Percutaneous Edge-to-Edge Repair of Mitral Regurgitation as a Bail-Out Strategy in Critically Ill Patients

Abstract: Percutaneous edge-to-edge mitral valve repair using the MitraClip device has evolved as a new tool for the treatment of severe mitral valve regurgitation. This technique has been evaluated in both surgical low- and high-risk patients. The aim of this study was to assess the feasibility and efficacy of MitraClip implantation in critically ill, unstable patients with severe mitral regurgitation who would persistently need inotropes or who could not be weaned from a ventilator. Six patients with the above-mentioned criteria were identified among the 87 patients that were treated with MitraClip implantation between October 2009 and January 2012 at our institution. All patients were considered as surgical high-risk patients with a Society of Thoracic Surgeons (STS) score between 8.0% and 56.9%. In all patients, MitraClip implantation was successfully achieved without relevant complications. More importantly, all patients showed rapid clinical improvement within a few days, allowing discontinuation of inotropes and/or weaning from a respirator and finally a transfer to a regular ward or discharge home. These data emphasize the safety profile of the MitraClip system in multimorbid, high-risk patients. In addition, it demonstrates the applicability of this treatment in unstable and critically ill conditions as a tool for acute stabilization. 

J INVASIVE CARDIOL 2013;25(2):69-72

Key words: mitral valve repair, heart failure

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Percutaneous edge-to-edge mitral valve repair using the MitraClip device has evolved as a promising tool for the treatment of severe mitral valve regurgitation. This technique has been evaluated in patients who are eligible for surgery in multicenter trials.^1,2 Recently, the first randomized controlled study (EVEREST II, ClinicalTrials.gov NCT00209274) demonstrated superior safety compared to surgical mitral valve repair with inferior clinical efficacy, but similar improvements in clinical outcomes.² An increasing number of studies have now shown feasibility and safety of MitraClip implantation in high-risk patients, including patients with severely reduced ejection fraction.^3-11 In summary, these publications give evidence that it is safe and effective to use this technique in patients with advanced age and/or extensive multimorbidity and/or severe heart failure. This combination of a high safety profile and sufficient efficacy in reducing mitral valve regurgitation may lead to MitraClip implantations even in acute and critically ill conditions. Unstable patients with very high surgical risks are not ideal candidates for emergent surgery. Therefore, the aim of this study was to retrospectively analyze patients who underwent MitraClip implantation and who were in a critically ill condition. This condition was defined as a patient who could not be weaned from inotropes, who could not be weaned from a ventilator, or who was not stable enough to leave an intensive care unit and be treated on a regular ward, after at least 2 weeks of intensive care treatment.

Methods

From October 2009 to January 2012, a total of 87 patients were treated with MitraClip implantation at our institution. Of these 87 patients, 6 were in persistent unstable condition according to the above-mentioned criteria. All patients suffered from symptomatic severe mitral valve regurgitation and already had optimal medical therapy or were on inotropes. All patients were surgically or interventionally revascularized, if appropriate. None of these patients were ideal surgical candidates due to extensive comorbidities. Prior to MitraClip implantation, all patients received transthoracic (TTE) and transesophageal echocardiography (TEE) to quantify mitral valve regurgitation and to judge morphologic suitability for MitraClip implantation. Main exclusion criteria were morphologic properties of the mitral valve that would make MitraClip implantation impossible or unlikely, as published previously.¹¹ All patients were informed about specific risks and alternatives and gave informed written consent to the MitraClip procedure and pre- and postinterventional monitoring (data collection). The study protocol was in accordance with the local ethics committee.

TTE and TEE were performed using commercially available ultrasound diagnostic systems (iE33, Philips Medical Systems) by experienced investigators unaware of the study and according to current recommendations.¹² Three cardiac cycles were stored in cine loop format for offline analysis. Offline analysis of echocardiography examinations was conducted on a commercial workstation (Centricity Cardiology CA1000 2.0, GE Medical Systems) by two independent expert investigators who were unaware of the patients’ clinical statuses and were not involved in MitraClip implantation procedures. Since the prevalence of eccentric mitral regurgitation in the study population was high, the method of the proximal isovelocity surface area (PISA) for grading mitral regurgitation was not employed. Instead, mitral regurgitation was graded in a semiquantitative manner with color Doppler, added to the assessment of the width of the vena contracta. This was similarly used for the post-implant grading of mitral regurgitation.     

The endovascular edge-to-edge mitral valve repair has been previously described.^1,2 All procedures were performed using the 24 Fr MitraClip device (Abbott Vascular). All clips were implanted under general anesthesia and TEE control. Hemostasis was achieved by compression of the vein for 12 hours. Patients were transferred to our intensive care unit after the procedure (for at least 24 hours).

