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Commonality Between Depression and Heart Failure

Published:December 07, 2011DOI:https://doi.org/10.1016/j.amjcard.2011.10.039
      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.
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      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.
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      Coexistence of Depression and HF

      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.
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      In patients with known cardiac disease depression also predicts future events independent of disease severity and other risk factors such as smoking or diabetes.
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      Depression as a risk factor for mortality in patients with coronary heart disease: a meta-analysis.
      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.
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      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.
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      • Mills P.J.
      Depression in heart failure: a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes.
      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).
      • Rutledge T.
      • Reis V.A.
      • Linke S.E.
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      • Mills P.J.
      Depression in heart failure: a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes.
      Clarke et al
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      • Bourassa M.G.
      Psychosocial factors as predictors of functional status at 1 year in patients with left ventricular dysfunction.
      showed that psychosocial factors including several related to depression predicted functional status after 1 year in patients with left ventricular dysfunction and Jiang et al
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      • O'Connor C.M.
      Relationship of depression to increased risk of mortality and rehospitalization in patients with congestive heart failure.
      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.
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      • Fonarow G.C.
      • Abraham W.T.
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      • Greenberg B.H.
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      • Stough W.G.
      • Yancy C.W.
      • Young J.B.
      Depression and clinical outcomes in heart failure: an OPTIMIZE-HF analysis.
      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.
      • Evangelista L.S.
      • Ter-Galstanyan A.
      • Moughrabi S.
      • Moser D.K.
      Anxiety and depression in ethnic minorities with chronic heart failure.
      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.
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      • Anderson G.
      • Donnan P.T.
      • MacDonald T.
      Social deprivation increases cardiac hospitalisations in chronic heart failure independent of disease severity and diuretic non-adherence.
      Despite extensive research (Table 1) the interaction between HF and depression is incompletely understood.
      • Gottlieb S.S.
      • Khatta M.
      • Friedmann E.
      • Einbinder L.
      • Katzen S.
      • Baker B.
      • Marshall J.
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      • 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.
      • Faller 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?.
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      • Havranek E.P.
      • Becker D.M.
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      • 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.
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      • 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.
      • Fonarow 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).
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      • Gaulden L.
      • Christenson R.H.
      • Koch G.G.
      • Hinderliter A.L.
      Relationship of depression to death or hospitalization in patients with heart failure.
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      • 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.
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      • Gelbrich G.
      • Störk S.
      • Fallgatter A.
      • Deckert J.
      • Faller H.
      • Ertl G.
      MOOD-HF Investigators
      Rationale 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).
      • Gottlieb 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.
      • O'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 Investigators
      Safety 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.
      • Yeh G.Y.
      • McCarthy E.P.
      • Wayne P.M.
      • Stevenson L.W.
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      • Davis R.B.
      • Phillips R.S.
      Tai chi exercise in patients with chronic heart failure: a randomized clinical trial.
      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 failure
      StudyStudy TypeLVEFSubjectsDuration (months)Conclusion of Study
      Gottlieb et al
      • Gottlieb 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.
      (2004)
      Prospective<40%15512Age, gender, and race similar to general population; treatment may improve QOL
      Faller et al
      • Faller 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?.
      (2007)
      Prospective23133Depression produced poorer outcomes in patients with HF; prevalence 13% and associated with high mortality
      Bekelman et al
      • Bekelman 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.
      (2007)
      Cross sectional60Depression was associated with decrease in QOL; treatment of depression may improve QOL
      Bekelman et al
      • Bekelman 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.
      (2007)
      Cross sectional60Spiritual well-being may improve QOL and decrease HF
      Fonarow et al
      • Fonarow 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).
      (2008)
      Prospective4,8612–3No difference in mortality by day of admission or discharge for HF hospitalizations
      Sherwood et al
      • Sherwood 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.
      (2007)
      Prospective<40%20436Depression was associated with adverse prognosis in HF; worse outcomes with antidepressant therapy
      Lesman-Leegte et al
      • Lesman-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.
      (2009)
      Prospective95818Depression was associated with poor outcomes in patients with HF
      Angermann et al
      • Angermann C.E.
      • Gelbrich G.
      • Störk S.
      • Fallgatter A.
      • Deckert J.
      • Faller H.
      • Ertl G.
      MOOD-HF Investigators
      Rationale 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).
      (2007)
      Double-blind placebo-controlled RCT<40%70012–24Effects of escitalopram on mortality, depression, anxiety, cognitive function, QOL, expenditures; result pending
      Gottlieb et al
      • Gottlieb 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.
      (2007)
      Double-blind placebo-controlled RCT283Paroxetine CR decreased depression significantly in patients with HF
      O'Connor e al
      • O'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 Investigators
      Safety 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.
      (2010)
      Double-blind placebo-controlled RCT<45%4693Sertraline did not improve depression in patients with HF
      Yeh et al
      • Yeh 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.
      (2011)
      Single-blind parallel-group RCT<40%10012 weeksTai chi exercise may improve QOL, mood, and exercise self-efficacy in patients with HF
      CR = continuous release; LVEF = left ventricular ejection fraction; QOL = quality of life; RCT = randomized controlled trial.
      Figure thumbnail gr1
      Figure 1Cause and effect relation between heart failure and depression.
      Molecular pathways and mechanisms can be grouped into 4 categories: neurohormonal activation, inflammatory mediators, arrhythmias, and hypercoagulability.

