Combined Safety Endpoint Research Articles

Direct oral anticoagulants versus percutaneous left atrial appendage occlusion in atrial fibrillation: 5-year outcomes

BackgroundLAAO is an emerging option for thromboembolic event prevention in patients with NVAF. We previously reported data on comparison between LAAO and DOAC at two-year follow-up in NVAF patients at HBR (HAS-BLED ≥3). AimsLimited data are available on long term follow-up. We aimed to evaluate the efficacy and safety of DOACs versus LAAO indication after 5 years. MethodsWe enrolled 193 HBR treated with LAAO and 189 HBR patients with DOACs. At baseline, LAAO group had higher HAS-BLED (4.2 vs 3.3, p < 0.001) and lower CHADS-VASc (4.3 vs. 4.7, p = 0.005). After 1:1 PSM, 192 patients were included (LAAO n = 96; DOACs n = 96). ResultsAt 5-year follow-up the rate of the combined safety and effectiveness endpoint (ISTH major bleeding and thromboembolic events) was significantly higher in LAAO group (p = 0.042), driven by a higher number of thromboembolic events (p = 0.047). The rate of ISTH-major bleeding events was similar (p = 0.221). After PSM no significant difference in the primary effectiveness (LAAO 13.3% vs DOACs 9.5%, p = 0.357) and safety endpoint (LAAO 7.5% vs DOACs 7.5%; p = 0.918) were evident. Overall bleeding rate was significantly higher in DOACs group (25.0% vs 13.7%, p = 0.048), while a non-significant higher number of TIA was reported in LAAO group (5.4% vs 1.1%, p = 0.098). All-cause and cardiovascular mortality were higher in LAAO group at both unmatched and matched analysis. ConclusionWe confirmed safety and effectiveness of both DOAC and LAAO in NVAF patients at HBR, with no significant differences in thromboembolic events or major bleeding were at 5-year follow-up. The observed increased mortality after LAAO warrants further investigations in RCTs.

Non-contrast transcatheter aortic valve implantation for patients with aortic stenosis and chronic kidney disease: a pilot study.

Acute kidney injury (AKI) is frequently observed after transcatheter aortic valve implantation (TAVI). Of note, it is associated with a threefold increase in all-cause and cardiac death. We propose a new non-contrast strategy for evaluating and performing the TAVI procedure that can be especially valuable for patients with aortic stenosis (AS) and chronic kidney disease (CKD) to prevent AKI. Patients with severe symptomatic AS and CKD stage ≥3a were evaluated for TAVI using four non-contrast imaging modalities for procedural planning: transesophageal echocardiogram (TEE), cardiac magnetic resonance, multidetector computed tomography (MDCT), and aortoiliac CO2 angiography. Patients underwent transfemoral (TF) TAVI using the self-expandable Evolut R/Pro, and the procedures were guided by fluoroscopy and TEE. Contrast MDCT and contrast injection at certain checkpoints during the procedure were used in a blinded fashion to guarantee patient safety. A total of 25 patients underwent TF-TAVI with the zero-contrast technique. The mean age was 79.9 ± 6.1 years, 72% in NYHA class III/IV, with a mean STS-PROM of 3.0% ± 1.5%, and creatinine clearance of 49 ± 7 ml/min. The self-expandable Evolut R and Pro were implanted in 80% and 20% of patients, respectively. In 36% of the cases, the transcatheter heart valve (THV) chosen was one size larger than the one by contrast MDCT, but none of these cases presented adverse events. Device success and the combined safety endpoint (at 30 days) both achieved 92%. Pacemaker implantation was needed in 17%. This pilot study demonstrated that the zero-contrast technique for procedural planning and THV implantation was feasible and safe and might become the preferable strategy for a significant population of CKD patients undergoing TAVR. Future studies with a larger number of patients are still needed to confirm such interesting findings.

1661. Evaluation of Cefazolin &amp;lt; 3 g vs. 3 g Treatment Doses for Cellulitis in Patients Who Weigh ≥ 120 kg within a Large, Community Health System

Abstract Background Cefazolin 3 g is recommended for obese patients weighing &amp;gt; 120 kg preoperatively; however, there is no available evidence to suggest 3 g for treatment dosing of cefazolin in this population. This study aims to provide the first clinical data of its kind on the efficacy and safety of high-dose cefazolin in the treatment of cellulitis in obese patients using a modified Desirability of Outcomes Ranking (DOOR) methodology. Methods This is a multi-center, retrospective cohort study including adults weighing &amp;gt; 120 kg at the time of admission who received ≥ 48 hours of cefazolin monotherapy for cellulitis. Patients were gathered in a 3:1 ratio between the &amp;lt; 3 g dosing (standard-dose; SD) and 3 g dosing (high-dose; HD) groups. Patients were excluded if they had co-infections, bacteremia, bilateral lower extremity cellulitis, or if they received &amp;gt; 48 hours of concomitant antibiotics. The primary endpoint of efficacy and safety as determined by modified DOOR criteria was compared between obese patients who received HD and those who received SD between 1/1/2021 and 12/31/2021. The DOOR is a patient-centered methodology that uses combined efficacy and safety endpoints to help inform better clinical decision-making. Results A total of 68 patients were included; 51 received SD and 17 received HD cefazolin. There were no differences in mean age nor baseline kidney function or severity of illness between groups. The median patient weights were 140.6 kg and 160 kg for the SD and HD groups, respectively (p = 0.07). Patients achieving clinical success (resolution of cellulitis within 10 days or clinical improvement upon discharge) was higher in the HD vs SD group (70.6% vs 41%; p=0.036) (Figure 1). Conclusion Cefazolin 3 g was associated with higher clinical success in patients &amp;gt; 120 kg with cellulitis. Further study is necessary to confirm these results. Disclosures Elizabeth B. Hirsch, PharmD, FCCP, FIDSA, Melinta: Advisor/Consultant|MeMed: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support.

