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• W2078235044 abstract "Heart failure (HF) and depression are debilitating diseases with significant effects on functional status and real and perceived quality of life. Despite many advances in therapy for HF mortality remains high. Depression and HF have been recognized to coexist but this does not imply a causative relation. Depressed patients develop more symptoms, have worse compliance with medication regimens, are slower to return to work and social activities, and seem to have a poorer quality of life. In patients with known cardiac disease depression also predicts future events independent of disease severity and other risk factors such as smoking or diabetes mellitus. In conclusion, this review attempts to address the cause/effect relation, if any, between HF and depression and the role of treatment of depression in the setting of HF. Heart failure (HF) and depression are debilitating diseases with significant effects on functional status and real and perceived quality of life. Despite many advances in therapy for HF mortality remains high. Depression and HF have been recognized to coexist but this does not imply a causative relation. Depressed patients develop more symptoms, have worse compliance with medication regimens, are slower to return to work and social activities, and seem to have a poorer quality of life. In patients with known cardiac disease depression also predicts future events independent of disease severity and other risk factors such as smoking or diabetes mellitus. In conclusion, this review attempts to address the cause/effect relation, if any, between HF and depression and the role of treatment of depression in the setting of HF. Heart failure (HF) and depression have profound effects on functional status and quality of life. Considering the high coprevalence of HF and depression this review addresses factors that are common to the 2 conditions and outlines reasons that a cause/effect relation may be too simplistic. Indeed, HF and depression may create a vicious cycle in which they worsen each other, leading to their combination being more severe than the additive effects of each considered in isolation. HF affects approximately 5 million Americans with 550,000 new cases diagnosed each year.1Hunt S.A. Abraham W.T. Chin M.H. Feldman A.M. Francis G.S. Ganiats T.G. Jessup M. Konstam M.A. Mancini D.M. Michl K. Oates J.A. Rahko P.S. Silver M.A. Stevenson L.W. Yancy C.W. 2009 Focused update to the 2005 ACC/AHA guidelines for the diagnosis and management of heart failure in adults.Circulation. 2009; 119: e391-e479PubMed Google Scholar Mortality of HF remains high with approximately 20% dying within 1 year of their diagnosis and a 5-year mortality of 59% in men and 45% in women despite advances in therapy.2Lloyd-Jones D. Adams R.J. Brown T.M. Carnethon M. Dai S. De Simone G. Ferguson T.B. Ford E. Furie K. Gillespie C. Go A. Greenlund K. Haase N. Hailpern S. Ho P.M. Howard V. Kissela B. Kittner S. Lackland D. Lisabeth L. Marelli A. McDermott M.M. Meigs J. Mozaffarian D. Mussolino M. Nichol G. Roger V.L. Rosamond W. Sacco R. Sorlie P. Roger V.L. Thom T. Wasserthiel-Smoller S. Wong N.D. Wylie-Rosett J. American Heart Association, Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke statistics—2010 update: a report from the American Heart Association.Circulation. 2010; 121: e46-e215PubMed Google Scholar Depression has been predicted to increase in incidence and occurs in 1 of 6 residents in the United States. It is a global burden and appears to increase the incidence of other co-morbidities such as diabetes and coronary artery disease in addition to increased mortality from suicides.3Krishnan V. Nestler E.J. The molecular neurobiology of depression.Nature. 