Review of Bleeding and Thrombotic Risks Associated With Antithrombotic Therapy After Transcatheter Structural Heart Interventions.

Transcatheter structural heart interventions have drastically evolved over the past 2 decades. However, most catheterization procedures require the deployment of devices in the body; therefore, the adhesion of thrombi to those devices is a major problem, resulting in the requirement of a period of postprocedural antithrombotic regimen. However, in recent years, bleeding associated with these antithrombotic therapies has also become a major concern, attracting the attention of investigators. This is complicated by the fact that patients at high thrombotic risk are also at high bleeding risk, making the issue of administrating antithrombotic therapy challenging. The objective of this review was to identify the important issues and summarize the current status of postoperative antithrombotic therapy and assessment of the bleeding risk following transcatheter structural heart interventions such as transcatheter aortic valve replacement, transcatheter edge-to-edge repair, and transcatheter left atrial appendage occlusion.

Perioperative changes in coagulation and platelet contribution to clot strength after transcatheter aortic valve implantation: A study using thromboelastography and conventional markers.

INTRODUCTION: Thrombotic and haemorrhagic complications have been reported following transcatheter aortic valve implantation (TAVI). However, few reports have studied perioperative changes in coagulation and platelet function after TAVI. Furthermore, there are no clear guidelines for antithrombotic therapy. This study aimed to examine the perioperative changes in coagulation and platelet contribution to clot strength after TAVI using thromboelastography (TEG 6s; Hemonetics). METHODS: This prospective observational study included 15 patients scheduled to undergo TAVI for severe aortic stenosis. TEG 6s global haemostasis was used to record three measurements: on the day of surgery (immediately before the operation) and postoperative days 1 and 3. The reaction time R to thrombosis; K and α, which represent the rate of thrombosis; and the maximum amplitude (MA) were measured from the kaolin thromboelastography (TEG) curves. The coagulation index (CI) was calculated from the measurement results to assess thrombotic tendency. In addition, MA was converted to elastic clot strength, and platelet function was assessed by the difference, Gp, in elastic strength depending on platelet activation. RESULTS: R and K decreased, and α tended to increase in kaolin TEG on days 1 and 3 after TAVI, indicating elevated coagulation function compared with the preoperative period, but MA and CI did not show significant changes. Gp decreased significantly on days 1 and 3, suggesting a decrease in the platelet contribution to clot strength. CONCLUSIONS: Compared with the preoperative period, coagulation tended to increase, and platelet contribution to clot strength decreased from days 1 to 3 after TAVI.

Impact of Gender on Mortality After Transcatheter Edge-to-Edge Repair for Functional Mitral Regurgitation.

Recent studies suggested short-term mortality after transcatheter edge-to-edge repair (TEER) was comparable between men and women. However, the gender-specific prognostic difference in the long-term follow-up after TEER is still unknown. To evaluate the impact of gender on long-term mortality after TEER for functional mitral regurgitation (FMR) using multicenter registry data. We retrospectively analyzed 1,233 patients (male 60.3%) who underwent TEER for FMR at 24 centers. The impact of gender on all-cause death and hospitalization for heart failure (HF) after TEER was evaluated using multivariate regression analysis and propensity score (PS) matching methods. During the 2-year follow-up, 207 all-cause death and 263 hospitalizations for HF were observed after TEER for FMR. Men had a significantly higher incidence of all-cause death than women (18.6% vs 14.1%, log-rank p = 0.03). After adjustment by multivariate Cox regression and PS matching, the male gender was significantly associated with a higher incidence of all-cause mortality after TEER than the female gender (hazard ratio 2.11, 95% confidence interval 1.42 to 3.14 in multivariate Cox regression; hazard ratio 1.89, 95% confidence interval 1.03 to 3.48 in PS matching). The gender-specific prognostic difference was even more pronounced after 1-year of TEER. On the contrary, there was no gender-related difference in hospitalization for HF after TEER. In conclusion, women with FMR had a better prognosis after TEER than men, whereas this was not observed in hospitalization for HF. This result might indicate that women with FMR are more likely to benefit from TEER.

