Concomitant coronary artery disease (CAD) and valvular heart disease is a common problem in the ageing population. It is estimated that the prevalence of mitral regurgitation and aortic stenosis in individuals over the age of 70 is 10 % and 4 %, respectively.1,2 Among patients presenting with symptomatic aortic stenosis, concurrent CAD occurs in over 50 % of those over 70 years of age and over 65 % of those over 80 years of age.3,4 However, elderly patients often have more co-morbidities, are more likely to have had a previous cardiac operation, and are less tolerant of complex cardiac surgery. Furthermore, the addition of coronary artery bypass grafting (CABG) at the time of valve surgery doubles the operative risk of the procedure.5-8 Interest in hybrid procedures, defined for the purpose of this review as surgical valve repair/replacement and percutaneous coronary intervention (PCI) (hybrid valve), has intensified with the emergence of minimally invasive surgical techniques, improved coronary stent technology, increased collaboration between cardiac surgeons and interventional cardiologists, and the introduction of hybrid operating suites. The complementary goals of minimising the morbidity of surgical procedures and optimising resource utilisation have driven development of new solutions for concurrent valvular and coronary heart disease.
Indications and Patient Selection
The primary purpose of a hybrid valve/PCI is to substitute PCI for bypass grafting with saphenous vein grafts (SVGs), particularly for lesions not in the left anterior descending (LAD) coronary artery.5 With the current excellent performance of drug-eluting coronary stents (DES), restenosis and thrombosis rates of DES may be less than the estimated rate of SVG failure of 20 % at 12 months.9,10 The two most common clinical objectives of hybrid procedures are to facilitate minimally invasive surgery and to reduce overall operative morbidity and mortality by transforming a single, high-risk surgery into two less risky procedures. Minimally invasive valve surgery, via upper hemisternotomy for the aortic valve or right mini-thoracotomy for the mitral valve, has been shown to reduce operative pain, to require less blood transfusion, to provide a superior cosmetic result, and to be associated with faster recovery and a shorter hospital length of stay.5,10,11
Reoperative coronary bypass grafting in a patient with valvular disease poses a particular challenge in cardiac surgery. The hybrid approach is of particular benefit in reoperative patients who have had prior CABG with patent grafts.5,9,12 The technical difficulty of accessing lateral wall targets, safely dissecting patent bypass grafts and obtaining exposure often precludes safe surgery, and these risks are not reflected in traditional scoring systems. Hybrid valve/PCI may be particularly useful in this regard and can dramatically simplify a challenging open valve and CABG surgery by substituting PCI for reoperative bypass grafting in lesions amenable to PCI.5
Hybrid procedures offer a reasonable alternative to traditional surgery for patients who meet the following basic criteria:
- non-LAD coronary lesions, not amenable to internal mammary bypass grafting;
- PCI that is technically feasible and likely durable from a procedural standpoint; and
- ability to tolerate the required antiplatelet and anticoagulation regimens.
Procedural Details
Two-stage Procedures
The concept of the hybrid operation emerged in the mid-1990s as a strategy for coronary revascularisation in the setting of acute myocardial infarction (AMI).13 In the most common scenario, a patient who presented with an AMI was emergently taken for angioplasty and found to have multivessel disease. The culprit lesion was treated percutaneously and the remaining coronary disease was treated with a subsequent CABG. Thereafter, staged PCI and CABG, frequently with off-pump or minimally invasive CABG, was developed as a treatment option for elective coronary revascularisation.14-17
Expanding on this concept, it was realised that patients with valvular disease who presented with an AMI could be managed similarly. First described in 2005 by Byrne et al., the hybrid approach was defined as a staged procedure with initial PCI in the cardiac catheterisation laboratory followed by open valve surgery during the same admission.18 With further experience it became apparent this hybrid approach could be extended to elective procedures. Brinster et al. reported the use of a hybrid approach in 18 high-risk, elderly patients with aortic stenosis who were found to have CAD amenable to PCI during the pre-operative coronary angiogram.19 PCI was performed with DES either the night before or morning of the aortic valve replacement (AVR). This strategy produced excellent outcomes and paved the way for single-stage procedures.
Single-stage Procedures
With the advent of the hybrid operating room, the PCI and CABG could be performed concurrently in a 'one-stopÔÇÖ hybrid approach,10which was quickly extrapolated to hybrid valve/PCI procedures.5,20 For complex, mixed coronary and valvular disease, especially in the reoperative setting, this strategy has proven especially useful. Not only does the patient potentially benefit from the improved convenience and safety of a single procedure, but resource utilisation may be improved due to use of a single clinical team and procedure room, and possibly decreased duration of hospitalisation.21
A single-stage strategy, utilising the hybrid operating suite, has become the standard approach at our institution. Pre-procedure planning goes beyond that typical for a surgical valve/CABG - the anticoagulation strategy and bleeding risks must be taken into consideration, the appropriate surgical and interventional equipment must be available, and the hybrid room must be staffed with individuals knowledgeable in both open cardiac surgery and interventional cardiology.
