“It is said an Eastern monarch once charged his wise men to invent him a sentence to be ever in view, and which should be true and appropriate in all times and situations. They presented him the words, “And this too, shall pass away.” How much it expresses! How chastening in the hour of pride! How consoling in the depths of affliction!” – Abraham Lincoln, September 30, 1859
Though these may be words of consolation, the happiest and the saddest man in the world have through their extreme emotional states, inadvertently put themselves at risk of Takotsubo’s Cardiomyopathy. Takotsubo’s is characterised by a temporary reversible abnormality of the left ventricle of the heart in the absence of coronary heart disease. The most frequent abnormality of the left ventricle is a ballooned apex, with the condition named after the rounded pot used to catch octopus in Japan. The condition is commonly referred to as Broken Heart Syndrome, however evidence from the International Takotsubo Registry which recorded 1750 cases of Takotsubo’s from 2011-2014 suggest a small subgroup of patient also experience Takotsubo’s following a preceding pleasant emotional event (The ‘Happy Heart’ subgroup) [1]. If the happiest and saddest man can survive the complications of the condition, their Takotsubo’s too, shall pass.
The clinical presentation of Takotsubo’s cardiomyopathy commonly mimics the Acute Coronary Syndromes (ACS): sudden onset chest pain, ECG abnormalities including ST segment elevation in the anterior leads (56%), T wave inversion (39%), pathological Q waves, QT prolongation, new bundle branch block and elevated cardiac enzymes (Troponin, pro-NT-BNP) [2-4]. Takotsubo’s is estimated to represent up to 2% of all patients presenting with clinical manifestation of ACS [3]. Given the clinical and biochemical presentation, it is essentially impossible to distinguish from ACS until coronary artery disease is excluded by angiography, although the combination of ST depression in AvR and absence of ST elevation in V1 is thought to reveal Takotsubo’s with 91% sensitivity [5]. The aetiology of the condition isn’t fully understood, but is likely to be related to a combination of catecholamine excess and oestrogen deficiency, with the majority of cases occurring in post-menopausal women with underlying cardiovascular risk factors [6]. Serum catecholamine levels in Takotsubo patients during the acute phase have been found to be elevated 2-3 times that of control populations [7]. The most important diagnostic intervention is Coronary Angiography to exclude coronary artery stenosis alongside echocardiogram to identify LV hypo-kinesia, typically at the apex. The complete diagnostic criteria, though not fully accepted is the following [8]:
- Newly diagnosed ECG abnormalities
- Transient apical dyskinesia or akinesia, detected by Ecocardiography colordoppler, beyond a single coronary artery distribution
- Nonobstructive coronary artery disease (stenosis < 50%) at angiography
- Absence of: myocarditis, pheochromocytome, head trauma and intracranial haemorrhage, hypertrophic cardiomiopathy.
For patient’s not suitable for coronary angiography, LV ventriculography (LV gram) or Cardiovascular Magnetic Resonance (CMR) scan can aid diagnosis. Complete recovery of ventricular function after a few days to weeks is typical. The acute phase of Takotsubo’s carries better prognosis to an anterior STEMI with lower comparative incidence across cohort studies of the following complications: cardiac rupture (3% vs 1%), cardiogenic shock (5.3%, vs. 14.85%), pulmonary oedema (6.3% vs 14.85%) and cardiac arrest (5.3% vs 19.8%) [9]. In hospital mortality rates for Takotsubo cases are 3.16% compared to 9.9% for anterior STEMI [9].
Treatment is primarily empirical with supportive management, with beta blockade as the mainstay of treatment as recommended by European Society of Cardiology (ESC) Guidelines [10]. Some patients will also require anticoagulation. Calcium channel blockers, endothelin antagonists and adenosine are likely to become established therapies for Takotsubo’s in the future.
