Multivessel Coronary Drug - Eluting Stenting Alone in Patients
with Significant Ischemic Mitral Regurgitation: A 4-Year Follow

In the presence of concomitant significant ischemic mitral regurgitation (MR) and multivessel coronary artery disease (CAD), common practice is treatment with combined surgical mitral valve repair or replacement (MVR) and coronary bypass (CABG). Some have advocated revascularization with bypass surgery as a stand alone treatment for ischemic MR,^1–3 however, these studies have mostly focused on patients with mild-tomoderate range MR. With the advent of drug-eluting stents (DES), the rates of restenosis and repeat target lesion revascularizations have significantly dropped.^4,5 Clinical outcomes of percutaneous coronary interventions (PCI) may be achieving durability to rival that of surgical revascularization approaches^6–8 with less invasiveness and procedural risk. Given the substantial mortality rates of combined mitral valve and coronary bypass surgery reported as high as 13%,⁹ routine referral to cardiac surgery for patients with simultaneous significant MR and multivessel CAD must be reconsidered. Is there a role for PCI with DES as a stand alone treatment for patients with concomitant significant ischemic MR and multivessel CAD?

Methods
In the year 2003 (from January 1 to December 31), a single medical center in Honolulu, Hawaii, treated 6 patients with concomitant significant ischemic MR and multivessel CAD. The severity of MR was assessed by standard transthoracic echocardiography. Coronary angiography with direct visualization of stenoses > 70% was used to determine significant CAD. All 6 patients presented with clinical evidence of myocardial ischemia; 2 patients had reversible defects on stress nuclear scintigraphy and 4 patients presented with acute coronary syndrome or non-ST-elevation myocardial infarction.
All 6 patients had at least moderate/severe-to-severe grade mitral valve regurgitation. All patients also had demonstrable, severe three-vessel CAD.
The patients were treated according to routine care of the managing physicians. All of the patients were referred to the cardiac surgery department for consultation. The distribution of the types of index procedure is the following: 2 patients underwent PCI alone (after being declined by the cardiac surgery department), 2 underwent CABG alone and 2 received combined CABG/MVR — both valves were repaired rather than replaced. All patients were retrospectively followed for 4 years for major adverse cardiac events (MACE): cardiac death, myocardial infarction and target lesion revascularization.
Medical management of all of the patients included beta-blockers and afterload reduction with either an angiotensin-converting enzyme inhibitor (ACE I), an angiotensin II receptor-blocker (ARB) or isosorbidehydralazine. Continuous treatment of the patients with these medications occurred before and after the index procedure, as well as during the follow-up period. The choice of afterload reduction was made based on intolerances and renal function. Dosages were titrated based on the patients’ heart rate and blood pressure response.

Results

The baseline clinical characteristics of the patients are shown in Table 1. The characteristics were chosen based on significant predictive mortality risk factors as determined by the American College of Cardiology National Cardiovascular Data Registry (ACC-NCDR) and the Society of Thoracic Surgeons National Cardiac Surgery Database (STS) for the periprocedural PCI and operative surgical outcomes, respectively.^9,10 Important criteria from both predictive models were highlighted in the follow up. In addition, 1 patient received an intra-aortic balloon pump due to shock prior to the index procedure and was from the PCI-only group.
Clinical follow up after the index procedure showed significant improvement in MR in all of the treated patients, irrespective of the procedure performed (Table 2). Not all patients received complete revascularization due to technical infeasibility. Four of the 6 patients had remaining significant single-vessel CAD after revascularization: 1 patient was from the PCI arm, 2 patients were from the CABG arm and 1 patient was from the combined surgical arm. Significant improvement in left ventricular ejection fraction (LVEF) was observed in both patients from the PCI-only arm, in 1 of 2 patients from the CABG-only arm and no LVEF improvement was observed in the combined surgical arm. At 48 months, 1 patient in the CABG-only arm died from a cardiac cause. No other significant clinical endpoint was observed in the other patients during this period (Table 2).

