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Department of Cardiovascular Surgery, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, Chiba, JapanDepartment of Cardiovascular Surgery, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, JapanDepartment of Cardiovascular Surgery, Toranomon Hospital, Minato-ku, Tokyo, Japan
In minimally invasive aortic valve replacement via a right minithoracotomy for patients with significant aortic insufficiency, optimal cardioplegia delivery procedures remain controversial. This study aimed to describe and evaluate endoscopically assisted selective cardioplegia delivery in minimally invasive aortic valve replacement for aortic insufficiency.
Between September 2015 and February 2022, 104 patients (mean age, 66.0 ± 14.3 years) with moderate or greater aortic insufficiency underwent endoscopically assisted minimally invasive aortic valve replacement at our institutions. For myocardial protection, potassium chloride and landiolol were systemically administered before aortic crossclamping, and cold crystalloid cardioplegia was delivered selectively to the coronary arteries using step-by-step endoscopic procedures. The early clinical outcomes were also evaluated.
Eighty-four patients (80.7%) had severe aortic insufficiency, and 13 patients (12.5%) had aortic stenosis and moderate or greater aortic insufficiency. A regular prosthesis was used in 97 cases (93.3%), and a sutureless prosthesis was used in 7 cases (6.7%). The mean operative, cardiopulmonary bypass, and aortic crossclamping times were 169.3 ± 36.5, 102.4 ± 25.4, and 72.5 ± 21.8 minutes, respectively. No patients underwent a conversion to full sternotomy or required mechanical circulatory support during or after surgery. No operative deaths or perioperative myocardial infarctions occurred. The median intensive care unit and hospital stays were 1 and 5 days, respectively.
Endoscopically assisted selective antegrade cardioplegia delivery is safe and feasible for treating minimally invasive aortic valve replacement in patients with significant aortic insufficiency.
Cardioplegia delivery can be complicated in minimally invasive AVR for significant AI due to the unavailability of antegrade delivery via the ascending aorta and limited surgical access. Our step-by-step endoscopically assisted selective cardioplegia delivery is a safe and feasible method for such conditions.
Minimally invasive aortic valve replacement (AVR) is often performed using antegrade long-interval crystalloid cardioplegia.
is necessary. Furthermore, there is no standardized cardioplegia delivery method for minimally invasive AVR in patients with AI. Retrograde cardioplegia carries the risk of coronary sinus injury, which is difficult to repair via a minithoracotomy.
The coronary ostia, especially the right coronary ostium, is often difficult to identify and cannulate securely under direct vision through a minithoracotomy. Blind cannulation may risk coronary artery injury or insufficient cardioplegia delivery to the patient.
We performed endoscopic minimally invasive AVR using endoscopically assisted selective antegrade cardioplegia for patients with moderate or greater AI. The present study describes our endoscopically assisted cardioplegia delivery technique; assesses its technical feasibility, safety, and effectiveness; and evaluates its perioperative and postoperative clinical outcomes.
Patients and Methods
Study Design, Patients, and Outcomes
This study was a multicenter, retrospective review of consecutive patients with moderate or greater AI who underwent endoscopic minimally invasive AVR between September 2015 and February 2022. The study was approved by the Institutional Review Board of the Tokyo Bay Urayasu Ichikawa Medical Center (Number 766, May 27, 2022), Toranomon Hospital (Number 2044, June 22, 2022), and Juntendo University Hospital (Number E22-0267, August 17, 2022). All operations were performed or supervised by a single surgeon (M.T.) using the same approach and cardioplegia protocol (selective antegrade cardioplegia alone) at 3 different hospitals: Tokyo Bay Urayasu Ichikawa Medical Center (since September 2015), Toranomon Hospital (since June 2019), and Juntendo University Hospital (since December 2021). The AI grade was determined by quantitative or semiquantitative measurements on preoperative echocardiography. In some cases with less than moderate AI, selective antegrade cardioplegia after regular antegrade cardioplegia was used to achieve or maintain cardiac asystole. We excluded those cases using a combination of regular antegrade and selective antegrade cardioplegia.