Cardiac magnetic resonance imaging versus computed tomography to guide transcatheter aortic valve replacement: study protocol for a randomized trial (TAVR-CMR)

BackgroundThe standard procedure for the planning of transcatheter aortic valve replacement (TAVR) is the combination of echocardiography, coronary angiography, and cardiovascular computed tomography (TAVR-CT) for the exact determination of the aortic valve dimensions, valve size, and implantation route. However, up to 80% of the patients undergoing TAVR suffer from chronic renal insufficiency. Alternatives to reduce the need for iodinated contrast agents are desirable. Cardiac magnetic resonance (CMR) imaging recently has emerged as such an alternative. Therefore, we aim to investigate, for the first time, the non-inferiority of TAVR-CMR to TAVR-CT regarding efficacy and safety end-points.MethodsThis is a prospective, randomized, open-label trial. It is planned to include 250 patients with symptomatic severe aortic stenosis scheduled for TAVR based on a local heart-team decision. Patients will be randomized in a 1:1 fashion to receive a predefined TAVR-CMR protocol or to receive a standard TAVR-CT protocol within 2 weeks after inclusion. Follow-up will be performed at hospital discharge after TAVR and after 1 and 2 years. The primary efficacy outcome is device implantation success at discharge. The secondary endpoints are a combined safety endpoint and a combined clinical efficacy endpoint at baseline and at 1 and 2 years, as well as a comparison of imaging procedure related variables. Endpoint definitions are based on the updated 2012 VARC-2 consensus document.DiscussionTAVR-CMR might be an alternative to TAVR-CT for planning a TAVR procedure. If proven to be effective and safe, a broader application of TAVR-CMR might reduce the incidence of acute kidney injury after TAVR and thus improve outcomes.Trial registrationThe trial is registered at ClinicalTrials.gov (NCT03831087). The results will be disseminated at scientific meetings and publication in peer-reviewed journals.

Contemporary Outcome Trends in Transcatheter Aortic Valve-in-Valve Implantation Versus Redo Aortic Valve Replacement

As valve-in-valve (ViV) transcatheter aortic valve implantation is still an evolving method, we evaluated the development of early and midterm outcomes after ViV and conventional redo-surgical aortic valve replacement (SAVR) over the past 2 decades. In-hospital databases were retrospectively screened for patients ≥60 years treated for failing bioprosthetic aortic valves at our center. Clinical and follow-up characteristics were compared between patients who underwent ViV or redo-SAVR according to valve academic research consortium-2 (VARC-2) definitions. The comparison of outcome parameters was adjusted for baseline differences between groups. Between June 2002 and April 2020, 209 patients with ViV and 65 redo-SAVR patients met inclusion criteria. No significant differences were found in 30 days (ViV 3.8%, SAVR 3.1%, p=0.778) or 6-month mortality (ViV 14.0%, SAVR 7.5%, p=0.283). As patients with ViV less frequently experienced acute kidney injury (stage II or III) and life-threatening bleeding, they more frequently reached the 30-day VARC-2 combined safety end point (79.2% vs 61.5%, odds ratio [OR] 2.540, p=0.023). Patients with ViV less frequently reached clinical efficacy (68.3% vs 84.6%, OR 0.408, p=0.041) and device success (79.9% vs 92.3%, OR 0.311, p=0.040) end points, because of higher frequency of postprocedural transvalvular gradients >20 mm Hg. However, over the past decade, VARC-2 clinical efficacy and device success rates continuously increased in ViV cases. In conclusion, ViV and SAVR were associated with similar acute mortality and different beneficial and adverse outcome profiles in this single-center cohort. Results after ViV procedures have continuously improved over the past years.

Prospective study on embolization of intracranial aneurysms with the pipeline device (PREMIER study): 3-year results with the application of a flow diverter specific occlusion classification

BackgroundThe pipeline embolization device (PED; Medtronic) has presented as a safe and efficacious treatment for small- and medium-sized intracranial aneurysms. Independently adjudicated long-term results of the device in treating these...

Clinical benefit of left atrial appendage closure in octogenarians.

