Abstract
Background
Adult survivors of childhood cancer experience an increased risk of cardiovascular disease. Surgical therapy is often high risk, particularly in survivors with history of mediastinal radiation. Transcatheter valve intervention for these patients is an evolving field.
Case Summary
A 58-year-old woman with history of Hodgkin lymphoma s/p mediastinal radiation therapy and recent coronary artery bypass grafting presented with recurrent congestive heart failure. Echocardiography revealed moderate-severe aortic insufficiency, severe mitral regurgitation/mild mitral stenosis, and severe tricuspid regurgitation. After receiving transcatheter aortic valve replacement requiring extracorporeal membrane oxygenation support, she remained balloon pump dependent. Given her mild mitral stenosis, transcatheter edge-to-edge repair was not feasible, and she was treated with transcatheter mitral valve replacement on an emergency use basis. She was ultimately discharged home.
Discussion
Multivalvular disease in survivors of childhood cancer present anatomical challenges and transcatheter valve therapies will play an increasing role in these patients.
Take-Home Message
Survivors of childhood cancer can develop severe coronary artery and complex valvular disease. Some of these patients, particularly those with history of chest radiation, will have a hostile mediastinum with elevated surgical risk; transcatheter interventions could be an alternative therapy. For patients with mixed mitral valve disease, Transcatheter mitral valve replacement is feasible but is limited to research devices until one or more technologies are commercially available.
Key words: childhood cancer survivor, mediastinal radiation, severe aortic insufficiency, transcatheter aortic valve replacement, transcatheter mitral valve replacement
Graphical Abstract
Given advances in the treatment of childhood cancer, more than 83% will survive ≥5 years; >70% will survive ≥35 years.1 Of these ∼500,000 survivors, those treated with anthracyclines/mediastinal radiation have a particularly elevated risk of cardiovascular disease. Radiation causes valvular fibrosis/calcification in up to 81% of survivors by 20 years, most commonly affecting the aortic/mitral valves,2 with porcelain aorta in up to 60%.3 Although transcatheter aortic valve replacement (TAVR) has been safe and effective in patients with radiation-associated aortic stenosis,3 transcatheter treatment of radiation-associated mitral disease is limited because transcatheter edge-to-edge repair is not optimal for calcific/restricted leaflets, and late mitral stenosis is a concern.4 Transcatheter mitral valve replacement (TMVR) is an alternative, but most patients are excluded from TMVR trials.5 Childhood cancer survivors in particular often have exclusionary factors such as coexistent valvular lesions or anatomical exclusions.
History of Presentation
We present a 58-year-old woman with congestive heart failure 2 months after coronary artery bypass grafting (CABG). Preoperative coronary angiography revealed 3-vessel coronary artery disease (Figure 1, Video 1); echocardiography suggested moderate AI. Computed tomography (CT) showed porcelain aorta (Figure 2), so our heart team planned for pump-assisted CABG without aortic cross-clamping. Because of scarring, the left internal mammary artery could not be harvested, and the patient received a saphenous vein graft (SVG) to the left anterior descending artery with SVG limb to obtuse marginal, and SVG to posterior descending artery. Two months after CABG, she was admitted with cardiogenic shock requiring dobutamine.
Figure 1.
Coronary Angiography
(A) Selective coronary angiography of the left coronary artery. (B) Selective coronary angiography of the right coronary artery.
Figure 2.
Cardiac CT
(A) Cardiac computed tomography (CT) showing aortic calcification in the transverse plane. (B) Cardiac CT showing aortic calcification in the coronal plane.
Past Medical History
At 25 years of age, the patient was treated for Hodgkin lymphoma with chemotherapy/mantle radiation, and in her 40s she developed moderate aortic/mitral regurgitation (MR). Her history was also notable for percutaneous coronary intervention to the right coronary artery (2018) and permanent pacemaker (2021).
