Mitral Annulus Calcification Abramowitz, Yigal, MD; Jilaihawi, Hasan, MD; Chakravarty, Tarun, MD ...
Journal of the American College of Cardiology,
10/2015, Letnik:
66, Številka:
17
Journal Article
Recenzirano
Odprti dostop
Abstract Mitral annulus calcification (MAC) is a chronic, degenerative process in the fibrous base of the mitral valve. Although MAC was initially thought to be an age-related degenerative process, ...there is accumulating evidence that other mechanisms, such as atherosclerosis and abnormal calcium-phosphorus metabolism, also contribute to the development of MAC. Despite its frequency, the clinical relevance of MAC is grossly underappreciated. Indeed, MAC is associated with an increased incidence of cardiovascular disease, mitral valve disease, arrhythmias, and mortality. MAC also influences the outcomes of cardiac surgery and interventions, and its clinical relevance may well increase substantially in the forthcoming era of transcatheter mitral valve replacement. In this paper, we review the available published data to provide a consistent, clinically relevant description of MAC on the basis of contemporary imaging. We describe the pathophysiological mechanisms contributing to the formation of MAC and the clinical implications of this disease entity.
A finding of reduced aortic-valve leaflet motion was noted on computed tomography (CT) in a patient who had a stroke after transcatheter aortic-valve replacement (TAVR) during an ongoing clinical ...trial. This finding raised a concern about possible subclinical leaflet thrombosis and prompted further investigation.
We analyzed data obtained from 55 patients in a clinical trial of TAVR and from two single-center registries that included 132 patients who were undergoing either TAVR or surgical aortic-valve bioprosthesis implantation. We obtained four-dimensional, volume-rendered CT scans along with data on anticoagulation and clinical outcomes (including strokes and transient ischemic attacks TIAs).
Reduced leaflet motion was noted on CT in 22 of 55 patients (40%) in the clinical trial and in 17 of 132 patients (13%) in the two registries. Reduced leaflet motion was detected among patients with multiple bioprosthesis types, including transcatheter and surgical bioprostheses. Therapeutic anticoagulation with warfarin, as compared with dual antiplatelet therapy, was associated with a decreased incidence of reduced leaflet motion (0% and 55%, respectively, P=0.01 in the clinical trial; and 0% and 29%, respectively, P=0.04 in the pooled registries). In patients who were reevaluated with follow-up CT, restoration of leaflet motion was noted in all 11 patients who were receiving anticoagulation and in 1 of 10 patients who were not receiving anticoagulation (P<0.001). There was no significant difference in the incidence of stroke or TIA between patients with reduced leaflet motion and those with normal leaflet motion in the clinical trial (2 of 22 patients and 0 of 33 patients, respectively; P=0.16), although in the pooled registries, a significant difference was detected (3 of 17 patients and 1 of 115 patients, respectively; P=0.007).
Reduced aortic-valve leaflet motion was shown in patients with bioprosthetic aortic valves. The condition resolved with therapeutic anticoagulation. The effect of this finding on clinical outcomes including stroke needs further investigation. (Funded by St. Jude Medical and Cedars-Sinai Heart Institute; Portico-IDE ClinicalTrials.gov number, NCT02000115; SAVORY registry, NCT02426307; and RESOLVE registry, NCT02318342.).
Transcatheter aortic valve replacement (TAVR) indications are expanding, leading to an increasing number of patients with bicuspid aortic stenosis undergoing TAVR. Pivotal randomized trials conducted ...to obtain US Food and Drug Administration approval excluded bicuspid anatomy.
To compare the outcomes of TAVR with a balloon-expandable valve for bicuspid vs tricuspid aortic stenosis.
Registry-based prospective cohort study of patients undergoing TAVR at 552 US centers. Participants were enrolled in the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapies Registry from June 2015 to November 2018.
TAVR for bicuspid vs tricuspid aortic stenosis.
Primary outcomes were 30-day and 1-year mortality and stroke. Secondary outcomes included procedural complications, valve hemodynamics, and quality of life assessment.
