How does heart failure manifest itself in different regions of the world? Preliminary results of an international registry study. Furthermore, can game consoles actually improve the performance of heart failure patients?
The global observational study within the REPORT-HF registry examines patients hospitalized with acute heart failure (AHF) anywhere in the world either for the first time (de novo) or for decompensation of a chronic form. For this purpose, it collects data from over 300 centers in more than 40 countries. In addition to demographics, clinic, comorbidities, treatment patterns, quality of life, and in-hospital and post-discharge mortality are assessed. The goal of the prospective program: Generate hypotheses for international clinical trials, raise global health policy awareness of the condition, and stimulate discussions on current clinical practice and guideline implementation. In total, slightly fewer than 20,000 adults are participating in the three-year follow-up after the 32-month inclusion phase, which has now been completed. Some results from the former period (i.e. from the index phase of hospitalization) were now available at the ESC-HF in Vienna.
Differences raise questions
While one-fifth presented with de novo heart failure in North America, a full four-fifths did so in Southeast Asia. The remaining regions were in between with about one third. The difference in time to initial (intravenous) therapy is striking. Whereas in Eastern Europe and Southeast Asia, initial treatment is generally initiated quickly – certain measures while still in the outpatient clinic, others directly upon arrival at the hospital – it takes considerably longer in North America. From the patient’s perspective, the difference is tangible: the faster IV therapy is initiated, the faster his symptoms improve. While IV diuretics were used comparably globally, this was not true for vasoactive IV drugs. The reasons for decompensation and hospitalization were also very different: While lack of adherence to medications and diet was more common in North America (19%), ischemic events could be observed more often in Southeast Asia, the Western Pacific region, and the Eastern Mediterranean and Africa (16-26%). In addition, in the Western Pacific region, infections such as pneumonia were among the most common reasons at 19%.
REPORT-HF is the first robust international AHF registry. Unlike existing registers, it collects data in a total of seven different world regions (including North, Central/South America, Western, Eastern Europe, Eastern Mediterranean and Africa, Southeast Asia and Western Pacific) simultaneously and can present them comparatively in a kind of “global snapshot.” The sometimes surprising deviations in therapy may have various causes. For example, temporal treatment delays showed similar patterns across large regions. Thus, it appears to be less due to individual hospitals than to regional factors that patients were treated at different rates and, if necessary, referred to the cardiac/intensive care unit or to the ward. Did the increasingly overcrowded emergency wards and hospitals in the USA have an influence, or simply the fact that many patients in the USA feel “less ill” or “less sick”? presented more unspecific? Indeed, a finding of REPORT-HF was also that the leading symptom of AHF, dyspnea at rest, was less dominant in these areas (72% at presentation versus 88% in Southeast Asia, for example). X-ray chest showed less congestion. Many an emergency patient without such pulmonary symptoms but with e.g. swollen legs/abdomen and sudden weight gain seems not to have made it to the “top priority list” in the US and therefore remained behind other emergencies such as sepsis, trauma, etc. for a longer time in the crowded emergency department.
As always, insufficient guideline implementation could be responsible for the deviating use of IV medications. In addition, the approval status as well as national preferences regarding certain drugs or a different interpretation of the existing evidence may play a role.
The poor adherence to diet and medications in the United States is likely due in part, as is often the case, to the U.S. insurance system with its problematic access to constant medical care and financial challenges in obtaining medications.
Ultimately, the study fails to explain the exact reasons for the regional differences in therapy. Indeed, at least on the basis of the characteristics collected, it cannot be argued that AHF patients differ fundamentally internationally. Ultimately, it is probably more important to ask whether the different approaches to therapy are reflected in a different outcome. This is not the case, at least as far as the time to therapy is concerned. Neither mortality nor length of hospital stay has been affected. In addition to renal function, congestion signs on x-ray, and systolic blood pressure, IV vasodilators also had an effect on length of hospital stay: Those who received such medications appeared to require shorter hospitalization across the board.