2008; 455: 894-902Crossref PubMed Scopus (2010) Google Scholar Depressed patients develop more symptoms, have worse compliance with medication regimens, are slower to return to work and social activities, and seem to have a poorer quality of life.4Musselman D.L. Evans D.L. Nemeroff C.B. The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment.Arch Gen Psychiatry. 1998; 55: 580-592Crossref PubMed Scopus (1358) Google Scholar In patients with known cardiac disease depression also predicts future events independent of disease severity and other risk factors such as smoking or diabetes.5Barth J. Schumacher M. Herrmann-Lingen C. Depression as a risk factor for mortality in patients with coronary heart disease: a meta-analysis.Psychosom Med. 2004; 66: 802-813Crossref PubMed Scopus (1060) Google Scholar Data specifically identifying depression as a cause for development of HF are lacking but it is likely that an association exists between the 2 conditions. Women have a greater risk of developing HF (hazard ratio 1.96) even after adjustment for co-morbidities.6Williams S.A. Kasl S.V. Heiat A. Abramson J.L. Krumholz H.M. Vaccarino V. Depression and risk of heart failure among the elderly: a prospective community-based study.Psychosom Med. 2002; 64: 6-12Crossref PubMed Scopus (40) Google Scholar Clinically significant depression has been reported in 21.5% of patients with HF in general with estimates of the prevalence of patients with HF and depression varying from 11% to 35% in the outpatient setting and 35% to 70% in the inpatient population.7Rutledge T. Reis V.A. Linke S.E. Greenberg B.H. Mills P.J. Depression in heart failure: a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes.J Am Coll Cardiol. 2006; 48: 1527-1537Abstract Full Text Full Text PDF PubMed Scopus (1127) Google Scholar Occurrence of depression in HF also varies depending on whether questionnaires (19%) or diagnostic interviews (33%) are used to detect depression and by New York Heart Association classification HF severity (11% in class I vs 42% in class IV).7Rutledge T. Reis V.A. Linke S.E. Greenberg B.H. Mills P.J. Depression in heart failure: a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes.J Am Coll Cardiol. 2006; 48: 1527-1537Abstract Full Text Full Text PDF PubMed Scopus (1127) Google Scholar Clarke et al8Clarke S.P. Frasure-Smith N. Lespérance F. Bourassa M.G. Psychosocial factors as predictors of functional status at 1 year in patients with left ventricular dysfunction.Res Nurs Health. 2000; 23: 290-300Crossref PubMed Scopus (66) Google Scholar showed that psychosocial factors including several related to depression predicted functional status after 1 year in patients with left ventricular dysfunction and Jiang et al9Jiang W. Alexander J. Christopher E. Kuchibhatla M. Gaulden L.H. Cuffe M.S. Blazing M.A. Davenport C. Califf R.M. Krishnan R.R. O'Connor C.M. Relationship of depression to increased risk of mortality and rehospitalization in patients with congestive heart failure.Arch Intern Med. 2001; 161: 1849-1856Crossref PubMed Scopus (757) Google Scholar showed that major depression in patients with HF was associated with a twofold increase in mortality and a threefold increase in hospitalization independent of any other identified risk factors. Patients who have concurrent HF and depression also have increased medical costs of 25% to 40%. A history of depression in patients with HF at hospitalization is a predictor of increased length of stay and increased 60- to 90-day mortality.10Albert N.M. Fonarow G.C. Abraham W.T. Gheorghiade M. Greenberg B.H. Nunez E. O'Connor C.M. Stough W.G. Yancy C.W. Young J.B. Depression and clinical outcomes in heart failure: an OPTIMIZE-HF analysis.Am J Med. 2009; 122: 366-373Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar Evaluation of depression and HF across ethnic groups is limited. Non-Hispanic blacks with chronic HF had higher levels of anxiety and depression compared to Hispanics.11Evangelista L.S. Ter-Galstanyan A. Moughrabi S. Moser D.K. Anxiety and depression in ethnic minorities with chronic heart failure.J Card Fail. 2009; 15: 572-579Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Higher levels of depression were noted in women than in men (37% vs 33%) and nonwhites than in whites (77% and 67%, respectively) despite generally high levels of support with a lack of support associated with an increase in cardiac events.12Struthers A.D. Anderson G. Donnan P.T. MacDonald T. Social deprivation increases cardiac hospitalisations in chronic heart failure independent of disease severity and diuretic non-adherence.Heart. 