We collected data from our institutional cardiac surgery database and patients' medical records. Outcome measures included perioperative mortality, perioperative myocardial infarction, peak postoperative creatine kinase-MB (CK-MB) and troponin levels, postoperative use of vasopressors or inotropic agents for more than 24 hours, and postoperative left ventricular ejection fraction (LVEF) on predischarge echocardiography. Perioperative myocardial infarction was defined according to the presence of at least 2 of the following criteria: (1) postoperative CK-MB of 100 mg/L or troponin T of 3.0 mg/L, (2) postoperative development of new pathologic Q waves as indicated by electrocardiogram (>0.03 seconds), and (3) a new regional left ventricular or right ventricular wall motion abnormality on echocardiography. Operative mortality was defined as death within 30 days or in-hospital mortality. Continuous data were presented as mean ± standard deviation or median, and categorical variables were presented as percentages and frequencies.
Preoperative Assessment and Patient Selection
All patients underwent preoperative computed tomography angiography (CTA) and routine preoperative examinations. On CTA, the ascending aorta was carefully assessed for its intrathoracic position, angle, size, and presence of calcified and atheromatous disease. Arterial and venous access routes were also carefully assessed to rule out atheromatous, sclerotic, or anomalous diseases. Coronary arteries were routinely assessed using coronary CTA or interventional coronary angiography for their ostial location and size, and the presence of stenotic lesions.
We carefully selected patients for endoscopic minimally invasive AVR to avoid the negative impacts of its shortcomings on surgical outcomes. Our absolute contraindications for surgical intervention included heavily calcified ascending aorta, ascending aorta dilatation greater than 45 mm, and acute aortic regurgitation with cardiogenic shock. Relative contraindications were active endocarditis, severe left ventricular dysfunction, severe pulmonary dysfunction, poor peripheral arterial access, renal insufficiency not tolerating contrast CTA, chest deformity, and a history of right thoracotomy.
Approach and establishment of cardiopulmonary bypass
The patient was placed in a partially left lateral position. A right minithoracotomy was performed with a 4- to 5-cm skin incision in the right anterior or anterolateral position. The location of the minithoracotomy was determined on the basis of the CTA findings. The second intercostal anterior approach was selected for the vertical aorta, and the third intercostal anterolateral approach was selected for the horizontal aorta (Figure 1). A soft-tissue retractor was placed without sacrificing the right internal thoracic artery. A rib spreader was not used routinely; however, in some cases with a very narrow intercostal space, a rib spreader was used for a few minutes after performing a minithoracotomy to widen the intercostal space (ICS) sufficient to pass the prosthetic valve. A 5.5-mm port was placed in the ICS, one rib lower than the main incision for a 5-mm 4K endoscopy (Karl Storz). Both 30° and 45° scopes were used. A carbon dioxide line was placed through a small hole in the fifth ICS, and the thoracic cavity and pericardial space were filled with carbon dioxide during surgery. These 2 small holes were used to insert chest tubes at the end of surgery. We occasionally placed another 5.5-mm port in the intercostal space, 1 rib higher than the main incision for the left-hand instruments when the main incision was very narrow.
A 2- to 3-cm oblique incision was made above the right inguinal crease. A purse-string suture was then placed in the femoral artery and vein. After heparinization, femoral venous and arterial cannulation was performed using the Seldinger technique and transesophageal echocardiogram (TEE) guidance. If any of the descending thoracic, abdominal, or iliac arteries showed significant atheromatous disease on CTA, the right axillary artery was selected instead of the femoral artery.
After establishing a cardiopulmonary bypass, the pericardium was opened and retracted. The venting tube was placed into the left ventricle through the main incision and right superior pulmonary vein.
