Publications by authors named "Tarun Chakravarty"

128 Publications

Temporal Trends, Characteristics, and Outcomes of Infective Endocarditis After Transcatheter Aortic Valve Replacement.

Clin Infect Dis 2021 Mar 18. Epub 2021 Mar 18.

Quebec Heart and Lung Institute, Laval University, Quebec City, Canada.

Background: Procedural improvements combined with the contemporary clinical profile of patients undergoing transcatheter aortic valve replacement (TAVR) may have influenced the incidence and outcomes of infective endocarditis (IE) following TAVR. We aimed to determine the temporal trends, characteristics, and outcomes of IE post-TAVR.

Methods: Observational study including 552 patients presenting definite IE post-TAVR. Patients were divided in 2 groups according to the timing of TAVR (historical cohort [HC]: before 2014; contemporary cohort [CC]: after 2014).

Results: Overall incidence rates of IE were similar in both cohorts (CC vs HC: 5.45 vs 6.52 per 1000 person-years; P = .12), but the rate of early IE was lower in the CC (2.29‰ vs 4.89‰, P < .001). Enterococci were the most frequent microorganism. Most patients presented complicated IE ( CC: 67.7%; HC: 69.6%; P = .66), but the rate of surgical treatment remained low (CC: 20.7%; HC: 17.3%; P = .32). The CC exhibited lower rates of in-hospital acute kidney injury (35.1% vs 44.6%; P = .036) and in-hospital (26.6% vs 36.4%; P = .016) and 1-year (37.8% vs 53.5%; P < .001) mortality. Higher logistic EuroScore, Staphylococcus aureus etiology, and complications (stroke, heart failure, and acute renal failure) were associated with in-hospital mortality in multivariable analyses (P < .05 for all).

Conclusions: Although overall IE incidence has remained stable, the incidence of early IE has declined in recent years. The microorganism, high rate of complications, and very low rate of surgical treatment remained similar. In-hospital and 1-year mortality rates were high but progressively decreased over time.
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http://dx.doi.org/10.1093/cid/ciaa1941DOI Listing
March 2021

Cerebral Embolic Protection and Outcomes of Transcatheter Aortic Valve Replacement: Results from the TVT Registry.

Circulation 2021 Feb 23. Epub 2021 Feb 23.

Cardiovascular Research Foundation, New York, NY; St. Francis Hospital, Roslyn, NY.

Stroke remains a devastating complication of transcatheter aortic valve replacement (TAVR), which has persisted despite refinements in technique and increased operator experience. While cerebral embolic protection devices (EPDs) have been developed to mitigate this risk, data regarding their impact on stroke and other outcomes after TAVR are limited. We performed an observational study using data from the STS/ACC-TVT Registry. Patients were included if they underwent elective or urgent transfemoral TAVR between January 2018 and December 2019. The primary outcome was in-hospital stroke. To adjust for confounding, the association between EPD use and clinical outcomes was evaluated using instrumental variable (IV) analysis, a technique designed to support causal inference from observational data, with site-level preference for EPD use within the same quarter of the procedure as the instrument. We also performed a propensity score-based secondary analysis using overlap weights. Our analytic sample included 123,186 patients from 599 sites. The use of EPD during TAVR increased over time, reaching 28% of sites and 13% of TAVR procedures by December 2019. There was wide variation in EPD use across hospitals, with 8% of sites performing >50% of TAVR procedures with an EPD and 72% performing zero procedures with an EPD in the last quarter of 2019. In our primary analysis using the IV model, there was no association between EPD use and in-hospital stroke (adjusted relative risk (0.90 [95% CI: 0.68, 1.13], absolute risk difference -0.15% [95% CI: -0.49, 0.20]). However, in our secondary analysis using the propensity score-based model, EPD use was associated with 18% lower odds of in-hospital stroke (adjusted OR 0.82 [95% CI 0.69, 0.97], absolute risk difference -0.28% [95% CI: -0.52, -0.03]). Results were generally consistent across the secondary endpoints as well as subgroup analyses. In this nationally-representative observational study, we did not find an association between EPD use for TAVR and in-hospital stroke in our primary IV analysis, and found only a modestly lower risk of in-hospital stroke in our secondary propensity-weighted analysis. These findings provide a strong basis for large-scale RCTs to test whether EPDs provide meaningful clinical benefit for patients undergoing TAVR.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052874DOI Listing
February 2021

Left-Sided Venous Access: A Technique to Simplify and Improve Success of Tricuspid Valve Clip Repair.

JACC Cardiovasc Interv 2021 Mar 13;14(5):581-582. Epub 2021 Jan 13.

Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jcin.2020.11.044DOI Listing
March 2021

Transcatheter Aortic Valve Implantation in Patients With Severe Aortic Stenosis Hospitalized With Acute Heart Failure.

Am J Cardiol 2021 04 28;144:100-110. Epub 2020 Dec 28.

Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, California. Electronic address:

Optimal timing and outcomes of transcatheter aortic valve implantation (TAVI) in patients presenting with acute heart failure (AHF) remain unclear. In this consecutive cohort of 1,547 patients with severe aortic stenosis undergoing TAVI, the AHF status at admission was collected, and patients were classified into AHF and elective TAVI groups. In the AHF group, early TAVI was defined as TAVI performed ≤60 hours after emergency room arrival. The primary outcome was all-cause mortality at 30-day and 2-year after TAVI. There were 139 (9%) patients who underwent TAVI while hospitalized with AHF. At baseline, this group had higher rates of chronic kidney disease, higher Society of Thoracic Surgeons score, and lower left ventricular ejection fraction. After adjusting for baseline differences, the AHF group had significantly higher all-cause mortality at 30-day and 2-year than the elective TAVI group (8% vs 2%; p = 0.002, and 33% vs 18%; p = 0.002, respectively). In the AHF group, 43 (31%) patients underwent early treatment with TAVI. No significant difference in all-cause mortality at 30-day was observed between early and non-early TAVI groups (5% vs 10%; p = 0.617). All-cause mortality at 2-year was lower in the early TAVI groups (16% vs 40%, log-rank p = 0.022); however, after multivariable adjustment, the difference was barely statistically significant (p = 0.053). In conclusion, TAVI in patients with AHF was associated with worse short and long-term outcomes. In AHF setting, early TAVI did not significantly reduce all-cause mortality at 30-day; however, it showed a strong trend for lower all-cause mortality at 2-year.
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http://dx.doi.org/10.1016/j.amjcard.2020.12.046DOI Listing
April 2021

Computed tomography angiography-derived extracellular volume fraction predicts early recovery of left ventricular systolic function after transcatheter aortic valve replacement.

Eur Heart J Cardiovasc Imaging 2021 Jan;22(2):179-185

Mark Taper Imaging Center, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90028, USA.

Aims : Recovery of left ventricular ejection fraction (LVEF) after aortic valve replacement has prognostic importance in patients with aortic stenosis (AS). The mechanism by which myocardial fibrosis impacts LVEF recovery in AS is not well characterized. We sought to evaluate the predictive value of extracellular volume fraction (ECV) quantified by cardiac CT angiography (CTA) for LVEF recovery in patients with AS after transcatheter aortic valve replacement (TAVR).