Body Surface Radiation Exposure in Interventional Echocardiographers During Structural Heart Disease Procedures.

Background: The distribution of radiation exposure on the body surface of interventional echocardiographers during structural heart disease (SHD) procedures is unclear. Objectives: This study estimated and visualized radiation exposure on the body surface of interventional echocardiographers performing transesophageal echocardiography by computer simulations and real-life measurements of radiation exposure during SHD procedures. Methods: A Monte Carlo simulation was performed to clarify the absorbed dose distribution of radiation on the body surface of interventional echocardiographers. The real-life radiation exposure was measured during 79 consecutive procedures (44 transcatheter edge-to-edge repairs of the mitral valve and 35 transcatheter aortic valve replacements [TAVRs]). Results: The simulation demonstrated high-dose exposure areas (>20 µGy/h) in the right half of the body, especially the waist and lower body, in all fluoroscopic directions caused by scattered radiation from the bottom edge of the patient bed. High-dose exposure occurred when obtaining posterior-anterior and cusp-overlap views. The real-life exposure measurements were consistent with the simulation estimates: interventional echocardiographers were more exposed to radiation at their waist in transcatheter edge-to-edge repair than in TAVR procedures (median 0.334 µSv/mGy vs 0.053 µSv/mGy; P < 0.001) and in TAVR with self-expanding valves than in those with balloon-expandable valves (median 0.067 µSv/mGy vs 0.039 µSv/mGy; P < 0.01) when the posterior-anterior or the right anterior oblique angle fluoroscopic directions were used. Conclusions: During SHD procedures, the right waist and lower body of interventional echocardiographers were exposed to high radiation doses. Exposure dose varied between different C-arm projections. Interventional echocardiographers, especially young women, should be educated regarding radiation exposure during these procedures. (The development of radiation protection shield for catheter-based treatment of structural heart disease [for echocardiologists and anesthesiologists]; UMIN000046478).

Predictors of bioprosthetic valve dysfunction after transcatheter aortic valve implantation.

Background: Recently, the Valve Academic Research Consortium (VARC)-3 criteria redefined bioprosthetic valve dysfunction (BVD) after transcatheter aortic valve implantation (TAVI). However, the rate of BVD is scarcely reported in current practice. Aims: We aimed to evaluate the rate and predictors of BVD after TAVI based on the VARC-3 criteria. Methods: We retrospectively analysed patients who had undergone TAVI using single-centre data. BVD was reported as exposure-adjusted event rates with a patient-year unit (per 100 patient-years). Predictors of BVD after TAVI were analysed using Fine-Gray competing risk regression to account for the competing risk of death. Results: Among 514 patients, the rate of BVD was 7.5 events per 100 patient-years (n=74) at a median follow-up of 1.9 years. The main cause of BVD was moderate or severe prosthesis-patient mismatch (PPM; n=59). The Fine-Gray model demonstrated that predilatation was associated with a lower rate of BVD, mainly moderate or severe PPM (adjusted subdistribution hazard ratio [sub-HR] 0.42, 95% confidence interval [CI]: 0.21-0.88). In a subgroup analysis, the patients with a small aortic annulus (area <400 mm2 or perimeter <72 mm) tended to benefit from predilatation (p for interaction=0.03). The same regression model also demonstrated that a small balloon-expandable valve (BEV; ≤23 mm) was associated with a higher rate of BVD (adjusted sub-HR 2.46, 95% CI: 1.38-4.38). Conclusions: Our study suggested that the rate of BVD in patients undergoing TAVI is relatively low at midterm follow-up. Predilatation, particularly in small annuli and small BEV might have an impact on BVD, mainly caused by moderate or severe PPM, after TAVI.

Changes in platelet function and coagulation after transcatheter aortic valve implantation evaluated with thromboelastography.