2000; 83: 12-16Crossref PubMed Scopus (78) Google Scholar Despite extensive research (Table 1) the interaction between HF and depression is incompletely understood.13Gottlieb S.S. Khatta M. Friedmann E. Einbinder L. Katzen S. Baker B. Marshall J. Minshall S. Robinson S. Fisher M.L. Potenza M. Sigler B. Baldwin C. Thomas S.A. The influence of age, gender, and race on the prevalence of depression in heart failure patients.J Am Coll Cardiol. 2004; 43: 1542-1549Abstract Full Text Full Text PDF PubMed Scopus (353) Google Scholar, 14Faller H. Störk S. Schowalter M. Steinbüchel T. Wollner V. Ertl G. Angermann C.E. Depression and survival in chronic heart failure: does gender play a role?.Eur J Heart Fail. 2007; 9: 1018-1023Crossref PubMed Scopus (66) Google Scholar, 15Bekelman D.B. Havranek E.P. Becker D.M. Kutner J.S. Peterson P.N. Wittstein I.S. Gottlieb S.H. Yamashita T.E. Fairclough D.L. Dy S.M. Symptoms, depression, and quality of life in patients with heart failure.J Card Fail. 2007; 13: 643-648Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar, 16Bekelman D.B. Dy S.M. Becker D.M. Wittstein I.S. Hendricks D.E. Yamashita T.E. Gottlieb S.H. Spiritual well-being and depression in patients with heart failure.J Gen Intern Med. 2007; 22: 470-477Crossref PubMed Scopus (150) Google Scholar, 17Fonarow G.C. Abraham W.T. Albert N.M. Stough W.G. Gheorghiade M. Greenberg B.H. O'Connor C.M. Nunez E. Yancy C.W. Young J.B. Day of admission and clinical outcomes for patients hospitalized for heart failure: findings from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF).Circ Heart Fail. 2008; 1: 50-57Crossref PubMed Scopus (66) Google Scholar, 18Sherwood A. Blumenthal J.A. Trivedi R. Johnson K.S. O'Connor C.M. Adams Jr, K.F. Dupree C.S. Waugh R.A. Bensimhon D.R. Gaulden L. Christenson R.H. Koch G.G. Hinderliter A.L. Relationship of depression to death or hospitalization in patients with heart failure.Arch Intern Med. 2007; 167: 367-373Crossref PubMed Scopus (268) Google Scholar, 19Lesman-Leegte I. van Veldhuisen D.J. Hillege H.L. Moser D. Sanderman R. Jaarsma T. Depressive symptoms and outcomes in patients with heart failure: data from the COACH study.Eur J Heart Fail. 2009; 11: 1202-1207Crossref PubMed Scopus (80) Google Scholar, 20Angermann C.E. Gelbrich G. Störk S. Fallgatter A. Deckert J. Faller H. Ertl G. MOOD-HF InvestigatorsRationale and design of a randomised, controlled, multicenter trial investigating the effects of selective serotonin re-uptake inhibition on morbidity, mortality and mood in depressed heart failure patients (MOOD-HF).Eur J Heart Fail. 2007; 9: 1212-1222Crossref PubMed Scopus (79) Google Scholar, 21Gottlieb S.S. Kop W.J. Thomas S.A. Katzen S. Vesely M.R. Greenberg N. Marshall J. Cines M. Minshall S. A double-blind placebo-controlled pilot study of controlled-release paroxetine on depression and quality of life in chronic heart failure.Am Heart J. 2007; 153: 868-873Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 22O'Connor C.M. Jiang W. Kuchibhatla M. Silva S.G. Cuffe M.S. Callwood D.D. Zakhary B. Stough W.G. Arias R.M. Rivelli S.K. Krishnan R. SADHART-CHF InvestigatorsSafety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial.J Am Coll Cardiol. 