Methods And Results : In 109 pre-TAVR patients with LVEF <50% at baseline echocardiography, CTA-derived ECV was calculated as the ratio of change in CT attenuation of the myocardium and the left ventricular (LV) blood pool before and after contrast administration. Early LVEF recovery was defined as an absolute increase of ≥10% in LVEF measured by post-TAVR follow-up echocardiography within 6 months of the procedure. Early LVEF recovery was observed in 39 (36%) patients. The absolute increase in LVEF was 17.6 ± 8.8% in the LVEF recovery group and 0.9 ± 5.9% in the no LVEF recovery group (P < 0.001). ECV was significantly lower in patients with LVEF recovery compared with those without LVEF recovery (29.4 ± 6.1% vs. 33.2 ± 7.7%, respectively, P = 0.009). In multivariable analysis, mean pressure gradient across the aortic valve [odds ratio (OR): 1.07, 95% confidence interval (CI): 1.03-1.11, P: 0.001], LV end-diastolic volume (OR: 0.99, 95% CI: 0.98-0.99, P: 0.035), and ECV (OR: 0.92, 95% CI: 0.86-0.99, P: 0.018) were independent predictors of early LVEF recovery.

Conclusion : Increased myocardial ECV on CTA is associated with impaired LVEF recovery post-TAVR in severe AS patients with impaired LV systolic function.
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http://dx.doi.org/10.1093/ehjci/jeaa310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822636PMC
January 2021

Optimal Medical Therapy Following Transcatheter Aortic Valve Implantation.

Am J Cardiol 2021 02 19;141:62-71. Epub 2020 Nov 19.

Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, California. Electronic address:

Limited data exist on optimal medical therapy post-transcatheter aortic valve implantation (TAVI) for late cardiovascular events prevention. We aimed to evaluate the benefits of beta-blocker (BB), renin-angiotensin system inhibitor (RASi), and their combination on outcomes following successful TAVI. In a consecutive cohort of 1,684 patients with severe aortic stenosis undergoing TAVI, the status of BB and RASi treatment at discharge was collected, and patients were classified into 4 groups: no-treatment, BB alone, RASi alone, and combination groups. The primary outcome was a composite of all-cause mortality and rehospitalization for heart failure (HHF) at 2-year. There were 415 (25%), 462 (27%), 349 (21%), and 458 (27%) patients in no-treatment, BB alone, RASi alone, and combination groups, respectively. The primary outcome was lower in RASi alone (21%; adjusted hazard ratio [HR]: 0.58; 95% confidence interval [CI]: 0.42 to 0.81) and combination (22%; HR: 0.53; 95% CI: 0.39 to 0.72) groups than in no-treatment group (34%) but no significant difference between RASi alone and combination groups (HR: 1.14; 95% CI: 0.80 to 1.62). The primary outcome results were maintained in a sensitivity analysis of patients with reduced left ventricular systolic function. Furthermore, RASi treatment was an independent predictor of 2-year all-cause mortality (HR: 0.68; 95% CI: 0.51 to 0.90), while that was not observed in BB therapy (HR: 0.94; 95% CI: 0.71 to 1.25). In conclusion, post-TAVI treatment with RASi, but not with BB, was associated with lower all-cause mortality and HHF at 2-year. The combination of RASi and BB did not add an incremental reduction in the primary outcome over RASi alone.
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http://dx.doi.org/10.1016/j.amjcard.2020.11.010DOI Listing
February 2021

Risk of Coronary Obstruction Due to Sinus Sequestration in Redo Transcatheter Aortic Valve Replacement.

JACC Cardiovasc Interv 2020 11;13(22):2617-2627

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Objectives: The aim of this study was to evaluate the risk of coronary obstruction due to sinus sequestration in redo transcatheter aortic valve replacement (TAVR) using post-TAVR computed tomography (CT).

Background: Little information is available regarding the risk of coronary obstruction due to sinus sequestration in redo TAVR inside a previously implanted TAV.

Methods: Post-TAVR CT of 66 patients who received an Evolut R or Evolut PRO and 345 patients who received a SAPIEN 3 were analyzed. Redo TAVR was considered at risk of coronary obstruction due to sinus sequestration if: 1) the prior TAV commissure level was above sinotubular junction (STJ); and 2) the distance between TAV and STJ was <2.0 mm in each coronary sinus.

Results: In total, 45.5% in the Evolut R/Evolut PRO group and 2.0% in the SAPIEN 3 group had CT-identified risk of sinus sequestration at 1 or both coronary arteries (p < 0.001). CT-identified risk of sinus sequestration was observed in 39.4% for the left coronary artery and 24.2% for the right coronary artery in the Evolut R/Evolut PRO group, while those percentages were 2.0% for the left coronary artery and 0.6% for the right coronary artery in the SAPIEN 3 group. In a coronary-level analysis, overlaps between the first TAV commissural posts and coronary ostium were observed in 45.2% in the Evolut R/Evolut PRO group and 11.1% in in the SAPIEN 3 group among coronary arteries at CT-identified risk of sinus sequestration.

Conclusions: The risk of sinus sequestration in redo TAVR should be carefully screened by CT, especially in patients with low STJ height. TAV with low commissure height that was designed to achieve commissure-to-commissure alignment with the native aortic valves may be preferable to avoid the risk of coronary obstruction due to sinus sequestration and allow for a preventive leaflet laceration procedure in future redo TAVR. (Assessment of TRanscathetEr and Surgical Aortic BiOprosthetic Valve Thrombosis and Its TrEatment With Anticoagulation [RESOLVE]; NCT02318342).
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http://dx.doi.org/10.1016/j.jcin.2020.09.022DOI Listing
November 2020

Safety Profile of an Intra-Annular Self-Expanding Transcatheter Aortic Valve and Next-Generation Low-Profile Delivery System.

JACC Cardiovasc Interv 2020 11 20;13(21):2467-2478. Epub 2020 Jul 20.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Objectives: The aim of this study was to characterize the safety profile of an intra-annular self-expanding valve with a next-generation low-profile delivery system (DS).

Background: Key design modifications to the FlexNav DS include the addition of a hydrophilic-coated, integrated sheath and stability layer to facilitate gradual, controlled deployment in vessels with diameter ≥5 mm.

Methods: Patients were pooled from 2 concurrent prospective, multicenter, single-arm studies (FlexNav DS arm of PORTICO IDE [Portico Re-Sheathable Transcatheter Aortic Valve System U.S. IDE Trial] [n = 134] and the FlexNav EU CE Mark Study [n = 46]) for the analysis. The primary endpoint was Valve Academic Research Consortium-2-defined major vascular complications at 30 days. Clinical outcomes and valve performance were assessed through 30 days by an independent clinical events committee and an echocardiography core laboratory, respectively.

