Background
For patients with severe, symptomatic aortic stenosis (AS) who are poor surgical candidates, transcatheter aortic valve replacement (TAVR) provides a less invasive approach, aimed at improving symptoms, functional capacity, and survival. Patients with hematologic neoplasms represent a high-risk subset of patients, with an increased risk of bleeding and infection. 1 As a result, these patients have classically been excluded from clinical investigation in TAVR. However, if not for AS, many of these patients can anticipate years of longevity with close hematologic follow-up and treatment. 2 Take-Home Message • Transcatheter aortic valve replacement appears to be a viable therapy for select patients with hematologic neoplasms and severe aortic stenosis, with minimal periprocedural complications and favorable survival at 1 year post-procedure.
Existing literature regarding TAVR in patients with hematologic neoplasms is limited, with mixed case results. While some have demonstrated successful procedures with minimal complications, others have highlighted the increased perioperative morbidity and mortality associated with this high-risk population. 3 , 4 , 5 , 6 , 7 Our case series adds to the existing literature and seeks to better characterize outcomes of TAVR in patients with hematologic neoplasms and severe AS.
Methods
Patients with AS presenting for management evaluation and noted to have hematologic neoplasms in their active clinical history were prospectively monitored in a clinical registry, including clinical characteristics and malignancy history. All patients had severe AS and were evaluated by a multidisciplinary heart team, which determined that aortic valve intervention was feasible. After accrual of 10 consecutive patients with follow-up data, procedural features and postprocedural outcomes were assessed. Hematologic neoplasms were defined according to World Health Organization classifications, encompassing myeloid, lymphoid, plasma cell, and histiocytic/dendritic neoplasms characterized by lineage, cell maturity, genetic features, and clinical behavior. 8
Cases
Case 1
A 78-year-old man with myelodysplastic syndrome (MDS) complicated by transfusion-dependent anemia and thrombocytopenia presented with exertional dyspnea and chest discomfort, progressing to NYHA functional class III symptoms. Given his favorable response to chemotherapy and encouraging prognosis, the decision was made to proceed with TAVR.
After multiple transfusions, his preprocedural hemoglobin level and platelet count were 9.0 g/dL and 90 × 10 3 /μL, respectively. He underwent successful TAVR without complication and was discharged home on postoperative day (POD) 1. He was started on clopidogrel monotherapy for 3 months before transitioning to aspirin monotherapy. At 1 year post-procedure, he remained clinically stable from a cardiac perspective and reported significant symptomatic improvement consistent with NYHA functional class I-II symptoms.
Case 2
A 67-year-old man with polycythemia vera and post-polycythemia vera myelofibrosis presented with NYHA functional class III exertional dyspnea. His myelofibrosis was clinically stable on ruxolitinib, prompting the decision to proceed with TAVR.
Before TAVR, his hemoglobin level and platelet count were 12.2 g/dL and 107 × 10 3 /μL, respectively. He underwent successful TAVR without intraoperative complications. His postoperative course was complicated by acute respiratory failure due to transfusion-related acute lung injury after a packed red blood cell transfusion. He was discharged home on POD 11 on aspirin monotherapy. Postoperatively, he reported resolution of dyspnea and marked improvement in energy levels. At 15 months post-TAVR, he was diagnosed with acute lymphoblastic leukemia. He remained clinically stable from a cardiac perspective until he died of septic shock 21 months post-TAVR.
Case 3
A 77-year-old woman with MDS with increased blasts, grade 2, presented with NYHA functional class III dyspnea and fatigue. She was undergoing chemotherapy with azacitidine and venetoclax, and her MDS was complicated by transfusion-dependent anemia, requiring chronic biweekly transfusions. Stem cell transplantation had been planned, but was deferred due to severe AS. As her MDS was considered to be manageable, the decision was made to proceed with TAVR.
Before TAVR, her hemoglobin level and platelet count were 6.9 g/dL and 39 × 10 3 /μL, respectively. She underwent successful TAVR without complications. She was discharged home on POD 1 with aspirin monotherapy. She underwent successful stem cell transplantation 2 months post-TAVR and had no cardiac complications 2.5 years post-TAVR.
