Analysis of mortality in patients with heart failure after de­compen­sation during long-term follow-up in specialized medical care and in real clinical practice

Background Mortality from chronic heart failure (CHF) remains high and entails serious demographic losses worldwide. The most vulnerable group is patients after acute decompensated HF (ADHF) who have a high risk of unfavorable outcome.
Aim To analyze risks of all-cause death (ACD), cardiovascular death (CVD), and death from recurrent ADHF in CHF patients during two years following ADHF in long-term follow-up with specialized medical care and in real-life clinical practice.
Material and methods The study successively included 942 CHF patients after ADHF. 510 patients continued out-patient treatment in a specialized CHF treatment center (CHFTC) (group 1) and 432 patients refused of the management in the CHFTC and were managed in out-patient clinics at the place of patient’s residence (group 2). Causes of death were determined based on inpatient hospital records, postmortem reports, or outpatient medical records. Cases of ACD, CVD, death from ADHF, and a composite index (CVD and death from ADHF) were analyzed. Statistical analysis was performed with the software package Statistica 7.0 for Windows, SPSS, and statistical package R.
Results Patients of group 2 were older, more frequently had functional class (FC) III CHF and less frequently FC I CHF compared to group 1. Women and patients with preserved left ventricular ejection fraction (LV EF) prevailed in both groups. Results of the Cox proportional hazards model for ACD, CVD, death from ADHF, and the composite mortality index showed that belonging to group 2 was an independent predictor for increased risk of death (р<0.001). An increase in CCS score by 1 also increased the risk of death (р<0.001). Baseline CHF FC and LV EF did not influence the mortality in any model. Female gender and a higher value of 6-min walk test (6MW) independently decreased the risk of all outcomes except for CVD. An increase in systolic BP by 10 mm Hg reduced risk of all fatal outcomes. At two years of follow-up in groups 2 and 1, ACD was 29.9 % and 10.2 %, (OR, 3.7; 95 % CI: 2.6–5.3; p <0.001), CVD was 10.4 % and 1.9 % (OR, 5.9; 95 % CI: 2.8–12.4; p<0.001), death from ADHF was 18.1 % and 6.0 % (OR, 3.5; 95 % CI: 2.2–5.5; p<0.001), and the composite mortality index was 25.2 % and 7.7 % (OR, 4.1; 95 % CI: 2.7–6.1; р<0.001). Analysis of all outcomes by follow-up period (3 and 6 months and 1 and 2 years) showed that the difference between groups 2 and 1 in risks of any fatal outcome was maximal during the first 6 months.
Conclusion The follow-up in the system of specialized medical care reduces risks of ACD, CVD, and death from ADHF. The first 6 months following discharge from the hospital was a vulnerability period for patients after ADHF. The CCS score impaired the prognosis whereas baseline LV EF and CHF FC did not influence the long-term prognosis after ADHF. Protective factors included female gender and higher values of 6MW and systolic BP.

1. Tsao CW, Lyass A, Enserro D, Larson MG, Ho JE, Kizer JR et al. Temporal Trends in the Incidence of and Mortality Associated with Heart Failure with Preserved and Reduced Ejection Fraction. JACC: Heart Failure. 2018;6(8):678–85. DOI: 10.1016/j.jchf.2018.03.006

2. Simpson J, Jhund PS, Silva Cardoso J, Martinez F, Mosterd A, Ramires F et al. Comparing LCZ696 with Enalapril According to Baseline Risk Using the MAGGIC and EMPHASIS-HF Risk Scores. Journal of the American College of Cardiology. 2015;66(19):2059–71. DOI: 10.1016/j.jacc.2015.08.878

3. McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR et al. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). European Journal of Heart Failure. 2013;15(9):1062–73. DOI: 10.1093/eurjhf/hft052

4. Scrutinio D, Guida P, Passantino A, Lagioia R, Raimondo R, Venezia M et al. Female gender and mortality risk in decompensated heart failure. European Journal of Internal Medicine. 2018;51:34–40. DOI: 10.1016/j.ejim.2018.01.011

