All-comers Patient Population Research Articles

Sirolimus-coated balloon in all-comer population of coronary artery disease patients: the EASTBOURNE DIABETES prospective registry

BackgroundThe outcomes of percutaneous coronary intervention (PCI) in diabetic patients are still suboptimal, and it is unclear if diabetic patients might derive a benefit from the use of drug-coated balloons.AimsTo evaluate the impact of diabetes mellitus on the outcomes of patients undergoing PCI with sirolimus-coated balloon (SCB) MagicTouch (Concept Medical, India).MethodsWe conducted a subgroup analysis of the prospective, multicenter, investigator-initiated EASTBOURNE registry, evaluating the performance of MagicTouch SCB in patients with and without diabetes. The study primary endpoint was target lesion revascularization (TLR) at 12-month follow-up. Secondary clinical endpoints were major adverse clinical events (MACE), death, myocardial infarction (MI), and BARC 2–5 bleedings.ResultsAmong 2,083 enrolled patients, a total of 864 suffered from diabetes (41.5%). Patients with diabetes had a numerically higher occurrence of TLR (6.5% vs. 4.7% HR 1.38, 95%CI 0.91–2.08), all-cause death (3.8% vs. 2.6%, HR 1.81, 95%CI 0.95–3.46), and MACE (12.2% vs. 8.9%; HR 1.26 95%CI 0.92–1.74). The incidence of spontaneous MI was significantly higher among diabetic patients (3.4% vs. 1.5%, HR 2.15 95%CI 1.09–4.25); bleeding events did not significantly differ. The overall incidence of TLR was higher among in-stent restenosis (ISR) as compared to de-novo coronary lesions, irrespectively from diabetes status.ConclusionsIn the EASTBOURNE DIABETES registry, diabetic patients treated with the MagicTouch SCB did not have a significant increase in TLR when compared to non-diabetic patients; moreover, diabetic status did not affect the study device performance in terms of TLR, in both de-novo lesions and ISR.

Etiologies and predictors of mortality in an all-comer population of patients with non-ischemic heart failure

BackgroundDespite progress in diagnosis and therapy of heart failure (HF), etiology and risk stratification remain elusive in many patients.MethodsThe My Biopsy HF Study (German clinical trials register number: DRKS22178) is a retrospective monocentric study investigating an all-comer population of patients with unexplained HF based on a thorough workup including endomyocardial biopsy (EMB).Results655 patients (70.9% men, median age 55 [45/66] years) with non-ischemic, non-valvular HF were included in the analyses. 489 patients were diagnosed with HF with reduced ejection fraction (HFrEF), 52 patients with HF with mildly reduced ejection fraction (HFmrEF) and 114 patients with HF with preserved ejection fraction (HFpEF). After a median follow-up of 4.6 (2.5/6.6) years, 94 deaths were enumerated (HFrEF: 68; HFmrEF: 8; HFpEF: 18), equating to mortality rates of 3.3% and 11.6% for patients with HFrEF, 7.7% and 15.4% for patients with HFmrEF and 5.3% and 11.4% for patients with HFpEF after 1 and 5 years, respectively. In EMB, we detected a variety of putative etiologies of HF, including incidental cardiac amyloidosis (CA, 5.8%). In multivariate logistic regression analysis adjusting for age, sex and comorbidities only CA, age and NYHA functional class III + IV remained independently associated with all-cause mortality (CA: HRperui 3.13, 95% CI 1.5–6.51; p = 0.002).ConclusionsIn an all-comer population of patients presenting with HF of unknown etiology, incidental finding of CA stands out to be independently associated with all-cause mortality. Our findings suggest that prospective trials would be helpful to test the added value of a systematic and holistic work-up of HF of unknown etiology.Graphical abstract

Evaluation of Ultrathin Strut Biodegradable Polymer-Coated Sirolimus-Eluting Stents in an All-Comers Patient Population: 1-Year Results of the S-FLEX Slovakia Registry.

