Comparative myocardial protection of endoaortic balloon versus external clamp in minimally invasive mitral valve surgery

Abstract

Aims 

Minimally invasive mitral valve surgery leads to shorter postoperative recovery time, cosmetic advantages and significant pain reduction compared with the standard sternotomy approach. Both an external aortic clamp and an endoaortic balloon occlusion can be used to manage the ascending aorta and the myocardial protection. In this study, we aimed to compare these two strategies in terms of effectiveness of myocardial protection and associated early postoperative outcomes.

Methods 

We investigated the retrospective records of prospectively collected data of patients treated by minimally invasive mitral valve surgery from March 2014 to June 2019. A total of 180 cases (78 in the external aortic clamp group and 102 in the endoaortic balloon clamp group) were collected. A propensity weighting analysis was adopted to adjust for baseline variables.

Results 

The endoaortic balloon clamp presented higher EuroSCORE II (higher reoperative surgery rate). The intra- and postoperative data were similar between the two groups: the postoperative troponin-I levels, peak of serum lactates and rate of myocardial infarction were also comparable. The endoaortic clamp group recorded longer operative, cardiopulmonary bypass and cross-clamp times. The external clamp group showed a higher rate of postoperative atrial fibrillation and conduction block.

Conclusions 

In experienced centers, the use of the endoaortic balloon clamp is safe, reproducible and comparable to the external aortic clamp regarding the effectiveness of myocardial protection: its employment might facilitate minimally invasive mitral valve surgery.

Introduction

The origin of minimally invasive mitral valve surgery (MIMVS) dates to the mid-1990s and has evolved rapidly.^1–5 MIMVS facilitates postoperative recovery and results in cosmetic advantage, but it requires dedicated training and a learning curve.^2–15 Literature data demonstrate the reliability, reproducibility, and safety of MIMVS, which has becomes a valid alternative to conventional sternotomy.^1,3,4,16 One of the main challenges of MIMVS lies in achieving optimal myocardial protection.⁸ Ultimately, two methods for ascending aortic control and clamping are possible in MIMVS: the external aortic clamp (EAC), applied through a right chest access, and the endoaortic catheter balloon clamp (EABC), introduced from the femoral artery into the ascending aorta and deployed just above the sinotubular junction.^6,7,17 In the EAC technique, cardioplegia is delivered into the aortic root through a needle and aortic root venting is achieved through the same line.⁷ The EABC system consists of a triple lumen catheter, the central lumen delivering the cardioplegia and venting the aortic root.⁷ The EABC device has been recently re-introduced after being further optimized. The EABC is a different concept of clamp because it consists of an endoaortic occlusion. The EAC allows the aorta to be clamped with greater confidence of closure. Instead, the EABC, if not well supervised, could have a partial occlusion, and consequently it could determine a partial coronary perfusion. The intraoperative control of the correct endoaortic clamp function should be performed by all the members of the surgical team: the surgeon has the direct vision of any heart contraction, the anesthesiologist by monitoring of the radial pressure and the perfusionist by monitoring of the cardiopulmonary bypass pressure. To date, only a few reports have compared the EAC and the EABC techniques in a single-center investigation, and none has specifically focused on issues related to intraoperative myocardial protection.⁶ Our objective was to contribute to this debate and evaluate the differential effectiveness of myocardial protection, and its potential fallouts on early postoperative outcomes, between these two techniques.

Methods

Study population

We retrospectively analyzed the prospectively collected data of patients who received standardized MIMVS performed by three surgeons (A.A., P.G.P. and A.A.) at our Institution Humanitas Gavazzeni in Bergamo (Italy) during the March 2014–June 2019 period. All consecutive patients who underwent MIMVS for mitral valve dysfunction (included both regurgitation and stenosis) were included, irrespective of its etiology (degenerative, rheumatic, infectious-endocarditis, secondary ischemic, congenital or other); all types of repair/replacement were included. We also included reoperation or patients undergoing combined procedures such as tricuspid valve repair, closure of interatrial septal defects or of the left atrial appendage. All patients were free from significant coronary artery disease.

Preoperative, intraoperative and early postoperative data were obtained from hospital records and included in a dedicated electronic database. We retrieved information from 180 patients: 78 patients received MIMVS using the EAC and 102 patients had the EABC.

All patients underwent preoperative coronary angiography, chest X-ray, transthoracic or transesophageal echocardiography and a computer tomography scan (CT-scan) of the entire aorta. We routinely performed cardiac enzymes, especially troponin-I (TNI), before and after the operation. In the same way, postoperative electrocardiography (ECG) data and complications were collected in the database and analyzed.

