Faculty Bibliography
Searched for:
in-biosketch:true
person:willim33
Total Results:
242
Progression of Tricuspid Regurgitation After Surgery for Ischemic Mitral Regurgitation
BACKGROUND:Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain. OBJECTIVES:The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery. METHODS:Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years. RESULTS:Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04). CONCLUSIONS:After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).
PMID: 33573741
ISSN: 1558-3597
CID: 5450812
Journal of the American Society of Echocardiography. 2021:34(1):89-96.DOI: 10.1016/j.echo.2020.08.019
Three-Dimensional Imaging and Dynamic Modeling of Systolic Anterior Motion of the Mitral Valve
Left ventricular outflow tract (LVOT) obstruction in hypertrophic cardiomyopathy (HCM) is often caused by systolic anterior motion (SAM) of the mitral valve caused by the interplay between increased left ventricular (LV) wall thickness and an abnormal mitral valve anatomy and geometry. Three-dimensional (3D) echocardiographic imaging of the mitral valve has revolutionized the practice of cardiology, paving the way for new methods to see and treat valvular heart disease. Here we present the novel and incremental value of 3D transesophageal echocardiography (TEE) of SAM visualization. This review first provides step-by-step instructions on acquiring and optimizing 3D TEE imaging of SAM. It then describes the unique and novel findings using standard 3D TEE rendering as well as dynamic mitral valve modeling of SAM from 3D data sets, which can provide a more detailed visualization of SAM features. The findings include double-orifice LVOT caused by the residual leaflet, the dolphin smile phenomenon, and delineation of SAM width. Finally, the review discusses the essential role of 3D TEE imaging for preprocedural assessment and intraprocedural guidance of surgical and novel percutaneous treatments of SAM.
PMID: 33059963
ISSN: 1097-6795
CID: 4641632
Consensus Document on Non-Suitability for Transcatheter Mitral Valve Repair by Edge-to-Edge Therapy
EMBASE:2012308194
ISSN: 2474-8706
CID: 4909532
Transcatheter Mitral Valve Edge-to-Edge Repair for Patients With Surgical Mitral Valve Repair Failure and Severe Mitral Regurgitation [Meeting Abstract]
ISI:000715526900356
ISSN: 0735-1097
CID: 5074302
Computed Tomography Annular Dimensions: A Novel Method to Compare Prosthetic Valve Hemodynamics
BACKGROUND:Cardiac Surgical Societies Valve Labeling Task Force consensus document acknowledged inconsistent sizing and labelling of prosthetic heart valves. This study compared labeled size, internal diameter, and hemodynamics of different surgical and transcatheter valve types implanted into the same size annulus, measured by pre-procedural computed tomography (CT). METHODS:Patients were retrospectively sorted into 3 CT- annular diameter size groups: small (<23mm), medium (23-26mm), and large (>26mm). Surgical valves were sorted into 4 categories based on tissue and design: (stentless porcine, standard stented bovine, wraparound stented bovine and stented porcine). Comparisons were made within the surgical types and to a transcatheter valve. Echocardiograms were independently assessed and CTs were centrally measured. RESULTS:726 surgical and 923 transcatheter valve paired data sets were analyzed. Among the various valve types implanted into the same size CT annulus there were significant differences for size, internal diameter, and hemodynamics within all 3 size groups. Root enlargement procedures occurred in 1.2% with no differences across valve types or size groups. Transcatheter valve hemodynamics were similar to stentless valves and were significantly better than all stented valves. There was no difference in hemodynamics between the 2 bovine stented valve types and stented porcine valves were inferior to all valve types. CONCLUSIONS:This study documents prosthetic heart valve sizing and labelling inconsistencies exist. Using preoperative CT annular dimensions is the most accurate method to compare size, internal diameter, and hemodynamics of bioprosthetic aortic valves because it compares values between various valve types implanted into the same size annulus.
PMID: 32289296
ISSN: 1552-6259
CID: 4401332
Journal of the American College of Cardiology. 2020:Conference:(Thirty).DOI: 10.1016/j.jacc.2020.09.363
TCT CONNECT-342 Outcomes of MitraClip Repair in Primary Mitral Regurgitation Patients With STS Repair Score of Less Than 6% and STS Replacement Score of Less Than 8%: Results From the Global EXPAND Study [Meeting Abstract]
Background: Transcatheter mitral valve repair with the MitraClip system has been shown to be safe and effective for the treatment of significant primary mitral regurgitation (MR) in patients deemed prohibitive risk for surgery. This analysis evaluated the outcomes of MitraClip repair in primary MR subjects with STS PROM (Society of Thoracic Surgeons Predicted Risk of Mortality) score <6% for surgical repair and <8% for replacement from the global EXPAND (A Contemporary, Prospective Study Evaluating Real-World Experience of Performance and Safety for the Next Generation of MitraClip Devices) study.
