By Michael H. Crawford, MD, Editor

SYNOPSIS: An analysis of the International Takotsubo Registry showed that long-term mortality is similar to that observed in patients with acute coronary syndromes but varies widely depending on the triggering event. Emotional trigger patients receive the best prognosis, and acute neurological events receive the worst prognosis. Investigators recommended categorizing stress cardiomyopathies by the triggering event rather than wall motion distribution.

SOURCES: Ghadri JR, Kato K, Cammann VL, et al. Long-term prognosis of patients with Takotsubo syndrome. J Am Coll Cardiol 2018;72:874-882.

Sharkey SW, Maron BJ. Survival after Takotsubo, revisited. J Am Coll Cardiol 2018;72:883-884.

Although initially viewed as a relatively benign condition, it is becoming clear that stress cardiomyopathy (SCM) often resembles acute coronary syndromes (ACS) clinically. Investigators from the International Takotsubo Registry (InterTAK) sought to determine the relationship between the triggering event and outcome in SCM. The InterTAK database includes patients from 25 hospitals in nine countries in Europe and the United States who were recruited between 2011 and 2014. These patients were compared to an age- and sex-matched cohort of ACS patients in the Zurich ACS Registry. The SCM patients were categorized by their triggering event into four groups: emotional stress; physical activities, medical illness, or procedures; neurologic disorders; or no identifiable trigger. The primary endpoint was mortality. There were 455 patients in the SCM group and 455 in the ACS group, including 233 with ST-segment elevation myocardial infarction (MI), and 222 with non-ST-elevation MI. Long-term mortality was similar between SCM patients and ACS patients (P = 0.49).

To assess the effects of triggers on outcomes, 1,613 patients with SCM with clear differentiation of the triggers, including no trigger, were selected from the InterTAK database. There were 485 patients in the emotional trigger group, 532 with a physical trigger, 98 with a neurologic disorder, and 498 with no trigger. Patients with emotional triggers experienced better outcomes than ACS patients. Patients with physical or neurological triggers received a worse prognosis compared to ACS patients. Physical stress (hazard ratio [HR], 3.78; 95% confidence interval [CI], 2.21-6.44), neurologic disease (HR, 5.76; 95% CI, 2.96-11.2), and no trigger (HR, 2.14; 95% CI, 1.2-3.82) were potent predictors of five-year mortality compared to emotional trigger patients.The authors concluded that, overall, SCM patients demonstrated long-term outcomes similar to ACS patients, but certain triggering conditions support a benign vs. life-threatening course.

COMMENTARY

In the 1990s, reports appeared describing a unique basal left ventricular (LV) cardiomyopathy with apical sparing that was seen in some cases of intracerebral hemorrhage. This is the opposite of the more common apical wall motion abnormalities in coronary artery disease. Also, the LV areas involved did not conform to the usual coronary artery territories. In the early 2000s, reports appeared, mainly from Japan, of an apical ballooning cardiomyopathy with clinical features suggestive of acute MI but with normal coronary arteries. Because of the LV angiographic appearance that resembled an octopus-trapping jar, Japanese researchers called it Takotsubo syndrome. In many of these early reports, the syndrome seemed to be precipitated by emotional stress and was observed more often in women. In the last decade, a mid-LV wall version of Takotsubo was described by Mayo Clinic physicians. Now, it is clear that all these conditions are manifestations of some emotional or physical stress and are more properly called SCM, even though the particular stress is not always easily discernible.

Instead of using the wall motion abnormality pattern, Ghadri et al proposed classifying SCM based on the initiating stress. They identified three basic stress categories: I-emotional, II-physical (which is divided into two subcategories, IIa physical activity, medical illness, or postprocedural, and IIb, which is neurologic disease), and III-no identified stress. Their argument for this classification is their data showed different mortality outcomes for these three categories. Type II is divided because neurologic disease patients receive a worse prognosis than other physical stress SCM patients. Ghadri et al believe this categorization based on prognosis makes more clinical sense than one based on where the wall motion abnormalities are.

The data supporting this categorization from the InterTAK Registry are not surprising since physical trauma, such as surgery, and serious diseases, such as subarachnoid hemorrhage, affect prognosis regardless of the presence or absence of SCM. Clearly layering a cardiomyopathy on top of these conditions will only increase mortality. Interestingly, even when no trigger is found, the prognosis is worse than if there was a clear emotional trigger. Ghadri et al also confirmed what others have shown: Long-term mortality for SCM is equal to that of ACS (20% at five years for both), but varies by stressor. The five-year mortality for SCM in the registry was 30% for physical trauma, 15% for no triggering event, and 9% for emotional stress. Thus, there seems to be two drivers of mortality: the cardiomyopathy and the triggering illness. Cardiomyopathy usually improves or normalizes, especially in the emotional stress category. When it does not, mortality increases. Also, when SCM is so profound as to cause cardiogenic shock, mortality naturally increases.