Results: One hundred forty high-risk and 40 extreme-risk subjects enrolled between October 15, 2018, and December 10, 2019, from 28 sites in the United States, Australia, and Europe who underwent attempted transfemoral Portico valve implantation were included. The mean age was 85.1 ± 5.6 years, 60% were women, the mean Society of Thoracic Surgeons score was 5.3%, and 96.1% presented with ≥1 frailty factor. Technical device success was 96.7%. At 30 days, the rate of major vascular complications was 5.0%, with 4.4% of complications adjudicated as access site-related (3.3% transcatheter aortic valve replacement DS access site-related). Death (0.6%) and disabling stroke (1.1%) were rare. The rate of new permanent pacemaker implantation was 15.4%. Echocardiography revealed a mean gradient of 7.1 ± 3.2 mm Hg, mean valve area of 1.77 ± 0.41 cm, and a 4.1% rate of moderate paravalvular leak at 30 days.

Conclusions: Portico valve implantation with the FlexNav DS was associated with an excellent safety profile at 30 days.
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http://dx.doi.org/10.1016/j.jcin.2020.06.041DOI Listing
November 2020

Prognostic Value of Computed Tomography-Derived Extracellular Volume in TAVR Patients With Low-Flow Low-Gradient Aortic Stenosis.

JACC Cardiovasc Imaging 2020 12 28;13(12):2591-2601. Epub 2020 Oct 28.

Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, California, USA; Mark Taper Imaging Institute, Cedars Sinai Medical Center Los Angeles, California, USA.

Objectives: The association between extracellular volume (ECV) measured by computed tomography angiography (CTA) and clinical outcomes was evaluated in low-flow low-gradient (LFLG) aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR).

Background: Patients with LFLG AS comprise a high-risk group with respect to clinical outcomes. Although ECV, a marker of myocardial fibrosis, is traditionally measured with cardiac magnetic resonance, it can also be measured using cardiac CTA. The authors hypothesized that in LFLG AS, increased ECV may be associated with adverse clinical outcomes.

Methods: In 150 LFLG patients with AS who underwent TAVR, ECV was quantified using pre-TAVR CTA. Echocardiographic and clinical information including all-cause death and heart failure rehospitalization (HFH) was obtained from electronic medical records. A Cox proportional hazards model was used to evaluate the association between ECV and death+HFH.

Results: During a median follow-up of 13.9 months (range 0.07 to 28.9 months), there were 31 death+HFH events (21%). Patients who experienced death+HFH had a greater median Society of Thoracic Surgery score (9.9 vs. 4.7; p < 0.01), lower left ventricular ejection fraction (42.3 ± 20.2% vs. 52.7 ± 17.2%; p < 0.01), lower mean transvalvular gradient (24.9 ± 8.9 mm Hg vs. 28.1 ± 7.3 mm Hg; p = 0.04) and increased mean ECV (35.5 ± 9.6% vs. 29.9 ± 8.2%; p < 0.01) compared with patients who did not experience death+HFH. In a multivariable Cox proportional hazards model, increase in ECV was associated with increase in death+HFH, (hazard ratio per 1% increase: 1.04, 95% confidence interval: 1.01 to 1.09; p < 0.01).

Conclusions: In patients with LFLG AS, CTA measured increase in ECV is associated with increased risk of adverse clinical outcomes post-TAVR and may thus serve as a useful noninvasive marker for prognostication.
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http://dx.doi.org/10.1016/j.jcmg.2020.07.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850162PMC
December 2020

Anticoagulation Therapy After Transcatheter Aortic Valve Replacement.

Curr Cardiol Rep 2020 Oct 10;22(12):175. Epub 2020 Oct 10.

Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA.

Purpose Of Review: We review the prevalence; natural history; impact of subclinical clinical thrombosis on valve hemodynamics, clinical outcomes, and valve durability; and the role of anticoagulation after transcatheter aortic valve replacement (TAVR).

Recent Findings: Subclinical leaflet thrombosis is a dynamic finding present in both transcatheter and surgical bioprosthetic aortic valves. This finding is less prevalent in patients on anticoagulation and resolves following initiation of anticoagulation. Routine anticoagulation after TAVR in high-surgical-risk patients was associated with increased mortality and thromboembolic complications. In the absence of a clinical indication for anticoagulation, there is no reason to initiate anticoagulation after TAVR for the prevention of subclinical leaflet thrombosis. In patients with an established indication for anticoagulation, for instance, atrial fibrillation, clinical or symptomatic valve thrombosis, or a clinical event related to valve thrombosis, anticoagulation should be initiated or continued after TAVR to treat the clinical indication.
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http://dx.doi.org/10.1007/s11886-020-01425-8DOI Listing
October 2020

Transcatheter Edge-to-Edge Mitral Valve Repair With the MitraClip G4 System.

JACC Cardiovasc Interv 2020 10 30;13(20):2402-2414. Epub 2020 Sep 30.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Objectives: The primary objective of this study was to evaluate the effectiveness of the MitraClip G4 in the reduction of mitral regurgitation (MR).

Background: The next-generation MitraClip G4 system was recently introduced for the treatment of MR in the United States.

Methods: The study included consecutive patients undergoing transcatheter mitral edge-to-edge repair for MR with the MitraClip G4. The key outcome was the proportion of patients with MR reduction to ≤2+ at 30 days.

Results: Fifty-nine patients (median age 77 years, 62.7% men) were treated with the MitraClip G4. Reduction of MR to ≤2+ was achieved in 57 patients (96.6%) during the procedure, 58 patients (98.3%) at discharge, and 57 patients (96.6%) by 30 days. The median number of MitraClips used per patient was 2 (interquartile range: 1 to 3). Wide clips (NTW/XTW) were used in 82.7% of patients. The XTW clip was used most frequently as the first clip in patients with degenerative MR (65.4%) and the NTW clip in those with secondary MR (72.7%). The independent grasping mechanism was used in 49.2% of patients.

Conclusions: Use of the MitraClip G4 system was associated with excellent reduction in MR to ≤2+ in 96.6% of patients at 30 days. The availability of multiple MitraClip G4 sizes, especially the wide clips, and the ability to independently grasp leaflets are the likely contributors to MR reduction.
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http://dx.doi.org/10.1016/j.jcin.2020.06.053DOI Listing
October 2020

The Impact of Valvuloarterial Impedance on Left Ventricular Geometrical Change after Transcatheter Aortic Valve Replacement: A Comparison between Valvuloarterial Impedance and Mean Pressure Gradient.