Investigations
Transthoracic echocardiography (TTE) showed moderate-to-severe aortic insufficiency (AI) (Figure 3, Video 2) without aortic stenosis, severe MR/mild mitral stenosis (Figure 4, Video 3), and severe tricuspid regurgitation (Figure 4, Video 4). TAVR CT showed minimal leaflet/annular calcium with annular area = 439 mm2 and sinuses >30 mm, and peripheral arteries were >7 mm with moderate calcification (Figure 5).
Figure 3.
Transthoracic Echocardiography of AI
(A) Parasternal long axis view of aortic insufficiency (AI). (B) Apical 5-chamber view of AI. (C) Continuous-wave Doppler of AI.
Figure 4.
Transthoracic Echocardiography of Mitral Valve and Tricuspid Valve
(A) Transthoracic image of the mitral valve. (B) Transthoracic image of the mitral valve with color Doppler. (C) Pulsed wave Doppler of the mitral valve. (D) Right ventricular inflow view of the tricuspid valve. (E) Right ventricular inflow view of the tricuspid valve with color Doppler.
Figure 5.
Transcatheter Aortic Valve CT
(A) Computed tomography (CT) of the aortic valve during systole. (B) CT of aortic valve during diastole. (C) CT of aortic annulus. (D) CT of aortic sinuses. (E) CT of abdominal aorta and iliofemoral vessels.
Management
Given cardiogenic shock and hostile mediastinum, our team deemed her high-to-extreme surgical risk. In managing multivalvular disease, we felt that addressing her aortic sufficiency first was most appropriate. Because of inotrope dependency and severe MR/tricuspid regurgitation (TR), she was excluded from ALIGN-AR trial with JenaValve (Edwards Lifesciences).6 Therefore, we proceeded with TAVR using a 29 mm Navitor (Abbott Vascular), corresponding to 21% oversizing (perimeter-derived diameter).
Transcatheter aortic valve replacement
The left femoral vein and artery were accessed percutaneously using ultrasound for 7-F sheaths. The right femoral artery was accessed and pre-closed with two 6-F Perclose ProGlides (Abbott Vascular), followed by insertion of a 14-F Gore DrySeal (Gore Medical). The valve was crossed in standard fashion, followed by exchange for a Safari 2 wire (Boston Scientific). With wire introduction, blood pressure declined despite epinephrine, so we deployed the 29-mm Navitor valve, repositioning once for optimal depth (Video 5). After deployment, the patient developed ventricular fibrillation (VF). During cardiopulmonary resuscitation, a left femoral artery sheath was changed to a 15-F Tandem cannula (LivaNova) and a 23-F venous cannula was inserted into the right femoral vein. With extracorporeal membrane oxygenation (ECMO) initiated, the mean blood pressure stabilized to ∼70 mm Hg. Transesophageal echocardiography (TEE) showed valve migration into the aorta during cardiopulmonary resuscitation (Figure 6, Video 6). The valve was redeployed at the optimal depth (3-5 mm) (Figure 6, Video 6).
Figure 6.
Echocardiography of Fluoroscopy of TAVR Deployment
(A) Transesophageal echocardiography (TEE) showing complete blood stasis (arrowheads) and aortic displacement of transcatheter aortic valve replacement (TAVR) (arrow). (B) TEE of initial TAVR deployment. (C) TEE of fully deployed TAVR. (D) TEE of the left atrial (LA) cannula (arrow). (E, F) TEE showing mild paravalvular leak (PVL). (G) Fluoroscopy of TAVR and LA cannula (black arrow).
Because VF persisted despite defibrillation, we assumed that left ventricular (LV) distention was perpetuating VF and that the patient would require LV decompression. Instead of LV venting with Impella (Johnson & Johnson) given TAVR, we inserted a left atrial (LA) cannula for LA venting. After transseptal puncture via left femoral vein using the VersaCross system (Boston Scientific), a 21-F ProtekSolo cannula (LivaNova) was advanced into the left upper pulmonary vein over the VersaCross wire and connected to the right atrial cannula; VF spontaneously converted to normal rhythm.