2010; 56: 692-699Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, 23Yeh G.Y. McCarthy E.P. Wayne P.M. Stevenson L.W. Wood M.J. Forman D. Davis R.B. Phillips R.S. Tai chi exercise in patients with chronic heart failure: a randomized clinical trial.Arch Intern Med. 2011; 171: 750-757Crossref PubMed Scopus (162) Google Scholar However, many common pathways and feedback loops may link HF and depression (Figure 1) . These interactions can worsen HF and depression contributing to further decompensation in the 2 conditions.Table 1Selected studies on depression in heart failureStudyStudy TypeLVEFSubjectsDuration (months)Conclusion of StudyGottlieb et al13Gottlieb S.S. Khatta M. Friedmann E. Einbinder L. Katzen S. Baker B. Marshall J. Minshall S. Robinson S. Fisher M.L. Potenza M. Sigler B. Baldwin C. Thomas S.A. The influence of age, gender, and race on the prevalence of depression in heart failure patients.J Am Coll Cardiol. 2004; 43: 1542-1549Abstract Full Text Full Text PDF PubMed Scopus (353) Google Scholar (2004)Prospective<40%15512Age, gender, and race similar to general population; treatment may improve QOLFaller et al14Faller H. Störk S. Schowalter M. Steinbüchel T. Wollner V. Ertl G. Angermann C.E. Depression and survival in chronic heart failure: does gender play a role?.Eur J Heart Fail. 2007; 9: 1018-1023Crossref PubMed Scopus (66) Google Scholar (2007)Prospective23133Depression produced poorer outcomes in patients with HF; prevalence 13% and associated with high mortalityBekelman et al15Bekelman D.B. Havranek E.P. Becker D.M. Kutner J.S. Peterson P.N. Wittstein I.S. Gottlieb S.H. Yamashita T.E. Fairclough D.L. Dy S.M. Symptoms, depression, and quality of life in patients with heart failure.J Card Fail. 2007; 13: 643-648Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar (2007)Cross sectional60Depression was associated with decrease in QOL; treatment of depression may improve QOLBekelman et al16Bekelman D.B. Dy S.M. Becker D.M. Wittstein I.S. Hendricks D.E. Yamashita T.E. Gottlieb S.H. Spiritual well-being and depression in patients with heart failure.J Gen Intern Med. 2007; 22: 470-477Crossref PubMed Scopus (150) Google Scholar (2007)Cross sectional60Spiritual well-being may improve QOL and decrease HFFonarow et al17Fonarow G.C. Abraham W.T. Albert N.M. Stough W.G. Gheorghiade M. Greenberg B.H. O'Connor C.M. Nunez E. Yancy C.W. Young J.B. Day of admission and clinical outcomes for patients hospitalized for heart failure: findings from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF).Circ Heart Fail. 2008; 1: 50-57Crossref PubMed Scopus (66) Google Scholar (2008)Prospective4,8612–3No difference in mortality by day of admission or discharge for HF hospitalizationsSherwood et al18Sherwood A. Blumenthal J.A. Trivedi R. Johnson K.S. O'Connor C.M. Adams Jr, K.F. Dupree C.S. Waugh R.A. Bensimhon D.R. Gaulden L. Christenson R.H. Koch G.G. Hinderliter A.L. Relationship of depression to death or hospitalization in patients with heart failure.Arch Intern Med. 2007; 167: 367-373Crossref PubMed Scopus (268) Google Scholar (2007)Prospective<40%20436Depression was associated with adverse prognosis in HF; worse outcomes with antidepressant therapyLesman-Leegte et al19Lesman-Leegte I. van Veldhuisen D.J. Hillege H.L. Moser D. Sanderman R. Jaarsma T. Depressive symptoms and outcomes in patients with heart failure: data from the COACH study.Eur J Heart Fail. 2009; 11: 1202-1207Crossref PubMed Scopus (80) Google Scholar (2009)Prospective95818Depression was associated with poor outcomes in patients with HFAngermann et al20Angermann C.E. Gelbrich G. Störk S. Fallgatter A. Deckert J. Faller H. Ertl G. MOOD-HF InvestigatorsRationale and design of a randomised, controlled, multicenter trial investigating the effects of selective serotonin re-uptake inhibition on morbidity, mortality and mood in depressed heart failure patients (MOOD-HF).Eur J Heart Fail. 2007; 9: 1212-1222Crossref PubMed Scopus (79) Google Scholar (2007)Double-blind placebo-controlled RCT<40%70012–24Effects of escitalopram on mortality, depression, anxiety, cognitive function, QOL, expenditures; result pendingGottlieb et al21Gottlieb S.S. Kop W.J. Thomas S.A. Katzen