Takotsubo syndrome presenting with left bundle branch block in an octogenarian. Is hyponatremia a pathogeni c “common ground”?

Elpidio Santillo✉, Pierpaolo D’Onofrio, Luciano Marini Demetrio Postacchini, Lucio Cardinali

1. Cardiac Rehabilitation Unit, Geriatric-Rehabilitative Department, IRCCS-INRCA, Fermo, Italy; 2. Geriatrics Unit, Geriatric-Rehabilitative Department, IRCCS-INRCA, Fermo, Italy

Takotsubo syndrome (TTS) is a cardiovascular condition characterized by a transient cardiac dysfunction, generally involving the apical segments of left ventriculum, in absence of significant coronary artery disease.[1]It frequently affects postmenopausal women, following physical or psychological stress.[2]

TTS often mimicks an acute myocardial infarction(AMI), presenting with symptoms as chest pain, dyspnea, palpitations and, less commonly, pre-syncope and syncope.

In most cases of TTS, alterations in ventricular kinetics are associated with electrocardiographic anomalies, mainly the depression or the elevation of STsegment and the inversion of T-wave.[1]

More rarely, TTS is accompanied by disturbances in ventricular conduction such as bundles branch block.[3,4]

The etiology of TTS is not yet fully understood, but numerous pathogenic factors have been proposed including a disproportionate sympathetic stimulation of the heart, an excess of catecholamines, coronary vasospasm, a cardiac microvascular dysfunction, inflammation and hormonal disturbances.[5,6]

Hyponatremia has also been observed in many patients with TTS.[7,8]

Hence, it has been hypothesized that conditions capable of causing hyponatremia as the syndrome of inappropriate antidiuretic hormone secretion might contribute to the pathogenesis of TTS.[9]

To our knowledge, forms of TTS in the course of hyponatremia with associated left bundle branch block (LBBB) on the electrocardiogram (ECG) have not yet been reported in octogenarian patients.

Herein, we describe the case of an 88-year-old female patient, admitted to the Geriatrics Unit of our Institute for fatigue, fever, cough and exertional dyspnoea. In her history, the patient presented hypertension, paroxysmal atrial fibrillation, and chronic obstructive pulmonary disease (COPD). She was on therapy with direct oral anticoagulant (rivaroxaban 15 mg once daily), beta-blocker (bisoprolol 1.25 mg once daily), and thiazide diuretic (hydrochlorothiazide 12.5 mg once daily). Before admission, the patient lived at her home and was completely autonomous in activities of daily living. At presentation, coarse crackles and expiratory wheezes at lungs’ bases were detectable on thorax auscultation. The patient had also ankle oedema. Her blood pressure was 140/70 mmHg and oxygen saturation was 95% in room gas.

The ECG documented atrial fibrillation with heart rate 90 beats/min and mild left intraventricular conduction delay (Figure 1A).

Laboratory examinations showed leucocytosis(leucocytes’ count: 16,800/uL), elevation of inflammatory markers (C-reactive protein: 19.2 mg/dL),hyponatremia (Na+: 129 mEq/L) and high N-terminal pro-brain natriuretic peptide values (4680 ng/L). Molecular swab for research of SARS-Cov-2 RNA was negative.

The chest X-ray evidenced mild lung congestion.Heart’s ultrasonography (Figure 1B) disclosed left ventricular hypertrophy, preserved ejection fraction of left ventriculum (55%) without wall motion anomalies and dilation of inferior vena cava (2.2 cm)with reduced respiratory variations.

Figure 1 Echocardiographic and electrocardiographic features at admission and at exordium of takotsubo syndrome. (A): Basal electrocardiogram: atrial fibrillation, mild intraventricular conduction delay; (B): basal echocardiographic four chamber systolic view: contraction of apical segments of left ventriculum is preserved; (C): electrocardiogram on takotsubo syndrome exordium: although recovering normal sinus rhythm, complete left bundle block is now evident. Concordant ST-segment elevation in D1 lead ＞ 1 mm (arrows) is suggestive of myocardial infarction according Sgarbossa criteria; and (D): echocardiographic four chamber systolic view on takotsubo syndrome exordium: apical ballooning of left ventriculum is evident (arrows).

Hence, acute exacerbation of COPD and decompensated heart failure (HF) with preserved ejection fraction were diagnosed. The patient started intravenous therapy with antibiotic (amoxicillin 1 g twice daily), furosemide (20 mg twice daily), and methylprednisolone (20 mg twice daily). Moreover, to counteract the worsening of hyponatremia, hydrochlorothiazide was discontinued. A restricted intravenous fluid administration [NaCl 0.9% (500 mL) once daily] was also ensured, obtaining a slightly passive fluid balance was. The patient had an initial improvement with resolution of the fever and reduction of exertional dyspnoea and ankle oedema. However,on the third day of hospitalization, her conditions suddenly worsened for the onset of chest discomfort,rest dyspnoea and pre-syncopal symptoms. Her blood pressure was 100/60 mmHg, the heart rate was 88 beats/min and oxygen saturation was 94% in room gas.