5. Okumura N, Jhund PS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL et al. Importance of Clinical Worsening of Heart Failure Treated in the Outpatient Setting: Evidence From the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF). Circulation. 2016;133(23):2254–62. DOI: 10.1161/CIRCULATIONAHA.115.020729

6. Chen J, Normand S-LT, Wang Y, Krumholz HM. National and Regional Trends in Heart Failure Hospitalization and Mortality Rates for Medicare Beneficiaries, 1998-2008. JAMA. 2011;306(15):1669–78. DOI: 10.1001/jama.2011.1474

7. McMurray JJV, DeMets DL, Inzucchi SE, Køber L, Kosiborod MN, Langkilde AM et al. A trial to evaluate the effect of the sodium-glucose co‐transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA‐HF). European Journal of Heart Failure. 2019;21(5):665–75. DOI: 10.1002/ejhf.1432

8. Maggioni AP, Dahlström U, Filippatos G, Chioncel O, Leiro MC, Drozdz J et al. EURObservational Research Programme: The Heart Failure Pilot Survey (ESC-HF Pilot). European Journal of Heart Failure. 2010;12(10):1076–84. DOI: 10.1093/eurjhf/hfq154

9. Maggioni AP, Dahlström U, Filippatos G, Chioncel O, Crespo Leiro M, Drozdz J et al. EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). European Journal of Heart Failure. 2013;15(7):808–17. DOI: 10.1093/eurjhf/hft050

10. Fomin I.V. Chronic heart failure in Russian Federation: what do we know and what to do. Russian Journal of Cardiology. 2016;8:7–13. [Russian: Фомин И.В. Хроническая сердечная недостаточность в Российской Федерации: что сегодня мы знаем и что должны делать. Российский Кардиологический Журнал. 2016;8:7-13]. DOI: 10.15829/1560-4071-2016-8-7-13

11. Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation. 1993;88(1):107–15. DOI: 10.1161/01.CIR.88.1.107

12. Bleumink GS, Knetsch AM, Sturkenboom MCJM, Straus SMJM, Hofman A, Deckers JW et al. Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. European Heart Journal. 2004;25(18):1614–9. DOI: 10.1016/j.ehj.2004.06.038

13. Levy D, Kenchaiah S, Larson MG, Benjamin EJ, Kupka MJ, Ho KKL et al. Long-term trends in the incidence of and survival with heart failure. The New England Journal of Medicine. 2002;347(18):1397–402. DOI: 10.1056/NEJMoa020265

14. Maggioni AP, Anker SD, Dahlström U, Filippatos G, Ponikowski P, Zannad F et al. Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12 440 patients of the ESC Heart Failure Long-Term Registry. European Journal of Heart Failure. 2013;15(10):1173–84. DOI: 10.1093/eurjhf/hft134

15. Shah KS, Xu H, Matsouaka RA, Bhatt DL, Heidenreich PA, Hernandez AF et al. Heart Failure with Preserved, Borderline, and Reduced Ejection Fraction. Journal of the American College of Cardiology. 2017;70(20):2476–86. DOI: 10.1016/j.jacc.2017.08.074

16. Zarrinkoub R, Wettermark B, Wändell P, Mejhert M, Szulkin R, Ljunggren G et al. The epidemiology of heart failure, based on data for 2.1 million inhabitants in Sweden. European Journal of Heart Failure. 2013;15(9):995–1002. DOI: 10.1093/eurjhf/hft064

17. Lainscak M, Blue L, Clark AL, Dahlström U, Dickstein K, Ekman I et al. Self-care management of heart failure: practical recommendations from the Patient Care Committee of the Heart Failure Association of the European Society of Cardiology. European Journal of Heart Failure. 2011;13(2):115–26. DOI: 10.1093/eurjhf/hfq219

18. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137–61. DOI: 10.1161/CIR.0000000000000509