S. Vesely M.R. Greenberg N. Marshall J. Cines M. Minshall S. A double-blind placebo-controlled pilot study of controlled-release paroxetine on depression and quality of life in chronic heart failure.Am Heart J. 2007; 153: 868-873Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar (2007)Double-blind placebo-controlled RCT283Paroxetine CR decreased depression significantly in patients with HFO'Connor e al22O'Connor C.M. Jiang W. Kuchibhatla M. Silva S.G. Cuffe M.S. Callwood D.D. Zakhary B. Stough W.G. Arias R.M. Rivelli S.K. Krishnan R. SADHART-CHF InvestigatorsSafety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial.J Am Coll Cardiol. 2010; 56: 692-699Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar (2010)Double-blind placebo-controlled RCT<45%4693Sertraline did not improve depression in patients with HFYeh et al23Yeh G.Y. McCarthy E.P. Wayne P.M. Stevenson L.W. Wood M.J. Forman D. Davis R.B. Phillips R.S. Tai chi exercise in patients with chronic heart failure: a randomized clinical trial.Arch Intern Med. 2011; 171: 750-757Crossref PubMed Scopus (162) Google Scholar (2011)Single-blind parallel-group RCT<40%10012 weeksTai chi exercise may improve QOL, mood, and exercise self-efficacy in patients with HFCR = continuous release; LVEF = left ventricular ejection fraction; QOL = quality of life; RCT = randomized controlled trial. Open table in a new tab CR = continuous release; LVEF = left ventricular ejection fraction; QOL = quality of life; RCT = randomized controlled trial. Molecular pathways and mechanisms can be grouped into 4 categories: neurohormonal activation, inflammatory mediators, arrhythmias, and hypercoagulability. A compensatory mechanism in response to physiologic stress over time, neurohormonal activation and autonomic hyperactivity become pathologic and contribute to worsening left ventricular function rather than compensation. Autonomic arousal and hypothalamic–pituitary–adrenocortical axis hyperactivity causes vasoconstriction and volume expansion. Initially this maintains perfusion during low-output states but eventually increases blood pressure. As this develops the heart's ability to respond appropriately is overwhelmed by excessive afterload and volume expansion, leading to worsening cardiac function. This causes further increases in sympathetic tone, activation of the renin–angiotensin–aldosterone system, and development or worsening of HF.24Pepper G.S. Lee R.W. Sympathetic activation in heart failure and its treatment with beta-blockade.Arch Intern Med. 1999; 159: 225-234Crossref PubMed Scopus (87) Google Scholar These pathways have also been linked to the development of depression.25Plotsky P.M. Owens M.J. Nemeroff C.B. Psychoneuroendocrinology of depression Hypothalamic-pituitary-adrenal axis.Psychiatr Clin North Am. 1998; 21: 293-307Abstract Full Text Full Text PDF PubMed Scopus (560) Google Scholar This creates a feedback loop in which these diseases upregulate and worsen the same processes that initially caused them. When HF and depression coexist in patients, disease management programs for HF may not be effective.26Jaarsma T. Lesman-Leegte I. Hillege H.L. Veeger N.J. Sanderman R. van Veldhuisen D.J. COACH InvestigatorsDepression and the usefulness of a disease management program in heart failure: Insights from the COACH (Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure) study.J Am Coll Cardiol. 