OBJECTIVESWhether left atrial appendage closure (LAAC) in octogenarians yield similar net clinical benefit compared to younger patients, was the purpose of the present study.METHODSTwo real-world LAAC registries, enrolling 744 consecutive Amplatzer and Watchman patients from 2009 to 2018, were retrospectively analyzed.RESULTSAll events are reported per 100 patient-years. Two hundred and sixty one octogenarians and 483 non-octogenarians with a mean follow-up of 1.7 ± 1.3 and 2.3 ± 1.6 years, and a total of 1,502 patient-years were included. Octogenarians had a higher risk for stroke (CHA2DS2-VASc score: 5.2 ± 1.2 vs. 4.3 ± 1.7, P < 0.0001) and bleeding (HAS-BLED score: 3.3 ± 0.8 vs. 3.1 ± 1.1, P = 0.001). The combined safety endpoint of major periprocedural complications and major bleeding events at follow-up was comparable (30/446, 6.7% vs. 47/1056, 4.4%; hazard ratio [HR] = 1.2; 95% confidence interval [CI]: 0.73−1.98;P = 0.48) between the groups. The efficacy endpoint of all-cause stroke, systemic embolism, and cardiovascular/unexplained death occurred more often in octogenarians (61/446, 13.7% vs. 80/1056, 7.6%; HR = 7.0; 95% CI: 4.53−10.93;P < 0.0001). Overall, octogenarians had a lower net clinical benefit, i.e., the composite of all above mentioned hazards, from LAAC compared to younger patients (82/446, 18.4% vs. 116/1056, 11.0%; HR = 4.6; 95% CI: 3.11−7.0;P < 0.0001). Compared to the anticipated stroke rate, the observed rate decreased by 41% in octogenarians and 53% in non-octogenarians. The observed bleeding rate was reduced by 10% octogenarians and 41% non-octogenarians. CONCLUSIONSLAAC can be performed with similar safety in octogenarians as compared to younger patients. On the long-term, it both reduces stroke and bleeding events, although to a lesser extent than in non-octogenarians.

Implementation of a remote rapid access chest pain service during the COVID-19 pandemic

BackgroundRapid Access Chest Pain Clinic (RACPC) is a vital service in many hospitals in the UK, providing early specialist input for patients with suspected coronary artery disease referred via the Emergency Department (ED) or primary care (1). When the COVID-19 pandemic forced hospitals to refine their outpatient systems (2), our Trust continued the RACPC service remotely via telephone consultations.PurposeTo examine the long-term viability of this service, we designed a study to compare the outcomes of patients seen remotely during the pandemic to patients seen face to face.MethodsWe performed a retrospective cohort study. The remote group (n=217) were patients seen over 4 weeks in April 2020, all having telephone consultations. The control group (n=368) were patients assessed face to face in the same 4-week period in 2019. Outcomes being analysed included: mode of investigation; interventions performed; and a 12 month combined safety endpoint of ED attendance with chest pain, re-referral to cardiology and hospitalisation for cardiac issue. Subgroup analysis was performed based on typicality of symptoms defined by NICE (3).ResultsBaseline characteristics were similar between groups. In both 2019 and 2020, the largest subgroup of patients were those with non-anginal chest pain (64%, 71%). There were significant differences in investigation and management between the two cohorts (Figure 1). In 2020, a higher proportion of patients were discharged with no investigation (57% vs 23%, p<0.0001). This was driven primarily by changes in management of patients with non-anginal chest pain. There were significantly higher rates of investigation of this subgroup in 2019 by either CT Coronary Angiography (25% versus 4.5%, p<0.001) or functional testing (25% versus 6.5%, p<0.001), with a much higher rate of reassurance and discharge in 2020 (81% versus 36%, p<0.0001). More patients received coronary intervention in 2019 than in 2020 (2.4% vs 0%, p=0.02). In 2020, higher proportions of patients were commenced on medical therapy without further investigation when presenting with atypical (28% versus 1%, p<0.0001) or typical angina (63% versus 11.4%, p<0.0001) (Figure 2). There was no significant difference in the 12 month combined safety endpoint (1.3% in 2019 versus 2.3% in 2020, p=0.39), and no reported cardiac deaths.ConclusionsDuring the pandemic, as expected, fewer patients were investigated for coronary artery disease, with the preference being to commence medical therapy initially. This did not have a significant effect on safety endpoints. Importantly, clinicians felt comfortable with assessing and discharging patients with non-anginal chest pain remotely in 2020. This is key to the viability of a remote RACPC model, as this subgroup forms the majority of the referrals. We suggest that RACPC is appropriate for a remote model in the long term, in view of the relatively low-risk population and clear management guidelines.Funding AcknowledgementType of funding sources: None. Figure 1. Investigation based on symptomsFigure 2. Patient receiving medical therapy only

Clinical results and 30-day outcomes of self-expanding transcatheter aortic valves: comparative case-matched analysis of CoreValve® versus ACURATE neo™.

