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CASE REPORT

CLINICAL CASE

Red Blood Cell Fragmentation SyndromeAfter Placement of MitraClip

Christopher D. Barrett, MD, Lukasz Cerbin, MD, Aken Desai, MD, John D. Carroll, MD

ABSTRACT

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An 87-year-old woman with a history of trastuzumab-induced left ventricular dysfunction underwent the MitraClip

(Abbott Vascular, Santa Clara, California) procedure for myxomatous mitral regurgitation. She presented a month later

with severe intravascular hemolytic anemia, attributed to the MitraClip. She underwent surgical mitral valve replacement

and had resolution of hemolysis. (Level of Difficulty: Advanced.) (J Am Coll Cardiol Case Rep 2020;2:1084–8)

© 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an

open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

HISTORY OF PRESENT ILLNESS

An 87-year-old African-American woman with a his-tory of chemotherapy-induced myocardial dysfunc-tion initially presented with symptoms of orthopnea,dyspnea with minimal exertion, and lower extremityedema. She was found to have myxomatous mitralvalve disease on surface echocardiography with a leftventricular ejection of fraction (LVEF) of 58%.Transesophageal echocardiogram showed severedegenerative mitral valve disease with 3þ mitralregurgitation, most of which resulted from poor

EARNING OBJECTIVES

To develop a differential diagnosis forrecurrent dyspnea and fatigue followingMitraClip placement.To recognize hemolytic anemia as a rarecomplication of the MitraClip procedure.To demonstrate that hemolysis secondary toMitraClip can be corrected with surgicalmitral valve replacement.

N 2666-0849

m the Division of Cardiology, University of Colorado School of Medicine

y have no relationships relevant to the contents of this paper to disclose

e authors attest they are in compliance with human studies committees

tutions and Food and Drug Administration guidelines, including patient co

JACC: Case Reports author instructions page.

nuscript received February 18, 2020; revised manuscript received May 1,

coaptation of the A2-P2 leaflets (Figures 1 and 2,Videos 1 and 2). No isolated leaflet flail or prolapsewas identified.

The patient was evaluated in a multidisciplinaryvalve clinic and determined to be a high-risk candi-date for surgical mitral valve replacement due to age,frailty, and history of breast cancer with chest radia-tion. She was instead referred for a percutaneousmitral valve repair with a MitraClip system (AbbottVascular, Santa Clara, California), which she under-went in April 2019. She had 2 NTR clips placed be-tween the A2 and P2 mitral valve leaflets. Bytransesophageal echocardiogram, residual 2þ mitralregurgitation was noted at the end of the procedure,with a mean diastolic gradient across the mitral valveof 3 mm Hg at a heart rate of 82 beats/min. The degreeof residual mitral regurgitation was acceptable andexpected in this case because it is challenging toachieve minimal residual mitral regurgitation usingtranscatheter edge to edge repair devices, particularlyin degenerative mitral valve that can be classified asBarlow’s disease rather than an isolated flail leaflet.She was discharged without incident on post-procedure day 3.

https://doi.org/10.1016/j.jaccas.2020.05.009

, Aurora, Colorado. The authors have reported that

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and animal welfare regulations of the authors’ in-

nsent where appropriate. For more information, visit

2020, accepted May 6, 2020.

AB BR E V I A T I O N S

AND ACRONYM S

LVEF = left ventricular

ejection fraction

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She presented to the hospital 1 month afterdischarge with recurrent dyspnea and fatigue. Shealso noted dark brown urine without associatedflank pain or dysuria. She was afebrile with ablood pressure of 191/92 mm Hg, heart rate of123 beats/min, and oxygen saturation of 95% onambient air. Physical exam showed jugularvenous distension, inspiratory crackles, and bilat-eral lower extremity edema. On cardiac examshe was tachycardic with a regular rhythm andhad a 4/6 holosystolic murmur radiating to theapex. She had no friction rub or extra heartsounds.

