What are the clinical features and pathogenesis of Takotsubo (stress) cardiomyopathy?

Clinical Features and Pathogenesis of Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy (TTS) is a transient, stress-induced dysfunction of the left ventricle that predominantly affects postmenopausal women (90%) following emotional or physical stressors, characterized by symptoms mimicking acute coronary syndrome but occurring in the absence of obstructive coronary artery disease. 1

Clinical Presentation

Key Features

• Demographics: Strong female predominance (90%), particularly postmenopausal women 2, 1
• Symptoms:
  • Chest pain (similar to acute myocardial infarction)
  • Dyspnea
  • Occasionally cardiogenic shock or hemodynamic instability 1
• Triggers:
  • Emotional stress (grief, fear, anger)
  • Physical stressors (surgery, critical illness, chemotherapy) 1

Diagnostic Findings

• ECG Abnormalities:
  • ST-segment elevation (typically less pronounced in lead V1 compared to anterior STEMI)
  • Progressive T-wave inversion
  • QT interval prolongation 1
• Cardiac Biomarkers:
  • Modest elevation of cardiac troponin (disproportionately low compared to the extensive wall motion abnormalities) 2, 1
• Imaging:
  • Characteristic regional wall motion abnormalities (apical ballooning)
  • Normal coronary arteries on angiography 2, 1

Pathogenesis

The exact pathophysiological mechanisms remain incompletely understood, but several key factors have been implicated:

Primary Mechanisms

1. Catecholamine Surge:

   • Excessive release of catecholamines following emotional or physical stress 2, 1
   • Direct catecholamine-mediated myocardial toxicity

2. Microvascular Dysfunction:

   • Coronary microvascular spasm
   • Impaired coronary microcirculation 1

3. Neurohormonal Brain-Heart Interactions:

   • Complex interplay between the central nervous system and cardiovascular system 1

Structural and Functional Changes

• Myocardial Stunning: Transient myocardial dysfunction that recovers completely within weeks 1
• Myocardial Edema: Present in affected regions without late gadolinium enhancement on cardiac MRI 1
• Ventricular Involvement Patterns:
  • Classic/apical form (most common): Apical and mid-ventricular hypokinesis with basal hypercontractility
  • Mid-ventricular form: Mid-ventricular hypokinesis with apical and basal hypercontractility
  • Basal form (inverted takotsubo): Basal hypokinesis with apical hypercontractility
  • Biventricular involvement in approximately 25% of cases 1

Diagnostic Approach

Key Diagnostic Criteria

1. Transient regional wall motion abnormalities extending beyond a single coronary territory
2. Absence of obstructive coronary artery disease or acute plaque rupture
3. New ECG abnormalities or modest elevation of cardiac biomarkers
4. No evidence of myocarditis 1

Diagnostic Tools

• InterTAK Diagnostic Score: Score ≥70 indicates high probability of TTS 1
• Comprehensive cardiac workup:
  • ECG
  • Serial troponin measurements
  • BNP measurement
  • Echocardiogram
  • Coronary angiography 1

Management and Prognosis

Treatment

• Acute Phase:
  • Supportive care
  • ACE inhibitors or ARBs (first-line therapy, associated with improved survival and reduced recurrence) 1, 3
  • Anticoagulation for patients with severe LV dysfunction due to risk of LV thrombus 2, 1

Prognosis

• Overall: Excellent prognosis with approximately 95% of patients making full recovery 1, 3
• Recovery Timeline: LV function typically normalizes within 3-4 weeks 1
• Recurrence Rate: Approximately 5% 1
• Complications:
  • Left ventricular outflow tract obstruction (in ~20% of cases)
  • LV thrombus formation
  • Cardiogenic shock (rare)
  • Arrhythmias 2, 1

Clinical Pitfalls and Considerations

• TTS can be easily misdiagnosed as acute myocardial infarction due to similar presentation 4, 5
• Beta-blockers, despite theoretical benefit, have not shown survival benefit or prevention of recurrence 1
• Follow-up imaging at 1-4 weeks is essential to confirm resolution of wall motion abnormalities 1
• Long-term ACE inhibitor or ARB therapy may be beneficial to prevent recurrence 1, 3