Supraflex (Sahajanand Medical Technologies Limited, Surat, India) is a new-generation, biodegradable polymer-coated sirolimus-eluting stent (SES) designed on an ultrathin (60 µm) cobalt-chromium platform with a flexible 'S-link.' The S-FLEX Slovakia registry aimed to assess the safety and effectiveness of Supraflex SES in an all-comers population, with a subgroup of diabetic patients. This was a prospective, observational, multi-center, post-market registry conducted between February 2018 and May 2019. All consecutive patients with symptomatic coronary artery disease scheduled for percutaneous coronary intervention with Supraflex SES were enrolled. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, target vessel myocardial infarction (TV-MI), or clinically indicated target lesion revascularization (CI-TLR) by percutaneous or surgical methods at 1-year follow-up. Stent thrombosis was a safety endpoint. A total of 413 patients was assessed (145 diabetics and 268 nondiabetics). At 1-year follow-up, the primary endpoint of TLF occurred in 5.1% patients, comprised of 3.9% cardiac deaths, 0.5% TV-MI, and 0.7% CI-TLR. Overall stent thrombosis occurred in 0.5% patients at 1-year follow-up. In the subgroup analysis, TLF occurred in 6.2% diabetics and 4.5% nondiabetics (P =.433) and comprised 4.8% and 3.4% cardiac deaths (P =.447), 0.7% and 0.4% TV-MI (P =.653), and 0.7%, and 0.7% CI-TLR (P =.952) in diabetics and non-diabetics, respectively. Overall stent thrombosis occurred in 0.7% diabetic and 0.4% non-diabetic patient (P =.659). This registry demonstrates favourable clinical outcomes after the implantation of the ultrathin biodegradable polymer coated Supraflex SES in an all-comers population, with event rates that were similar in diabetic and nondiabetic patients.

Longitudinal assessment of coronary microvascular dysfunction in an all-comer patient population detects the highly dynamic natural history of this condition

Abstract Introduction Coronary microvascular dysfunction (CMD) is a common condition contributing to heterogenous cardiac diseases, such as myocardial ischemia and heart failure. However, little is known regarding the natural history of CMD, as most studies assessing this condition were performed cross-sectionally. Therefore, we investigated the evolution over time of microvascular function in an all-comer population, to assess the natural history of CMD. Methods 273 patients undergoing elective coronary angiography at two timepoints at least 6 months apart were included; average time between the two coronary angiographies was 34±21 months. Microvascular function was measured retrospectively by means of angiography-based index of microvascular resistance (aIMR) at both timepoints in the same vessel (LAD in 93.4% of cases, LCx in 1.5%, RCA in 4.8%), in order to assess variation of microvascular function over time. An aIMR ≥25 was considered indicative of CMD. Results Of the included 273 patients, 107 presented CMD at inclusion (39.2%); average aIMR at baseline was 23.2±8.0. At the second timepoint, after an average of 34±21 months, average aIMR was significantly increased compared to baseline (24.4±8.6, p=0.013). Interestingly, in spite of an overall increased average aIMR expressing a tendentially worsening microvascular function over time, of the 107 patients with CMD at inclusion only 61 (22.3% of the total population) still presented CMD at follow-up. On the contrary, 46 patients with CMD at inclusion (16.8%) showed an improved coronary microvascular function with an aIMR<25. On the other hand, 60 patients (22.0%) with initially normal aIMR developed de novo CMD at control angiography. Conclusion In our study longitudinally assessing CMD in an all-comer population, we could show that average microvascular function shows a mild overall worsening over time. However, our data show that CMD is a highly dynamic condition with high rates of improvement and worsening over time. The assessment of the clinical predictors of these variations may shed further light on the still incompletely understood pathogenesis of CMD and mainly on its natural history.