J Clin Med 2020 Sep 29;9(10). Epub 2020 Sep 29.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Increase in left ventricular (LV) mass develops as a compensatory mechanism against pressure overload in aortic valve stenosis. However, long-standing LV geometrical changes are related to poor prognosis. The LV geometrical change occurs after transcatheter aortic valve replacement (TAVR). The present study aimed to investigate the relationship between improvement in valvuloarterial impedance (Zva) and change in LV mass index (LVMI) and the ratio of LVMI to LV end-diastolic volume index (LVMI/LVEDVI). We compared these relationships to that between Zva and mean pressure gradient (MPG). Baseline and follow-up transthoracic echocardiograms of 301 patients who underwent TAVR from November 2011 to December 2015 were reviewed. Spearman correlation coefficient (ρ) was used to compare ΔLVMI and ΔLVMI/LVEDVI with Zva or MPG. The correlation between ΔZva and ΔLVMI (ρ = 0.47, < 0.001) was superior to that between ΔMPG and ΔLVMI (ρ = 0.15, = 0.009) ( for comparison < 0.001). The correlation between ΔZva and ΔLVMI/LVEDVI was statistically significant (ρ = 0.54, < 0.001); in contrast, that of ΔMPG and ΔLVMI/LVEDVI was not. The improvement in Zva after TAVR was more closely related to LVMI and LVMI/LVEDVI reduction than MPG reduction.
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http://dx.doi.org/10.3390/jcm9103143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600915PMC
September 2020

Bicuspid Aortic Valve Morphology and Outcomes After Transcatheter Aortic Valve Replacement.

J Am Coll Cardiol 2020 09;76(9):1018-1030

Cedars-Sinai Medical Center, Smidt Cedars-Sinai Heart Institute, Los Angeles, California. Electronic address:

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: 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).
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http://dx.doi.org/10.1016/j.jacc.2020.07.005DOI Listing
September 2020

Outcomes of Patients with Severe Aortic Stenosis and Left Ventricular Obstruction Undergoing Transcatheter Aortic Valve Implantation.

Am J Cardiol 2020 10 28;133:105-115. Epub 2020 Jul 28.

Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, California. Electronic address:

Scarce data exist on clinical features and prognosis of patients with severe aortic stenosis (AS), concomitant with left ventricular obstruction (LVO). We aimed to evaluate the prevalence, characteristics, and outcomes in patients with severe AS and LVO undergoing transcatheter aortic valve implantation (TAVI). Consecutive patients with severe AS undergoing TAVI between January 2013 to December 2017 at our institution were included. Significant LVO was defined as resting peak left ventricular (LV) systolic gradient ≥30 mm Hg on pre-TAVI echocardiography. We analyzed the primary composite outcome of all-cause mortality and rehospitalization for heart failure (HHF) at 1-year in patients with LVO and those without LVO in the overall and propensity-matched populations. Among 1,729 patients who underwent TAVI, significant LVO was observed in 31 (1.8%) patients. This group was more likely to be female, had smaller aortic annulus and LV cavity, and received a smaller size of the transcatheter heart valve. The most common phenotype of LV hypertrophy causing LVO was concentric LV hypertrophy (58%), and mid-LV obstruction was more common than LV outflow tract obstruction (77% vs 23%, respectively). After adjustment for baseline differences, the primary outcome was not significantly different between patients with LVO and those without LVO (15% vs 16%, respectively; hazard ratio: 0.83; 95% confidence interval: 0.19 to 3.72; p = 0.809). In conclusion, in patients undergoing TAVI, concomitant LVO was relatively uncommon and occurred more often at mid-LV. The presence of pre-TAVI LVO was not associated with worse outcomes defined as increase all-cause mortality or HHF at 1-year.
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http://dx.doi.org/10.1016/j.amjcard.2020.07.051DOI Listing
October 2020

Intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): a randomized, placebo-controlled, double-blinded trial.

Eur Heart J 2020 09;41(36):3451-3458

Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.

Aims: Cardiosphere-derived cells (CDCs) are cardiac progenitor cells that exhibit disease-modifying bioactivity in various models of cardiomyopathy and in previous clinical studies of acute myocardial infarction (MI), dilated cardiomyopathy, and Duchenne muscular dystrophy. The aim of the study was to assess the safety and efficacy of intracoronary administration of allogeneic CDCs in the multicentre, randomized, double-blinded, placebo-controlled, intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR) trial.

Methods And Results: We enrolled patients 4 weeks to 12 months after MI, with left ventricular ejection fraction (LVEF) ≤45% and LV scar size ≥15% of LV mass by magnetic resonance imaging (MRI). A pre-specified interim analysis was performed when 6-month MRI data were available. The trial was subsequently stopped due to the low probability of detecting a significant treatment effect of CDCs based on the primary endpoint. Patients were randomly allocated in a 2:1 ratio to receive CDCs or placebo in the infarct-related artery by stop-flow technique. The primary safety endpoint was the occurrence, during 1-month post-intracoronary infusion, of acute myocarditis attributable to allogeneic CDCs, ventricular tachycardia- or ventricular fibrillation-related death, sudden unexpected death, or a major adverse cardiac event (death or hospitalization for heart failure or non-fatal MI or need for left ventricular assist device or heart transplant). The primary efficacy endpoint was the relative percentage change in infarct size at 12 months post-infusion as assessed by contrast-enhanced cardiac MRI. We randomly allocated 142 eligible patients of whom 134 were treated (90 to the CDC group and 44 to the placebo group). The mean baseline LVEF was 40% and the mean scar size was 22% of LV mass. No primary safety endpoint events occurred. There was no difference in the percentage change from baseline in scar size (P = 0.51) between CDCs and placebo groups at 6 months. Compared with placebo, there were significant reductions in LV end-diastolic volume (P = 0.02), LV end-systolic volume (P = 0.02), and N-terminal pro b-type natriuretic peptide (NT-proBNP) (P = 0.02) at 6 months in CDC-treated patients.

Conclusion: Intracoronary infusion of allogeneic CDCs in patients with post-MI LV dysfunction was safe but did not reduce scar size relative to placebo at 6 months. Nevertheless, the reductions in LV volumes and NT-proBNP reveal disease-modifying bioactivity of CDCs.

Trial Registration: Clinicaltrials.gov identifier: NCT01458405.
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http://dx.doi.org/10.1093/eurheartj/ehaa541DOI Listing
September 2020

Valve-in-Valve for Degenerated Transcatheter Aortic Valve Replacement Versus Valve-in-Valve for Degenerated Surgical Aortic Bioprostheses: A 3-Center Comparison of Hemodynamic and 1-Year Outcome.

J Am Heart Assoc 2020 07 9;9(14):e013973. Epub 2020 Jul 9.

Cedars-Sinai Smidt Heart Institute Los Angeles CA.

