Unique phenotypes of Typical and Inverted Takotsubo Cardiomyopathy in Young Females
Shantanu Sengupta Vikram Alsi Vipul Mohan Bimalpreet Kaur J.C. Mohan
Sengupta Hospital and Medical Research Centre , Nagpur and Ridge Heart Centre , New Delhi
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Classic Takotsubo cardiomyopathy (TC) is a disorder characterized by transient dysfunction of the apical portion of the left ventricle (LV), with compensatory hyperkinesis of the basal walls, producing ballooning of the apex with systole in the absence of coronary artery disease. TC was first described by Satoh et al in 1990 (1) in Japan. The name of the disorder is taken from the Japanese name for an octopus trap (tako-tsubo) that has a similar configuration as to the affected left ventricle . More than 80% of the patients are post-menopausal females. TC is a clinical syndrome of reversible stress-induced regional or global left ventricular systolic dysfunction characterized by typical chest pain, acute dyspnoea or cardiovascular collapse following emotional and physical stress, with variable electrocardiographic changes, mild increase in cardiac enzymes, and without any abnormality in coronary arteries.
Over 90% reported cases of TC are in females > 50 years of age. Since 2005 , several reports have described either typical or inverted TC in young females with variable presentations(2-9). The triggers mentioned were acute hypoglycemia, amphetamine misuse, pregnancy, emotional stress , flare-up of multiple sclerosis, use of epinephrine for management of anaphylaxis, non-cardiac surgery, severe pain, cocaine use, opioid withdrawal or car accidents(8,9). We present 3 cases of a transient cardiomyopathy, noted in young women with associated emotional , physical or pharmacologic triggering events, that are distinct in that they all manifested initially with acute pulmonary oedema with systolic akinesis involving different LV segments with rapidrecovery. One patient had typical apical ballooning ( takotsubo syndrome), the other had apical-sparing ( inverted Takotsubo or squid syndrome ) and the third had akinesis involving apical and mid-segments up to insertion of papillary muscles. This kind of broken heart syndrome in young females is a unique entity and broadens the horizon of potentially life threatening reversible left ventricular systolic dysfunction in absence of coronary artery disease.
Case 1
A 31 years old female was admitted in intensive care unit with acute onset breathlessness. She had a fight with her husband 2 hours prior to her complaints. She had no family history of heart disease. Blood pressure (BP) and heart rate (HR) on admission were 90/65 mm Hg and 110 bpm respectively. She was tachypnoeic with oxygen saturation of 80% at room air. Electrocardiography (ECG) showed T wave inversion in lead V1 to V5. She was in acute pulmonary edema. A Transthoracic Echocardiogram demonstrated moderate left ventricular (LV) systolic dysfunction with ejection fraction of 30%. There was marked apical ballooning with basal hyperkinesis. Results of laboratory analysis showed a peak serum Troponin T level of 1.2 ng/ml (normal range 0.06–0.1). She needed ventilatory support and intraaortic balloon pump insertion because systolic blood pressure was in the range of 50-70 mmHg with marked arterial desaturation. She recovered next day on this management, but had a recurrence with worsening akinesis 48 hours later. She recoveredCorrespondence: Dr. KK Talwar, Department of Cardiology, Post-Graduate Institute of Medical Education & Research, Chandigarh, India
Email: kktalwar_chd@dataone.in
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completely in a weeks time. Her coronary angiography done revealed normal epicardial coronaries. Repeat echocardiography revealed resolution of wall motion abnormalities with ejection fraction of 60%. There has been no recurrence to date.
Case 2
A 21 years old a nurse , felt lower abdomen pain and dizziness while recording BP of a patient. Doctor on duty noticed some evanescent facial rash. She was given subcutaneous injection of epinephrine for possible anaphylaxis. Immediately she developed acute chest pain and breathlessness. She was immediately shifted to intensive care unit. She had no significant past history. Her HR and BP120 bpm and 80/60 mm Hg . She was tachypnoeic with oxygen saturation of 80% at room air. Electrocardiography (ECG) showed T wave inversion in lead V1 to V5. She was in acute pulmonary edema. A Transthoracic Echocardiogram demonstrated moderate left ventricular (LV) systolic dysfunction with ejection fraction of 35%. There was apical hyperkinesis with severe akinesis of basal and mid left ventricular segments. Results of laboratory analysis showed a peak serum Troponin T level of 0.6 ng/ml (normal range 0.06–0.1). She needed ventilatory support and intraaortic balloon pump insertion because systolic blood pressure was in the range of 50-70 mmHg with marked arterial desaturation. She experienced 4 episodes of polymorphic ventricular tachycardia on first day of presentation. She recovered completely on the 4th day and her repeat echocardiography revealed normal LV systolic function with ejection fraction of 60%. Her coronary angiography revealed normal epicardial arteries. There has been no recurrence till date.
