First Patient

A 68-year female had a past medical history significant for coronary artery disease (CAD) managed by drug-eluting stent in right coronary artery, hypertension, diabetes mellitus and underwent bilateral lung transplant in November 2020 for pulmonary fibrosis. Her immediate posttransplant recovery was complicated by prolonged ventilation, delayed wound healing and acute lung rejection type A1 requiring prolonged hospitalization. During follow-up, the patient had repeated episodes of lung transplant rejection type A1 due to unknown reasons, gastroesophageal reflux disease, one episode of sepsis due to Pseudomonas and Escherichia coli infections and acute kidney injury that required antibiotics. Her most recent admission in March 2022 was prompted by worsening dyspnea, without orthopnea, aspiration, or wheezing.

A chest computed tomography (CT) scan showed new ground-glass opacities throughout right and left upper lobe, suggestive of an acute inflammatory process. Bronchoscopy revealed white to yellow mucopurulent secretions involving multiple bronchopulmonary subsegments of bilateral lungs. However, bronchoalveolar lavage culture was negative. An echocardiogram performed at admission showed normal biventricular function, with a left ventricular ejection fraction (LVEF) of 65% and a right ventricle systolic pressure (RVSP) of 36 mmHg. All valves were functioning properly. Her esophagogram was normal. Donor-specific antibody testing was negative. Doppler ultrasound revealed a nonocclusive deep vein thrombosis (DVT) in the right internal jugular vein, an occlusive DVT in the right mid-femoral vein, and nonocclusive DVTs in the right common femoral, popliteal, and gastrocnemius veins. During hospitalization, chest X-rays showed worsening diffuse interstitial thickening and hazy airspace opacities, suggestive of pulmonary edema or infection.

Antibiotics were escalated and the patient had an initial improvement followed by gradual deterioration of respiratory status over next week, requiring high-flow nasal cannula at 40 L/min with inhaled nitric oxide (iNO) and finally requiring intubation with mechanical ventilation. The patient was initially managed with pressure-controlled ventilation, with fraction of inspired oxygen (FiO₂) at 80% and a positive end-expiratory pressure (PEEP) of 5 cm of H₂O. Over the next two days, PEEP increased to 10 cm of H₂O, with iNO of 20 ppm and FiO₂ increased to 100% without significant improvement. In arterial blood gas (ABG) analysis, partial pressure of oxygen (PaO₂) was 89.7 mmHg and partial pressure of carbon dioxide (PaCO₂) was 30.8 mmHg. The patient was initiated on epinephrine 0.02 µg/kg/min and vasopressin 0.04 U/hr for hypotension. Epinephrine was gradually escalated, and norepinephrine was also initiated. With vasopressors, her heart rate was 108/min, sinus rhythm and blood pressure (BP) were 116/74 mmHg, without signs of congestive heart failure, pulmonary edema, or cardiogenic shock.

High-sensitivity troponin T was 41 ng/L. Electrocardiogram (ECG) showed a normal sinus rhythm with tachycardia, a QRS duration of 96 ms, and diffuse ST-T elevation. Echocardiography revealed severe LV dysfunction with LVEF 14%, accompanied by layering LV thrombus and severe pulmonary hypertension (RVSP 68 mmHg) . LV apex was balloon out while only the basal segment was contracting, suggesting TTCM (Figures 1C, 1D, 1E). There was mild mitral regurgitation (MR) and moderate tricuspid regurgitation (TR). In view of deteriorating respiratory status, the multidisciplinary team decided to place the patient on VV-ECMO.

Fig. 1 - Intraoperative transesophageal echocardiography imaging of a mid-esophageal modified 5-chamber view (A), transgastric basal short-axis view, (C), transgastric mid-chamber short-axis view (D), and transgastric apical short-axis view (E). Left ventricular ejection fraction calculated at 14% via 3-D volumetrics (B). The images show basal contractility (C) with mid-chamber (D) and apical hypokinesis (E), consistent with Takotsubo/stress-induced cardiomyopathy. Post veno-venous extracorporeal membrane oxygenation on day 1 shows resolution of regional wall motion abnormalities in transthoracic apical 2-chamber view in Mayo Clinic format with the left ventricle on the left side of the screen (F).

