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Cox-MAZE IV Combined with Coronary Artery Bypass Graft and Mitral Valve Replacement

Andrew Del Re 1; Marco Zenati, MD 2
1 The Warren Alpert Medical School of Brown University
2 Brigham & Women’s Hospital, VA Boston Healthcare System


Cardiovascular disease is a leading cause of morbidity and mortality in the United States and abroad, manifesting as shortness of breath, exercise intolerance, palpitations, and chest pain. Common cardiovascular diseases include coronary artery disease (5.6% of the U.S. population), atrial fibrillation (0.95% of the U.S. population), and diseases affecting the heart valves (2.5% of the U.S. population).1-3 While the majority of cases are treated medically, more advanced or severe cases are treated surgically or endovascularly, warranting an open discussion between the provider and the patient to decide the most appropriate treatment modality given the specific characteristics and preferences of the procedure and the patient. 

The Cox-MAZE IV is a surgical procedure to treat atrial fibrillation that utilizes mainly applied radiofrequency and cryothermal energy (as opposed to the “cut-and-sew” techniques in prior iterations) to treat atrial fibrillation.4-7 Coronary Artery Bypass Grafting (CABG) allows for the bypass of stenotic or occluded coronary arteries through the use of arterial or venous conduits. Mitral valve repair, or replacement, can be used for correcting mitral valve disease. Though the aforementioned procedures address different pathologies of the heart, some or all may be necessary at the same time due to concomitant disease.      

The Cox-MAZE IV combined with Coronary Artery Bypass Graft and Mitral Valve Replacement is a singular surgical procedure that is carefully planned and executed to address arrhythmic, coronary, and valvular disease while minimizing time on cardiopulmonary bypass (CPB) with an arrested heart. 

Case Overview


The Cox-MAZE IV with Coronary Artery Bypass Graft (LIMA → LAD) and Mitral Valve Replacement addresses a combination of concomitant long-standing persistent atrial fibrillation, critical stenosis of the left anterior descending coronary artery, and mitral valve insufficiency. Through a combination of radiofrequency-induced coagulative necrosis and cryoablation on both the left and right atria, atrial fibrillation can be eliminated to restore normal sinus rhythm. Through a rerouting of the left internal mammary artery to a site distal to the obstruction of the LAD, the jeopardized myocardium can be adequately reperfused. Lastly, the cause of the severe mitral valve regurgitation, in this case, was deemed to be ischemic/ functional due to severe coronary artery disease and associated maladaptive left ventricular remodeling. Unlike other causes of MR, Randomized clinical trials have shown no significant clinical difference between MV repair vs. replacement at 1 year or 2 years after surgery. However, the patients in the repair group had significantly more recurrences of moderate or severe MR.89 In this case, the mitral valve was replaced using a bioprosthetic valve.

Focused History of the Patient

This patient was referred to Cardiac Surgery with worsening effort intolerance and shortness of breath secondary to known congestive heart failure (recently escalated from NYHA Class II to Class III), likely caused by this patient’s long-standing mitral valve disease. On further assessment, the patient was found to have persistent long-standing atrial fibrillation, as well as 95% stenosis of the proximal LAD. Had this patient had isolated disease in the coronary arteries or mitral valve, this patient may have been a candidate for percutaneous therapy rather than open surgical therapy; however, the presence of concomitant disease renders the surgical approach a more efficient “one-stop-shop” option.

Typical Physical Exam

Patients presenting with long-standing persistent atrial fibrillation, coronary artery disease, and mitral valve disease may experience a wide constellation of symptoms related to the irregular rhythm of the heart as well as its implications on systemic organ perfusion or heart failure, in addition to myocardial perfusion. These symptoms include chest pain, shortness of breath, palpitations, reduced exercise tolerance, weakness, dizziness, and fatigue. Heart failure symptoms, and symptoms related to congestive liver dysfunction such as paroxysmal nocturnal dyspnea, orthopnea, and hepatomegaly. Stroke is a known complication of atrial fibrillation and patients may present with cognitive or sensorimotor dysfunction related to prior episodes of embolic stroke. Patients may present relatively late in their disease course if their disease is not severe enough to cause the aforementioned symptoms.

Typical Imaging

Patients with endorsed cardiovascular complaints and a consistent medical history concerning cardiovascular disease will have a standard workup including an assessment of cardiac function through an electrocardiogram, echocardiogram, and cardiac catheterization. In addition, in the case of an extensive history of peripheral vascular disease, transient ischemic attacks (TIA) or neck bruits on the physical exam a duplex ultrasound of the neck can be obtained to confirm vascular patency. The presence of significant carotid artery stenosis has implications for the hemodynamic management during CPB. 