Due to the limited number of patients, no statistical analysis has been applied. Therefore, an individual description of each case will be presented.

Results

All patients were considered to be surgical high-risk patients with a Society of Thoracic Surgeons (STS) score between 8.0% and 56.9%. Interestingly, the STS score did not necessarily reflect the extent of the critical condition, showing the lowest score (8.0%) in one of the sickest patients. Patients’ baseline characteristics are summarized in Table 1. All 6 patients were successfully implanted with one or two MitraClips. A schematic summary of the patients’ hospital courses is shown in Figure 1. In the following section, the individual patients will be described:

Patient 1. A 61-year-old male patient with an STS score of 8.0% was initially admitted to our hospital with an acute ST-elevation myocardial infarction. The left main stem was occluded and was successfully revascularized with thrombus aspiration and stent implantation. The patient was in pulmonary edema upon admission and had to be intubated prior to the cardiac catheterization. Despite revascularization, the patient developed a severely reduced left ventricular function with an ejection fraction of 20%. In the following weeks, a mitral regurgitation (MR) was detected with increasing severity, finally reaching an MR grade 4+. In addition, the patient developed repetitive respiratory tract infections including septicemia 2 months after the myocardial infarction. The patients could not be extubated at any time and had been tracheotomized two weeks after admission. After being free of infections, the patient could still not be weaned from the ventilator. Finally, a MitraClip implantation with two clips was successfully performed on day 75 after admission. After another 6 days, the patient was completely weaned from the respirator and was decannulated and transferred to a regular ward after another week.

Patient 2. A 70-year-old male patient with an STS score of 48.5% was initially admitted to our hospital with an acute non-ST elevation myocardial infarction and pulmonary edema. The patient had undergone coronary bypass surgery 16 years ago. Further comorbidities included terminal renal failure, severe chronic obstructive pulmonary disease, peripheral vascular disease with prior bypass surgery, cerebrovascular disease with prior stent implantation, and severely reduced left ventricular ejection fraction (EF) of 30%. Despite interventional revascularization (stent implantation of the left circumflex artery) and optimal fluid management, the patient could not be weaned from inotropes. Thus, a newly diagnosed severe mitral regurgitation was successfully treated with MitraClip implantation on day 37 after admission. Inotropes were discontinued 1 day after implantation and the patient was discharged home 7 days later. 

Patient 3. A 63-year-old male patient with an STS score of 29.9% was initially admitted to our hospital with an acute non-ST elevation myocardial infarction. The patient had undergone coronary bypass surgery 2 years prior. Upon admission, the left internal mammary artery was degenerated and the patient received a stent into the left main coronary artery. He showed a new onset of severe mitral regurgitation due to papillary muscle dysfunction with signs of severe heart failure and severely reduced left ventricular ejection fraction (30%). Due to persistent need of inotropes, the patient was successfully treated with MitraClip implantation on day 16 after admission. Inotropes were discontinued 1 day after implantation and the patient was transferred to a regular ward 8 days later.

Patient 4. A 73-year-old female patient with an STS score of 9.8% was initially admitted to our hospital with an acute ST-elevation myocardial infarction. The left anterior descending artery was occluded and was successfully revascularized with thrombus aspiration and stent implantation. She showed a new onset of severe mitral regurgitation due to papillary muscle dysfunction with signs of severe heart failure and severely reduced left ventricular ejection fraction (20%). In addition, the patient suffered from severe chronic obstructive pulmonary disease and peripheral vascular disease. The patient could not be discharged home for 3 months due to repetitive pulmonary edemas. Finally, the patient was successfully treated with MitraClip implantation at day 113 after initial admission and could be transferred to a regular ward 6 days later, being weaned from inotropes.

Patient 5. An 81-year-old male patient with an STS score of 56.9% was initially admitted to our hospital with severe decompensated heart failure and pulmonary edema due to ischemic cardiomyopathy (25%) requiring intubation and mechanical ventilation. This patient also suffered from terminal renal failure, prior stroke, and peripheral vascular disease requiring bypass surgery 2 years prior. Cardiac angiography showed significant stenosis of the left circumflex coronary artery, which was treated by stent implantation. The patient could be extubated after 5 days, but persistently required inotropes despite optimal fluid management. Echocardiography showed severe eccentric mitral regurgitation due to dilatation of the left ventricular annulus and tethering of the posterior mitral leaflet. Finally, the patient was successfully treated with MitraClip implantation on day 10 after initial admission and discharged home 3 days later.