To evaluate myocardial protection, we considered the Fourth Universal Definition of Myocardial Infarction:¹⁸ elevation of TNI values >10 times the 99th percentile of the upper reference limit in patients with normal baseline TNI values or, in patients with elevated preoperative TNI, postoperative TNI rise >20%, and any of the following criteria: new Q pathological waves; angiographically documented new coronary occlusion; imaging evidence of new loss of viable myocardium or new regional wall-motion abnormality distinctive for an ischemic aetiology.¹⁸ We also evaluated certain additional parameters regarding hemodynamic stability, namely the use of vasopressors/inotropic drugs in the intensive care unit (ICU) at 0, 6 and 24 h; the difficulty of weaning from cardiopulmonary bypass (CPB) or the use of an intra-aortic balloon pump (IABP); the peak in intraoperative and postoperative lactates levels. We also considered postoperative ventricular fibrillation or arrhythmia, length of ICU stay and mortality rate.

We performed a propensity weighting analysis to obtain two more confrontable groups based on the baseline variables.

Patients’ informed consent for the surgical procedure was obtained. All data collected in this study were managed anonymously and the local review board approved the study. Individual patient consent to be included in the study was waived due to its retrospective nature.

Surgical technique

Our surgical MIMVS technique has been previously described.^19–21 Briefly, a 4–6 cm right anterolateral mini-thoracotomy at the fourth or third intercostal space (working port) was performed. A 30° camera or an Endocamaleon camera (Karl Storz Inc., Tuttlingen, Germany), introduced through a second port, was adopted for video-assistance.¹⁹ An additional port was utilized for cardiotomy suction and carbon dioxide insufflation.¹⁹ Peripheral cardiopulmonary bypass (CPB) was established by the cannulation of the femoral artery and vein and conducted under hypothermia.¹⁹

In patients operated with the employment of the EAC, the Chitwood or Cygnet clamp was used with the application of a costal retractor at the working port. Cardioplegia was administered through an aortic root needle.¹⁹ In patients treated with EABC, the endoaortic balloon (Intraclude; Edwards Lifesciences Inc., Irvine, CA, USA) was adopted for ascending aortic endo-clamping, administration of cardioplegia and root venting; it was advanced retrogradely from the right femoral artery under transesophageal echocardiography guidance.¹⁹ Myocardial protection was obtained by cold crystalloid cardioplegia (HTK solution, Custodiol, Franz Köhler Chemie GmbH, Bensheim, Germany) in all cases.¹⁹

The choice of using EAC or EABC was the surgeons’ decision and based on preoperative evaluation of the patient through CT-scan: the presence of ascending aortic diameter >35 mm was considered a relative contraindication to the EABC, whereas >40 mm was an absolute contraindication; a right common femoral artery diameter <8 mm was a contraindication to EABC; a scrupulous assessment of the presence and extension of arterial and mitral calcification was also performed.¹⁹ Reoperative surgery represented a preferential indication for EABC.

Anesthetic management consisted of general anesthesia, the positioning of a dual-lumen endotracheal tube for the exclusion of the right lung and the percutaneous cannulation of the right internal jugular vein for venous drainage in addition to right femoral venous cannulation.¹⁹

Statistical analysis

Data were presented as mean ± standard deviation (continuous variables) or as percentages (categorical variables). Intergroup comparison was conducted using the two-tailed Student's t-test after verification of normal distribution of data (Kolmogorov–Smirnoff test), and using the Chi-square test. The alpha level was 0.05.

To assess the impact of EABC vs. EAC on the outcomes and to adjust for confounding, a doubly robust method that combines regression model with inverse probability treatment weighting (IPTW) by propensity score was applied.²² In our study, a total of 11 covariates including preoperative characteristics were used in the model. The full list of these covariates is listed in Table 1, and Table 2, Supplemental Digital Content, https://links.lww.com/JCM/A507. Using the estimated propensity scores as weights, an inverse probability weighting (IPW) model was used to generate a weighted cohort.²³C-statistics were calculated to ascertain the validity of the propensity score.