Method(s): EXPAND is a prospective, multicenter, international, single-arm study that enrolled subjects at 57 centers in Europe and the United States. All echocardiograms were analyzed by an independent echo core laboratory, and major adverse events were adjudicated by an independent clinical events committee. Study outcomes included MR severity, procedural outcomes, major adverse events, New York Heart Association functional class and KCCQ (Kansas City Cardiomyopathy Questionnaire) score.
Result(s): Four hundred and twenty subjects with primary MR had adequate baseline echocardiographic imaging for assessment by the echo core laboratory. Of the 420 subjects, at least 166 patients either had an STS repair score <6% and an STS replacement score <8%. Average age was 77.2 +/- 10.4 years old, and 54% of the subjects were men. STS PROM score for surgical repair was 2.9 +/- 1.3% and replacement was 4.6 +/- 1.8%. Echo core laboratory-adjudicated acute procedural success, defined as survival to discharge with a successful implant resulting in reduction to MR severity <=2+, was achieved in 93.4% of the subjects. Clinical events committee-adjudicated all-cause mortality rate at 30 days was 1.2% (n = 2), and major adverse events rate was 4.2% (n = 7). MR reduction to <=2+ and MR <=1+ were achieved in 98% and 89% of subjects at 30 days, respectively. The reduction in MR severity was also associated with a significant reduction in left ventricle end-diastolic dimension (52.9 +/- 6.8 mm to 49.9 +/- 7.2 mm; n = 144; p < 0.0001) and volume (126.1 +/- 50.5 ml to 114.5 +/- 44.9 ml; n = 138; p < 0.0001). There were also improvements in functional capacity (69% New York Heart Association functional class III/IV at baseline vs. 18% at 30 days; p < 0.0001) and quality of life (mean change in KCCQ score from baseline to 30 days: +18.7 +/- 24.0; p < 0.0001). Univariate analysis of MR reduction (2 grades or more) were baseline MR severity (p < 0.0001), peak E velocity (p < 0.037), mean mitral gradient (p < 0.026), presence of ruptured chordae (p < 0.001), leaflet flail (p < 0.0002), leaflet billowing (p < 0.0001), and prolapse or flail gap (p < 0.037).
Conclusion(s): In patients with primary MR and an STS repair risk score <6% and replacement score <8%, the MitraClip NTR and XTR system was found to be safe and effective at reducing MR and improving left ventricular remodeling and was associated with significant improvements in quality of life and functional capacity. Categories: STRUCTURAL: Valvular Disease: Mitral
Copyright
Method(s): EXPAND is a prospective, multicenter, international, single-arm study that enrolled subjects at 57 centers in Europe and the United States. All echocardiograms were analyzed by an independent echo core laboratory, and major adverse events were adjudicated by an independent clinical events committee. Study outcomes included MR severity, procedural outcomes, major adverse events, New York Heart Association functional class and KCCQ (Kansas City Cardiomyopathy Questionnaire) score.
Result(s): Four hundred and twenty subjects with primary MR had adequate baseline echocardiographic imaging for assessment by the echo core laboratory. Of the 420 subjects, at least 166 patients either had an STS repair score <6% and an STS replacement score <8%. Average age was 77.2 +/- 10.4 years old, and 54% of the subjects were men. STS PROM score for surgical repair was 2.9 +/- 1.3% and replacement was 4.6 +/- 1.8%. Echo core laboratory-adjudicated acute procedural success, defined as survival to discharge with a successful implant resulting in reduction to MR severity <=2+, was achieved in 93.4% of the subjects. Clinical events committee-adjudicated all-cause mortality rate at 30 days was 1.2% (n = 2), and major adverse events rate was 4.2% (n = 7). MR reduction to <=2+ and MR <=1+ were achieved in 98% and 89% of subjects at 30 days, respectively. The reduction in MR severity was also associated with a significant reduction in left ventricle end-diastolic dimension (52.9 +/- 6.8 mm to 49.9 +/- 7.2 mm; n = 144; p < 0.0001) and volume (126.1 +/- 50.5 ml to 114.5 +/- 44.9 ml; n = 138; p < 0.0001). There were also improvements in functional capacity (69% New York Heart Association functional class III/IV at baseline vs. 18% at 30 days; p < 0.0001) and quality of life (mean change in KCCQ score from baseline to 30 days: +18.7 +/- 24.0; p < 0.0001). Univariate analysis of MR reduction (2 grades or more) were baseline MR severity (p < 0.0001), peak E velocity (p < 0.037), mean mitral gradient (p < 0.026), presence of ruptured chordae (p < 0.001), leaflet flail (p < 0.0002), leaflet billowing (p < 0.0001), and prolapse or flail gap (p < 0.037).