Description of the Single-stage Valve and Percutaneous Coronary Intervention Procedure in a Non-reoperative Patient
In our practice, the patient is loaded with clopidogrel 300 milligrams (mg) at the time of transfer to the operating room. Once inside the hybrid suite, the patient is positioned supine and standard anaesthesia protocols are followed regarding monitoring, lines and intubation. For a minimally invasive aortic valve replacement, a small, approximately 4-6 centimetres (cm), skin incision is made, centred over the angle of Louis at the second intercostal space, and the hemisternotomy is completed with a 'J' to the right fourth intercostal space. Haemostasis is achieved and the thymus divided, and aorta exposed by creating a standard pericardial well. For a minimally invasive mitral repair or replacement, a right mini-thoracotomy is utilised for direct access to the mitral valve.
Once surgical exposure is complete, attention is turned to the PCI. Femoral artery access is gained with the modified Seldinger technique and a 6 or 7 French size (Fr) sheath is placed for the intervention. The patient is given a PCI dose of heparin, usually 5,000 units, and the PCI is completed in the standard fashion.
The full cardiopulmonary bypass dose of heparin is then administered, the patient is cannulated, and the valve operation completed. Pacing wires and chest tubes are placed with the heart decompressed. After the conclusion of cardiopulmonary bypass, a partial heparin reversal (typically half the protamine dose) is administered, the patient is decannulated, haemostasis is achieved and the chest is closed. As a final step, the femoral artery access site is closed with a percutaneous closure device or manual compression per institution protocol (see Table 1).
Single-stage Valve and Percutaneous Coronary Intervention in Reoperative Patients
For a reoperative patient, the steps are altered slightly to take into account the extensive dissection often needed due to adhesions. The ternotomy or mini-thoracotomy, all necessary mediastinal dissection, and vascular access are completed prior to the administration of any anticoagulation. Subsequently, a PCI dose of heparin is administered and the intervention completed.
Attention is then turned to the valve operation, full anticoagulation is administered and cardiopulmonary bypass cannulas are placed.
Clopidogrel 300 mg is given via a nasogastric tube at the time of placement of the cross-clamp. The operation is completed in the typical fashion for the respective valve repair/replacement. Partial heparin reversal is administered at the time of decannulation, with full reversal if excessive bleeding is present. The chest is then closed and femoral artery haemostasis is achieved. (See Table 2).
Results
Several observational series have now been published describing the results of hybrid valve/PCI procedures. In a series reported by Byrne et al. of 26 patients with an average estimated Society of Thoracic Surgeons risk of mortality of 22 %, hybrid AVR and PCI proved feasible and safe with operative mortality in only one of the 26 patients (3.8 %).18 In this series, the surgical valve replacement was performed as a staged procedure, on average five days after the PCI. All patients were treated with aspirin and 69 % received clopidogrel at the time of operation. However, the series was largely dominated by high-risk patients presenting in cardiogenic shock secondary to myocardial infarction, and an increase in peri-operative blood loss and transfusion requirements were observed, mitigating some of the benefit of the hybrid approach. (See Table 3).
Brinster et al. reported a prospective observational series of 18 patients who underwent hybrid AVR and PCI.19 All patients who underwent PCI were treated with aspirin 325 mg and clopidogrel 300 mg initial load (followed by 75 mg daily), and PCI was followed by within 24 hours. In this series, one operative death occurred, but no late deaths were seen at up to 19 months of follow-up. There were no reoperations for bleeding and blood loss was minimal with mean transfusion of packed red blood cells less than one unit. In addition to decreased transfusion rates, this hybrid strategy was associated with a decreased length of stay.
Subsequently, Santana et al. directly analysed the outcomes of a staged hybrid valve/PCI approach to that of traditional surgery.22 In a retrospective analysis of 65 consecutive, matched patients who underwent planned PCI followed within 60 days (median 24 days) byeither aortic and/or mitral valve surgery, there were no in-hospital deaths in the hybrid population, no difference in transfusion rates and no reoperations for bleeding.