FIGURE 1 Transesophageal Echocardiogram at 60� Omniplane Befor

Mitral valve visualized by transesophageal echocardiography in a mid-es

and post–MitraClip procedure after presentation with intravascular hem

MEDICAL HISTORY

The patient has a history of stage III breastcancer diagnosed in 2011 for which she un-derwent lumpectomy, lymph node dissec-

tion, and adjuvant chemotherapy with chestradiation in 2012. She subsequently developedtrastuzumab-induced cardiac dysfunction withdecline in her LVEF from normal to 25%, and globalhypokinesis of the left ventricle. Echocardiogram atthat time showed mild-to-moderate mitral valveregurgitation without prolapse of the mitral valveleaflets. Trastuzumab therapy was stopped, and she

e and After MitraClip Placement

ophageal commissural view prior to the MitraClip procedure (A, B),

olysis (C, D).

FIGURE 2 Transesophageal Echocardiogram at 120� Omniplane Before and After MitraClip Placement

Mitral valve visualized by transesophageal echocardiogram in a mid-esophageal view at 120-degree omniplane before the MitraClip procedure

(A, B), and post–MitraClip procedure (C, D).

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was treated with guideline-directed medical therapyand had recovery of her LVEF to 65% by 2018 withonly mild mitral regurgitation.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis for her symptoms includedhemolytic anemia related to her MitraClip procedure,clip failure with single leaflet detachment, progres-sion of mitral stenosis, and hypertensive crisisresulting in symptoms of worsening congestive heartfailure.

INVESTIGATIONS

Electrocardiogram (ECG) showed sinus tachycardiawith biatrial enlargement and left ventricular hyper-trophy by voltage criteria. Repeat transthoracicechocardiogram showed normal LVEF with moderatemitral regurgitation that appeared similar to her post-MitraClip echocardiogram. There was no evidence ofsingle leaflet detachment. There was no new leafletprolapse, flail, or perforation. Her transmitral dia-stolic gradient was measured at 5 mm Hg at a heart

FIGURE 3 3-Dimensional Transesophageal Echocardiography After MitraClip Placement

Three-dimensional imaging of the mitral valve by transesophageal echocardiography following MitraClip procedure showing residual mitral

regurgitation via multiple (medial and lateral) regurgitant jets.

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rate of 96 beats/min. Repeat transesophageal echo-cardiogram showed a high-velocity regurgitant jetlateral to the 2 MitraClips (Figures 1 to 3, Videos 3, 4,5, and 6). The peak regurgitant velocity was 6.0 m/swith a peak systolic gradient of 144 mm Hg.

Laboratory evaluation was notable for a decline inhemoglobin from 14.3 g/dl at the time of her Mitra-Clip procedure to 9.3 g/dl at the time of admission.Dipstick urinalysis showed dark urine with a largequantity of blood but few red blood cells by micro-scopy (Table 1). No leukocytosis, pulmonary in-filtrates, or urinary infection were identified.Peripheral blood smear showed 3þ schistocytes,serum haptoglobin was <30 mg/dl, serum lactatedehydrogenase was elevated at 2,153 U/l, reticulo-cyte index was 3.8, and a direct agglutination testwas negative. Given her race, she was evaluated forglucose-6-phosphate dehydrogenase (G6PD) defi-ciency as a cause of hemolysis and was found tohave normal G6PD enzyme activity level (16.3 U/l).

MANAGEMENT

The patient was initially managed with intravenousantihypertensive and diuretic therapy. She wastransfused to maintain a serum hemoglobin >8 g/dl.Hematology was consulted and agreed with thediagnosis of intravascular hemolysis associated withher MitraClip procedure. Despite symptomaticimprovement with blood pressure control and vol-ume optimization, it was considered unlikely that

she would sustain long-term improvement with anongoing intravascular hemolysis requiring bloodtransfusion. No cause of hemolysis was identifiedother than MitraClip placement with a high-velocityand turbulent regurgitant jet. She was thereforereferred to cardiac surgery for reconsideration ofmitral valve replacement. She underwent cardiacsurgery with removal of the 2 MitraClips andplacement of a 27-mm Magna Ease bioprostheticmitral valve. Postoperative echocardiogram showedmildly reduced left ventricular systolic function(LVEF 48%) and normal functioning prostheticmitral valve with a mean gradient of 2.9 mm Hg at aheart rate of 101 beats/min and trace prostheticregurgitation. She was discharged home on post-operative day 12. Follow-up laboratory testingshowed resolution of anemia and normalization oflactate dehydrogenase.

