7th March 2024

Cardiomyopathies

Dilated Cardiomyopathy 

Background

Cardiomyopathies are heart muscle disorders with abnormalities of either systolic or diastolic function in which there is a primary abnormality of the heart muscle itself i.e., in the absence of coronary artery disease, hypertension, valvular heart disease or congenital heart disease. These disorders can be due to changes in the nature of the underlying intracellular make-up, deposition of pathological material in the intercellular space or abnormal function of cardiac muscle. 

The subclassification of cardiomyopathies remains an evolving field as we understand more about their pathologies, but a standard classification would include:

• Dilated Cardiomyopathy (DCM)
• Hypertrophic cardiomyopathy (HCM)
• Restrictive Cardiomyopathy (RCM)
• Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
• Unclassified – including Takotsubo cardiomyopathy and Left Ventricular non-compaction

Once classified as above, the cardiomyopathies can be subclassified as familial/genetic vs non-familial/non-genetic/acquired.

There is still ongoing discussion about these terms, particularly as some hypertrophic conditions can lead to restrictive physiology, which can lead to confusion regarding nomenclature. 

Symptomatology is largely related to the effect that the underlying pathology has on cardiac function. Conditions in which the underlying pathology is acquired as part of a multi-system disorder (such as HCM in the context of Friedrich’s ataxia) are likely to display a much wider range of symptoms, whilst those with intrinsic cardiac disease will show signs and symptoms purely of cardiac dysfunction related to the exact effect that the pathology has on the function heart.

All patients with a suspected cardiomyopathy should initially be investigated with:

• A full and thorough history with a focus on family history to elucidate any potentially inherited conditions. Specific questions should be asked about any history of sudden death or epilepsy in the family – often a misdiagnosis in the context of cardiogenic syncope
• Basic observations including temperature, heart rate, blood pressure, respiratory rate and oxygen saturation
• Blood tests including full blood count, renal function, liver function tests, NT pro-BNP, troponin, bone profile, cholesterol and HbA1C
• 12-lead ECG – at least 2 if the symptoms are acute to help rule out dynamic ECG changes
• Echocardiogram

Natriuretic peptides (BNP and NT-pro BNP) will be elevated almost without fail in cases with overt heart failure, as the release of these biomarkers is caused by elevations of intraventricular pressure.

There are some additional investigations pertinent to the individual classes of cardiomyopathy which will be discussed in the relevant sections.

Treatment will be related to either amelioration of the underlying disease process, treatment of impaired cardiac function, or aimed at prevention of further deleterious sequelae caused by the disease such as arrhythmia causing haemodynamic instability or sudden cardiac death.

Pathology

Dilated cardiomyopathy (DCM) is likely the most common of the cardiomyopathies. It is characterised by an enlarged and globally poorly contractile left ventricle. As with many of the following cardiomyopathies, it can be both acquired or inherited.

The genetic subtypes are numerous and include mutations in cytoskeletal or sarcomeric protein and nuclear membrane abnormalities. The acquired subtypes can include myocarditis, thiamine deficiency, alcohol and tachycardia induced cardiomyopathies. Peripartum cardiomyopathy is a form of DCM, in which the DCM occurs in the peripartum period, most typically in the post-partum period.

Signs and symptoms

DCM typically manifests signs and symptoms related to chamber enlargement and systolic dysfunction and thus will lead to typical signs and symptoms of heart failure. 

Symptoms

• Shortness of breath
• Orthopnoea
• Paroxysmal Nocturnal Dyspnoea
• Peripheral oedema

Signs

• Elevated JVP
• 3rd heart sound – gallop heart rhythm
• Displaced apex laterally towards the axilla
• Crepitations on auscultation

In the context of specific disorders leading to a DCM, such as alcohol abuse or thiamine deficiency, you will also see signs and symptoms of the specific disease, such as chronic liver disease and malnutrition, respectively.

Investigations 

The diagnosis of DCM requires imaging demonstrating cardiac dilation, typically with a left ventricular ejection fraction <45% and an LV end-diastolic diameter >117% of the predicted value, with other causes of myocardial disease excluded.

This is most commonly diagnosed on echocardiography, given the greater availability of the modality, but it can be seen or confirmed via other modalities such as cardiac MRI. Cardiac MRI can also provide useful information regarding the quality of the myocardial tissue including myocardial fibrosis, a greater extent of which is a poor prognostic marker. Both will often show an element of functional valvular regurgitation i.e., valvular disease due to dilation of the valve annulus not due to an intrinsic defect in the valve itself.

Reductions in global longitudinal strain and strain rate can also be seen prior to dilation and reductions in ejection fraction.

ECG can be relatively nonspecific, showing ST or T wave changes, sinus tachycardia or a bundle branch block due to the increased distance that the electrical impulses have to travel in the enlarged heart.

Given that genetic links are not uncommon, it is standard to perform a detailed family tree and offer genetic counselling if a link is suggested. This can involve inviting other family members in for genetic testing to identify the nature of the putative mutation.

Treatment

Dilated cardiomyopathies are typically treated as per standard medical therapy for heart failure. If there is a clear precipitant, then this should be treated if possible, otherwise there are conservative, medical and interventional treatments according to a range of parameters, including left ventricular ejection fraction as per standard heart failure guidelines.

All patients with symptoms of fluid overload should be considered for a diuretic, typically a loop diuretic in the first instance. For patients with reduced left ventricular ejection fraction, medications that they should be offered include: 

• ACE inhibitor/ Angiotensin receptor blocker/ Angiotensin receptor blocker + Neprolysin inhibitor (ARNI)
• Beta blockade 
• Mineralocorticoid receptor antagonist
• Sodium Glucose Transporter Type 2 Inhibitors

Interventional options include:

• Ablation for ventricular tachycardias
• Implantable cardiac defibrillator for those with DCM and a confirmed disease-causing mutation at high risk for sudden cardiac death
• Cardiac resynchronisation therapy +/- defibrillator – dependent upon ejection fraction, NYHA classification and QRS duration
• Left ventricular assist device – either as bridging to transplant or as destination therapy
• Cardiac transplant

References

• Classification of the cardiomyopathies: a position statement from the European society of cardiology working group on myocardial and pericardial diseases. Available at https://academic.oup.com/eurheartj/article/29/2/270/433902
• https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.116.309396
• https://patient.info/doctor/dilated-cardiomyopathies
• https://www.nice.org.uk/guidance/ta314/documents/arrythmias-icds-heart-failure-cardiac-resynchronisation-fad-document2

Hypertrophic Cardiomyopathy

Pathology

HCM is defined as myocardial hypertrophy in the absence of abnormal loading conditions (such as hypertension or valvular disease like aortic stenosis), which would otherwise precipitate a compensatory myocardial thickening. 

HCM is one of the most common of the cardiomyopathies, and left ventricular hypertrophy without abnormal loading conditions is seen in approximately 0.2% of the population – though not all of these will experience signs and symptoms of cardiac disease. 

The symptoms experienced in HCM are typically caused by cellular disarray, leading to disorganised left ventricular architecture and increased myocardial thickening. This can lead to left ventricular diastolic dysfunction due to impaired relaxation, abnormal intramural coronary arteries and dynamic obstruction of the left ventricular outflow tract (LVOT).

HCM is more commonly genetically inherited in an autosomal dominant manner, and almost all components of the sarcomere can be involved. Commonest include the beta myosin heavy chain, myosin binding protein C and troponins I and T. There are many other genetic conditions which can lead to an HCM including Fabry’s disease, Noonan’s syndrome and Friedreich’s Ataxia. Non-genetic causes include AL amyloid and obesity.

Signs and symptoms

The commonest presenting symptom in HCM is dyspnea, but it can also present with chest pain, palpitations and syncope.

Systolic function as measured by ejection fraction is typically preserved, though abnormalities of contractile function are often seen when assessing ventricular deformation parameters (LV global longitudinal strain and strain rate), while diastolic function is often impaired by the abnormalities of the hypertrophied musculature and failure of myocardial relaxation. Dyspnea thus occurs due to elevated intracardiac pressures as the myocardium fails to relax adequately to maintain low intrachamber pressures leading to raised pulmonary artery pressures.

Chest pain can occur due to the increased metabolic demands of the hypertrophied muscle. If the hypertrophy outstrips the vascular supply, then a supply/demand mismatch can lead to relative ischaemia despite normal epicardial coronary vessels.

Palpitations can occur due to arrhythmias generated in the hypertrophied muscle. Ventricular arrhythmias are not uncommon and are a cause for concern, with intervention with antiarrhythmics or device therapy commonly considered.

LVOT obstruction can occur due to hypertrophy of the septal myocardium. This interferes with the normal flow of blood through the LVOT and, ultimately, the aortic valve. If this is sufficiently diminished, then blood will not reach the aorta to perfuse the coronary arteries nor the carotid arteries to perfuse the brain. This can lead to chest pain in the former and syncope or presyncope in the latter. These are concerning symptoms in HCM and require urgent investigation, as unexplained syncope in the context of HCM is a significant risk marker for sudden cardiac death.

Classical examination findings include a forceful, non-displaced apical beat accompanied by a jerky (otherwise called bisferiens) pulse. The irregular pulse of atrial fibrillation is a common finding, seen in approximately 1/5 of patients.

On auscultation, if the outflow tract is obstructed one can hear a systolic murmur radiating to both mitral and aortic regions, with the volume increased on Valsalva and diminished on release. This occurs because in Valsalva there is less venous return due to the increased intrathoracic pressure. This leads to an underfilled left ventricle, allowing the septum to block off the outflow tract. Conversely, when Valsalva is released, increased blood flow helps to splint open the outflow tract, reducing the obstruction and thus reducing the murmur. An additional sound of an S4 can also be heard due to turbulent flow in a non-compliant ventricle.

In comparison, the opposite effect is seen in aortic stenosis, in which a reduction in flow due to Valsalva leads to a quieter murmur, while the increase in flow post Valsalva causes a louder murmur due to more turbulent flow through the stenotic valve.

Investigations

The ECG findings of HCM are normally relatively striking and most patients will have an abnormal ECG, though the findings on ECG do not correlate well with clinical outcome.

ECG can show:

• Voltage criteria for left ventricular hypertrophy (S wave in V1 + tallest R wave in V5-V6 >35mm)
• Left atrial enlargement (p mitrale (bifid p waves))
• Short PR intervals (accessory pathways are more common in patients with HCM)
• Atrial fibrillation and supraventricular tachycardias are common
• Giant T wave inversions seen in the precordial leads
• Narrow, “dagger-like” q waves in the inferior and lateral leads

Echocardiography is the most common confirmatory diagnostic test. This will typically show asymmetric septal hypertrophy with a ratio of septal wall to posterior wall thickness >1.4:1. The LV is typically non-dilated and systolic function is preserved as measured by left ventricular ejection fraction, though deformation parameters are often reduced. Systolic anterior motion of the anterior mitral leaflet can also be seen. A velocity gradient across the left ventricular outflow tract can be seen, and in the absence of this being found despite typical myocardial hypertrophy, echocardiography while performing Valsalva manoeuvre or an exercise test should be considered to assess for dynamic left ventricular outflow tract obstruction.

Cardiac MRI can provide similar information to echocardiography but with better tissue characterisation and may be better at identifying areas which are difficult to image on echo due to impaired echocardiographic windows. 

Treatment

The management of hypertrophic cardiomyopathy is very dependent upon the extent of the pathology and the consequent symptoms.

For patients with significant arrhythmias, these can be treated as normal, though in the context of atrial fibrillation, drugs such as flecainide are typically avoided.

For patients with left ventricular outflow tract (LVOT) gradients, beta blockers, or rate limiting calcium channel blockers are effective at reducing this by acting as negative inotropes which reduces the risk of outflow tract obstruction.

Mavacamten is a myosin-actin cross-bridge inhibitor, a novel agent which, at the time of writing, is not yet approved for use in HCM but appears to have a positive impact on LVOT gradient, NYHA functional class, dyspnoea scores and NT pro-BNP levels in symptomatic HCM patients.

Patients with symptoms due to outflow tract obstruction refractory to drug therapy can be considered for a surgical myomectomy or alcohol septal ablation to reduce the outflow tract gradient.

Online calculators exist to predict 5-year risk of sudden cardiac death. For patients with a 5-year risk of SCD <4%, an ICD is generally not indicated, in patients with a risk of 4 to less than 6%, an ICD may be considered and in patients with a 5-year risk ≥6%, an ICD should be considered.

First degree relatives of patients with HCM should be screened with echocardiography and ECG to look for the typical abnormalities as described above. The children of affected children should be screened routinely until the age of 20. If HCM is not discovered by this stage, then it is unlikely to occur in later life.

References

• https://patient.info/doctor/hypertrophic-cardiomyopathy-pro
• https://www.ahajournals.org/doi/10.1161/CIR.0000000000000937
• https://www.thelancet.com/article/S0140-6736(20)31792-X/fulltext
• 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).
• A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD).

Restrictive Cardiomyopathy 

Pathology

Restrictive cardiomyopathy (RCM) is an umbrella term for pathologies in which there is increased stiffness of the myocardium, leading to increased pressure with only small increases in volume. It is thought to be one of the least common forms of cardiomyopathy.

A number of pathologies can lead to restrictive physiology; Genetic causes include troponin I abnormalities, familial amyloidosis, and Fabry’s disease, while acquired causes can include light chain amyloidosis, drug induced RCM, carcinoid syndrome, anthracycline chemotherapy and radiation. Haemochromatosis can be either genetically inherited through the HFE gene or acquired through repeated blood transfusions, as can sometimes be seen in thalassaemia.

It has previously been taught that systolic function is preserved in patients with these disorders, but contraction is rarely normal in these conditions and abnormalities of systolic function can be demonstrated on myocardial deformation imaging.

Signs and symptoms

RCM leads to increased myocardial stiffness. By the time of diagnosis, this has usually led to typical signs of heart failure described above, such as dyspnoea, fatigue, and pulmonary and peripheral oedema, but due to the increased ventricular stiffness on examination, you may also hear a loud third heart sound, due to abrupt cessation of rapid ventricular filling.

A majority of patients with RCM will also develop atrial fibrillation due to elevated filling pressures and subsequent left atrial enlargement, the latter of which is strongly correlated with the presence of atrial fibrillation. This will lead to the presence of an irregularly irregular pulse and may lead to patients experiencing palpitations alongside worsening dyspnoea and presyncope.

RCM is most commonly idiopathic in nature, with amyloidosis being the most common identifiable cause. If amyloid is discovered, then the patient may manifest other signs and symptoms of the underlying pathology, such as features of myeloma in AL amyloid, signs of iron deposition such as a change in skin colour and liver failure in haemochromatosis or carpal tunnel syndrome due to systemic amyloid deposition.

Investigations

Echocardiography will typically show thickened myocardium and thickened valves with small ventricular cavity sizes. It will also demonstrate impaired filling with diastolic dysfunction due to impaired relaxation caused by the increase in myocardial stiffness.

ECG findings in RCM will typically include low voltage QRS complexes, as well as varying blocks including bundle branch block or complete heart block. Atrial fibrillation is common and, thus, this may also be seen on the ECG. You may also see ‘pseudo-infarction’ Q waves present.

RCM is typically idiopathic in nature, though amyloid is the commonest identifiable cause in the western world. Other causes can include Sarcoidosis and infiltrative diseases such as haemochromatosis or Fabry’s disease.

Sarcoid would be suggested by the presence of systemic granulomas seen on imaging with elevated serum ACE levels and hypercalcaemia. Fabry’s can be diagnosed by assessing for low levels of alpha-galactosidase A on blood tests. Haemochromatosis can be diagnosed through assessment of ferritin and transferrin saturation, while suspicion of a genetic inheritance should lead to assessment for mutation of the HFE gene.

Given that amyloid is a significant and treatable cause of RCM, its presence or absence should be investigated. There are two commonly acquired types, AL and AA amyloid – the former caused by light chain deposition and the latter by overproduction of acute phase proteins, typically in chronic inflammation. AL more commonly affects the heart and is the more common of the two subtypes.

Investigation for AL amyloid should include a myeloma screen with protein electrophoresis and urinary Bence-Jones protein analysis. 

Investigation for AA amyloid include amyloid scintigraphy (a nuclear imaging modality) to assess organ distribution, while fat biopsy can confirm presence when it demonstrates red-green birefringence under polarised light after staining with congo red.

Transthyretin amyloidosis is the most common inherited systemic form of amyloidosis and if suspected after imaging tests then genetic testing can be performed.

Treatment

If an underlying disease process is found which is amenable to treatment then this can be actively targeted. Unfortunately, in many cases, the underlying pathology is not responsive to treatment.

In the absence of an identifiable cause, then, the treatment is largely based upon symptoms; cardiac transplantation can be considered in certain patients, particularly the young, while optimal medical therapy is given for heart failure with reduced ejection fraction as described above for DCM.  Atrial fibrillation is a very common consequence due to the elevated left atrial pressures so often rate control and anticoagulation are employed.

Pacemakers can be considered in those with conduction system disease, whilst implantable cardioverter defibrillators can be provided in high-risk patients.

References

• https://patient.info/doctor/restrictive-cardiomyopathy
• https://www.ahajournals.org/doi/full/10.1161/circresaha.117.310982
• https://www.hindawi.com/journals/rrp/2017/2874902/

Arrhythmogenic Right Ventricular Cardiomyopathy

Pathology

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is perhaps the simplest of the cardiomyopathies to describe as it has one common pathology – there is progressive replacement of myocardial tissues with adipose tissue, typically in the right ventricular inflow, outflow and apex leading to the name.  This leads to a particular morphology with dilation and aneurysm of the right ventricle, best seen on echo or particularly MRI, but with characteristic changes also seen on ECG.

It can also occur in the left ventricle, where a DCM phenotype is more commonly seen.

It is exclusively genetic, largely caused by autosomal dominant genes encoding proteins in the cardiomyocyte desmosome, although it is also seen in some autosomal recessive conditions such as Naxos and Carvajal syndromes.

Signs and symptoms 

ARVC generally presents with palpitations or syncopal symptoms, though sudden death caused by right ventricular arrhythmias can be the first symptom of the disease.

It has three typical phases – concealed phase, electrical disorder then RV failure.

In the concealed phase, there may be no significant symptoms and sudden death in the context of intense exercise may occur in this phase.

In those with an overt electrical disorder there may be palpitations, presyncope or syncope due to ventricular arrhythmias.

Those with RV failure will see some of the typical signs and symptoms of ‘right-sided’ heart failure – peripheral oedema, ascites, elevated JVP and hepatic congestion with hepatomegaly.

Ultimately, this can progress and left ventricular involvement can lead to biventricular failure and a similar picture to a dilated cardiomyopathy.

Investigations

ARVC is commonly diagnosed through imaging modalities requested as a result of suspicious ECG findings or symptoms.

Typical ECG features will include T wave inversion in V1-V3, QRS widening in V1-V3 and frequent ventricular ectopics. The most specific finding is that of an epsilon wave – a small deflection at the end of the QRS complex which represents post-excitation of the RV myocytes.

Echocardiography will typically demonstrate RV outflow tract dilation and reduction in RV fractional area change (a similar measure to ejection fraction in the LV but measured in one plane rather than two)

Cardiac MRI is very useful in demonstrating the underlying pathology, with RV enlargement and thinning, fatty infiltration and fibrosis of the wall.

If there is a suspicion of familial inheritance then genetic testing can be performed to identify the genetic abnormality and genetic counselling should be offered to first degree family members.

Treatment

Heart failure in the context of ARVC should be treated as per guidelines with optimal medical therapy as described above for DCM.

In the context of relatively low levels of electrical abnormalities, antiarrhythmic beta blockers such as sotalol or amiodarone are effective at controlling arrhythmias.

For patients with episodes of sustained VT or any episodes of VF, drugs can be trialed to reduce their likelihood, with EP studies to assess for continued inducibility of malignant arrhythmias. In certain patients, catheter ablation can also be considered.

For those in whom these arrhythmias remain inducible, those with overt arrhythmias outside of the EP setting, or in those with severe systolic dysfunction of either ventricle, an implantable cardiac defibrillator is typically required and is effective in preventing arrhythmogenic sudden death.

As per DCM, patients with end-stage heart failure may need consideration for device therapy or transplantation.

References

• https://www.heartrhythmjournal.com/article/S1547-5271(19)30438-2/fulltext
• https://www.bsecho.org/common/Uploaded%20files/Education/Protocols%20and%20guidelines/ARVC.pdf
• https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-8/Takotsubo-cardiomyopathy

Unclassified – including Takotsubo Cardiomyopathy and Left Ventricular non-compaction

Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy occurs in the context of transient but significant sympathetic nervous system activation, typically after a significantly emotional event such as a bereavement or sudden bad news, though it can also occur in response to a substantial positive emotion or significant physical event such as prolonged vomiting. The underlying pathophysiology is not completely understood, but it typically leads to apical ballooning of the left ventricle with preserved basal function, and this picture on imaging should raise suspicion of a takotsubo cardiomyopathy.

Signs and symptoms

As alluded to above, takotsubo cardiomyopathy typically occurs in the context of a significant physiological stressor or emotional event, so the history will normally be suggestive of this. 

Subsequent to this, the patient will classically complain of significant chest pain, which may well sound ischaemic in nature – crushing, central, causing shortness of breath – which can progress to acute left ventricular failure and pulmonary oedema. This occurs due to a sudden reduction in the function of the left ventricle, typically the mid and apical portions, manifesting as worsening shortness of breath, orthopnoea and signs of pulmonary congestion with crepitations on examination.

Investigations

The diagnosis of Takotsubo’s cardiomyopathy is commonly suspected due to a typical history of a stressful emotional or physical event with ischaemic sounding chest pain. It is a diagnosis of exclusion, and an acute coronary syndrome should be excluded in the first instance through invasive coronary angiography. If there are no clear culprit lesions for the disease on angiography, then Takotsubo can be considered.

Classical Takotsubo’s can be suspected by typical echocardiographic findings of left ventricular mid cavity and apical ballooning with relative preservation of basal ventricular function. In general, if there are regional wall motion abnormalities that do not fit a particular coronary pattern, then takotsubo should be considered. There are non-classical versions of Takotsubo’s cardiomyopathy in which apical and mid-cavity ballooning are not the echocardiographic findings but these are less common.

ECG will typically show ST segment change or T wave inversion, similar to that of an acute coronary syndrome, though it may not be consistent with a particular coronary territory and is more likely to be global.

Bloods – Troponin and BNP will typically be elevated, which normally leads to suspicion of an acute coronary syndrome in the acute setting.

As a diagnosis of exclusion, it also must be ensured that there is no concomitant myocarditis, head trauma or phaeochromocytoma to cause a similar but pathophysiologically distinct syndrome.

Treatment

Once diagnosed, if there is any evidence of impaired LV function it is typically treated as per any other cause of heart failure. This will entail optimal medical therapy, with echocardiographic and outpatient cardiology follow up.

Some centres will give aspirin or anticoagulation, though there is no good data to support this approach and current treatments are not backed by any well evidenced guidelines.

Left Ventricular non-compaction

Left ventricular non-compaction presents with prominent left ventricular trabeculae and deep inter-trabeculae recesses. They have thickened myocardial walls with a thin compacted epicardial layer and thickened endocardial layer.

 It is not easily classified and it is unclear if it is a separate cardiomyopathy or a morphological trait seen in many distinct pathologies. It frequently has a genetic component, with abnormalities in actin and lamin implicated, whilst asymptomatic relatives of an index case often show abnormalities on imaging.

Signs and symptoms

Symptoms of LV non-compaction can be relatively vague and non-specific. In some patients, it may be picked up incidentally on imaging, whilst in others they may present with arrhythmias or symptoms from thromboemboli, though the typical signs and symptoms of heart failure are the commonest presenting feature.

Investigations

LV noncompaction is a diagnosis made via imaging techniques, most commonly echocardiography and often followed up with MRI. There are different diagnostic criteria, but a commonly used one includes the following:

• A two layered myocardium in which the non-compacted layer is thicker than the compacted myocardium
• >3 prominent trabeculations protruding from the LV wall, apical to the papillary muscles
• Perfused intertrabecular space

Cardiac MR gives improved tissue resolution in comparison to Echo and can better differentiate between compacted and non-compacted myocardium and it is often used to help make the diagnosis when good echo images are not achievable.

Treatment

Patients with symptomatic heart failure are treated as per standard heart failure protocols, depending on their ejection fraction. Patients with persistent arrhythmias are treated according to the nature of their arrhythmia while those with regular ventricular arrhythmias can be provided with implantable cardioverter defibrillators to reduce the risk of sudden death. 

Hypertrabeculation of the left ventricle also predisposes to clot formation. As a result, many of these patients are formally anticoagulated, either with a coumadin or, more commonly, a direct oral anticoagulant, to reduce the risk of systemic embolisation.

References 

• https://academic.oup.com/eurheartj/article/39/22/2047/5025411
• https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-8/Takotsubo-cardiomyopathy
• https://www.ncbi.nlm.nih.gov/books/NBK537025/
• https://www.hindawi.com/journals/crp/2016/5172308/tab1/