Case 4
An 84-year-old man with chronic lymphocytic leukemia presented with NYHA functional class III symptoms, including progressive dyspnea, fatigue, dizziness, and near-syncope. His chronic lymphocytic leukemia had been stable for years without the need for treatment initiation; hence, the decision was made to proceed with TAVR.
His pre-TAVR hemoglobin level and platelet count were 11.2 g/dL and 141 × 10 3 /μL, respectively. He underwent successful TAVR without complications and was discharged home on POD 1 with aspirin monotherapy. Post-TAVR, he experienced complete resolution of symptoms (NYHA functional class I). He remained without cardiac complications 1 year post-procedure.
Case 5
A 70-year-old man with monoclonal gammopathy of undetermined significance presented with NYHA functional class IV dyspnea on milrinone infusion and a left ventricular ejection fraction of 30%. His monoclonal gammopathy of undetermined significance was stable, without any active therapy, and it was decided to proceed with TAVR.
His pre-TAVR hemoglobin level and platelet count were 13.5 g/dL and 168 × 10 3 /μL, respectively. He underwent successful TAVR without procedural complications. He was weaned off of milrinone on POD 2 and discharged home on POD 6 on aspirin monotherapy. After TAVR, his NYHA symptoms improved to functional class II, and transthoracic echocardiograms at 6 and 12 months post-TAVR showed a left ventricular ejection fraction of 60%. At 15 months post-TAVR, he developed a new onset of shortness of breath and underwent percutaneous coronary intervention with placement of 1 stent for a left anterior descending artery occlusion, but otherwise remained without cardiac complications.
Case 6
A 75-year-old man with transfusion-dependent MDS with ringed sideroblasts and multilineage dysplasia was transferred from an outside hospital for consideration of emergent valve-in-valve TAVR in the setting of acute decompensated heart failure and respiratory failure, requiring vasopressor support and intubation. Fourteen days prior, he had experienced a cardiac arrest of unknown etiology. He had previously undergone surgical aortic valve replacement with a bioprosthetic valve 10 years before this presentation.
His pre-TAVR hemoglobin level and platelet count were 9.7 g/dL and 80 × 10 3 /μL, respectively. He underwent successful TAVR without immediate complications. Postoperatively, he continued to experience further respiratory decompensation and died of persistent respiratory failure on POD 8.
Case 7
A 58-year-old man with transfusion-dependent acute myeloid leukemia (AML) presented with NYHA functional class III symptoms, including progressive fatigue and dyspnea on exertion. Given the favorable response of his AML to chemotherapy with venetoclax and azacitidine, his life expectancy was estimated to be >1 year, and the decision was made to proceed with TAVR.
His pre-TAVR hemoglobin level and platelet count were 7.8 g/dL and 70 × 10 3 /μL, respectively. He underwent successful TAVR without complication and was discharged home on POD 1 on aspirin monotherapy. Two months post-TAVR, he presented to an outside hospital with nausea, vomiting, and altered mental status. He was diagnosed with infective endocarditis involving his native tricuspid valve with presumed involvement of the prosthetic aortic valve. Given his general medical condition and pancytopenia, he was deemed a poor surgical candidate and explantation of the valve was not pursued. At 3 months post-TAVR, he died of complications due to an unexpected relapse of AML.
Case 8
A 77-year-old man with transfusion-dependent MDS with increased blasts, grade 1 was evaluated for continued NYHA functional class III-IV symptoms, with dyspnea on exertion, chest pain, and fatigue, despite 2 prior balloon aortic valvuloplasties, last performed 13 months prior. It was determined that he had a reasonable life expectancy in the setting of his MDS, and the decision was made to proceed with TAVR.
His pre-TAVR hemoglobin level and platelet count were 10.9 g/dL and 55 × 10 3 /μL, respectively. He underwent successful TAVR without an operative complication. His postoperative course was complicated by a drop in hemoglobin necessitating a packed red blood cell transfusion, as well as prolonged fevers. Given pancytopenia, an extensive infectious work-up was performed; however, no etiology was identified. He was discharged to a rehabilitation facility on POD 10 on aspirin monotherapy. He remained without further cardiac complications at 1 year post-procedure.