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Fig. 1 - Intraoperative transesophageal echocardiography imaging of a mid-esophageal modified 5-chamber view (A), transgastric basal short-axis view, (C), transgastric mid-chamber short-axis view (D), and transgastric apical short-axis view (E). Left ventricular ejection fraction calculated at 14% via 3-D volumetrics (B). The images show basal contractility (C) with mid-chamber (D) and apical hypokinesis (E), consistent with Takotsubo/stress-induced cardiomyopathy. Post veno-venous extracorporeal membrane oxygenation on day 1 shows resolution of regional wall motion abnormalities in transthoracic apical 2-chamber view in Mayo Clinic format with the left ventricle on the left side of the screen (F).

After administering a heparin dose of 100 u/kg, percutaneous cannulation of left internal jugular vein was performed with a 21 Fr arterial HLS cannula (Maquet Cardiopulmonary AG, Hirrlingen, Germany), and left femoral vein was cannulated with a 25 Fr venous HLS cannula (Maquet Cardiopulmonary AG, Hirrlingen, Germany). The cannulae were connected to ECMO circuit taking care to prevent air trapping. VV-ECMO was initiated at 3,000 rotations/min, with a flow of 3.2 L/min, sweep of 1.5 L/min and FiO₂ of 100%. Ventilation was reduced to rest vent setting with PEEP of 10 cm of H₂O, rate of 10 and pressure support of 10 cm of H₂O. To prevent the risk of bleeding, no further anticoagulation was initiated for the next 24 hours and the later patient was initiated on a bivalirudin infusion, aiming for an activated partial thromboplastin time (aPTT) of 40-60 seconds.

The patient tolerated the procedure well, with an immediate decrease in vasopressors after ECMO initiation. Within the next day, the patient was completely weaned off vasopressors and her pulmonary status improved. A follow-up echocardiography after 2 days showed normal biventricular function, with a LVEF of 65%, RVSP of 38 mmHg, mild MR, and mild TR (Figure 1F). The patient was successfully weaned off ECMO, decannulated after six days, and extubated after 12 days. During her hospitalization, her liver function tests and renal function remained normal, with good urine output. However, in the next four days, patient’s respiratory status deteriorated again, requiring intubation. The family decided to redirect the care to comfort, and the patient expired 30 days after hospitalization.

Second Patient

A 78-year-old male, with a medical history significant for chronic renal insufficiency, secondary hyperparathyroidism, and Crohn's disease, who underwent proctocolectomy in 1997 with end ileostomy, underwent elective laparotomy, small bowel resection and revision of ileostomy in March 2022. Preoperative echocardiography showed normal biventricular function, LVEF of 62% and RVSP of 32 mmHg. All valves were functioning well. Coronary angiography showed minimal CAD.

The patient initially recovered well after surgery and was extubated and transitioning to oral intake on postoperative day 2. On postoperative day 6, the patient developed acute respiratory failure and septic shock due to aspiration, requiring intubation, antibiotic therapy, and vasopressors (vasopressin 0.02 U/hr). Liver function test was normal. Serum creatinine increased from 1.25 mg/dL to 1.83 mg/dL, with decrease in urine output, suggesting acute kidney injury.