Specific to mitral valve, Umakanthan et al. described the Vanderbilt experience with 32 consecutive patients who underwent a hybrid procedure, including PCI and mitral valve surgery. Of these procedures, 28 (89 %) were performed as a single-stage procedure in a hybrid operating room.21 The observed in-hospital mortality rate was 3 % (1/32) and survival at one and two years was 96 % and 89 %, respectively. The series was expanded to 39 patients and reported by Solenkova et al., noting a predicted mortality for conventional CABG/ mitral of 14.1 % versus an observed in-hospital mortality of only 2.6 % (1/39).10
Procedural Timing
The optimal relative timing of the staged hybrid valve/PCI procedures remains unknown. A one-stop, or single-stage procedure may be appealing with respect to convenience, patient safety and resource utilisation. However, the ability to perform a single-stage procedure may be limited by the availability of appropriate staff and facilities.23,24 The single-stage approach requires a hybrid suite that can accommodate the equipment to perform the PCI as well as full cardiopulmonary bypass-based cardiac surgery; this includes general anaesthesia, transoesophageal echocardiography, the perfusion team and the cardiopulmonary bypass machine, in addition to the standard operating team and equipment. The risk-benefit profile of a single-stage procedure may also become unfavourable in the setting of significant renal dysfunction and certain other clinical circumstances. Finally, the management of required antiplatelet and anticoagulation therapies may be challenging based on the relative timing of the hybrid procedures.
Anticoagulation Management
Regardless of the hybrid strategy employed, concern remains over the impact of clopidogrel, or other antiplatelet therapies, at the time of cardiac surgery. The early hybrid experience was associated with increased blood loss and higher transfusion rates, which was attributed to the use of clopidogrel at the time of the valve operation.18 The subsequent strategy of shortening the duration between stages offered the potential to circumvent the increased risk of bleeding based on the pharmacokinetics of clopidogrel. However, more contemporary data suggests the risk of surgical bleeding while on clopidogrel may be overestimated.25
Furthermore, the risk of bleeding may be significantly reduced with the introduction of novel anticoagulants and antiplatelet agents. Cangrelor (The Medicines Company, Parsippany, New Jersey, US), an intravenous adenosine diphosphate receptor antagonist with a short half-life and rapid onset, has been shown to be safe and effective during PCI. The Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) PHOENIX trial was a recently published, double-blinded, placebo-controlled trial of 11,145 patients undergoing urgent or elective PCI.26 The use of cangrelor was associated with a reduction in the rate of ischaemic events, including stent thrombosis, without an increase in severe bleeding. Although the effect of cangrelor in surgical patients is unknown, an intravenous antiplatelet agent with rapid onset that could be administered precisely at the time of PCI might prove to be highly beneficial with respect to the hybrid PCI/valve procedure.
Cost-effectiveness
In the current era of closely scrutinised healthcare spending, the cost-effectiveness of hybrid procedures must be further evaluated prior to broad adoption. The available literature suggests the hybrid valve/PCI approach is safe and effective, and may be associated with lower blood transfusion rates, shorter lengths of stay, and ultimately lower cost.5,9,19,20 Further cost savings may be realised by implementation of a single-stage approach, since only one hybrid suite and personnel team are utilised. Further study is necessary to truly delineate the cost-effectiveness of the hybrid valve/PCI approach.
Transcatheter Valve Replacement and Percutaneous Coronary Intervention
Fully transcatheter approaches to valvular and coronary heart disease, including PCI and transcatheter aortic valve replacement (TAVR), are beyond the scope of this review.27 However, a truly hybrid strategy involving open surgery and TAVR has been proposed as a means of addressing aortic stenosis and CAD (particularly LAD lesions) in a patient who is inoperable due to anatomic factors, such as hostile chest, porcelain aorta, complex reoperation, or patent right internal mammary artery crossing anterior to the aorta. The hybrid strategy in this regard combines a TAVR (transfemoral, transapical or transaortic) and open or minimally invasive direct coronary bypass grafting through a left mini-thoracotomy.28-35 Further study is necessary to better understand the risks and benefits of this new hybrid approach.
Conclusion
With advances in stent technology and surgical technique, a hybrid procedure offers a unique approach to complex valve and coronary pathology and may become a more common strategy as longer-term outcomes become available. As experience is gained with minimally invasive techniques, a broader range of patients may benefit from hybrid valve/PCI procedures. The hybrid operating room has enabled new strategies to address complex cardiac disease. The single-stage approach to concomitant coronary and valvular disease is an excellent alternative to traditional open surgery. By transforming a complex, high-risk, operation into two procedures, excellent outcomes can be achieved with potential cost savings from a single procedure room and team, quicker patient recovery and decreased length of stay without added risk of bleeding. Additional study is necessary to truly understand the benefit of this innovative approach.