Abstract
Aims
Acute heart failure (AHF) has an impact on human health worldwide. Despite guidelines for treatment and management of AHF, mortality rates remain high. The main objective of this study was to compare standard in‐hospital treatment and management of AHF against current clinical guidelines and variations across regions.
Methods
Between February 2018 and May 2021, investigators were approached to participate in the STRONG‐HF study. The lead investigator at 158 sites in 20 countries completed a site feasibility questionnaire. Sites were grouped by country into five different regions: Africa and the Middle East, Eastern Europe, Russia, South America, and Western Europe.
Results
According to the questionnaires, there are large differences in how patients present due to AHF and where in the hospital they are treated. There were significant differences in reported percentage of AHF patients receiving angiotensin converting enzymes inhibitors across the regions (P < 0.001), mostly due to prescription of more angiotensin II receptor blockers and angiotensin receptor‐neprilysin inhibitors in South America and Western Europe. Reported beta‐blocker use was high across all of the regions. Device therapy and percutaneous interventions were more common in Europe. Sites reported a 5 to 8 day length of stay, while in Russia most have a 10 to 12 day length of stay. Regions reported that AHF patients follow up with a community cardiologist or general practitioner post‐discharge, although follow‐up was commonly more than 1 month post discharge, and not all sites had the capability to measure natriuretic peptides post discharge.
Conclusions
In this analysis of feasibility questionnaires, most sites reported general adherence to ESC guidelines for treatment and management of AHF patients although percutaneous and device therapy was less common outside Europe and follow‐up after discharge took place late and was not as extensive as recommended. There were wide variations seen within and across regions in some areas.
Keywords: Acute heart failure, Feasibility questionnaire, Regions, Adherence, Guidelines
Introduction
Acute heart failure (AHF) poses a significant economic and human health burden globally. 1 This disease has an established prevalence in high‐income countries and incidence is increasing in low‐ and middle‐income countries due to demographic transitions. 2
AHF is characterized by a constellation of symptoms, causing great heterogeneity within AHF patients. 1 As a result, guidelines have been published to assist clinicians in properly diagnosing, managing, and treating the various manifestations of AHF. 3 However, recent studies have found that adherence in practice to the established guidelines is suboptimal 4 and there are differences in the dosages of guideline‐recommended medical therapy at discharge by region. 5 In‐hospital and post‐hospital discharge mortality rates remain high for AHF, despite targeted guidelines for management and treatment of AHF. 1
Hospital admission for AHF are followed by high morbidity and mortality 6 and hence establishing management plans for patients with acute decompensated chronic heart failure (HF) and de novo AHF is important. The main objective of this study was to compare standard in‐hospital treatment and management of AHF against current clinical guidelines and variations across regions.
Methods
We developed and distributed a site feasibility questionnaire for sites that were interested in participating in a prospective, multicentre, randomized parallel group trial, the STRONG‐HF study. The methods for this study have been described elsewhere. 7 Site feasibility questionnaires were distributed between February 2018 and May 2021. The lead principal investigator at each site was asked to fill out the questionnaire to the best of their knowledge prior to a decision regarding whether it would be appropriate to include their site in the STRONG‐HF trial. The questionnaire asked principal investigators about the management and treatment of HF in their facility and in their practice. Questionnaire items included patient presentation, unit or ward patients are sent to after a positive AHF diagnosis, number of AHF patients per month, average in‐hospital length of stay (LOS), procedures and lab examinations at admission for AHF, pharmacological treatment, and follow‐up post‐discharge.
A total of 158 sites from 20 countries were included in the study which were grouped by region (Africa and Middle East: Mozambique, Nigeria, South Africa, Tunisia, Turkey; Eastern Europe: Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Serbia, Slovakia, Ukraine; Russia: Russia; South America: Argentina, Colombia; Western Europe: Austria, France, Israel) (Table 1 ).
Table 1.
Number of sites included by region and country
| Region/country | n (%) |
|---|---|
| Total | 158 |
| Africa and Middle East | 22 (13.9) |
| Mozambique | 2 |
| Nigeria | 2 |
| South Africa | 2 |
| Tunisia | 7 |
| Turkey | 9 |
| Eastern Europe | 65 (41.1) |
| Bulgaria | 4 |
| Croatia | 5 |
| Czech Republic | 3 |
| Hungary | 9 |
| Poland | 10 |
| Romania | 11 |
| Serbia | 5 |
| Slovakia | 11 |
| Ukraine | 7 |
| Russia | 21 (13.3) |
| Russia | 21 |
| South America | 29 (18.4) |
| Argentina | 21 |
| Colombia | 8 |
| Western Europe | 21 (13.3) |
| Austria | 6 |
| France | 9 |
| Israel | 6 |
Statistical methods
This questionnaire was originally developed to assess whether the conduct of the STRONG‐HF study was feasible at a given site. However, we analysed responses in order to determine adherence to guidelines and differences between regions for AHF management and treatment. To describe the overall responses of the sites, continuous response variables are presented as n, mean (SD), minimum, and maximum, and categorical response variables are presented as n (%). Continuous response variables were compared among regions using ANOVA while categorical response variables were compared using a χ 2 test. Ordinal response variables were compared across regions using the Cochran–Mantel–Haenszel χ 2 test. Free‐text responses were allowed for some questions, resulting in non‐mutually exclusive categories; all responses reported by investigators in each region are shown, and the total could be more than 100%. For those questions with response categories that were not mutually exclusive, univariate analysis of each response was performed in the same fashion as mutually exclusive variables and p‐values were adjusted for multiple comparisons for categories with > 2 responses in all regions using the Bonferroni–Holm correction. Two‐sided P < 0.05 was considered statistically significant. All analyses were carried out using SAS 9.4 (SAS Institute, Cary, NC, USA).