2010; 55: 1837-1843Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Patients with HF have increased proinflammatory cytokines such as interleukin-1, interleukin-2, interleukin-6, interleukin-10, and tumor necrosis factor, which may contribute to development of HF.27Blum A. Miller H. Pathophysiological role of cytokines in congestive heart failure.Annu Rev Med. 2001; 6: 95-103Google Scholar Initially the inflammatory cascade is protective because it allows the heart to respond appropriately to physiologic stress through cardiac myocyte hypertrophy and protection from apoptosis. However, as HF progresses these cytokines become maladaptive and play an important role in ventricular remodeling, uncoupling of β-adrenergic receptors, apoptosis, and contractile dysfunction resulting in pathogenesis of HF.27Blum A. Miller H. Pathophysiological role of cytokines in congestive heart failure.Annu Rev Med. 2001; 6: 95-103Google Scholar Inflammatory pathways also activate the hypothalamic–pituitary–adrenocortical axis, which can be pathologic and feed into the negative loop described in the previous section. Levels of proinflammatory cytokines correlate with disease severity and markers of inflammation such as high-sensitivity-C reactive protein and D-dimer may be used to monitor therapy of acute HF exacerbations.28Nair N. Jupiter D. Dehmer G.J. Gongora E. Farmer C. Song J. Puschett J. Prockop D. Addition of CRP and D-dimer enhance the predictive value of BNP in heart failure.Vasc Med. 2011; 16: 220Google Scholar Depression has also been identified as a cause of inflammation and markers such as high-sensitivity-C reactive protein, fibrinogen, tumor necrosis factor, and interleukin-6 are increased in depressed patients with no cardiac disease.29Narang R. Cleland J.G. Erhardt L. Ball S.G. Coats A.J. Cowley A.J. Dargie H.J. Hall A.S. Hampton J.R. Poole-Wilson P.A. Mode of death in chronic heart failure A request and proposition for more accurate classification.Eur Heart J. 1996; 17: 1390-1403Crossref PubMed Scopus (182) Google Scholar Arrhythmias are a major cause of morbidity in patients with HF with 25% to 50% of deaths in this condition considered arrhythmogenic.29Narang R. Cleland J.G. Erhardt L. Ball S.G. Coats A.J. Cowley A.J. Dargie H.J. Hall A.S. Hampton J.R. Poole-Wilson P.A. Mode of death in chronic heart failure A request and proposition for more accurate classification.Eur Heart J. 1996; 17: 1390-1403Crossref PubMed Scopus (182) Google Scholar Decreased heart rate variability (HRV) occurs in HF and has been associated with arrhythmias and increased morbidity and mortality.30Lombardi F. Mortara A. Heart rate variability and cardiac failure.Heart. 1998; 80: 213-214PubMed Google Scholar Decreased HRV is a marker of decreased parasympathetic tone, which exposes the heart to unopposed stimulation by sympathetic nerves and thus may provoke ventricular arrhythmias. High levels of norepinephrine and interleukin-6 are associated with decreased HRV, implying that autonomic arousal, inflammation, and arrhythmias may be interrelated. Depressed patients have a similar tendency to arrhythmias and decreased HRV even in the absence of HF, which could indicate a similar imbalance between autonomic sympathetic/parasympathetic balance and regulation.31Gorman J.M. Sloan R.P. Heart rate variability in depressive and anxiety disorders.Am Heart J. 2000; 140: 77-83Abstract Full Text Full Text PDF PubMed Scopus (382) Google Scholar Depression also is associated with longer QT intervals, decreased baroreflex cardiac control, and ventricular arrhythmias.32Minoretti P. Politi P. Martinelli V. Emanuele E. Bertona M. Falcone C. Geroldi D. QT interval duration in apparently healthy men is associated with depression-related personality trait neuroticism.J Psychosom Res. 2006; 61: 19-23Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar Although there is no evidence that these create a tendency toward worsening depression, given the high prevalence of sudden cardiac death in patients with HF this arrhythmogenic tendency of depression may contribute to a synergistic effect. Several antidepressant drug classes, particularly tricyclic antidepressants, are known to decrease HRV and cause prolonged QT intervals, which have implications for treatment decision.33van Noord C. Straus S.M. Sturkenboom M.C. Hofman A. Aarnoudse A.J. Bagnardi V. Kors J.A. Newton-Cheh C. Witteman J.C. Stricker B.H. Psychotropic drugs associated with corrected QT interval prolongation.J Clin Psychopharmacol. 