INTRODUCTION: The possibility of hypercoagulability during the perioperative period of transcatheter aortic valve implantation (TAVI) has been noted; however, there is still a controversy regarding the appropriate perioperative antithrombotic therapy. The study investigated coagulation and platelet functions during the TAVI perioperative period using thromboelastography (TEG) 6s platelet mapping. METHODS: A prospective observational study was conducted on 25 patients undergoing TAVI. TEG platelet mapping was performed at three time points: on admission to the operating room (before heparinisation), on postoperative day (POD) 1 and on POD 3. Perioperative changes observed included: maximum clot strength (MAHKH), clot strength without platelet function (MAActF), time to initiation of clots formation by coagulation factors (RHKH) and platelet function (Gp). Gp is activated by thrombin, and not affected by antiplatelet agents. It is calculated as [(5000×MAHKH)/(100 - MAHKH)] - [(5000×MAActF)/(100 - MAActF)]. Finally, MAADP/AA and GADP/AA, which reflect clot strength and platelet aggregation mediated by ADP/thromboxane A2 receptors, respectively, were also examined using the same method as for Gp. RESULTS: MAHKH continued to decrease until POD 3, indicating antithrombotic change after TAVI. Gp continuously decreased for 3 days after TAVI, while MAActF increased significantly on POD 3. Furthermore, RHKH shortened on POD 1 and POD 3, suggesting increased coagulation capacity after TAVI. Finally, GADP in clopidogrel-naive patients was reduced for 3 days after TAVI, while GAA in aspirin-naive patients showed no significant change perioperatively. CONCLUSIONS: In this study involving TEG platelet mapping, coagulation capacity increased while platelet function decreased, resulting in antithrombotic change for 3 days after TAVI. The ADP receptor system may be implicated in the decreased platelet function. These results may be useful for considering optimal perioperative antithrombotic therapy in TAVI.

Validation of reliability and predictivity of membrane septum length measurements for pacemaker need after transcatheter aortic valve replacement.

OBJECTIVES: To assess the inter methodological agreement of membrane septum (MS) length measurement and additive value for risk stratification of new pacemaker implantation (PMI) over the established predictors after transcatheter aortic valve replacement (TAVR). BACKGROUND: Recent studies have suggested MS length and implantation depth (ID) as predictors for PMI after TAVR. However, the measurement of MS length is neither uniform nor validated in different cohort. METHODS: We retrospectively analyzed patients who underwent TAVR at five centers. The MS length was measured by two previously proposed methods (coronal and annular view method). Predictive ability of risk factors, including MS length and ID, for new PMI within 30 days after TAVR were evaluated. RESULTS: Among 754 patients of study population, 31 patients (4.1%) required new PMI within 30 days of TAVR. There was a weak correlation (ρ = 0.47) and a poor agreement between the two methods. The ID and the difference between MS length and ID (ΔMSID), were independent predictors for new PMI, whereas MS length alone was not. Further, for predicting new PMI after TAVR, discrimination performance was not significantly improved when MS length was added to the model with ID alone (integrated discrimination improvement = 0, p= 0.99; continuous net-reclassification improvement = 0.10, p= 0.62). CONCLUSIONS: External validity and predictive accuracy of MS length for PMI after TAVR were not sufficient to provide better risk stratification over the established predictors in our cohort. Moreover, the ID and ΔMSID, but not MS length alone, are predictive of future PMI after TAVR.

Effect of oral tolvaptan for 1 year in patients with functional mitral regurgitation.