Conclusion(s): In patients with primary MR and an STS repair risk score <6% and replacement score <8%, the MitraClip NTR and XTR system was found to be safe and effective at reducing MR and improving left ventricular remodeling and was associated with significant improvements in quality of life and functional capacity. Categories: STRUCTURAL: Valvular Disease: Mitral
Copyright
EMBASE:2008355533
ISSN: 1558-3597
CID: 4659302
Journal of the American College of Cardiology. 2020:Conference:(Thirty).DOI: 10.1016/j.jacc.2020.09.103
TCT CONNECT-89 Impact of Pre-Existent Atrial Fibrillation on Clinical Outcomes After Transcatheter or Surgical Aortic Valve Replacement for Severe Aortic Stenosis: An Analysis From the PARTNER 3 Trial [Meeting Abstract]
Background: This study sought to determine the clinical impact of pre-existent atrial fibrillation or flutter (AF) in low-risk patients with severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) in the randomized PARTNER 3 trial.
Method(s): Patients with severe AS at low surgical risk were randomized 1:1 to TAVR versus SAVR. Analyses were performed in the as-treated population. Clinical outcomes at 2 years were analyzed according to pre-existent AF.
Result(s): Among 948 patients included in the analysis, 452 (47.7%) underwent SAVR and 496 (52.3%) underwent TAVR. History of AF was present in 168 patients (17.6%) (88 of 452 [19.5%] and 80 of 496 [16.1%] treated with SAVR and TAVR, respectively). Compared with patients without AF, patients with AF were more frequently men and Caucasian, and had a more frequent history of prior pacemaker implant and higher body mass index. At 2 years, patients with AF had higher unadjusted rates of the composite outcome of death, stroke, or rehospitalization (21.2% vs. 12.9%; p = 0.007) and rehospitalization (15.3% vs. 9.4%; p = 0.03) but not all-cause death (3.8 vs. 2.6%; p = 0.45) or stroke (4.8% vs. 2.6%; p = 0.12). In adjusted analyses, patients with AF had a higher risk for the composite outcome of death, stroke, or rehospitalization (hazard ratio [HR]: 1.80; 95% confidence interval [CI]: 1.20 to 2.71; p = 0.0046) and rehospitalization (HR: 1.8; 95% CI: 0.12 to 2.90; p = 0.015), but not death (HR: 1.26; 95% CI: 0.49 to 3.20; p = 0.63) or stroke (HR: 2.11; 95% CI: 0.86 to 5.23; p = 0.10). There was no interaction between treatment modality and AF on the composite outcome (p inter = 0.83).
Conclusion(s): In the PARTNER 3 trial, low surgical risk patients with severe AS and preexistent AF had increased risk for the composite outcome of death, stroke, or rehospitalization at 2 years compared with patients without AF, irrespective of treatment with TAVR or SAVR. Categories: STRUCTURAL: Valvular Disease: Aortic
Copyright
Method(s): Patients with severe AS at low surgical risk were randomized 1:1 to TAVR versus SAVR. Analyses were performed in the as-treated population. Clinical outcomes at 2 years were analyzed according to pre-existent AF.
Result(s): Among 948 patients included in the analysis, 452 (47.7%) underwent SAVR and 496 (52.3%) underwent TAVR. History of AF was present in 168 patients (17.6%) (88 of 452 [19.5%] and 80 of 496 [16.1%] treated with SAVR and TAVR, respectively). Compared with patients without AF, patients with AF were more frequently men and Caucasian, and had a more frequent history of prior pacemaker implant and higher body mass index. At 2 years, patients with AF had higher unadjusted rates of the composite outcome of death, stroke, or rehospitalization (21.2% vs. 12.9%; p = 0.007) and rehospitalization (15.3% vs. 9.4%; p = 0.03) but not all-cause death (3.8 vs. 2.6%; p = 0.45) or stroke (4.8% vs. 2.6%; p = 0.12). In adjusted analyses, patients with AF had a higher risk for the composite outcome of death, stroke, or rehospitalization (hazard ratio [HR]: 1.80; 95% confidence interval [CI]: 1.20 to 2.71; p = 0.0046) and rehospitalization (HR: 1.8; 95% CI: 0.12 to 2.90; p = 0.015), but not death (HR: 1.26; 95% CI: 0.49 to 3.20; p = 0.63) or stroke (HR: 2.11; 95% CI: 0.86 to 5.23; p = 0.10). There was no interaction between treatment modality and AF on the composite outcome (p inter = 0.83).