Discussion
This study is a retrospective 4-year clinical follow up of 6 consecutive patients within 1 calendar year from a single center who presented with concomitant significant CAD and MR undergoing a corrective procedure involving PCI alone, CABG alone or combined CABG + MVR. Despite routine referral of such patients to cardiac surgery for CABG with or without MVR, the less invasive approach of PCI alone using DES fared well over the 4 years without reaching any of the MACE endpoints of cardiac death, MI or TLR, as compared with the CABG alone and CABG + MVR patients. The only patient who reached MACE endpoints with cardiac death during the 4 years was from the CABG-only group. Interestingly, while all 6 patients had significant improvement in MR after the index procedure, improvement in LVEF was only observed in the 2 patients in the PCI-alone group and 1 of 2 patients in the CABG-only group. Both patients in the combined CABG + MVR group and 1 of 2 patients in the CABG-only group showed no LVEF improvement. The latter was the patient who suffered cardiac death during the follow-up period.
Despite CABG being the benchmark for complete revascularization, incomplete revascularization was observed in all categories of procedures in this study: 1 of 2 patients in the PCI-alone group, both patients in the CABG-only group and 1 of 2 in the combined group. All patients began with severe three-vessel CAD, and all of the incompletely revascularized patients had 1 remaining nonrevascularized vessel.
The traditional notion of complete revascularization involving side branches has been challenged in the era of coronary stents.^11–13 Side branches, and perhaps even nondominant right coronary arteries, appear to confer no significant adverse outcome when left alone after stenting of the parent vessels. As observed in this study, CABG may not always provide more complete revascularization than PCI. Especially in smaller-caliber vessels, surgical techniques may encounter similar difficulties as percutaneous approaches. Secondly, as PCI pharmacology, equipment and techniques improve to tackle complex coronary lesions such as chronic total occlusions and bifurcation lesions,^14–16 improvement in success rates of chronic total occlusions and other difficult lesions will likely continue.^8,17 The “completeness” of revascularization between CABG and PCI is, therefore, becoming negligible. Lastly, as the durability of bypass conduits continues to be challenged by DES,^6–8 the gap between CABG and PCI in the era of DES is diminishing.
The calculated mortality risk of CABG + MVR, in general, can be several-fold of that for PCI alone.^9,10 PCI alone is not the solution for all patients with simultaneous significant MR and CAD, especially when the MR is not ischemic in nature. PCI alone, however, can be utilized as the first choice of corrective procedure. If there is no significant improvement in the MR during subsequent follow up, patients can be referred for MVR alone, which carries a lower surgicalmortality risk. Even when patients require MVR after PCI as a staged or hybrid procedure, the overall risks are reduced.¹⁸
Lastly, due to recent concern for subacute stent thrombosis with DES, prolonged administration of antiplatelet agents was given to patients receiving PCI in the study as recommended. During the retrospective follow-up period, there had been no major bleeding events with any of the studied patients. One PCI-alone patient, while still receiving clopidogrel, developed an episode of transient ischemic attack (TIA) 18 months after the procedure without a clear etiology. Another patient who underwent CABG + MVR developed postoperative TIA which resolved at discharge. The small sample size of this study cannot draw conclusions regarding the potential effects from prolonged antiplatelet therapy.
Study limitations. Limitations of this study include nonrandomization, the study’s retrospective nature, the small number of patients, the fact that it was a single-center experience and the selection bias. The choice of index procedure was based on the cardiac surgeon’s preference and confidence with each case, and was not randomly assigned. Specifically, the 2 patients receiving PCI alone were rejected for surgery due to anatomy and comorbidity issues. Contrary to expectations, these high-risk surgical patients fared well after PCI in subsequent follow up. The choice for CABG alone versus CABG + MVR was an intraoperative decision, and again not randomized. Because of the small sample size, no meaningful statistical analysis can be deduced from this study.

Conclusions
As PCI operators improve technical skills in complex coronary interventions along with the availability of DES, PCI alone can be a viable first treatment option for patients with combined significant CAD and ischemic MR. The subsequent surgical procedure, if necessary, is likely to be less risky with MVR and may result in less or no need for CABG. Large, prospective, randomized clinical studies are needed to further validate this attractive approach to treat this challenging group of patients.

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