Table 1 - Preoperative baseline characteristics

Variables	EAC (N = 78)	EABC (N = 102)	P-value
Age [years, mean (SD)]	60.38 (13.83)	63.04 (12.42)	0.178
Gender (F, %)	27 (34.6)	50 (49.0)	0.074
BMI [mean (SD)]	25.44 (4.42)	24.97 (4.44)	0.486
BSA [m2, mean (SD)]	1.85 (0.21)	1.78 (0.22)	0.036
EF [%,mean (SD)]	58.03 (5.87)	56.05 (7.49)	0.056
PAPs [mmHg, mean (SD)]	35.60 (6.95)	37.81 (9.89)	0.094
Creatinine level [mg/dl, mean (SD)]	1.04 (0.77)	0.91 (0.23)	0.112
Peripheral vascular disease (%)	36 (46.2)	65 (63.7)	0.028
Diabetes (%)	6 (7.7)	5 (4.9)	0.645
EuroSCORE II [mean (SD)]	1.26 (1.07)	1.97 (2.32)	0.012
NYHA (%)			0.017
I	1 (1.3)	6 (5.9)
II	53 (67.9)	47 (46.1)
III	22 (28.2)	41 (40.2)
IV	2 (2.6)	8 (7.8)
AF (%)	24 (30.8)	38 (37.3)	0.454

AF, atrial fibrillation; BMI, body mass index; BSA, body surface area; EABC, endoaortic balloon clamp; EAC, external aortic clamp; EF, ejection fraction; PAPs, pulmonary artery pressure systolic.

Statistical analysis was performed using cobalt packages of R software (version 4.2.1; R Foundation for Statistical Computing, Vienna, Austria).

Results

Preoperative

Table 1 shows the baseline characteristics of the two cohorts. The Mean European System for Cardiac Operative Risk Evaluation (EuroSCORE) II was significantly higher in the EABC group (1.26 ± 1.07 vs. 1.97 ± 2.32 for the EAC vs. EABC cohort, respectively; P-value 0.006). We treated more REDO-operations in the EABC group: 19 patients (18.6%) vs. 1 patient (1.3%) in the EAC group.

Intra- and postoperative

Table 2 presents the intraoperative characteristics of the two cohorts.

Table 2 - Intraoperative characteristics

Variables	EAC (N = 78)	EABC (N = 102)	P-value
Operative time [min, mean (SD)]	227.22 (56.44)	254.77 (42.21)	<0.001
CPB time [min, mean (SD)]	138.53 (31.89)	147.00 (33.80)	0.089
Clamp time [min, mean (SD)]	95.79 (19.67)	108.59 (26.41)	<0.001
Cardioplegia [ml, mean (SD)]	1682.47 (434.53)	1651.54 (364.00)	0.612
CPB T [minimum value °C, mean (SD)]	32.47 (4.42)	31.74 (1.53)	0.132
Peak of lactates [mmol/l, mean (SD)]	1.82 (0.87)	2.16 (1.24)	0.043

CPB, cardiopulmonary bypass; EABC, endoaortic balloon clamp; EAC, external aortic clamp; T, temperature.

We conducted isolated mitral valve repair in most of the cases (Table S1, Supplemental Digital Content, https://links.lww.com/JCM/A507).

The total operative time and cross-clamp time were significantly longer in the EABC group before propensity score adjusting (Table 2). The intraoperative lactate’ peak was higher in the EABC group in the unadjusting analysis (Table 2). Conversely, we noticed no meaningful differences regarding the intraoperative variables between the two matched groups, including CPB and aortic clamp times, total operative time and nadir CPB temperature (Table 2).

The operative mortality rates were similar in the two groups (Table 3). The mean peak postoperative TNI value in the EAC and EABC groups was, respectively, 8225.9 ± 18808.5 ng/l and 6710.5 ± 8411.8 ng/l (P = 0.52, Table 3). The rate of postoperative acute myocardial infarction is similar in the two cohorts (unmatched: EAC 4% vs. EABC 1%; Table 3) and there was no difference in the use of IABP between the two groups (P = 0.88; Table 3). The rate of utilization of one or two inotropic drugs in EABC patients was respectively 72.5% and 13.7%. Similarly, in the EAC group, one or two inotropic drugs were adopted respectively in 64.1% and 20.5% of patients. The rate of any cardiac adverse events was significantly higher in the EAC group (P = 0.002). Such a difference was essentially driven by a higher rate of atrial tachyarrhythmias (postoperative atrial fibrillation, AF) and brady-arrhythmias (atrioventricular block with or without need for permanent pacemaker implantation). The rate of MI was similar among groups in all comparisons (Table 3). No endoclamp balloon failure was registered in the EABC group. Six patients of the EABC group were converted to median sternotomy due to the follow complications: circumflex coronary artery occlusion; bleeding of the left atrium; adverse anatomy to perform a mitral valve substitution with a mini-invasive approach; impossibility to well positioning the endoclamp; difficult and impossible cannulation of the femoral artery; pleural adhesions and important pulmonary bullous emphysema. No conversion to median sternotomy was performed in the EAC group.