Routinely available inflammation biomarkers as predictors of adverse outcomes following coronary angiography

Abstract Background Inflammatory activation plays a pivotal role in the development and progression of atherosclerosis and subsequently in coronary artery disease (CAD). Several biomarkers of inflammation such as C-reactive protein (CRP), leucocytes, and neutrophile-to-lymphocyte ratio (NLR), are considerable predictors of adverse events in CAD patients. The presence of underlying inflammation may also affect net outcomes of patients undergoing coronary angiography and percutaneous coronary intervention (PCI). However, the association between inflammatory activation and patient outcomes after coronary angiography remain widely unclear. Purpose The study goal was to investigate the predictive value of routinely used inflammation biomarkers including CRP, leukocytes and NLR in a large all-comer patient population undergoing coronary angiography. We aimed to gain additional insights into the association of inflammatory markers with patient outcomes to take a step towards personalized risk stratification for CAD patients. Methods A total of 12 642 patients undergoing coronary angiography between 2010 and 2021 with full laboratory analysis were enrolled in this observational study. CRP, leucocytes and NLR were analysed for possible effects on all-cause and cardiovascular mortality. We further investigated target lesion revascularization (TLR) after PCI in the presence of underlying inflammation as an intervention-specific endpoint. Results 3300 (26%) patients presented with acute coronary syndromes (ACS) and 4145 (33%) patients were treated with PCI. All investigated inflammatory biomarkers (CRP, leukocytes, NLR) were significantly associated with all-cause mortality and especially with cardiovascular mortality in both acute and elective patients. This association remained highly significant after adjusting for demographic and clinical variables. While CRP was strongly related with cardiovascular mortality in STEMI patients (ad. HR per 1 SD: 1.35 [95%-CI: 1.14 – 1.59]), no significant association was observed in NSTEMI patients (ad. HR per 1 SD: 1.04 [95%-CI: 0.92 – 1.17]; p for interaction: 0.007; figure 1). Notably, CRP was not found to be associated with TLR in patients undergoing acute or elective PCI (ad. HR per 1 SD: 0.99 [95%-CI: 0.88 – 1.11]; p-value: 0.857). However, we found a highly significant association between NLR and TLR in both acute and elective patients (ad. HR per 1SD: 1.27 [95%-CI: 1.12 – 1.43]; p-value: <0.001). Conclusion Inflammatory activation is associated with increased mortality in patients undergoing coronary angiography. Although the impact of inflammation on interventional outcomes may be assumed, our study did not show significant associations between CRP and TLR. However, NLR emerged as a robust predictor of adverse events after PCI. Thus, while CRP does not impact the interventional outcome of PCI, a modulation of the cellular immune response does.Figure 1

France LILI (LIthopLastie Intracoronaire)

BackgroundIntravascular lithotripsy (IVL) is a novel and appealing device for the preparation of coronary calcified lesions before stenting. This technology has received CE mark and FDA approval, according to the data of the CAD studies. However, these clinical trials show numerous limits as the exclusion of a subset of lesions (Left main, CTO, in stent restenosis …) and patients’ over-selection. In this view, applications of IVL results in daily practice are debatable according to the lack of evidence in unselected patients. MethodsFRANCE-LILI is a prospective national academic registry evaluating the safety and effectiveness of adjunctive intravascular lithotripsy in coronary angioplasty in an all-comers patient population in France. The registry is registered with the ClinicalTrials.gov database (NCT05113407) and managed by the French Coronary Atheroma and Interventional Cardiology Group (GACI) of the French Society of Cardiology (FSC).France LILI will prospectively enroll 500 subjects. The primary endpoint is target vessel failure (TVF) at one year, defined as a composite of cardiac death, myocardial infarction (MI) according to the Academic Research Consortium-2 (ARC-2) definition (except for an MI clearly attributed to a non-target vessel) and revascularization of the target vessel. All endpoints are evaluated and confirmed by an independent adjudication committee. ConclusionThis national prospective academic registry will provide fruitful data on IVL in an unselected population of complex coronary lesions.

Transcatheter aortic valve implantation versus surgical aortic valve replacement in patients at low to intermediate surgical risk: rationale and design of the randomised DEDICATE Trial.