DISCUSSION

This is a patient who underwent a MitraClip proced-ure for severe degenerative mitral regurgitation. Shesubsequently developed a red blood cell fragmenta-tion syndrome, very likely related to turbulent flowacross her mitral valve. This probably resulted from asmall, high-velocity, mitral regurgitant jet in thelateral aspect of the valve (P1-P2 commissure) adja-cent to the MitraClip. It is less likely that red bloodcell shearing would occur from low-velocity ante-grade flow across the two MitraClip devices. No other

TABLE 1 Laboratory Trends Suggestive of Intravascular Hemolysis Following MitraClip

Procedure With Resolution in Hemolysis and Hemoglobinuria After Surgical Clip Removal

and Mitral Valve Replacement

BeforeMitraClip

AfterMitraClip

Post -Mitral ValveReplacement

HGB, g/dl 14.4 8.2 14.2

HCT, % 42.8 26.3 42

LDH, U/l — 2,153 284

Total bilirubin, mg/dl 0.9 2.6 1.3

Hematuria on microscopy Negative 3þ Negative

RBC on urine microscopy(cells per high power field)

0-3 4-10 0-3

HCT ¼ hematocrit; HGB ¼ hemoglobin; LDH ¼ lactate dehydrogenase; RBC ¼ red blood cells.

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plausible causes of hemolytic anemia were identifiedin this case, and hemolysis resolved after referral forsurgical MitraClip explant and bioprosthetic mitralvalve replacement.

The safety and efficacy of percutaneous mitralvalve repair with the MitraClip system have been wellestablished in select patients (1,2), and proceduralvolume has increased worldwide for management ofpatients with severe mitral regurgitation who are athigh risk for cardiac surgery (3,4). Hemolytic anemiais a rare, but well-described complication of surgical

mitral valve repair (5). Clinically significant hemolysishas only been previously reported once after percu-taneous MitraClip placement (6). Management ofMitraClip-associated red blood cell fragmentationsyndrome with MitraClip removal has not been pre-viously reported.

FOLLOW-UP

The patient had resolution of hemolysis and hemo-globinuria as well as normalization of her hemoglobinafter surgical MitraClip explant and mitral valvereplacement. She was recently diagnosed withrecurrent biventricular systolic heart failure, which isbeing managed in the ambulatory setting.

CONCLUSIONS

This case is an example of intravascular hemolyticanemia occurring secondary to MitraClip placement, arare adverse event that was alleviated with surgicalvalve replacement.

ADDRESS FOR CORRESPONDENCE: Dr. ChristopherD. Barrett, University of Colorado Hospital, 12505 East16th Avenue, 3rd Floor, Aurora, Colorado 80045.E-mail: cdsbarrett@gmail.com. Twitter: @cdsbarrett1.

RE F E RENCE S

1. Feldman T, Foster E, Glower DD, et al. Percu-taneous repair or surgery for mitral regurgitation.N Engl J Med 2011;364:1395–406.

2. Stone GW, Lindenfeld J, Abraham WT, et al.Transcatheter mitral-valve repair in patientswith heart failure. N Engl J Med 2018;379:2307–18.

3. Maisano F, Franzen O, Baldus S, et al.Percutaneous mitral valve interventions in thereal world: early and 1-year results from theACCESS-EU, a prospective, multicenter, non-randomized post-approval study of the MitraClip

therapy in Europe. J Am Coll Cardiol 2013;62:1052–61.

4. Zhou S, Egorova N, Moskowitz G, et al. Trendsin MitraClip, mitral valve repair, and mitral valvereplacement from 2000 to 2016. J Thorac Car-diovasc Surg 2020 Jan 20 [E-pub ahead of print].

5. Abourjaili G, Torbey E, Alsaghir T, Olkovski Y,Costantino T. Hemolytic anemia following mitralvalve repair: a case presentation andliterature review. Exp Clin Cardiol 2012;1:248–50.

6. Yokoyama H, Mizuno S, Saito S. Sub-acute hemolytic anemia after transcatheter

edge-to-edge mitral valve repair: a casereport. Catheter Cardiovasc Interv 2020;95:1230–4.

KEY WORDS echocardiography, hemolysis,insufficiency, MitraClip, mitral valve, valverepair

APPENDIX For supplemental videos,please see the online version of this paper.