The pericardial reflection was dissected behind the ascending aorta at the level of the upper edge of the right pulmonary artery to pass a crossclamp. Immediately before aortic crossclamping, 20 mEq potassium chloride and 50 mg landiolol were systemically administered to reduce myocardial oxygen consumption. Then, the distal ascending aorta was crossclamped using a transthoracic Chitwood clamp (Scanlan International, Inc). After aortic crossclamping, a transverse aortotomy was performed, a cell saver sucker was inserted into the aortic root to empty all the blood, the anterior proximal aortic wall was lifted with a sucker, and the right coronary ostium was visualized using an endoscope. Cardioplegia was subsequently delivered directly into the right coronary artery with a 9F 3.0 mm 90° coronary perfusion cannula (Sorin Group Italia Srl). The malleable shaft was slightly bent to match the angle of the right coronary artery. Subsequently, the proximal aortic wall was lifted with a right coronary perfusion cannula, the cell saver sucker was withdrawn, the left coronary ostium was visualized using endoscopy, and the cardioplegia was delivered directly to the left coronary artery with an 11F, 3.5 mm, 135° coronary perfusion cannula (Sorin Group Italia Srl). A 6-inch DLPTM Coronary Ostia Cannulae (Medtronic), a universal type with a silicon soft tip, was used for the short left main trunk (Figure 2). These step-by-step procedures are illustrated in Figure 3 and Video Abstract.
We used cold (4 °C) modified St Thomas 2 cardioplegia solution, in which 4 g mannitol and 4 mEq/L potassium chloride were added to 500 mL of commercially available St Thomas 2 solution. We administered 30 mL/kg as the first dose and 15 mL/kg as the additional dose of the cardioplegia solution when cardiac electric activity was observed or 60 minutes after the first dose.
Valve replacement and cardiopulmonary bypass weaning
After achieving adequate cardiac arrest, the aortic valve cusps were excised, and the prosthesis was implanted with a pledgeted noneverting or everting mattress sutures. A knot pusher or Cor-knot automated fastener (LSI Solutions) was used to tie the sutures.
The aortotomy was closed with a combination of a horizontal mattress and running sutures. Those sutures were started from both ends of the aortotomy and held by 2 tourniquets at the middle of the aortotomy. The aortic root vent was not placed, and the heart was de-aired from the left ventricular vent and untied aortotomy suture line by filling the heart and inflating the lungs before unclamping the aorta. We placed a ventricular wire on the anterior wall of the right ventricle guided by the endoscopy after unclamping the aorta if the pacing is necessary. We removed air further from the aortotomy line by loosening the tourniquets holding the aortotomy sutures. Then, the aortotomy sutures were tied after confirming complete de-airing on TEE, and cardiopulmonary bypass was discontinued.
Postoperative exams and follow-up
Serum CK-MB and troponin T levels were serially measured until they peaked out. Postoperative echocardiography was performed before discharge and 6 months after surgery.
Patient demographic data, baseline data, and preoperative echocardiographic characteristics are shown in Table 1. We have performed 760 cases of surgical AVR, including combined operations, from September 2015 to February 2022. Of those, 226 (29.7%) were minimally invasive surgeries via right minithoracotomy. The study cohort included 104 patients, of whom 84 were male (80.8%) with a mean age of 66.0 ± 14.0 years. Their mean Society of Thoracic Surgeons score was 1.9% ± 1.8%. Eighty-eight patients (84.6%) had severe AI, 16 patients (15.4%) had moderate AI, and 11 patients (10.6%) had AS and AI. Twenty-six patients (25.0%) had nontricuspid aortic valve, including unicuspid valve in 1 patient (1.0%), bicuspid valve in 23 patients (22.1%), and quadricuspid valve in 2 patients (1.9%). Five patients (4.8%) had coronary artery anomalies, originating from the right coronary artery from the left aortic sinus of Valsalva in 2 patients (1.9%) and from the coronary artery above the sinotubular junction in 3 patients (2.9%).
All values are presented as mean ± standard deviation or absolute number (%). NYHA, New York Heart Association; COPD, chronic obstructive pulmonary disease; PCI, percutaneous coronary intervention; GFR, glomerular filtration ratio; STS, Society of Thoracic Surgery.