Of the 1750 patients recorded on the International Takotsubo’s Registry, 89.8% were women. 36% of cases resulted from somatic/physical triggers e.g vigorous exercise, subarachnoid haemorrhage, seizure, post-operative pain, alcohol and opiate withdrawal, invasive medical procedures, sexual intercourse. 28.5% of patients had no identifiable trigger. 27.7% of patients had a clear emotional trigger (n=485), of these patients a small subset of 20 (4.1%) were identified with ‘happy heart syndrome’. Presentation, clinical course and outcomes were similar between happy and broken heart patients. It is theorised that the joyful and socially desirable events and the more classical negative emotional events have a shared final common pathway in the brain-heart axis [1]. The following table which classifies all emotional trigger events from the International Takotsubo’s Registry has been livened up by a few of my cartoons of questionable artistic standing.
Broken heart events (emotional, n = 465) [1]
| 1. Grief/loss (n = 107) | |
| Death of spouse | 6.5% (30/465) |
| Attending a funeral | 3.4% (16/465) |
| Death in the family (no more details) | 3.2% (15/465) |
| Death of mother/father | 2.8% (13/465) |
| Death of a child | 1.9% (9/465) |
| Death of brother/sister | 1.7% (8/465) |
| Death of a friend | 1.5% (7/465) |
| Close person moving | 1.1% (5/465) |
| Loss of home | 0.4% (2/465) |
| Grief/loss (no details) | 0.4% (2/465) |
| 2. Panic/fear/anxiety (n = 107) | |
| Illness of a close person | 6.5% (30/465) |
| Accident (car/ship/plane) | 2.4% (11/465) |
| Fall | 2.2% (10/465) |
| Fire/flooding (house damaged) | 1.5% (7/465) |
| Robbery/burglary | 1.3% (6/465) |
| Anxiety (no details) | 1.3% (6/465) |
| Feared of own hospitalization | 1.1% (5/465) |
| Fear of surgery/medical intervention | 1.1% (5/465) |
| Worried about own illness | 0.9% (4/465) |
| Panic attack | 0.9% (4/465) |
| Being threatened by someone | 0.9% (4/465) |
| Court date | 0.6% (3/465) |
| Caught by the police | 0.4% (2/465) |
| Animal/pet hurt | 0.4% (2/465) |
| Nightmare | 0.2% (1/465) |
Stuck in bathtub  | 0.2% (1/465) |
| Loneliness | 0.2% (1/465) |
Frightened of difficult ski slope  | 0.2% (1/465) |
| Frightened of a dog | 0.2% (1/465) |
Airplane crash in flight simulator  | 0.2% (1/465) |
Investing in stock market  | 0.2% (1/465) |
| Locked herself out | 0.2% (1/465) |
| 3. Interpersonal conflict (n = 78) | |
| Family problems | 6.2% (29/465) |
| Problems with children | 3.2% (15/465) |
| Depression | 2.4% (11/465) |
| Relationship problems/divorce | 0.6% (3/465) |
| Burdening/stressful phone call | 0.6% (3/465) |
| Suicide attempt | 0.6% (3/465) |
| Taking care of a person | 0.6% (3/465) |
| Drug abuse | 0.4% (2/465) |
| Father disinherited the patient | 0.2% (1/465) |
| Problems with tenants | 0.2% (1/465) |
| Problems with physician | 0.2% (1/465) |
| Abused by a relative | 0.2% (1/465) |
| Spoke about difficult childhood for the first time | 0.2% (1/465) |
| Psychotic neighbour | 0.2% (1/465) |
Supposed to meet ex-partner on vacation  | 0.2% (1/465) |
| Discussion with priest at a church meeting | 0.2% (1/465) |
| Disappointed by a friend | 0.2% (1/465) |
| 4. Anger/frustration (n = 77) | |
| Argument (no more details) | 5.2% (24/465) |
| Argument with family | 3.7% (17/465) |
| Argument with spouse | 2.2% (10/465) |
| Argument with neighbour | 1.3% (6/465) |
| Argument at work | 0.9% (4/465) |
| Angry with child | 0.9% (4/465) |
| Argument with employer | 0.4% (2/465) |
| Argument with friend | 0.4% (2/465) |
| Argument with brother/sister | 0.4% (2/465) |
| Angry, lost purse | 0.2% (1/465) |
Angry, old tree being logged  | 0.2% (1/465) |
| Angry, stuck in a traffic congestion | 0.2% (1/465) |
| Frustrated, favourite football team lost game | 0.2% (1/465) |
| Frustrated, car was stolen | 0.2% (1/465) |
| Argument requiring police involvement | 0.2% (1/465) |
| 5. Financial/employment problems (n = 37) | |
| Stress at work | 6.7% (31/465) |
| Retirement | 0.6% (3/465) |
| Financial problems | 0.4% (2/465) |
| Debt | 0.2% (1/465) |
| 6. Others (n = 59) | |
| No details | 12.7% (59/465) |
Happy heart events (n = 20)
| Patient 1 | Birthday party |
| Patient 2 | Son’s wedding |
| Patient 3 | Meeting after 50 years with friends from high school |
| Patient 4 | Preparing 50th wedding anniversary (pleasant anticipation) |
| Patient 5 | Positive job interview |
| Patient 6 | Wedding |
| Patient 7 | Favourite driver won race car competition |
| Patient 8 | Becoming grandmother |
| Patient 9 | Surprise farewell celebration |
| Patient 10 | Son’s company opening |
| Patient 11 | Favourite rugby team won game |
| Patient 12 | Emotional speaking during a friend’s birthday |
| Patient 13 | Celebrating 80th birthday |
| Patient 14 | Winning several jackpots at the casino  |
| Patient 15 | Celebration of normal PET-CT scan  |
| Patient 16 | Visiting opera with her family |
| Patient 17 | Family party |
| Patient 18 | Unexpected visit from favourite nephew |
| Patient 19 | Grandchildren visiting from London (abroad) |
| Patient 20 | Becoming great grandmother |
Though the mechanism for Takotsubo’s Cardiomyopathy is poorly understood, the associated risks to patients and the need for clinical awareness is as relevant as ever. Clinicians should be on alert to their own biases when taking a history and be open minded – no single emotional trigger accounts for the majority of Takotsubo’s cases. Through arranging diagnostic investigations and taking a comprehensive history, clinicians can clinch a diagnosis, monitor for complications and discontinue ACS treatment earlier. The old saying rings true for Takotsubo’s: the heights of our joy mirror the depths of our despair.
References
[1] Ghadri JR, Sarcon A, Diekmann J, Bataiosu DR, Cammann VL, Jurisic S, et al. Happy heart syndrome: role of positive emotional stress in takotsubo syndrome. European heart journal. 2016 Oct 1;37(37):2823-9.
[2] Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, et al. Clinical features and outcomes of takotsubo (stress) cardiomyopathy. New England Journal of Medicine. 2015 Sep 3;373(10):929-38.
[3] Y-Hassan S, Tornvall P. Epidemiology, pathogenesis, and management of takotsubo syndrome. Clinical Autonomic Research. 2018 Feb;28:53-65.
[4] Carita P, Fazio G, Novo G, Novo G. Takotsubo cardiomyopathy. E-Journal of Cardiology Practice. 2010;8.
[5] Kosuge M, Ebina T, Hibi K, Morita S, Okuda J, Iwahashi N, et al. Simple and accurate electrocardiographic criteria to differentiate takotsubo cardiomyopathy from anterior acute myocardial infarction. Journal of the American College of Cardiology. 2010 Jun 1;55(22):2514-6.
[6] Amin HZ, Amin LZ, Pradipta A. Takotsubo cardiomyopathy: a brief review. Journal of medicine and life. 2020 Jan;13(1):3.
[7] Wittstein IS, Champion HC. Myocardial stunning due to sudden emotional stress. New England Journal of Medicine. 2005 May 5;352(18):1924-5.
[8] Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. American heart journal. 2008 Mar 1;155(3):408-17.
[9] Zalewska-Adamiec M, Bachorzewska-Gajewska H, Tomaszuk-Kazberuk A, Nowak K, Drozdowski P, Bychowski J, Krynicki R, Musial WJ, et al. Takotsubo cardiomyopathy: serious early complications and two-year mortality–a 101 case study. Netherlands Heart Journal. 2016 Sep;24:511-9.
[10] Lyon AR, Bossone E, Schneider B, Sechtem U, Citro R, Underwood SR, et al. Current state of knowledge on Takotsubo syndrome: a Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology. European journal of heart failure. 2016 Jan;18(1):8-27.