19. Russo MJ, Gelijns AC, Stevenson LW, Sampat B, Aaronson KD, Renlund DG et al. The Cost of Medical Management in Advanced Heart Failure During the Final Two Years of Life. Journal of Cardiac Failure. 2008;14(8):651–8. DOI: 10.1016/j.cardfail.2008.06.005

20. DeVore AD, Thomas L, Albert NM, Butler J, Hernandez AF, Patterson JH et al. Change the management of patients with heart failure: Rationale and design of the CHAMP-HF registry. American Heart Journal. 2017;189:177–83. DOI: 10.1016/j.ahj.2017.04.010

21. Gelbrich G, Störk S, Kreißl-Kemmer S, Faller H, Prettin C, Heuschmann PU et al. Effects of structured heart failure disease management on mortality and morbidity depend on patients’ mood: results from the Interdisciplinary Network for Heart Failure Study: Effects of structured HF management depend on patients’ mood. European Journal of Heart Failure. 2014;16(10):1133–41. DOI: 10.1002/ejhf.150

22. Shlyakhto E.V., Zvartau N.E., Villevalde S.V., Yakovlev A.N., Soloveva A.E., Alieva A.S. et al. Cardiovascular risk management system: prerequisites for developing, organization principles, target groups. Russian Journal of Cardiology. 2019;24(11):69–82. [Russian: Шляхто Е.В., Звартау Н.Э., Виллевальде С.В., Яковлев А.Н., Соловьева А.Е., Алиева А.С. и др. Система управления сердечно-сосудистыми рисками: предпосылки к созданию, принципы организации, таргетные группы. Российский кардиологический журнал. 2019;24(11):69–82]. DOI: 10.15829/1560-4071-2019-11-69-82

23. Polyakov D.S., Fomin I.V., Badin Yu.V., Vaisberg A.R., Valikulova F.Yu., Shechrbinina E.V. et al. Effects of systolic and diastolic blood pressure and its changes between successive hospitalizations on prognosis for patients with acute decompensated CHF. Russian Heart Failure Journal. 2017;18 (3):178–84. [Russian: Поляков Д. С., Фомин И. В., Бадин Ю. В., Вайсберг А. Р., Валикулова Ф. Ю. Щербинина Е. В. и др. Влияние уровня систолического и диастолического артериального давления и его динамики между последовательными госпитализациями на прогноз пациента с ХСН при острой декомпенсации. Журнал Сердечная Недостаточность. 2017;18(3):178-84]. DOI: 10.18087/rhfj.2017.3.2357

24. Vinogradova N.G. The prognosis of patients with chronic heart failure, depending on adherence to observation in a specialized heart failure treatment center. Kardiologiia. 2019;59(10S):13–21. [Russian: Виноградова Н.Г. Прогноз пациентов с хронической сердечной недостаточностью в зависимости от приверженности к наблюдению в специализированном центре лечения сердечной недостаточности. Кардиология. 2019;59(10S):13-21]. DOI: 10.18087/cardio.n613

25. Fomin I.V., Vinogradova N.G. Organization of specialized medical care for patients with chronic heart failure. CardioSomatics. 2017;8(3):10–5. [Russian: Фомин И.В., Виноградова Н.Г. Организация специализированной медицинской помощи больным с хронической сердечной недостаточностью. CardioСоматика. 2017;8(3):10-5]

26. Fomin I.V., Vinogradova N.G., Farzaliev M.I., Allakhverdieva S.M., Krylova A.N., Samarina A.S. et al. Efficiency of observing patients in the setting of a specialized center for treatment of chronic heart failure. Emergency cardiology and cardiovascular risks. 2018;2(1):221–9. [Russian: Фомин И.В., Виноградова Н.Г., Фарзалиев М.И., Аллахвердиева С.М., Крылова А.Н., Самарина А.С. и др. Эффективность наблюдения пациентов в условиях специализированного центра лечения хронической сердечной недостаточности. Неотложная кардиология и кардиоваскулярные риски. 2018;2(1):221-9]