In all cases, cardiac asystole was successfully obtained and maintained with selective antegrade cardioplegia only. The intraoperative variables are summarized in Table 2. All patients successfully underwent minimally invasive AVR without conversion to sternotomy. None of the patients required mechanical circulatory support for weaning off cardiopulmonary bypass. A standard bioprosthetic or mechanical prosthesis was implanted without an automated suture fastening device in 88 patients (81.5%) and with an automated suture fastening device in 13 patients (12.0%). A sutureless bioprosthesis was implanted in 7 patients (6.5%) with aortic stenosis. The mean cardiopulmonary bypass and aortic crossclamping times were 102.4 ± 25.4 minutes and 72.5 ± 21.8 minutes, respectively. The first dose of cardioplegia was administered with a mean initial dose of 1939.9 ± 216.8 mL and a total dose of 2038.9 ± 341.3 mL. Eighty-six patients (79.6%) did not require an additional dose of cardioplegia, 17 patients (16.3%) required a second dose, and 1 patient (0.9%) required a third dose. The mean time to the end of the first dose of cardioplegia from aortic crossclamping was 3.7 ± 2.1 minutes.
Table 2Perioperative outcomes (n = 104)
Mean ± standard deviation or number (percentage)
Implanted aortic valve prosthesis
without automated fastener
with automated fastener
Operative time (min)
169.3 ± 36.5
175.7 ± 35.8
without automated fastener
145.3 ± 24.4
with automated fastener
137.3 ± 31.2
CPB time (min)
102.4 ± 25.4
106.2 ± 25.7
without automated fastener
91.5 ± 15.7
with automated fastener
77.1 ± 15.6
Aortic crossclamping time (min)
72.5 ± 21.8
75.5 ± 22.2
without automated fastener
64.5 ± 15.2
with automated fastener
51.6 ± 11.6
Cardioplegia solution dose volume (mL)
2038.9 ± 341.3
First dose volume
1939.9 ± 216.8
Second dose volume
544.4 ± 249.0
Third dose volume
400.0 ± 0
Additional cardioplegia solution delivery
Time to end of first dose cardioplegia
From aortic crossclamping (min)
3.6 ± 2.1
Conversion to full sternotomy
Mechanical circulatory support
All values are presented as mean ± standard deviation or absolute number (%). CPB, Cardiopulmonary bypass.
The operative outcomes are shown in Table 3. There was no operative death, and the median intensive care unit and postoperative hospital stays were 1 (1-28) days and 5 (4-53) days, respectively. One patient required reexploration of the chest through the same minithoracotomy because of postoperative bleeding. One patient with a preoperative LVEF of 20% required inotrope administration for more than 24 hours postoperatively and developed postoperative acute kidney injury. Apart from these, there were no major complications. The highest postoperative CK-MB and troponin T values were 21.5 ± 15.0 U/L and 1.44 ± 1.56 mg/L, respectively. No patient had a perioperative myocardial infarction.
Table 3Postoperative outcomes
Median (range) or number (percentage)
ICU stay (d)
In-hospital stay (d)
Reexploration for bleeding
Perioperative myocardial infarction
Highest CK-MB (U/L)
21.0 ± 14.7
Troponin T (mg/L)
1.3 ± 1.4
Inotrope administration (>24 h)
New-onset atrial fibrillation
Prolonged ventilation (>48 h)
Acute kidney injury
Surgical site infection
ICU stay and in-hospital stay are presented as median (minimum value–maximum value), and other values are presented as mean ± standard deviation or absolute number (%). ICU, Intensive care unit; CK, creatine kinase-MB.
The echocardiographic outcomes are summarized in Table 4. Predischarge echocardiography revealed that the left ventricular end-diastolic dimension had decreased from 56.5 ± 8.4 mm to 50.5 ± 7.5 mm. LVEF also decreased from 53.3% ± 9.1% to 46.2% ± 11.4%. None of the patients had mild or severe perivalvular regurgitation. On 6-month echocardiography, the left ventricle end-diastolic dimension further decreased to 44.6 ± 6.1 mm, and LVEF improved to 56.5% ± 7.3％, which was higher than the mean preoperative LVEF.
