Addressing Comorbidities in Cardiomyopathy

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

Comorbidities are all too common in cardiomyopathy patients, especially for those with heart failure (HF). More than 85% of HF patients have two or more additional chronic conditions. While the overall burden of comorbidities has remained fairly stable over the past decade or two, one study showed an increase in the number of patients with three or more noncardiovascular comorbidities; and the more comorbidities, the higher the risk for hospitalization and death.

Based on Centers for Medicare & Medicaid Services claims data, hypertension tops the list of the most common co-occurring chronic conditions among people with HF, seen in 80.7% of those under age 65 and 84.2% of those 65 and older. Diabetes coexists with HF in some 59% of those under age 65 and 46% of seniors. Anemia is present in about half and hyperlipidemia in about 60% of both age groups. Chronic kidney disease is seen in 42-45%, while atrial fibrillation (AF) makes the top of the chart only for the older group, at about 28%.

Blood Pressure

Once cardiomyopathy impacts cardiac output, the relationship between blood pressure and outcomes shifts. In patients with HF, prognosis is actually better for hypertensive than normotensive individuals.

In the ATLAS trial, for instance, low systolic blood pressure at baseline was associated with chronic HF death. A propensity score-matched analysis also linked systolic blood pressure of 120 mmHg or less to cardiovascular and HF mortalities and all-cause, cardiovascular, and HF hospitalizations that was independent of other baseline characteristics.

"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," notes UpToDate. "This observation makes it difficult to study the benefits of antihypertensive therapy in this population."

Indeed, while the 2022 American College of Cardiology/American Heart Association guidelines give a class I recommendation for HF with reduced ejection fraction (HFrEF) that hypertension be treated with maximally tolerated doses of medication as directed by hypertension guidelines, the document acknowledges the lack of trial evidence for the impact of goal blood pressure reduction on outcomes. 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.

Management does differ somewhat in hypertrophic cardiomyopathy (HCM). Guidelines recommend caution when introducing therapies for coexisting conditions in HCM, such as hypertension, which is present in some 35-50% of adult HCM patients and even higher proportions of sarcomere variant-negative patients.

"Even in asymptomatic patients, knowing that they have provocable obstruction can influence ... choices of therapies for concomitant conditions (e.g., diuretics or vasodilators for patients with hypertension)," the guidelines note, although suggesting sticking with the same target blood pressure targets as in the general primary prevention guidelines.

While left ventricular pressure overload imposed by elevated systemic blood pressure could trigger or exacerbate left ventricular hypertrophy, diuretics and vasodilators can cause or worsen symptoms related to left ventricular outflow tract obstruction. So, "if symptoms are present, or emerge after the initiation of the medication, it may be necessary to up-titrate medications being used for obstructive HCM or consider alternative therapies for the comorbid condition," the guidelines suggest.

Beta-blockers or non-dihydropyridine calcium channel blockers are often used first-line in such symptomatic cases, and low-dose diuretics can also be useful.

Atrial Fibrillation

Cardiomyopathy and AF are commonly found together, with a complex interplay.

In one large research database, concomitant AF was found in 2.3% of patients with HCM, 7.0% with restrictive cardiomyopathy, and 5.9% with dilated cardiomyopathy. Mortality was modestly more likely for hypertrophic and dilated cardiomyopathy patients with both conditions, although the difference was not significant for restrictive cardiomyopathy. AF was associated with higher odds of hospitalization, incident heart failure, and incident stroke across all cardiomyopathy subtypes.

In HCM, conventional stroke risk scores don't work well at prediction. "In view of the substantial stroke risk, periodic AF surveillance would allow for early intervention with anticoagulants in high-risk patients," HCM guidelines note. "Asymptomatic AF detected by cardiac devices or monitors also increases risk of stroke, so the decision to anticoagulate should take into considerations the duration of episodes as well as underlying risk factors."

Those guidelines recommend anticoagulation for all patients with clinical AF and HCM regardless of CHA₂DS₂-VASc score, with direct-acting oral anticoagulants as the first-line option and vitamin K antagonists as second-line option.

A number of rhythm control drugs have been shown to be effective in this population and are preferred over a rate-control strategy. But when those fail or aren't tolerated, preference is given to non-dihydropyridine calcium channel blockers, beta-blockers, or a combination thereof.