Transcatheter aortic valve replacement (TAVR) is associated with excellent results in patients with severe aortic stenosis. In highly calcified aortic anuli with increased risk of annulus rupture and in favor of the supra-annular design, self-expandable prostheses are frequently used. In this regard, we aimed to perform a comparative analysis of clinical and 30-day outcomes after TAVR using the self-expanding CoreValve® Evolut R or ACURATE neo™ prosthesis. Out of 343 consecutive patients treated with either CoreValve® Evolut R or ACURATE neo™ from January 2014 to December 2017, 76 patients were assigned each per group after 1:1 propensity score matching in regard of preoperative characteristics. Pre- and periprocedural outcomes were retrospectively collected and assessed. Outcomes at 30 days are reported according to the established Valve Academic Research Consortium (VARC-2) criteria. Device success and 30-day survival accounted for 93.4% (n = 71), respectively 97.4% (n = 74) in both groups (p = 1.00). No statistically significant differences regarding clinical parameters were observed. The combined safety endpoint at 30 days was comparable (84.2% (n = 64) CoreValve® vs 85.5% (n = 65) ACURATE neo™; p = 0.848). Except a trend toward higher stroke (p = 0.08) and pacemaker (p = 0.07) rate in the CoreValve® group, major vascular complications, incidence of life-threatening or disabling bleeding, and incidence of postoperative acute kidney injury were comparable. Postoperative hemodynamic parameters showed no significant differences between the implanted valves. Both self-expandable prostheses showed good postoperative hemodynamic performance with a low incidence of severe paravalvular leakage, all- cause mortality, and comparable clinical outcomes.

A randomized evaluation of the TriGuard™ HDH cerebral embolic protection device to Reduce the Impact of Cerebral Embolic LEsions after TransCatheter Aortic Valve ImplanTation: the REFLECT I trial

The REFLECT I trial investigated the safety and effectiveness of the TriGuard™ HDH (TG) cerebral embolic deflection device in patients undergoing transcatheter aortic valve replacement (TAVR). This prospective, multicentre, single-blind, 2:1 randomized (TG vs. no TG) study aimed to enrol up to 375 patients, including up to 90 roll-in patients. The primary combined safety endpoint (VARC-2 defined early safety) at 30 days was compared with a performance goal. The primary efficacy endpoint was a hierarchical composite of (i) all-cause mortality or any stroke at 30 days, (ii) National Institutes of Health Stroke Scale (NIHSS) worsening at 2-5 days or Montreal Cognitive Assessment worsening at 30 days, and (iii) total volume of cerebral ischaemic lesions detected by diffusion-weighted magnetic resonance imaging at 2-5 days. Cumulative scores were compared between treatment groups using the Finkelstein-Schoenfeld method. A total of 258 of the planned, 375 patients (68.8%) were enrolled (54 roll-in and 204 randomized). The primary safety outcome was met compared with the performance goal (21.8% vs. 35%, P < 0.0001). The primary hierarchical efficacy endpoint was not met (mean efficacy score, higher is better: -5.3 ± 99.8 TG vs. 11.8 ± 96.4 control, P = 0.31). Covert central nervous system injury was numerically lower with TG both in-hospital (46.1% vs. 60.3%, P = 0.0698) and at 5 days (61.7 vs. 76.2%, P = 0.054) compared with controls. REFLECT I demonstrated that TG cerebral protection during TAVR was safe in comparison with historical TAVR data but did not meet the predefined effectiveness endpoint compared with unprotected TAVR controls.

Rationale and design of a randomized clinical trial comparing safety and efficacy of myval transcatheter heart valve versus contemporary transcatheter heart valves in patients with severe symptomatic aortic valve stenosis: The LANDMARK trial

The recent approval of transcatheter aortic valve replacement (TAVR) in patients with low operative risk has paved the way for the introduction of novel and potentially improved technologies. The safety and efficacy of these novel technologies should be investigated in randomized control trials against the contemporary TAVR devices. The objective of the LANDMARK trial is to compare the balloon-expandable Myval transcatheter heart valve (THV) series with contemporary THV (SAPIEN THV and Evolut THV series) series in patients with severe symptomatic native aortic stenosis. The LANDMARK trial (ClinicalTrials.govNCT04275726, EudraCT number 2020-000,137-40) is a prospective, randomized, multinational, multicenter, open-label, and noninferiority trial of approximately 768 patients treated with TAVR via the transfemoral approach. Patients will be allocated in a 1:1 randomization to Myval THV series (n = 384) or to contemporary THV (n = 384) (either of SAPIEN THV or Evolut THV series). The primary combined safety and efficacy endpoint is a composite of all-cause mortality, all stroke (disabling and nondisabling), bleeding (life-threatening or disabling), acute kidney injury (stage 2 or 3), major vascular complications, prosthetic valve regurgitation (moderate or severe), and conduction system disturbances (requiring new permanent pacemaker implantation), according to the Valve Academic Research Consortium-2 criteria at 30-day follow-up. All patients will have follow-up to 10 years following TAVR. The LANDMARK trial is the first randomized head-to-head trial comparing Myval THV series to commercially available THVs in patients indicated for TAVR. We review prior data on head-to-head comparisons of TAVR devices and describe the rationale and design of the LANDMARK trial.

