Perioperative Complications and Outcomes of 12 Patients Bridged to Heart Transplantation by Extracorporeal Membrane Oxygenation

doi:10.21203/rs.3.rs-4184890/v1

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Perioperative Complications and Outcomes of 12 Patients Bridged to Heart Transplantation by Extracorporeal Membrane Oxygenation

https://doi.org/10.21203/rs.3.rs-4184890/v1

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Background: Cardiogenic shock (CS) is characterized by end-organ hypoperfusion resulting from low cardiac output. Venous-artery extracorporeal membrane oxygenation (VA-ECMO), is widely used in patients presenting with refractory cardiogenic shock. The decision to use VA-ECMO as a bridge to heart transplantation has become widely accepted as a short-term option. However, complications can develop within weeks, which makes it unsuitable for bridging to transplantation and even affects the prognosis.

Methods：Data were collected from 12 patients who received extracorporeal membrane oxygenation (ECMO) as a bridge to heart transplantation between October 2020 and October 2021. General perioperative characteristics, ECMO-related complications, and posttransplantation survival were summarized.

Results：The 12 patients were male, with an average age of 45.33 years and an average BMI of 22.87 kg/m2. The main primary diseases were myocardial infarction (7 cases), dilated cardiomyopathy (4 cases), and fulminant myocarditis (1 case); the average ECMO maintenance time before transplantation was 14.25 days, the longest preoperative maintenance time was 37 days, the overall ECMO perioperative survival rate was 75.00%, and the 30-day survival rate was 91.67%. The main complications in the perioperative period are gastrointestinal bleeding, distal limb ischemia of the perfusion tube and distal limb ischemia requiring fasciotomy during ECMO maintenance, bleeding after transplantation in the operative area requiring reoperation for bleeding, and poor healing at the ECMO cannulation insertion site.

Conclusion：ECMO as a bridge to heart transplantation is a feasible treatment option for patients with end-stage heart failure and refractory cardiogenic shock. We should be aware of the complications related to ECMO management.

heart transplantation

extracorporeal circulation support

ECMO

complications

outcomes

Heart failure is a clinical disease with high morbidity and high mortality rates and is associated with repeated hospitalizations (1–4). Acute heart failure is associated with a rapid worsening of clinical symptoms and signs (5, 6), including new-onset heart disease and acute exacerbations of chronic heart failure. Cardiogenic shock is the most serious clinical manifestation of acute heart failure, which is characterized by severe circulatory failure and is accompanied by hypotension and organ hypoperfusion in addition to a high mortality rate (7). Patients with cardiogenic shock should be identified and treated as soon as possible. In addition, mechanical circulatory support (MCS) effectively improves organ perfusion in patients with refractory cardiogenic shock (7). Among them, VA-ECMO plays an important role in end-organ perfusion support in patients with cardiogenic shock. In addition to cardiopulmonary function support, VA-ECMO can improve systemic organ perfusion (8) and is considered to be organ function support for refractory cardiogenic shock patients in the ICU transitioning to rehabilitation, those with a ventricular assist device or who have undergone heart transplantation, etc., which can be used to assess outcomes (9, 10). There have been case reports on the use of VA-ECMO as a bridge to heart transplantation worldwide (11), but there are few descriptions of the perioperative maintenance process. In this article, we describe the patients who received VA-ECMO as a bridge to heart transplantation in our hospital in the previous year and discuss the impact of VA-ECMO as a bridge to heart transplantation on perioperative complications.

Patient selection: A total of 12 patients who received VA-ECMO as a bridge to heart transplantation in the critical care unit of a tertiary medical center between 2020 and 2021 were retrospectively analyzed (Fig. 1). The general conditions of the 12 patients who received ECMO as a bridge to transplantation and the clinical complications and outcomes in the transplantation patients during the perioperative period were summarized.

ECLS procedure: Cannulas were placed percutaneously by vessel puncture, guidewire placement, and serial dilation (Seldinger technique), and access was permitted via femoral vessels, which will be described in detail in the Results section. A 16- to 18-Fr arterial cannula and 21- to 24-Fr venous cannula were used depending on the patient’s blood vessel diameter. Distal perfusion cannulas (DPC) were routinely placed because of the poor distal artery flow after peripherally placed cannulas. A Swan-Ganz catheter was inserted to measure the pulmonary vascular resistance index (PVRI) before the operation, and SvO2 greater than 70% of the internal jugular vein was maintained during ECLS. The ECLS system was implanted under full heparinization, and heparin titration was performed with bedside measurement of activated partial thromboplastin time (aPTT, target value 1.5 to 2.5 times normal) every 4 h (12). Postcardiac transplantation management and antirejection medical therapy were based on the 2010 guidelines for the care of heart transplantation recipients (13).