27. Mareev V.Yu., Ageev F.T., Arutyunov G.P., Koroteev A.V., Mareev Yu.V., Ovchinnikov A.G. et al. SEHF, RSC and RSMSIM national guidelines on CHF diagnostics and treatment (fourth revision) Approved at the SEHF Congress on December 7, 2012, at the SEHF Board of Directors meeting on March 31, 2013, and at the RSC Congress on September 25, 2013. Russian Heart Failure Journal. 2013;14(7):379–472. [Russian: Мареев В.Ю., Агеев Ф.Т., Арутюнов Г.П., Коротеев А.В., Мареев Ю.В., Овчинников А.Г. и др. Национальные рекомендации ОССН, РКО и РНМОТ по диагностике и лечению ХСН (четвертый пересмотр). Утверждены на Конгрессе ОССН 7 декабря 2012 года, на Правлении ОССН 31 марта 2013 и Конгрессе РКО 25 сентября 2013 года. Журнал Сердечная Недостаточность. 2013;14(7):379-472.]

28. Mareev V.Yu., Fomin I.V., Ageev F.T., Arutiunov G.P., Begrambekova Yu.L., Belenkov Yu.N. et al. Clinical guidelines. Chronic heart failure (CHF). Russian Heart Failure Journal. 2017;18(1):3–40. [Russian: Мареев В.Ю., Фомин И.В., Агеев Ф.Т., Арутюнов Г.П., Беграмбекова Ю.Л., Беленков Ю.Н. и др. Клинические рекомендации. Хроническая сердечная недостаточность (ХСН). Журнал Сердечная Недостаточность. 2017;18(1):3–40]. DOI: 10.18087/rhfj.2017.1.2346

29. R Core Team (2018). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2018. [Internet] 2018. Available at: https://www.r-project.org/

30. Polyakov D.S., Fomin I.V., Vaysberg A.R. EPOCHA-D-CHF: gender differences in the prognosis of patients with CHF af-ter acute decompensation (part 2). Kardiologiia. 2019;59(4S): 33– 43. [Russian: Поляков Д.С., Фомин И.В., Вайсберг А.Р. ЭПОХА-Д-ХСН: Гендерные различия в прогнозе жизни больных хсн при острой декомпенсации сердечной недостаточности (часть 2). Кардиология. 2019;59(4S):33-43]. DOI: 10.18087/cardio.2654

31. Fomin I.V., Mareev V.Yu., Zherbinina E.V. Indicators of the prevalence of heart failure and the effectiveness of its therapy, depending on the severity of the disease. Russian Heart Failure Journal. 2002;3(2):69–70. [Russian: Фомин И.В., Мареев В.Ю., Щербинина Е.В. Показатели распространенности сердечной недостаточности и эффективности ее терапии в зависимости от тяжести заболевания. Журнал сердечная недостаточность. 2002;3(2):69-70]

32. Vinogradova N.G. Effectiveness of specialized medical care in patients with chronic heart failure. Russian Heart Failure Journal. 2017;18(2):122–32. [Russian: Виноградова Н.Г. Эффективность специализированной медицинской помощи больным хронической сердечной недостаточностью. Журнал Сердечная недостаточность. 2017;18(2):122-32]. DOI: 10.18087/rhfj.2017.2.2313

33. Polyakov D.S., Fomin I.V., Valikulova F.Yu., Vaisberg A.R., Kraiem N., Badin Yu.V. et al. The EPOCHA-CHF epidemiological program: decompensated chronic heart failure in real-life clinical practice (EPOCHA-D-CHF). Russian Heart Failure Journal. 2016;17(5):299–305. [Russian: Поляков Д.С., Фомин И.В., Валикулова Ф.Ю., Вайсберг А.Р., Краием Н., Бадин Ю.В. и др. Эпидемиологическая программа ЭПОХА-ХСН: Декомпенсация хронической сердечной недостаточности в реальной клинической практике (ЭПОХА-Д-ХСН). Журнал Сердечная Недостаточность. 2016;17(5):299–305]. DOI: 10.18087/rhfj.2016.5.2239

