Combined procedures for the treatment of patients with complex cardiac disease involve the combination of percutaneous coronary intervention (PCI) with surgical therapy in an attempt to achieve optimal benefit by using less invasive methods where possible. This was first described by Angelini et al,1 by combining a left internal mammary artery graft to the left anterior descending coronary artery with PCI of the other coronary arteries. Since this initial coronary revascularization, various other therapeutic or “hybrid” combinations have been developed as alternatives to conventional surgical approaches. These combined approaches have been used in the treatment of atrial fibrillation, complex thoracic aortic aneurysms, and in patients with concomitant coronary artery and valvular disease.2–5
In the treatment of patients with coronary artery and valvular disease, requiring intervention, the standard approach is a combination of coronary artery bypass grafting with valve surgery performed via a median sternotomy.6 However, the operative mortality for a combined coronary artery bypass grafting with valve surgery is 8.9%, compared with 4.4% for isolated valve surgery.7 The concept of a combined approach of PCI followed by valve surgery is based on the hypothesis that the combined risk of mortality of the two lesser procedures will be lower than the mortality incurred during the conventional combined surgery. This treatment strategy has been performed using either a median sternotomy or a less invasive approach. It has also been performed as a staged approach, with varying time intervals between PCI and surgery, as well as a single-stage approach where cardiac surgery is performed in the same operative setting as PCI. With this background, a review of the literature of a combined approach of PCI followed by cardiac valve surgery was performed to better understand the potential benefits, limitations, and the unanswered questions associated with this treatment strategy.
Search Strategy and Study Selection
The study was performed according to the PRISMA guidelines.8 A literature review was performed using PubMed, EMBASE, Ovid, and the Cochrane library, of all scientific articles published through March 2016. The search terms used in various combinations included the following: hybrid, staged, PCI, mitral valve repair or replacement, aortic valve replacement, hybrid surgery, mitral, aortic, coronary, aortic valve, and mitral valve. Two authors (O.S., C.G.M.) independently screened the studies identified by the literature search, and the corresponding reference lists of included articles were also assessed for pertinent studies.
A total of 675 abstracts were identified. From these 675 studies, we identified 12 original studies, case series or case reports available as full-length articles in the English language. Excluded were studies using percutaneous transcatheter valve procedures. In addition, four studies were excluded from the analysis because of duplication of the data.2,9–11 There were three publications excluded because they consisted of a case series of two patients or were isolated case reports.12–14 A total of five studies were thus included in the final analysis.15–19
Data Abstraction and Quality Assessment
Three authors (O.S., S.S., C.G.M.) reviewed and extracted the data from the studies included in the review. The information extracted included the following: the number of patients, baseline demographics, extent and clinical presentation of coronary artery disease, type(s) of valve operation performed, time interval between PCI and valve surgery, and the antiplatelet regimen at the time of valve surgery. The operative and follow-up clinical outcomes extracted included the following: predicted and observed mortality, hospital length of stay, and bleeding complications. The study quality and risk of publication bias was assessed using the Cochrane Collaboration's tool for assessing risk of bias.20
The results are presented as percentages, ranges, mean ± standard deviation, or median and interquartile range (IQR or 25%–75%), as appropriate. Because not all the studies had every variable reported, the number of patients or n (the denominator) is mentioned in every calculation.
All of the studies were single-center experiences, with three being retrospective and two being prospective observational in nature. A total of 324 patients were reported from the five studies. Among the baseline comorbidities, a history of cerebrovascular accident was present in 48 patients (14.8%); the mean left ventricular ejection fraction ranged from 37% to 55%; 75 patients (23.1%) had previous cardiac surgery; and 31 patients (9.5%) had an acute coronary syndrome at presentation (Table 1).
The interval between PCI and valve surgery ranged from both procedures being performed simultaneously to a median of 38 days (IQR, 18–65 days). Data on stent usage were available for 293 patients. Balloon angioplasty alone was performed in eight patients (2.7%), bare metal stents were used in 78 patients (26.6%), and drug-eluting stents were used in 207 patients (70.7%). Of the 292 patients of which perioperative antiplatelet use was reported, 237 (81.7%) received aspirin, 245 (84.2%) received clopidogrel, and 218 (74.6%) received both (Table 2).