Background As transcatheter aortic valve replacement (TAVR) is expected to progress into younger patient populations, valve-in-TAVR (ViTAVR) may become a frequent consideration. Data on ViTAVR, however, are limited. This study investigated the outcome of ViTAVR in comparison to valve in surgical aortic valve replacement (ViSAVR), because ViSAVR is an established procedure for higher-risk patients requiring repeated aortic valve intervention. Methods and Results Clinical and procedural data of patients who underwent ViTAVR at 3 sites in the United States and Germany were retrospectively compared with data of patients who underwent ViSAVR at Cedars-Sinai Medical Center, according to Valve Academic Research Consortium-2 criteria. A total of 99 consecutive patients, 52.5% women, with a median Society of Thoracic Surgeons score of 7.2 were identified. Seventy-four patients (74.7%) underwent ViSAVR, and 25 patients (25.3%) underwent ViTAVR. Balloon-expandable devices were used in 72.7%. ViSAVR patients presented with smaller index devices (21.0 versus 26.0 mm median true internal diameter; <0.001). Significantly better postprocedural hemodynamics (median prosthesis mean gradient, 12.5 [interquartile range, 8.8-16.2] versus 16.0 [interquartile range, 13.0-20.5] mm Hg; =0.045) were observed for ViTAVR compared with the ViSAVR. Device success, however, was not different (79.2% and 66.2% for ViTAVR and ViSAVR, respectively; =0.35), as were rates of permanent pacemaker implantation (16.7% versus 5.4%; =0.1). One-year-mortality was 9.4% and 13.4% for ViTAVR and ViSAVR, respectively (log-rank =0.38). Conclusions Compared with ViSAVR, ViTAVR provides acceptable outcomes, with slightly better hemodynamics, similar device success rates, and similar 1-year mortality.
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http://dx.doi.org/10.1161/JAHA.119.013973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660709PMC
July 2020

Self-expanding intra-annular versus commercially available transcatheter heart valves in high and extreme risk patients with severe aortic stenosis (PORTICO IDE): a randomised, controlled, non-inferiority trial.

Lancet 2020 09 25;396(10252):669-683. Epub 2020 Jun 25.

Cardiovascular Institute, Los Robles Regional Medical Center, Thousand Oaks, CA, USA.

Background: Randomised trial data assessing the safety and efficacy of the self-expanding intra-annular Portico transcatheter aortic valve system (Abbott Structural Heart, St Paul, MN, USA) compared with any commercially available valves are needed to compare performance among designs.

Methods: In this prospective, multicentre, non-inferiority, randomised controlled trial (the Portico Re-sheathable Transcatheter Aortic Valve System US Investigational Device Exemption trial [PORTICO IDE]), high and extreme risk patients with severe symptomatic aortic stenosis were recruited from 52 medical centres experienced in performing transcatheter aortic valve replacement in the USA and Australia. Patients were eligible if they were aged 21 years or older, in New York Heart Association functional class II or higher, and had severe native aortic stenosis. Eligible patients were randomly assigned (1:1) using permuted block randomisation (block sizes of 2 and 4) and stratified by clinical investigational site, surgical risk cohort, and vascular access method, to transcatheter aortic valve replacement with the first generation Portico valve and delivery system or a commercially available valve (either an intra-annular balloon-expandable Edwards-SAPIEN, SAPIEN XT, or SAPIEN 3 valve [Edwards LifeSciences, Irvine, CA, USA]; or a supra-annular self-expanding CoreValve, Evolut-R, or Evolut-PRO valve [Medtronic, Minneapolis, MN, USA]). Investigational site staff, implanting physician, and study participant were unmasked to treatment assignment. Core laboratories and clinical event assessors were masked to treatment allocation. The primary safety endpoint was a composite of all-cause mortality, disabling stroke, life-threatening bleeding requiring transfusion, acute kidney injury requiring dialysis, or major vascular complication at 30 days. The primary efficacy endpoint was all-cause mortality or disabling stroke at 1 year. Clinical outcomes and valve performance were assessed up to 2 years after the procedure. Primary analyses were by intention to treat and the Kaplan-Meier method to estimate event rates. The non-inferiority margin was 8·5% for primary safety and 8·0% for primary efficacy endpoints. This study is registered with ClinicalTrials.gov, NCT02000115, and is ongoing.

Findings: Between May 30 and Sept 12, 2014, and between Aug 21, 2015, and Oct 10, 2017, with recruitment paused for 11 months by the funder, we recruited 1034 patients, of whom 750 were eligible and randomly assigned to the Portico valve group (n=381) or commercially available valve group (n=369). Mean age was 83 years (SD 7) and 395 (52·7%) patients were female. For the primary safety endpoint at 30 days, the event rate was higher in the Portico valve group than in the commercial valve group (52 [13·8%] vs 35 [9·6%]; absolute difference 4·2, 95% CI -0·4 to 8·8 [upper confidence bound {UCB} 8·1%]; p=0·034, p=0·071). At 1 year, the rates of the primary efficacy endpoint were similar between the groups (55 [14·8%] in the Portico group vs 48 [13·4%] in the commercial valve group; difference 1·5%, 95% CI -3·6 to 6·5 [UCB 5·7%]; p=0·0058, p=0·50). At 2 years, rates of death (80 [22·3%] vs 70 [20·2%]; p=0·40) or disabling stroke (10 [3·1%] vs 16 [5·0%]; p=0·23) were similar between groups.

Interpretation: The Portico valve was associated with similar rates of death or disabling stroke at 2 years compared with commercial valves, but was associated with higher rates of the primary composite safety endpoint including death at 30 days. The first-generation Portico valve and delivery system did not offer advantages over other commercially available valves.

Funding: Abbott.
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http://dx.doi.org/10.1016/S0140-6736(20)31358-1DOI Listing
September 2020

Subclinical Leaflet Thrombosis in Transcatheter and Surgical Bioprosthetic Valves: PARTNER 3 Cardiac Computed Tomography Substudy.

J Am Coll Cardiol 2020 06;75(24):3003-3015

Columbia University Medical Center/NewYork-Presbyterian Hospital, New York, New York.

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: 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 (n = 221) or surgery (n = 214). Serial 4-dimensional CTs were performed at 30 days and 1 year and were analyzed independently by a core laboratory.

Results: The incidence of HALT increased from 10% at 30 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 30 days (13% vs. 5%; p = 0.03), but not at 1 year (28% vs. 20%; p = 0.19). The presence of HALT did not significantly affect aortic valve mean gradients at 30 days or 1 year. Patients with HALT at both 30 days and 1 year, compared with those with no HALT at 30 days and 1 year, had significantly increased aortic valve gradients at 1 year (17.8 ± 2.2 mm Hg vs. 12.7. ± 0.3 mm Hg; p = 0.04).

Conclusions: Subclinical leaflet thrombosis was more frequent in transcatheter compared with surgical valves at 30 days, but not at 1 year. The impact of HALT on thromboembolic complications and structural valve degeneration needs further assessment.
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http://dx.doi.org/10.1016/j.jacc.2020.04.043DOI Listing
June 2020

Allogeneic cardiosphere-derived cells (CAP-1002) in critically ill COVID-19 patients: compassionate-use case series.

Basic Res Cardiol 2020 05 12;115(4):36. Epub 2020 May 12.

Cedars-Sinai Medical Center, Smidt Heart Institute, 127 S. San Vicente Boulevard, Advanced Health Sciences Pavilion, Third Floor, Suite A3100, Los Angeles, CA, 90048, USA.