In addition, in case of prior cardiac surgeries, history of radiation or signs of thoracic aortic calcification a CT scan of the chest can be obtained to ascertain anatomy. 

Natural History

Atrial fibrillation is a condition attributed to a variety of different intrinsic and extrinsic causes, such as myocardial infarction, valvular disease, and recent cardiac surgery, in addition to other non-cardiac causes such as substance use, electrolyte abnormalities, and thyroid hormone imbalance. Long-standing mitral regurgitation leads to left atrial dilatation. In addition, long-standing atrial fibrillation can lead to annular dilatation and functional mitral valve regurgitation.10 In regards to the mitral valve regurgitation, Carpentier proposed a functional classification rather than prior classification schemes based on etiology to characterize the MR.11 In type 1 dysfunction the cusp motion is normal. In contrast, in type II dysfunction there is excessive valve motion. Finally, in type III dysfunction the cusp motion is restricted during diastole (IIIa) or systole (IIIb). This patient had tethering of valve leaflet most likely secondary to distortion of the left ventricular geometry. 

Ischemic cardiomyopathy is another common cause of congestive heart disease. This patient was found to have a 95% stenosis of the left anterior descending artery which supplies the anterolateral myocardium, apex, interventricular septum, and 45-55% of the left ventricle. 

Left untreated, the congestive heart failure in this patient would continue to worsen with resultant reduction in physical activity tolerance and reduced life expectancy.12-17 In addition, his atrial fibrillation puts him at risk of cardiogenic embolic diseases such as stroke, acute limb ischemia, or acute mesenteric ischemia. Using this patient’s medical history, we can calculate a CHA₂DS₂-VASc score to assess their risk for stroke, which may warrant treatment with anticoagulation therapy to mitigate that risk.18 Lastly, his critical LAD stenosis puts him at risk of plaque rupture and myocardial infarction.

Options for Treatment

In the case of newly diagnosed atrial fibrillation, patients are treated to both prevent systemic thromboembolism as well as achieve rhythm or rate control through antiarrhythmic therapy.19 In addition to medications, management of risk factors such as blood pressure or cholesterol is advised. In certain patient groups, such as those undergoing long-term rhythm control, those with long-standing persistent atrial fibrillation, or hemodynamically unstable patients, electric cardioversion may be warranted.20 If the patients continue to have symptoms and do not respond to medical therapy or cardioversion, they may be considered for percutaneous or surgical ablation, depending on the details of their specific case.2122

Valvular diseases may be treated using transcatheter or surgical techniques. Transcatheter therapies have found widespread use in treating a wide spectrum of aortic valvular diseases and some mitral and tricuspid valvular lesions.23 They have the advantage of being minimally invasive and are often performed using percutaneous techniques. For most mitral valve lesions, surgical valvular replacement remains the current gold standard modality for the treatment of valvular disease. The surgical approach to repair or replacement of the mitral valve is varied and includes traditional median sternotomy, right anterior thoracotomy, or minimally invasive approaches. Given the concomitant surgical procedures performed in this case, a median sternotomy was chosen. The ascending aorta was the site of arterial cannulation and a bicaval approach was used for venous return. CPB was initiated and the heart was then arrested via administration of the cold cardioplegic solution. If at all possible, the mitral valve lesion should be repaired.24 An exception is functional ischemic MR, as in the case of this patient. In this subgroup of patients repair vs. replacement have shown no difference in terms of survival, and in fact, the repair is associated with more risk of recurrence of MR.25-28 This patient underwent MV replacement using a bioprosthetic valve. The choice of valve type depends on the patient's age, comorbidities, and the ability to undergo lifelong anticoagulation therapy.2930

Coronary artery disease is the most common cardiovascular disease worldwide, and its management depends on the degree of symptoms, findings on coronary angiography, and effects on the heart’s contractility.31 In healthy but high-risk patients, prevention of coronary artery disease through means of lifestyle management (such as control of blood pressure, blood sugar, and blood cholesterol in addition to smoking cessation) is initially attempted. If patients develop significant atherosclerotic disease, they may become candidates for percutaneous or surgical therapy. Percutaneous coronary intervention (PCI) involves cannulating a peripheral artery (oftentimes the radial artery) and passage of a catheter with a balloon and stents attached through the patient’s blood vessels to access the coronary arteries of the heart. The wire is used to “cross” the stenotic portion of the vessel followed by balloon angioplasty and subsequent stent placement. The current generation of coronary stents is drug-eluting with improved maintenance of patency. While the surgical option is more invasive, extensive prior research has identified certain groups of patients that benefit from coronary artery bypass grafting (CABG) operation instead of PCI.32-35 Surgical management of coronary artery disease involves isolation and grafting of an appropriate conduit vessel (arterial such as the left internal mammary artery (LIMA), radial, right gastroepiploic artery, and rarely ulnar arteries vs. venous conduits such as an autologous saphenous vein or cryopreserved venous grafts) to a site distal to the obstruction as identified on coronary angiography. Coronary artery bypass grafting can occur on a non-beating heart with cardiopulmonary bypass (known as “on-pump” CABG) or on a beating heart with or without the need for cardiopulmonary bypass. The decision to perform on-pump versus off-pump CABG is made at the discretion of the surgeon as they afford unique risks and benefits but may have similar efficacy.36