Results
In‐hospital management
Most (55.2%) sites reported that AHF patients present to the hospital via ambulance, and 76.0% reported that the patients present via emergency room. There was a significant difference among the regions in sites that reported AHF patients present via ambulance, with fewer sites reporting this presentation category in Africa and the Middle East (18.2%) and the majority of sites in Russia reporting this presentation category (95.2%) (P < 0.001). Most sites reported that AHF patients present to their hospital via the emergency room in Africa and the Middle East, Eastern Europe, South America, and Western Europe (77.3%, 74.2%, 86.2%, and 100%), while only 42.9% of sites in Russia reported patients presenting via the emergency room (P = 0.001). Many sites in South America reported patients presenting via other clinics, departments, or physicians (69.0%), while sites in the other regions reported this category less often (P = 0.018) (Table 2 ).
Table 2.
Presentation and admittance locations and number of acute heart failure patients per month reported by sites within region
| Question | Statistic | Africa and Middle East (N = 22) | Eastern Europe (N = 65) | Russia (N = 21) | South America (N = 29) | Western Europe (N = 21) | P‐value |
|---|---|---|---|---|---|---|---|
| How do patients with Acute HF present to your hospital/clinic? a , b | |||||||
| Admitted c | n (%) | 1 (4.5%) | 1 (1.6%) | 0 | 0 | 0 | |
| Ambulance | n (%) | 4 (18.2%) | 34 (54.8%) | 20 (95.2%) | 18 (62.1%) | 9 (45.0%) | <0.001 |
| Cardiology department | n (%) | 13 (59.1%) | 19 (30.6%) | 9 (42.9%) | 14 (48.3%) | 7 (35.0%) | 0.306 |
| CICU c | n (%) | 0 | 0 | 0 | 1 (3.4%) | 0 | |
| Emergency department | n (%) | 17 (77.3%) | 46 (74.2%) | 9 (42.9%) | 25 (86.2%) | 20 (100.0%) | 0.001 |
| Emergency clinics c | n (%) | 0 | 2 (3.2%) | 0 | 0 | 0 | |
| General physicians c | n (%) | 0 | 6 (9.7%) | 0 | 0 | 1 (5.0%) | |
| HF clinic c | n (%) | 0 | 0 | 0 | 1 (3.4%) | 0 | |
| ICU c | n (%) | 0 | 0 | 0 | 2 (6.9%) | 2 (10.0%) | |
| Internal medicine | n (%) | 5 (22.7%) | 11 (17.7%) | 6 (28.6%) | 10 (34.5%) | 6 (30.0%) | 0. 459 |
| Local HF clinic c | n (%) | 0 | 1 (1.6%) | 0 | 0 | 0 | |
| Other clinics/depts/physicians | n (%) | 6 (27.3%) | 20 (32.3%) | 7 (33.3%) | 20 (69.0%) | 6 (30.0%) | 0. 018 |
| Outpatient clinic c | n (%) | 1 (4.5%) | 1 (1.6%) | 0 | 0 | 1 (5.0%) | |
| Referred c | n (%) | 3 (13.6%) | 6 (9.7%) | 0 | 4 (13.8%) | 2 (10.0%) | |
| Where does the patient go once positively diagnosed with AHF? a , b | |||||||
| Cardiology department | n (%) | 16 (72.7%) | 44 (68.8%) | 15 (75.0%) | 11 (37.9%) | 18 (90.0%) | 0. 006 |
| CICU | n (%) | 9 (40.9%) | 24 (37.5%) | 9 (45.0%) | 12 (41.4%) | 8 (40.0%) | 0.982 |
| Coronary c | n (%) | 0 | 2 (3.1%) | 0 | 2 (6.9%) | 0 | |
| Emergency room | n (%) | 3 (13.6%) | 5 (7.8%) | 7 (35.0%) | 9 (31.0%) | 4 (20.0%) | 0.034 |
| HF clinic c | n (%) | 0 | 0 | 0 | 1 (3.4%) | 0 | |
| ICU c | n (%) | 4 (18.2%) | 14 (21.9%) | 1 (5.0%) | 8 (27.6%) | 3 (15.0%) | |
| Internal medicine c | n (%) | 5 (22.7%) | 10 (15.6%) | 1 (5.0%) | 12 (41.4%) | 9 (45.0%) | |
| Private practice c | n (%) | 0 | 0 | 0 | 1 (3.4%) | 0 | |
| How many patients with AHF do you treat per month? | |||||||
| <10 | n (%) | 2 (9.5%) | 3 (4.6%) | 1 (4.8%) | 6 (20.7%) | 0 | 0.026 d |
| 10–20 | n (%) | 12 (57.1%) | 32 (49.2%) | 9 (42.9%) | 9 (31.0%) | 11 (55.0%) | |
| 20–30 | n (%) | 5 (23.8%) | 13 (20.0%) | 4 (19.0%) | 12 (41.4%) | 3 (15.0%) | |
| >30 | n (%) | 2 (9.5%) | 17 (26.2%) | 7 (33.3%) | 2 (6.9%) | 6 (30.0%) |
Abbreviations: AHF, acute heart failure; HF, heart failure; ICU, intensive care unit.
Response categories are not mutually exclusive.
P‐value adjusted for multiple comparisons using Bonferroni–Holm correction.
Statistical comparisons not made due to 1 or more regions having ≤2 responses in a category.
P‐value from CMH test.
After an AHF diagnosis is confirmed, the majority of sites in Africa and the Middle East, Eastern Europe, Russia, and Western Europe reported that patients are admitted to the cardiology ward (72.7%, 68.8%, 75.0%, and 90.0%, respectively). In contrast, the most commonly reported units in the South America region were the cardiovascular intensive care unit (CICU) and internal medicine (41.4% and 41.4%). Though a statistical comparison was not performed due to too few responses in Russia, a higher percentage of patients are sent to Internal Medicine after an AHF diagnosis in South America and Western Europe (41.4% and 45.0%) compared with other regions. Sites in Russia had the highest proportion of sites who reported treating more than 30 AHF patients per month (33.3%), while sites in the South American region had the highest proportion of sites who reported treating <10 AHF patients per month (20.7%) (Table 2 ).