There are no definitive therapies for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Therefore, new therapeutic strategies are needed to improve clinical outcomes, particularly in patients with severe disease. This case series explores the safety and effectiveness of intravenous allogeneic cardiosphere-derived cells (CDCs), formulated as CAP-1002, in critically ill patients with confirmed coronavirus disease 2019 (COVID-19). Adverse reactions to CAP-1002, clinical status on the World Health Organization (WHO) ordinal scale, and changes in pro-inflammatory biomarkers and leukocyte counts were analyzed. All patients (n = 6; age range 19-75 years, 1 female) required ventilatory support (invasive mechanical ventilation, n = 5) with PaO/FiO ranging from 69 to 198. No adverse events related to CAP-1002 administration were observed. Four patients (67%) were weaned from respiratory support and discharged from the hospital. One patient remains mechanically ventilated as of April 28th, 2020; all survive. A contemporaneous control group of critically ill COVID-19 patients (n = 34) at our institution showed 18% overall mortality at a similar stage of hospitalization. Ferritin was elevated in all patients at baseline (range of all patients 605.43-2991.52 ng/ml) and decreased in 5/6 patients (range of all patients 252.89-1029.90 ng/ml). Absolute lymphocyte counts were low in 5/6 patients at baseline (range 0.26-0.82 × 10/µl) but had increased in three of these five patients at last follow-up (range 0.23-1.02 × 10/µl). In this series of six critically ill COVID-19 patients, intravenous infusion of CAP-1002 was well tolerated and associated with resolution of critical illness in 4 patients. This series demonstrates the apparent safety of CAP-1002 in COVID-19. While this initial experience is promising, efficacy will need to be further assessed in a randomized controlled trial.
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http://dx.doi.org/10.1007/s00395-020-0795-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214858PMC
May 2020

Coronary Access After TAVR.

JACC Cardiovasc Interv 2020 03;13(6):693-705

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Objectives: The aim of this study was to assess the incidence of unfavorable coronary access after transcatheter aortic valve replacement (TAVR) using post-implantation computed tomography (CT).

Background: Real-world data regarding coronary access after TAVR assessed using post-implantation CT are scarce.

Methods: Post-TAVR CT of 66 patients treated with Evolut R or Evolut PRO valves and 345 patients treated with SAPIEN 3 valves were analyzed. The distance from inflow of the transcatheter heart valve (THV) to the coronary ostia and the overlap between THV commissures and the coronary ostia were assessed. Coronary access was defined as unfavorable if the coronary ostium was below the skirt or in front of the THV commissural posts above the skirt in each coronary artery.

Results: CT-identified features of unfavorable coronary access were observed in 34.8% (n = 23) for the left coronary artery and 25.8% (n = 17) for the right coronary artery in the Evolut R/Evolut PRO group, while those percentages were 15.7% (n = 54) for the left coronary artery and 8.1% (n = 28) for the right coronary artery in the SAPIEN 3 group. In the Evolut R/Evolut PRO group, 16 coronary engagements were performed after TAVR, while 64 coronary engagements were performed in the SAPIEN 3 group after TAVR. In an engagement-level analysis, the success rates of selective coronary engagement were significantly lower in patients with CT-identified features of unfavorable coronary access compared with those with favorable coronary access in both the Evolut R/Evolut PRO (0.0% vs. 77.8%; p = 0.003) and SAPIEN 3 (33.3% vs. 91.4%; p = 0.003) groups.

Conclusions: Coronary access may be challenging in a significant proportion of patients after TAVR. THVs with low skirt or commissure height and large open cells that are designed to achieve commissure-to-commissure alignment with the native aortic valve may facilitate future coronary access. (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Thrombosis and Its Treatment With Anticoagulation [RESOLVE]; NCT02318342).
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http://dx.doi.org/10.1016/j.jcin.2020.01.216DOI Listing
March 2020

Timing and Outcomes of Percutaneous Coronary Intervention in Patients Who Underwent Transcatheter Aortic Valve Implantation.

Am J Cardiol 2020 05 8;125(9):1361-1368. Epub 2020 Feb 8.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Limited data exist regarding the timing of percutaneous coronary intervention (PCI) in patients with coronary artery disease who underwent transcatheter aortic valve implantation (TAVI). We aimed to investigate clinical outcomes of patients who underwent TAVI and planned PCI according to the timing of PCI in relation to the TAVI. Consecutive patients with severe aortic stenosis who underwent TAVI with planned PCI between January 2013 and November 2017 were included. Patients were divided according to the timing of PCI. The primary end point was major adverse cardiac and cerebrovascular events, defined as a composite of all-cause death, myocardial infarction, unplanned revascularization, and stroke. Among 1,756 patients who underwent TAVI, 258 patients underwent planned PCI either before TAVI (n = 143, 55.4%), concomitantly with TAVI (n = 77, 29.8%), or after TAVI (n = 38, 14.7%). All patients in the post-TAVI PCI group were treated using balloon-expandable valves, and neither hemodynamic instability during TAVI nor PCI-related complications were observed. In a multivariable analysis, the timing of PCI was not associated with 2-year major adverse cardiac and cerebrovascular events rate (concomitant vs pre-TAVI, hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.52 to 1.66; p = 0.79; post- vs pre-TAVI, HR: 0.45; 95% CI: 0.18 to 1.16; p = 0.10). In conclusion, there were no significant differences in terms of mid-term outcomes among pre-TAVI, concomitant, and post-TAVI PCI groups when the timing of PCI was carefully selected by heart team.
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http://dx.doi.org/10.1016/j.amjcard.2020.01.043DOI Listing
May 2020

Coronary Protection to Prevent Coronary Obstruction During TAVR: A Multicenter International Registry.

JACC Cardiovasc Interv 2020 03 12;13(6):739-747. Epub 2020 Feb 12.

Cedars-Sinai Medical Center, Los Angeles, California.

Objectives: The aim of this study was to investigate the safety and efficacy of coronary protection by preventive coronary wiring and stenting across the coronary ostia in patients at high risk for coronary obstruction after transcatheter aortic valve replacement (TAVR).

Background: Coronary obstruction following TAVR is a life-threatening complication with high procedural and short-term mortality.

Methods: Data were collected retrospectively from a multicenter international registry between April 2011 and February 2019.

Results: Among 236 patients undergoing coronary protection with preventive coronary wiring, 143 had eventually stents implanted across the coronary ostia after valve deployment. At 3-year follow-up, rates of cardiac death were 7.8% in patients receiving stents and 15.7% in those not receiving stents (adjusted hazard ratio: 0.42; 95% confidence interval: 0.14 to 1.28; p = 0.13). There were 2 definite stent thromboses (0.9%) in patients receiving stents, both occurring after TAVR in "valve-in-valve" procedures. In patients not receiving stents, there were 4 delayed coronary occlusions (DCOs) (4.3%), occurring from 5 min to 6 h after wire removal. Three cases occurred in valve-in-valve procedures and 1 in a native aortic valve procedure. Distance between the virtual transcatheter valve and the protected coronary ostia <4 mm was present in 75.0% of patients with DCO compared with 30.4% of patients without DCO (p = 0.19).

