Takotsubo cardiomyopathy can present with transient apical, midventricular, or basal left ventricular ballooning patterns. Reported recurrences of this cardiomyopathy are few. We present the cases of 2 elderly women who each had 3 episodes of takotsubo cardiomyopathy in various ballooning patterns. We explore the potential pathophysiologic mechanisms, and we discuss the best treatment approach for this disease, which carries a substantial risk of in-hospital complications.

Variants of takotsubo cardiomyopathy (TC), including its midventricular and basal forms, have been defined but are less prevalent than the classic apical ballooning shape. Single recurrences of TC are infrequent, and multiple recurrences are even rarer. We describe the cases of 2 patients who each had 3 episodes of TC, and we discuss the ballooning patterns.

Case Summaries

Patient 1

In March 2015, a 67-year-old white woman was admitted to the hospital because of severe dyspnea. She was being treated for chronic obstructive pulmonary disease exacerbation. Her electrocardiographic (ECG) results were abnormal, and her serum cardiac biomarker levels were elevated; however, cardiac catheterization revealed only mild-to-moderate nonobstructive coronary artery disease (CAD). A left ventriculogram showed akinesis of the mid walls but preserved contractility of the basal and apical wall segments, a pattern consistent with the midventricular variant of TC (Fig. 1). We supplemented her current β-blocker with an angiotensin receptor blocker. Four months later, an echocardiogram showed normal left ventricular (LV) contractility of all wall segments.

Fig. 1

Patient 1. On first presentation, left ventriculograms (right anterior oblique views) during A) diastole and B) systole show regional wall-motion abnormalities of a midventricular variant of takotsubo cardiomyopathy, consisting of akinetic mid wall segments and hyperkinetic basal and apical wall segments.

Supplemental motion image is available for Figure 1.

Fig. 1

Patient 1. On first presentation, left ventriculograms (right anterior oblique views) during A) diastole and B) systole show regional wall-motion abnormalities of a midventricular variant of takotsubo cardiomyopathy, consisting of akinetic mid wall segments and hyperkinetic basal and apical wall segments.

Supplemental motion image is available for Figure 1.

In March 2016, the patient presented with gastrointestinal symptoms and was diagnosed with gastritis. Although her serum cardiac biomarker levels were elevated again, cardiac catheterization revealed stable CAD. A left ventriculogram showed a recurrent midventricular TC pattern despite her angiotensin receptor and β-blocker therapy (Fig. 2A). These medications were continued, and the LV wall-motion abnormalities resolved one month later.

Fig. 2

Patient 1. On A) second and B) third presentation, left ventriculograms (right anterior oblique views) during systole show regional wall-motion abnormalities consistent with a midventricular variant of takotsubo cardiomyopathy.

Supplemental motion images are available for Figure 2A and 2B.

Fig. 2

Patient 1. On A) second and B) third presentation, left ventriculograms (right anterior oblique views) during systole show regional wall-motion abnormalities consistent with a midventricular variant of takotsubo cardiomyopathy.

Supplemental motion images are available for Figure 2A and 2B.

The patient's third episode of midventricular TC occurred in the presence of colitis 26 months after the initial event (Fig. 2B). Normal LV systolic function was noted one month later (Table I).

TABLE I.

Clinical Characteristics of Patient 1

Clinical Characteristics of Patient 1
Clinical Characteristics of Patient 1

Patient 2

In March 2016, a 75-year-old white woman, hospitalized for treatment of severe gastritis, reported chest discomfort and dyspnea. An ECG showed ischemic changes, and the patient's serum cardiac biomarker levels were elevated. Cardiac catheterization revealed only mild CAD; however, a left ventriculogram showed a large area of apical and mid wall akinesis and ballooning, consistent with classic TC (Fig. 3). The patient's borderline-low blood pressures precluded heart failure therapy. Two months later, an echocardiogram showed normal LV wall motion.

Fig. 3

Patient 2. On first presentation, left ventriculograms (right anterior oblique views) during A) diastole and B) systole show regional wall-motion abnormalities consistent with classic apical ballooning takotsubo cardiomyopathy.

Supplemental motion image is available for Figure 3.

Fig. 3

Patient 2. On first presentation, left ventriculograms (right anterior oblique views) during A) diastole and B) systole show regional wall-motion abnormalities consistent with classic apical ballooning takotsubo cardiomyopathy.

Supplemental motion image is available for Figure 3.

Five months later, the patient had respiratory failure during treatment for cholecystitis. Transthoracic echocardiograms revealed depressed LV systolic function with a different wall-motion abnormality: mid and basal wall akinesis with preserved apical wall contractility, consistent with the basal variant of TC (Fig. 4A). No cardiac catheterization was performed, and again the patient's low blood pressures precluded heart failure therapy. Normal LV wall motion was noted one month later.