Treatment
Sites were asked to indicate the average percentage of AHF patients who are treated with angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), angiotensin receptor‐neprilysin inhibitors (ARNi), mineralocorticoid receptor antagonists (MRA), and beta‐blockers at their institution. There were significant differences between regions in the mean percentage of AHF patients reported to be prescribed ACEis (P < 0.001). Sites in Africa and the Middle East, Eastern Europe, and Russian regions had higher mean percentage of reported ACEi use in AHF patients (76.2%, 77.0%, and 74.5%, respectively), while sites in South America and Western Europe regions had a slightly lower mean percentage of reported ACEi use (57.4% and 66.2%). The most commonly reported ACEi used at sites in Africa and the Middle East, Eastern Europe, and Western Europe was ramipril, while most sites in Russia and South America reported enalapril to be most commonly used in practice. Western European sites reported the highest mean percentages of AHF patients prescribed <50% of the European Cardiology Society (ESC) recommended dose for treatment of AHF with ACEi (45.4%), while sites in Africa and Middle East, Eastern Europe, Russia, South America reported the highest mean percentages of AHF patients receiving 50–100% of the recommended dose (40.0%, 46.7%, 44.8%, and 43.9%, respectively). However, the differences between regions in reported adherence to recommended dosing were not significant. Reported mean percentage of AHF patients receiving ARBs ranged from 18.6% (Eastern Europe) to 32.1% (South America) between the regions (P = 0.002). The most commonly reported ARB used in practice in Africa and the Middle East, Eastern Europe, and Western Europe regions was valsartan (66.7%, 77.6%, and 84.6%, respectively). The most commonly reported ARB used in practice was losartan in the Russian and South America regions (86.7% and 65.5%). Only two sites in the South American region reported commonly using candesartan in their practice, while more sites in other regions reported commonly using this medication. There were significant differences between regions in mean percentage of AHF patients prescribed ARNi (P < 0.001). Sites in South America had higher mean percentage of reported ARNi use in AHF patients (20.4%), while sites in Africa and Middle East had a lower mean percentage of reported ARNi use (1.4%). In any regions, sites in Africa and Middle East, Eastern Europe, Russia, South America, and Western Europe reported the highest mean percentages of AHF patients prescribed 50–100% of the recommended dose (45.8%, 37.6%, 53.6%, 38.0%, and 32.5%, respectively). Sites in all regions reported a relatively high mean percentage of AHF patients prescribed beta‐blockers. The two most commonly reported beta‐blockers given in the Africa and Middle East region were carvedilol (63.2%) and bisoprolol (52.6%). Bisoprolol was reported to be the most frequently prescribed beta‐blocker at most sites in Eastern Europe, Western Europe, and Russia (87.9%, 92.9%, and 86.7%, respectively), while in South America, carvedilol was reported (80.0%). All regions reported the highest mean percentage of patients receiving the 50–100% of beta‐blocker dosing recommended by ESC guidelines, except for Western Europe where the mean percentage of patients was highest for <50% dosing recommended by ESC guidelines. Reported MRA use in AHF patients ranged from 51.9% to 73.9% between regions (P = 0.001). Most sites in all regions indicated that the most commonly used MRA was spironolactone (Table 3 ).
Table 3.
Medication use, procedures, and devices in patients with acute heart failure
| Question | Statistic | Africa and Middle East (N = 22) | Eastern Europe (N = 65) | Russia (N = 21) | South America (N = 29) | Western Europe (N = 21) | P‐value |
|---|---|---|---|---|---|---|---|
| Percent of patients prescribed ACEi | n | 20 | 65 | 21 | 29 | 20 | |
| Mean (SD) | 76.2 (16.85) | 77.0 (13.66) | 74.5 (12.17) | 57.4 (17.86) | 66.2 (17.07) | <0.001 | |
