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Reverse Takotsubo Cardiomyopathy During Liver Transplantation: Expert Commentary

  • Kelly G. Ural
    Correspondence
    Address correspondence to Kelly Ural, MD, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA 70121.
    Affiliations
    Ochsner Clinic Foundation, Department of Anesthesiology and Perioperative Medicine, New Orleans, LA

    The University of Queensland Medical School, Ochsner Clinical School, New Orleans, LA
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  • Jay E. Trusheim
    Affiliations
    Ochsner Clinic Foundation, Department of Anesthesiology and Perioperative Medicine, New Orleans, LA

    The University of Queensland Medical School, Ochsner Clinical School, New Orleans, LA
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Published:December 16, 2022DOI:https://doi.org/10.1053/j.jvca.2022.12.010
      TAKOTSUBO CARDIOMYOPATHY (TC), otherwise known as “broken-heart syndrome,” is a condition of which most anesthesiologists are aware; however, the Case Conference by Vannucci et al.
      • Vannucci A
      • Kurian D
      • Kacha A
      • et al.
      Reverse Takotsubo stress cardiomyopathy during liver transplantation.
      points to a variation that is less familiar. Reverse Takotsubo cardiomyopathy (rTC) differs from traditional TC in that hypokinesis and/or akinesis is observed in the basilar portion of the left ventricle (LV) in contrast to the apical hypokinesis seen in the traditional form. In this case report, a patient with no prior cardiac history became acutely hypotensive and had severe depression of her LV function just prior to reperfusion during liver transplantation. Intraoperative transesophageal echocardiography (TEE) demonstrated basal akinesis and apical hyperkinesis. One might assume the patient had a traditional myocardial infarction (MI) given the high troponin scores of 478 ng/L and elevated brain natriuretic peptide of 50,000 pmol/L; however, cardiac catheterization ruled out obstructive coronary disease. With a combination of diuresis and inotropic therapy, the patient recovered to an ejection fraction of 43% at the time of discharge. It is important for anesthesiologists to become familiar with this condition so it can be recognized promptly and treated.

      Pathophysiology

      Takotsubo cardiomyopathy is an acute, reversible myocardial injury characterized by regional LV dysfunction. The exact mechanism is not fully understood, but it has been proposed that excessive endogenous or exogenous catecholamines present during stress states lead to microvascular dysfunction and coronary artery spasm.
      • Pelliccia F
      • Kaski JC
      • Crea F
      • Camici PG.
      Pathophysiology of Takotsubo syndrome.
      The levels of catecholamines in patients with TC have been found to be up to 3 times higher than in patients presenting with acute MI, and elevated levels of norepinephrine have been found in the coronary sinus in some patients with TC. These catecholamine surges may cause direct effects on myocardiuminducing arrhythmias, cellular injury, and mitochondrial dysfunction also referred to as “catecholaminergic stunning”.
      • Lyon AR
      • Citro R
      • Schneider B
      • et al.
      Pathophysiology of Takotsubo syndrome: JACC state-of-the-art review.
      Postmenopausal women are at an increased risk due to an increased sympathetic drive and reported higher baseline levels of anxiety, stress, and sleep disturbances. They also have higher levels of neuropeptides, such as Neuropeptide Y, which becomes activated during stress and can have a direct effect on microvascular dysfunction.
      • Medina de Chazal H
      • Del Buono MG
      • Keyser-Marcus L
      • et al.
      Stress cardiomyopathy diagnosis and treatment: JACC state-of-the-art review.
      Given the higher risk in this population, a lack of estrogen also has been considered a significant risk factor. Estrogen produces atrial natriuretic peptide, which is thought to be cardioprotective against the adverse effects of catecholamine surge.
      • Ueyama T
      • Hano T
      • Kasamatsu K
      • Yamamoto K
      • Tsuruo Y
      • Nishio I.
      Estrogen attenuates the emotional stress-induced cardiac responses in the animal model of Tako-tsubo (Ampulla) cardiomyopathy.
      It is unclear why some patients have a stress response strong enough to trigger TC and others do not. General anesthesia does not appear to blunt this response. On the contrary, surgery and general anesthesia are known risk factors.
      • Lyon AR
      • Citro R
      • Schneider B
      • et al.
      Pathophysiology of Takotsubo syndrome: JACC state-of-the-art review.
      Agarwal et al. published a systematic review of TC cases and found numerous factors in the perioperative period that may contribute to the development of this condition. They also pointed out that it is possible for volatile anesthetics to confer some cardioprotective effects.
      • Agarwal S
      • Bean MG
      • Hata JS
      • et al.
      Perioperative Takotsubo cardiomyopathy: A systematic review of published cases.
      More research is needed to understand the role these agents play. This patient was on multiple vasoactive infusions prior to the event. The case report states, “...circulation was supported with.…phenylephrine, vasopressin, norepinephrine to maintain mean arterial pressures greater than 65 mmHg.” Whether this patient's event occurred due to exogenous catecholamines, endogenous catecholamines, or a combination of both, remains unknown.