Patient 6. A 64-year-old male patient with an STS score of 10.7% was initially admitted to our hospital with decompensated heart failure and pulmonary edema due to dilated cardiomyopathy with an ejection fraction of 25%. He had been hospitalized for 1 month prior to MitraClip implantation and was hospitalized twice within the last 12 months. In addition to a newly diagnosed severe mitral regurgitation, the patient also suffered from severe renal failure and chronic obstructive pulmonary disease. Due to repetitive pulmonary edema, the patient was successfully treated with implantation of 2 MitraClips on day 30 after initial admission. The patient was then discharged home 4 days later.

All patients showed a significant reduction of their mitral regurgitation after the MitraClip implantation in echocardiography control examinations, varying between 1+ and 2+ regurgitation. No patient showed any signs of mitral valve stenosis. No patient had any pericardial effusion. No vascular complications were reported and no blood transfusion was needed. Follow-up in these patients was limited, since 3 patients died within 1 year (patient 2 due to pneumonia, patient 3 due to septicemia with multi-organ failure, and patient 6 due to sudden cardiac death) and patient 5 was lost to follow-up. Patient 1 and patient 4 were still alive after 1 year with stable echocardiographic results. Compared to our regular patients who have received MitraClips at our institution, the patients in this report had significantly higher surgical risks (STS score, 27.3 ± 21% vs 12.2 ± 2%; P<.01). This was mainly due to more severe comorbidities (not necessarily taking into account the acute critical situation), most likely translating into the higher 1-year mortality (50% vs 13%). 

Discussion

Several studies have shown feasibility and safety of MitraClip implantation in low-risk and high-risk patients. Most centers use this technique for patients who are not ideal candidates for surgery due to very high surgical risks and/or severely reduced EF. 

In this small study, we report about our experience in extremely sick, unstable patients who received MitraClip implantation as a bail-out strategy to achieve stabilization. All patients were considered as surgical high-risk patients and were not able to leave an intensive care unit due to their critical clinical condition. Despite the advanced multimorbidity of these patients with their critical condition, MitraClip implantation was successfully achieved in all 6 patients without relevant complications. This verifies our previous findings about safety of the MitraClip procedure.¹¹ 

As far as the low numbers of patients allow, no technical differences were seen between these patients and our regular patients when duration and challenges in MitraClipimplantation are compared. However, cardiac anesthesiologists reported higher catecholamine demand during anesthesia.

More interestingly, all patients showed remarkably rapid improvement in their clinical condition, leading to transfer to a regular ward or discharge within a few days. This result has several important implications. 

First, it emphasizes the usefulness of endovascular edge-to-edge repair of severe mitral valve regurgitation in high-risk patients for whom surgical mitral valve repair is considered to be too risky. Basically, no patient group seems to be too unstable for this procedure, unless even inotropes would be insufficient to maintain circulation during anesthesia. 

It also emphasizes the need to focus more on mitral regurgitation in patients with cardiovascular instability. All patients had relevant problems in addition to their mitral regurgitation (such as severely reduced EF). Nevertheless, in all patients, the sole reduction of mitral regurgitation to grade 1+ or 2+ was apparently sufficient to rapidly improve their clinical condition. This suggests that severe mitral regurgitation might be even underestimated as a leading problem in similar patients.

Finally, MitraClip implantation should be part of the evaluation process of patients on cardiovascular intensive care units, if mitral regurgitation is present. This might include a review of patients together with interventionalists as a routine concept.

A critical aspect in these patients is the overall extremely high 1-year mortality, despite the initial success. This is mainly due to the combination of multimorbidity, age, prolonged intensive care treatment, and severely reduced EF. Even without any mitral regurgitation, the one mortality would have been high. Nevertheless, MitraClip implantation showed initial stabilization, giving the patients a chance for survival. It is conceivable that some of the surviving patients would not have survived 1 year without MitraClip implantation.

Our study’s main limitation is related to the number of patients. Here, we only describe single cases that do not allow any statistical analysis or strong recommendations. This is due to the overall low absolute numbers of MitraClip implantations that can be performed in a single center and the selection of “extreme” cases. Nevertheless, at this still quite early stage of the endovascular edge-to-edge repair concept of mitral regurgitation, these data are important and encouraging. We have gained a new tool that allows a rescue procedure in unstable patients with very low procedural risks and remarkable clinical efficacy. Therefore, further focused analysis of this very patient population should be attempted both in single- and multicenter studies. Only then will we also be able to judge the prognostic value of this technique in critically ill patients.

References

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From the Department of Cardiology, University of Heidelberg, Heidelberg, Germany.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted June 6, 2012, provisional acceptance given July 2, 2012, final version accepted July 27, 2012. 

Address for correspondence: Raffi Bekeredjian, MD, Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Email: raffi.bekeredjian@med.uni-heidelberg.de