| Min, Max | 40, 100 | 40, 95 | 60, 97 | 25, 90 | 40, 100 | ||
| Please indicate which are the most common ACEi used in your practice a , b | |||||||
| CAPTOPRIL c | n (%) | 7 (36.8%) | 4 (7.0%) | 3 (16.7%) | 0 | 0 | |
| ENALAPRIL | n (%) | 5 (26.3%) | 20 (35.1%) | 13 (72.2%) | 29 (100.0%) | 7 (38.9%) | <0.001 |
| FOSINOPRIL c | n (%) | 0 | 1 (1.8%) | 2 (11.1%) | 0 | 0 | |
| LISINOPRIL c | n (%) | 3 (15.8%) | 10 (17.5%) | 4 (22.2%) | 0 | 4 (22.2%) | |
| PERINDOPRIL c | n (%) | 5 (26.3%) | 38 (66.7%) | 8 (44.4%) | 0 | 3 (16.7%) | |
| QUINALAPRIL c | n (%) | 0 | 1 (1.8%) | 0 | 0 | 0 | |
| RAMIPRIL c | n (%) | 9 (47.4%) | 48 (84.2%) | 4 (22.2%) | 0 | 17 (94.4%) | |
| TRANDOLAPRIL c | n (%) | 1 (5.3%) | 13 (22.8%) | 0 | 0 | 0 | |
| ZOFENOPRIL c | n (%) | 0 | 6 (10.5%) | 0 | 0 | 0 | |
| Percentage of patients prescribed ACEi by ESC dosage recommendation categories a , b | |||||||
| ACEi % < 50% dose | n | 19 | 60 | 21 | 29 | 16 | |
| Mean (SD) | 33.0 (18.93) | 30.2 (19.35) | 27.6 (16.55) | 37.0 (24.30) | 45.4 (20.16) | 0.142 | |
| Min, Max | 5, 67 | 0, 90 | 10, 80 | 0, 90 | 5, 80 | ||
| ACEi % 50–100% dose | n | 19 | 60 | 21 | 29 | 16 | |
| Mean (SD) | 40.0 (20.14) | 46.7 (18.98) | 44.8 (13.55) | 43.9 (21.95) | 37.1 (17.76) | 0.377 | |
| Min, Max | 10, 95 | 5, 100 | 20, 70 | 10, 100 | 10, 70 | ||
| ACEi % 100% dose | n | 19 | 60 | 21 | 29 | 16 | |
| Mean (SD) | 29.6 (24.35) | 22.8 (17.95) | 27.6 (17.79) | 19.1 (14.26) | 15.6 (9.11) | 0.163 | |
| Min, Max | 3, 90 | 0, 80 | 0, 70 | 0, 50 | 0, 30 | ||
| Percent of patients prescribed ARB | n | 21 | 65 | 21 | 29 | 20 | |
| Mean (SD) | 20.0 (16.20) | 18.6 (12.29) | 19.9 (11.79) | 32.1 (18.05) | 24.6 (18.34) | 0.002 | |
| Min, Max | 0, 55 | 5, 50 | 3, 40 | 5, 80 | 5, 85 | ||
| Please indicate which are the most common ARB used in your practice a , b | |||||||
| CANDESARTAN c | n (%) | 7 (38.9%) | 26 (44.8%) | 3 (20.0%) | 2 (6.9%) | 7 (53.8%) | |
| IRBESARTAN c | n (%) | 3 (16.7%) | 2 (3.4%) | 1 (6.7%) | 0 | 0 | |
| LOSARTAN c | n (%) | 7 (38.9%) | 18 (31.0%) | 13 (86.7%) | 19 (65.5%) | 1 (7.7%) | |
| OLMESARTAN c | n (%) | 0 | 2 (3.4%) | 0 | 0 | 0 | |
| TELMISARTAN c | n (%) | 0 | 10 (17.2%) | 2 (13.3%) | 0 | 0 | |
| VALSARTAN | n (%) | 12 (66.7%) | 45 (77.6%) | 9 (60.0%) | 15 (51.7%) | 11 (84.6%) | 0.086 |
| Percentage of patients prescribed ARB by ESC dosage recommendation categories a , b | |||||||
| ARB % <50% dose | n | 18 | 62 | 20 | 28 | 14 | |
| Mean (SD) | 32.8 (17.34) | 29.3 (23.65) | 25.5 (17.91) | 38.2 (23.50) | 41.1 (21.84) | 0.381 | |
| Min, Max | 5, 70 | 0, 90 | 10, 80 | 0, 90 | 0, 70 | ||
| ARB % 50–100% dose | n | 18 | 62 | 20 | 28 | 14 | |
| Mean (SD) | 37.9 (15.52) | 46.1 (20.09) | 44.5 (15.30) | 42.7 (22.30) | 34.0 (15.85) | 0.390 | |
| Min, Max | 10, 60 | 5, 85 | 20, 70 | 10, 100 | 3, 60 | ||
| ARB % 100% dose | n | 18 | 62 | 20 | 29 | 14 | |
| Mean (SD) | 26.5 (20.99) | 23.5 (19.14) | 30.0 (19.53) | 22.2 (22.66) | 18.3 (14.05) | 0. 471 | |
| Min, Max | 0, 80 | 0, 70 | 0, 70 | 0, 100 | 0, 50 | ||
| Percentage of patients prescribed ARNi | n | 21 | 65 | 20 | 29 | 19 | |
| Mean (SD) | 1.4 (2.42) | 7.0 (9.80) | 5.5 (5.12) | 20.4 (20.60) | 16.5 (18.35) | <0.001 | |
| Min, Max | 0, 8 | 0, 50 | 0, 20 | 0, 80 | 0, 85 | ||
| Percentage of patients prescribed ARNi by ESC dosage recommendation categories a , b | |||||||
| ARNi % <50% dose | n | 6 | 47 | 14 | 27 | 13 | |
| Mean (SD) | 29.2 (31.05) | 29.6 (30.66) | 19.3 (25.26) | 34.4 (26.97) | 25.4 (27.19) | 0.916 | |
| Min, Max | 0, 80 | 0, 100 | 0, 80 | 0, 100 | 0, 100 | ||
| ARNi % 50–100% dose | n | 6 | 47 | 14 | 27 | 13 | |
| Mean (SD) | 45.8 (29.40) | 37.6 (27.10) | 53.6 (27.90) | 38.0 (25.62) | 32.5 (29.81) | 0.815 | |
| Min, Max | 20, 100 | 0, 100 | 10, 100 | 0, 100 | 0, 100 | ||
| ARNi % 100% dose | n | 6 | 47 | 14 | 27 | 13 | |
| Mean (SD) | 25.0 (27.39) | 18.0 (19.52) | 27.1 (28.94) | 20.2 (23.55) | 29.5 (27.07) | 0.916 | |
| Min, Max | 0, 50 | 0, 80 | 0, 90 | 0, 100 | 0, 95 | ||
| Percentage of patients prescribed MRA | n | 21 | 65 | 20 | 29 | 20 | |
| Mean (SD) | 69.8 (23.26) | 73.9 (16.87) | 70.1 (20.37) | 70.4 (20.61) | 51.9 (19.37) | 0.001 | |