The effect of the oral selective vasopressin V2-receptor antagonist tolvaptan for chronic phase therapy on patients with FMR remains unclear. We aimed to determine the efficacy of oral tolvaptan in patients with significant functional mitral regurgitation (FMR) to reduce the mortality and rehospitalization due to worsening heart failure (HF). We enrolled 219 patients (mean age 76 ± 9 years, 59.4% men) who were admitted at our hospital due to congestive HF during different two 1-year periods. The patients were divided into 2 groups: those who had significant FMR (MR ≥ grade 2 [n = 76]) and those who did not (MR < grade 2 [n = 143]) at discharge. The patients were further divided into a study group that received tolvaptan during follow-up and a control group that did not receive tolvaptan. We used an inverse probability of treatment weighting method with the primary end point defined as overall all-cause mortality and rehospitalization due to worsening HF within 1 year. Of the 76 patients with significant FMR at discharge, 2 of 20 (10%) who were administered tolvaptan died and 8 (40%) were readmitted to a hospital. Of the 56 patients who did not receive tolvaptan, 2 (3.5%) died and 18 (27.5%) required rehospitalization. After multiple adjustments, there were no significant differences for overall survival and rehospitalization between the groups (log-rank p = 0.700 and 0.510, respectively). Our results suggest that oral tolvaptan administration in addition to conventional diuretics had less impact on outcomes in patients with significant FMR.

Wearable cardioverter-defibrillators after myocardial infarction: a review of its clinical utility and unmet needs in current clinical practice.

Sudden cardiac death is one of the leading causes of death in the older population. Compared with the general population, patients who experienced a myocardial infarction are four to six times more likely to experience sudden cardiac death. Though primary percutaneous coronary intervention considerably reduces mortality in patients who experienced a myocardial infarction, a non-negligible number of sudden cardiac deaths still occurs. Despite the high incidence rate of sudden cardiac deaths during the first month after myocardial infarction, prophylactic use of implantable cardioverter-defibrillators has so far failed to convey a survival benefit. Therefore, current clinical guidelines recommend that cardioverter-defibrillator implantation is contraindicated until 90 days after myocardial infarction. Wearable cardioverter-defibrillators were first approved for clinical use in 2002 and are currently considered as a bridge to therapy in patients with myocardial infarction with a reduced left ventricular ejection fraction in whom cardioverter-defibrillator implantation is temporarily not indicated. However, there is insufficient recognition among interventional cardiologists of the use of wearable cardioverter-defibrillators for preventing sudden cardiac death after myocardial infarction. Hence, we reviewed the evidence of the efficacy of wearable cardioverter-defibrillators used in patients following myocardial infarction to achieve better management of sudden cardiac death.

Balloon Post-Dilatation Improves Long-Term Valve Performance After Balloon-Expandable Valve Implantation.

BACKGROUND: The impact of balloon post-dilatation (BPD) on short- and long-term valve performance after Sapien 3 (S3) implantation is unknown. This study aimed to evaluate the impact of balloon post-dilatation (BPD) on short- and long-term valve performance after the implantation of S3. METHODS: A total of 846 patients implanted with S3 from the OCEAN-TAVI registry were included in this study. The patients were divided into BPD and non-BPD groups. The clinical outcomes and valve functions were compared. RESULTS: The BPD group included 173 (20.4%) patients and the non-BPD group comprised 673 (79.6%) patients. The prosthesis-patient mismatch (PPM) rates were significantly lower in the BPD group than in the non-BPD group before and after propensity score matching at in-hospital follow-up (before matching: 12 [7.1%] vs. 108 [16.3%], p = 0.002; after matching: 8 [6.3%] vs. 19 [14.8%], p = 0.027) and at 1-year follow-up (before matching: 14 [12.5%] vs. 112 [23.6%], p = 0.010; after matching: 9 [10.5%] vs. 19 [22.1%], p = 0.039). The rates of acute kidney injury, cardiac tamponade, and in-hospital cardiovascular death were significantly higher in the BPD group than in the non-BPD group (acute kidney injury: 22 [12.7%] vs. 33 [4.9%], p < 0.001; cardiac tamponade: 3 [1.7%] vs. 2 [0.3%], p = 0.028; in-hospital cardiovascular death: 4 [2.3%] vs. 3 [0.4%], p = 0.016). After matching, these clinical outcomes were similar between the BPD and non-BPD groups. CONCLUSIONS: The BPD group demonstrated better short- and long-term valve performance. Caution is needed to avoid procedure-related complications in patients undergoing BPD.