Antazoline for pharmacological cardioversion of atrial fibrillation: the results of the high-volume multicenter CANT study

Abstract Background Antazoline mesylate represents a first generation antihistamine with quinidine-like antiarrhythmic properties, which allows for rapid and effective termination of atrial fibrillation (AF). Despite its widespread use in Polish emergency departments, paucity of data exists concerning safety and efficacy of antazoline in comparison to other antiarrhythmic agents. Purpose This study aimed to evaluate the pooled hitherto data on effectiveness and safety of pharmacological Cardioversion with intravenous ANTazoline (CANT Study) in short-duration atrial fibrillation. Methods This retrospective observational study was performed in 5 medical centers and comprised 1300 patients with paroxysmal or persistent AF who underwent emergent pharmacological cardioversion in the real-world setting of emergency or cardiology department. The choice of antiarrhythmic drug was left to the discretion of attending physician. The exclusion criteria involved permanent AF, other supraventricular arrhythmias, including atrial flutter, chronic antiarrhythmic therapy or preemptive electrical cardioversion. The primary endpoint was restoration of sinus rhythm up to 12 hours after antiarrhythmic drug infusion. The combined safety endpoint was bradycardia &amp;lt;45 bpm, hypotension, syncope or death. Results The mean age of study population was 67.7±11.6 years and the majority of patients were men (52.9%). The median AF episode duration was 10 (4; 24) hours, while median CHA2DS2-VASc score was 3 (2; 4) pts. Antazoline alone was administered in 45.6% of patients (n=593); amiodarone in 22.1% (n=287); propafenone in 11.5% (n=150); sotalol in 0.5% (n=6), while 20.3% (n=264) received overlapping antiarrhythmic therapy. Antazoline had the highest rhythm conversion rate (Figure), which was comparable to propafenone (78.2% vs 72.7%; RR 1.08; 95% CI:0.97–1.20; P=0.175) and superior to amiodarone (vs 66.9%; RR 1.17, 95% CI:1.07–1.28; P=0.0008) and collective amiodarone/propafenone/sotalol treatment (vs 68.6%; RR 1.14; 95% CI:1.06–1.23; P=0.0006). The rate of combined safety endpoint was comparable in patients treated with antazoline and other antiarrhythmic drugs (5.2% vs 3.9%; P=0.297). Among patients treated with antazoline, 29 exhibited bradycardia &amp;lt;45 bpm and 5 patients suffered from hypotension, but no case of syncope, nor in-hospital death was reported. Conclusion Antazoline appears to be an effective antiarrhythmic drug for cardioversion of atrial fibrillation, which is associated with low rate of relatively benign adverse events. Figure 1 Funding Acknowledgement Type of funding source: None

Impact of annular and cusps calcification on occurrence of paravalvular leak after transcatheter aortic valve replacement with intra- versus supra-annular devices

Abstract Introduction Severe annular and valve cusps calcification is frequent among patients treated with transcatheter aortic valve replacement (TAVR). Severe annular calcification increases the risk of paravalvular leak (PVL) and was associated with worse outcomes. Whether it is accompanied by an independent effect of calcifications localized on cusps and whether the impact of cusps/annular calcification depends on supra vs intra-annular valve design is unknown. Purpose To assess the impact of cusps/annular calcifications on occurrence of moderate PVL after successful TAVR with devices of either intra- or supra-annular design. Methods 282 consecutive patients (80.3±7.6 yrs, 63% female) with baseline 384-slice CT scan were successfully treated with TAVR between Jul 2012 and Oct 2017, either with intra-annular or supra-annular devices. Severe annular calcification (clear protrusion) and severe cusps calcification (Rosenhek 4 score) were identified using a Syngo Via. Results 138 (48.9%) patients were treated with intra-annular and 144 (51.15) with supra-annular devices. Whereas severe annular calcification was similar (23.9% vs 20.1%), there was more severe cusps calcification among intra-annular valves (52.9% vs 41.7%, p=0.073). Intra-annular devices were used less frequently among bicuspid aortic valves, were also of smaller diameter, less frequently deployed after pre-dilation, and less frequently post-dilated. Post-procedure mean aortic gradient tended to be higher among intra-annular devices. Moderate PVL was less frequent among intra- vs supra-annular valves (14.5% vs 34.0%, p&amp;lt;0.001). However, PVL occurrence was higher (30.3%) among those (33/138, 23.9%) treated with an intra-annular valve who had severe annular calcification vs 9.5% in pts treated with an intra-annular TAVR who did not have severe annular calcification (p=0.008) unlike in patients treated with a supra-annular valve who had a high frequency of PVL with or without severe annular calcium (37.9% vs 33.0%). After excluding patients with severe annular calcium (n=62, 22%), moderate PVL was similar between those with vs without severe cusp calcification whether treated with intra- or supra-annular valves (11.8% vs 7.4% and 29.3% vs 35.1%, respectively). Combined VARC-2 safety endpoints plus 2-yr mortality occurrence were lower for intra- vs supra-annular devices (30.4% vs 43.8%, p=0.026). Conclusions Moderate PVL after intra-annular TAVR device deployment occurs in 30% of patients with protruding annular calcification. Severe cusps calcification unaccompanied by annular calcium was not associated with PVL occurrence. Higher frequency of moderate PVL (34%) seen after supra-annular valve deployment appears to be related to other parameters rather than presence of severe annular or cusps calcification. Funding Acknowledgement Type of funding source: None

Cost-effectiveness of adding a non-invasive acoustic rule-out test in the evaluation of patients with suspected stable angina pectoris. Design of the randomized multicenter FILTER-SCAD trial