| Min, Max | 0, 100 | 20, 100 | 25, 100 | 15, 96 | 10, 85 | ||
| Please indicate which are the most common MRA used in your practice a , b | |||||||
| EPLERENONE c | n (%) | 0 | 34 (65.4%) | 6 (40.0%) | 8 (27.6%) | 5 (38.5%) | |
| SPIRONOLACTONE | n (%) | 15 (93.8%) | 45 (86.5%) | 15 (100.0%) | 24 (82.8%) | 12 (92.3%) | 0. 437 |
| Percentage of patients prescribed an MRA by ESC dosage recommendation categories a , b | |||||||
| MRA % <50% dose | n | 17 | 61 | 17 | 28 | 15 | |
| Mean (SD) | 14.7 (22.11) | 18.0 (21.97) | 18.2 (25.49) | 19.3 (24.97) | 36.7 (35.59) | 0.193 | |
| Min, Max | 0, 90 | 0, 90 | 0, 80 | 0, 90 | 0, 100 | ||
| MRA % 50–100% dose | n | 17 | 61 | 17 | 28 | 15 | |
| Mean (SD) | 35.3 (29.61) | 44.8 (22.67) | 37.6 (26.99) | 30.9 (24.31) | 38.3 (23.27) | 0.193 | |
| Min, Max | 0, 100 | 0, 95 | 0, 80 | 5, 100 | 0, 100 | ||
| MRA % 100% dose | n | 17 | 60 | 17 | 29 | 15 | |
| Mean (SD) | 50.0 (31.02) | 36.6 (27.68) | 43.5 (34.86) | 51.6 (33.44) | 25.0 (26.93) | 0.106 | |
| Min, Max | 0, 100 | 0, 100 | 0, 100 | 0, 100 | 0, 70 | ||
| Percentage of patients prescribed beta‐blockers | n | 21 | 65 | 20 | 29 | 20 | |
| Mean (SD) | 82.8 (13.72) | 83.4 (10.97) | 85.0 (13.96) | 87.8 (8.84) | 81.9 (12.04) | 0. 368 | |
| Min, Max | 50, 100 | 30, 99 | 50, 100 | 60, 100 | 50, 98 | ||
| Please indicate which are the most common beta‐blockers used in your practice a , b | |||||||
| ATENOLOL c | n (%) | 0 | 0 | 0 | 1 (4.0%) | 0 | |
| BISOPROLOL | n (%) | 10 (52.6%) | 51 (87.9%) | 13 (86.7%) | 11 (37.9%) | 13 (92.9%) | <0.001 |
| CARVEDILOL | n (%) | 12 (63.2%) | 30 (61.2%) | 7 (46.7%) | 20 (80.0%) | 7 (50.0%) | 0.212 |
| CORNEDITOL c | n (%) | 0 | 1 (2.0%) | 0 | 0 | 0 | |
| METOPROLOL c | n (%) | 9 (47.4%) | 35 (60.3%) | 10 (66.7%) | 4 (13.8%) | 2 (14.3%) | |
| NEBIVOLOL c | n (%) | 4 (21.1%) | 14 (28.6%) | 1 (6.7%) | 1 (4.0%) | 2 (14.3%) | |
| Percentage of patients prescribed a beta‐blockers by ESC dosage recommendation categories a , b | |||||||
| BB % <50% dose | n | 20 | 62 | 18 | 29 | 17 | |
| Mean (SD) | 34.0 (19.30) | 35.1 (22.08) | 32.2 (17.84) | 31.2 (19.67) | 44.5 (22.75) | 0.931 | |
| Min, Max | 5, 80 | 0, 80 | 10, 70 | 0, 80 | 10, 90 | ||
| BB % 50–100% dose | n | 20 | 62 | 18 | 29 | 17 | |
| Mean (SD) | 41.5 (18.50) | 45.1 (18.06) | 46.4 (15.42) | 42.2 (21.86) | 36.6 (19.25) | 0.956 | |
| Min, Max | 10, 70 | 10, 80 | 20, 75 | 0, 100 | 5, 80 | ||
| BB % 100% dose | n | 20 | 62 | 18 | 29 | 17 | |
| Mean (SD) | 24.3 (20.41) | 20.4 (18.21) | 21.7 (12.83) | 23.4 (18.08) | 16.6 (12.91) | 0.956 | |
| Min, Max | 0, 80 | 0, 80 | 5, 50 | 0, 80 | 0, 50 | ||
| Procedures and devices | |||||||
| What percent of heart failure patients receive revascularization with PCI | n | 20 | 65 | 20 | 29 | 19 | |
| Mean (SD) | 35.3 (22.67) | 30.7 (21.21) | 13.3 (12.85) | 29.7 (22.48) | 39.9 (21.09) | 0.002 | |
| Min, Max | 0, 80 | 0, 85 | 0, 50 | 5, 80 | 8, 80 | ||
| What percent of heart failure patients receive revascularization with CABG | n | 20 | 65 | 19 | 29 | 17 | |
| Mean (SD) | 17.6 (13.39) | 12.8 (13.83) | 6.9 (9.41) | 14.7 (17.67) | 9.1 (5.48) | 0.102 | |
| Min, Max | 0, 50 | 0, 50 | 0, 40 | 0, 70 | 0, 20 | ||
| What percent of heart failure patients have an ICD | n | 20 | 65 | 19 | 29 | 20 | |
| Mean (SD) | 17.2 (14.27) | 22.1 (23.43) | 5.8 (11.09) | 17.7 (17.92) | 34.3 (21.96) | <0.001 | |
| Min, Max | 0, 50 | 0, 90 | 0, 50 | 0, 70 | 5, 95 | ||
| What percent of heart failure patients have a CRT | n | 20 | 65 | 18 | 29 | 19 | |
| Mean (SD) | 8.9 (5.30) | 11.6 (12.71) | 3.7 (4.83) | 10.8 (12.15) | 24.1 (22.01) | <0.001 | |
| Min, Max | 0, 20 | 0, 60 | 0, 20 | 0, 50 | 4, 80 |
Abbreviations: ACEi, angiotensin converting enzyme inhibitors; ARB, angiotensin II receptor blockers; BB, beta‐blockers; CABG, coronary artery bypass grafting; CRT, cardiac resynchronization therapy; ICD, implantable cardioverter‐defibrillators; PCI, percutaneous coronary intervention.
Response categories are not mutually exclusive.
P‐value adjusted for multiple comparisons using Bonferroni–Holm correction.