Conclusion(s): In the PARTNER 3 trial, low surgical risk patients with severe AS and preexistent AF had increased risk for the composite outcome of death, stroke, or rehospitalization at 2 years compared with patients without AF, irrespective of treatment with TAVR or SAVR. Categories: STRUCTURAL: Valvular Disease: Aortic
Copyright
EMBASE:2008355195
ISSN: 1558-3597
CID: 4659322
Journal of the American College of Cardiology. 2020:Conference:(Thirty).DOI: 10.1016/j.jacc.2020.09.497
TCT CONNECT-468 Postoperative Atrial Fibrillation or Flutter Following Transcatheter or Surgical Aortic Valve Replacement for Severe Aortic Stenosis in Patients at Low Surgical Risk: An Analysis From the PARTNER 3 Trial [Meeting Abstract]
Background: We sought to determine the incidence and clinical impact of new-onset postoperative atrial fibrillation or flutter (POAF) in low-risk patients with severe aortic stenosis treated with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).
Method(s): In the PARTNER 3 trial, patients with severe aortic stenosis at low surgical risk were randomized to TAVR or SAVR. POAF was defined as any atrial fibrillation occurring within the index hospitalization. Analyses were performed in the as-treated population; patients with preexistent AF were excluded. Outcomes at 2 years were analyzed according to POAF.
Result(s): Among 781 patients included in the analysis, POAF occurred in 152 (19.5%) (TAVR: 18/415 [4.3%]; SAVR: 134/366 [36.6%]). Compared with patients without POAF, those with POAF were older (74.7 vs. 73.0, p = 0.0013). At 2 years, patients with new POAF had similar unadjusted rates of the primary composite outcome of all-cause death, stroke or procedure/device or heart failure-related rehospitalization (16.6% vs. 12.0%, p = 0.10), and the individual endpoints of rehospitalization (12.1% vs. 8.7%, p = 0.19) and all-cause death (2.7% vs. 2.6%, p = 0.93). In contrast, patients with new POAF had higher rates of all bleeding (33.7% vs. 21.0%, p = 0.007) and major bleeding (14.5% vs. 8.3%, p = 0.016) and a trend toward a higher rate of stroke (4.6% vs. 2.1%, p = 0.07) at 2 years compared with patients without POAF. In adjusted analyses, POAF did not predict the primary composite outcome (hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.64 to 1.92; p = 0.71), rehospitalization (HR: 1.24; 95% CI: 0.65 to 2.36; p = 0.51), all-cause death (HR: 0.97; 95% CI: 0.29 to 3.21; p = 0.96), stroke (HR: 1.61; 95% CI: 0.5 to 5.18; p = 0.42), or bleeding (HR: 1.15; 95% CI: 0.0.80 to 1.66; p = 0.44) at 2 years. There was no interaction between treatment modality and POAF on the primary composite outcome (p interaction = 0.51).
Conclusion(s): In the PARTNER 3 trial, in low-risk patients undergoing TAVR or SAVR, the development of POAF was more frequent following SAVR than TAVR and was not associated with increased adjusted risk for the composite outcome of death, stroke, or procedure/device or heart failure-related rehospitalization at 2 years, irrespective of treatment modality. Categories: STRUCTURAL: Valvular Disease: Aortic
Copyright
Method(s): In the PARTNER 3 trial, patients with severe aortic stenosis at low surgical risk were randomized to TAVR or SAVR. POAF was defined as any atrial fibrillation occurring within the index hospitalization. Analyses were performed in the as-treated population; patients with preexistent AF were excluded. Outcomes at 2 years were analyzed according to POAF.
Result(s): Among 781 patients included in the analysis, POAF occurred in 152 (19.5%) (TAVR: 18/415 [4.3%]; SAVR: 134/366 [36.6%]). Compared with patients without POAF, those with POAF were older (74.7 vs. 73.0, p = 0.0013). At 2 years, patients with new POAF had similar unadjusted rates of the primary composite outcome of all-cause death, stroke or procedure/device or heart failure-related rehospitalization (16.6% vs. 12.0%, p = 0.10), and the individual endpoints of rehospitalization (12.1% vs. 8.7%, p = 0.19) and all-cause death (2.7% vs. 2.6%, p = 0.93). In contrast, patients with new POAF had higher rates of all bleeding (33.7% vs. 21.0%, p = 0.007) and major bleeding (14.5% vs. 8.3%, p = 0.016) and a trend toward a higher rate of stroke (4.6% vs. 2.1%, p = 0.07) at 2 years compared with patients without POAF. In adjusted analyses, POAF did not predict the primary composite outcome (hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.64 to 1.92; p = 0.71), rehospitalization (HR: 1.24; 95% CI: 0.65 to 2.36; p = 0.51), all-cause death (HR: 0.97; 95% CI: 0.29 to 3.21; p = 0.96), stroke (HR: 1.61; 95% CI: 0.5 to 5.18; p = 0.42), or bleeding (HR: 1.15; 95% CI: 0.0.80 to 1.66; p = 0.44) at 2 years. There was no interaction between treatment modality and POAF on the primary composite outcome (p interaction = 0.51).
