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MUNICH -- A history of cancer in patients with takotsubo cardiomyopathy, or "broken-heart syndrome," almost doubled their risk of major clinical adverse cardiac events, a meta-analysis showed.

The relative risk of clinical events in patients with this stress-associated syndrome and either current or past cancer increased to 1.82 when compared to takotsubo patients with no history of cancer. Most of the increased risk came in the form of post-hospital discharge events, as the rate of in-hospital events did not differ significantly between the two groups, Francesco Santoro, MD, of the University of Foggia in Italy, reported here at the European Society of Cardiology annual congress.

"We found that takotsubo cardiomyopathy patients who had ever had cancer were at greater risk of adverse events, particularly after discharge from hospital," said Santoro. "More research is needed to clarify the reasons for this. These patients may benefit from standard therapy for heart failure, especially an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, and a beta-blocker."

A careful follow-up is recommended for all patients with takotsubo, but particularly those who have a history of cancer. The follow-up should include backscatter analysis at 3 and 6 months and again at 1 year, said Santoro.

Takotsubo syndrome is a type of acute heart failure that may mimic acute myocardial infarction (MI), including reversible left ventricular dysfunction. Associated with a variety of emotional and physical stressors, the syndrome most often occurs in menopausal women. Treatment with certain cancer drugs has been associated with the syndrome, particularly 5-fluorouracil, but also rituximab (Rituxan), vascular endothelial growth factor antagonists, and vascular disrupting agents, said Santoro.

"Many people believe takotsubo is caused mainly by emotional stress, but that's not true," he said. "Between 30% and 35% of patients with takotsubo have emotional stressors. Another 40% or so have an identifiable physical stressor. The remaining 30% or so have no clear cause."

In some instances takotsubo syndrome occurs in patients who have cancer or a history of cancer. A of 24,000 patients hospitalized for takotsubo syndrome, MI, or orthopedic procedures, showed a significantly higher prevalence of cancer in the takotsubo group (14.4%) as compared with either of the other two groups (9%-10%, P<0.0001).

To examine the association between cancer and takotsubo syndrome, Santoro and colleagues performed a systematic literature review and meta-analysis. They identified three published studies involving a total of 554 patients with takotsubo syndrome, 113 (20%) of whom had a current malignancy or history of cancer. The most common types of cancer associated with the stress-related cardiomyopathy were gastrointestinal (23%), lung and breast (17% each), and skin and hematologic (10% each).

Outcomes of interest were separated into in-hospital events (life-threatening arrhythmias, cardiogenic shock, and thromboembolism) and post-discharge events (all-cause mortality and rehospitalization for cardiovascular disease).

The 554 patients had a total of 708 clinical events, 268 in hospital and 440 after discharge. The 113 patients with a history of cancer accounted for 169 events versus 539 for the 441 patients with no cancer history. Comparison of the incidence of clinical events in the two groups showed a statistically significant increase in the cancer group, reflected in a risk ratio (RR) of 1.82 (95% CI 1.37-2.41, P<0.001).

In an analysis of clinical events by timing, the post-discharge incidence remained significantly increased in the patients with a history of cancer (RR 2.08, 95% CI 1.50-2.87, P<0.01). The incidence of in-hospital events was numerically higher in the cancer group, but not significantly increased (RR 1.30, 95% CI 0.74-2.29, P=0.36).

Analyses of the individual types of clinical events yielded no significant differences between patients with or without cancer.

In response to a question from program moderator Mai Tone Lønnebakken, MD, PhD, of the University of Bergen in Norway, Santoro said no specific characteristics have been identified to distinguish patients with a history of cancer from the other patients with takotsubo syndrome.

"They are similar to the general population of patients with takotsubo syndrome," said Santoro. "I don't have any tricks. If a patient doesn't have a clear stressor, then maybe you should look for cancer."

Coronary angiography remains the principal diagnostic test. He called MRI the "gold standard" test, but said the imaging is sometimes difficult to perform in acute situations. Slightly elevated troponin and elevated brain natriuretic peptide have been associated with some cases of takotsubo syndrome.

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