Statistical comparisons not made due to 1 or more regions having ≤2 responses in a category.
Procedures and devices
Sites were asked to indicate the average percentage of AHF patients that undergo certain procedures at their institution. Sites in the Africa and Middle East, Eastern Europe, South America, and Western Europe regions reported similar average percentages of patients who underwent percutaneous coronary intervention (PCI) (35.3%, 30.7%, 29.7%, and 39.9%, respectively), while Russia reported a lower percentage of patients who underwent PCI than all other regions (13.3%; P = 0.002). There was no significant difference between regions in the reported mean percentage of AHF patients who underwent coronary artery bypass grafting with higher percentages in Africa and Middle East (17.6%) and South America (14.7%) vs. Eastern Europe (12.8%), Russia (6.9%) and Western Europe (9.1%) (P = 0.102). The Western Europe region reported higher average percentages of patients receiving implantable cardioverter‐defibrillators (ICD) (34.3%) and cardiac resynchronization therapy (CRT) (24.1%) compared with the other regions, with Russia having the lowest percentage (5.8% and 3.7%, respectively) (Table 3 ).
Laboratory tests and imaging
The majority of sites in all regions reported that they are able to measure NT‐proBNP in AHF patients on admission (range: 72.7–95.2%) and at sites where chest X‐rays can be performed, they are routinely done (range: 75.0–100.0%). All sites in every region reported that they can perform echocardiograms for AHF patients on admission, though the average reported percentage of patients who have an echocardiogram is lower in Western Europe (81.8%), South America (86.1%), and Eastern Europe (89.4%) compared with African and Middle East (96.1%) and Russia (94.4%) (P = 0.116) (Table 4 ).
Table 4.
Laboratory assessments and imaging during the first 1–2 days of admission for AHF
| Question | Statistic | Africa and Middle East (N = 22) | Eastern Europe (N = 65) | Russia (N = 21) | South America (N = 29) | Western Europe (N = 21) | P‐value |
|---|---|---|---|---|---|---|---|
| Ability to measure NT‐proBNP? | n (%) | 16 (72.7%) | 51 (78.5%) | 17 (85.0%) | 25 (86.2%) | 20 (95.2%) | 0.305 |
| Ability to perform chest X‐ray? | n (%) | 22 (100%) | 65 (100%) | 20 (95.2%) | 28 (96.6%) | 20 (95.2%) | 0.419 |
| If yes, is chest X‐ray routinely done (in all patients)? | n (%) | 15 (75.0%) | 52 (86.7%) | 17 (89.5%) | 28 (100.0%) | 18 (90.0%) | 0.114 |
| Ability to perform echocardiogram? | n (%) | 22 (100.0%) | 65 (100.0%) | 21 (100.0%) | 28 (100.0%) | 21 (100.0%) | |
| If yes, percentage of patients that have echocardiography done during an AHF admission | n | 21 | 55 | 19 | 28 | 20 | |
| Mean (SD) | 96.1 (12.12) | 89.4 (21.06) | 94.4 (10.63) | 86.1 (19.31) | 81.8 (27.19) | 0.116 | |
| Min, Max | 45, 100 | 10, 100 | 60, 100 | 20, 100 | 1, 100 |
Abbreviation: AHF, acute heart failure.
Length of stay
Sites were asked to indicate the approximate percentage of AHF patients at their institution for each LOS category (<5, 5–8, 8–10, 10–12, 12–14, and >14 days). There were significant differences between regions in the mean percentage of AHF patients reported for each LOS category, except for the longest LOS category (>14 days) where low mean percentages of patients were reported in all regions. In Africa and the Middle East, Eastern Europe, South America, and Western Europe regions, the highest mean percentage of AHF patients were reported to have an average 5–8 day LOS (33.3%, 36.3%, 40.0%, and 38.7%, respectively). In contrast, sites in Russia reported the highest mean percentage of AHF patients having 10–12 day LOS (35.7%) (Table 5 ).
Table 5.
Percentage of length of stay categories for AHF patients by region
| Question | Statistic | Africa and Middle East (N = 22) | Eastern Europe (N = 65) | Russia (N = 21) | South America (N = 29) | Western Europe (N = 21) | P‐value b |
|---|---|---|---|---|---|---|---|
| What is the LOS on average for AHF patients in your hospital? a | |||||||
| Percent LOS < 5 days | n | 20 | 61 | 19 | 29 | 18 | |
| Mean (SD) | 22.5 (22.85) | 9.6 (11.89) | 2.1 (3.73) | 33.9 (30.69) | 19.8 (25.63) | <0.001 | |
| Min, Max | 0, 80 | 0, 50 | 0, 10 | 0, 90 | 0, 90 | ||
| Percent LOS 5–8 days | n | 20 | 61 | 19 | 29 | 18 | |
| Mean (SD) | 33.3 (19.42) | 36.3 (21.07) | 10.3 (9.43) | 40.0 (24.02) | 38.7 (26.74) | <0.001 | |
| Min, Max | 5, 80 | 0, 83 | 0, 40 | 10, 100 | 0, 100 | ||
| Percent LOS 8–10 days | n | 20 | 61 | 19 | 29 | 18 | |
| Mean (SD) | 22.3 (15.61) | 24.8 (16.21) | 31.8 (21.10) | 12.9 (14.55) | 22.7 (20.57) | 0.013 | |
| Min, Max | 5, 60 | 0, 70 | 0, 80 | 0, 60 | 0, 80 | ||
| Percent LOS 10–12 days | n | 20 | 61 | 19 | 29 | 18 | |
| Mean (SD) | 11.0 (9.21) | 14.9 (14.01) | 35.7 (19.80) | 6.4 (6.15) | 9.3 (12.06) | <0.001 | |
| Min, Max | 0, 30 | 0, 60 | 10, 70 | 0, 20 | 0, 50 | ||
| Percent LOS 12–14 days | n | 20 | 61 | 19 | 29 | 18 | |
| Mean (SD) | 6.8 (8.58) | 9.2 (8.91) | 15.9 (22.58) | 3.3 (5.38) | 5.2 (6.62) | 0.004 | |
| Min, Max | 0, 30 | 0, 50 | 0, 80 | 0, 20 | 0, 25 | ||
| Percent LOS > 14 days | n | 20 | 61 | 19 | 29 | 18 | |
| Mean (SD) | 4.3 (4.87) | 5.5 (7.87) | 4.3 (5.80) | 3.5 (7.60) | 4.6 (5.99) | 0.762 | |
| Min, Max | 0, 20 | 0, 50 | 0, 23 | 0, 40 | 0, 22 |
Response categories are not mutually exclusive.