Table 3 - Postoperative characteristics

Variables	Overall series			Doubly robust adjustment‡
	EAC (N = 78)	EABC (N = 102)	P-value	Odds ratio	95% CI	P-value
TNI [ng/l, mean (SD)]	8225.97 (18808.53)	6710.55 (8411.77)	0.52§	−1995.62§	2741.20§	0.47§
Peak lactate [mean (SD)]	4.55 (3.07)	4.44 (2.65)	0.80	−0.10§	0.42§	0.81§
Mechanical ventilation time [h, mean (SD)]	14.14 (33.06)	14.42 (19.41)	0.94	−3.40§	6.11§	0.58§
ICU stay [h, mean (SD)]	70.28 (64.08)	71.70 (71.14)	0.89	−0.48§	9.86§	0.96§
EF (%)	55.56 (6.58)	54.55 (5.49)	0.27	0.43§	1.09§	0.70§
Hospital stay [days, mean (SD)]	11.86 (16.05)	10.86 (4.62)	0.56	−9.56§	9.04§	0.29§
Cardiac complications (%)
Atrial tachyarrhythmia	17 (21.8)	20 (19.6)
MI	3 (3.8)	1 (1.0)	0.02	0.37	0.19–0.71	0.003
MI + arrhythmia	1 (1.3)	2 (2.0)
Brady + PM	16 (20.5)	10 (9.8)
Operative mortality (%)	2 (2.6)	0 (0.0)	0.36	N.A.	N.A.	N.A.
IABP (%)	2 (2.6)	3 (2.9)	1.00	0.70	0.11–4.62	0.71
First inotropic drug at 6 h (% of patients)	16 (32.0)	30 (41.1)	0.40	1.05	0.48–2.33	0.90

Brady, bradyarrhythmias; CI, confidence interval; EABC, endoaortic balloon clamp; EAC, external aortic clamp; EF, ejection fraction; IABP, intra-aortic balloon pump; ICU, intensive care unit; MI, myocardial infarction; PM, pacemaker; TNI, troponin-I.

^‡Reference for the events: EAC cohort.

^§Linear regression has been expressed as standard regression coefficient, standard error and P-value.

The postoperative general complications (neurological, kidney, infectious and vascular) are similar between the two groups: the rate of postoperative stroke in EAC and EABC groups was respectively 1.2% and 1.9%; an acute kidney injury (AKI) affected 11.5% and 5.8% of EAC and EABC patients, respectively; one patient for each groups had an urinary tract infection (UTI); one patient from the EAC group developed early postoperative endocarditis and one of the EABC patients manifested a systemic infection; in the EAC group one patient had an intraoperative aortic dissection while two EABC patients developed a deep venous thrombosis (DVT) and one a femoral arterial-venous fistula at the peripheral access. The total hospital stay was comparable in both the EAC and EABC (Table 3).

As shown in Table 2, Supplemental Digital Content, https://links.lww.com/JCM/A507 and Figs. 1 and 2, all the covariates of the weighted cohort resulted as balanced between groups. The C-statistics of the propensity score was 0.68 (Fig. 1, Supplemental Digital Content, https://links.lww.com/JCM/A507). Under the doubly robust estimation framework, the regression models demonstrated that EABC was associated with a significantly lower risk of cardiac complications [odds ratio (OR) 0.37; 95% confidence interval (CI), 0.19–0.71; P = 0.003]. No significant differences were observed between the two groups with regard to the other outcomes of interest assessed under the doubly robust estimation framework (Table 3).

Fig. 1: The figure shows the distributional balance between the two groups. The C-statistic of the propensity score was 0.68.

Fig. 2: All the covariates of the weighted cohort resulted balanced between groups.

Discussion

Our study indicated that the use of the EABC seems to provide essentially similar myocardial protection and to associate with similar postoperative outcome than the EAC. EAC recipients tended to show a higher rate of atrial tachyarrhythmias (AF) and conduction block than EABC recipients.

The advantage of the EABC consists of the direct delivery of cardioplegia into the aortic root via of the device itself avoiding an extra purse-string suture in the ascending aorta and an extra port.^14,25

The first manufactured EABC was described in animal reports and was released in 1998 by Heartport.²⁶ Since then, other competing devices have been developed until the latest Edwards Lifesciences (Irvine, CA, USA) Intraclude© device that was routinely used in our series of patients.²⁶