Case 9
A 73-year-old man with blastic plasmacytoid dendritic cell neoplasm, status post bone marrow transplant, presented with NYHA functional class III symptoms of fatigue and exertional dyspnea. Given the prolonged life expectancy of at least 3 to 4 years, the decision was made to proceed with TAVR.
His pre-TAVR hemoglobin level and platelet count were 9.1 g/dL and 47 × 10 3 /μL, respectively. He underwent successful TAVR without an operative complication. Approximately 6 hours post-TAVR, he was found to have right-sided facial droop and right upper extremity pronator drift. Brain MRI revealed 3 small embolic ischemic strokes, with the etiology possibly related to the TAVR procedure. Given his stroke, he was started on a 2-week course of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel, before transitioning to clopidogrel monotherapy. He was discharged home on POD 6 in stable condition. Post-TAVR, he experienced an improvement in symptoms to NYHA functional class I. At 3 years post-procedure, he continued to do well without further cardiac complications.
Case 10
A 74-year-old man with a history of multiple myeloma presented with NYHA functional class III symptoms, including progressive exertional dyspnea and fatigue. He was anticipating undergoing treatment for multiple myeloma. In consultation with his oncologist, it was determined that he had a reasonable life expectancy, and the decision was made to proceed with TAVR.
His pre-TAVR hemoglobin level and platelet count were 12.0 g/dL and 203 × 10 3 /μL, respectively. He underwent successful TAVR without an operative complication. He was discharged home on POD 1 on DAPT with aspirin and clopidogrel. Three days post-discharge, he represented to the emergency department with concern for palpitations and was found to be in new-onset atrial fibrillation. He subsequently underwent successful direct current cardioversion to normal sinus rhythm and returned home. At follow-up, he reported an improvement in his dyspnea and improvement to NYHA functional class I-II. At 2 years post-TAVR, he continued to do well from a cardiac perspective and was without further TAVR-related complications.
Discussion
While TAVR has become an established option for patients with severe AS who are poor surgical candidates, patients with hematologic neoplasms represent a unique and high-risk patient population, classically excluded from clinical investigation. As such, there is limited existing literature on this patient subset.
We present the largest known case series of consecutive patients in this cohort, suggesting that TAVR may be a viable therapy for select patients with hematologic neoplasms and severe symptomatic AS. All 10 patients underwent successful TAVR without intraoperative complications or bleeding-related complications, despite many patients having significant anemia and thrombocytopenia. Further, there were no peri-procedural bleeding complications and only one peri-procedural stroke. Of the 9 patients who underwent elective, nonemergent TAVR, 8 were alive at least 1 year post-procedure, with the one death related to unexpected hematologic complications rather than TAVR or cardiac complications.
In addition to procedural success, almost all patients in our series reported significant improvement in heart failure symptoms and overall quality of life, with several patients transitioning from NYHA functional class III or IV symptoms to functional class I or II. Echocardiographic parameters demonstrated consistent improvement in aortic valve hemodynamics following TAVR across the cohort ( Table 1 ). Furthermore, improvement in cardiac status after TAVR may increase treatment options for the underlying malignancy. In one of our cases, improved cardiac status post-TAVR allowed the patient to undergo stem cell transplantation, which had previously been deferred. Previous case reports have reported similar instances in which severe AS limited a patient's ability to undergo treatment for their underlying malignancy. 1 Table 1 Pre- and Post-TAVR Echocardiographic Parameters Patient Left Ventricular Ejection Fraction (%) Pre-TAVR AV Peak Velocity (m/s) Pre-TAVR AV Mean Gradient (mm Hg) Pre-TAVR AV Area (cm 2 ) Pre-TAVR Dimensionless Index Post-TAVR AV Peak Velocity (m/s) Post-TAVR AV Mean Gradient (mm Hg) Post-TAVR AV Area (cm 2 ) Post-TAVR Dimensionless Index 1 55-60 4.2 42 0.9 0.24 1.75 7 2.1 0.56 2 50-55 3.56 29 0.8 0.24 2.42 12 1.5 0.49 3 60-65 4.03 36 0.8 0.43 1.9 6 1.8 0.92 4 60-65 4.01 30 0.8 0.25 1.41 4 3.1 1.02 5 35-40 2.89 19 0.8 0.24 1.16 3 2.0 0.67 6 60-65 3.8 35 0.65 0.21 1.1 5 2.2 0.76 7 60-65 4.98 65 0.75 0.22 2.33 12 1.8 0.52 8 60-65 4.35 42 0.8 0.25 1.16 3 2.0 0.67 9 60-65 4.18 43 0.66 0.19 1.85 7 1.52 0.44 10 65-70 3.34 7 1.0 0.32 1.79 7 2.3 0.73 TAVR = transcatheter aortic valve replacement.