Of 81 822 consecutive patients with aortic stenosis (2726 bicuspid; 79 096 tricuspid), 2691 propensity-score matched pairs of bicuspid and tricuspid aortic stenosis were analyzed (median age, 74 years interquartile range {IQR}, 66-81 years; 39.1%, women; mean SD STS-predicted risk of mortality, 4.9% 4.0% and 5.1% 4.2%, respectively). All-cause mortality was not significantly different between patients with bicuspid and tricuspid aortic stenosis at 30 days (2.6% vs 2.5%; hazard ratio HR, 1.04, 95% CI, 0.74-1.47) and 1 year (10.5% vs 12.0%; HR, 0.90 95% CI, 0.73-1.10). The 30-day stroke rate was significantly higher for bicuspid vs tricuspid aortic stenosis (2.5% vs 1.6%; HR, 1.57 95% CI, 1.06-2.33). The risk of procedural complications requiring open heart surgery was significantly higher in the bicuspid vs tricuspid cohort (0.9% vs 0.4%, respectively; absolute risk difference RD, 0.5% 95% CI, 0%-0.9%). There were no significant differences in valve hemodynamics. There were no significant differences in moderate or severe paravalvular leak at 30 days (2.0% vs 2.4%; absolute RD, 0.3% 95% CI, -1.3% to 0.7%) and 1 year (3.2% vs 2.5%; absolute RD, 0.7% 95% CI, -1.3% to 2.7%). At 1 year there was no significant difference in improvement in quality of life between the groups (difference in improvement in the Kansas City Cardiomyopathy Questionnaire overall summary score, -2.4 95% CI, -5.1 to 0.3; P = .08).
In this preliminary, registry-based study of propensity-matched patients who had undergone transcatheter aortic valve replacement for aortic stenosis, patients with bicuspid vs tricuspid aortic stenosis had no significant difference in 30-day or 1-year mortality but had increased 30-day risk for stroke. Because of the potential for selection bias and the absence of a control group treated surgically for bicuspid stenosis, randomized trials are needed to adequately assess the efficacy and safety of transcatheter aortic valve replacement for bicuspid aortic stenosis.
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
2
/FiO
2
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
3
/µl) but had increased in three of these five patients at last follow-up (range 0.23–1.02 × 10
3
/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.
Abstract Subclinical leaflet thrombosis was recently described in a randomized trial of transcatheter aortic valve replacement. It was subsequently demonstrated in a series of registries that this ...was a commonly observed imaging finding seen in all transcatheter and surgical bioprostheses. The phenomenon has aroused considerable interest due to the as-yet-undefined risk for later clinical events and the possibility of pharmacological intervention with anticoagulation. Subclinical leaflet thrombosis is easily detected noninvasively by technically suitable computed tomography (CT) with a high degree of concordance to transesophageal echocardiography findings. The CT hallmarks were noted to be hypoattenuated leaflet thickening (HALT) associated with reduced leaflet motion (RELM). The combination of HALT and RELM signified hypoattenuation affecting motion, the standardized imaging endpoint used. This paper describes the systematic CT evaluation methodology that was devised during the Portico trial investigation and U.S. Food and Drug Administration submission; it also highlights the need for an ongoing discussion among experts to enable, with the help of the Valve Academic Research Consortium, standardization of reporting of this imaging finding to cater to the present and future needs of clinical trials.
Abstract Objectives This study sought to develop a robust and definitive risk model for new permanent pacemaker implantation (PPMI) after SAPIEN 3 (third generation balloon expandable valve) (Edwards ...Lifesciences, Irvine, California) transcatheter aortic valve replacement (third generation balloon expandable valve TAVR), including calcification in the aortic-valvular complex (AVC). Background The association between calcium in the AVC and need for PPMI is poorly delineated after third generation balloon expandable valve TAVR. Methods At Cedars-Sinai Heart Institute in Los Angeles, California, a total of 240 patients with severe aortic stenosis underwent third generation balloon expandable valve TAVR and had contrast computed tomography. AVC was characterized precisely by leaflet sector and region. Results The total new PPMI rate was 14.6%. On multivariate analysis for predictors of PPMI, pre-procedure third generation balloon expandable valve TAVR, right bundle branch block (RBBB), shorter membranous septum (MS) length, and noncoronary cusp device-landing zone calcium volume (NCC-DLZ CA) were included. Predictive probabilities were generated using this logistic regression model. If 3 pre-procedural risk factors were present, the c-statistic of the model for PPMI was area under the curve of 0.88, sensitivity of 77.1%, and specificity of 87.1%; this risk model had high negative predictive value (95.7%). The addition of the procedural factor of device depth to the model, with the parameter of difference between implantation depth and MS length, combined with RBBB and NCC-DLZ CA increased the c-statistic to 0.92, sensitivity to 94.3%, specificity to 83.8%, and negative predictive value to 98.8% Conclusions By using a precise characterization of distribution of calcification in the AVC in a single-center, retrospective study, NCC-DLZ CA was found to be an independent predictor of new PPMI post–third generation balloon expandable valve TAVR. The findings also reinforce the importance of short MS length, pre-existing RBBB, and ventricular implantation depth as important synergistic PPMI risk factors. This risk model will need validation by future prospective multicenter studies.