      Neurohormonal activation

      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.
      • Pepper G.S.
      • Lee R.W.
      Sympathetic activation in heart failure and its treatment with beta-blockade.
      These pathways have also been linked to the development of depression.
      • Plotsky P.M.
      • Owens M.J.
      • Nemeroff C.B.
      Psychoneuroendocrinology of depression Hypothalamic-pituitary-adrenal axis.
      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.
      • Jaarsma T.
      • Lesman-Leegte I.
      • Hillege H.L.
      • Veeger N.J.
      • Sanderman R.
      • van Veldhuisen D.J.
      COACH Investigators
      Depression 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.

      Inflammatory mediators

      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.
      • Blum A.
      • Miller H.
      Pathophysiological role of cytokines in congestive heart failure.
      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.
      • Blum A.
      • Miller H.
      Pathophysiological role of cytokines in congestive heart failure.
      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.
      • Nair 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.
      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.
      • Narang 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.

      Arrhythmias

      Arrhythmias are a major cause of morbidity in patients with HF with 25% to 50% of deaths in this condition considered arrhythmogenic.
      • Narang 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.
      Decreased heart rate variability (HRV) occurs in HF and has been associated with arrhythmias and increased morbidity and mortality.
      • Lombardi F.
      • Mortara A.
      Heart rate variability and cardiac failure.
      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.
      • Gorman J.M.
      • Sloan R.P.
      Heart rate variability in depressive and anxiety disorders.
      Depression also is associated with longer QT intervals, decreased baroreflex cardiac control, and ventricular arrhythmias.
      • Minoretti 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.
      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.
      • van 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.
      There is some early evidence, however, that selective serotonin reuptake inhibitors have a protective effect, but this needs further study.
      • McFarlane 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.

      Hypercoagulability

      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.
      • Al-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.
      Patients with HF have higher levels of von Willebrand factor, plasma viscosity, and fibrinogen and platelet activity.
      • Shantsila E.
      • Lip G.Y.
      The endothelium and thrombotic risk in heart failure.
      • Dunkman W.B.
      • Johnson G.R.
      • Carson P.E.
      • Bhat G.
      • Farrell L.
      • Cohn J.N.
      The V-HeFT VA Cooperative Studies Group
      Incidence of thromboembolic events in congestive heart failure.
      Anxiety and psychological stress may precipitate hypercoagulability owing to activation of the coagulability and inhibitory activities of the fibrinolytic system.
      • Geiser F.
      • Meier C.
      • Wegener I.
      • Imbierowicz K.
      • Conrad R.
      • Liedtke R.
      • Oldenburg J.
      • Harbrecht U.
      Association between anxiety and factors of coagulation and fibrinolysis.

      Behavioral Actions and Compliance

      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 al
      • Monane M.
      • Bohn R.L.
      • Gurwitz J.H.
      • Glynn R.J.
      • Avorn J.
      Noncompliance with congestive heart failure therapy in the elderly.
      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.
      • Wang 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.
      A large meta-analysis showed that depression is linked to a threefold increase in noncompliance across some diseases.
      • DiMatteo 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.
      Despite recent advances in telemedicine, monitoring compliance remains a substantial challenge in the patient with HF.
      • Nieuwenhuis M.M.
      • van der Wal M.H.
      • Jaarsma T.
      The body of knowledge on compliance in heart failure patients: we are not there yet.
      Tailoring antidepressant therapy can be key to controlling depression in HF and decrease cardiovascular side effects.
      • Tousoulis 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.
      • Leftheriotis 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.
      However, definitive relations are currently unclear.

      Future Directions

      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,
      • O'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 Investigators
      Safety 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.
      • Jiang W.
      • Krishnan R.
      • Kuchibhatla M.
      • Cuffe M.S.
      • Martsberger C.
      • Arias R.M.
      • O'Connor C.M.
      SADHART-CHF Investigators
      Characteristics of depression remission and its relation with cardiovascular outcome among patients with chronic heart failure (from the SADHART-CHF Study).
      whereas smaller studies have shown improvements in symptoms of depression, quality of life, and compliance when patients are treated.
      • Thombs 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.
      • Rollman 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.
      • Rieckmann 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.

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