2009; 29: 9-15Crossref PubMed Scopus (86) Google Scholar There is some early evidence, however, that selective serotonin reuptake inhibitors have a protective effect, but this needs further study.34McFarlane A. Kamath M.V. Fallen E.L. Malcolm V. Cherian F. Norman G. Effect of sertraline on the recovery rate of cardiac autonomic function in depressed patients after acute myocardial infarction.Am Heart J. 2001; 142: 617-623Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar Although hypercoagulability has been linked to HF most directly in the setting of ischemic cardiomyopathy, data demonstrating a relation between hypercoagulable states and depression are less clear. It is known that HF contributes to a hypercoagulable state and that anticoagulation lowers mortality but a causal relation has not been established.35Al-Khadra A.S. Salem D.N. Rand W.M. Udelson J.E. Smith J.J. Konstam M.A. Warfarin anticoagulation and survival: a cohort analysis from the Studies of Left ventricular Dysfunction.J Am Coll Cardiol. 1998; 31: 749-753Abstract Full Text Full Text PDF PubMed Scopus (197) Google Scholar Patients with HF have higher levels of von Willebrand factor, plasma viscosity, and fibrinogen and platelet activity.36Shantsila E. Lip G.Y. The endothelium and thrombotic risk in heart failure.Thromb Haemost. 2009; 102: 185-187PubMed Google Scholar, 37Dunkman W.B. Johnson G.R. Carson P.E. Bhat G. Farrell L. Cohn J.N. The V-HeFT VA Cooperative Studies GroupIncidence of thromboembolic events in congestive heart failure.Circulation. 1993; 87: VI94-VI101Crossref PubMed Scopus (179) Google Scholar Anxiety and psychological stress may precipitate hypercoagulability owing to activation of the coagulability and inhibitory activities of the fibrinolytic system.38Geiser F. Meier C. Wegener I. Imbierowicz K. Conrad R. Liedtke R. Oldenburg J. Harbrecht U. Association between anxiety and factors of coagulation and fibrinolysis.Psychother Psychosom. 2008; 77: 377-383Crossref PubMed Scopus (58) Google Scholar Behavioral actions may also affect the interaction of HF and depression. Depressed patients are less active, have worse compliance with medication and diet, and are more likely to abuse tobacco and alcohol. Such behavioral issues in our view may contribute to the development and worsening of HF and negatively affect self-image, which can in turn worsen depression. Diuretics result in frequent urination and possibly social embarrassment, aldosterone antagonists can cause gynecomastia and body dysmorphia in men, and β blockers can cause insomnia, fatigue, and sexual dysfunction, among other issues. This amplifies the central theme in our opinion that these 2 conditions create a cycle in which each worsens the other, leading to worse outcomes and treatment challenges. Compliance with treatment regimens is challenging in patients with HF. Treatment regimens are frequently complex, often involving multiple medications taken several times daily; thus the mental burden on patients to take their medications correctly is high. Noncompliance is a factor in a large number of HF-related hospitalizations and has been shown to be an independent risk factor for mortality even when the therapy is placebo. Monane et al39Monane M. Bohn R.L. Gurwitz J.H. Glynn R.J. Avorn J. Noncompliance with congestive heart failure therapy in the elderly.Arch Intern Med. 1994; 154: 433-437Crossref PubMed Scopus (251) Google Scholar followed 7,200 patients with HF and found a compliance rate of only 10% with an average of 111 days per year when patients took no medications at all. Coping mechanisms can be maladaptive and using them can worsen HF, although their loss can lead to worsening depression. Given the disabling nature of HF and the complexity of many treatment regimens, it is therefore not surprising that depression is linked to poor compliance. In patients with hypertension depression is an independent risk factor for noncompliance.40Wang P.S. Bohn R.L. Knight E. Glynn R.J. Mogun H. Avorn J. Noncompliance with antihypertensive medications: the impact of depressive symptoms and psychosocial factors.J Gen Intern Med. 2002; 17: 504-511Crossref PubMed Scopus (303) Google Scholar A large meta-analysis showed that depression is linked to a threefold increase in noncompliance across some diseases.41DiMatteo M.R. Lepper H.S. Croghan T.W. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence.Arch Intern Med. 2000; 160: 2101-2107Crossref PubMed Scopus (3000) Google Scholar Despite recent advances in telemedicine, monitoring compliance remains a substantial challenge in the patient with HF.42Nieuwenhuis M.M. van der Wal M.H. Jaarsma T. The body of knowledge on compliance in heart failure patients: we are not there yet.J Cardiovasc Nurs. 2011; 26: 21-28Crossref PubMed Scopus (15) Google Scholar Tailoring antidepressant therapy can be key to controlling depression in HF and decrease cardiovascular side effects.43Tousoulis D. Antonopoulos A.S. Antoniades C. Saldari C. Stefanadi E. Siasos G. Stougianos P. Plastiras A. Korompelis P. Stefanadis C. Role of depression in heart failure—choosing the right antidepressive treatment.Int J Cardiol. 2010; 140: 12-18Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 44Leftheriotis D. Flevari P. Ikonomidis I. Douzenis A. Liapis C. Paraskevaidis I. Iliodromitis E. Lykouras L. Kremastinos D.T. The role of the selective serotonin re-uptake inhibitor sertraline in nondepressive patients with chronic ischemic heart failure: a preliminary study.Pacing Clin Electrophysiol. 2010; 33: 1217-1223Crossref PubMed Scopus (14) Google Scholar However, definitive relations are currently unclear. There are several areas where information about the relation between HF and depression are lacking such as data on the effectiveness of treatment for depression and how this modifies the pathways shared by HF and depression. Existing studies with specific drugs such as the Safety and Efficacy of Sertraline for Depression in Patients with Congestive Heart Failure (SADHART-CHF) trial and others have shown no difference in cardiovascular outcomes,45O'Connor C.M. Jiang W. Kuchibhatla M. Silva S.G. Cuffe M.S. Callwood D.D. Zakhary B. Stough W.G. Arias R.M. Rivelli S.K. Krishnan R. SADHART-CHF InvestigatorsSafety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial.J Am Coll Cardiol. 2010; 56: 692-699Abstract Full Text Full Text PDF PubMed Scopus (386) Google Scholar, 46Jiang W. Krishnan R. Kuchibhatla M. Cuffe M.S. Martsberger C. Arias R.M. O'Connor C.M. SADHART-CHF InvestigatorsCharacteristics of depression remission and its relation with cardiovascular outcome among patients with chronic heart failure (from the SADHART-CHF Study).Am J Cardiol. 2011; 107: 545-551Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar whereas smaller studies have shown improvements in symptoms of depression, quality of life, and compliance when patients are treated.47Thombs B.D. de Jonge P. Coyne J.C. Whooley M.A. Frasure-Smith N. Mitchell A.J. Zuidersma M. Eze-Nliam C. Lima B.B. Smith C.G. Soderlund K. Ziegelstein R.C. Depression screening and patient outcomes in cardiovascular care: a systematic review.JAMA. 2008; 300: 2161-2171Crossref PubMed Scopus (381) Google Scholar, 48Rollman B.L. Belnap B.H. LeMenager M.S. Mazumdar S. Houck P.R. Counihan P.J. Kapoor W.N. Schulberg H.C. Reynolds III, C.F. Telephone-delivered collaborative care for treating post-CABG depression: a randomized controlled trial.JAMA. 2009; 302: 2095-2103Crossref PubMed Scopus (262) Google Scholar, 49Rieckmann N. Gerin W. Kronish I.M. Burg M.M. Chaplin W.F. Kong G. Lespérance F. Davidson K.W. Course of depressive symptoms and medication adherence after acute coronary syndromes: an electronic medication monitoring study.J Am Coll Cardiol. 2006; 48: 2218-2222Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar" @default.
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