Prevalence and Predictors of Sepsis Death in Patients With Chronic Heart Failure and Reduced Left Ventricular Ejection Fraction

Andrew M N Walker, Michael Drozd, Marlous Hall, Peysh A Patel, Maria Paton, Judith Lowry, John Gierula, Rowenna Byrom, Lorraine Kearney, Robert J Sapsford, Klaus K Witte, Mark T Kearney, Richard M Cubbon, Andrew M N Walker, Michael Drozd, Marlous Hall, Peysh A Patel, Maria Paton, Judith Lowry, John Gierula, Rowenna Byrom, Lorraine Kearney, Robert J Sapsford, Klaus K Witte, Mark T Kearney, Richard M Cubbon

Abstract

Background Noncardiovascular death is increasingly common in people with chronic heart failure ( CHF ), yet its causes remain poorly characterized. We aimed to define the prevalence of sepsis death in people with CHF and to ascertain its risk marker profile. Methods and Results We conducted a prospective cohort study of 1802 patients with CHF and left ventricular ejection fraction ≤45% attending CHF clinics in 4 United Kingdom hospitals between 2006 and 2014. Mode of death was defined over a 10.3-year follow-up period (mean 4 years). Competing risk regression defined mode-specific hazard ratios for sepsis, other noncardiovascular, progressive heart failure, and sudden cardiac death in relation to established heart failure prognostic markers. Of 737 deaths, 173 (23.5%) were due to sepsis; respiratory tract infections accounted for 69.9% (n=121) of these events. Those who died from sepsis were older, had higher platelet counts, and had a higher prevalence of chronic obstructive pulmonary disease than those who died from other causes. Sepsis death was independently associated with older age (hazard ratio=1.05; 95% confidence interval 1.03-1.07), greater prevalence of chronic obstructive pulmonary disease (2.43; 1.74-3.40), male sex (1.73; 1.16-2.60), lower log serum vitamin D (0.68; 0.49-0.95), and higher platelet count (1.002; 1.000-1.005) than nonsepsis death. Established heart failure prognostic markers exhibited different patterns of association with sepsis death, other noncardiovascular death, progressive heart failure death, and sudden cardiac death. Conclusions Sepsis is a major contributor to death in people with CHF and has a different risk marker profile from other modes of death, suggesting that it may be amenable to targeted preventative strategies.

Keywords: heart failure; morbidity/mortality; sepsis.

Figures

Figure 1
Figure 1
Sepsis death in relation to other common modes of death. A, Relative contribution of modes of death to overall mortality, with sepsis (represented by the hatched region) accounting for over half of noncardiovascular deaths. B, Relative contribution of primary sources of sepsis to overall sepsis deaths. CV indicates cardiovascular; GI, gastrointestinal; HF, heart failure.
Figure 2
Figure 2
Cumulative incidence of sepsis death in relation to other common modes of death. Cumulative incidence functions illustrating sepsis, other noncardiovascular, progressive heart failure, and sudden cardiac death during follow‐up.
Figure 3
Figure 3
Predictors of sepsis death differ from those of alternate modes of death. Heat map of relative variable contributions to multivariate models predicting mode‐specific or all‐cause mortality, illustrating the distinct risk marker association with sepsis death. More intense red tones denote a greater percentage contribution of a variable to the global Wald score for prediction of a specific mode of death. COPD indicates chronic obstructive pulmonary disease; CV, cardiovascular; eGFR, estimated glomerular filtration rate; HF, heart failure; Ln, natural logarithm; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association.

