Author + information
- Christopher D. Barrett, MD∗ (, )@cdsbarrett1,
- Lukasz Cerbin, MD,
- Aken Desai, MD and
- John D. Carroll, MD
- ↵∗Address for correspondence:
Dr. Christopher D. Barrett, University of Colorado Hospital, 12505 East 16th Avenue, 3rd Floor, Aurora, Colorado 80045.
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.)
History of Present Illness
An 87-year-old African-American woman with a history of chemotherapy-induced myocardial dysfunction initially presented with symptoms of orthopnea, dyspnea with minimal exertion, and lower extremity edema. She was found to have myxomatous mitral valve disease on surface echocardiography with a left ventricular ejection of fraction (LVEF) of 58%. Transesophageal echocardiogram showed severe degenerative mitral valve disease with 3+ mitral regurgitation, most of which resulted from poor coaptation of the A2-P2 leaflets (Figures 1 and 2, Videos 1 and 2). No isolated leaflet flail or prolapse was identified.
• To develop a differential diagnosis for recurrent dyspnea and fatigue following MitraClip placement.
• To recognize hemolytic anemia as a rare complication of the MitraClip procedure.
• To demonstrate that hemolysis secondary to MitraClip can be corrected with surgical mitral valve replacement.
The patient was evaluated in a multidisciplinary valve clinic and determined to be a high-risk candidate for surgical mitral valve replacement due to age, frailty, and history of breast cancer with chest radiation. She was instead referred for a percutaneous mitral valve repair with a MitraClip system (Abbott Vascular, Santa Clara, California), which she underwent in April 2019. She had 2 NTR clips placed between the A2 and P2 mitral valve leaflets. By transesophageal echocardiogram, residual 2+ mitral regurgitation was noted at the end of the procedure, with a mean diastolic gradient across the mitral valve of 3 mm Hg at a heart rate of 82 beats/min. The degree of residual mitral regurgitation was acceptable and expected in this case because it is challenging to achieve minimal residual mitral regurgitation using transcatheter edge to edge repair devices, particularly in degenerative mitral valve that can be classified as Barlow’s disease rather than an isolated flail leaflet. She was discharged without incident on post-procedure day 3.
She presented to the hospital 1 month after discharge with recurrent dyspnea and fatigue. She also noted dark brown urine without associated flank pain or dysuria. She was afebrile with a blood pressure of 191/92 mm Hg, heart rate of 123 beats/min, and oxygen saturation of 95% on ambient air. Physical exam showed jugular venous distension, inspiratory crackles, and bilateral lower extremity edema. On cardiac exam she was tachycardic with a regular rhythm and had a 4/6 holosystolic murmur radiating to the apex. She had no friction rub or extra heart sounds.
The patient has a history of stage III breast cancer diagnosed in 2011 for which she underwent lumpectomy, lymph node dissection, and adjuvant chemotherapy with chest radiation in 2012. She subsequently developed trastuzumab-induced cardiac dysfunction with decline in her LVEF from normal to 25%, and global hypokinesis of the left ventricle. Echocardiogram at that time showed mild-to-moderate mitral valve regurgitation without prolapse of the mitral valve leaflets. Trastuzumab therapy was stopped, and she was treated with guideline-directed medical therapy and had recovery of her LVEF to 65% by 2018 with only mild mitral regurgitation.
The differential diagnosis for her symptoms included hemolytic anemia related to her MitraClip procedure, clip failure with single leaflet detachment, progression of mitral stenosis, and hypertensive crisis resulting in symptoms of worsening congestive heart failure.
Electrocardiogram (ECG) showed sinus tachycardia with biatrial enlargement and left ventricular hypertrophy by voltage criteria. Repeat transthoracic echocardiogram showed normal LVEF with moderate mitral regurgitation that appeared similar to her post-MitraClip echocardiogram. There was no evidence of single leaflet detachment. There was no new leaflet prolapse, flail, or perforation. Her transmitral diastolic gradient was measured at 5 mm Hg at a heart rate of 96 beats/min. Repeat transesophageal echocardiogram showed a high-velocity regurgitant jet lateral to the 2 MitraClips (Figures 1 to 3, Videos 3, 4, 5, and 6). The peak regurgitant velocity was 6.0 m/s with a peak systolic gradient of 144 mm Hg.