Definition

1. Refractory cardiogenic shock: Shock and organ insufficiency caused by low cardiac output despite optimal drug support (14).

Perioperative definition: the period from VA-ECMO maintenance to the time when patients were discharged from the ICU and can receive rehabilitation after heart transplantation.

Discharged from ICU standard: No organ function support is required (blood pressure is stable without vasoactive drugs, and the patient has ventilator independence, stable kidney and liver functions, with no potential infection)

Discharged from cardiac surgery: the concentration of tacrolimus (FK-506) in the blood was stable; the wound healed well; there was no potential risk of infection; and regular outpatient follow-up was achieved.

As shown in Table 1, all 12 patients were male, with an average age of 45.33 years and an average BMI of 22.87 kg/m2. The primary diseases distributed among the patients were myocardial infarction (7 cases), and all of the myocardial infarction patients underwent coronary artery angiography (CAG), which showed 3-vessel coronary artery disease (CAD), and the culprit vessel was reperfused; dilated cardiomyopathy (4 cases); and myocarditis (1 case). The average ECMO maintenance time before transplantation was 14.25 days, and the longest preoperative maintenance time was 37 days. The left ventricular ejection fraction (LVEF) was measured using the biplanar Simpson technique, and the LVEF ranged from 12–32%, with an average LVEF of 23.4%. Among them, 2 patients were treated with intra-aortic balloon pumps (IABP) combined with VA-ECMO as a bridge to heart transplantation. Allograft heart transplantation was successfully performed in all 12 patients, and the average aortic cross-clamp time in the operation was 57.5 min. Nine patients survived, 3 patients died, and the overall survival rate was 75.00%. Among them, Patient 3 was considered to have primary graft failure and ultimately died of multiple organ failure on the 7th day after transplantation; Patient 7 died of a bloodstream infection and septic shock on the 67th day after the operation; and Patient 9 had a mediastinum infection and suddenly died from an ascending aorta rupture (intraoperatively, the incision was 0.5 cm above the anastomosis, and the mediastinal infection eroded the blood vessels). The total perioperative ECMO survival rate was 75.00%, and the 30-day survival rate was 91.67%.

Table 1

Patient characteristics.
	Primary disease	sex	age	BMI(kg/m2)	Demographics and comorbidity	Previous CAG
Patient 1	myocardial infarction	Male	45	22.03	smoking	3-vessel CAD
Patient 2	fulminant myocarditis	Male	57	27.04	smoking	CAG negative
Patient 3	dilated cardiomyopathy	Male	37	21.71		CAG negative
Patient 4	myocardial infarction	Male	37	23.67	smoking	3-vessel CAD
Patient 5	myocardial infarction	Male	59	21.25	diabetes	3-vessel CAD
Patient 6	myocardial infarction	Male	45	21.22	smoking	3-vessel CAD
Patient 7	myocardial infarction	Male	35	27.68	diabetes	3-vessel CAD
Patient 8	dilated cardiomyopathy	Male	46	27.78		CAG negative
Patient 9	dilated cardiomyopathy	Male	59	20.76		CAG negative
Patient 10	dilated cardiomyopathy	Male	28	18.36		CAG negative
Patient 11	myocardial infarction	Male	65	22.49	diabetes	3-vessel CAD
Patient 12	myocardial infarction	Male	31	20.41		3-vessel CAD

