Severe Intravascular Hemolysis Following Mitral Valve Repair

ABSTRACT: We report two cases of severe intravascular hemolysis (IVH) following mitral valve repair using a Cosgrove-Edwards ring. In both cases, the degree of mitral regurgitation (MR) seen postoperatively worsened significantly compared to intraoperative transesophageal echocardiogram. Both patients required reoperation with mitral valve replacement with immediate resolution of the hemolysis. We hypothesize that the mitral regurgitation in the setting of an inadequate mitral valve repair is responsible for the hemolysis and propose various mechanisms to explain this pathophysiology. Although IVH remains a rare complication following mitral valve repair, possible screening recommendations should be considered for early detection and treatment given the growing number of mitral valve repairs being performed.

Key words: hemolysis, mitral regurgitation, postoperative complications, heart surgery

Mitral valve repair for regurgitant lesions has become popular due to the improved early and long term morbidity and mortality compared with mitral valve replacement.^1,2 Common complications requiring reoperation following mitral valve repair include dehiscence of the prosthetic mitral ring, improper ring size, or residual regurgitation due to interrupted sutures.³ Severe intravascular hemolysis (IVH) following mitral valve repair remains a rare but important entity to acknowledge and treat appropriately. We present two cases of severe IVH following mitral valve repair that required reoperation with immediate resolution of the hemolysis. Case 1. A 68-year-old woman with a prior history of coronary artery disease with stenting to the right coronary artery (RCA) in 2001 developed progressive dyspnea and fatigue with minimal exertion. Cardiac catheterization revealed mild to moderate (50–60%) in-stent restenosis of the RCA. Left ventriculogram showed normal left ventricular function with moderate to severe MR. Transesophageal echocardiogram (TEE) revealed poor coaptation of the mitral valve leaflets with severe (4+) MR by color flow doppler with moderate left atrial enlargement and mild to moderate aortic regurgitation. The effective regurgitant orifice (ERO) by the PISA method was 0.44 cm2, consistent with severe MR. During surgery, the only abnormality was a dilated annulus with an otherwise intact mitral valve. A #28 Cosgrove-Edwards ring was inserted and both saline injection under pressure into the left ventricle and intraoperative TEE revealed no significant MR. A vein graft to the right coronary artery was also performed. Postoperatively, the patient developed ST segment elevation in the inferior leads with reciprocal ST segment depression in the anterior-lateral leads. There was no hemodynamic instability but subsequent increases in serum levels of CK-MB were seen. The ECG changes and myocardial injury were attributed to air in the coronary arteries at the time of surgery. The patient also developed postoperative atrial fibrillation and a transthoracic echocardiogram (TTE) performed during this time showed a reduced ejection fraction of 40% with global hypokinesis and moderately severe eccentric MR (anteromedial jet) (Figure 1A). Atrial fibrillation spontaneously resolved and the patient was discharged in stable condition on postoperative day-8 with the plan to repeat the echocardiogram to evaluate the residual MR. Three weeks after surgery, the patient was readmitted for shortness of breath with a hematocrit of 21%. Coagulation studies revealed an INR of 9.4 while on coumadin and a gastrointestinal hemorrhage was ruled out with a negative stool hemoccult and normal upper endoscopy. LDH, total bilirubin, and reticulocyte count level were elevated at 2254 U/L, 3.1 mg/dL and 10.0% respectively while the haptoglobin was decreased at 6.5 mg/dL confirming intravascular hemolysis. Direct Coombs test was negative and no other causes for anemia or hemolysis were identified. Repeat echocardiogram was performed which demonstrated persistent moderate to severe MR with the same eccentric jet directed anteromedially (Figure 1B). Due to the severe hemolysis and the underlying significant MR, the patient underwent reoperation that revealed an intact annuloplasty ring. Poor coaptation of the mitral valve leaflets was observed. Both the anterior mitral valve leaflet and annuloplasty ring were removed and replaced with a #25 Carpentier-Edwards bioprosthetic pericardial valve. Intraoperative TEE revealed no periprosthetic leak. Immediately after surgery, the hemolysis resolved, and there was no evidence of MR on transthoracic echocardiogram (Figure 1C). Case 2. A 47-year-old male with a history of myxomatous mitral valve and prolapse of the anterior mitral valve leaflet had evidence of moderate to severe MR, left ventricular enlargement with an end-diastolic dimension of 71 mm and end-systolic dimension of 41 mm, an ejection fraction of 76% and left atrial enlargement. He underwent mitral valve repair that revealed a myxomatous valve with a few ruptured