Cardiogenic Shock in a Healthy Young Woman With Acute Onset Abdominal and Chest Pain

The past medical history was significant for endometriosis with partial hysterectomy, as well as migraine headaches. There was no history of prior cardiac or neurological conditions. Family history was noncontributory. The patient was an occasional smoker but denied other substance use. She took no medications and had never received menopausal hormone therapy.

A 48-year-old woman presented to the emergency department with sudden onset of intense left upper abdomen with radiation to the anterior chest and back accompanied by dyspnea. Several minutes after the pain began, she experienced numbness in her trunk and legs and profound leg weakness. She was taken by ambulance to her local facility and found to be in shock with elevated troponins. Initial resuscitative measures were instituted, and she was airlifted to our tertiary care center. A timeline of the patient’s presentation and diagnostic imaging can be found in Figures 1 and 2 ( Videos 1 , 2 , and 3 ). Learning Objectives • Consider Takotsubo cardiomyopathy as a cause of cardiogenic shock in healthy women. • Recognize atypical subtypes of Takotsubo cardiomyopathy. • Recognize neurological events as triggers for Takotsubo cardiomyopathy in women. Figure 1 Left Ventriculography in Midvariant Takotsubo Syndrome Left ventriculogram at (left) end-diastole and (right) end-systole, demonstrating preserved basal and apical function with severe akinesis of midsegments. Figure 2 Timeline of Patient Presentation AVM = arteriovenous malformation; MRI = magnetic resonance imaging. Online Video 1 Apical 4-Chamber View at Presentation Severe hypokinesis of the midsegments with relatively preserved basal and apical function is seen. Online Video 2 Apical 4-Chamber View Taken 5 Days Following Presentation Although there continues to be hypokinesis of the midsegments, overall systolic function has improved. Online Video 3 Apical 4-Chamber View Performed 1 Month After Presentation Complete normalization of left ventricular systolic function is noted. • Consider Takotsubo cardiomyopathy as a cause of cardiogenic shock in healthy women. • Recognize atypical subtypes of Takotsubo cardiomyopathy. • Recognize neurological events as triggers for Takotsubo cardiomyopathy in women. Consider Takotsubo cardiomyopathy as a cause of cardiogenic shock in healthy women. Recognize atypical subtypes of Takotsubo cardiomyopathy. Recognize neurological events as triggers for Takotsubo cardiomyopathy in women. Left Ventriculography in Midvariant Takotsubo Syndrome Left ventriculogram at (left) end-diastole and (right) end-systole, demonstrating preserved basal and apical function with severe akinesis of midsegments. Timeline of Patient Presentation AVM = arteriovenous malformation; MRI = magnetic resonance imaging. Apical 4-Chamber View at Presentation Severe hypokinesis of the midsegments with relatively preserved basal and apical function is seen. Apical 4-Chamber View Taken 5 Days Following Presentation Although there continues to be hypokinesis of the midsegments, overall systolic function has improved. Apical 4-Chamber View Performed 1 Month After Presentation Complete normalization of left ventricular systolic function is noted. On initial assessment, she remained in significant distress with ongoing chest and abdominal pain. She was noted to be hypotensive and tachycardic with cool extremities. Blood pressure was 74/46 mm Hg, and heart rate was 105 beats/min and regular. She was afebrile. Auscultation revealed a normal S 1 and S 2 with no murmurs or extra heart sounds. Jugular venous pressure was estimated to be 6 cm above the sternal angle. On auscultation, bibasilar crackles were present at the lung bases. A limited bedside point-of-care ultrasound examination revealed global severe reduction in left ventricular (LV) ejection fraction (LVEF). Inotropic and pressor support was initiated, and she was admitted to the hospital. Subsequent neurological examination revealed the patient to be alert and oriented. Cranial nerve and upper extremity testing results were normal. Strength testing results were normal in all but the left leg, where all muscle groups were found to have 4/5 strength. Sensation was altered to pinprick on the left between T4 and the knee and on the right between T6 and L2. Reflexes were brisk in the lower limbs, and the Babinski reflex was present bilaterally.

Repeat echocardiogram 4 weeks after presentation showed complete normalization of the previously depressed LVEF and resolution of all regional wall motion abnormalities ( Video 3 ). An agitated saline contrast study was also done and demonstrated delayed appearance of bubbles in the left-sided chambers, a finding consistent with intrapulmonary shunting and the presence of pulmonary AVM. The patient was discharged with neurological rehabilitative exercises and continues to do well from a cardiac perspective. She will be followed up by neurology and genetics services.