Abstract Background Patients with suspected stable coronary artery disease (CAD) are selected for further non-invasive or invasive diagnostic tests depending on their pre-test probability (PTP) of obstructive CAD. However, the PTP, based on age, sex, and type of angina, has shown to grossly overestimate the likelihood of obstructive CAD. Consequently, the use of diagnostic tests has increased over the last decades despite a low diagnostic yield (6–7%). The CAD-score is a risk stratification score for obstructive CAD measured using a novel non-invasive acoustic device, and when added to PTP has shown excellent rule-out capabilities. Purpose To investigate if the addition of the CAD-score to a standard diagnostic examination is superior in terms of reducing overall number of diagnostic procedures and non-inferior in terms of safety as compared to a standard PTP-guided strategy when evaluating patients with suspected stable CAD. Methods The FILTER-SCAD trial is a randomized, controlled, multicenter trial expected to include 2000 subjects ≥30 years of age without known CAD referred for outpatient assessment for suspected CAD at 5 hospitals in Denmark and Sweden. First subject was randomized on October 22, 2019. Subjects will be randomized 1:1 to either 1) a control group undergoing standard diagnostic examination (SDE) according to current guidelines, or 2) an intervention group undergoing SDE plus a CAD-score measurement, using permuted block randomization stratified by study site and PTP (very low vs. low-intermediate). Follow-up will be 12 months for a primary endpoint of cumulative number of diagnostic tests and a combined secondary safety endpoint of all-cause death, non-fatal myocardial infarction, unstable angina pectoris, heart failure, and ischemic stroke. Questionnaires assessing symptom severity, quality of life, life style measures, and medical treatment will be collected at baseline, 3 months, and 12 months after randomization. The study is powered to detect superiority in terms of cumulative number of diagnostic tests with a power of 80% and a significance level of 0.05, and non-inferiority on the safety endpoint with a power of 90% and a significance level of 0.05. The study is conducted in compliance to the principles of the Declaration of Helsinki of the World Medical Association. ClinicalTrials.gov ID: NCT04121949. Results One study site is currently enrolling. Preliminary baseline data is available on the first 77 (44% males) enrolled patients (median age 61 years IQR (51–72) and PTP 22% IQR (13–38)) showing successful randomization with even distribution of baseline characteristic between the two groups including sex, age, and PTP. Perspectives The FILTER-SCAD trial will investigate whether it is feasible to reduce resource consumption without compromising safety in the outpatient assessment of patients with suspected CAD using a simple, non-invasive acoustic device. Enrollment and follow-up are expected to be completed spring 2022. Funding Acknowledgement Type of funding source: Other. Main funding source(s): The company Acarix A/S har provided an unrestricted grant for the study. The Foundation “Fonden for Faglig Udvikling i Speciallægepraksis” has provided a grant for the study.

Impact of individual stroke risk on outcome after Amplatzer left atrial appendage closure in patients with atrial fibrillation.

To investigate periprocedural and long-term outcome of left atrial appendage closure (LAAC) using Amplatzer occluders with respect to individual pre-procedural stroke risk. LAAC is a proven strategy for prevention from stroke and bleeding in patients with nonvalvular atrial fibrillation not amenable to oral anticoagulation. Whether individual pre-procedural stroke risk may affect procedural and long-term clinical outcome after LAAC is unclear. Multicenter study of consecutive patients who underwent Amplatzer-LAAC. Using pre-procedural CHADS2 score, outcomes were compared between a low (0-2 points) and a high stroke risk group (3-6 points). Five hundred consecutive patients (73.9 ± 10.1 years) who underwent Amplatzer-LAAC. Two hundred and forty eight had preprocedural CHADS2 score ≤ 2 points (low-risk group) and the remaining 252 patients had 3-6 points (high-risk group). Periprocedural complication rates (6.0% vs. 5.6%, p=.85), procedural success (LAAC without major periprocedural or device-related complications or major para-device leaks: 89.4% vs. 87.9%, p=.74), and 30-day-mortality (2.4% vs. 2.6%, p=.77) were comparable. After 1,346 patient-years (PY), the long-term composite efficacy endpoint (stroke, systemic embolism, cardiovascular, and unexplained death) was reached in 23/653 (3.5/100 PY) versus 52/693 (7.5/100 PY); HR=2.13; 95%-CI, 1.28-3.65, p=.002) with stroke rates 67% and 68% lower than anticipated by preprocedural CHADS2 score. Combined safety endpoint (major periprocedural complications and major, life-threatening or fatal bleedings) occurred in 22/653 (3.4/100 PY) versus 28/693 (4.0/100 PY); HR=1.20; 95%-CI, 0.66-2.20, p=.52). Compared with patients at low risk of stroke, LAAC with Amplatzer devices is associated with similar safety and efficacy in high-risk patients in our study.