One of the reasons limiting the use of the EABC is the need for the surgeon's procedural proficiency.^10,19 A cardiothoracic center can be defined as an ‘experienced center in EABC-MIMVS’ if >50 procedures have been performed, as the safe employment of this device entails a learning curve to allow effective use of the EABC in MIMVS with the same level of proficiency as an EAC.^10,14,27 All patients included in the present study were consistently operated on after the end of our learning curve. As a comparison, our EABC-EAC unmatched and matched cohorts did not identify statistically meaningful differences in main outcome measure. EABC is particularly advantageous in minimally invasive reoperative surgery, as it allows the need to control the aorta by separation of the surrounding adhesions. Herein, the EABC group showed a greater average EuroSCORE II due to a higher rate of reoperative surgery. We also considered the EABC to be extremely versatile, as previously underlined.^14,25 Our study and literature data consolidate the use of EABC in REDO patients.^14,25

During MIMVS, the quality of myocardial protection through peripheral access is a main key to procedural success; nonetheless, it has been scarcely investigated. Although some previous studies have compared the overall clinical outcomes among EAC and EABC recipients, none has specifically focused on myocardial protection-related outcomes. Some articles reported the rates of perioperative myocardial infarction, but this outcome was not systematically provided.²³ In some of these papers, the postoperative level of myocardial enzymes (CK and TNI) did not differ between the two techniques.^23,24 Herein, we considered the TNI level only as a biomarker of myocardial injury, according to the recent definition of postoperative MI. Concordantly with these reports, the peak postoperative TNI values in our study did not significantly differ between the two matched and unmatched cohorts, and no significant differences occurred in the rate of postoperative MI.^28,29 We did not limit our analysis to the TNI level but we specifically evaluated a panel of myocardial protection-related outcomes, like Lebon et al.^8,18 However, this report presented a retrospective study and compared myocardial protection between MIMVS and the standard sternotomy approach.⁸ Conversely, we compared two different strategy of aortic management (EAC and EABC) in MIMVS. We also performed a matched cohort analysis to eliminate potential bias due, for example, to preoperative left ventricular function/dimension or weight of the operation. Similar to the results presented by Lebon et al.,⁸ in our series the patients treated using the EABC showed a higher use of noradrenaline as the first inotropic drug than the EAC group (matched cohorts: P-value = 0.02). This is probably due to a longer CPB and aortic clamp time in EABC patients (matched cohorts: P-value = 0.95 and 0.49, respectively) that could determine a systemic inflammatory response syndrome with hyperdynamic circulation and vasodilatation.^8,30 Similarly to literature data, we registered a longer CPB, cross-clamp time, and total operative time in the EABC group than the EAC. However, this was not significantly different.^11,12,31,32

The debate regarding the best strategy to use, either the EAC or EABC, is still open. Data from the literature have shown inconclusive results about the possible differences in perioperative outcomes.⁷ Recent papers have described a greater rate of vascular postoperative complications when the EABC was adopted, in particular a higher risk of iatrogenic aortic dissection and lower limb ischemia, but with no significant differences.^6,7,11 However, the Port Access International Registry reported a reduction in the risk of iatrogenic aortic dissection, from 1.3% to 0.8%, when the EABC was used. This was thanks to the adoption of more flexible probes and a better adherence to the preoperative imaging evaluation.⁷ Curiously, in our series, we found one postoperative aortic lesion (aortic dissection) in the EAC group, and two DVT and one femoral arterial-venous fistula at the peripheral access in the EABC groups. In the first report, the EABC group registered more postoperative strokes than the EAC.³¹ More recent studies have described no difference in mortality and stroke rate between the two groups thanks to experienced centers and better patient preoperative assessment regarding anatomy and clinical history.^{13,24,29,31,32}

In our study, postoperative atrial fibrillation (FA) and conduction block alteration with the need for a PM appeared more frequently in the EAC group. We have hypothesized that EABC means a no-touch technique with respect to the sinus node and left atrial roof, although, the literature lacks confirmation of this.

Study limitation

There are a few study limitations. The most important is the retrospective/observational design of the study with its inherent biases. Moreover, although the decision to use the EABC or EAC is based on the accuracy of the preoperative patient evaluation, it is, ultimately, the surgeon's choice. Due to the single-center nature of the study, the sample size is limited, particularly in the matched cohorts. For example, the considerable rate of postoperative MI in the matched cohorts compared with the unmatched cohorts should be interpreted from this perspective. For the same reason, cardiac complications were analyzed in aggregate form. Nonetheless, the single-center design ensures uniformity of protocols with respect to myocardial protection, conduction of CPB and management of minimally invasive surgery technologies.

Conclusion

In MIMVS experienced centers, myocardial protection and early postoperative outcomes are similar in EAC and EABC groups. The EABC is safe, effective, and more versatile than the EAC.

Conflicts of interest

There are no conflicts of interest.

Dr Anselmi discloses an association with Edwards Lifesciences Inc. (proctoring and speaker fees).