We present an enigmatic case of a healthy 48-year-old woman presenting in cardiogenic shock as a result of the midvariant of Takotsubo cardiomyopathy triggered by intense upper abdominal and chest pain secondary to hemorrhage from a previously undiagnosed thoracic spinal AVM, likely related to a previously unrecognized genetic syndrome. Takotsubo, or stress-induced cardiomyopathy, is a relatively common yet poorly understood entity characterized by transient ventricular dysfunction in the setting of normal coronary arteries. It affects predominantly postmenopausal women ( 1 ), and it is often preceded by an emotional or physical trigger ( 2 ). Although the pathophysiology is incompletely understood, sympathetic stimulation is thought to lead to cardiac dysfunction ( 3 ). The classical and most common variant of Takotsubo cardiomyopathy is the apical-ballooning variant ( 4 ), occurring in about 80% of all cases ( 5 ). The midventricular variant, as seen in this patient, is present in only 15%. Cardiogenic shock can complicate Takotsubo cardiomyopathy and lead to death. In this patient, cardiogenic shock developed secondary to a marked and sudden decrease in LV systolic function. In other cases, hyperdynamic function of the basal segments can lead to LV outflow tract obstruction. This is critical to recognize because inotropes and diuresis can worsen the gradient and lead to hemodynamic collapse. Beta-blockade, volume repletion, and alpha-antagonists are mainstays of care in this scenario. Neurological disorders have been identified as frequent triggers for Takotsubo cardiomyopathy. Ischemic stroke, subarachnoid hemorrhage, and seizures have all been reported, and atypical variants of Takotsubo are more common when there is a concomitant neurological disorder ( 5 ). Interestingly, structural differences in the brain’s limbic system have been found among women who have Takotsubo cardiomyopathy ( 4 ) when compared with healthy control subjects. In this case spinal cord injury and associated intense pain, rather than emotional stress, led to cardiac dysfunction. This finding further supports the link between neurological injury and Takotsubo cardiomyopathy. Spinal cord syndromes appear to be less common triggers for this disorder, although an inverted Takotsubo cardiomyopathy has been previously reported as a result of bleeding of a spinal AVM ( 6 ). To our knowledge, this is the first reported case of a spinal AVM causing midventricular-variant Takotsubo cardiomyopathy.

The patient was weaned from dobutamine and norepinephrine infusions, and she was started on a beta-blocker and, subsequently, angiotensin-converting enzyme inhibitor therapy. Her cardiac symptoms quickly resolved over a matter of days. Repeat transthoracic echocardiography 5 days after admission showed improvement in LV systolic function, with a visually estimated LVEF of 50% ( Video 2 ). Neurological consultation was obtained, and spinal angiography was performed to evaluate potential vascular anomalies. This imaging revealed a small arteriovenous malformation (AVM) involving the ventral spinal cord at the level of T6-7 supplied by the anterior spinal artery. Additional small arteriovenous shunts were noted along the esophagus and within the left side of the neck from the left ascending cervical artery. Although there were no cutaneous or mucosal abnormalities noted on examination, the radiographic findings were thought to be suggestive of previously undiagnosed hereditary hemorrhagic telangiectasia, and genetic testing is pending.

Takotsubo cardiomyopathy affects predominantly women and can manifest as cardiogenic shock. Atypical variants can be seen and have been associated with neurological triggers.

The initial differential diagnosis was expansive in this previously well woman presenting with abdominal and chest pain associated with cardiogenic shock and neurological findings. The cardiovascular differential diagnosis included acute myocardial infarction secondary to atherosclerotic coronary artery disease, coronary vasospasm or spontaneous coronary artery dissection, aortic dissection (because both cardiac and neurological findings were present), and myocarditis, either idiopathic or secondary to an inflammatory condition. Similarly, the differential diagnosis for her neurological deficits was broad, but given the pattern of weakness and sensory changes, a spinal cord lesion was suspected.

Baseline laboratory test results were obtained and revealed a normal complete blood count, normal electrolytes, and normal renal function. Initial troponin T was elevated at 436 ng/ml, and lactate was 4.6 mg/dl. Electrocardiogram showed sinus tachycardia with right-axis deviation, without significant ST-segment or T-wave changes. The patient underwent selective coronary catheterization. This revealed no abnormalities of the coronary arteries. Left ventriculogram demonstrated preserved basal and apical function with severe hypokinesis of the midsegments ( Figure 1 ). Computed tomography angiography showed no evidence of aortic dissection. A formal transthoracic echocardiogram was performed while the patient was still receiving dobutamine and norepinephrine infusions. The left ventricle was mildly enlarged, with an LVEF of 25% to 30% and segmental wall motion abnormalities consistent with midvariant Takotsubo cardiomyopathy: basal and apical segments had preserved function, whereas all midsegments were severely hypokinetic ( Video 1 ). There was no evidence of systolic anterior motion of the mitral valve or outflow tract obstruction. C-reactive protein, thyroid-stimulating hormone, and thyroxine, were within normal limits, and test results for hepatitis B and C and human immunodeficiency virus serology, antinuclear antibody, and rheumatoid factor, as well as a vasculitis panel, were all negative. Magnetic resonance imaging of the head was within normal limits. However, magnetic resonance imaging of the spine revealed a longitudinally extensive cord signal abnormality extending from C5-6 to T11 consistent with punctate spinal cord hemorrhages at C7-T1, T6-7, and T10-11. An underlying vascular malformation could not be excluded.