Short- and long-term outcomes for the surgical treatment of acute pulmonary embolism.

OBJECTIVES: Acute pulmonary embolism can be a life-threatening condition with a high mortality. The treatment choice is a matter of debate. The early and late outcomes of patients treated with surgical pulmonary embolectomy for acute pulmonary embolism in a single center were analyzed.
METHODS: All consecutive patients operated on for pulmonary embolism between January 2002 and March 2017 were reviewed. Patient demographics and pre- and postoperative clinical data were retrieved from our patient registry, and risk factors for in-hospital and long-term mortality were identified.
RESULTS: In total, 175 patients (mean age 59±3 years, 50% male) were operated on for acute pulmonary embolism. In-hospital mortality was 19% (34/175). No differences were found when comparing surgery utilizing a beating heart or cardioplegic arrest. Risk factors for in-hospital mortality were age >70 years [odds ratio (OR) 4.8, confidence interval (CI) 1.7-13.1, p=0.002], body surface area <2 m2 (OR 4.7, CI 1.6-13.7, p=0.004), preoperative resuscitation (OR 14.1, CI 4.9-40.8, p<0.001), and the absence of deep vein thrombosis (OR 9.6, CI 2.5-37.6, p<0.001). Follow-up was 100% complete with a 10-year survival rate of 66.4% in 141/175 patients surviving to discharge. Once discharged from hospital, none of the risk factors identified for in-hospital mortality were relevant for long-term survival except the absence of deep vein thrombosis (OR 3.2, CI 1.2-8.2, p=0.019). The presence of malignancy was a relevant risk factor for long-term mortality (OR 4.3, CI 1.8-10.3, p=0.001).
CONCLUSION: Surgical pulmonary embolectomy as a therapy for acute pulmonary embolism demonstrates excellent short- and long-term results in patients with an otherwise life-threatening disease, especially in younger patients with a body surface area >2 m2 and pulmonary embolism caused by deep vein thrombosis. Pulmonary embolectomy should therefore not be reserved as a treatment of last resort for clinically desperate circumstances. ©2018 Dohle K., et al., published by De Gruyter, Berlin/Boston.

Introduction

Pulmonary embolism (PE) is a common clinical condition with a broad variety of clinical presentations, and an age- and race-dependent annual incidence of up to 88/100,000 patients [1]. It is responsible for 12% of all deaths in Europe [2].

As Trendelenburg’s procedure is one of the oldest heart operations and PE was Gibbon’s trigger to invent the heart-lung machine, as the prerequisite for modern heart surgery, PE is an important disease for the cardiac surgeon. Historical results were fatal until Kirschner was successful in 1924. Decades later, mortality remained high despite the support of cardiopulmonary bypass (CPB). Therefore, in the current European guidelines, surgical embolectomy is only recommended in high-risk patients with failed lysis or contraindications to lysis [3]. Although often used in clinically desperate circumstances, current literature demonstrates good short- and long-term results for surgical embolectomy – comparable with those of thrombolytic therapy. This gives rise to a new debate about the role of surgical embolectomy in the treatment of PE [4].

In this retrospective single-center study, we analyzed the early and late outcomes of surgical embolectomy among patients with acute PE, and analyzed predictors for in-hospital mortality and long-term survival.

Patients and methods

Study population and data source

According to our center’s protocol, patients transferred for PE are reviewed by a multidisciplinary team. Patients with massive embolism, hemodynamic instability, postresuscitation status, or failed lysis or contraindications to lysis are referred for surgical embolectomy. Approval from our Institutional Ethics Committee was obtained for this retrospective data analysis (2018-13098-Epidemiologie). The International Classification of Disease codes, tenth revision, were used to identify patients operated on for acute PE from our institutional database. In total, 175 adult patients were operated on for acute PE between January 2002 and March 2017 in our institution. Patients’ demographics, clinical data, and follow-up details were retrieved from our institutional database and medical records. Patients’ demographics, preoperative clinical status, comorbidities and risk factors for PE, surgical strategy and findings, as well as in-hospital and long-term outcomes were analyzed.