Conclusion(s): In the PARTNER 3 trial, in low-risk patients undergoing TAVR or SAVR, the development of POAF was more frequent following SAVR than TAVR and was not associated with increased adjusted risk for the composite outcome of death, stroke, or procedure/device or heart failure-related rehospitalization at 2 years, irrespective of treatment modality. Categories: STRUCTURAL: Valvular Disease: Aortic
Copyright
EMBASE:2008355389
ISSN: 1558-3597
CID: 4659312
Bicuspid Aortic Valve Morphology and Outcomes After Transcatheter Aortic Valve Replacement
BACKGROUND:Bicuspid aortic stenosis accounts for almost 50% of patients undergoing surgical aortic valve replacement in the younger patients. Expanding the indication of transcatheter aortic valve replacement (TAVR) toward lower-risk and younger populations will lead to increased use of TAVR for patients with bicuspid aortic valve (BAV) stenosis despite the exclusion of bicuspid anatomy in all pivotal clinical trials. OBJECTIVES/OBJECTIVE:This study sought to evaluate the association of BAV morphology and outcomes of TAVR with the new-generation devices. METHODS:Patients with BAV confirmed by central core laboratory computed tomography (CT) analysis were included from the international multicenter BAV TAVR registry. BAV morphology including the number of raphe, calcification grade in raphe, and leaflet calcium volume were assessed with CT analysis in a masked fashion. Primary outcomes were all-cause mortality at 1 and 2 years, and secondary outcomes included 30-day major endpoints and procedural complications. RESULTS:A total of 1,034 CT-confirmed BAV patients with a mean age of 74.7 years and Society of Thoracic Surgeons score of 3.7% underwent TAVR with contemporary devices (n = 740 with Sapien 3; n = 188 with Evolut R/Pro; n = 106 with others). All-cause 30-day, 1-year, and 2-year mortality was 2.0%, 6.7%, and 12.5%, respectively. Multivariable analysis identified calcified raphe and excess leaflet calcification (defined as more than median calcium volume) as independent predictors of 2-year all-cause mortality. Both calcified raphe plus excess leaflet calcification were found in 269 patients (26.0%), and they had significantly higher 2-year all-cause mortality than those with 1 or none of these morphological features (25.7% vs. 9.5% vs. 5.9%; log-rank p < 0.001). Patients with both morphological features had higher rates of aortic root injury (p < 0.001), moderate-to-severe paravalvular regurgitation (p = 0.002), and 30-day mortality (p = 0.016). CONCLUSIONS:Outcomes of TAVR in bicuspid aortic stenosis depend on valve morphology. Calcified raphe and excess leaflet calcification were associated with increased risk of procedural complications and midterm mortality. (Bicuspid Aortic Valve Stenosis Transcatheter Aortic Valve Replacement Registry; NCT03836521).
PMID: 32854836
ISSN: 1558-3597
CID: 4581542
Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous n-acetylcysteine
Glucose 6-phosphate dehydrogenase (G6PD) deficiency facilitates human coronavirus infection due to glutathione depletion. G6PD deficiency may especially predispose to hemolysis upon coronavirus disease-2019 (COVID-19) infection when employing pro-oxidant therapy. However, glutathione depletion is reversible by N-acetylcysteine (NAC) administration. We describe a severe case of COVID-19 infection in a G6PD-deficient patient treated with hydroxychloroquine who benefited from intravenous (IV) NAC beyond reversal of hemolysis. NAC blocked hemolysis and elevation of liver enzymes, C-reactive protein (CRP), and ferritin and allowed removal from respirator and veno-venous extracorporeal membrane oxygenator and full recovery of the G6PD-deficient patient. NAC was also administered to 9 additional respirator-dependent COVID-19-infected patients without G6PD deficiency. NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm that warrant follow-up confirmatory studies in the setting controlled clinical trials.
PMCID:7374140
PMID: 32707089
ISSN: 1521-7035
CID: 4539812
