Radiation-Associated Heart Disease: Management Pearls from a New Expert Review

JACC panel gives guidance on nuanced care of a very complex disease

Radiation-associated cardiac disease (RACD) — which typically arises years or decades after a cancer patient undergoes radiation therapy to the chest — should be systematically screened for and monitored, with management delivered by an experienced multidisciplinary team of cardiovascular specialists. So recommends a new review of RACD from an expert scientific panel convened by the Journal of the American College of Cardiology (JACC), which also calls for particularly careful consideration in the timing and planning of cardiovascular surgery or transcatheter intervention in patients with RACD.

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The review, which was published online by JACC on Aug. 12, is a consensus effort by an international group of seven experts based on their experience with RACD over the past 20 years. The article covers a description of at-risk groups, clinical manifestations, screening recommendations, and management and surgical considerations.

“Radiation-associated heart disease can have diverse presentations that overlap with other cardiac conditions, and it may arise so long after the radiation exposure that clinicians may not think of it,” says lead and corresponding author Milind Desai, MD, Director of Clinical Operations, Cardiovascular Medicine, at Cleveland Clinic, and one of three physicians from Cleveland Clinic’s Miller Family Heart & Vascular Institute on the expert panel. “But recognizing it is important, as management considerations are paramount to a patient’s quality of life and long-term survival.”

Who is at risk?

The review drew mostly on available data from patients who received radiation therapy for breast cancer or Hodgkin’s lymphoma, although patients who have received radiation for other cancers in the thorax are also at risk.

Identified factors conferring higher risk include:

  • Age younger than 50 at time of radiation therapy
  • Existing cardiovascular risk factors or disease
  • Lack of shielding or cobalt as the radiation source
  • High cumulative dose (>30 Gy) or high dose of radiation fractions (>2 Gy/day)
  • Tumor in or next to the heart
  • Anterior or left chest radiation
  • Concomitant chemotherapy, particularly with anthracyclines or trastuzumab

Manifestations of RACD

The wide range of cardiac complications associated with RACD — as well as pulmonary damage from radiation — make diagnosis particularly challenging, the panel notes. The main cardiac manifestations include the following:

  • Myocardial dysfunction, which is likely related to diffuse fibrosis and which may manifest as impaired functional capacity without heart failure or as heart failure with preserved ejection fraction
  • Valvular disease presenting as progressive valve thickening and calcification that results in valve stenosis and/or regurgitation, with left-sided valves more often affected
  • Pericardial disease, including pericarditis and sometimes chronic pericardial inflammation with resulting constriction that can be difficult to distinguish from restriction caused by underlying myocardial fibrosis
  • Vasculopathy typically marked by long, tubular, concentric and frequently noncalcific lesions; resulting porcelain aorta may preclude percutaneous intervention or surgery
  • Conduction system dysfunction related to fibrosis, with many patients requiring a pacemaker

Pulmonary fibrosis is another common consequence of radiation therapy, usually manifesting after many years.

“The possibility of radiation-associated pulmonary disease should be an important consideration when contemplating cardiac surgery for RACD,” says review co-author Douglas Johnston, MD, Vice Chairman of Cardiothoracic Surgery at Cleveland Clinic. “Pulmonary complications are a major source of perioperative morbidity and mortality.”

Screening of cancer survivors

The review recommends the following surveillance strategy for patients who have a history of chest radiation therapy:

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  • Annual history and physical examination with a focus on signs and symptoms of RACD
    > If signs and symptoms are present, testing as needed to evaluate
  • Screening echocardiography to assess structural abnormalities, ventricular performance and valvular disease
    > First time: Five years after exposure in high-risk patients, 10 years after exposure in others
    > Reassess every five years
  • Functional noninvasive stress testing to screen for coronary artery disease (CAD)
    > First time: Five to 10 years after exposure in high-risk patients
    > Reassess every five years

Specialized imaging plays a role to better evaluate RACD and for preoperative assessment and planning. It should be assumed that patients suffered radiation injury to the aorta, ventricles, pericardium, lungs and chest wall. Tests to consider include:

  • Multidetector cardiac CT for preoperative evaluation and planning, to provide full assessment of aortic, valvular and intravalvular calcium, and in some instances noninvasive coronary angiography
  • Nuclear scintigraphy to assess myocardial ischemia
  • Cardiac MRI to assess myocardial fibrosis and pericardial constriction and as an adjunct to echocardiography in some cases
  • Left and right heart catheterization with simultaneous pressure measurements to distinguish constrictive pericarditis from myocardial restriction
  • Extracardiac vascular ultrasonography of the carotid and subclavian arteries
  • Pulmonary function testing

“Significant radiation exposure is a critical risk factor that does not show up on standard preoperative risk stratification scores,” notes cardiologist Patrick Collier, MD, PhD, who is Co-Director of Cleveland Clinic’s Cardio-Oncology Center but was not involved in this expert review. “For truly informed consent, these patients require more detailed preoperative testing to better assess comorbidity, procedural risk and optimal treatment strategies.”

Team management, timing of surgery or transcatheter therapy

The review provides specific management guidance, starting with the recommendation that patients be managed by an experienced team of cardiologists, imaging specialists, interventionalists and cardiothoracic surgeons.

Medical therapy should follow standard guidelines, as no RACD-specific therapies have been identified and validated. However, most patients with significant symptoms eventually require invasive therapies.

The authors recommend that surgery generally be delayed to later in the disease course than would be the case in the absence of prior radiation therapy. Radiation injury to the lungs and pleura with resultant lymphatic dysfunction makes patients susceptible to intrathoracic fluid retention after surgery, significantly hampering recovery and diminishing long-term quality of life.

“Avoiding redo surgery should be a paramount consideration,” says Dr. Johnston. “All issues, such as replacing multiple valves, should be taken care of during the first operation if at all possible.”

Thorough and systematic preoperative planning is critical, as is flexibility in dealing with unexpected reconstruction problems, he adds. The authors specifically recommend an aggressive approach to double-valve replacement because of the tendency of RACD patients to have extensive calcification and a small aortic root and mitral annulus. Because radiation-damaged valve tissue tends to thicken and scar over time, replacement is preferred over repair, particularly for the mitral valve.

“Surgery for RACD often involves resection of extensive calcium and reconstruction of multiple areas of the heart, including the aorta and the annuli of the mitral and aortic valves,” says Dr. Johnston. “Our team’s experience with other complex multivalve surgery, in the setting of reoperation or endocarditis, has been essential to success in patients with RACD.”

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For RACD patients with CAD as the primary manifestation, percutaneous coronary intervention is usually preferred unless concomitant valvular disease can be addressed simultaneously with surgery.

Regarding transcatheter aortic valve replacement (TAVR), aortic valve disease more frequently involves extensive calcification of the valves and blood vessels, as well as severe conduction abnormalities, posing potential complications. With extensive planning, TAVR is still the preferred strategy for severe isolated aortic stenosis in this setting, particularly if transfemoral access can be safely employed.

“Careful evaluation of other valvular lesions needs to be undertaken, and if there is evidence of advanced multivalvular disease (with or without concomitant CAD), surgery might be the preferred option,” says Dr. Desai, who is also Professor of Medicine at Cleveland Clinic Lerner College of Medicine. “In terms of transcatheter mitral valve therapies, there needs to be further evolution before their routine clinical implementation.”

Postoperative considerations

The article identified a number of postoperative problems that tend to occur in this population:

  • Chronic pleural and pericardial effusions
  • Conduction system disturbances, often requiring longer temporary pacing
  • Prolonged postoperative diuresis, sometimes for weeks
  • Fibrosis-induced limitation of cardiac output, requiring avoidance of beta-blocker overuse and consideration of higher pacemaker rates

Minimizing future risk

The authors point out that improvements in radiotherapy protocols over the years means that patients currently undergoing radiation therapy are expected to be at less risk for RACD in the future.

“The oncology community has made considerable progress in minimizing unwanted exposures,” says Brian Griffin, MD, another review co-author and Cleveland Clinic’s Section Head of Cardiovascular Imaging. “But efforts in this arena are still a priority, as there remain significant practice variations in radiation delivery and many questions are yet unanswered.”