34. Di Tano G, De Maria R, Gonzini L, Aspromonte N, Di Lenarda A, Feola M et al. The 30-day metric in acute heart failure revisited: data from IN-HF Outcome, an Italian nationwide cardiology registry. European Journal of Heart Failure. 2015;17(10):1032–41. DOI: 10.1002/ejhf.290

35. Polyakov D.S., Fomin I.V., Vaisberg A.R. Evaluation of long-term predictors in patients with acute decompensated heart failure depending on age: the results of the EPOCHA-D-CHF study. Clinical gerontology. 2019;25 (3–4):39–47. [Russian: Поляков Д. С., Фомин И. В., Вайсберг А. Р. Оценка предикторов долгосрочного прогноза у пациентов с острой декомпенсацией сердечной недостаточности в зависимости от возраста: результаты исследования ЭПОХА-Д-ХСН. Клиническая геронтология. 2019;25(3-4):39-47]. DOI: 10.26347/1607-2499201903-04039-047

36. Dreyer RP, Dharmarajan K, Hsieh AF, Welsh J, Qin L, Krumholz HM. Sex Differences in Trajectories of Risk After Rehospitalization for Heart Failure, Acute Myocardial Infarction, or Pneumonia. Circulation: Cardiovascular Quality and Outcomes. 2017;10(5):165–71. DOI: 10.1161/CIRCOUTCOMES.116.003271

37. Jessup M, Piña IL. Is it important to examine gender differences in the epidemiology and outcome of severe heart failure? The Journal of Thoracic and Cardiovascular Surgery. 2004;127(5):1247–52. DOI: 10.1016/j.jtcvs.2003.09.032

38. Boytsov S.A., Balanova Yu.A., Shal’nova S.A., Deev A.D., Artamonova G.V., Gatagonova T.M. et al. Arterial hypertension among persons aged 25-64: prevalence, awareness, treatment and control. By the data from ECCD. Cardiovascular Therapy and Prevention. 2014;13(4):4–14. [Russian: Бойцов С.А., Баланова Ю.А., Шальнова С.А., Деев А.Д., Артамонова Г.В., Гагатонова Т.М. и др. Артериальная гипертония среди лиц 25-64 лет: распространенность, осведомленность, лечение и контроль по материалам исследования ЭССЕ. Кардиоваскулярная терапия и профилактика. 2014;13(4):4-14]. DOI: 10.15829/1728-8800-2014-4-4-14

39. Cooper-DeHoff RM, Gong Y, Handberg EM, Bavry AA, Denardo SJ, Bakris GL et al. Tight Blood Pressure Control and Cardiovascular Outcomes Among Hypertensive Patients with Diabetes and Coronary Artery Disease. JAMA. 2010;304(1):61–8. DOI: 10.1001/jama.2010.884

40. Vidal-Petiot E, Ford I, Greenlaw N, Ferrari R, Fox KM, Tardif J-C et al. Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: an international cohort study. The Lancet. 2016;388(10056):2142–52. DOI: 10.1016/S0140-6736(16)31326-5

41. Ferreira JP, Duarte K, Pfeffer MA, McMurray JJV, Pitt B, Dickstein K et al. Association between mean systolic and diastolic blood pressure throughout the follow-up and cardiovascular events in acute myocardial infarction patients with systolic dysfunction and/or heart failure: an analysis from the High-Risk Myocardial Infarction: BP and outcomes in myocardial infarction. European Journal of Heart Failure. 2018;20(2):323–31. DOI: 10.1002/ejhf.1131

42. Wells R, Rahman M. SPRINT and the Kidney: What Have We Learned? Current Hypertension Reports. 2018;20(11):95. DOI: 10.1007/s11906-018-0895-6