Table 4Echocardiographic outcomes
Preoperative (n = 104)
At discharge (n = 104)
At 6 mo (n = 81)
56.5 ± 8.4
50.5 ± 7.5
44.6 ± 6.1
40.7 ± 8.9
37.8 ± 9.1
29.4 ± 5.3
53.3 ± 9.1
46.9 ± 11.4
56.5 ± 7.3
10.6 ± 1.8
11.3 ± 1.9
10.8 ± 1.8
10.4 ± 1.8
11.2 ± 1.7
10.5 ± 1.6
RVSP (mm Hg)
22.1 ± 11.2
23.3 ± 7.6
22.6 ± 5.4
Mild or greater
All values are presented as mean ± standard deviation or absolute number (%). LVEDD, Left ventricular end-diastolic dimension; LVESD, left ventricular end-systolic dimension; LVEF, left ventricular ejection fraction; IVS, interventricular septum; LVPW, left ventricular posterior wall; RVSP, right ventricular systolic pressure.
This study focused on patients with moderate or greater AI who underwent endoscopic minimally invasive AVR to determine the validity of our myocardial protection strategy. Although there have been many reports on minimally invasive cardiac surgery (MICS), to the best of our knowledge, there are no coherent reports specific to minimally invasive AVR for AI.
Our myocardial protection strategy consists of the following: (1) no use of retrograde cardioplegia; (2) systemic administration of potassium chloride and ultra-short-acting beta-blockers before crossclamping; and (3) step-by-step endoscopically assisted selective antegrade cardioplegia delivery. In the present study, cardiac asystole was achieved smoothly in all cases. None of the patients experienced difficulty weaning off cardiopulmonary bypass or developed perioperative myocardial infarction. None of the patients required prolonged use of inotropic agents except for 1 patient with preoperative LVEF of 20%. These findings indicate that our myocardial protection strategy is feasible and safe for minimally invasive endoscopic AVR in patients with AI (Figure 4) (Video Abstract).
Previous studies have reported a combination of regular antegrade and selective antegrade cardioplegia delivery for AI cases,
wherein some amount of cardioplegia is administered via the aortic root cannula, followed by aortotomy and selective antegrade for additional administration. This protocol has some uncertainty in terms of how much cardioplegia is delivered to the coronary arteries with the initial antegrade delivery through the aortic root cannula and may cause a delay in securing cardioplegia. In minimally invasive surgery, a retrograde cardioplegia cannula can be placed percutaneously
or through the right atrium under TEE guidance. However, placing a retrograde cardioplegia cannula requires extra maneuvers and time, further increasing the risk of coronary sinus injury. Coronary sinus injury is highly challenging to repair in a limited operating space and often requires conversion to full sternotomy. Therefore, we believe that selective antegrade delivery alone is the simplest and most reliable method for minimally invasive AVR in patients with AI.
Selective antegrade cardioplegia can be reliably administered when the coronary ostia is visible. However, coronary ostia have variations in size, position, and angle, and in some cases may not be visible under direct vision in minimally invasive AVR. Endoscopy overcomes the difficulty of visualization. The step-by-step procedure (Figure 3) using an endoscope and a coronary perfusion cannula with a rigid, malleable shaft allows for quick and secure direct coronary cannulation. Coronary arteries were successfully cannulated under endoscopic assistance in all cases. The average time from crossclamp to completion of the first dose of cardioplegia was 3.7 minutes. Furthermore, there was no delay in cardiac asystole, although we did not record the time to cardiac asystole. In addition to the importance of endoscopic techniques for rapid cannulation, it is essential to evaluate the location, size, and angle of the coronary arteries using preoperative coronary CTA or interventional coronary angiography. The prevalence of coronary artery anomalies was 7.9% in CTA.
In our cohorts, 5 patients (4.8%) experienced coronary anomalies. Anomalies were identified in all patients before surgery, and direct coronary cannulation was performed successfully.
