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\begin{document}

\title{FAST MYOCARDIAL RECOVERY ENSURED BY THE COMBINED USE OF V-A ECMO and
IMPELLA CP IN CARDIOGENIC SHOCK RELATED TO A PHEOCHROMOCYTOMA CRISIS}



\author[1]{Andrea Montalto}%
\author[2]{Francesca Nicolo'}%
\author[2]{Vincenzo Polizzi}%
\author[2]{Marina Comisso}%
\author[2]{Francesco Musumeci}%
\affil[1]{San Camillo Forlanini Hospital}%
\affil[2]{Affiliation not available}%


\vspace{-1em}



  
  \date{March 14, 2025}


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\selectlanguage{english}
\begin{abstract}
Pheochromocytoma is a rare catecholamine-secreting tumor derived from
chromaffin cells in the adrenal glands. A pheochromocytoma `crisis'
(PCC) can cause haemodynamic instability and end-organ damage or
dysfunction. An excessive stimulation of cardiac myocytes could lead to
myocardial damage with cardiogenic shock (CS). Use of mechanical
circulatory support (MCS) might find an indication in this scenario as a
bridge to myocardial recovery. We present the case of a patient
successfully supported with ECMO (ExtraCorporeal Membrane Oxygenation)
combined with IMPELLA CP heart pump (Abiomed Danvers, MA), for left
ventricular (LV) unloading. MCS was used to favour myocardial recovery
and avoid cardiac remodeling.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Pheochromocytoma related cardiomyopathy could be lead to a refractory CS
for that a rescue procedure with an Extracorporeal Life Support (ECLS)
application, such as ECMO, to sustain the circulation and the organ
perfusion giving time to the myocardium for complete recovery, is
mandatory. A few cases of patients suffering from
pheochromocytoma-induced CS requiring MCS have been previously reported
in literature {[}1{]}, but no case approached with a combined use of
ECMO and Impella (for LV unloading). We describe the first successful
treatment of a pheochromocytoma-induced CS with the combined use of
peripheral V-A ECMO and IMPELLA CP, with subsequent complete and fast
recovery of the myocardial function.

\textbf{Case Report:}

A 28-year old female was admitted to our Hospital with ventricular
arrhythmia, hypotension and respiratory failure secondary to pulmonary
oedema. Blood pressure was 70 / 40 mmHg with heart rate being 130 beats
/ min and significant ST elevation in V1-V3 leads. Despite inotropic and
vasoconstrictor support (noradrenaline 0.05 \selectlanguage{greek}μ\selectlanguage{english}g/kg/min and dobutamine 10
\selectlanguage{greek}μ\selectlanguage{english}g/kg/min), the echocardiogram revealed a poor biventricular function
(left ejection fraction {[}EF{]} \textless{} 25\%). Blood test
documented elevated troponin-I levels (54,7 ng/mL). Because of the
worsening hemodynamic instability and metabolic acidosis, mechanical
ventilation was started and a~V-A ECMO device was implanted through the
surgical cannulation of the right femoral artery (Return, 17 French
BIO-MEDICUS \textsuperscript{TM} cannula) and the right femoral vein
(Access, 21 French Multi--Stage BIO-MEDICUS\textsuperscript{?} cannula).
A 9 French reperfusion cannula was distally inserted in the main femoral
artery to prevent limb ischemia. Therefore, the unloading of the LV was
obtained by inserting an IMPELLA-CP, through the left femoral artery. A
trans-aortic 2,5 L/m flow was obtained. Heparin was continuously
administrated to maintain activated clotting time between 150 and 200
sec. An emergency coronary angiography detected patent coronary
arteries. An endomyocardial biopsy was also performed to exclude acute
myocarditis. The urinary catecholamine levels were several times higher
than normal\textbf{;} Epinephrine 2980 \selectlanguage{greek}µ\selectlanguage{english}g/day (normal range2-14 \selectlanguage{greek}µ\selectlanguage{english}g/day);
Norepinephrine 3876 \selectlanguage{greek}µ\selectlanguage{english}g/day (normal range 230-120 \selectlanguage{greek}µ\selectlanguage{english}g/day); Homovanillic
acid 75 mg/day (normal renage \textless{}15 mg/day); Vanilmandelic acid
85,5 mg/day (normal range\textless{}8 mg/day). A subsequent abdominal
computed tomography revealed the presence of a 5 cm nodular lesion
within the left adrenal gland {[}Fig. 1{]}, highly suggestive for the
diagnosis of pheochromocytoma. A pharmacological therapy comprehensive
of alpha- and beta-blockade was therefore started. A very fast recovery
was observed and the weaning from ECMO was started after only 24 hours
of full support; the patient was discontinued from ECLS on day 4. The
IMPELLA-CP was then switched to 1,5 L/m flow, on day 5. On day 6, it was
safely removed \textbf{{[}Fig 2{]}} and a completely recovery of EF was
assessed by echocardiographic evaluation (EF \textgreater{} 60\%). The
patient underwent adrenalectomy 3 weeks after the initial emergency
presentation and the histological examination confirmed the diagnosis of
pheochromocytoma\textbf{.} The post-procedural course was uneventful and
10 days later the patient was discharged from our department.