Laboratory evaluation was notable for a decline in hemoglobin from 14.3 g/dl at the time of her MitraClip procedure to 9.3 g/dl at the time of admission. Dipstick urinalysis showed dark urine with a large quantity of blood but few red blood cells by microscopy (Table 1). No leukocytosis, pulmonary infiltrates, or urinary infection were identified. Peripheral blood smear showed 3+ schistocytes, serum haptoglobin was <30 mg/dl, serum lactate dehydrogenase was elevated at 2,153 U/l, reticulocyte index was 3.8, and a direct agglutination test was negative. Given her race, she was evaluated for glucose-6-phosphate dehydrogenase (G6PD) deficiency as a cause of hemolysis and was found to have normal G6PD enzyme activity level (16.3 U/l).
The patient was initially managed with intravenous antihypertensive and diuretic therapy. She was transfused to maintain a serum hemoglobin >8 g/dl. Hematology was consulted and agreed with the diagnosis of intravascular hemolysis associated with her MitraClip procedure. Despite symptomatic improvement with blood pressure control and volume optimization, it was considered unlikely that she would sustain long-term improvement with an ongoing intravascular hemolysis requiring blood transfusion. No cause of hemolysis was identified other than MitraClip placement with a high-velocity and turbulent regurgitant jet. She was therefore referred to cardiac surgery for reconsideration of mitral valve replacement. She underwent cardiac surgery with removal of the 2 MitraClips and placement of a 27-mm Magna Ease bioprosthetic mitral valve. Postoperative echocardiogram showed mildly reduced left ventricular systolic function (LVEF 48%) and normal functioning prosthetic mitral valve with a mean gradient of 2.9 mm Hg at a heart rate of 101 beats/min and trace prosthetic regurgitation. She was discharged home on postoperative day 12. Follow-up laboratory testing showed resolution of anemia and normalization of lactate dehydrogenase.
This is a patient who underwent a MitraClip procedure for severe degenerative mitral regurgitation. She subsequently developed a red blood cell fragmentation syndrome, very likely related to turbulent flow across her mitral valve. This probably resulted from a small, high-velocity, mitral regurgitant jet in the lateral aspect of the valve (P1-P2 commissure) adjacent to the MitraClip. It is less likely that red blood cell shearing would occur from low-velocity antegrade flow across the two MitraClip devices. No other plausible causes of hemolytic anemia were identified in this case, and hemolysis resolved after referral for surgical MitraClip explant and bioprosthetic mitral valve replacement.
The safety and efficacy of percutaneous mitral valve repair with the MitraClip system have been well established in select patients (1,2), and procedural volume has increased worldwide for management of patients with severe mitral regurgitation who are at high risk for cardiac surgery (3,4). Hemolytic anemia is a rare, but well-described complication of surgical mitral valve repair (5). Clinically significant hemolysis has only been previously reported once after percutaneous MitraClip placement (6). Management of MitraClip-associated red blood cell fragmentation syndrome with MitraClip removal has not been previously reported.
The patient had resolution of hemolysis and hemoglobinuria as well as normalization of her hemoglobin after surgical MitraClip explant and mitral valve replacement. She was recently diagnosed with recurrent biventricular systolic heart failure, which is being managed in the ambulatory setting.
This case is an example of intravascular hemolytic anemia occurring secondary to MitraClip placement, a rare adverse event that was alleviated with surgical valve replacement.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Case Reports author instructions page.
- Abbreviations and Acronyms
- left ventricular ejection fraction
- Received February 18, 2020.
- Revision received May 1, 2020.
- Accepted May 6, 2020.
- 2020 The Authors
- Maisano F.,
- Franzen O.,
- Baldus S.,
- et al.
- Zhou S.,
- Egorova N.,
- Moskowitz G.,
- et al.
- Abourjaili G.,
- Torbey E.,
- Alsaghir T.,
- Olkovski Y.,
- Costantino T.
- Yokoyama H.,
- Mizuno S.,
- Saito S.