Consensus Document on Non-Suitability for Transcatheter Mitral Valve Repair by Edge-to-Edge Therapy
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.
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
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
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
Bicuspid Aortic Valve Morphology andÂ Outcomes After Transcatheter AorticÂ 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; nÂ =Â 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 pÂ <Â 0.001). Patients with both morphological features had higher rates of aortic root injury (pÂ <Â 0.001), moderate-to-severe paravalvular regurgitation (pÂ =Â 0.002), and 30-day mortality (pÂ =Â 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. (BicuspidÂ Aortic Valve Stenosis Transcatheter Aortic Valve Replacement Registry; NCT03836521).
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.
The COVID-19 Pandemic and Acute Aortic Dissections in New York: A Matter of Public Health [Letter]
Subclinical Leaflet Thrombosis in Transcatheter and Surgical BioprostheticÂ Valves: PARTNER 3 Cardiac Computed Tomography Substudy
BACKGROUND:Subclinical leaflet thrombosis, characterized by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion observed on 4-dimensional computed tomography (CT), may represent a form of bioprosthetic valve dysfunction. OBJECTIVES/OBJECTIVE:The U.S. Food and Drug Administration mandated CT studies to understand the natural history of this finding, differences between transcatheter and surgical valves, and its association with valve hemodynamics and clinical outcomes. METHODS:The PARTNER 3 (The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low-Risk Patients With Aortic Stenosis) CT substudy randomized 435 patients with low-surgical-risk aortic stenosis to undergo transcatheter aortic valve replacement (nÂ =Â 221) or surgery (nÂ =Â 214). Serial 4-dimensional CTs were performed at 30Â days and 1 year and were analyzed independently by a core laboratory. RESULTS:The incidence of HALT increased from 10% at 30Â days to 24% at 1 year. Spontaneous resolution of 30-day HALT occurred in 54% of patients at 1 year, whereas new HALT appeared in 21% of patients at 1 year. HALT was more frequent in transcatheter versus surgical valves at 30Â days (13% vs. 5%; pÂ =Â 0.03), but not at 1 year (28% vs. 20%; pÂ =Â 0.19). The presence of HALT did not significantly affect aortic valve mean gradients at 30Â days or 1 year. Patients with HALT at both 30Â days and 1 year, compared with those with no HALT at 30Â days and 1 year, had significantly increased aortic valve gradients at 1 year (17.8 Â± 2.2Â mmÂ Hg vs. 12.7. Â± 0.3 mm Hg; pÂ =Â 0.04). CONCLUSIONS:Subclinical leaflet thrombosis was more frequent in transcatheter compared with surgical valves at 30Â days, but not at 1 year. The impact of HALT on thromboembolic complications and structural valve degenerationÂ needs further assessment.
Echocardiographic Results of Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients: The PARTNER 3 Trial
Background: The objective of this study is to compare echocardiographic findings in low risk patients with severe aortic stenosis (AS) following surgical (SAVR) or transcatheter aortic valve replacement (TAVR). Methods: The Placement of Aortic Transcatheter Valves 3 (PARTNER 3) trial randomized 1000 patients with severe AS and low surgical risk to undergo either transfemoral TAVR with the balloon-expandable SAPIEN 3 valve or SAVR. Transthoracic echocardiograms obtained at baseline, and at 30 days and 1 year post-procedure were analyzed by a consortium of 2 echocardiography core laboratories. Results: The percentage of moderate/severe aortic regurgitation (AR) was low and not statistically different between TAVR vs. SAVR groups (30 days: 0.8% vs. 0.2%; p=0.38). However, mild AR was more frequent following TAVR vs. SAVR (30 days: 28.8% vs. 4.2 %; p<0.001). At 1 year, mean transvalvular gradient (13.7Â±5.6 vs. 11.6Â±5.0 mmHg; p=0.12) and aortic valve area (1.72Â±0.37 vs. 1.76Â±0.42 cm2; p=0.12) were similar in TAVR vs. SAVR. The percentage of severe prosthesis-patient mismatch (PPM) at 30 days was low and similar between TAVR and SAVR (4.6 vs. 6.3%, p=0.30). Valvulo-arterial impedance (Zva), which reflects total left ventricular hemodynamic burden, was lower with TAVR vs. SAVR at 1 year (3.7Â±0.8 vs. 3.9Â±0.9 mmHg/mL/m2 ; p<0.001). Tricuspid annulus plane systolic excursion (TAPSE) decreased and the percentage of moderate/severe tricuspid regurgitation increased from baseline to 1 year in SAVR, whereas remained unchanged in TAVR. Irrespective of treatment arm, high Zva and low TAPSE, but not moderate/severe AR or severe PPM, were associated with increased risk of the composite endpoint of mortality, stroke and re-hospitalization at 1 year. Conclusions: In patients with severe AS and low surgical risk, TAVR with the SAPIEN 3 valve was associated with similar percentage of moderate/severe AR compared with SAVR, but higher percentage of mild AR. Transprosthetic gradients, valve areas, percentage of severe PPM, and LV mass regression were similar in TAVR versus SAVR. SAVR was associated with significant deterioration of RV systolic function and greater tricuspid regurgitation, which persisted at 1 year. High Zva and low TAPSE were associated with worse outcome at 1 year whereas AR or severe PPM were not. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02675114.