Noteworthy, the ECG displayed important changes consistent in new-onset LBBB, and ST-segment elevation, indicative of AMI according to the Sgarbossa criteria (Figure 1C).[10]Urgent laboratory test evidenced increased plasma troponin (1039 ng/L)and severe hyponatremia (Na+: 120 mEq/L).

The patient underwent another echocardiographic examination which showed severe global ventricular dysfunction with ejection fraction of 28% and dyskinesia of apical segments of the left ventricle (apical ballooning, Figure 1D). Overall, cardiac ultrasonography features were evocative of TTS, but the clinical, electrocardiographic and laboratory data could support the diagnosis of AMI.

Hence, the patient was referred to the Haemodynamics Department to perform the coronary angiogram, which excluded stenosing atherosclerotic lesions, thus confirming the diagnosis of TTS (Figure 2A-2C). Since the patient remained clinically stable, on the second day from coronary angiography, she was readmitted to the Geriatrics Ward. At readmission,she had mild residual signs of congestive HF and persistent hyponatremia (Na+: 130 mEq/L). Therefore, the treatment of congestive HF and the parenteral correction of hyponatremia was prosecuted with caution, via the administration of gradually lower doses of intravenous furosemide together with isotonic saline.

Patient’s clinical course was favourable with complete resolution of HF decompensation and COPD exacerbation. On the tenth day after readmission, she was discharged to her home, with normal natremia(Na+: 137 mEq/L).

Figure 2 Coronary angiogram images. Electrocardiographic and echocardiographic features at discharge. (A ＆ B): Left coronary angiogram: no obstructive atherosclerotic lesion; (C): right coronary angiogram: no obstructive atherosclerotic lesion; (D): electrocardiogram on discharge: complete left bundle block is now resolved; and (E): echocardiographic four chamber systolic view on discharge: the“apical ballooning” is no longer present.

Pre-discharge electrocardiography evidenced the resolution of LBBB, while echocardiography showed a full recovery of wall motion anomalies of apical segments of the left ventriculum (Figure 2D ＆ 2E).

On discharge, to reduce the risk of recurrent hyponatremia, a low dose calcium channel blocker was prescribed to the patient instead of hydrochlorothiazide for the chronic treatment of hypertension.

Present clinical case shows that TTS can dramatically affect older individuals. Certainly, elderly diagnosed with TTS appear more predisposed to developing HF than younger patients and, in addition,experience worse prognostic outcomes.[11,12]In our case, not only the emotional stress for the hospitalization, but also the history of COPD could have triggered the TTS.[13]

Importantly, the case we described confirms that the association between TTS and hyponatremia can be observed even in geriatric patients. In the reported case, hyponatremia could have been consequent of both diuretic therapy and the water retention related to HF. On the other hand, the recent diuretic administration, the presentation of sodium imbalance in a non-euvolemic status and the good response of the patient to saline isotonic, rendered inconsistent the hypothesis of the syndrome of inappropriate antidiuretic hormone.[14]

Interestingly, the association between hyponatremia and TTS could be causal in nature. In fact, in the course of hyponatremia, myocardiocytes suffer for a state of intracellular calcium overload, which predisposes to both heart contraction disorders and arrhythmogenesis.[9,15]In addition, hyponatremia has been already associated with the development heart conduction disorders including the LBBB as we observed in present case.[16,17]Of note, the detection of LBBB during TTS provides prognostic information, since its occurrence increases the risk of cardiogenic shock, ventricular arrhythmia, acute congestive HF and sudden death.[4]

However, when TTS presents with LBBB, clinicians face often the challenge of the differential diagnosis with AMI.

In such cases, Sgarbossa’s electrocardiographic criteria may be helpful in advising towards a diagnosis of AMI.[10]

The ECG aspects to be examined according to these criteria are: the extent of ST-segment elevation (≥ 1 mm) in a concordant QRS lead, the concordant STsegment depression (≥ 1 mm) in the leads V1, V2, or V3, and an excessively discordant ST-segment elevation (≥ 5 mm) in a lead with negative QRS. The score assigned to these items is 5 points, 3 points and 2 points, respectively. In patients with LBBB and suspected AMI, obtaining ≥ 3 points is considered diagnostic of AMI. However, in cases of TTS with associated LBBB, the accuracy of Sgarbossa criteria in excluding AMI remains to be proven. Undoubtedly, beyond the ECG, heart ultrasonography remains a fundamental tool in guiding clinicians towards the right diagnosis of TTS.[18]

In fact, the echocardiogram provides fundamental data on ventricular wall motion, also allowing the detection of the most common complications observed during TTS such as the obstruction to the outflow tract of the left ventricle and the acute mitral regurgitation onset.[19]

In conclusion, the present case suggests that hyponatremia might be a “common ground” for TTS and LBBB manifestation in elderly patients. Future studies should investigate if the prompt correction of hyponatremia might prevent the onset of TTS and intraventricular conduction delay, especially in those elderly with recent emotional or physical stress. Drugs associated with the risk of hyponatremia, such as thiazide diuretics, should be used with caution in chronic therapies of elderly.

ACKNOWLEDGMENTS

All authors had no conflicts of interest to disclose.