Autologous cardiosphere-derived cells (CDCs) were the first therapeutic modality to demonstrate myocardial regeneration with a decrease in scar size and an increase in viable, functional tissue. ...Widespread applicability of autologous CDC therapy is limited by the need for patient-specific myocardial biopsy, cell processing, and quality control, resulting in delays to therapy and inherent logistical and economic constraints. Preclinical data had demonstrated equivalent efficiency of allogeneic to autologous CDCs. The ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration (ALLSTAR) trial is a multicenter randomized, double-blind, placebo-controlled phase 1/2 safety and efficacy trial of intracoronary delivery of allogeneic CDCs (CAP-1002) in patients with myocardial infarction (MI) and ischemic left ventricular dysfunction. The phase 1 safety cohort enrolled 14 patients in an open-label, nonrandomized, dose-escalation safety trial. The phase 2 trial is a doubleblind, randomized, placebo-controlled trial that will compare intracoronary CDCs to placebo in a 2:1 allocation and will enroll up to 120 patients. The primary endpoint for both phases is safety at 1 month. For phase 2, the primary efficacy endpoint is relative change from baseline in infarct size at 12 months, as assessed by magnetic resonance imaging. The ALLSTAR trial employs a “seamless” WOVE 1 design that enables continuous enrollment from phase 1 to phase 2 and will evaluate the safety of intracoronary administration of allogeneic CDCs and its efficacy in decreasing infarct size in post-MI patients.
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 Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy 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 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 no procedures with an EPD in the last quarter of 2019. In our primary analysis using the instrumental variable 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 to 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 odds ratio, 0.82 95% CI, 0.69-0.97; absolute risk difference, -0.28% 95% CI, -0.52 to -0.03). Results were generally consistent across the secondary end points, 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 instrumental variable 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 randomized, controlled trials to test whether EPDs provide meaningful clinical benefit for patients undergoing TAVR.
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).
...Little information is available regarding the risk of coronary obstruction due to sinus sequestration in redo TAVR inside a previously implanted TAV.
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.
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.
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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Significant mitral regurgitation (MR) constitutes an important co-existing valvular heart disease burden in the setting of aortic valve stenosis. There are conflicting reports on the impact of ...significant MR on outcomes after transcatheter aortic valve implantation (TAVI). We evaluated the impact of MR on outcomes after TAVI by performing a meta-analysis of 8 studies involving 8,927 patients reporting TAVI outcomes based on the presence or absence of moderate-severe MR. Risk ratios (RRs) were calculated using the inverse variance random-effects model. None-mild MR was present in 77.8% and moderate-severe MR in 22.2% of the patients. The presence of moderate-severe MR at baseline was associated with increased mortality at 30 days (RR 1.35, 95% confidence interval CI 1.14 to 1.59, p = 0.003) and 1 year (RR 1.24, 95% CI 1.13 to 1.37, p <0.0001). The increased mortality associated with moderate-severe MR was not influenced by the cause of MR (functional or degenerative MR; RR 0.90, 95% CI 0.62 to 1.30, p = 0.56). The severity of MR improved in 61 ± 6.0% of patients after TAVI. Moderate-severe residual MR, compared with none-mild residual MR after TAVI, was associated with significantly increased 1-year mortality (RR 1.48, 95% CI 1.31 to 1.68, p <0.00001). In conclusion, baseline moderate-severe MR and significant residual MR after TAVI are associated with an increase in mortality after TAVI and represent an important group to target with medical or transcatheter therapies in the future.
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