Surgical techniques

All patients were given heparin after median sternotomy and cannulated for CPB. Embolectomy was performed using mild hypothermic or normothermic CPB, with or without aortic cross clamp, according to the surgeon’s preference. The main pulmonary artery was opened longitudinally and, if necessary, the incision was extended into the left main pulmonary artery. In some cases, an additional incision was made in the right main pulmonary artery between the ascending aorta and superior vena cava. Clots were extracted under direct vision using forceps and suction. Temporary reduction of CPB flow was occasionally needed for optimal visualization.

Statistical analysis

Statistical computations and Figures 2 and 3 were done using GraphPad Prism version 7.0a for Mac (GraphPad Software, La Jolla, CA, USA), Wizard Pro data analysis version 1.9.7 (Evan Miller, Chicago, IL, USA), and SPSS 22.0 for MAC (SPSS Inc., Chicago, IL, USA).

Normal assumption of continuous variables was validated using the Shapiro-Wilk test. If the assumption did not hold, the Wilcoxon signed-rank test was used. The influence of the identified variables on in-hospital mortality and long-term survival was analyzed with a multiple logistic regression model using the identified covariates. All statistical tests were two-sided with the alpha level set at 0.05 for statistical significance. All frequency data are presented as percentages, and all continuous data as mean±standard deviation. The confidence interval (CI) is 95%.

Results

Patient population and characteristics (Table 1)

A total of 175 adult patients underwent surgical embolectomy for acute PE during the study period. The mean age was 59±17.2 years, and 87 patients (50%) were men. The mean body surface area (BSA) was 2.04±0.253 m2 across all patients. PE was diagnosed with computed tomography (CT) angiography in 151 patients and echocardiography alone in 24 patients. Nearly all the patients had a massive thrombus volume (97%) located centrally or bilaterally in the main pulmonary arteries (94%). Further details are shown in Tables 1 and 2.

Table 1:

Patient characteristics, including predisposing factors for lung embolism, in in-hospital survivors and patients deceased in hospital.

	Total (n=175)	In-hospital survivors (n=141)	In-hospital deaths (n=34)	p-Value
Patient characteristics
Age (years)	59.3±17.2	57.7±16.8	66.3±17.1	0.008
Male	87 (50%)	74 (53%)	13 (38%)	0.136
BSA	2.04±0.25	2.06±0.26	1.96±0.22	0.036
Predisposing factors for PE
Coagulopathy	22 (13%)	20 (14%)	2 (6%)	0.19
Nicotine use	31 (18%)	27 (19%)	4 (12%)	0.311
Oral contraception	9 (5%)	9 (6%)	0 (0%)	0.13
DVT	70 (40%)	66 (47%)	4 (12%)	<0.001
Prior pulmonary embolism	11 (6.3%)	9 (6%)	2 (6%)	0.914
Malignancy	50 (29%)	38 (27%)	12 (35%)	0.334

Significant p-values are marked bold.

Table 2:

Clinical status at the time of presentation, surgical strategy, and operative findings.

	Total (n=175)	In-hospital survivors (n=141)	In-hospital deaths (n=34)	p-Value
Preoperative clinical status
CPR	40 (23%)	19 (13%)	21 (62%)	<0.001
Shock	112 (64%)	10 (7.1%)	11 (32.4%)	<0.001
Respiratory insufficiency	23 (13%)	21 (15%)	2 (6%)	0.163
Failed preoperative lysis	11 (6.3%)	4 (3%)	7 (21%)	<0.001
Surgical findings and surgical strategy
Central or bilateral thrombus	165 (94%)	134 (95%)	31 (91%)	0.384
Massive thrombus volume	169 (97%)	138 (98%)	31 (91%)	0.054
Cardioplegic arrest	103 (59%)	86 (61%)	17 (50%)	0.242
Beating heart	72 (41%)	55 (39%)	17 (50%)	0.242
Re-sternotomy	20 (11%)	12 (9%)	7 (21%)	0.035

Significant p-values are marked bold.