Quality of Life After Ministernotomy Versus Full Sternotomy Aortic Valve Replacement

Quality of life and patient satisfaction after ministernotomy have never been compared to conventional full sternotomy in randomized trials. The QUALITY-AVR trial is a single-blind, single-center, independent, randomized clinical trial comparing ministernotomy to full sternotomy in patients with isolated severe aortic stenosis scheduled for elective aortic valve replacement. One hundred patients were randomized in a 1:1 computational fashion. The primary endpoint was a difference between intervention groups of ≥0.10 points in change from baseline quality of life Questionnaire EuroQOL-index, measured at 1, 6, or 12 months. Secondary endpoints were differences in change from other baseline EuroQOL-index utilities, cardiac surgery-specific satisfaction questionnaire (SATISCORE), a combined safety endpoint of 4 major adverse complications at 1 month (all-cause mortality, acute myocardial infarction, neurologic events, and acute renal failure), bleeding through drains within the first 24 hours, intubation time, and other minor endpoints. Clinical follow-up was scheduled at baseline, 1, 6, and 12 months after randomization. Change from baseline mean difference EQ-5D-index was +0.20 points (95% confidence interval 0.10-0.30, P < 0.001) and median difference +0.14 (95% confidence interval 0.06-0.22, P < 0.001), favoring the ministernotomy group at 1 month. Patient satisfaction was also better at 1 month (Satiscore 83 ± 9 vs 77 ± 13 points; P = 0.010). The ministernotomy group had significantly less bleeding in the first 24 hours (299 ± 140 vs 509 ± 251 mL, P = 0.001). Ministernotomy provides a faster recovery with improved quality of life and satisfaction at 1 month compared to full sternotomy.

P1842Impact of left ventricular outflow tract sphericity on transcatheter heart valve hemodynamics and outcome after transcatheter aortic valve implantation

Abstract Background Accurate assessment of aortic annulus and left ventricular outflow tract (LVOT) anatomy is mandatory for appropriate device selection in order to achieve optimal deployment of transcatheter heart valves (THV). Aim To evaluate the impact of LVOT shape as determined by the sphericity index (ratio of long and short LVOT diameter) on THV hemodynamics. Methods 1000 consecutive patients diagnosed with severe symptomatic aortic stenosis and undergoing TAVI between May 2008 and July2017 were analyzed. Assessment of aortic root dimensions including the LVOT was performed by contrast-enhanced multidetector computed tomography (MDCT) in all patients. The primary endpoint was 30-day device success as defined by the VARC-2 criteria. Secondary endpoints included all-cause mortality, cardiovascular mortality, permanent pacemaker implantation (PPI), and a 30-day combined early safety endpoint (all-cause mortality, all strokes, life threatening bleeding, acute kidney injury stage 2 or 3, CAD obstruction requiring intervention, major vascular complication, valve related dysfunction requiring repeat intervention). Results Patients were divided into 3 groups according to LVOT sphericity index (SI) quartiles. The three groups (low-SI: 0.4–0.63, n=250; mid-SI: 0.64–0.75, n=500; high-SI: 0.76–1.0, n=250) were well balanced in terms of baseline characteristics, except for gender distribution with more female patients in the low-SI group (36.8% vs. 49.0% vs. 60.0%; p=0.ehz748.05941). Assessment of calcification volume and Agatston score demonstrated significantly higher aortic valve and LVOT calcification in the high-SI group. The primary endpoint of device success after 30-days did not differ between the 3 groups (92.4% vs 91.9% vs. 87.9%; p=NS). However, moderate or severe paravalvular regurgitation (PAR) occurred significantly more often in the high-SI as compared to the other groups (4.1% vs. 5.2% vs. 10.6%; p=0.004 for low-SI vs. high-SI). In contrast, PPI rates, the early safety endpoint at 30 days, and all-cause mortality at 1 year did not differ between the groups. In the high-SI group implantation of a BE valve was associated with a significantly higher rate of device success as compared to SE valves (93.8% vs. 82.2%, p=0.007). This difference was driven by a higher rate of moderate or severe PAR (6.9% vs. 15.3%, p=0.007) in patients treated with SE valves. Moreover, patients in the high-SI group receiving a SE valve required more often a PPI than those treated with a BE valve (26.2% vs 13.3%, p=0.012). There was no difference between the THV types in the other SI groups in terms of primary and secondary endpoints. Conclusion A more circular LVOT is associated with higher aortic valve and LVOT calcification. Implantation of a SE THV results in higher rates of moderate or severe PAR and persistent conduction disorder requiring PPI in such patients.

Daptomycin dosing in obese patients: analysis of the use of adjusted body weight versus actual body weight.

Background:Food and Drug Administration–approved daptomycin dosing uses actual body weight, despite limited dosing information for obese patients. Studies report alterations in daptomycin pharmacokinetics and creatine phosphokinase elevations associated with higher weight-based doses required for obese patients. Limited information regarding clinical outcomes with alternative daptomycin dosing strategies in obesity exists.Objective:This study evaluates equivalency of clinical and safety outcomes in obese patients with daptomycin dosed on adjusted body weight versus a historical cohort using actual body weight.Methods:This retrospective, single center study compared equivalency of outcomes with two one-sided tests in patients with body mass index ⩾30 kg/m2 who received daptomycin dosed on actual body weight versus adjusted body weight. The primary outcome was clinical failure. Secondary outcomes included 90-day readmission and 90-day mortality. A combined safety endpoint included creatine phosphokinase elevation, patient-reported myopathy, and rhabdomyolysis.Results:A total of 667 patients were screened for inclusion; 101 patients were analyzed with 50 in the actual body weight cohort and 51 in the adjusted body weight cohort. The two regimens were statistically equivalent for clinical failure (2% actual body weight versus 4% adjusted body weight; p < 0.001 for equivalency). The two regimens were also statistically equivalent for 90-day mortality (6% actual body weight versus 4% adjusted body weight; p = 0.0014 for equivalency). Limitations include single center, retrospective design, and sample size. Daptomycin dosing intensified throughout the study period.Conclusion:The two daptomycin dosing cohorts were statistically equivalent for both clinical failure and 90-day mortality. More data are needed to assess outcomes with higher (⩾8 mg/kg/day) daptomycin doses in this patient population.