Fig. 4

Patient 2. A) On second presentation, a transthoracic echocardiogram during systole shows a basal variant of takotsubo cardiomyopathy. Apical wall contractility is preserved, whereas the mid and basal left ventricular wall segments are akinetic. B) On third presentation, a transthoracic echocardiogram during systole shows a second episode of the basal variant of takotsubo cardiomyopathy.

Supplemental motion images are available for Figure 4A and 4B.

Fig. 4

Patient 2. A) On second presentation, a transthoracic echocardiogram during systole shows a basal variant of takotsubo cardiomyopathy. Apical wall contractility is preserved, whereas the mid and basal left ventricular wall segments are akinetic. B) On third presentation, a transthoracic echocardiogram during systole shows a second episode of the basal variant of takotsubo cardiomyopathy.

Supplemental motion images are available for Figure 4A and 4B.

The patient had a third episode of cardiomyopathy with a repeat basal variant of TC, 12 months after her first event, in the presence of gastritis (Fig. 4B). We observed normal LV wall motion 3 months later (Table II).

TABLE II.

Clinical Characteristics of Patient 2

Clinical Characteristics of Patient 2
Clinical Characteristics of Patient 2

Discussion

A syndrome of transient LV systolic dysfunction in the absence of obstructive CAD, TC is diagnosed in 1.7% to 3.5% of patients who present with suspected acute coronary syndrome.1,2  The classic apical ballooning shape predominates; however, the midventricular and basal variants occur in 16.8% to 40% of patients.3–5  Although investigators in observational studies have compared the respective clinical profiles of classic and variant TC, information about recurrent TC is sparse because only a few events have been reported. In one observational study of patients with only apical ballooning, the annual recurrence rate after initial presentation was 2.9% in the first 4 years and 1.3% thereafter.6  In a mixed population of TC patients who had classic and variant forms, the annual recurrence rate was also low (1%–1.5%).7,8  These series described primarily single recurrences of TC, and only a handful of reports have been about patients whose recurrent TC had variant ballooning patterns.9,10 

Our patients each had 3 episodes of TC within a relatively short period of 1 to 2 years. Each episode was triggered by stress, and all 6 resultant cardiomyopathies were uncovered during the management of noncardiac illness. Patient 1 had only midventricular TC, whereas Patient 2 initially had classic apical ballooning and then the basal variant. We detected no pathologic findings associated with transient LV ballooning patterns, such as pheochromocytoma, Doppler echocardiographic evidence of mid-LV or LV outflow tract obstruction, or left anterior descending coronary artery wraparound or myocardial bridging.11,12  Consistent with previous reports in which individuals with recurrent versus isolated TC were compared, we found no obvious demographic or clinical features that distinguished our patients from those in whom TC occurred once. Both were post-menopausal women who had elevated serum biomarker levels and variable ST-segment ECG changes with or without QTc prolongation.4,7,13 

The recognition of recurrent TC, especially with transient ballooning of different LV wall segments in the same individual, challenges some current theories on TC pathophysiology. The impact of a catecholamine surge on LV myocardial wall segments with varying β-receptor densities is frequently used to explain focal ballooning; however, this theory is not supported by the different recurrent ballooning patterns in Patient 2. In addition, the idea that one episode of stress-induced cardiomyopathy is protective in terms of precluding same-wall-segment recurrence14  is not supported by our findings in Patient 1, in whom the recurrent LV ballooning shapes were identical. Nevertheless, sympathetic overflow is accepted as the prerequisite to pathophysiology. The roles of hormonal influences and innate susceptibility remain elusive.

Even though no prognostic differences are apparent among the variants,15  TC is not benign and carries substantial risk. Despite the transience of cardiomyopathy, our patients were both at risk of in-hospital complications and long-term major adverse cardiac and cerebrovascular events, like those in patients whose acute coronary syndrome is due to obstructive CAD.3  Therefore, preventing recurrent TC is crucial; however, the approach to the problem is unknown. Of note, ongoing heart failure therapy did not prevent recurrences in our first patient, a finding corroborated by data that support the neutrality of β-blockade in preventing recurrence.3,4  Nevertheless, it appears clear that long-term survival prospects are improved in TC patients who are given a renin-angiotensin system inhibitor, so this class of medications should always be incorporated into the acute treatment algorithm depending on the patient's tolerance.3 

Our report adds to the sparse body of literature on recurrent TC and the spectrum of transient focal ballooning. Multiple recurrence in the same individual is rarely reported and is most likely a result of underrecognition. Clinicians must familiarize themselves with TC in its variant forms and respond appropriately to patients who present with the characteristic profiles. More frequent identification of this complex syndrome will enable scrutiny of its natural course and reveal insights into more effective prevention.

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Author notes

From: Department of Cardiovascular Sciences (Drs. Korabathina, Labovitz, Mishkin, and Turner), University of South Florida Morsani College of Medicine, Tampa, Florida 33612; and Departments of Family Medicine (Dr. Porcadas) and Cardiovascular Medicine (Dr. Korabathina), Bayfront Health Medical Center, St. Petersburg, Florida 33701