Risk factors for in-hospital mortality

The overall in-hospital mortality was 19% (34/175). The mean age of hospital survivors (HS group) was significantly lower compared to the group of patients who died in hospital (IHD group, 57.7±16.8 vs. 66.3±17.1 years, p=0.008). The mean BSA of the HS group was significantly higher compared to the IHD group (2.06±0.26 vs. 1.96±0.22 m2, p=0.036).

Almost two-third of the patients in the IHD group were under cardiopulmonary resuscitation (CPR) at the time of presentation, which was significantly more compared to the HS group (62% vs. 13%, p<0.001; Table 2). Significantly more patients who had failed previous lysis therapy were found in the IHD group (21% vs. 6.3%, p<0.001). The rate of deep vein thrombosis (DVT) was significantly higher in the HS group (47%) compared to the IHD group (12%, p<0.001; Figure 1). No differences were found regarding the surgical technique used (with or without cardioplegic arrest), or in the size and distribution of the thrombus material.

Figure 1:

In-hospital mortality stratified for age, BSA, preoperative CPR, and DVT.

In a multivariate logistic regression model, age >70 years [odds ratio (OR)=4.8, CI 1.7–13.1, p=0.002], BSA <2 m2 (OR 4.7, CI 1.6–13.7, p=0.004), preoperative resuscitation (OR 14.1, CI 4.9–40.8, p<0.001), and non-DVT-associated lung embolism (OR 9.6, CI 2.5–37.6, p<0.001) were found to be relevant risk factors for in-hospital death (Table 3). The receiver-operating characteristic analysis showed a good fitting of this model [area under curve (AUC)=0.84, Figure 2]. Based on this model, the predicted in-hospital mortality rate for patients older than 70 years, with lower body mass (<2 m2 BSA), without DVT, and post-CPR status was 56%. The predicted in-hospital mortality rate for younger patients (<70 years), with a higher body mass (>2 m2 BSA), with DVT, and without preoperative CPR was only 3.5%.

Table 3:

Multivariate logistic regression model with risk factors for in-hospital mortality.

Risk factor	OR	95% CI	p-Value
Age >70 years	4.8	1.7–13.1	0.002
BSA <2 m2	4.7	1.6–13.7	0.004
Preoperative CPR	14.1	4.9–40.8	0.001
No DVT	9.6	2.5–37.6	0.001

Significant p-values are marked bold.

Figure 2:

AUC of 0.84 demonstrating the good fitting of the chosen model.

Long-term results

The follow-up rate was 100% with a mean follow up time of 4.6±3.3 years. The long-term survival rates of the HS group were 78% at 5 years and 66% at 10 years. Once discharged from the hospital, none of the risk factors identified for in-hospital mortality were relevant for long-term survival except for the absence of DVT (OR 3.2, CI 1.2–8.2, p=0.019) or the presence of malignancy (OR 4.3, CI 1.8–10.3, p=0.001; Figure 3). Approximately one-third of the PE patients without DVT were diagnosed with a malignant tumor. This was significantly more compared to those patients with a DVT (36% vs. 17%, p=0.01). The 10-year survival rate of patients with a DVT and without cancer was 89%.

Figure 3:

Kaplan-Meier survival curves of all patients, and then stratified for patients with or without DVT and with or without malignancy.

Discussion

In a nationwide US inpatient registry for surgical embolectomy after PE, including >2700 patients between 1999 and 2008, the overall mortality was 27.2% [5]. In a meta-analysis including 46 case series with 1300 patients, Stein et al. reported a mortality rate for surgical pulmonary embolectomy of 32% between 1961 and 1985, which declined to 20% between 1985 and 2005 [6]. Although these results look devastating, they should be considered in the context of the preoperative status of these patients assigned to surgical embolectomy with hemodynamic instability in 74% and preoperative cardiac arrest in 32%. Results from a German registry with >1000 patients treated non-surgically, with anticoagulation and thrombolysis alone, demonstrated mortality rates of 65% for patients with cardiac arrest, 25% for patients with cardiogenic shock, and 15% for patients with hypotension [7].