Table 1

(continued)
	ECMO mode	Catheter Site		Catheter size		DPC size	Preoperative ECMO maintenance time	ECMO + IABP	Left ventricular unloading
	ECMO mode	Venous cannula (femoral vein)	Artery cannula (femoral artery)	Venous cannula	Artery cannula	DPC size	Preoperative ECMO maintenance time	ECMO + IABP	Left ventricular unloading
Patient 1	V-A ECMO	Left side	Right side	24Fr	18Fr	8.5Fr	2 days	No		Newly diagnosed HF
Patient 2	V-A ECMO	Right side	Left side	21Fr	15Fr	8Fr	14 days	No	preoperation	Newly diagnosed HF
Patient 3	V-A ECMO	Right side	Left side	20Fr	16Fr	8Fr	6 days	No		Known chronic HF
Patient 4	V-A ECMO	Right side	Left side	24Fr	18Fr	8.5Fr	37 days	Yes		Newly diagnosed HF
Patient 5	V-A ECMO	Right side	Right side	22Fr	16Fr	8Fr	26 days	No		Newly diagnosed HF
Patient 6	V-A ECMO	Left side	Left side	24Fr	16Fr	8Fr	24 days	No		Newly diagnosed HF
Patient 7	V-A ECMO	Right side	Left side	22Fr	15Fr	8Fr	4 days	Yes		Newly diagnosed HF
Patient 8	V-AV ECMO	Right side	Left side	22Fr	16Fr	8Fr	11 days	No	preoperation	Known chronic HF
Patient 9	V-A ECMO	Right side	Right side	22Fr	16Fr	8Fr	21 days	No		Already on the waiting list
Patient 10	V-A ECMO	Left side	Right side	21Fr	16Fr	8Fr	3 days	No		Already on the waiting list
Patient 11	V-AV ECMO	Left side	Right side	22Fr	16Fr	8Fr	15 days	No		Newly diagnosed HF
Patient12	V-A ECMO	Right side	Right side	24Fr	18Fr	8Fr	8 days	No		Newly diagnosed HF

Table 1. (continued)

	Preoperative Intubation time	Preoperative Renal replacement	EF Calculated By echocardiography	PVRI（wood unit）	Intraoperative aortic cross-clamp time (minutes)
Patient 1	6 days		28%	3	67 min
Patient 2	14 days	yes	15%	4.3	72 min
Patient 3	6 days	yes	20%	3.8	52 min
Patient 4	51 days	yes	21%	2.7	48 min
Patient 5	26 days	yes	28%	3.5	65 min
Patient 6	24 days	yes	27%	3.2	43 min
Patient 7	11 days	yes	12%	4.8	56 min
Patient 8	11 days	yes	24%	4.2	67 min
Patient 9	30 days	yes	20%	4.5	66 min
Patient 10	3 days	yes	26%	5.5	49 min
Patient 11	15 days	yes	28%	4.4	51 min
Patient 12	12 days	yes	32%	3.8	54 min

HF=Heart Failure; DPC= distal perfusion cannulas

Among the 12 patients who underwent VA-ECMO bridged to heart transplantation (Table 2), the femoral vessels were the preferred access points in the patients, and different catheter sizes were selected according to the target vessels’ diameters, as were the DPC catheters. Lower extremity ischemia (LEI) occurred in 3 patients, and 1 of the 3 patients with LEI even required lower extremity fasciotomy (LEF). Except for the ECMO cannulation site, the bleeding manifestations we observed were mainly related to gastrointestinal bleeding, and 4 patients had postoperative bleeding requiring reoperation, but postoperative bleeding did not appear to be necessarily associated with patient outcomes. In addition to monitoring, ECMO-related complications mainly manifested as poor healing at the cannulation insertion site (5 cases). Average total length of ICU stay: 52.25 days. It seemed that poor healing at the insertion site was not related to catheter size or comorbidity.

Table 2

Perioperative ECMO-related complications and outcomes in patients bridged to transplantation.
	Complications	ICU-stay length	Outcomes	predischarge echocardiographic data
	Complications	ICU-stay length	Outcomes	LVEF (%)	TAPSE (mm)
Patient 1	LEI + LEF	52 days	Discharge	62	15
Patient 2	Gastrointestinal bleeding	38 days	Discharge	65	13
Patient 3	/	14 days	Died			Died because of PGD, CS, result in MOF at 7 days post-HT
Patient 4	LEI	79 days	Discharge	55	13
Patient 5	Reoperation for bleeding	105 days	Discharge	60	14
Patient 6	Insertion site poor healing + Gastrointestinal bleeding + Reoperation for bleeding	61 days	Discharge	69	17
Patient 7	LEI + Insertion site poor healing	67 days	Died			Died of a blood infection after pressure ulcer debridement
Patient 8	Insertion site poor healing	27 days	Discharge	66	14
Patient 9	Insertion site poor healing + Gastrointestinal bleeding + Reoperation for bleeding	70 days	Died			Died of an ascending aorta rupture after mediastinum infection
Patient 10	Reoperation for bleeding	27 days	Discharge	55	12
Patient 11	Insertion site poor healing	49 days	Discharge	68	16
Patient 12	Gastrointestinal bleeding	38 days	Discharge	65	15
(LEI = lower extremity ischemia; LEF = lower extremity fasciotomy; PGD = primary graft dysfunction; CS = cardiogenic shock; MOF = multiple organ failure)

Before the patients were discharged, echocardiography was used to assess LVEF and tricuspid annular plane systolic excursion (TAPSE), and the average LVEF was 62.78% and TAPSE was 14.3 mm.