Table 1
Pre- and Post-TAVR Echocardiographic Parameters
TAVR = transcatheter aortic valve replacement.
| Patient | Left Ventricular Ejection Fraction (%) | Pre-TAVR AV Peak Velocity (m/s) | Pre-TAVR AV Mean Gradient (mm Hg) | Pre-TAVR AV Area (cm 2 ) | Pre-TAVR Dimensionless Index | Post-TAVR AV Peak Velocity (m/s) | Post-TAVR AV Mean Gradient (mm Hg) | Post-TAVR AV Area (cm 2 ) | Post-TAVR Dimensionless Index |
| 1 | 55-60 | 4.2 | 42 | 0.9 | 0.24 | 1.75 | 7 | 2.1 | 0.56 |
| 2 | 50-55 | 3.56 | 29 | 0.8 | 0.24 | 2.42 | 12 | 1.5 | 0.49 |
| 3 | 60-65 | 4.03 | 36 | 0.8 | 0.43 | 1.9 | 6 | 1.8 | 0.92 |
| 4 | 60-65 | 4.01 | 30 | 0.8 | 0.25 | 1.41 | 4 | 3.1 | 1.02 |
| 5 | 35-40 | 2.89 | 19 | 0.8 | 0.24 | 1.16 | 3 | 2.0 | 0.67 |
| 6 | 60-65 | 3.8 | 35 | 0.65 | 0.21 | 1.1 | 5 | 2.2 | 0.76 |
| 7 | 60-65 | 4.98 | 65 | 0.75 | 0.22 | 2.33 | 12 | 1.8 | 0.52 |
| 8 | 60-65 | 4.35 | 42 | 0.8 | 0.25 | 1.16 | 3 | 2.0 | 0.67 |
| 9 | 60-65 | 4.18 | 43 | 0.66 | 0.19 | 1.85 | 7 | 1.52 | 0.44 |
| 10 | 65-70 | 3.34 | 7 | 1.0 | 0.32 | 1.79 | 7 | 2.3 | 0.73 |
Finally, consideration should be given to the postoperative antiplatelet regimen for patients with hematologic neoplasms. While DAPT has historically been standard after TAVR, patients with hematologic neoplasms and other transfusion-dependent cytopenias may benefit from antiplatelet monotherapy to reduce bleeding risk. Given the high bleeding risk inherent to hematologic neoplasms, antiplatelet therapy in our cohort was individualized, with monotherapy favored in the absence of an alternative indication for DAPT. Of the 9 patients who were discharged, 8 were placed on monotherapy with either aspirin or clopidogrel, and 1 was on DAPT. This approach was well tolerated and appeared to balance minimizing bleeding risk while providing protection against thromboembolic events. Our study was limited by a single-center experience, designed as a case series with a small sample size and the absence of a comparison group, which may limit generalizability. In addition, follow-up duration varied substantially (median 13.5 months), as many patients were referred for TAVR and then returned to local cardiologists after routine 1 year post-TAVR follow-up, limiting uniform long-term outcome assessment. Visual Summary Patient Characteristics and Outcomes Summary Patient Age, y Sex Neoplasm Preop Hgb (g/dL) Preop Platelets (×10 3 /μL) Transfusion Dependent Preop NYHA Functional Class Stroke Bleeding Complication Postop Pacing Required Postop Hospital Stay (d) 1-Year Mortality 1 78 M MDS 9 90 Yes 3 No No No 1 No 2 67 M PPV-MF 12.2 107 No 3 No No No 11 No 3 77 F MDS-IB2 6.9 39 Yes 3 No No No 1 No 4 84 M CLL 11.2 141 No 3 No No No 1 No 5 70 M MGUS 