Post-TAVR hospital course
Within 48 hours, the patient was extubated, weaning off ECMO 6 days later. She continued to require inotropes, and repeat TTE showed a normally functioning TAVR with severe MR/TR (Figure 7, Video 7). Given hemodynamics, we inserted an intra-aortic balloon pump (IABP) to facilitate hemodynamic/volume optimization.
Figure 7.
TEE of TAVR, Mitral, and Tricuspid Valves
(A) TEE of TAVR with no AI in short axis (B) TEE of TAVR with no AI in long axis. (C, D) TEE x-plane of mitral valve with color Doppler. (E, F) TEE x-plane of tricuspid valve with color Doppler. Abbreviations as in Figures 3 and 6.
After 5 days, IABP weaning to 1:2 caused increased filling pressures/respiratory distress; another weaning trial 2 days later was unsuccessful. Given IABP dependency and high-risk surgical options, we reviewed her TAVR CT for TMVR feasibility and determined her suitable for the Sapien M3 (Edwards Lifesciences) (Figure 8). Given hemodynamics, she was not a candidate for the ENCIRCLE trial,7 so we requested emergency use of the Sapien M3 valve.
Figure 8.
Transcatheter Mitral Valve Computed Tomography
(A) Mitral valve perimeter in systole. (B) Mitral valve perimeter in diastole computed tomography. (C) Sapien M3 virtual valve analysis. (D) Neo left ventricular outflow tract (LVOT) assessment.
Transcatheter mitral valve replacement
The left femoral vein and artery were accessed percutaneously using ultrasound and two 7-F sheaths were placed. The right femoral vein was accessed percutaneously using ultrasound, preclosed with two 6-F Perclose ProGlides, and an 8-F sheath was placed. The persistent atrial septal defect from the LA cannula was crossed with a VersaCross sheath. The Dock Delivery system was advanced into LA toward medial commissure. After the tip was lowered into LV, the dock was advanced to the first full circle and the position confirmed with fluoroscopy/TEE. After 3 circles were completed (Figure 9, Video 8), the dock was released and delivery system removed. The M3 valve was advanced into position and deployed using rapid pacing (nominal volume + 4 cm3) (Figure 10, Video 9). After deployment, the delivery system was changed to a 26-F Gore DrySeal, and atrial septostomy was closed with a 30-mm Gore Cardioform septal occluder (Figure 10, Video 9). The left femoral artery and right femoral vein were perclosed, with a figure-of-8 stitch applied over left femoral vein.
Figure 9.
Fluoroscopic and Echocardiographic View of M3 Dock Deployment
(A) Fluoroscopic view of M3 dock tip in left ventricle (LV). (B) Transesophageal echocardiography (TEE) views of M3 dock tip in the LV. (C) Three-dimensional TEE of M3 dock tip in. (D) Fluoroscopic view of second loop formation. (E) TEE views of second loop. (F) Transgastric short-axis TEE view of second loop. (G) Fluoroscopic view of complete dock formation. (H) TEE view of complete dock formation. (I) Three-dimensional TEE of complete dock formation.
Figure 10.
Fluoroscopic and Echocardiographic View of M3 Valve Deployment
Fluoroscopy and echocardiography of M3 being deployed inside dock. TAVR = transcatheter aortic valve replacement; TMVR = transcatheter mitral valve replacement.
Outcome and Follow-Up
The patient had no vascular or neurological complications. The IABP was weaned 2 days later, followed by inotrope weaning. One week later, she was discharged home. One month after discharge, she had minimal dyspnea on exertion; TTE showed excellent TAVR/TMVR function with residual moderate-to-severe TR (Video 10).