References

    1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER III, Moy G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner TB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee . Heart disease and stroke statistics—2014 update. Circulation. 2014;129:e28–e292.
    1. Cubbon RM, Gale CP, Kearney LC, Schechter CB, Brooksby WP, Nolan J, Fox KA, Rajwani A, Baig W, Groves D, Barlow P, Fisher AC, Batin PD, Kahn MB, Zaman AG, Shah AM, Byrne JA, Lindsay SJ, Sapsford RJ, Wheatcroft SB, Witte KK, Kearney MT. Changing characteristics and mode of death associated with chronic heart failure caused by left ventricular systolic dysfunction: a study across therapeutic eras. Circ Heart Fail. 2011;4:396–403.
    1. Christiansen MN, Køber L, Weeke P, Vasan RS, Jeppesen JL, Smith JG, Gislason GH, Torp‐Pedersen C, Andersson C. Age‐specific trends in incidence, mortality, and comorbidities of heart failure in Denmark, 1995 to 2012. Circulation. 2017;135:1214–1223.
    1. Chen J, Normand SL, Wang Y, Krumholz HM. National and regional trends in heart failure hospitalization and mortality rates for Medicare beneficiaries, 1998–2008. JAMA. 2011;306:1669–1678.
    1. Shen L, Jhund P, Petrie M, Claggett B, Barlera S, Cleland JGF, Dargie HJ, Granger CB, Kjekshus J, Køber L, Latini R, Maggioni AP, Packer M, Pitt B, Solomon SD, Swedberg K, Tavazzi L, Wikstrand J, Zannad F, Zile MR, McMurray JJV. Declining risk of sudden death in heart failure. N Engl J Med. 2017;377:41–51.
    1. Lee DS, Gona P, Albano I, Larson MG, Benjamin EJ, Levy D, Kannel WB, Vasan RS. A systematic assessment of causes of death after heart failure onset in the community: impact of age at death, time period, and left ventricular systolic dysfunction. Circ Heart Fail. 2011;4:36–43.
    1. Ueda T, Kawakami R, Horii M, Sugawara Y, Matsumoto T, Okada S, Nishida T, Soeda T, Okayama S, Somekawa S, Takeda Y, Watanabe M, Kawata H, Uemura S, Saito Y. Noncardiovascular death, especially infection, is a significant cause of death in elderly patients with acutely decompensated heart failure. J Card Fail. 2014;20:174–180.
    1. Alon D, Stein GY, Korenfeld R, Fuchs S. Predictors and outcomes of infection‐related hospital admissions of heart failure patients. PLoS One. 2013;8:e72476.
    1. Logeart D, Isnard R, Resche‐Rigon M, Seronde MF, de Groote P, Jondeau G, Galinier M, Mulak G, Donal E, Delahaye F, Juilliere Y, Damy T, Jourdain P, Bauer F, Eicher JC, Neuder Y, Trochu JN; Heart Failure of the French Society of Cardiology . Current aspects of the spectrum of acute heart failure syndromes in a real‐life setting: the OFICA study. Eur J Heart Fail. 2013;15:465–476.
    1. Witte KK, Patel PA, Walker AMN, Schechter CB, Drozd M, Sengupta A, Byrom R, Kearney LC, Sapsford RJ, Kearney MT, Cubbon RM. Socioeconomic deprivation and mode‐specific outcomes in patients with chronic heart failure. Heart. 2018;104:993–998.
    1. Witte KK, Drozd M, Walker AM, Patel PA, Kearney JC, Chapman S, Sapsford RJ, Gierula J, Paton MF, Lowry J, Kearney MT, Cubbon RM. Mortality reduction associated with β‐adrenoceptor inhibition in chronic heart failure is greater in patients with diabetes. Diabetes Care. 2017;41:136–142.
    1. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.
    1. Witte KK, Byrom R, Gierula J, Paton MF, Jamil HA, Lowry JE, Gillott RG, Barnes SA, Chumun H, Kearney LC, Greenwood JP, Plein S, Law GR, Pavitt S, Barth JH, Cubbon RM, Kearney MT. Effects of vitamin D on cardiac function in patients with chronic HF: the VINDICATE study. J Am Coll Cardiol. 2016;67:2593–2603.
    1. Vaduganathan M, Patel RB, Michel A, Shah SJ, Senni M, Gheorghiade M, Butler J. Mode of death in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2017;69:556–569.
    1. Kumar G, Kumar N, Taneja A, Kaleekal T, Tarima S, McGinley E, Jimenez E, Mohan A, Khan RA, Whittle J, Jacobs E, Nanchal R; Milwaukee Initiative in Critical Care Outcomes Research (MICCOR) Group of Investigators . Nationwide trends of severe sepsis in the 21st century (2000–2007). Chest. 2011;140:1223–1231.
    1. Liu V, Escobar G, Greene J, Soule J, Whippy A, Angus DC, Iwashyna TJ. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA. 2014;312:90–92.
    1. Ford DW, Goodwin AJ, Simpson AN, Johnson E, Nadig N, Simpson KN. A severe sepsis mortality prediction model and score for use with administrative data. Crit Care Med. 2016;44:319–327.
    1. Aliberti S, Amir A, Peyrani P, Mirsaeidi M, Allen M, Moffett B, Myers J, Shaib F, Cirino M, Bordon J, Blasi F, Ramirez JA. Risk factors for clinical failure in hospitalized patients with community‐acquired pneumonia. Chest. 2008;134:955–962.
    1. Vardeny O, Claggett B, Udell JA, Packer M, Zile M, Rouleau J, Swedberg K, Desai AS, Lefkowitz M, Shi V, McMurray JJV, Solomon SD; PARADIGM‐HF Investigators . Influenza vaccination in patients with chronic heart failure: the PARADIGM‐HF trial. JACC Heart Fail. 2016;4:152–158.
    1. Bhatt AS, DeVore AD, Hernandez AF, Mentz RJ. Can vaccinations improve heart failure outcomes? Contemporary data and future directions. JACC Heart Fail. 2016;4:152–158.
    1. de Haan K, Groeneveld ABJ, de Geus HRH, Egal M, Struijs A. Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta‐analysis. Crit Care. 2014;18:660.
    1. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov‐Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Griffiths CJ, Janssens W, Laaksi I, Manaseki‐Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S Jr, Stelmach I, Kumar GT, Urashima M, Camargo CA Jr. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta‐analysis of individual participant data. BMJ. 2017;356:i6583.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa