Right Ventricle Takotsubo Cardiomyopathy with Abnormal Echocardiographic Right Heart Haemodynamics

Abbreviations

ECG, Electrocardiogram

LV, Left ventricle

RV, Right ventricle

TC, Takotsubo cardiomyopathy

TTE, Transthoracic echocardiogram

INTRODUCTION

Takotsubo cardiomyopathy (TC) is an acute and reversible cardiomyopathy that is often triggered by psychological and physical stressful events. Most cases of TC affect the left ventricle (LV), with few cases reported to be isolated to the right ventricle (RV).¹ We describe an uncommon case of isolated RV TC with abnormal echocardiographic right heart haemodynamics.

CASE

The patient is a 89-year-old Chinese lady with past medical history of hypertension, hyperlipidaemia, previous lacunar stroke, mild cognitive impairment, left posterior communicating artery aneurysm and cerebral amyloid angiopathy which were conservatively managed. There was no personal or family history of cardiac disease. She presented to the emergency department with left lower rib pain and low blood pressure with systolic blood pressure of 70 mmHg. A few days prior to the event, the patient was wedged between the washbasin and her domestic helper when her domestic helper experienced a syncopal episode in the toilet. On arrival at the emergency department, the patient was noted to be hypotensive with blood pressure of 89/54 mmHg and heart rate of 100 beats per minute. She was afebrile and had normal oxygen saturations. Physical examination was unremarkable except for localised left chest wall tenderness over the 5th intercostal space. 12-lead electrocardiogram (ECG) showed T wave inversion from V₁ to V₄ and a new incomplete right bundle branch block (Figure 1A). Troponin I was elevated at a peak of 522.9 ng/L (normal range 0-17.4 ng/L). Creatinine kinase was 64 U/L (normal range 20-300 U/L) and creatinine kinase-MB was 3.8 ug/L (normal range 1.0-6.0 ug/L). Chest X-ray was unremarkable and did not reveal any rib fractures (Figure 1B). After one pint of fluid resuscitation, the blood pressure of the patient improved to within normal limits and she was admitted to the general ward.

Figure 1.

12-lead electrocardiogram, chest radiography and magnetic resonance imaging of heart. (A) 12 lead electrocardiogram showing T wave inversion from V₁ to V₄ and a new incomplete right bundle branch block. (B) Chest radiography did not show any consolidation, pleural effusion or abnormalities. (C) Magnetic resonance imaging of heart with short axis view during the late gadolinium phase showing absence of late gadolinium enhancement.

Transthoracic echocardiogram (TTE) performed on day 2 showed preserved LV ejection fraction of 60% as well as a markedly dilated RV with hypokinetic RV apex.² Indexed RV areas measured 11.9 cm²/m² at end-diastole and 10.1 cm²/m² at end-systole. Fractional area change of RV was 34%. Tricuspid annular plane systolic excursion was 1.5 cm. There was also moderately severe tricuspid regurgitation. Eccentricity index at end-systole and end-diastole were 1.21 and 1.19 respectively. Pulmonary flow acceleration time was 80 ms. Pulmonary artery systolic pressure was estimated at 53 mmHg, using estimated right atrial pressure of 8 mmHg with a dilated but collapsible inferior vena cava (Figure 2). Calculated pulmonary vascular resistance was 3.2 WU by Abbas Formula, suggesting pre-capillary pulmonary hypertension. Calculated pulmonary wedge capillary pressure was estimated at 14.1 mmHg by Nagueh Formula. In comparison, TTE done 1 year ago showed normal chamber sizes and function, mild tricuspid regurgitation and pulmonary artery systolic pressure of 29 mmHg, using estimated right atrial pressure of 3 mmHg with a non-dilated and collapsible inferior vena cava.

Figure 2.

Transthoracic echocardiogram images. (A) End diastolic phase on admission (apical 4 chamber view). (B) End systolic phase on admission (apical 4 chamber view). (C) End diastolic phase during outpatient review (apical 4 chamber view). (D) End systolic phase during outpatient review (apical 4 chamber view). (E) Moderately severe tricuspid regurgitation during 2D colour imaging of tricuspid regurgitation on admission. (F) Dense tricuspid regurgitation signal with elevated maximum velocity peaking of 3.5 m/s on continuous wave doppler interrogation of tricuspid regurgitation on admission. (G) Return to baseline mild tricuspid regurgitation on outpatient review on 2D colour imaging of tricuspid regurgitation 3 weeks after. (H) Return to normal tricuspid regurgitation maximum velocity with peak of 2.2 m/s on continuous wave doppler interrogation of tricuspid regurgitation outpatient review 3 weeks after.

With suggestion of pre-capillary pulmonary hypertension and RV dilation from TTE, a computed tomography scan of the pulmonary arteries was performed and did not detect pulmonary embolism (Supplementary Figure 1). The computed tomography scan of the pulmonary arteries also incidentally picked up a left 7^th rib fracture. Right and left heart catherization were not performed in view of advanced age and multiple co-morbidities. Cardiac magnetic resonance imaging showed normal LV size and function. The RV apex was dyskinetic with normokinesia of the basal and mid-cavity RV myocardium. The RV ejection fraction was mildly reduced at 50% with indexed end diastolic volume and indexed end systolic volume measured at 63 ml/m² and 32 ml/ m² respectively. No late gadolinium enhancement was seen in the LV or RV (Figure 1C). The working diagnosis was RV TC with abnormal echocardiographic right heart haemodynamics. The patient was managed conservatively with supportive therapy including intravenous hydration and analgesia for her pain from rib fracture. She developed new onset paroxysmal atrial fibrillation and was started on bisoprolol, digoxin and apixaban. The patient was discharged after 1 week of hospitalisation. Repeat TTE 3 weeks after discharge showed complete recovery of the RV systolic function, improvement of tricuspid regurgitation to mild and normalisation of pulmonary artery systolic pressure (27 mmHg), using right atrial pressure of 3 mmHg (Figure 2). The patient was asymptomatic and well.

Supplementary Figure 1.

Computed tomography of pulmonary arteries which did not show evidence of pulmonary embolism.

DISCUSSION

TC, also known as stress cardiomyopathy is an acute and transient (< 21 days) cardiac dysfunction that often affects post-menopausal elderly women (about 90% of all cases reported especially in bigger cohorts).³ Our patient presented with hypotension and elevated troponin levels. TTE showed new RV dilation, RV apical hypokinesia and was suggestive of pre-capillary pulmonary hypertension. Computed tomography of the pulmonary arteries did not demonstrate acute pulmonary embolism. Cardiac magnetic resonance imaging was not suggestive of acute myocardial infarction and myocarditis. Repeat TTE three weeks from the presentation demonstrated complete resolution of RV dilation, RV apical hypokinesia and no pulmonary hypertension. This acute, transient and reversible RV dysfunction that was precipitated by the physical and emotional trigger experienced by our patient is consistent with the diagnosis of RV TC.

The revised Mayo Clinic criteria for diagnosis of TC includes (a) transient dyskinesis of ventricular myocardium, (b) regional wall motion abnormalities beyond a single epicardial vascular distribution, (c) absence of obstructive coronary artery disease, (d) new electrocardiographic abnormalities or modest troponin elevation as well as (e) absence of pheochromocytoma and myocarditis.⁴ Although TC is more commonly described with LV involvement, there have been case reports describing TC with isolated RV involvement or biventricular involvement.¹ The Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology in 2018 included RV involvement as one of the diagnostic criteria and a variant of TC.³

The exact pathophysiology of TC remains elusive but higher levels of circulating catecholamines, which are released during emotional and physiological stress, have been observed in patients with TC.⁵ One proposed hypothesis is that stressors in the form of emotional and physical triggers result in extreme sympathetic activation, releasing epinephrine and norepinephrine from the adrenal glands. The central role of adrenergic stimulation has been supported by several animal models.⁶ The surge in catecholamines may result in multivessel coronary spasm, microvascular dysfunction or direct myocyte toxicity as well as arrhythmias such as atrial fibrillation.⁷ This can affect both the LV and RV. Our patient developed RV dyskinesia, RV dilation as well as atrial fibrillation. Furthermore, our patient also had suggestion of pre-capillary pulmonary hypertension accompanying the RV dysfunction on TTE. We postulate that the surge in catecholamine levels induced vasoconstriction of the pulmonary vessels resulting in development of possible pre-capillary pulmonary hypertension. This has been previously described in both in vitro and in vivo studies.^8,9 In our patient, the abnormal echocardiographic right heart haemodynamics on TTE resolved after 3 weeks, likely following reduction of catecholamine levels from the initial emotional and physical trigger.

Our patient displayed characteristic features of RV TC in terms of clinical features, ECG and TTE findings seen in previous case reports. As summarised by Carreras-Mora et al., these features include development of non-deep negative T waves in leads V₁ to V₄ on serial ECGs, in contrast to deep anterolateral negative T waves in typical LV TC, dilation of affected ventricle, which is not commonly observed in typical LV TC, with reverse McConnell’s sign (apical RV hypokinesia with sparing of mid and basal RV segments) and severe clinical presentation at onset with rapid clinical recovery.^1,10

Limitations of our case report include the lack of right and left heart catheterization data to confirm pulmonary hypertension as determined by non-invasive methods of echocardiography. A plausible differential to RV TC is this case would be direct trauma of RV apex.

LEARNING POINT

We report a case of RV TC with abnormal echocardiographic right heart haemodynamics as well as characteristic features of RV TC that are distinct from typical TC. RV TC may not be as uncommon as previously thought. A high index of suspicion is needed to diagnose this unique form of RV cardiomyopathy.

DECLARATION OF CONFLICT OF INTEREST

All the authors declare no conflict of interest.