Rationale for Treatment

The goals of treatment in a Cox-MAZE IV with Coronary Artery Bypass Graft and Mitral Valve Repair are to provide freedom from atrial tachyarrhythmias with the return to normal sinus rhythm, while simultaneously reducing the chronic hemodynamic and structural consequences of the untreated mitral valve and coronary artery disease. This patient presented with worsening congestive heart failure (from NYHA stage II to NYHA stage III).

Special Consideration

As for any involved operation, the decision to perform the procedure depends on the indication for the operation as well as determining the ability of the patient to withstand the operation. Open heart surgery utilizing the CPB carries significant risks of mortality and morbidity. These include bleeding and need for transfusion of blood and blood products, temporary or permanent damage to different organ systems including the kidneys, liver, and the need for long-term ventilatory support. In addition, there is some risk of stroke and other thromboembolic events. These risks should be carefully balanced against the perceived benefits that the patient will attain from the operation. In addition to the insight gained by the surgeon and the “eyeball test”, there are various subjective tools for calculating the risks of mortality and morbidity for each patient for a specific operation. One of the most commonly used tools is the STS Predicted Risk of Mortality (PROM) calculator available online ( In this case, it was deemed that the patient will be able to tolerate the procedure and the benefits of the operation outweigh the risks.  


This procedure addresses this patient’s atrial fibrillation, mitral valve disease, and coronary artery disease in one single procedure. It is paramount that the total global ischemic time of the heart be minimized. Therefore, careful planning and orchestration of the different steps of the procedure are necessary. One approach is to perform parts of the operation off-pump with a beating heart. 

Following standard vertical midline incision with median sternotomy, the LIMA was identified and exposed using a skeletonization technique. This technique has the advantage of preserving surrounding fat, lymphatics, nerves, and muscle (in contrast to a “pedicled graft”, which contains the artery and the aforementioned surrounding structures). The benefits of this technique include the minimization of sternal ischemia, lowered risk of mediastinitis, and longer graft length as compared with a pedicled graft.3738 The bifurcation of the left internal mammary artery to the superior epigastric and pericardial phrenic arteries were preserved so as to not disrupt collateral blood flow to the sternum. After the isolation and ligation of the release of the left internal mammary artery, a bulldog was placed at the open end to allow the left internal mammary artery to distend under its own pressure. Topical papaverine was then applied to the external surface of the artery to promote vasodilation. 

In preparation for cardiopulmonary bypass, the pericardium was exposed and opened to access the heart, where the edges of the pericardium were suspended to the chest wall to maximize exposure. Short-axis and long-axis epiaortic ultrasounds of the ascending aorta were then performed to assess candidacy for cannulation, as this area is not well visualized during transesophageal echocardiography, and significant intraluminal or mobile atheromatous disease of the ascending aorta warrants exploration for alternative sites of cannulation. No significant atherosclerotic disease precluding standard aortic cannulation was identified. Attempts to cardiovert the patient to normal sinus rhythm was undertaken to confirm the type of atrial fibrillation as longstanding persistent (i.e., “permanent”). After systemic heparinization, purse-string sutures were placed in the distal ascending aorta and IVC and SVC for arterial and venous cannulation respectively. Appropriate size cannulas were used in consultation with the perfusionist and according to the patient’s body surface area (BSA) to achieve adequate cardiac output on the pump. Antegrade cardioplegia cannula was placed in the ascending aorta for delivery of the cardioplegia solution. 

The basic parts of the biatrial Cox-Maze IV procedure have been well documented in the literature.39 This patient underwent first bilateral pulmonary vein isolation with bipolar radiofrequency clamps, followed by the right atrial lesions, left atrial lesions, and exclusion of the left atrial appendage with the AtriClip device (AtriCure). In this procedure, we first isolated the right pulmonary veins en bloc using a bipolar radiofrequency clamp, administering five transmural ablations. After isolation of the IVC and SVC by snaring the caval tapes and with the beating heart, we then proceeded with a right atriotomy. Two longitudinal lesions towards the orifice of the IVC and SVC were generated as well as a lesion directed towards the right atrial appendage with three applications of the bipolar radiofrequency energy device. With the tricuspid valve exposed, we then applied another lesion using a cryothermal malleable probe towards the tricuspid annulus to complete the right atrial lesions of the Maze. In the creation of this last lesion, care was taken to avoid the AV node located in the “triangle of Koch.” Lastly, epicardial lesions using cryoablation were performed at the left isthmus and coronary sinus, concluding the pre-cardioplegic lesions of the MAZE procedure.