Conclusions: In patients undergoing TAVR at high risk for coronary obstruction, preventive stent implantation across the coronary ostia is associated with good mid-term survival rates and low rates of stent thrombosis. Patients undergoing coronary protection with wire only have a considerable risk for DCO.
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http://dx.doi.org/10.1016/j.jcin.2019.11.024DOI Listing
March 2020

Mitral Regurgitation in Low-Flow, Low-Gradient Aortic Stenosis Patients Undergoing TAVR: Insights From the TOPAS-TAVI Registry.

JACC Cardiovasc Interv 2020 03 12;13(5):567-579. Epub 2020 Feb 12.

Quebec Heart & Lung Institute, Laval University, Quebec City, Quebec, Canada. Electronic address:

Objectives: This study sought to determine the incidence, clinical impact, and changes over time of mitral regurgitation (MR) in patients with low-flow, low-gradient aortic stenosis (LFLG-AS) undergoing transcatheter aortic valve replacement (TAVR).

Background: Few data exist on the clinical impact and changes in severity over time of MR in patients with LFLG-AS undergoing TAVR.

Methods: A total of 308 TAVR candidates with LFLG-AS were included. Patients were categorized according to MR severity at baseline, and presence of MR improvement at 12-month follow-up. Clinical outcomes were assessed at 1 and 12 months (+ echocardiography), and yearly thereafter.

Results: Baseline mild and moderate-to-severe MR were present in 118 (38.3%) and 115 (37.3%) patients, respectively. MR was of functional and mixed etiology in 77.2% and 22.7% of patients, respectively. A total of 131 patients (42.5%) died after a median follow-up of 2 (1 to 3) years. Baseline moderate-or-greater MR had no impact on mortality (hazard ratio [HR]: 1.34; 95% confidence interval [CI]: 0.72 to 2.48) or heart failure hospitalization (HR: 1.02; 95% CI: 0.49 to 2.10). At 1-year follow-up, MR improved in 44.3% of patients and remained unchanged/worsened in 55.7%. The lack of MR improvement was associated with a higher risk of all-cause and cardiac mortality (HR: 2.02; 95% CI: 1.29 to 3.17; HR: 3.03; 95% CI: 1.27 to 7.23, respectively), rehospitalization for cardiac causes (HR: 1.50; 95% CI: 1.04 to 2.15), and an increased overall-mortality/heart failure rehospitalization (HR: 1.94; 95% CI: 1.25 to 3.02). A higher baseline left ventricular end-diastolic diameter and a higher increase in left ventricular ejection fraction were found to be independent predictors of MR improvement at 1-year follow-up (odds ratio: 0.69; 95% CI: 0.51 to 0.94; and odds ratio: 0.81; 95% CI: 0.67 to 0.96, respectively).

Conclusions: Most TAVR candidates with LFLG-AS had some degree of MR, of functional origin in most cases. MR improved in about one-half of patients, with larger left ventricular size and a higher increase in left ventricular ejection fraction post-TAVR determining MR improvement over time. The lack of MR improvement at 1 year was associated with poorer outcomes.
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http://dx.doi.org/10.1016/j.jcin.2019.11.042DOI Listing
March 2020

Investigation of Computed-Tomography Based Predictors of Acute Stroke Related to Transcatheter Aortic Valve Replacement: Aortic Wall Plaque Thickness Might be a Predictive Parameter of Stroke.

J Invasive Cardiol 2020 Feb;32(2):E18-E26

Cedars-Sinai Heart Institute, 127 S. San Vicente Blvd, Suite A3421, Los Angeles, CA 90048 USA.

Objectives: Little information is available on computed tomography (CT)-based predictors of stroke related to transcatheter aortic valve replacement (TAVR). The objective of this study was to determine whether anatomical features of the aortic valve and aorta visualized by CT are predictive parameters of stroke.

Methods: The study included 1270 patients who underwent preprocedural contrast-enhanced CT assessment and TAVR for severe aortic valve stenosis. Twenty-six patients (2.5%) who developed acute strokes that occurred within 48 hours after TAVR and 104 matched patients without strokes were identified, using 1:4 propensity-score matching. The degree of hypoattenuation in the aortic valve leaflets, calcium volume of the aortic valve, and plaque thickness in the aortic wall (the ascending aorta, aortic arch, and descending thoracic aorta) were assessed.

Results: There were no differences between the two groups in the degree of hypoattenuation in the aortic valve leaflets and calcium volume of the aortic valve. The plaque thickness of the aortic arch and descending aorta were greater in the stroke group than in the non-stroke group: aortic arch, 2.4 mm (IQR, 1.3-2.8 mm) vs 1.8 mm (IQR, 1.4-2.2 mm), respectively (P<.01); and descending aorta, 2.9 mm (IQR, 2.1-4.2 mm) vs 2.8 mm (IQR, 2.1-3.6 mm); respectively (P=.049).

Conclusion: Aortic wall plaque thickness measured by contrast-enhanced CT might be a predictive parameter of strokes that occur within 48 hours after TAVR.
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February 2020

Use of a Dual-Filter Cerebral Embolic Protection Device in Thoracic Endovascular Aortic Repair.

Ann Vasc Surg 2020 May 22;65:54.e1-54.e4. Epub 2020 Jan 22.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Division of Vascular Surgery, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA.

Background: The risk of periprocedural stroke after thoracic endovascular aortic repair (TEVAR) ranges from 3% to 8%. Although cerebral embolic protection devices (CEPD) are widely utilized in transcatheter aortic valve replacement, there are currently no Food and Drug Administration approved CEPDs for use in TEVAR. We report our initial experience with the off-label use of a dual-filter CEPD in patients undergoing TEVAR.

Methods: Two patients at high risk for embolic stroke underwent TEVAR for descending thoracic aortic aneurysms (DTAAs) at a single institution. A dual-filter CEPD (Sentinel; Boston Scientific, Marlborough, MA) was used in an off-label fashion in both cases. Patient 1 was a 62-year-old woman with a 6.2-cm DTAA, extending from the left subclavian artery (LSCA) to the diaphragm (Zones 3-5) and associated with extensive atherosclerotic disease of the aortic arch. Patient 2 was a 78-year-old woman with a 6.3-cm DTAA, extending from the LSCA (Zone 2) to the sixth intercostal space (Zone 4) with associated mural thrombus. Given the proximity of the aneurysm to the LSCA, a left carotid-subclavian bypass was performed for planned LSCA coverage.

Results: Through a percutaneous right radial artery approach using a 6F sheath, the Sentinel dual-filter CEPD was delivered over a 0.014″ guidewire into the thoracic aorta. Under fluoroscopic guidance, the 2 filters were sequentially deployed in the innominate and left common carotid arteries, respectively. Appropriately sized devices were successfully delivered and deployed in the proximal and distal landing zones, respectively. Two devices were used for each patient. Completion angiograms showed successful exclusion of the DTAAs in both cases, without evidence of endoleak. The CEPD filters were retrieved in standard fashion without difficulty. Pathology demonstrated successful capture of embolic debris and fibrin clot in both patients. Neither patient exhibited neurological deficits or device-related complications. Both patients remained neurologically intact at 1- and 2-month follow-up, respectively. Surveillance angiograms revealed successful exclusion of the aneurysm without any evidence of endoleak.

