Title: Extra Corporeal Membrane Oxygenation (ECMO) as a bridge to recovery in a patient with cirrhotic cardiomyopathy
1. Describe the clinical course of new onset acute systolic heart failure in a patient after liver transplantation.
2. Highlight the importance of preoperative evaluation for cirrhotic cardiomyopathy.
3. Evaluate the role of Arterio-venous (A-V) ECMO as a bridge to recovery in a patient with cirrhotic cardiomyopathy after liver transplant
4. Highlight the high risk of complications from ECMO in post liver transplant patients.
Abstract:
Cirrhotic cardiomyopathy is frequently present in patients with end-stage liver disease awaiting liver transplantation. The marked peripheral vasodilatation of end-stage cirrhosis masks a latent myocardial dysfunction and hence the diagnosis is difficult in the resting state. The stress associated with the procedure can precipitate acute heart failure in the perioperative period. The treatment is usually supportive with gradual resolution of symptoms, however the management of refractory acute heart failure and associated multi-organ involvement from cirrhotic cardiomyopathy can be challenging. Veno-Arterial Extra Corporeal Membrane Oxygenation (VA-ECMO) therapy could be beneficial in this scenario and provide a bridge to recovery. Although the use of ECMO for hepato-pulmonary syndrome following liver transplantation has been described, the use of ECMO for cirrhotic cardiomyopathy has never been studied. We describe the case of a 54-year-old patient with a normal cardiac workup who developed a new onset acute systolic heart failure after a deceased liver transplant. He developed refractory cardiogenic shock with multi-organ failure and was put on VA- ECMO. Despite some improvement in his cardiac function, the patient could not be weaned from ECMO and died 15 days after ECMO placement. To our knowledge, this is the first case describing use of ECMO for post-transplant cirrhotic cardiomyopathy.
Case Description:
A 54-year-old man suffering from alcohol related liver cirrhosis (model for end stage liver disease (MELD) score 28) presented for deceased donor liver transplant. Cirrhosis was complicated with hepatic encephalopathy, ascites, and esophageal varices. He also had hypertension, and non-insulin dependent diabetes mellitus. His preoperative echocardiogram revealed normal size and systolic function of both the right and left ventricles with no regional wall motion abnormalities (ejection fraction 65%). There was no significant valvular abnormality and pulmonary pressures were normal.
The surgical course was complicated by a blood loss of 5.5 liter, for which he received 3 L of plasmalyte, 1L of 5% albumin, 16 units of fresh frozen plasma, 15 units of leucocyte depleted red blood cell, 3 units of leucocyte depleted platelet concentrate, and 3 units of cryoprecipitate. The patient was not extubated at the end of surgery and was admitted to the surgical intensive care unit (SICU) for further management.
In the SICU, his systolic blood pressure (SBP) continued to stay in the range of 90 – 100 mmHg requiring intermittent use of a norepinephrine drip titrated to keep the SBP above 100 mm Hg. He was extubated on postoperative day (POD) 3, after meeting all the necessary criteria. Few hours after extubation the patient developed increased work of breathing with increasing oxygen requirements. Chest X-ray revealed findings consistent with acute pulmonary edema. He received aggressive diuresis with intermittent doses of I.V. furosemide and I.V. chlorothiazide along with continuous positive airway pressure (CPAP) therapy leading to resolution of the episode. On POD 6, he developed a similar episode of acute pulmonary edema and oliguria, requiring escalating doses of furosemide along with an infusion of chlorothiazide with minimal response. A Transthoracic echocardiogram (TTE) showed dilated left and right atria with severely reduced systolic function (EF 25%) and diffuse hypokinesis of the left ventricle (LV), which was new from his preoperative TTE. The right ventricle (RV) appeared dilated with globally reduced function. An Electrocardiogram (EKG) showed prolonged QTc interval (454 ms) which was also a change from the baseline. After discussions with the cardiology team, a dopamine infusion was started at 2.5 mcg/kg/min and titrated to keep SBP above 100 mm Hg. On POD 7, he developed new onset atrial flutter along with delirium and episodes of desaturation requiring re-intubation and mechanical ventilation. Over the course of the next few days, he developed progressively worsening hypotension (requiring multiple inotropes and pressors), and recurrent supraventricular tachyarrhythmias (transitioning later to ventricular tachycardia). A Swan Ganz catheter placed at this time revealed right atrial pressure (RAP) 12 mmHg, right ventricular end diastolic pressure (RVEDP) 15 mmHg, pulmonary artery pressure (PAP) of 31/17 mmHg with mean PAP 21 mmHg and pulmonary capillary wedge pressure (PCWP) 18 mmHg. In view of his worsening renal function, continuous renal replacement therapy (CRRT) was initiated.