Our results, spanning a time period of 15 years from 2002, with an overall in-hospital mortality of 19%, are very similar to these meta-analysis and registry results. Like in other patient cohorts [6, 7], our in-hospital mortality was significantly higher in patients with cardiac arrest (53%) or cardiogenic shock (10%). By multivariate regression analysis, other significant risk factors could be identified. While age is always associated with more comorbidities and worse outcomes in cardiac surgery, our finding of a BSA of <2 m2 and non-DVT-related PE as risk factors for in-hospital mortality are noticeable.

The paradox of lower mortality and morbidity in obese cardiac surgery patients is known and has recently been demonstrated in a meta- and registry analysis with >500,000 patients [8]. Thus far, no explanations have been proven but according to different hypotheses, higher BSA might reduce the diluting effects caused by extracorporeal circulation. Furthermore, relatively lower blood loss might prevent bleeding and its subsequent complications.

Non-DVT-related PE is often associated with a history of or a newly diagnosed cancer. Different retrospective studies and registries have proved an increased in-hospital mortality for acute PE in patients with cancer [9, 10]. Cancer is therefore a parameter in the PE severity index suggested by the current guidelines [3]. The different in-hospital mortality rates for DVT and non-DVT patients with acute PE might, inter alia, be caused by the natural history of the cancer, which is also demonstrated in our long-term results. Meanwhile, the thrombus architecture and mechanical characteristics of DVT and non-DVT thrombus might differ, as suggested by rare reports about the fibrin network in the surgically removed thrombus after PE in DVT patients [11, 12]. This might influence the technical success of surgical embolectomy and fibrinolytic agents.

According to the current European guidelines, early mortality risk-adapted treatment strategies are encouraged [3]. Primary reperfusion strategies with fibrinolytic agents in intermediate-risk patients showed no significant survival benefit but a significantly increased risk for major bleeding (11.5%), hemorrhagic stroke (2%) [13], and death [14]. Therefore, fibrinolysis is no longer recommended in intermediate-risk patients [15]. In high-risk patients, defined by shock or hypotension, systemic thrombolysis is currently the recommended treatment strategy. Surgical embolectomy is recommended if systemic thrombolysis is contraindicated (previous or current stroke, recent major surgery, or gastrointestinal bleeding) or has failed.

Interestingly, there is no evidence for the superiority of thrombolysis over surgical embolectomy in high-risk or intermediate-high-risk patients, while contemporary results for surgical embolectomy are improving and comparative studies show long-term benefits for surgical embolectomy. In a recently published meta-analysis, including contemporary studies from 1998 until 2017 with 1101 surgical embolectomy patients and a preoperative cardiac arrest rate of 21%, the overall mortality rate was 14% and only 6.8% in patients were without preoperative CPR [16]. In a large retrospective study comparing the short- and long-term outcomes of 2111 patients undergoing thrombolysis (88%) or surgical embolectomy (12%), similar early mortality (15.2% vs. 13.2%) and 5-year survival rates (72.4% vs. 76.1%) were found despite the obviously different morbidity of the two groups and a significantly higher rate of recurrent PE after thrombolysis [17]. Another study comparing the postoperative results of systemic fibrinolysis and surgical embolectomy by single-photon emission CT found similar mortality rates but significantly less diffusion impairment after surgical embolectomy [18]. Other authors found significantly better right ventricular unloading after surgical embolectomy compared to systemic fibrinolysis, as measured using right ventricular diameter and pulmonary artery pressures [19].

With a growing body of evidence for a comparable safety profile, some authors suggest surgical embolectomy as the first-line therapy for patients with acute high- and intermediate-high-risk PE [4]. Like others [20], we see the urgent need for randomized controlled trials comparing the outcomes of surgical embolectomy with the current first-line treatment strategy. As our small retrospective study demonstrated, further differentiation of patients and their risk factors might lead to better patient-tailored treatment strategies. Most probably, surgical embolectomy should no longer be a treatment of last resort reserved only for clinically desperate circumstances.

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