Impact of Diabetes Mellitus on Vascular Healing Process After Everolimus-Eluting Stent Implantation: An Optical Coherence Tomography Study.

BACKGROUND/PURPOSE: To study the impact of diabetes mellitus (DM) on vascular healing process after implantation of everolimus-eluting stent (EES). METHODS/MATERIALS: Data from 3 prospective studies (HEAL-EES, REVER, and RESERVOIR), including patients with EES implantation and OCT follow-up, were merged. Differences in vascular healing process assessed by OCT were compared between DM and non-DM using generalized estimating equations. Neointimal proliferation, neointimal signal pattern (high, low, and layered), and uncovered/malapposed struts were evaluated. RESULTS: A total of 96 lesions (61 DM lesions and 35 non-DM lesions) were included. Mean OCT follow-up time was 8.9 ± 1.5 months and comparable between groups. DM were older, high frequently female and acute coronary syndrome, and received smaller stent than non-DM. No differences were observed in quantitative vascular healing process between groups. However, DM exhibited higher low and layered signal pattern neointima compared to non-DM at lesion level (p = 0.030) and cross-section level (p < 0.001). Uncovered/malapposed struts were comparable between groups. CONCLUSIONS: Quantitative vascular healing process was comparable between groups. However, DM was significantly associated with low signal pattern, which is characteristic of focal inflammation, after EES implantation. Further study might be required to study relationship between neointimal signal pattern and clinical events.

Association between periodontal bacteria and degenerative aortic stenosis: a pilot study.

PURPOSE: Although several reports have described the relationship between periodontal disease and cardiovascular disease, information about the association between periodontal disease and the progression of degenerative aortic stenosis (AS) is lacking. Therefore, we performed a retrospective, single-center, pilot study to provide insight into this potential association. METHODS: Data from 45 consecutive patients (19 men; median age, 83 years) with mild or moderate degenerative aortic stenosis were analyzed for a mean observation period of 3.3±1.9 years. The total amount of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis and titers of serum immunoglobulin G (IgG) against periodontal bacteria and high-sensitivity C-reactive protein (hs-CRP) were evaluated. Aortic valve area (AVA), maximal velocity (Vmax), mean pressure gradient (mean PG), and the Doppler velocity index (DVI) were evaluated. The change in each parameter per year ([ParameterLATEST-ParameterBASELINE]/Follow-up Years) was calculated from the retrospective follow-up echocardiographic data (baseline vs. the most recently collected data [latest]). RESULTS: No correlation was found between the concentration of periodontopathic bacteria in the saliva and AS status/progression. The anti-P. gingivalis antibody titer in the serum showed a significant positive correlation with AVA and DVI. Additionally, there was a negative correlation between the anti-P. gingivalis IgG antibody titer and mean PG. The hs-CRP concentration showed positive correlations with Vmax and mean PG. Meanwhile, a negative correlation was observed between the anti-P. gingivalis IgG antibody titer and ΔAVA/year and Δmean PG/year. The hs-CRP concentration showed positive correlations with Vmax and mean PG, and it was significantly higher in patients with rapid aortic stenosis progression (ΔAVA/year <-0.1) than in their counterparts. CONCLUSIONS: Our results suggest that periodontopathic bacteria such as A. actinomycetemcomitans and P. gingivalis are not directly related to the status/progression of degenerative AS. However, inflammation and a lower immune response may be associated with disease progression.

Fluttering Bioprosthetic Valve Leaflet Detected by Intravascular Ultrasound During Valve-in-Valve Transcatheter Aortic Valve Replacement.

