cardiovascular and device-related hospitalizations) or its components. However, there was a modest reduction in health care resource utilization with the remotely monitored patients, which was mainly due to a reduction in scheduled cardiovascular in-office visits.
These results raise some questions about the potential interest of telemonitoring in heart failure since they do not show a reduction in hospitalizations. Previous studies of implant-based monitoring have provided mixed results. The IN-TIME study3 used a call center 24/24 hours and 7/7 days, and the data showed a significant reduction in the primary outcome, which was entirely driven by a decrease in mortality. However, the thoracic impedance–based system used in the OPTILINK study was not associated with any benefit.4
Several explanations can be put forward including the fact that patients from several studies had mild heart failure and/or were optimally treated, which may have limited the impact of potential medical interventions or the need to change medications. Other limiting factors include the large amounts of information to be analyzed, the patients’ adherence to the system, and the reactivity of health care professionals, ie, the actions taken after receiving a warning signal. In any case, these two new studies, REM-HF and MORE-CARE, cast some doubt on the interest of implant-based telemonitoring systems as a substitute for the standard of care in the management of chronic heart failure.
IMPLANTATION OF A DEFIBRILLATOR FOR NONISCHEMIC CARDIOMYOPATHY
The current indications of an ICD in patients with HFREF are stronger in ischemic heart failure due to the results of the MADIT5 and SCD-HeFT6 trials than in dilated cardiomyopathy where only one trial—DINA- MIT7—suggested benefit.
Recently, the DANISH trial (DANISH study to assess the efficacy of ICDs in patients with nonischemic systolic heart failure on mortality)8 enrolled more than
1100 patients with dilated cardiomyopathy to evaluate the potential benefit of an ICD with or without cardiac resynchronization compared with the standard of care with or without cardiac resynchronization. The primary outcome was total mortality, but there was only a nonsignificant trend in favor of the ICD group.
In contrast, there was a significant 50% reduction in the secondary end point (sudden cardiac death). The authors also did subgroup analyses and found that, in the younger patients.
HEART FAILURE IN THE COMMUNITY: A HUGE BURDEN TO COME
Several epidemiological studies were presented during the meeting. Ragnar Danielsen (Iceland) presented the results from the AGES-Reykjavík study,9,10 which included 5706 randomly selected elderly partici- pants who were representative of the population of Iceland. The study assessed the prevalence of heart fail- ure in elderly people; the prevalence was 1.9% in patients 80 years old. Importantly, based on the predicted age distribution and the increase in the number of elderly people >70 years old, the study forecasts that the number of patients with heart failure will have increased 2.9 times by the year 2060.
Rahul Potluri (UK) presented another study, ACALM,11 which enrolled 457 000 patients hospitalized in the Midlands, UK from 2000 to 2014, 13 416 of whom were diagnosed with heart failure. The study assessed the number of readmissions within 5 years and recorded the vital status. The study confirmed that recurrent readmissions are the hallmark of heart failure: 42% of the studied population had 0-3 readmissions, 29% had 4-7 readmissions, and 14% had 8-11 readmissions. The study also calculated the risk of death associated with rehospitalizations and concluded that each readmission significantly increased the mortality risk by 2%.
Pardeep Jhund (UK) presented the results from a study that assessed the mortality and morbidity in a cohort of 14 546 patients with heart failure from Scotland.12 He observed that death was 15 per 100 patient-years and that cardiovascular hospitalizations were highly prevalent (31 per 100 patient-years), where half of these hospitalizations were related to heart failure. The median length of stay was 8 days. Noncardiovascular hospitalizations were also highly prevalent (49 per 100 patient-years), the most common specified causes being respiratory or gastrointestinal. Finally, the investigators looked at the rate of prescriptions for recommended medications, which was suboptimal, particularly for β-blockers and mineralocorticoid receptor antagonists (56% and 25% respectively in the subgroup with left ventricular dysfunction). Only a minority of patients were receiving the target doses recommended by the international guidelines (41% for angiotensin-converting enzyme inhibitors [ACE inhibitors], 19% for angiotensin receptor antagonists, and 20% for β-blockers).
These results highlight the facts that heart failure is a growing health care burden with increased prevalence, coexistent comorbidities, high mortality, and a high rate of recurrent hospitalizations and that the pharmacological management of patients with heart failure remains suboptimal. These findings should prompt governmental initiatives to anticipate the epidemic of heart failure, which is forecast due to the aging population in Western countries. In addition, these results should lead to specific studies to analyze the reasons why patients with heart failure do not receive recommended therapies and remain at low dosage of these treatments when prescribed.