And although catheter ablation doesn't have the same efficacy in HCM as in the general population and may need to be repeated more often or supplemented with antiarrhythmic medication, it's still an important option, according to the guidelines. While not often a solo procedure, a surgical maze procedure is an option if patients are getting surgical myectomy, the document added.

Indeed, in observational data, catheter ablation was associated with significantly lower risk of all‐cause mortality at 12 months across all cardiomyopathy subtypes.

Rhythm control is also preferred over rate control in restrictive cardiomyopathy when feasible.

For HF patients, randomized trials haven't shown rhythm control medications to be better than rate control and suggested that ablation may beat drugs for a rhythm control strategy. In the CASTLE-AF trial, ablation reduced the composite of all-cause mortality and hospitalization for worsening HF by a relative 38%, with a 47% reduction in death alone over about 38 months compared with antiarrhythmic drugs.

Because chronic HF is a hypercoagulable state and an independent risk factor for stroke, guidelines recommend anticoagulation for permanent-persistent-paroxysmal AF as reasonable regardless of other risk factors. The guidelines give a class I recommendation to anticoagulation when the CHA₂DS₂-VASc score is 2 or higher for men and 3 or greater for women, as typical for individuals with AF regardless of cardiomyopathy status. Direct-acting oral anticoagulants are preferred over warfarin for eligible patients.

For dilated cardiomyopathy patients in HF, a review suggested that beta-blockers be used only cautiously if at all in the setting of AF when cardiac output is low and there is severe restrictive physiology and probably not at all in amyloid light chain amyloidosis. Digoxin can also predispose to toxicity even at normal serum levels in this setting.

Anticoagulation is also indicated for cardiac amyloidosis patients with paroxysmal or chronic AF or a history of embolic stroke or transient ischemic attack, and probably for those with demonstrable intracardiac thrombus as well.

Other Comorbidities

Other coexisting conditions for which treatment may differ in the setting of cardiomyopathy include renal dysfunction, which increases the risk of toxicity from heart failure therapies and impairs response to diuretics. Data, though, are sparse about interactions on other aspects of treatment.

All HF patients should be assessed at baseline for anemia due to its high prevalence and independent association with HF disease severity. Guidelines recommend IV iron replacement as reasonable for HFrEF patients with iron deficiency, even in the absence of anemia. In the FAIR-HF trial, IV iron improved functional status and quality of life, whereas oral iron supplements have not shown such a benefit. However, erythropoietin-stimulating agents are not recommended for HF patients, due to an increased risk of stroke and other thrombotic events.

In accord with a number of trials that have shown SGLT2 inhibitors to improve HF measures regardless of diabetes status, guidelines recommend that type 2 diabetes patients get them both for HF outcomes in addition to hyperglycemia management.

Sleep-disordered breathing is also common in cardiomyopathy, affecting up to 70% of HCM patients, for instance.

Obstructive sleep apnea patients with HCM often have greater symptom burden and a greater prevalence of AF and other rhythm disturbances. But while diagnosis and treatment of this sleep-disordered breathing might reduce symptoms and arrhythmic complications, that has not been systematically tested, the HCM guideline notes.

In heart failure, daytime sleepiness isn't always a good indicator of obstructive sleep apnea. So, guidelines give a class 2a recommendation to formal sleep assessment to confirm clinically suspected diagnosis and differentiate between obstructive and central sleep apnea. That's important, because continuous positive airway pressure may be reasonable to improve sleep quality and decrease daytime sleepiness for obstructive sleep apnea, but adaptive servo-ventilation was actually shown to harm central sleep apnea patients with New York Heart Association class II to IV HFrEF in the SERVE-HF trial.

Read previous installments in this series:

Part 1: Cardiomyopathy: What are the Signs, What are the Symptoms?

Part 2: Diagnosing Cardiomyopathy: History, Examination, and Testing

Part 3: Cardiomyopathy: Epidemiology, Etiology, and Pathophysiology

Part 4: Case Study: Cardiomyopathy From Epinephrine in Anesthesia

Part 5: Cardiomyopathy: Cascade Screening for Families

Part 6: Cardiomyopathy: Outside the Office

Part 7: Deciding on Implantable Cardiac Devices for Cardiomyopathy

Part 8: Case Study: The Dangerous Habit That Led to Non-Ischemic Cardiomyopathy in a Healthy Man

Part 9: What to Know About Medical Therapy for Cardiomyopathy

Part 10: Inpatient Management of Cardiomyopathy

Up next: Managing Advanced Cardiomyopathy