After extensive multi-disciplinary discussions and in view of the patient’s worsening cardiogenic shock, a decision was made to initiate VA ECMO. A left femoral 25 Fr drainage cannula (Bio-Medicus, Medtronic, USA) and a left femoral 21 Fr return cannula (Bio-Medicus Medtronic, USA), were used for cannulation and the patient was transferred to the Heart and Vascular Intensive Care Unit (HVICU). ECMO was initiated at a blood flow of 4.3L/min and gas flow of ? at FiO2 of 90%. Despite being placed on ECMO and infusion of inotropes, the LV continued to remain distended with global hypokinesis, and an Impella device was placed. A TTE on POD 22 after clamping ECMO and the Impella device revealed improvement of LV systolic function. The Impella© device was discontinued on POD 26 and another clamp trial showed stable cardiac function and decision was made to wean the patient from ECMO. However, his liver transaminase enzymes started to increase and a liver duplex showed thrombosis of left portal vein and decreased flow in the hepatic arteries. His clinical condition started to worsen requiring re-initiation of inotropic and vasopressor support. His condition did not improve despite multiple transfusions and maximal inotropic and pressor support. After extensive discussions with the family, care was withdrawn, and the patient expired on POD 31.
Discussion:
Cirrhotic cardiomyopathy (CCM) is a spectrum of cardiac impairment characterized by an impaired contractile response to stress, diastolic dysfunction and electrophysiological abnormalities. This disorder has its origin in the cellular and functional changes that accompany end stage liver disease (ESLD), regardless of its etiology.1 Left ventricular ejection fraction (LVEF) at rest has been reported to be normal in patients with CCM.2,3 The reduced preload and afterload secondary to systemic arterial and venous vasodilatation associated with ESLD compensates for both the diastolic dysfunction and impaired contractility.4 During and after liver transplantation, however, there is an immense physiological demand on the recipient’s heart due to significant hemodynamic fluctuations, copious third space losses, and substantial blood loss. When subjected to such stress, the increase in contractility and cardiac output is significantly blunted, and volume and pressure load acutely unveil the previously asymptomatic latent cardiac disease. The resulting cardiac dysfunction negatively affects prognosis and survival rates, and induces the development of other complications like acute kidney injury, acute heart failure, pulmonary edema, life-threatening arrhythmias, infections, and graft failure.5
There is currently no specific treatment for cirrhotic cardiomyopathy. Patients are managed as for heart failure due to other etiologies with diuretics and careful management of their preload and afterload.6,7 ECMO is an established strategy for cardiopulmonary support with increasing use in patients with cardiovascular collapse. Case reports and series have demonstrated successful use of ECMO in patients with severe hepatopulmonary syndrome after liver transplantation to survive the post transplant period, as the outcome is generally favorable with reversal of hypoxemia.14, 15 Although there is no literature available for its use in heart failure resulting from CCM after liver transplantation, we believe ECMO can be used as a bridge in these patients as it is a reversible process, and there appears to be a recovery of functional, structural and electrophysiological abnormalities over time.(reference is at the end of this paragraph. No 5, 8-10 This is reflected in significant improvement in myocardial performance with normalization of systolic response to stress, improvement of diastolic function, and regression of QT prolongation from as early as three months post transplant.5,8-10
However, ECMO is a high-risk intervention with its antecedent complications. The use of ECMO to support patients in the post-transplantation period needs to be weighed against three main risks; anticoagulation, thrombosis and infection. Bleeding complications resulting from anticoagulation used during ECMO have been reported to be manageable even in postoperative period by minimization of heparin infusion rates to target aPTT in the lowest tolerable range (40-60 sec).16 Thrombosis remains a concern but appropriate use of anticoagulation has decreased the risk significantly. Post liver transplant receive immunosuppression and hence are at a higher risk of blood stream infections associated with indwelling devices in the form of ECMO cannulas. There are mechanical complications associated with the use of ECMO, the most notable being LV dilation and acute pulmonary edema. The high flow through the circuit needed to reduce the chance of circuit thrombosis creates a large amount of afterload for the LV to work against, which can commonly lead to LV distention and subsequently pulmonary edema. Strategies such as Impella® placement have been used to assist LV decompression, as was done in our patient. Frequent echocardiograms, daily chest radiographs and close monitoring of hemodynamics can also assist in identifying LV distention and worsening pulmonary edema, and assist in timing LV decompression.
The indications and situations in which ECMO has been tried continues to change, and the use of ECMO for sub-acute and chronic illnesses is now commonplace, as is the use of ECMO in patients with clinical problems such as sepsis, malignancy, and immunosuppression, which were previously regarded as contraindications.11,12 The survival of these patients can be as high as 50% to 75%.13
Although our patient’s cardiac function improved enough to be weaned from ECMO, he developed thrombotic complications in the form of portal venous and hepatic artery thrombosis resulting in graft failure. These complications were likely secondary to stasis resulting from prolonged low flow state while awaiting recovery of cardiac function on ECMO.
In conclusion, although we achieved the primary goal of improving cardiac function with the institution of ECMO, we could not prevent the mortality associated with the failing allograft. The role of ECMO for liver transplant patients who develop cardiac failure from CCM is unclear. ECMO may improve prognosis in select cases when aggressive and early treatment is instituted. More data is needed before institution of ECMO can be recommended as a bridge to recovery in patients who develop acute heart failure from CCM after liver transplantation.