Discussion
Survivors of childhood cancer face lifelong risks of cardiovascular disease. Valvular heart disease often results from mediastinal radiation, presenting with fibrotic/calcific changes. For mixed mitral disease, surgical therapy has been the only available option. The challenge arises when coexisting pathology (eg, severe aortic calcification) renders surgery high risk. Although surgery is possible with hypothermic circulatory arrest,8 risks of this approach must be weighed against possible alternatives.
Given the risks in our patient, we decided to treat her AI with TAVR; prior echocardiography suggested that her MR and TR were moderate when she was compensated, and we thought that her current condition was driven by volume overload from AI. Because she had AI without annular/leaflet calcium, we considered the JenaValve in the ALIGN-AR trial. However, inotropic requirements rendered her ineligible for the JenaValve and we had to proceed with a commercially available TAVR device. In this particular patient, we felt that appropriate oversizing to treat her valve would be safer with a self-expanding valve, although limited data suggest that new-generation balloon-expandable or self-expanding TAVRs perform similarly for AI.9 Choosing the Navitor over the Evolut (Medtronic) was institutional preference.
During TAVR, we did not anticipate her hemodynamic distress from wire placement in the LV; likely, one of her fibrotic leaflets was propped open, causing torrential AI. Our ability to deploy ECMO rapidly with use of LA vents for LV decompression was essential. We used the 21-F ProtekSolo cannula because its curved tip allows stable positioning in the left upper pulmonary vein and all inlet ports are on the LA side. Smaller venous cannulae, like the 15-F Bio-Medicus NextGen cannula (Medtronic), could be used but have straight end segments with inlet ports in both the LA and right atrial sides. Despite this support and successful TAVR, she remained inotrope and IABP dependent. We reconsidered mitral/tricuspid valve surgery using hypothermic fibrillatory arrest but still judged this a high risk.
Therefore, we evaluated her for TMVR and found her suitable for the Sapien M3 valve. Because her hemodynamics precluded the ENCIRCLE trial, we requested emergency use by fulfilling standard emergency use criteria.10 We proceeded with Sapien M3 implantation, but the presence of TAVR did make it more challenging because the dock interacted with the frame several times, requiring retraction and careful steering around the frame. After TMVR implantation, we decided to close her atrial septum to limit further volume loading of her right ventricle given her severe TR. After Sapien M3 implantation, her hemodynamics improved, leading to IABP and inotrope weaning.
Although successful, our approach has caveats. Experience treating AI with commercially available devices is limited, and we had to consider carefully the prosthesis oversizing for anchoring. Given the oversizing, it is helpful to use computer modeling to evaluate for annular injury (especially if using balloon-expandable TAVR) and to evaluate for coronary obstruction. Next, given her multivalvular disease and hemodynamic status, it is important to have an array of mechanical circulatory support for bailout. Finally, using emergency use of TMVR requires careful considerations of surgical alternatives and fulfillment of strict criteria.
Conclusions
We present a childhood cancer survivor treated with TAVR and emergency TMVR. With this population increasing, it will be important explore the full array of transcatheter valve therapies to help these patients facing difficult challenges.
Funding Support and Author Disclosures
Dr Thourani has received grant/research support from Abbott Vascular, Boston Scientific, AtriCure, CroíValve, Edwards Lifesciences, Highlife, JenaValve, LaPlace, Medtronic, Pi-Cardia, Tricares, and Trisol; and has equity in Dasi Simulations, Trisol, Pi-Cardia. Dr Yadav has served as a speaker and consultant for Edwards Lifesciences, Abbott, and Medtronic; has served on the advisory board for Dasi Simulations, Pi-Cardia, and Trisol; and has investment in Dasi Simulations and Excision Medical.
Take-Home Messages
-
•
Survivors of childhood cancer can develop severe coronary artery and complex valvular disease.
-
•
Some of these patients, particularly those with history of chest radiation, will have a hostile mediastinum with elevated surgical risk; transcatheter interventions could be an alternative therapy.
-
•
For patients with mixed mitral valve disease, TMVR is feasible but is limited to research devices until one or more technologies are commercially available.
