Takotsubo cardiomyopathy
Takotsubo cardiomyopathy or takotsubo syndrome (TTS), also known as stress cardiomyopathy, is a type of non-ischemic cardiomyopathy in which there is a sudden temporary weakening of the muscular portion of the heart.[4] It usually appears after a significant stressor, either physical or emotional; when caused by the latter, the condition is sometimes called broken heart syndrome.[5]
Takotsubo cardiomyopathy
Examples of physical stressors that can cause TTS are sepsis, shock, subarachnoid hemorrhage, and pheochromocytoma. Emotional stressors include bereavement, divorce, or the loss of a job.[6] Reviews suggest that of patients diagnosed with the condition, about 70–80% recently experienced a major stressor, including 41–50% with a physical stressor and 26–30% with an emotional stressor.[7][8] TTS can also appear in patients who have not experienced major stressors.[8][9]
The pathophysiology is not well understood, but a sudden massive surge of catecholamines such as adrenaline and norepinephrine from extreme stress or a tumor secreting these chemicals is thought to play a central role.[10] Excess catecholamines, when released directly by nerves that stimulate cardiac muscle cells, have a toxic effect and can lead to decreased cardiac muscular function or "stunning".[11][12] Further, this adrenaline surge triggers the arteries to tighten, thereby raising blood pressure and placing more stress on the heart, and may lead to spasm of the coronary arteries that supply blood to the heart muscle.[10] This impairs the arteries from delivering adequate blood flow and oxygen to the heart muscle.[10] Together, these events can lead to congestive heart failure and decrease the heart's output of blood with each squeeze.[10]
Takotsubo cardiomyopathy occurs worldwide.[11] The condition is thought to be responsible for 2% of all acute coronary syndrome cases presenting to hospitals.[11] Although TTS has generally been considered a self-limiting disease, spontaneously resolving over the course of days to weeks, contemporary observations show that "a subset of TTS patients may present with symptoms arising from its complications, e.g. heart failure, pulmonary edema, stroke, cardiogenic shock, or cardiac arrest". This does not imply that rates of shock/death of TTS are comparable to those of acute coronary syndrome (ACS), but that patients with acute complications may co-occur with TTS.[6] These cases of shock and death have been associated with the occurrence of TTS secondary to an inciting physical stressor such as hemorrhage, brain injury sepsis, pulmonary embolism or severe COPD.[11]
It occurs more commonly in postmenopausal women.[11] The name "takotsubo" comes from the Japanese word takotsubo "octopus trap", because the left ventricle of the heart takes on a shape resembling an octopus trap when affected by this condition.[13]
A study published in the Journal of the American Heart Association in October 2021 found a steady annual increase in takotsubo cardiomyopathy among both women and men from 2006 to 2017, with the sharpest increases among women 50 and older.[14]
Signs and symptoms[edit]
The typical presentation of takotsubo cardiomyopathy is chest pain with or without shortness of breath and associated electrocardiogram (ECG) changes mimicking a myocardial infarction of the anterior wall. During the course of evaluation of the patient, a bulging out of the left ventricular apex with a hypercontractile base of the left ventricle is often noted. It is the hallmark bulging-out of the apex of the heart with preserved function of the base that earned the syndrome its name takotsubo "octopus trap", in Japan, where it was first described.[15]
Stress is the main factor in takotsubo cardiomyopathy, with more than 85% of cases set in motion by either a physically or emotionally stressful event that prefaces the start of symptoms.[16] Examples of emotional stressors include grief from the death of a loved one, fear of public speaking, arguing with a spouse, relationship disagreements, betrayal, and financial problems.[16] Acute asthma, surgery, subarachnoid hemorrhage, chemotherapy, and stroke are examples of physical stressors.[16] In a few cases, the stress may be a happy event, such as a wedding, winning a jackpot, a sporting triumph, or a birthday.[17][18]
Risk factors[edit]
Stress trigger[edit]
Although there have been documented cases of TTS without a triggering stressor, it is widely recognized that TTS is preceded by a stressful or emotional event.[12] Case series looking at large groups of patients report that some patients develop takotsubo cardiomyopathy after experiencing emotional stress. Some patients have a preceding clinical stressor (such as a brain injury, asthma attack or exacerbation of a chronic illness) and research has indicated that this type of stress may even occur more often than emotionally stressful triggers.[9] Roughly one-third of patients have no preceding stressful event.[19] A 2009 large case series from Europe found that takotsubo cardiomyopathy was slightly more frequent during the winter season. This may be related to two possible/suspected pathophysiological causes: coronary spasms of microvessels, which are more prevalent in cold weather, and viral infections – such as Parvovirus B19 – which occur more frequently during the winter.[1]
Genetic risk factors[edit]
It is currently being investigated if certain genetic traits associated with catecholamine receptors found on cardiac muscle cells play a role in the development of TTS.[20] There is limited evidence tying TTS directly to a specific genetic expression or mutation, however there is currently a widely held hypothesis supporting the idea of the interaction between environmental factors and the interplay of genetic predisposition leading to the susceptibility to microvascular alterations that contribute to the TTS disease process.[6]
Hormonal dysregulation[edit]
Certain endocrine diseases including pheochromocytoma and thyrotoxicosis have been identified as potential risk factors for TTS.[21][22] The relationship between thyroid function and stress cardiomyopathy is marked by a dual phenotype, where both impending primary hyperthyroidism and a high set point of thyroid homeostasis (encoding type 2 allostatic load) are common phenomena.[23] A multi-centre observation study found normal thyroid function to be the exception rather than the rule in TTS.[23] Especially hyperthyroidism is highly prevalent in takotsubo cardiomyopathy, and it seems to predict a poor prognosis in terms of complications and mortality.[24] This observation was confirmed by results of the international GEIST registry, which demonstrated that thyrotoxicosis is associated with significantly increased fatality, whereas hypothyroidism indicates a better survival.[25]
Left ventriculography during systole showing apical ballooning akinesis with basal hyperkinesis in a characteristic takotsubo ventricle
Left ventriculogram during systole displaying the characteristic apical ballooning with apical motionlessness in a patient with takotsubo cardiomyopathy
(A) Echocardiogram showing dilatation of the left ventricle in the acute phase (B) Resolution of left ventricular function on repeat echocardiogram six days later
ECG showing sinus tachycardia and non-specific ST and T wave changes from a person with confirmed takotsubo cardiomyopathy
Several well regarded institutions of medical research have produced clinical criteria useful in diagnosing TTS. One of the first sets of guidelines was initially published in 2004 and again in 2008 by the Mayo Clinic. Other research institutions proposing diagnostic criteria include the Japanese Takotsubo Cardiomyopathy Study Group, Gothenburg University, Johns Hopkins University, the Takotsubo Italian Network and the Heart Failure Associates TTS Taskforce of the European Society of Cardiology.[36] All of the research institutions agree on at least two main criteria needed to accurately diagnose TTS: 1) transient left ventricular wall motion abnormality and 2) the absence of a condition obviously explaining this wall motion abnormality (coronary artery lesion, hypoperfusion, myocarditis, toxicity, etc.). Other commonly acknowledged criteria necessary for diagnosis include characteristic EKG changes and mild to modest elevation in cardiac troponin.[36]
Transient apical ballooning syndrome or takotsubo cardiomyopathy is found in 1.7–2.2% of patients presenting with acute coronary syndrome.[1] While the original case studies reported on individuals in Japan, takotsubo cardiomyopathy has been noted more recently in the United States and Western Europe. It is likely that the syndrome previously went undiagnosed before it was described in detail in the Japanese literature. Evaluation of individuals with takotsubo cardiomyopathy typically includes a coronary angiogram to rule out occlusion of the left anterior descending artery, which will not reveal any significant blockages that would cause the left ventricular dysfunction. Provided that the individual survives their initial presentation, the left ventricular function improves within two months.
The diagnosis of takotsubo cardiomyopathy may be difficult upon presentation. The ECG findings often are confused with those found during an acute anterior wall myocardial infarction.[37][38] It classically mimics ST-segment elevation myocardial infarction, and is characterised by acute onset of transient ventricular apical wall motion abnormalities (ballooning) accompanied by chest pain, shortness of breath, ST-segment elevation, T-wave inversion or QT-interval prolongation on ECG. Cardiac enzymes are usually negative and are moderate at worst, and cardiac catheterization usually shows absence of significant coronary artery disease.[1]
The diagnosis is made by the pathognomonic wall motion abnormalities, in which the base of the left ventricle is contracting normally or is hyperkinetic while the remainder of the left ventricle is akinetic or dyskinetic. This is accompanied by the lack of significant coronary artery disease that would explain the wall motion abnormalities. Although apical ballooning has been described classically as the angiographic manifestation of takotsubo, it has been shown that left ventricular dysfunction in this syndrome includes not only the classic apical ballooning, but also different angiographic morphologies such as mid-ventricular ballooning and, rarely, local ballooning of other segments.[1][39][40][41][42]
The ballooning patterns were classified by Shimizu et al. as takotsubo type for apical akinesia and basal hyperkinesia, reverse takotsubo for basal akinesia and apical hyperkinesia, mid-ventricular type for mid-ventricular ballooning accompanied by basal and apical hyperkinesia, and localised type for any other segmental left ventricular ballooning with clinical characteristics of takotsubo-like left ventricular dysfunction.[40]
In short, the main criteria for the diagnosis of takotsubo cardiomyopathy are: the patient must have experienced a stressor before the symptoms began to arise; the patient's ECG reading must show abnormalities from a normal heart; the patient must not show signs of coronary blockage or other common causes of heart troubles; the levels of cardiac enzymes in the heart must be elevated or irregular; and the patient must recover complete contraction and be functioning normally in a short amount of time.[43]
Prognosis[edit]
Despite the grave initial presentation in some of the patients, most of the patients survive the initial acute event, with a very low rate of in-hospital mortality or complications. Once a patient has recovered from the acute stage of the syndrome, they can expect a favorable outcome and the long-term prognosis is excellent for most.[1][15][39] Even when ventricular systolic function is heavily compromised at presentation, it typically improves within the first few days and normalises within the first few months.[1][30][31][32] Although infrequent, recurrence of the syndrome has been reported and seems to be associated with the nature of the trigger.[1][19] While men experience TTS at much lower rates than women, they also experience much higher rates of complication, reoccurrence, and mortality; the cause of this sex difference is still unknown, but it is hypothesized that the social aspect of the doctor-patient interaction affects the way that physicians recognize and generate individual treatment plans for men compared to women.[56] Stress cardiomyopathy is now a well-recognized cause of acute congestive heart failure, lethal abnormal heart rhythms, and rupture of the heart wall.[13]
Epidemiology[edit]
Takotsubo syndrome represents about 2% of all patients (and 5–6% of all female patients) who are initially diagnosed with acute coronary syndrome (ACS).[6][57] It accounts for 0.02% of all hospitalizations in the US.[6] About 90% of TTS patients are women,[6][57] whose mean age is about 68 years, and 80% of whom are older than 50 years.[6] About 2.2% of TTS cases had the reversed (basal) variant.[57] Recurrence rate of TTS is about 1.8% per-patient year.[6]