Conclusions: We report the novel off-label use of a dual-filter CEPD in 2 patients undergoing TEVAR. Pathological confirmation of embolic debris in the filters makes this a potential tool for stroke prevention during TEVAR in high-risk patients.
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http://dx.doi.org/10.1016/j.avsg.2020.01.077DOI Listing
May 2020

Allogeneic cardiosphere-derived cells for the treatment of heart failure with reduced ejection fraction: the Dilated cardiomYopathy iNtervention with Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial.

EuroIntervention 2020 Jul 17;16(4):e293-e300. Epub 2020 Jul 17.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Aims: The DYNAMIC trial assessed the safety and explored the efficacy of multivessel intracoronary infusion of allogeneic cardiosphere-derived cells (CDCs) in patients with heart failure and reduced ejection fraction (HFrEF). Here we report the results of the DYNAMIC trial.

Methods And Results: We enrolled 14 patients with EF ≤35% and NYHA Class III-IV despite maximal medical and device-based therapy in this single-centre, open-label trial. Intracoronary catheterisation delivered four escalating doses (totalling 37.5-75 million cells) by sequential non-occlusive technique to all three major coronary arteries. The primary safety endpoint was a composite of post-infusion TIMI flow, ventricular tachycardia/fibrillation, sudden death, major adverse cardiac events or acute myocarditis within 72 hours. Twelve patients were male and EF averaged 23.0% (±4.5%). No primary safety endpoints were observed. Two patients died of HFrEF progression nine and 12 months following infusion. Compared to baseline, there was an improvement in EF (26.8% vs 22.9%, p=0.023) and left ventricular end-systolic volume (139.5 vs 177.8 cm3, p=0.03) at six months. Quality of life (QoL) scores and NYHA class (p=0.006) improved at six months. At 12 months, the improvement in EF and QoL remained significant.

Conclusions: Global intracoronary infusion of allogeneic CDCs is safe and feasible. The efficacy of allogeneic CDCs in HFrEF needs to be tested in larger randomised trials.
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http://dx.doi.org/10.4244/EIJ-D-19-00035DOI Listing
July 2020

Anticoagulation After Surgical or Transcatheter Bioprosthetic Aortic Valve Replacement.

J Am Coll Cardiol 2019 09;74(9):1190-1200

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Background: There is paucity of evidence on the impact of anticoagulation (AC) after bioprosthetic aortic valve replacement (AVR) on valve hemodynamics and clinical outcomes.

Objectives: The study aimed to assess the impact of AC after bioprosthetic AVR on valve hemodynamics and clinical outcomes.

Methods: Data on antiplatelet and antithrombotic therapy were collected. Echocardiograms were performed at 30 days and 1 year post-AVR. Linear regression model and propensity-score adjusted cox proportional model were used to assess the impact of AC on valve hemodynamics and clinical outcomes, respectively.

Results: A total of 4,832 patients undergoing bioprosthetic AVR (transcatheter aortic valve replacement [TAVR], n = 3,889 and surgical AVR [SAVR], n = 943) in the pooled cohort of PARTNER2 (Placement of Aortic Transcatheter Valves) randomized trials and nonrandomized registries were studied. Following adjustment for valve size, annular diameter, atrial fibrillation, and ejection fraction at the time of assessment of hemodynamics, there was no significant difference in aortic valve mean gradients or aortic valve areas between patients discharged on AC vs. those not discharged on AC, for either TAVR or SAVR cohorts. A significantly greater proportion of patients not discharged on AC had an increase in mean gradient >10 mm Hg from 30 days to 1 year, compared with those discharged on AC (2.3% vs. 1.1%, p = 0.03). There was no independent association between AC after TAVR and adverse outcomes (death, p = 0.15; rehospitalization, p = 0.16), whereas AC after SAVR was associated with significantly fewer strokes (hazard ratio [HR]: 0.17; 95% confidence interval [CI]: 0.05-0.60; p = 0.006).

Conclusions: In the short term, early AC after bioprosthetic AVR did not result in adverse clinical events, did not significantly affect aortic valve hemodynamics (aortic valve gradients or area), and was associated with decreased rates of stroke after SAVR (but not after TAVR). Whether early AC after bioprosthetic AVR has impact on long-term outcomes remains to be determined. (Placement of AoRTic TraNscathetER Valves [PARTNERII A]; NCT01314313).
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http://dx.doi.org/10.1016/j.jacc.2019.06.058DOI Listing
September 2019

Antithrombotic Therapy and Cardiovascular Outcomes After Transcatheter Aortic Valve Replacement in Patients With Atrial Fibrillation.

JACC Cardiovasc Interv 2019 08;12(16):1580-1589

Clinical Trials Center, Cardiovascular Research Foundation, New York, New York; Department of Medicine, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York.

Objectives: The study sought to determine the patterns of antithrombotic therapy and association with clinical outcomes in patients with atrial fibrillation (AF) and CHADS-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category) score ≥2 following transcatheter aortic valve replacement (TAVR).

Background: The impact of antithrombotic regimens on clinical outcomes in patients with AF and severe aortic stenosis treated with TAVR is unknown.

Methods: In the randomized PARTNER II (Placement of Aortic Transcatheter Valve II) trial and associated registries, 1,621 patients with prior AF and CHADS-VASc score ≥2 comprised the study cohort. Outcomes were analyzed according to antithrombotic therapy.

Results: During the 5-year enrollment period, 933 (57.6%) patients were discharged on oral anticoagulant therapy (OAC). Uninterrupted antiplatelet therapy (APT) for at least 6 months or until an endpoint event was used in 544 of 933 (58.3%) of patients on OAC and 77.5% of patients not on OAC. At 2 years, patients on OAC had a similar rate of stroke (6.6% vs. 5.6%; p = 0.53) and the composite outcome of death or stroke (29.7% vs. 31.8%; p = 0.33), compared with no OAC. OAC with APT was associated with a reduced rate of stroke (5.4% vs. 11.1%; p = 0.03) and death or stroke (29.7% vs. 40.1%; p = 0.01), compared with no OAC or APT. Following adjustment, OAC with APT and APT alone were both associated with reduced rates of stroke compared with no OAC or APT (hazard ratio for OAC+APT: 0.43, 95% confidence interval: 0.22 to 0.85; p = 0.015; hazard ratio for APT alone: 0.32, 95% confidence interval: 0.16 to 0.65; p = 0.002), while OAC alone was not.

Conclusions: Among patients with prior AF undergoing TAVR, antiplatelet with or without anticoagulant therapy was associated with a reduced risk of stroke at 2 years, implicating multifactorial stroke mechanisms in this population.
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http://dx.doi.org/10.1016/j.jcin.2019.06.001DOI Listing
August 2019