\textbf{Discussion}

The mechanisms underlying the biventricular dysfunction following PCC
are not well established. Some proposed mechanisms include coronary
spasm with corresponding myocardial focal necrosis {[}2{]}, direct
cellular toxicity by increasing intracellular calcium concentration
{[}3{]}, damage induced by reactive oxygen species {[}4{]}, and
myocardial stunning due to receptor desensitization or down-regulation
{[}5{]}. The ECMO is the largely used device for the management of CS,
but highly increases the afterload of the LV worsening the pulmonary
edema and triggering inflammatory reactions {[}6{]} whose combined
effects If not interrupted, can ultimately lead to a chronic dilated
cardiomyopathy. An effective strategy could be achieved by using an
axial flow pumps such as the Impella system that ensures unloading of
the LV throughout the cardiac cycle, decrease total mechanical work and
myocardial oxygen demand, while lowering WS and improving subendocardial
coronary blood flow. Hekimian et al reported several cases managed by
ECMO implantation {[}7{]}, while Riester et
al.{[}\textsubscript{8}described Impella device implantation as first
choice. Our patient was haemodinamically instable, so ECMO implantation
was immediately performed, rather than Impella implantation alone. Our
case highlights the importance of combined treatment in these patients
to achieve an early recovery. As reported, we had significant
improvement in ventricular EF after only 24 hours of MCS. Weaning from
ECMO was started after 48 hours, allowing ECMO removal within 4 days.
The weaning from the IMPELLA has been slightly postponed ensuring
support in the early stages of ECMO removal. After only 6 days from the
implant, the IMPELLA was removed and a complete recovery of both
ventricles was observed. These findings suggest that LV unloading by
Impella support in addition to V-A ECMO may be particularly effective in
ensuring rapid recovery of myocardial function, following
catecholamine-mediated cardiomyopathy.

\textbf{Conflict of interest:} none declared.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Hekimian G, Kharcha F, Bre\selectlanguage{english}chot N, Schmidt M, Ghander C, Lebreton G,
  Girerd X, Tresallet C, Trouillet JL, Leprince P, Chastre J, Combes A,
  Luyt CE. Extracorporeal membrane oxygenation for
  pheochromocytoma-induced cardiogenic shock. \emph{Ann. Intensive
  Care}2016; 6:117\emph{.}
\item
  Simons M, Downing SE. Coronary vasoconstriction and catecholamine
  cardiomyopathy. \emph{Am Heart J} 1985; 109(2):297--304.
\item
  Opie LH, Walpoth B, Barsacchi R. Calcium and catecholamines: relevance
  to cardiomyopathies and significance in therapeutic strategies.\emph{J
  Mol Cell Cardiol} 1985; 17(Suppl 2):21--34.
\item
  Costa VM, Carvalho F, Bastos ML, Carvalho RA, Carvalho M, Remia\selectlanguage{english}o F.
  Contribution of catecholamine reactive intermediates and oxidative
  stress to the pathologic features of heart diseases. \emph{Curr Med
  Chem} 2011;18(15):2272--314.
\item
  Rosenbaum JS, Billingham ME, Ginsburg R, Tsujimoto G, Lurie KG,
  Hoffman BB. Cardiomyopathy in a rat model of pheochromocytoma.
  Morphological and functional alterations. \emph{Am J Cardiovasc
  Pathol} 1988;1(3):389--99.
\item
  Tscho\selectlanguage{english}pe C, Van Linthout S, Klein O, Mairinger T, Krackhardt F, Potapov
  EV, Schmidt G, Burkhoff D, Pieske B, Spillmann F. Mechanical Unloading
  by Fulminant Myocarditis: LV-IMPELLA, ECMELLA, BI-PELLA,and PROPELLA
  Concepts. \emph{J Cardiovasc Transl Res} 2019; 12:116--123.
\item
  Hekimian G, Kharcha F, Bre\selectlanguage{english}chot N, Schmidt M, Ghander C, Lebreton G,
  Girerd X, Tresallet C, Trouillet JL, Leprince P, Chastre J, Combes A
  and Luyt CE. Extracorporeal membrane oxygenation for
  pheochromocytoma-induced cardiogenic shock. \emph{Ann. Intensive
  Care}2016; 6:117.
\item
  Riester A, Weismann D, Quinkler M, Lichtenauer UD, Sommerey S,
  Halbritter R, Penning R, Spitzweg C, Schopohl J, Beuschlein F, Reincke
  M. Life-threatening events in patients with pheochromocytoma.\emph{Eur
  J Endocrinol} 2015; 173(6):757--64.
\end{enumerate}

\textbf{Legends:}

\textbf{Figure 1:} Image of abdominal computed tomography showing the
presence of a nodular lesion of 5 cm on the left adrenal gland.

\textbf{Figure 2:} Visualization of the progressive steps of weaning
from ECMO (red line) and IMPELLA (blue line). POD: post operative day.\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/figure-1--300-dpi/figure-1--300-dpi}

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\includegraphics[width=0.70\columnwidth]{figures/figure-2-600-dpi/figure-2-600-dpi}

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