NEW GUIDELINES ON THE MANAGEMENT OF HEART FAILURE
The updated version of the ESC guidelines on the diagnosis and the management of heart failure have been extensively discussed during the meeting. Several important changes have been introduced in the new version, including:
- A new algorithm for the diagnosis of nonacute-onset heart failure, which is based on an a priori probability, and that is determined using simple diagnostic tools (clinical history, signs, symptoms, and electrocardiograms) and then using natriuretic peptides and echocardiography or echocardiography directly if the dosage of natriuretic peptides is not routinely available.
- A new category for heart failure has been included that is based on the determination of ejection fraction: heart failure with midrange ejection fraction (HFMEF). HFMEF is defined by an ejection fraction between 40% and 49%, signs and/or symptoms, and elevated natriuretic peptides or evidence of structural cardiac abnormalities or diastolic dysfunction. The rationale for introducing this intermediate category is that the level of 40% to 49% already suggests that there is an alteration in systolic dysfunction, which may be a transitional phase from heart failure with preserved ejection fraction (HFPEF) to heart failure with reduced ejection fraction (HFREF) or conversely a transition from documented HFREF toward normal heart failure, but it can be argued that in this “gray zone,” there is no evidence to guide treatment.
- A new algorithm for the management of heart failure with reduced ejection fraction: ACE inhibitors (or angiotensin receptor antagonists if not tolerated), β-blockers, and mineralocorticoid receptor antagonists are the first steps of the pharmacological management. Then, three different options are proposed if the patients remain symptomatic: (i) angiotensin receptor-neprilysin inhibitor (ARNi) (sacubitril-valsartan combination) in patients tolerating ACE inhibitors or angiotensin receptor antagonists; (ii) ivabradine in patients with increased heart rate >70 bpm and in sinus rhythm; or (iii) cardiac resynchronization therapy in patients with a QRS >130 msec and in sinus rhythm. The new guidelines state that these three different options are not exclusive.
At the end of the 2016 annual meeting of the European Society of Cardiology, it was evident that substantial progress has been made in the management of heart failure. However, there are important areas where the situation remains suboptimal due to gaps in the evidence or to unmet medical needs, such as high rehospitalization rates, low titration of recommended medications, heart failure with preserved ejection fraction, and acute heart failure. In particular, acute heart failure remains a major concern for patients and physicians, and health care systems will be under strain if no action is taken to reduce the burden of this condition.
- Morgan JM, Dimitrov BD, Gill J, et al. Rationale and study design of the REM-HF study: remote management of heart failure using implanted devices and formalized follow-up procedures. Eur J Heart Fail. 2014;16:1039-1045.
- Boriani G, Da Costa A, Quesada A, et al; MORE-CARE Study Investigators. Effects of remote monitoring on clinical outcomes and use of healthcare resources in heart failure patients with biventricular defibrillators: results of the MORE-CARE multicentre randomized controlled trial. Eur J Heart Fail. 2016 Aug 28. Epub ahead of print.
- Hindricks G, Taborsky M, Glikson M, et al; IN-TIME study group. Implant-based multiparameter telemonitoring of patients with heart failure (IN-TIME): a randomised controlled trial. Lancet. 2014;384:583-590.
- Böhm M, Drexler H, Oswald H, et al; OptiLink HF Study Investigators. Fluid status telemedicine alerts for heart failure: a randomized controlled trial. Eur Heart J. 2016 Mar 16. Epub ahead of print.
- Moss AJ, Hall WJ, Cannom DS, et al; Multicenter Automatic Defibrillator Implantation Trial Investigators. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med. 1996;335:1933-1940.
- Bardy GH, Lee KL, Mark DB, et al; SCD-HeFT Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005;352:225-237.
- Hohnloser SH, Kuck KH, Dorian P, et al; DINAMIT Investigators. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med. 2004;351:2481-2488.
- Køber L, Thune JJ, Nielsen JC, et al; DANISH Investigators. Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med. 2016 Aug 27. Epub ahead of print.
- Danielsen R, Aspelund T, Harris TB, Gudnason V. The prevalence of aortic stenosis in the elderly in Iceland and predictions for the coming decades: the AGES-Reykjavík study. Int J Cardiol. 2014;176:916-922.
- Danielsen R, Einarsson H, Thorgeirsson G, Aspelund T, Gudnason V. Heart failure in the elderly and predictions for the future: the AGES-Reykjavik Study [abstract P5425]. Eur Heart J. 2016;37(suppl abstract):1109.
- Loudon BL, Gollop ND, Carter PR, Uppal H, Chandran S, Potluri R. Impact of cardiovascular risk factors and disease on length of stay and mortality in patients with acute coronary syndromes. Int J Cardiol. 2016;220:745-749.
- Jhund PS, McMurray JJV, Calado F, et al. High risk of morbidity and mortality in patients with heart failure and under treatment with evidence based therapies in the UK [abstract P1656]. Eur Heart J. 2016;37(suppl abstract):325.