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Managing Heart Failure Comorbidities

— Hypertension, atrial fibrillation, type 2 diabetes, and anemia care may require adjustment in HF

MedpageToday
Illustration of different comorbidities over a heart in failure
Key Points

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Management of comorbidities is an increasing part of heart failure (HF) care.

The shift in demographics to include a higher proportion of elderly individuals with heart failure with preserved ejection fraction (HFpEF), means that hypertension, diabetes mellitus, renal impairment, sleep apnea, arrhythmia, and other conditions present an increasing clinical challenge.

Comorbidities like hypertension, atrial fibrillation (AF), and diabetes, however, have also been linked to worse clinical outcomes. Indeed, of stable HF patients in the U.K. determined that comorbidity "accounts for the majority of lost life expectancy in people with heart failure."

Multimorbidity is common as well, with more than 85% of HF patients having . The more comorbidities, the higher the risk for .

The most common comorbidity in HF is hypertension, affecting more than 80% of patients, according to Centers for Medicare & Medicaid Services . High cholesterol follows, with a prevalence of about 60% among HF patients. Diabetes mellitus affects around half, as does anemia. Chronic kidney disease coexists with HF in 42-45% of patients, while AF is seen in about 28% of HF patients age 65 and older.

Hypertension

Paradoxically, higher blood pressure is actually associated with better outcomes in heart failure. Systolic blood pressure less than 120 mm Hg (not necessarily as a part of an antihypertensive treatment strategy) was independently linked to of death overall and from cardiovascular and HF causes as well as more cardiovascular-related and HF hospitalizations. The also showed higher morality in patients with low systolic pressure at baseline.

"It is likely that this correlation is a consequence of the fact that more severe cardiac dysfunction causes a decline in systemic blood pressure, making low blood pressure a marker for more advanced HF," and complicating research on benefits of antihypertensives in this population, notes .

Guidelines for HF generally recommend treating hypertension according to hypertension guidelines.

The 2022 American College of Cardiology/American Heart Association acknowledge the lack of trial evidence for the impact of goal blood pressure reduction on outcomes in HF with reduced ejection fraction (HFrEF).

Blood pressure-lowering has not been shown to improve outcomes in HFpEF either, an report for HFpEF notes. However, for these patients, "uncontrolled blood pressure may precipitate acute HF decompensation, and individuals with HFpEF can have an exaggerated hypertensive response to exercise."

Although achieving target doses of HF medications does help, optimal blood pressure goals and which antihypertensive regimens are best at achieving those goals are also not known.

In HFpEF, beta-blockers should generally be avoided for hypertension treatment given negative chronotropic effects whereas diuretic agents are preferred because they are often required for volume control, the consensus document points out.

On a practical note that applies across the HF spectrum, "Many combination antihypertensive medications are available as affordable generic formulations and may improve adherence in individuals with HFpEF who are at risk for polypharmacy and associated poor outcomes," the document added.

Atrial Fibrillation

Heart failure and AF have a complex relationship, in which AF may worsen HF, but also HF increases the risk of AF.

For HF patients, rhythm control medication hasn't proven superior to rate control medication in randomized trials. "Notably, aggressive rate control may be deleterious in HFpEF patients with AF due to significant LA [left atrial] dysfunction resulting in low stroke volume and inability to increase stroke volume during exertion," the HFpEF guidelines state. In HFrEF, nondihydropyridine calcium channel blockers like diltiazem and verapamil are contraindicated.

However, ablation beat antiarrhythmic drugs in the CASTLE-AF trial, with a relative 38% reduction in the composite of all-cause mortality and hospitalization for worsening HF and a 47% reduction in death alone over about 38 months. Just who is best treated with catheter-based approaches isn't entirely clear, a noted, but there was some signal in CASTLE-AF in that patients with left ventricular EF of at least 25% and those with persistent (vs paroxysmal) AF had more benefit.

In terms of other medication, guidelines recommend anticoagulation for chronic HF with AF, whether permanent, persistent, or paroxysmal and regardless of other risk factors, because it is a hypercoagulable state and an independent risk factor for stroke. Direct-acting oral anticoagulants are preferred over warfarin for eligible patients.

Other Comorbidities

Given the high prevalence of anemia in HF, all HF patients should be assessed after diagnosis.

If iron deficiency (ferritin <100 mg/L or 100-300 mg/L with transferrin saturation <20%) is found, IV repletion has a class 2a recommendation in HFrEF regardless of anemia, based on showing improved exercise capacity and quality of life. It's also recommended for iron deficiency in HFpEF, although haven't proven a benefit for HF. haven't been shown to help in HF -- likely due to poor absorption that's insufficient to restore iron stores in patients with HF.

Although anemia in HF has been linked to impaired erythropoietin production, the showed that the erythropoiesis-stimulating agent darbepoetin alpha (Aranesp) increased thrombotic events, including stroke, without a clinical outcome benefit.

Renal dysfunction -- also common in HF -- increases the risk of toxicity from HF therapies like furosemide and requires higher doses of loop diuretics. "Thus, careful evaluation of volume status is necessary when worsening kidney function occurs, as optimal management of the situation might involve intensification of diuretics rather than the opposite, a common error in the care of such patients," the JAMA review noted.

For patients with comorbid type 2 diabetes, as for all HF patients, SGLT2 inhibitors are recommended to improve outcomes. American Diabetes Association (ADA) guidelines recommend that this class be used first-line for hyperglycemia management for patients with diabetes whether they have HF or even are at high risk of it.

Treatment targets may differ among HF patients. The ADA calls for a glycosylated hemoglobin (HbA1c) goal of <7% to 7.5% for those with a lower comorbidity burden or less severe HF, whereas the <8% to 8.5% range is considered acceptable for older patients with higher comorbidity burden, polypharmacy, risk of hypoglycemia, or advanced HF.

Sleep-disordered breathing is also common in HF, but daytime sleepiness isn't always a good indicator of obstructive sleep apnea. Formal sleep assessment is recommended as reasonable to confirm clinically suspected diagnosis and differentiate between obstructive and central sleep apnea, which is necessary because continuous positive airway pressure treatment has a class 2a recommendation in obstructive sleep apnea whereas adaptive servo-ventilation harmed central sleep apnea patients in the .

Read previous installments of this series:

Part 1: Heart Failure: A Look at Low Ejection Fraction

Part 2: Exploring Heart Failure With Preserved Ejection Fraction

Part 3: Heart Failure With Reduced Ejection Fraction: Diagnosis and Evaluation

Part 4: Case Study: Lightheadedness, Fatigue in Man With Hypertension

Part 5: Heart Failure With Preserved Ejection Fraction: Diagnosis and Evaluation

Part 6: Heart Failure Medical Management