      Diagnosis

      In the typical form, TC involves apical hypokinesis and/or akinesis and basal hyperkinesis.
      • Medina de Chazal H
      • Del Buono MG
      • Keyser-Marcus L
      • et al.
      Stress cardiomyopathy diagnosis and treatment: JACC state-of-the-art review.
      On echocardiography, the heart mimics the shape of a Japanese fishing pot used to trap an octopus called “takotsubo.” The presentation in this case report varied in that the patient had the reverse—apical hyperkinesis and basal akinesis. This basal type of stress cardiomyopathy, or rTC, is rare, ranging from 1%-to-23% of all TC cases.
      • Awad HH
      • McNeal AR
      • Goyal H.
      Reverse Takotsubo cardiomyopathy: A comprehensive review.
      The triggering events and clinical features of rTC are similar to typical TC, and the management is similar. Diagnosis can be aided by using the International Takotsubo Diagnostic Criteria (InterTAK Diagnostic Criteria) or Revised Mayo criteria.
      • Ghadri JR
      • Wittstein IS
      • Prasad A
      • et al.
      International expert consensus document on Takotsubo syndrome (Part I): Clinical characteristics, diagnostic criteria, and pathophysiology.
      • Ghadri JR
      • Wittstein IS
      • Prasad A
      • et al.
      International expert consensus document on Takotsubo syndrome (Part II): Diagnostic workup, outcome, and management.
      • Prasad A.
      Apical ballooning syndrome: An important differential diagnosis of acute myocardial infarction.
      When comparing patients with TC to those with a typical MI, patients with TC are more likely to be female , have a preceding triggering event, and have an absence of ST-segment depression.
      • Ghadri JR
      • Cammann VL
      • Jurisic S
      • et al.
      A novel clinical score (InterTAK Diagnostic Score) to differentiate takotsubo syndrome from acute coronary syndrome: Results from the International Takotsubo Registry.
      Despite being thought of as reversible and, therefore, benign, there are substantial risks. Takotsubo cardiomyopathy can lead to LV outflow tract obstruction (LVOTO) and mitral regurgitation, given the hypercontractile basal segment of the LV. This can lead to other severe complications, including cardiogenic shock, with a 4%- to-5% in-hospital mortality.
      • Lyon AR
      • Citro R
      • Schneider B
      • et al.
      Pathophysiology of Takotsubo syndrome: JACC state-of-the-art review.
      Making the diagnosis of TC or one of its variants can be very difficult, especially without the use of TEE. Both can result in significant troponin elevation, elevated brain natriuretic peptides, and wall motion abnormalities. One potential differentiation between the 2 pathologic processes is the specific electrocardiogram changes seen. The ST depressions are common in acute coronary syndrome but uncommon in TC. The electrocardiogram changes with TC usually involve ST elevation, t-wave inversion, and QT prolongation, although this is not a ubiquitous feature. The distinction between these 2 disease states can be very beneficial since the management of the 2 conditions varies.

      Use of TEE in Liver Transplant

      The authors have focused much of the discussion around whether TEE should be used routinely in liver transplant patients, highlighting that “…this complication may go unrecognized if TEE monitoring is not adopted.…” The Society for the Advancement of Transplant Anesthesia recently released a position paper stating the benefits of TEE in liver transplant to guide real-time, rapid diagnosis and guide treatment, with a safety profile similar to cardiac surgical patients.
      • De Marchi L
      • Wang CJ
      • Skubas NJ
      • et al.
      Safety and benefit of transesophageal echocardiography in liver transplant surgery: A position paper from the Society for the Advancement of Transplant Anesthesia (SATA).
      Given that the diagnosis of Takotsubo is often difficult to make, an echocardiogram may not be the panacea; however, an echocardiogram can be extremely helpful in diagnosing specific wall motion abnormalities and ongoing management. It has been noted that LVOTO and systolic anterior motion of the mitral valve can occur in 14%-to-25% of patients.
      • Medina de Chazal H
      • Del Buono MG
      • Keyser-Marcus L
      • et al.
      Stress cardiomyopathy diagnosis and treatment: JACC state-of-the-art review.
      This is important to recognize because inotropic agents can lead to decreased filling and increased contractility, worsening the obstruction and cardiogenic shock. LVOTO, acute coronary syndrome, and TC may all appear very similar on other routine intraoperative monitors, but can be more readily differentiated with the routine use of intraoperative TEE.
      TEE also can be beneficial in diagnosing complications during venovenous bypass (VVB). VVB has been used in liver transplantation to decompress the surgical field and reduce the hemodynamic effects of inferior vena caval clamping. The use of VVB varies among leading transplant centers. Although VVB has potential benefits, complications can occur. Some of the complications that can directly affect cardiac output include hypothermia, air emboli, thrombotic emboli, infections, and bleeding.

      Treatment

      There are no randomized trials supporting any one specific treatment. The authors of this case report provided supportive therapy, which is the suggested approach given most patients will have a quick recovery of their cardiac function within a few weeks. Both the American College of Cardiology and the European Society of Cardiology recommend supportive care with the management of specific complications. In severe cases, the early use of mechanical circulatory support can be considered a bridge to recovery.
      • Lyon AR
      • Citro R
      • Schneider B
      • et al.
      Pathophysiology of Takotsubo syndrome: JACC state-of-the-art review.
      It is important to determine if there is the presence of LVOTO. In cases of LVOTO, it is important to reduce heart rate and maintain ventricular filling. If no LVOTO is present, drugs with positive inotropic action can be beneficial.

      Conclusion

      Reverse Takotsubo Cardiomyopathy is an acute cardiac condition that results in transient wall-motion abnormalities. Prognosis depends on prompt recognition and treatment. Anesthesiologists must remain vigilant and have a high index of suspicion if echocardiography supports the diagnosis.

      Conflict of interest

      None.

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      Linked Article

      • Reverse Takotsubo Stress Cardiomyopathy During Liver Transplantation
        Journal of Cardiothoracic and Vascular Anesthesia
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          Takotsubo cardiomyopathy (TC), also known as stress-induced cardiomyopathy or “broken heart syndrome,” is characterized by an acute, reversible ventricular wall motion abnormality.1 Typical TC involves apical hypokinesis/akinesis and basal hyperkinesis, but anatomic variants have been described, including a midventricular akinesis/hypokinesis and a basal wall motion abnormality, referred to as “reverse TC” (rTC).1 This is a rare form of TC that has been reported to have distinct clinical and diagnostic criteria.
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