What Is the Clinical Course of Advanced Heart Failure and How Do Implanted Cardiac Devices Alter This Course?

Introduction and Scope of the Problem

Heart failure is a chronic and progressive illness frequently associated with multiple comorbidities and is a leading cause of death in the United States. The illness is reaching epidemic numbers: an estimated 6.2 million people have heart failure, with the incidence approaching 21 per 1,000 adults over the age of 65. Data from 2016 indicate that heart failure is implicated in some manner in 1 in 8 deaths in the United States. Despite medical and surgical advances, 5-year adjusted case fatality rates after an initial hospitalization for patients with heart failure are approximately 42%. The estimated costs of heart failure in the United States in 2012 were in excess of $30.7 billion. Heart failure adversely affects quality of life because of its relatively high burden of symptoms, and as patients live longer with the disease, the population living with end-stage heart failure and symptoms refractory to medical therapy continues to grow.

Approximately 66% of patients with this disease have heart failure with reduced left ventricular ejection fraction (HFrEF). In patients with HFrEF, the percentage of blood pumped out of the left ventricle with each heart beat is 40% or less. Patients whose left ventricular ejection fraction is between 40% and 50% are considered to have borderline preserved ejection fraction (HFpEF, borderline), also called heart failure with midrange ejection fraction (HFmrEF). The remaining patients have heart failure with preserved left ventricular ejection fraction (HFpEF), characterized by a left ventricular ejection fraction of 50% or more.

Clinical characteristics among patients with HFmrEF and HFpEF tend to differ from those patients with HFrEF. Patients with HFmrEF and HFpEF are more likely to be older in age, female, and with underlying etiologies of hypertension, chronic obstructive pulmonary disease (COPD), and diabetes. Research is limited as to the most appropriate treatment approaches for these patients populations, with clinical trials of pharmacological therapy for patients with HFmrEF and HFpEF reporting mixed results. Thus treatment of these patients, inclusive of palliative management, focuses on the treatment of underlying conditions and associated symptoms including shortness of breath related to pulmonary congestion and peripheral edema. HFmrEF and HFpEF patients have slightly lower mortality rates relative to patients with HFrEF. However, morbidity outcomes including rates of hospitalization, symptom burden, and impairments to quality of life are similar across groups.

The American College of Cardiology/American Heart Association stages of heart failure, the most current scale in widespread use, characterize the progression of the disease and include stages A through D as follows.

• Stage A: Patients who are at risk for heart failure but are without structural heart disease and do not have symptoms; may include patients with hypertension, coronary artery disease, and diabetes. The goal of this stage is to identify these individuals early to modify risk factors to prevent them from developing heart failure.

• Stage B: Patients who are asymptomatic but have developed some structural heart disease. These may be patients with a previous myocardial infarction or uncontrolled hypertension resulting in cardiomegaly and reduced left ventricular ejection fraction, for example.

• Stage C: Patients with symptomatic heart failure. These patients have known structural heart disease and may have reduced exercise tolerance as a result of shortness of breath and fatigue.

• Stage D: Patients with refractory end-stage heart failure. These individuals have marked symptoms at rest and minimal exertion despite maximal medical therapy.

The New York Heart Association Classification is a tool for staging the functional capacity and symptom burden of a patient’s heart failure. It is an older scale that is being used less commonly in cardiology now. This scheme consists of classes I to IV.

• Class I: Asymptomatic—patients have no limitation of physical activity, and ordinary physical activity does not cause shortness of breath or other symptoms.

• Class II: Mild heart failure—patients have slight limitations in function; they will be comfortable at rest, but ordinary physical activity creates symptoms.

• Class III: Moderate heart failure—patients have marked limitations in their activity; although they are comfortable at rest, less than ordinary activity will cause symptoms.

• Class IV: Severe—patients cannot undertake any physical activity without discomfort and have symptoms of heart failure at rest.

Patients are often first diagnosed with Stage C heart failure, late in the disease course when both structural damage and symptoms are present. These patients may first present with symptomatic complaints to their primary care provider or are diagnosed only after their first hospitalization for an acute heart failure exacerbation. As a result, median heart failure survival following diagnosis is 2.1 years, with approximately 75% of patients dying within 5 years of heart failure diagnosis. A higher New York Heart Functional Class also portends poorer survival, with 5-year survival among patients with New York Heart Functional Class III or IV heart failure of approximately 49%.

Relevant Pathophysiology

This section focuses on the key pathophysiological elements relative to the practice of palliative medicine—mechanisms behind the symptoms seen most commonly in patients with advanced (Stage D) heart failure, the reasons the trajectory of heart failure is so difficult to predict, and the influence of new advanced medical technologies on this trajectory.

The relationship between the progression of heart failure and symptoms is complex. Heart failure is a systemic disease that affects the heart as well as other body systems. As heart failure progresses and cardiac function declines, symptom burden increases. Dyspnea is one of the more common symptoms and may be seen in more than 85% of patients with heart failure. Dyspnea may be due to volume overload related to pulmonary congestion as well as hypoperfusion. A patient’s dyspnea may progress from occurring with activity to occurring at rest and at night. Volume overload may be a prominent symptom and can manifest as ascites, abdominal bloating or discomfort, constipation, and peripheral edema.

Pain is also a common complaint among patients with heart failure. Data suggest that up to half of patients with heart failure will have pain, and this may include uncontrolled pain in specific regions (e.g., abdomen, chest, joints, legs) as well as generalized pain syndromes. Although still not completely understood, the cause of generalized pain may be due to inflammatory mediators and dysregulation of hormonal modulators and cytokines. Abdominal pain is more commonly related to hepatic congestion and consequent swelling of the liver capsule, and it may also be related to hypoperfusion of the abdominal viscera.

As many as 90% of patients may exhibit signs of fatigue, cachexia, and anorexia—all of which are related to the systemic effects of heart failure. Insomnia and disrupted sleep are also common symptoms, and many patients suffer from daytime somnolence and fatigue related to undiagnosed sleep apnea. Finally, psychological symptoms are significant, particularly anxiety and depression. Feelings of social isolation may also be increased in patients with heart failure, which may be related to fatigue and reduced exercise tolerance making it difficult for patients to leave their home and socialize with others.

The clinical trajectory of heart failure is unpredictable. While patients with cancer maintain their functional state for prolonged periods of time with rapid declines in function that often represents that death is imminent, the trajectory of heart failure exacerbations and recovery is not as predictable. Over their final years and months of life, patients with heart failure may have multiple acute periods of decline; however, these periods of decline are often punctuated with periods of partial recovery, complicating prognostication ( Fig. 47.1 ). Several prognostic models have been developed to predict mortality among patients with heart failure. These models perform reasonably well at the population level, but lack accuracy when applied to individual patients. Moreover, clinicians, as well as patients and families, often overestimate prognosis, making decision making and discussions around advance care planning and goals of care difficult.