In the past few decades, VA-ECMO has been increasingly developed and applied and is widely used in clinical practice. Its function of supporting clinical hemodynamics and assisting gas exchange is important for clinical diagnosis, treatment, and organ recovery. VA-ECMO increases survival and has great benefits (15, 16). At present, VA-ECMO has become an important rescue measure for critically ill patients, especially those with refractory cardiogenic shock who are transitioning to recovery or have undergone transplantation (16).

In this paper, 12 patients whose heart function could not be recovered after VA-ECMO could not be weaned from ECMO and were directly bridged to heart transplantation, and we found that the postoperative survival rate was 75.00%. It has been reported in the literature that the survival rate in patients receiving short-term VA-ECMO as a bridge to heart transplantation can reach 50% (10), and the prognosis is not significantly different from survival after heart transplantation in common recipients (17–19). In their series, the 1-year survival rate of 13 patients who received ECMO support after transplantation (1 with postoperative shock, 8 with cardiomyopathy, and 4 with acute myocardial infarction) as a bridge to transplantation was 51%. However, the duration of ECMO support before transplantation has not been described. Our data focused on the peri-operative time in those patients, and none of them died before undergoing heart transplantation, which was an amazing result compared to that of Poptsov’s study (20), despite having a much smaller sample of patients. In addition, the 30-day survival rate was 91.67%, which was higher than previously reported values.

The average maintenance time of preoperative ECMO support in our case series was 14.25 days. There have been reports in the literature suggesting that during the bridging process, the maintenance time of VA-ECMO ranges from 7 to 14 days. However, the longest maintenance time in our patients was 37 days, which is longer than that reported in previous studies (20–23).

The main perioperative ECMO-related complications in 12 patients bridged to transplant included gastrointestinal bleeding, limb ischemia with or without fasciotomy, bleeding after transplantation in the operative area that requires reoperation to stop the bleeding, and poor healing around the puncture wound after ECMO was removed, which was common after weaning from ECMO support, and it has been reported that these complications might affect the outcomes (24). However, in our case series, we did not find a relationship between the complications. Therefore, due to the small sample size, it remains unclear whether perioperative complications are associated with the outcome.

In conclusion, as the utilization of temporary MCS devices, including IABP, percutaneous ventricular assist devices (pVADs) and ECMO, has become increasingly common, the proportion of patients bridged directly to heart transplantation has exponentially increased. Compared to other MCS devices, ECMO provides a more stable flow for CS patients and is widely used in patients with unstable cardiac electrical activity (25). Although we did not have any experience with other MCS devices bridged to heart transplantation, the outcomes in patients with ECMO were satisfactory. VA-ECMO should be regarded as a bridge to emergency heart transplantation. However, ECMO-related complications are also our focus.

Ethics approval and consent to participate

This study have been performed in accordance with the Declaration of Helsinki, and was approved by the Medical Research Ethics committee of the First Affiliated Hospital, Zhejiang University School of Medicine. Written informed consent was obtained from all individual participants or from the legal representative (i.e., spouse or first-degree relatives) if the participants deceased.

Consent for publication

Not applicable.

Availability of data and materials

The datasets generated during and analyzed during the current study are not publicly available due to the privacy of individuals that participated in the study but are available from the corresponding author on reasonable request.

Competing interest

None of the authors declare competing interests.

Funding

This study is not funded by any grant.

Authors' contributions

Dr. Xing Fang , Dr. Jueyan Yan and Dr. Tong Li wrote the main manuscript text and Dr. Zhipeng Xu and Dr. Jingchen Zhang prepared figures and tables. All authors reviewed the manuscript.

Acknowledgements

Not applicable.

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No competing interests reported.

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Perioperative Complications and Outcomes of 12 Patients Bridged to Heart Transplantation by Extracorporeal Membrane Oxygenation

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1 Introduction

2 Materials and Methods

3 Results

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