Clinical outcomes of heart-team-guided treatment decisions in high-risk patients with aortic valve stenosis in a health-economic context with limited resources for transcatheter valve therapies

Aims: Transcatheter aortic valve implantation (TAVI) is the preferred treatment modality for patients with severe aortic stenosis at high or prohibitive risk for surgical aortic valve replacement (SAVR). We aimed to evaluate real-world outcomes after treatment according to the decisions of the multidisciplinary heart team in a Belgian health-economic context.Methods and results: Four hundred and five high-risk patients referred to a tertiary centre between 1 March 2008 and 31 December 2015 were screened and planned to undergo SAVR, TAVI or medical treatment (MT). Patients undergoing SAVR had lower Society of Thoracic Surgeons scores and Euroscore-II when compared to TAVI or MT (median [IQR]: 6[4–8]; 7[5–10]; 8[6–13]; p < .001 and 6[4–10]; 8[5–15]; 8[4–16]; p = .006). At 1 year all-cause mortality was 14, 17 and 51% with SAVR, TAVI and MT, respectively (p < .001). Cardiovascular death and disabling stroke occurred in 9, 7 and 35% (p < .001) and 2, 2.7 and 1.7% (p = .91). According to Valve-Academic-Research-Consortium–II criteria, device success was 95 and 92% for TAVI and SAVR. The combined safety endpoint at 30 days favoured TAVI (22% vs. 47%) (p < .001). The combined efficacy endpoint at 1 year was comparable between groups (38 and 40%; p = .703). Finally, hospital stay was shorter with TAVI vs. SAVR (9[6–14] and 16[12–22] days; p < .001).Conclusions: Limited resources for transcatheter valve therapies in Belgium push a significant number of patients to SAVR, while TAVI in even higher risk patients translates into similar outcomes and shorter hospital stay. These findings underscore the need for broadening indications for TAVI, as well as readjustment of the budgetary allocations for hospitals in Belgium.

Thin composite wire strut, durable polymer-coated (Resolute Onyx) versus ultrathin cobalt–chromium strut, bioresorbable polymer-coated (Orsiro) drug-eluting stents in allcomers with coronary artery disease (BIONYX): an international, single-blind, randomised non-inferiority trial

During the past decade, many patients had zotarolimus-eluting stents implanted, which had circular shape cobalt-chromium struts with limited radiographic visibility. The Resolute Onyx stent was developed to improve visibility while reducing strut thickness, which was achieved by using a novel composite wire with a dense platinum-iridium core and an outer cobalt-chromium layer. We did the first randomised clinical trial to assess the safety and efficacy of this often-used stent compared with the Orsiro stent, which consists of ultrathin cobalt-chromium struts. We did an investigator-initiated, assessor-blinded and patient-blinded, randomised non-inferiority trial in an allcomers population at seven independently monitored centres in Belgium, Israel, and the Netherlands. Eligible participants were aged 18 years or older and required percutaneous coronary intervention with drug-eluting stents. After guide wire passage with or without predilation, members of the catheterisation laboratory team used web-based computer-generated allocation sequences to randomly assign patients (1:1) to either the Resolute Onyx or the Orsiro stent. Randomisation was stratified by sex and diabetes status. Patients and assessors were masked to allocated stents, but treating clinicians were not. The primary endpoint was target vessel failure at 1 year, a composite of cardiac death, target-vessel-related myocardial infarction, and target vessel revascularisation, and was assessed by intention to treat (non-inferiority margin 2·5%) on the basis of outcomes adjudicated by an independent event committee. This trial is registered with ClinicalTrials.gov, number NCT02508714. Between Oct 7, 2015, and Dec 23, 2016, 2516 patients were enrolled, 2488 of whom were included in the intention-to-treat analysis (28 withdrawals or screening failures). 1243 participants were assigned to the Resolute Onyx group, and 1245 to the Orsiro group. Overall, 1765 (70·9%) participants presented with acute coronary syndromes and 1275 (51·2%) had myocardial infarctions. 1-year follow-up was available for 2478 (99·6%) patients. The primary endpoint was met by 55 (4·5%) patients in the Resolute Onyx group and 58 (4·7%) in the Orsiro group. Non-inferiority of Resolute Onyx to Orsiro was thus established (absolute risk difference -0·2% [95% CI -1·9 to 1·4]; upper limit of the one-sided 95% CI 1·1%; pnon-inferiority=0·0005). Definite or probable stent thrombosis occurred in one (0·1%) participant in the Resolute Onyx group and nine (0·7%) in the Orsiro group (hazard ratio 0·11 [95% CI 0·01-0·87]; p=0·0112). The Resolute Onyx stent was non-inferior to Orsiro for a combined safety and efficacy endpoint at 1-year follow-up in allcomers. The low event rate in both groups suggests that both stents are safe, and the very low rate of stent thrombosis in the Resolute Onyx group warrants further clinical investigation. Biotronik and Medtronic.