Nevertheless: One aligns oneself internationally
Despite all the differences mentioned, one point should not be overlooked. Complementary to other registry studies (e.g. GREAT network, which also collects data on patients with AHF in the emergency department), it can be stated: AHF patients today are seemingly more similar than one might have assumed from previous studies and smaller registries. Phenotype, comorbidities, outcomes, and ultimately therapy for acute heart failure are moving closer together internationally, according to Prof. Sean Collins, MD, Nashville, presenter of the registry.
Via procalcitonin affect prognosis?
A further investigation at the congress also shows that the internationally widespread doctrine does not always stand on as firm a footing as assumed. The strategy of procalcitonin determination in differential diagnosis of concomitant pneumonia in AHF should actually be widespread throughout Europe, after all it is mentioned in the current ESC guideline of 2016 [1] – based on observational studies. The benefit of the procedure is the targeted use of an antibiotic, if necessary. However, the multicenter, randomized-controlled IMPACT-BIC-18 trial raised the question at the congress: Can prognosis really be improved by this knowledge or can procalcitonin be omitted before therapy and still generate a comparable outcome?
Background: Both AHF and pneumonia can cause dyspnea, so it is sometimes difficult to recognize concomitant pneumonia in an AHF patient. The ESC recommendation seems justified in that, according to an observational study called BACH [2], this biomarker actually makes the diagnosis of pneumonia much more accurate. According to the IMPACT-BIC-18 study with 792 patients, it is questionable whether procalcitonin-guided antibiotic therapy in a second step really provides a prognostic benefit compared with an approach based on standard characteristics. In the BACH study, patients with AHF and elevated procalcitonin levels (>0.21 ng/ml) clearly benefited from antibiotics: If they did not receive these drugs, they were significantly worse off (p=0.046). In contrast, individuals with low procalcitonin levels below 0.05 ng/ml fared better without antibiotics.
Study participants from IMPACT-BIC-18 arrived at the emergency department with dyspnea and suspected acute heart failure. Elevated levels of natriuretic peptides were a prerequisite for study inclusion. After that, a treatment decision was made randomized either on the basis of standard characteristics such as fever and leukocyte count or on the basis of additional procalcitonin.
What is certain is that there was no difference in mortality between the groups at 30 and 90 days (primary endpoint). However, and this is a weighty but, mortality in the overall study was 9.2%, much lower than anticipated. High-risk patients, i.e. those with a high mortality risk, were excluded from the study from the outset due to the selection criteria – in observational studies, however, they are part of the normal population. Pneumonia was therefore a rare event in the low-risk IMPACT-BIC-18 study sample, and procalcitonin levels were low, averaging 0.07 ng/ml (cutoff for pneumonia: 0.2 ng/ml – met in only about 16%).
If one thinks that the ESC recommendation should be reconsidered in view of the results, a second look shows that IMPACT-BIC-18 can only serve as a limited basis for revolutions due to the sample being of little relevance for everyday life. In the investigational arm, there was also evidence of problems with adherence to the study protocol. Study leader Prof. Dr. med. Martin Möckel of Charié Berlin does not see procalcitonin-guided antibiotic therapy at its end. IMPACT-BIC-18 also retrospectively confirmed the value of procalcitonin as a risk marker: The mortality of procalcitonin-positive patients was significantly higher than that of procalcitonin-negative patients. Future randomized trials would need to select their study samples differently to demonstrate an effect of the procalcitonin-guided approach after all. This was not possible in the specific population of IMPACT-BIC-18, which had little to do with everyday clinical practice.
Source: European Society of Cardiology Heart Failure (ESC-HF) 2018, May 26-29, 2018, Vienna.
Literature:
- Ponikowski P, et al: 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016 Jul 14; 37(27): 2129-2200.
- Maisel A, et al: Use of procalcitonin for the diagnosis of pneumonia in patients presenting with a chief complaint of dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial. Eur J Heart Fail 2012 Mar; 14(3): 278-286.
- O’Connor CM, et al: Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 2009 Apr 8; 301(14): 1439-1450.
- Cooper LB, et al: Psychosocial Factors, Exercise Adherence, and Outcomes in Heart Failure Patients. Insights From Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION). Circulation: Heart Failure 2015; 8: 1044-1051.
CARDIOVASC 2018; 17(4) – published 8.6.18 (ahead of print).