P‐values adjusted for multiple comparisons using Bonferroni–Holm correction.
LOS, length of stay.
Follow‐up
In the Africa and Middle East region most sites reported that a community cardiologist is the most common practitioner to follow up with AHF patients post‐discharge (54.5%). The most common practitioners reported to follow up with patients post‐discharge in Eastern Europe were community cardiologist (49.2%) or the principal investigator in an outpatient clinic (56.9%). In Russia, sites most commonly reported that a community cardiologist (76.2%) or general practitioner (61.9%) is responsible for follow‐up with AHF patients. Sites in the South America region reported that community cardiologists (55.2%), HF hospital clinics (55.2%), or the principal investigator's outpatient clinic (44.8%) typically are responsible for follow up with AHF patients. Sites in the Western European region most commonly reported community cardiologists (76.2%) being the practitioner to follow‐up with AHF patients, followed by HF hospital clinics (52.4%) (Table 6 ).
Table 6.
Follow‐up after an AHF admission
| Question | Statistic | Africa and Middle East (N = 22) | Eastern Europe (N = 65) | Russia (N = 21) | South America (N = 29) | Western Europe (N = 21) | P‐value b |
|---|---|---|---|---|---|---|---|
| Who usually follows the HF patient after discharge from your institution? a | |||||||
| Community cardiologist | n (%) | 12 (54.5%) | 32 (49.2%) | 16 (76.2%) | 16 (55.2%) | 16 (76.2%) | 0.185 |
| Community general physician c | n (%) | 0 | 23 (35.4%) | 13 (61.9%) | 5 (17.2%) | 8 (38.1%) | |
| HF hospital clinic c | n (%) | 8 (36.4%) | 22 (33.8%) | 2 (9.5%) | 16 (55.2%) | 11 (52.4%) | |
| Investigator's clinic | n (%) | 8 (36.4%) | 37 (56.9%) | 8 (38.1%) | 13 (44.8%) | 9 (42.9%) | 0.352 |
Response categories are not mutually exclusive.
P‐value adjusted for multiple comparisons using Bonferroni–Holm correction.
Statistical comparisons not made due to 1 or more regions having ≤2 responses in a category.
Typical time to follow‐up with a community cardiologist in the Africa and Middle East region was reported to be about 1 month post‐discharge. Follow‐up with a community cardiologist in the Eastern European region was reported to most often occur at 1 month post‐discharge and 1 month post‐discharge with the investigator in an outpatient clinic. In Russia, sites reported typical follow up with a community cardiologist at 1 month post‐discharge, and with a general practitioner at 1 week post‐discharge. Sites in the South America region reported follow‐up with a community cardiologist most commonly to occur 1 week post‐discharge and with an HF hospital clinic at 1 week post‐discharge. Finally, sites in the Western Europe region most commonly reported follow‐up with a community cardiologist at 1 month post‐discharge.
Discussion
Through our site feasibility survey, we were able to interpret the standard treatment for AHF patients in a large survey across five different regions. In general, the sites in our survey seem to be following ESC guidelines for standard treatment in a satisfactory manner. However, this survey did reveal some important differences and variations in treatment and management across regions.
In‐hospital management
The majority of sites in all regions reported presentation to the hospital via ambulance or the emergency room. The reported rates are consistent with other European studies that have looked at different pathways for AHF patients within hospital. 8 The most common unit that AHF patients were reported to be admitted to in our survey were the cardiology ward or CCU. However, this pathway would differ in hospitals that do not have a cardiology department. There is evidence that AHF patients admitted to the CCU or cardiology department have improved outcomes compared with AHF patients who are admitted to other hospital wards. 8 , 9 , 10 Reported average LOS in our survey was similar to average LOS reported in other AHF registries. 2 , 11 , 12 Previous registries have identified wide variation in LOS in South America, which may explain the lower reported LOS in our survey. 2 Of note, significant differences in LOS were found between Russia and the other regions. The results are in accordance with those of the post‐hoc analysis of PROTECT trial by Mentz et al., performed in 2033 patients with acute HF and renal dysfunction. 13
Treatment
An ACEi is recommended in the ESC 2021 guidelines for patients with HF with reduced ejection fraction. ARBs are recommended for patients who cannot tolerate ACEi or ARNi because of serious side effects and MRA is recommended for patients with HF with reduced ejection fraction. 3 Overall, the reported average percentage of patients prescribed ACEis and beta‐blockers was high in all regions. Some European registries have reported that as high as 80% of AHF patients receiving ACEis in their cohort. 12 Past AHF registries comparing regional differences in treatment have found much lower rates of beta‐blocker use in South America. 14
Guidelines recommend ARBs for symptomatic patients who cannot tolerate ACEi or ARNi, whereas ARBs have not reduced all‐cause mortality in any trial. Therefore, in all regions, the reported proportion of patients prescribed ACEi was higher than the proportion prescribed ARBs. For South America and Western Europe, however, the average proportion patients prescribed ACEi was lower than in other regions, and the average proportion of patients prescribed ARB was higher than in other regions.
ARNi is a relatively new HF drug and is recommended in the guidelines. However, with regard to prescription rates, reported rates of prescription are still far behind ACEi. In particular, in Africa and the Middle East, the average reported proportion of patients prescribed ARNi was remarkably low at <2%.