The aorta was then cross-clamped and Del Nido cardioplegia was delivered via an antegrade cardioplegic cannula through the aortic root, and an ice slush was topically administered to facilitate myocardial cooling, hastening cardiac arrest. Electrocardiography was used to confirm the complete cardiac arrest. 

Similar to the right pulmonary vein isolation, the left pulmonary vein isolation step involved five administrations of transmural and circumferential radiofrequency ablation. After a left atriotomy, the left atrial lesions consisted of the “box lesions” surrounding the orifice of the pulmonary veins as well as two linear lesions, the so-called “mitral line” to block conduction across the left atrial isthmus between the inferior pulmonary veins and the mitral valve annulus. This left isthmus line in the atrial myocardium is accompanied by a cryolesion in the coronary sinus in the same plane as the mitral line. The second linear lesion is placed from the left atrial appendage to the left superior pulmonary vein. After appropriate left atrial lesions were made, the AtriClip closure device was placed at the base of the left atrial appendage for exclusion from circulation and mitigation of cardioembolic risk. 

Attention was then turned to the coronary artery. An arteriotomy was done on the left anterior descending artery, and continuous sutures were placed circumferentially to complete the end-to-side anastomosis in a standard running fashion. 7-0 Prolene was used. 

Access to the left atrium for completion of the mitral valve replacement and remaining left atrial lesions of the MAZE procedure was done through a left atriotomy. As indicated previously, given the etiological cause of MR in this case the decision was made to proceed with bioprosthetic MV replacement. To complete a chordal-sparing replacement, the anterior leaflet of the mitral valve was partially removed, and the valve area was sized for appropriate prostheses. Some of the aforementioned left atrial Cox MAZE IV lesions were performed at this stage.  

Circumferential pledgeted mattress sutures were placed at the mitral valve annulus in preparation for prosthetic valve implantation. Once completed, the prosthetic valve was sutured in corresponding positions for appropriate alignment. Once all sutures were placed, the valve was pushed into place, and the sutures were then tied off against the annulus and cut, concluding the mitral valve replacement. The left atrium was then closed, concluding the procedure. 

Temporary epicardial pacing wires were then placed on the external surface of the heart to begin the process of weaning from cardiopulmonary bypass and allowing cardiac pacing. Calcium was administered and ventilation initiated by the anesthesiology team. After ensuring that the patient core temperature has reached 36 degrees celsius the patient was gradually weaned off of CPB The effect of heparin was reversed using protamine administration. The pericardiotomy, midline sternotomy, and vertical inline incision were closed.

The Cox-MAZE IV is an updated iteration of the classic Cox-MAZE III procedure, which was developed in 1987 by James Cox and his colleagues.4041 The Cox-MAZE procedure was initially developed to treat atrial fibrillation via “maze-like” surgical incisions in atrial tissue to interrupt large (>4 cm diameter) reentry circuits in both the left and the right atrium. The procedure further evolved over the following five years to become the Cox-MAZE III procedure, which utilizes a “cut-and-sew” technique and was previously regarded as the gold standard for the surgical treatment for atrial fibrillation before the introduction of alternative sources of energy for the ablation.

Outcomes data for Cox-MAZE procedures have been reassuring. In one study of 197 patients who received a MAZE, 89.3% of patients had freedom from atrial fibrillation after 10 years of follow-up. 42 A different study investigating only the most recent iteration of the Cox-MAZE procedure (Cox-MAZE IV) found 89% achieved freedom from atrial fibrillation at 12 months, and 78% of patients achieved freedom from both atrial fibrillation and antiarrhythmic medication at 12 months. 43

Short-term complications associated with MAZE procedures and CABG (such as in this patient) have been reflective of the extensive nature of the operation, such as prolonged ventilation, renal failure, and pneumonia. 44

Future directions for the Cox-MAZE procedure are focused on the identification and aggressive management of patients with atrial fibrillation, as early management of atrial fibrillation is associated with better postoperative outcomes, and a significant proportion of patients with atrial fibrillation are not being offered surgical ablative therapy even when they are undergoing other cardiac procedures. 4245


Cardiopulmonary Bypass

Isolator Synergy Clamp by Atricure

AtriClip by AtriCure

Prosthetic Mitral Valve by Edwards


Nothing to disclose.

Statement of Consent    

The patient referred to in this video article has given their informed consent to be filmed and is aware that information and images will be published online.


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