We report fluttering bioprosthetic leaflet, assessed by intravascular ultrasound, during valve-in-valve transcatheter aortic valve replacement, successfully treated by using chimney stenting. Valve-in-valve transcatheter aortic valve replacement is still a challenging situation, particularly in cases with a shallow distance between leaflet and coronary ostium; a multimodality imaging approach helped manage this situation. (Level of Difficulty: Intermediate.).

Comparison of long-term mortality in patients who underwent transcatheter aortic valve replacement with or without anti-atherosclerotic therapy.

Atherosclerosis is a risk factor for both aortic stenosis (AS) and coronary artery disease. This study aimed to investigate whether anti-atherosclerotic therapy (AT), defined as the simultaneous use of antiplatelet agents, statins, and renin aldosterone system inhibitors, had long-term clinical benefits for patients who underwent transcatheter aortic valve replacement (TAVR). Between October 2013 and May 2017, 2518 patients (31% men; median age, 85 years) who underwent TAVR in 14 Japanese centers were divided into two groups: patients who were prescribed anti-atherosclerotic therapy (AT, n = 567) and patients who were not (no AT, n = 1951). The median follow-up period for this cohort was 693 days (interquartile range, 389-870 days). Compared to no AT group, AT group was associated with significantly lower 2-year all-cause mortality (11.7% vs. 16.5%; log-rank p = 0.002) and 2-year cardiovascular mortality rates (3.5% vs. 6.0%; log-rank p = 0.017). In a propensity-matched cohort (n = 495 each; median follow-up, 710 days [IQR, 394 - 896 days]), patients in AT group had a lower prevalence of 2-year cardiovascular mortality (3.8% vs. 6.2%, log-rank p = 0.024) than that in the no AT group. In the multivariate stepwise regression analysis, AT was a significant predictor of cardiovascular mortality (hazard ratio 0.45; 95% confidence interval 0.25-0.80; p = 0.007). AT may improve survival in post-TAVR patients. Future studies are necessary to identify an optimal treatment regimen to improve long-term outcomes after TAVR.

Ischemic/bleeding event after short dual-antiplatelet therapy in patients with high bleeding risk: Sub-analysis of the MODEL U-SES study.

BACKGROUND: This analysis aimed to evaluate the clinical impact of high bleeding risk (HBR) on adverse events after percutaneous coronary intervention (PCI). METHODS: We retrospectively analyzed 1695 patients in the MODEL U-SES study, which was a multicenter, open-label, prospective observational study evaluating safety of 3-month dual antiplatelet therapy (DAPT) after Ultimaster stent (Terumo Corporation, Tokyo, Japan) implantation at 65 sites in Japan. Patients were divided into 2 groups (HBR/Non-HBR) according to modified Academic Research Consortium-HBR criteria. Ischemic/thrombotic event (cardiovascular death, myocardial infarction, ischemic stroke, and stent thrombosis) and bleeding event (Bleeding Academic Research Consortium 3 or 5) at 1 year were evaluated. RESULTS: Of 1695 patients, 840 patients were categorized as HBR and 855 patients were Non-HBR. One-year follow-up was completed in 95.3%. During 1-year follow-up, ischemic/thrombotic events were observed in 31 cases (1.8%) and bleeding events occurred in 21 cases (1.2%). Presence of HBR was significantly associated with higher incidence of ischemic/thrombotic events as compared to Non-HBR (adjusted hazard ratio, 0.16; 95% confidence interval, 0.05 to 0.50), whereas the incidence of bleeding events did not reach statistical significance between HBR and Non-HBR. In comparison of monotherapy after DAPT, P2Y12 inhibitor monotherapy after DAPT had comparable ischemic/thrombotic and bleeding events with aspirin monotherapy after DAPT in both HBR and Non-HBR. CONCLUSION: In contemporary PCI practice, nearly half of patients had HBR and presence of HBR significantly increased risk of ischemic/thrombotic events. Both aspirin and P2Y12 inhibitor monotherapy following short DAPT had low and comparable ischemic/bleeding events.