Footnotes
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 Author Center.
Appendix
For supplemental videos, please see the online version of this paper.
Appendix
Coronary Angiography
Selective coronary angiography of left and right coronary arteries.
Transthoracic Echocardiography of Aortic Valve
Parasternal long axis, apical 5-chamber views, and continuous wave Doppler of aortic valve.
Transthoracic Echocardiography of Mitral Valve
Apical of views of mitral valve with and without color Doppler.
Transthoracic Echocardiography of Tricuspid Valve
RV inflow view with and without color.
Fluoroscopy of TAVR Deployment
Fluoroscopy of TAVR deployment before the initiation of ECMO.
Echocardiography of Fluoroscopy of TAVR Deployment
TAVR displaced in aorta (upper panel), partially deployed (middle panel), and fully deployed with LA vent (bottom panel).
Transesophageal Echocardiography of TAVR, Mitral and Tricuspid Valves
TEE showing normal TAVR function with severe mitral and tricuspid regurgitation.
Fluoroscopic and Echocardiographic View of M3 Dock Deployment
(A) Fluoroscopic view of M3 dock tip in LV (B) TEE views of M3 dock tip in LV (C) 3D TEE of M3 dock tip in (D) Fluoroscopic view of second loop formation (E) TEE views of second loop (F) Transgastric short axis TEE view of second loop (G) Fluoroscopic view of complete dock formation (H) TEE view of complete dock formation (I) 3D TEE of complete dock formation
Fluoroscopic and Echocardiographic View of M3 Valve Deployment
(A) Fluoroscopy of M3 valve positioning (B) Echocardiography of M3 Valve positioning (C) Fluoroscopy of M3 valve deployed (D) Echocardiography of M3 valve deployed (E) Fluoroscopy of M3 and Gore Helex device (F) Echocardiography of Gore Helex device.
Follow-Up Transthoracic Echocardiography
One-month TTE showing excellent TAVR and TMVR function with moderate to severe TR.
References
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Associated Data
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Supplementary Materials
Coronary Angiography
Selective coronary angiography of left and right coronary arteries.
Transthoracic Echocardiography of Aortic Valve
Parasternal long axis, apical 5-chamber views, and continuous wave Doppler of aortic valve.
Transthoracic Echocardiography of Mitral Valve
Apical of views of mitral valve with and without color Doppler.
Transthoracic Echocardiography of Tricuspid Valve
RV inflow view with and without color.
Fluoroscopy of TAVR Deployment
Fluoroscopy of TAVR deployment before the initiation of ECMO.
Echocardiography of Fluoroscopy of TAVR Deployment
TAVR displaced in aorta (upper panel), partially deployed (middle panel), and fully deployed with LA vent (bottom panel).
Transesophageal Echocardiography of TAVR, Mitral and Tricuspid Valves
TEE showing normal TAVR function with severe mitral and tricuspid regurgitation.
Fluoroscopic and Echocardiographic View of M3 Dock Deployment
(A) Fluoroscopic view of M3 dock tip in LV (B) TEE views of M3 dock tip in LV (C) 3D TEE of M3 dock tip in (D) Fluoroscopic view of second loop formation (E) TEE views of second loop (F) Transgastric short axis TEE view of second loop (G) Fluoroscopic view of complete dock formation (H) TEE view of complete dock formation (I) 3D TEE of complete dock formation
Fluoroscopic and Echocardiographic View of M3 Valve Deployment
(A) Fluoroscopy of M3 valve positioning (B) Echocardiography of M3 Valve positioning (C) Fluoroscopy of M3 valve deployed (D) Echocardiography of M3 valve deployed (E) Fluoroscopy of M3 and Gore Helex device (F) Echocardiography of Gore Helex device.
Follow-Up Transthoracic Echocardiography
One-month TTE showing excellent TAVR and TMVR function with moderate to severe TR.