13.5 168 No 3 No No No 6 No 6 75 M MDS-RS-MLD 9.7 80 Yes 4 No No No 8 (death) 8 days post-op 7 58 M AML 7.8 70 Yes 3 No No No 1 3 months post-op 8 77 M MDS-IB1 10.9 55 Yes 3 No No No 10 No 9 73 M BPDCN 9.1 47 No 3 Yes No No 6 No 10 74 M Multiple myeloma 12 203 No 3 No No No 1 No AML = acute myeloid leukemia; BPDCN = blastic plasmacytoid dendritic cell neoplasm; CLL = chronic lymphocytic leukemia; F = female; Hgb = hemoglobin; M = male; MDS = myelodysplastic syndrome; MDS-IB1 = myelodysplastic syndrome with increased blasts, grade 1; MDS-IB2 = myelodysplastic syndrome with increased blasts, grade 2; MDS-RS-MLD = myelodysplastic syndrome with ring sideroblasts and multilineage dysplasia; MGUS = monoclonal gammopathy of undetermined significance; Post-op = postoperative; PPV-MF = post-polycythemia vera myelofibrosis; Pre-op = preoperative.
Visual Summary
Patient Characteristics and Outcomes Summary
AML = acute myeloid leukemia; BPDCN = blastic plasmacytoid dendritic cell neoplasm; CLL = chronic lymphocytic leukemia; F = female; Hgb = hemoglobin; M = male; MDS = myelodysplastic syndrome; MDS-IB1 = myelodysplastic syndrome with increased blasts, grade 1; MDS-IB2 = myelodysplastic syndrome with increased blasts, grade 2; MDS-RS-MLD = myelodysplastic syndrome with ring sideroblasts and multilineage dysplasia; MGUS = monoclonal gammopathy of undetermined significance; Post-op = postoperative; PPV-MF = post-polycythemia vera myelofibrosis; Pre-op = preoperative.
| Patient | Age, y | Sex | Neoplasm | Preop Hgb (g/dL) | Preop Platelets (×10 3 /μL) | Transfusion Dependent | Preop NYHA Functional Class | Stroke | Bleeding Complication | Postop Pacing Required | Postop Hospital Stay (d) | 1-Year Mortality |
| 1 | 78 | M | MDS | 9 | 90 | Yes | 3 | No | No | No | 1 | No |
| 2 | 67 | M | PPV-MF | 12.2 | 107 | No | 3 | No | No | No | 11 | No |
| 3 | 77 | F | MDS-IB2 | 6.9 | 39 | Yes | 3 | No | No | No | 1 | No |
| 4 | 84 | M | CLL | 11.2 | 141 | No | 3 | No | No | No | 1 | No |
| 5 | 70 | M | MGUS | 13.5 | 168 | No | 3 | No | No | No | 6 | No |
| 6 | 75 | M | MDS-RS-MLD | 9.7 | 80 | Yes | 4 | No | No | No | 8 (death) | 8 days post-op |
| 7 | 58 | M | AML | 7.8 | 70 | Yes | 3 | No | No | No | 1 | 3 months post-op |
| 8 | 77 | M | MDS-IB1 | 10.9 | 55 | Yes | 3 | No | No | No | 10 | No |
| 9 | 73 | M | BPDCN | 9.1 | 47 | No | 3 | Yes | No | No | 6 | No |
| 10 | 74 | M | Multiple myeloma | 12 | 203 | No | 3 | No | No | No | 1 | No |
Funding Support and Author Disclosures
Dr Mohanty has received consulting and speaking fees from Medtronic; and has received grant support from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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