Of the 324 patients, 42 (13%) underwent a traditional median sternotomy. Of these, 18 were in the study by Byrne et al,15 one in the study by Santana et al,18 which was an attempted hybrid minimally invasive approach but required conversion to a median sternotomy, and 23 from the study by George et al.19 The remainder of the patients (87%) underwent minimally invasive surgery. There were a total of 135 mitral valve operations (45.3%), 125 aortic valve replacements (41.9%), 1 tricuspid valve repair, and 43 double-valve surgery (12.7%). The cardiopulmonary bypass time was reported in three studies, being 141 minutes (range, 60–249 minutes), 110 minutes (IQR, 94–141 minutes), and 82.5 ± 25.2 minutes.15,18,19
The transfusion requirement in the perioperative period was reported in four studies and ranged from 1 to 3 U.15,16,18,19 A total of 13 patients (4%) underwent reoperation due to bleeding. Postoperative atrial fibrillation developed in 53 patients (16.3%), 6 (1.8%) had nonfatal cerebrovascular accidents, and 6 (1.8%) had acute kidney injury. The median hospital length of stay was reported in three studies, being 17 days (range, 6–24 days), 8 days (IQR, 6–10 days), and, in the third study, a mean ± SD of 8.3 ± 3.5 days for those who had primary valve surgery and 15.6 ± 22.3 days for those who underwent reoperative surgery.15,18,19
The Society of Thoracic Surgeons 30-day predicted risk of mortality was reported in three studies, being 22%, 8.7%, and, in the third study, 5.26% ± 3.13% in those undergoing primary surgery and 13.43% ± 8.37% in those undergoing reoperative surgery.15,17,19 The 30-day mortality data were available in all studies, ranging from 0% to 5.5% (Table 3). The 1-year survival ranged from 78% to 100%, and the follow-up period was from 1.3 to 5 years.
Combining PCI with valve surgery was first investigated in 2005 by Byrne et al15 in a single-center, retrospective study. The study consisted of 26 patients, 24 of whom underwent PCI for acute coronary syndromes, and two had reoperative valve surgery, followed by aortic or mitral valve surgery using a minimally invasive approach in eight patients, and a traditional median sternotomy in the rest. The operative mortality was 3.8%, which was much lower than the predicted mortality of 22%. However, because of the use of dual antiplatelet therapy, a high incidence of bleeding occurred, with 22 (85%) of the 26 patients requiring blood transfusions. Although this study was limited by its small sample size, it demonstrated the feasibility of using a combined approach in the treatment of coronary and valvular disease. This study was followed by a prospective observational study of 18 high-risk patients undergoing PCI and aortic valve surgery. In an attempt to reduce the incidence of bleeding noted in the previous study, the PCI was performed on the day of or the evening before the scheduled minimally invasive aortic valve replacement to avoid the antiplatelet effect of the drugs during surgery.16 There were no reoperations for bleeding, with eight patients (44%) requiring blood transfusions. There was one postoperative death from a colonic perforation and no late mortality at a mean follow-up of 19 months.
Subsequently, Umakanthan et al17 retrospectively evaluated 32 high-risk patients who underwent a combined approach of PCI and mitral valve surgery. A single-stage procedure of PCI followed by valve surgery performed in a hybrid operating suite was performed in 28 patients (87%). There were no bleeding-related deaths; however, the rate of reoperation for bleeding was 9%, which was felt to be due to the use of antiplatelet agents. The operative mortality was 3%, which was lower than the predicted mortality of 8.7%, and survival at 1 and 2 years was 96% and 89%, respectively, demonstrating that in a select group of high-risk patients, combining minimally invasive valve surgery and PCI allows a reduction in mortality, albeit at an increased risk of bleeding.