Reported MRA prescription was slightly higher than reported rates in other registries and meta‐analyses and indicates excellent adherence to MRA therapy reported by the sites in our survey. 2 , 15 Beta blocker prescription was reported to be high and seems to be consistent across areas. Of note for most medications there is an almost 1/3–1/3–1/3 distribution of patients prescribed doses that are <50% of the recommended dose, 50–100% of the recommended doses and 100% of the recommended doses, although this varies substantially from area to area.
Procedures
Reported percentages of patients treated with PCI was quite high in our survey. One global HF survey reported an average of 12.8% of AHF patients getting PCI in their cohort and other European HF surveys have reported PCI use in as low as 5.5% of HF patients. 10 , 16 The reported percentages of AHF patients receiving coronary artery bypass grafting was similar to rates that have been reported in other registries. 12 , 16 Widely varying rates of use of ICD and CRT was observed in our survey even within region. There is further investigation needed into why rates of these procedures vary so greatly (Table 3 ). Some of this reported high use of intervention may have been the result of the nature of the survey, assessing sites feasibility to do a study. This result in our survey is consistent with reports that the percentages of HF patients with implanted ICDs or CRTs are higher in Western Europe and lower in Russia. 13 In addition, in Western Europe, indications for ICD implantation have been reported to be higher for primary prevention (risk factors for sudden cardiac arrest without prior episode) than for secondary prevention (survivor of prior sustained ventricular tachyarrhythmia) (70% and 30%, respectively). 17 This may suggest that more HF patients may be candidates for ICD implantation in Western European sites.
Follow‐up
It is recommended that a post‐discharge follow‐up or management plan be established when an individual is hospitalized for AHF. The majority of regions in our survey reported that their AHF patients often follow up with a community cardiologist, although this was not a universal phenomenon and many patients do not have follow up with cardiologists post discharge. ESC guidelines recommend an early follow‐up visit at 1–2 weeks after discharge to assess signs of congestion, drug tolerance, and start and/or uptitrate evidence‐based therapy. 3 Most regions that reported that patients typically follow up with a general practitioner (GP) reported that follow up timing was usually 1 week post‐discharge (Eastern Europe, Russia, and Western Europe). However, most sites in the South America region reported follow up timing with a GP to be around 1 month post discharge. All regions that reported that patients typically follow up with a community cardiologist reported follow up timing being 1 week to 1 month post discharge. Many regions also reported follow‐up with a community cardiologist at 3 months post discharge (Africa and Middle East, Eastern Europe, Russia, and Western Europe). This incomplete follow up with cardiologists within 1–2 weeks of discharge is critical to the ability to quickly up titrate the doses of guidelines recommend medications. Indeed up titration to maximally tolerated doses of medications was not reported to occur in most patients probably since such uptitration is difficult to achieve unless patients are followed up rapidly and repeatedly in the immediate post discharge period. This issue is further compounded by the inability to perform measurements of natriuretic peptides in some institutions, limiting the ability to perform safe up titration of some guidelines recommended therapies.
Limitations
Several limitations of this study should be noted. Firstly, our study was limited to the information that was self‐reported by the site principal investigator. True rates may vary in practice. However, we stressed to investigators the importance of trying to be as accurate as possible when completing the survey. Secondly, we did not collect information on the patient populations and characteristics at these sites, so our inferences are limited to what is reported in similar populations in other registries. Thirdly, the questioning of candidate/selected centres for a RCT is likely to introduce a selection bias by selecting centre particularly invested in up‐to‐date care and overestimate guidelines adherence as compared with the general practice of the region. Lastly, we did not inquire about left ventricular EF, and therefore, it is unclear how HF treatment differentiated between patients with reduced EF and patients with preserved EF.
Conclusion
Our analysis using feasibility questionnaires for a global AHF study sought to better understand how AHF is being treated and managed at the global level. We also had the goal of comparing regions and observing whether most sites are following ESC guidelines. Our study showed that, in general, adherence to guidelines is satisfactory. However, there was wide variation across region and within region. The largest issue identified in this survey is that many sites lack the ability to follow up patients quickly after an admission and have this follow up be performed by a cardiologist. In many cases patients are followed up late after an admission (a month or more) and by a general practitioner. Such inadequate access to expert consultation may lead to partial implementation of guideline therapies, especially when combined with lack of access to assessment of natriuretic peptides levels. Future research is needed regarding why these differences exist and what resources may be provided in order to improve adherence to guidelines for the care of AHF patients.
Conflict of interest
Maria Novosadova, Koji Takagi, Priyanka Morishetty, Lauren Gaeta, Christopher Edwards, Beth A Davison and Gad Cotter are employees of Momentum Research Inc. Momentum Research Inc. has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics Inc., Corteria Pharmaceuticals, Roche Diagnostics Inc., Sanofi, Windtree Therapeutics Inc. and XyloCor Therapeutics. Lauren Gianchetti is employed at PPD, part of Thermo Fisher Scientific. Adrien Picod reported receiving a grant from 4TEEN4 outside the submitted work. Alexandre Mebazaa reported receiving personal fees from Novartis, Orion, Roche, Sanofi, Otsuka, Philips, and Servier; grants and personal fees from Adrenomed and Abbott; and grants from 4TEEN4 outside the submitted work.
Funding
Funding for the STRONG‐HF study is provided by Roche Diagnostics.
Acknowledgements
We thank the lead principal investigators at each site for their contributions.
Novosadova, M. , Gianchetti, L. , Takagi, K. , Morishetty, P. , Gaeta, L. , Edwards, C. , Davison, B. A. , Picod, A. , Mebazaa, A. , and Cotter, G. (2023) Global differences in acute heart failure treatment: analysis of the STRONG‐HF site feasibility questionnaire. ESC Heart Failure, 10: 2236–2247. 10.1002/ehf2.14370.
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