chordae on the lateral portion of the anterior mitral leaflet. Mitral valve repair was performed with chordal transfer and placement of a #34 Cosgrove-Edwards annuloplasty ring. Intraoperative TEE revealed trace MR; however, a repeat TTE a month later revealed moderate to severe MR. The patient returned three months later with complaints of dark urine, dyspnea on exertion and jaundice. Labs revealed a severe anemia with a hematocrit of 19.7%, an elevated total bilirubin of 2.9 mg/dL and LDH of 4002 U/L, and a peripheral blood smear showed schistocytes consistent with a hemolytic anemia. Direct and indirect Coombs test were negative and no other causes for anemia or hemolysis were identified. Repeat TTE revealed moderate to severe MR that appeared unchanged from the prior echo performed. Due to the persistent hemolysis and anemia requiring multiple blood transfusions, the patient underwent reoperation six months later that revealed complete disruption of the posterior annuloplasty ring with perforation of the posterior leaflet. The patient underwent mitral valve replacement with a #33 St. Jude valve with immediate resolution of the hemolysis postoperatively. Discussion. Intravascular hemolysis associated with valvular disease is commonly recognized in the setting of mechanical prosthetic valves and stenotic lesions. However, MR due to inadequate mitral valve repair as a cause of hemolysis is not well-known. Indications for reoperation following mitral valve repair include dehiscence of the prosthetic mitral ring or chordal repair, improper ring size, or residual regurgitation due to interrupted sutures.³ The causes of recurrent MR with an intact site of repair include a ruptured chordae tendinae and a flail or perforated leaflet.⁴ In our patients, resolution of the hemolysis with reoperation confirms the benefits of re-repair or mitral valve replacement for severe intravascular hemolysis as documented in one previous study.⁵ Several mechanisms may explain the etiology of hemolysis following mitral valve repair with or without an annuloplasty ring. The proposed mechanisms include: “whiplash motion” of disrupted sutures,⁶ annuloplasty ring dehiscence producing para-ring regurgitant jets,^7,8 protruding foreign materials such as suture material or pledgets that red blood cells may collide with,^9,10 nonendothelialization of sutures or rings,¹¹ and turbulent regurgitant jets against the left atrial wall.¹² Further studies have implicated certain hydrodynamic mechanisms that are associated with high shear stress which may produce hemolysis after inadequate mitral valve repair as assessed by 2-D and color flow Doppler echocardiography.¹³ The patterns of regurgitant flow associated with hemolysis include collision of the regurgitant jet against a solid structure such as a ring or pledget, rapid acceleration of the regurgitant jet through a small orifice ( 2 mm in diameter) and not constrained by a solid structure, or slow deceleration — eccentric regurgitant jet through a large orifice that adheres to the left atrial wall. In Case 1, the patient developed moderately severe eccentric MR with an anteromedial jet postoperatively from the mitral valve repair. The mechanism of collision was the most likely culprit of hemolysis as the anteromedial jet created a high shear stress against the Cosgrove-Edwards ring. In Case 2, the patient developed moderate to severe MR postoperatively. The hemolysis here was probably due to the rapid acceleration of the regurgitant jet through the perforated posterior leaflet. The occurrence of hemolysis following mitral valve repair is independent of the severity of MR and the presenting symptoms are usually within the first several months after the initial repair.¹⁴ Hemolysis occurred within the first month in Case 1 and within three months in Case 2. Furthermore, the degree of MR seen during intraoperative TEE may not accurately predict the severity of MR postoperatively, possibly because of the altered loading conditions induced by general anesthetics. The two cases presented both had minimal MR intraoperatively but subsequently developed moderate to severe MR. The MR was discovered a few days postoperatively in Case 1 and one month later in Case 2. Although mitral valve repair is associated with a lower early and long term morbidity and mortality than with mitral valve replacement, IVH after mitral valve repair remains a serious complication. Both the surgeon and cardiologist must suspect IVH if more than trivial MR is noted following mitral valve repair.¹⁵ Although rare, IVH represents a potentially lethal complication which can be reversed through reoperation, provided that it is detected early. Possible screening recommendations should be considered for early detection and treatment given the growing number of mitral valve repair operations being performed. In the absence of prior data, we propose that in addition to intraoperative TEE, patients be screened for recurrent MR, laboratory indices be monitored for hemolysis, and a postoperative TEE performed prior to discharge.