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Exercise Stress Testing Can Predict Outcome in Patients with Early Hypertrophic Cardiomyopathy

Heart & Vascular Institute Physician eNewsletter - Winter 2014
Exercise Stress Test

Patients with hypertrophic cardiomyopathy (HCM) experience left ventricular outflow tract (LVOT) obstruction, mitral regurgitation and diastolic dysfunction. These patients present with symptoms that may include dyspnea, angina or syncope. In asymptomatic or minimally asymptomatic patients, self-assessment of symptoms may not correlate with extent of damage.

Researchers at Cleveland Clinic found that exercise stress testing in active, younger patients with HCM with no self-reported symptoms often revealed the presence of impaired functional capacity. Moreover, they found that reduced exercise capacity—and not rest or exercise LVOT tract gradients—predicted long-term outcomes.

“Patients’ perceptions of their symptoms can be misleading. The degree of symptomatology does not necessary correlate with the extent of functional impairment, when measured objectively,” says Milind Desai, MD, of the Department of Cardiovascular Medicine, lead author of the study published in the Journal of the American College of Cardiology: Cardiovascular Imaging on November 20, 2013.

Testing for exercise tolerance

Exercise echocardiography is often used to evaluate HCM patients and is safe when performed at an experienced center. Dr. Desai and colleagues sought to determine the prognostic value of treadmill echocardiography on asymptomatic and minimally symptomatic HCM patients referred for clinical assessment and risk stratification.

The researchers selected 426 patients enrolled in Cleveland Clinic’s HCM Registry from January 1997 through December 2007. Patients needing invasive treatment for HCM were excluded from the study.

All participants underwent resting echocardiography, followed by a symptom-limited exercise treadmill test. Blood pressure, heart rate and electrocardiographic measurements were taken, along with resting and peak exercise rate pressure product, maximal predicted heart rate, percent-predicted maximal heart rate, drop in heart rate from peak to one minute post-exercise and metabolic equivalents (METS) achieved, as well as what would be expected based on age and gender.

The primary endpoint was a composite of death, appropriate ICD discharges, resuscitated sudden death and admission for heart failure. Deaths were recorded as sudden death, death from progressive heart failure or other.

During a mean followup of 8.7±3 years, 52 patients (12 percent) met the composite endpoint. There were 27 deaths (6 percent), 13 appropriate ICD discharges (3 percent) and 19 patients (4 percent) who developed heart failure requiring hospitalization, during follow-up. Deaths were sudden (17), due to heart failure (7) or ICD infection (1) or were of uncertain etiology (2). There were no sudden death resuscitations during follow-up. Eight patients (2 percent) suffered an embolic stroke. Among those who suffered events, resting and maximal LVOT gradients were not sufficiently elevated to recommend surgery.

What didn’t matter…and what did

The researchers divided the patients into three phenotypic subgroups: asymmetric septal hypertrophy with maximal LVOT obstruction ≥30 mm Hg, nonobstructive asymmetric septal hypertrophy (<30 mm Hg) and apical hypertrophy variant. Event rates were similar among these subgroups.

Percentage of age and gender-predicted METs achieved, heart-rate recovery (HRR) at one minute and atrial fibrillation (AF) were independent predictors of the composite outcomes.

The number of patients meeting the composite endpoint was significantly higher among those who achieved <7 METS, as compared to those who achieved ≥7 METS. Because exercise capacity is highly dependent upon age and gender, the researchers further divided patients into subgroups based on ratio of achieved METs to age-gender predicted METs as follows: >100 percent, 85-100 percent and < 85 percent. As expected, patients achieving <85 percent predicted METs had a higher body surface area, higher beta blocker use, greater maximal LV thickness and left atrial area. They were also significantly younger and less likely to be hypertensive. However, 55 percent reported no symptoms (NYHA Class I).

Among patients who achieved more than 100 percent of their age- and gender-predicted exercise METS, the event rate was very low, with a 1 percent event rate during follow-up. This contrasted with the group achieving < 85 percent, who had a 12 percent event rate.

The number of patients meeting the composite endpoint was significantly higher in the group with abnormal HRR (32 percent, as compared with 8 percent among those with normal HRR). The event rate was also significantly higher in patients with AF, as compared to those without (29 percent vs 10 percent).


Currently, interventional treatment for HCM is offered only to symptomatic patients. Myectomy, plus or minus mitral valve surgery or alcohol septal ablation, can be highly successful in relieving LVOT obstruction, often preventing or delaying the onset of heart failure. As a result, treatment may result in normal long-term survival.

The Cleveland Clinic study suggests that basing treatment decisions on symptoms alone may be insufficient.

“In asymptomatic or minimally asymptomatic patients with HCM, exercise stress testing may be useful in eliciting symptoms and identifying patients who may benefit from aggressive therapy,” says Dr. Desai.

Reviewed: 01/14

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