Transient left ventricular dysfunction syndrome (TLVDS), or Tako-Tsubo cardiomyopathy (TC), is a clinical entity in which patients present with features of acute coronary syndrome, electrocardiogram abnormalities, and transient left ventricular (apical or mid-ventricular) dysfunction. Patients usually recover from this condition four to six weeks after the event. The etiology or triggering factors of TC remains unknown. Various triggering factors have been associated with this syndrome, with one of the most recent being malignancies. In this case report we present a postmenopausal female with underlying advanced malignancy who presented with TC. This is consistent with a recent hypothesis that in addition to currently known triggering factors, malignancies might well trigger TC in the context of a stressor or paraneoplastic phenomenon.
Tako-Tsubo cardiomyopathy (TC) is a clinical entity first described in 1991 by Dote et al. [
There continues to be a constant evolution in our understanding of this unique condition as far as etiology, pathophysiology, and triggering factors are concerned. There are no large randomized or cohort studies available. Most of the information known comes from case reports and case series. Current incidence is unknown; however, some studies estimate 1% to 2% of all patients present with acute coronary syndrome, which puts the incidence at 7,000 to 14,000 cases per year. The condition is common in postmenopausal women, with a mean age of 58 to 75 years, and <3% under age 50 [
Triggering factors and their mechanisms continue to generate deep clinical interest. Recent retrospective studies [
A 66-year-old woman with hyperlipidemia and hypertension presented with acute onset of chest pressure. She denied any shortness of breath, diaphoresis, palpitations, presyncopal, or syncopal symptoms. She had no cardiac or diabetic history. She did not have regular medical care.
Clinically she was in mild distress with tachycardia at 120 bpm. Other vital signs were within normal limits. Physical examination was normal except for positive stool Guaiac test. Laboratory values were troponin I 6.5 ng/mL, creatinine kinase (isoenzyme—MB) 28.4 ng/mL, white blood cell count (WBC) 19600/uL with 0% bands, hemoglobin 10.9 g/dL, hematocrit 32.7%, normal platelets, alanine transaminase 36 U/L, aspartate transaminase 44 U/L, total alkaline phosphatase 234 U/L, sodium 133 mmol/L, and potassium 3.3 mmol/L.
Electrocardiogram (ECG) showed ST segment elevation in precordial leads V2-V3 (Figure
Significant ST segment elevation in precordial leads V1–V3 noted at the time of patient presentation.
Left ventricular apical akinesia and ballooning visualized during systole on echocardiography.
Anteroapical ballooning of left ventricle during systole as seen on left ventriculogram.
Because of her positive Guaiac test and mild anemia, she was advised to return in four weeks for a diagnostic colonoscopy. Colonoscopy revealed a colorectal mass with colonic obstruction. Histopathology was consistent with a poorly differentiated adenocarcinoma. Computed tomography (CT) of the abdomen and pelvis revealed stage IV adenocarcinoma for which an exploratory laparotomy with diverting sigmoid colostomy and mucous fistula was performed. This was followed by adjuvant chemotherapy with FOLFOX (folinic acid, fluorouracil, and oxaliplatin) regime. She is currently having a sixth cycle.
Repeat echocardiography at four weeks postcardiac event showed improved ejection fraction (60%) and resolution of the anteroapical akinesia. Final diagnosis was TC possibly triggered by underlying advanced malignancy.
The pathophysiology of TC remains largely unknown, but various hypotheses have been put forward including, but not limited to, autonomic dysfunction resulting in catecholamine-induced myocardial injury. In 70% of patients there is a triggering factor (psychosocial or physical) identified. Additional hypotheses include catecholamine-induced myocardial stunning, ischemia-mediated stunning due to coronary vasospasm, and myocarditis [
The most supported hypothesis is the catecholamine-induced myocardial stunning, as evidenced by the elevated levels of catecholamine prevalent in patients presenting with TC. Endomyocardial biopsies done in symptomatic patients have shown features of catecholamine toxicity [
Recently Burgdorf et al. [
What makes our case more interesting is the close relationship known to exist between adrenoceptor dysregulation and proliferation of adenocarcinoma cells, especially breast and colon [
Most patients present with symptoms of acute coronary syndrome, chest pain, shortness of breath, cardiac enzyme elevation (mild), ST segment elevation, T wave inversion, or QT prolongation. Rare presenting symptoms include syncope, cardiac arrest, cardiogenic shock, or congestive failure. Patients in the intensive care unit might have pulmonary edema. Unique to this entity is preceding emotional or physical stress, although this is absent in about 30% of cases.
Echocardiography reveals regional wall motion abnormalities. Definitive diagnosis is made on cardiac catheterization, which reveals two classical features: normal coronary arteries and aneurismal dilatation or ballooning of apical segment of the left ventricle (LV), appearing like a Japanese octopus trap on ventriculography. Other variants described are apical sparing or inverted tako-tsubo.
Various diagnostic criteria exist, none of which has been adopted universally. The common criteria used are the proposed Mayo Clinic criteria, initially proposed by Bybee et al. [
Management is supportive. Since by the time of diagnosis most patients are on treatment for acute coronary syndrome, this is usually continued. The benefit of beta-blockers is unknown although theoretically, since they have an anti-catecholamine effect, they are given, especially those with both alpha- and beta-receptor blockade, like carvedilol. Diuretics are recommended for heart failure. Precautions must be taken to avoid thrombolysis as it might cause harm. Short-term anticoagulation can be given to patients who present with atrial fibrillation or thrombus formation [
Complications include left ventricular free-wall rupture, ventricular arrhythmias, mitral regurgitation, left ventricular mural thrombus formation, dynamic intraventricular obstruction, and death [
This case hence raises two other interesting clinical issues. The first issue concerns which level of the troponin I elevation is clinically useful, and whether a degree of elevation matters. In this patient the troponin I elevation was not what we can refer to as modest, yet she did meet the modified Mayo Clinic diagnostic criteria. This challenges the clinical emphasis placed on “modest” troponin I elevation. The second issue is that the studies by Elesber [
The authors wish to thank Marie Fleisner and the Marshfield Clinic Research Foundation for their assistance and support in the preparation of this paper.