We administered potassium chloride and ultrashort-acting beta-blockers to reduce the myocardial oxygen demand from aortic crossclamping to cardiac asystole. Although the reduced heart rate was observed after systemic administration of potassium chloride and beta-blocker in some cases, cardiac asystole before cardioplegia delivery was not observed in any cases. Also, our study did not reveal its effectiveness because we did not compare the outcomes between cases with and without systemic administration of potassium chloride and beta-blocker. However, our protocol is theoretically effective for myocardial protection, and we think that it is important to reduce myocardial oxygen consumption by lowering the heart rate and contractility because the delay in cardioplegia delivery could occur in the limited working space. Previous studies have reported that hyperkalemic myocardial protection is both safe and effective. In a previous report on reoperative AVR in patients with a patent left internal thoracic artery graft, procedures were performed safely without dissection or clamping of the left internal thoracic artery using systemic hyperkalemia; there was no significant elevation of postoperative CK-MB.
Fibrillating the heart before aortic crossclamping is a reasonable method for achieving a “quiet” operative field. Several previous clinical studies have reported the safety and efficacy of ventricular fibrillation (VF) in MICS.
Another concern regarding VF is excess distension of the left ventricle associated with AI.
In nonsignificant (less than moderate) AI cases, we delivered the initial cardioplegia n a regular method via the ascending aortic cannula without systemic administration of potassium chloride and beta-blocker and delivered the second dose with endoscopically assisted selective antegrade way if necessary. We excluded these cases from this study because we wanted to focus on the effectiveness and safety of the initial endoscopically assisted selective antegrade cardioplegia. To simplify surgical procedures, single-dose cardioplegia is preferred in MICS.
We used a modified St Thomas 2 solution with a large initial dose of 30 mL/kg and an additional dose of 15 mL/kg if necessary, and have reported its effectiveness and safety in minimally invasive surgery.
St Thomas 2 cardioplegia was associated with lower postoperative peak levels of cardiac markers such as troponin and CK-MB compared with Bretschneider solution in propensity-weighted treatment groups. No studies have previously compared del Nido cardioplegia and St Thomas 2 single doses; therefore, their comparative efficacy remains unclear.
Another important aspect of myocardial protection is the reduction in the aortic crossclamping time. Although minimally invasive surgery has several advantages, it is associated with prolonged aortic crossclamping and cardiopulmonary bypass times. Automated fastening devices and sutureless prostheses have been shown to shorten the aortic crossclamping time.
In the present study, these devices were used in only a few cases because the automated fastening device was not commercially available until August 2021 and the sutureless valve has not been approved for pure AI cases. Automated fastening devices are routinely used for standard prostheses.
The present study has several limitations, mainly related to its retrospective, observational, and noncomparative nature. A comparison between regular antegrade cardioplegia and selective antegrade cardioplegia was not considered meaningful because of the difference in aortic valve etiology. We did not assess long-term outcomes such as survival, reoperation rate, and echocardiographic data. This study also reflects our initial experience with this approach, including the unavoidable learning curve.
Endoscopically assisted selective antegrade cardioplegia delivery is safe and useful for minimally invasive AVR in patients with significant AI.
Conflict of Interest Statement
The authors reported no conflicts of interest.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
Step-by-step endoscopically assisted selective antegrade cardioplegia delivery. Depiction of the sequence of procedures from aortotomy to the suction of blood in the sinus of Valsalva, administration of cardioplegia to the right coronary artery, administration of cardioplegia to the left coronary artery, and achieving cardiac asystole. Video available at: https://www.jtcvs.org/article/S2666-2507(23)00005-6/fulltext.
Minimally invasive aortic valve replacement via right anterior minithoracotomy: early outcomes and midterm follow-up.
This study was approved by the Institutional Review Board of Tokyo Bay Urayasu Ichikawa Medical Center: Number 766, May 27, 2022; Toranomon Hospital: Number 2044, June 22, 2022; and Juntendo University School of Medicine: Number E22 to 0267, August 17, 2022.