A 45-year-old man with a 5-year history of nonischemic cardiomyopathy with an ejection fraction of 30% was seen in routine follow-up in the heart failure (HF) clinic. He had only mild limitation of activity with New York Heart Association (NYHA) Functional Classification I to II symptoms. He had been on a stable regimen of guideline-directed medical therapy for at least 6 months.

In symptom review, he noted that he was having trouble sleeping though he did not have paroxysmal nocturnal dyspnea or orthopnea. He was not noted to snore or have nocturnal apneic episodes according to his wife. It was noted that he had lost 5 pounds and he stated that he had little appetite. He further noted that he had difficulty concentrating on tasks and that, although he had previously engaged in a routine walking regimen, he now had little interest in activity and spent most of his time sitting at home watching television.

He completed the Patient Health Questionnaire 9 (PHQ-9) while waiting for his appointment. The total score on the first part of this depression screening tool was 16, which was consistent with significant depression and suggested the need for treatment. The patient agreed that he was likely depressed and had “felt down” for many days over the past 2 months.

His physician discussed with him the problems of depression in patients with HF and they began discussions of treatment options.

Depression is a comorbidity common to most forms of heart disease.¹ However, it especially affects those with HF. Ferketich and Binkley analyzed a large cohort of respondents to the National Health Interview Survey (NHIS).¹ Of this cohort, 17,541 completed the K6 depression screen, which is a 6-item questionnaire designed for the NHIS. Table 8-1 shows the odds ratios for reporting depression in different cardiovascular disease categories as compared to those who did not report a history of cardiovascular disease. It can be seen that there is a progressive increase in the odds ratio for reporting symptoms of depression with the lowest odds ratio being in those with coronary heart disease and the highest odds ratio in those with HF. Therefore, although all patients with heart disease have an increased risk for having depression, those with HF have a 3.6 to 1 odds ratio compared to those without heart disease. As shown in Table 8-2, smaller studies have further demonstrated the increased prevalence of depression in those with HF.² Further, patients with HF and depression have increased mortality and an increase in the risk for hospital admission.

As these data show, clinicians caring for patients with HF will find that depression is a common problem and one that cannot be ignored in their care.

Although patients may feel dysphoric due to the physical limitations imposed by impaired cardiac function, there are clearly physiologic mechanisms that contribute to the concurrence of depression and HF. Figure 8-1 demonstrates 3 of these physiologic pathways. As the figure illustrates, there is a reciprocating cycle of mechanisms that promote both the progression of HF and depression.³

Among the mechanisms common to both HF and depression is imbalance of the autonomic nervous system.⁴ Increased sympathetic and decreased parasympathetic activity evolve early in the onset of HF and this autonomic imbalance likely contributes to vascular modeling, and promotes myocardial damage and enhanced arrhythmia risk.⁵ Similarly, autonomic imbalance is a signature of depression and appears to play a role not only in the progression of depression but also in associated adverse health outcomes.^3,6

Cytokine mediated inflammation is a second promoter of disease progression common to both depression and HF. Increases in inflammatory cytokines have been consistently demonstrated in patients with HF, and likely contribute to progressive myocardial necrosis as well as vascular damage.³ Cytokines also appear to function as neurotransmitters, and in this capacity have been shown to elicit depressive symptoms in animal models and to be associated with depressed mood in patients.³

Finally, both HF and depression are associated with increased risk for platelet aggregation and vascular thrombosis.² This hypercoagulability may be due to activation of platelets by both cytokine and sympathetic stimulation as well as increased expression of cell surface activators of platelet aggregation.

As shown in Figure 8-2, these mechanisms can all converge to simultaneously exacerbate depression and HF. Ferketich and Binkley reported that circulating levels of selected circulating cytokines were in fact significantly greater in patients with HF who were depressed as compared to those who were not.⁷ This suggests that the coexistence of these mechanisms may have additive detrimental effects in patients with both depression and HF. An intriguing but still unanswered question is whether treatment of either HF or depression will alleviate the symptoms and progression of the other.