Patient was initiated on continuous renal replacement therapy and initially managed with pressure-controlled ventilation with a FiO₂ at 70% and a PEEP of 5 cm of H₂O. Over the course of next 12 hours, patient developed refractory hypoxia despite positive pressure ventilation with FiO₂ of 100%, PEEP of 10 cm of H₂O and lung recruitment maneuvers. In ABG, PaO₂ was 46.2 mmHg and PaCO₂ was 66 mmHg. Contrast-enhanced chest CT was negative for pulmonary embolism and revealed multifocal pneumonia complicated by aspiration. Repeat echocardiography showed severe LV dysfunction, a LVEF of 30%, normal RV function, and normally functioning valves (Figures 2A and 2B). TTCM was diagnosed, and the patient was transferred to the intensive care unit (ICU) where a Swan-Ganz catheter was inserted. His cardiac output was 13 L/min and high-sensitivity troponin T was 37 ng/L. ECG showed normal sinus rhythm with tachycardia, QRS duration of 84 ms, and diffuse ST-T elevation. Over the next few hours, the patient’s condition deteriorated with hypotension, requiring multiple vasopressors (epinephrine 0.05 µg/kg/min, vasopressin 0.04 U/hr, norepinephrine 0.04 µg/kg/min and dobutamine 5 µg/kg/min), as well as high-flow nasal cannula at 40 L/min with iNO at 20 PPM. With vasopressors, heart rate was 104/min, sinus and BP was 122/76 mmHg. There were no signs of congestive heart failure, pulmonary edema, or cardiogenic shock. After multidisciplinary discussion, it was decided to initiate the VV-ECMO.

Fig. 2 - Intraoperative transesophageal echocardiography imaging of a transgastric mid-chamber short-axis view (A), and transgastric apical short-axis view (B). The images show severe mid-chamber akinesis (A) and apical hypokinesis (B), consistent with a reverse Takotsubo/stress-induced cardiomyopathy pattern. Post veno-venous extracorporeal membrane oxygenation on day 1 shows resolution of regional wall motion abnormalities in transthoracic modified apical 4-chamber view in Mayo Clinic format with the left ventricle on the left side of the screen (C) and a calculated 2-D biplane volumetric left ventricular ejection fraction of 59% per report.

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Fig. 2 - Intraoperative transesophageal echocardiography imaging of a transgastric mid-chamber short-axis view (A), and transgastric apical short-axis view (B). The images show severe mid-chamber akinesis (A) and apical hypokinesis (B), consistent with a reverse Takotsubo/stress-induced cardiomyopathy pattern. Post veno-venous extracorporeal membrane oxygenation on day 1 shows resolution of regional wall motion abnormalities in transthoracic modified apical 4-chamber view in Mayo Clinic format with the left ventricle on the left side of the screen (C) and a calculated 2-D biplane volumetric left ventricular ejection fraction of 59% per report.

Following the administration of 100 u/kg of heparin, percutaneous cannulation of the left internal jugular vein was performed with a 21 Fr arterial HLS cannula (Maquet Cardiopulmonary AG, Hirrlingen, Germany), and the left femoral vein was cannulated with a 25 Fr venous HLS cannula (Maquet Cardiopulmonary AG, Hirrlingen, Germany). The cannulae were connected to the ECMO circuit taking care to prevent air trapping. VV-ECMO was initiated at 2,800 rotations/min, with a flow of 3.0 L/min, sweep of 1.3 L/min and FiO₂ of 100%. Ventilation was reduced to rest vent setting with PEEP of 10 cm of H₂O, rate of 10 and pressure support of 10 cm of H₂O. To prevent the risk of bleeding, no anticoagulation was initiated for the next 24 hours, and later the patient was initiated on bivalirudin infusion aiming for an aPTT goal of 40-60 seconds. Intraoperative transesophageal echocardiography showed severe LV function with LVEF 15-20%, and normal functioning valve.

The procedure was uneventful, and the patient was shifted to the ICU on de-escalating dose of multiple vasopressors. In the ICU, repeat echocardiography after 24 hours showed normal LV size with mild basal-to-mid septal hypokinesis with LVEF of 59%. RV size and function were normal (Figure 2C). Vasopressors were weaned over the next 24 hours. Lung function improved over the next 2 days, and the patient was weaned off ECMO on postoperative day 2 and extubated on postoperative day 3. The ECG improved to normal. The patient gradually improved and was transferred to medicine department for further management and discharged on postoperative day 30. During hospitalization, the patient required continuous renal replacement therapy, followed by hemodialysis for 10 days, after which urine output improved. Echocardiography at the time of discharge showed normal biventricular function. At one-month follow-up, the patient was in good health.