Santana et al10 retrospectively evaluated 65 consecutive patients with coronary artery disease and either aortic (47.7%), mitral (36.9%), or combined aortic and mitral (15.4%) valve disease who underwent PCI followed by minimally invasive valve surgery within 60 days and compared them with 52 matched control patients who underwent conventional bypass grafting and valve surgery. The composite endpoint of death, renal failure, or stroke occurred in 1 (1.5%) in the hybrid group versus 15 (28.8%) in the conventional group (P = 0.001). Thus, compared with the standard median sternotomy coronary artery bypass grafting with concurrent valve surgery, the combined approach was associated with lower morbidity. These 65 patients were subsequently incorporated into a larger observational study of 222 patients with a median follow-up of 1.3 years.18 There were 181 patients (81.5%) who underwent one-vessel, 27 (12.2%) had two-vessel, and 14 (6.3%) had three-vessel PCI. The patients underwent primary or reoperative and single or double-valve surgery. The 30-day mortality was 3.6% (8 patients), and at a mean ± SD follow-up of 16.2 ± 12 months, six patients required PCI, with target-vessel revascularization performed in four patients (2.1%). The survival at 1 and 4.5 years was 91.9% and 88.3%, respectively, demonstrating good midterm outcomes.
Recently, George et al19 reported the feasibility and safety of a single-stage approach, where valve surgery was performed in the same operative setting as PCI, in a specially designed hybrid operating room. A total of 26 patients, of which 12 underwent primary valve surgery plus PCI procedures and 14 underwent reoperative valve surgery plus PCI, were evaluated. Excluded were patients with disease of the left anterior descending artery. The predicted mortality for the 12 patients undergoing primary surgery was 5.26% ± 3.13 and 13.43% ± 8.37 for the 14 patients undergoing reoperative surgery. A median sternotomy approach was used in 23 patients, whereas a minimally invasive approach was used in three patients. The patients underwent primary or reoperative and single- or double-valve surgery. There were no in-hospital deaths, with one patient having a cerebrovascular accident. At a mean ± SD follow-up of 680 ± 277 days, no additional deaths, cerebrovascular accidents, or myocardial infarctions were observed.
A concern with using PCI in these patients is that at times, one may not be able to achieve complete revascularization. This was evaluated in a study by Pineda et al,21 which consisted of 138 patients who underwent a staged approach of PCI followed by minimally invasive valve surgery. The results of 105 patients who achieved complete revascularization were compared with 33 patients who had incomplete revascularization. The patients with incomplete revascularization had a lower ejection fraction, a higher Society of Thoracic Surgeons mortality score, more previous myocardial infarctions, and multivessel coronary artery disease. There were no differences in postoperative complications, 30-day mortality, or 3-year survival (84% vs 83%, P = 0.68). However, at a median follow-up of 29 months, the incompletely revascularized patients had a higher incidence of acute coronary syndrome (2.9% vs 12.9%, P = 0.05).
The most common indications for a combined approach in the treatment of concomitant coronary artery and valve disease are the following: to facilitate minimally invasive surgery, to reduce overall operative morbidity and mortality by transforming a single, high-risk surgery into two less risky procedures, and to allow for revascularization in the setting of limited conduit options or poor target anatomy.19 The data demonstrate that in selected patients, a combined approach of PCI and valve surgery is safe and feasible with good short- and long-term outcomes. This applies to those with multivessel disease, those with incomplete revascularization, and those undergoing double-valve and/or reoperative valve surgery. The benefits have been demonstrated with either a median sternotomy or a minimally invasive approach.
There are significant limitations to the data presented. All the studies were single-center experiences and were retrospective or observational in nature. The size of the studies tended to be small. The patients were selected on the basis of favorable anatomy for this procedure, thereby introducing significant selection bias. By enlarge, the studies lacked control groups for comparison, and the follow-up period was fairly limited. The patients were also quite heterogeneous, with some undergoing either elective or urgent, primary or reoperative, and single- or double-valve surgery. The surgical approaches also varied, with some being performed via a minimally invasive and others via a median sternotomy approach. These limitations make it difficult to reach any firm conclusions.
In patients with concomitant coronary artery and valve disease, a combined approach of PCI and valve surgery via a minimally invasive or median sternotomy approach seems to be associated with favorable early and long-term outcomes. This approach may be more beneficial in the high-risk patients, especially those presenting with an acute coronary syndrome or those requiring reoperative valve surgery. However, the results are hampered by the heterogeneity of the methodological approaches of the studies, and no decision can be made regarding the optimum therapy. However, because of the advancements of transcatheter interventional therapeutics, we hypothesize that this combined treatment approach will significantly increase in the near future. Therefore, additional studies including adequately powered randomized trials are needed to determine the optimal approach in patients with combined coronary and valvular disease.
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