Case 3
A 31 years old multigravida was admitted with labour pains at 37 weeks intra-uterine gestation. Her prior obstetrical history included one uncomplicated caesarian section and one abortion. She had no family history of heart disease. She underwent an elective caesarian section under spinal anesthesia. Successful spinal anesthesia was achieved with hyperbaric bupivacaine (12 mg) and fentanyl (10 g) Initial blood pressure and heart rate obtained in the preoperative area were 107/65 mm Hg and 71 bpm respectively and were almost unchanged. Intraoperative period was uneventful with the birth of a healthy male baby. Immediately post-operative 1 hour she complained of chest discomfort and developed breathlessness. She was immediately shifted to Cardiac Care Unit (CCU). Her heart rate was 110 bpm, with blood pressure of 100/70, was tachypnoeic with oxygen saturation of 85% at room air. Electrocardiography (ECG) showed T wave inversion in lead V1 and V2 (Figure 1). She was started on oxygen therapy was mask, injectable Frusemide and injectable Enalapril. A Transthoracic Echocardiogram done in CCU demonstrated moderate left ventricular (LV) systolic dysfunction with hypokinesia of the mid-ventricular and apical segments. The basal segments showed preserved systolic function. There was evidence of mild mitral regurgitation. Results of laboratory analysis showed a peak serum Troponin T level of 0.40 ng/ml (normal range 0.06–0.1) and pro-BNP levels of 1325 pg/ml (normal range 124-226 pg/ml). She responded well to above therapy and a repeat transthoracic echocardiogram was performed 24 hours later, which revealed complete normalization of LV systolic function. She was discharged on the 5 post-operative day. She is on regular follow up since last 4 months and is asymptomatic.]
Discussion
Recognition and diagnosis of stress-related or catecholamine-induced reversible cardiomyopathy is on the rise. We present 3 unique cases of a transient cardiomyopathy in which akinesis was isolated to the apical segments ( classic Takotsubo syndrome) , apical and mid ventricular segments or basal left ventricular (LV) segments ( inverted takotsubo or squid syndrome ), with
Figure 1 : Patient 1: Apical ballooning in end-systolic frame in A4CV and ALAX views ( arrows)
Figure 2: Patient 1: A4CV and A2CV after recovery. Note absence of apical ballooning and decrease in end-systolic size.
Figure 3 : Patient 2: Modified parasternal long axis view in systole showing basal ballooning in upper panel with evidence of recovery in lower panel ( arrows)
Figure 4: Patient 2: Apical 4CV in systole. Upper panel shows apical sparing but basal segment dilatation . Lower panel ( after recovery) shows normal shape and size
Figure 5: Patient 3: Apical 4CV in systole. Upper panel shows apical and mid segmental ballooning with sparing of basal segment . Lower panel ( after recovery) shows normal shape and size of LV.
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hypercontractile function in the unaffected segments. The criteria of the syndrome described in earlier reports (1) are reversible wall motion abnormalities at the left ventricular apex extending beyond one coronary artery distribution, (2) the absence of obstructive epicardial coronary artery and (3) electro-cardiographic abnormalities resembling acute myocardial injury. Later studies added absence of significant head trauma, intracranial hemorrhage, pheochromocytoma, or other causes of myocardial dysfunction amongst criteria. However young pre-menopausal females who show rapid recovery of the left ventricular systolic dysfunction may not need the obligatory demonstration of normal coronary angiogram because of very low probability of obstructive CAD in these subjects. Major triggering factors for the syndrome are psychological stress, such as death of a family member or relative, unusual exercise, worsening of underlying disease and operation, in which conditions sympathetic nerve activity is activated . However use or misuse of sympathomimetic drugs as an initiator is being recognized more frequently (5-6, 8-9).
The cardiomyopathy can be classified into a left ventricular (LV) apical ballooning variant (classic Takotsubo cardiomyopathy—most common), an
inverted or reverse Takotsubo variant (basal akinesis with hyper dynamic apex), or a midventricular Takotsubo variant . A wide heterogeneity among left ventriculographic systolic silhouettes has lead some investigators to raise the question of whether the presence of apical ballooning is the end manifestation of different pathophysiologic processes or whether different entities have been grouped under the term “Tako-Tsubo” cardiomyopathy (10). In fact , Khush et al (11) differentiated patients with subarachnoid hemorrhage and LV dysfunction into “apical-sparing” and “apical-affected” groups, noting that the apical-sparing groups had higher ejection fractions. The reason of selective involvement of apical and/or midportion of the left ventricle with relative sparing of basal segments is unknown and might be partly explained by the evidence that apical myocardium has increased responsiveness to sympathetic stimulation (12). Differential distribution of adrenergic receptors in the left ventricular musculature could account for various phenotypes of Takotsubo syndrome. Clinical differences between various types of stress cardiomyopathy have been recently reported. According to Hahn et al (13), apex- sparing variety is characterized by younger age of onset, less female preponderance, less cardiogenic shock or pulmonary oedema and less ECG changes. This may be related to variable regional adrenergic function in the human left ventricle (14) rather than increased expression of secreted catecholamines which have been found to be within normal range despite markedly increased pro-NT-BNP and hs- CRP levels in stress cardiomyopathy (15).
Recent series have described clinical presentation in detail (13,16,17). Presenting features of TC are chest pain ( about 70%), acute dyspnoea (60%) or cardiogenic shock (24%). IABP used has been described in 10-20% cases. Most patients recover to be discharged within one week. In-hospital mortality is 4-6% and recurrence rate is <10%. Differential diagnosis include acute coronary syndrome, pheochromocytoma , acute hypocalcemia and acute myocarditis. Supportive treatment is the only therapy required. There are no guidelines for prophylactic or long-term treatment.
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