Transcatheter aortic valve implantation (TAVI) has become the preferred treatment option for patients with severe aortic stenosis at increased risk for surgical aortic valve replacement (SAVR) and for older patients irrespective of risk. However, in younger, low-risk patients for whom both therapeutic options, TAVI and SAVR, are applicable, the optimal treatment strategy remains controversial, as data on long-term outcomes remain limited. The DEDICATE-DZHK6 Trial is an investigator-initiated, industry-independent, prospective, multicentre, randomised controlled trial investigating the efficacy and safety of TAVI compared to SAVR in low- to intermediate-risk patients aged 65years or older. To evaluate both treatment strategies, approximately 1,404patients determined eligible for both TAVI and SAVR by the interdisciplinary Heart Team were randomised to TAVI or SAVR. Broad inclusion and strict exclusion criteria targeted an all-comers patient population. Procedures were performed according to local best practice with contemporary routine medical devices. The primary endpoints are acomposite of mortality or stroke at 1year and 5years in order to incorporate midterm efficacy results and complement early safety data. Primary outcomes will be tested sequentially for non-inferiority and superiority. The DEDICATE-DZHK6 Trial has been designed to mirror clinical reality for the treatment of severe aortic stenosis and provide unique information on overall outcomes after TAVI and SAVR that can be directly applied to clinical routines. Its results will help further define optimal treatment strategies for low- to intermediate-risk patients in whom both TAVI and SAVR are currently advisable.

Drug-Coated Balloon for the Treatment of Long-Segment Femoropopliteal Artery Disease: Pooled Analysis from the BIOLUX P-III SPAIN and BIOLUX P-III All-Comers Registry Long Lesion Subgroup

PurposeTo investigate the clinical performance and safety of the Passeo-18 Lux drug-coated balloon (DCB) in complex femoropopliteal Trans-Atlantic Inter-Society Consensus (TASC) C and D lesions in an all-comers patient population. Material and MethodsData from BIOLUX P-III SPAIN, a prospective, national, multicenter, postmarket all-comers registry conducted from 2017 to 2019, and a matching long lesion subgroup from the BIOLUX P-III All-Comers global registry conducted from 2014 to 2018 were pooled for analysis. The primary safety end point was freedom from major adverse events (MAEs) at 6 months, and the primary performance end point was freedom from clinically driven target lesion revascularization (fCD-TLR) at 12 months, both adjudicated by an independent clinical events committee. ResultsA total of 159 patients, of whom 32.7% had critical limb ischemia, were included in the Passeo-18 Lux long lesion cohort. The mean lesion length was 248.5 mm ± 71.6, and the majority were occluded (54.1%), calcified (87.4%), and of type TASC C (49.1%) or TASC D (50.9%). Freedom from MAEs was 90.6% (95% CI, 84.6–94.3) at 6 months and 83.9% (95% CI, 76.7–89.0) at 12 months. fCD-TLR was 84.4% (95% CI, 77.3–89.5) at 12 months. Freedom from target limb major amputation was 98.6% (95% CI, 94.6–99.7), and all-cause mortality was 5.3% (95% CI, 2.7–10.4) at 12 months. There were no device- or procedure-related deaths or amputations up to the 12-month follow-up. ConclusionPasseo-18 Lux DCB is safe and effective for the treatment of long femoropopliteal lesions in a real-word setting.

EUropean real-world outcomes with Pulsed field ablatiOn in patients with symptomatic atRIAl fibrillation: lessons from the multi-centre EU-PORIA registry.

Pulsed field ablation (PFA) is a new, non-thermal ablation modality for pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). The multi-centre EUropean Real World Outcomes with Pulsed Field AblatiOn in Patients with Symptomatic AtRIAl Fibrillation (EU-PORIA) registry sought to determine the safety, efficacy, and learning curve characteristics for the pentaspline, multi-electrode PFA catheter. All-comer AF patients from seven high-volume centres were consecutively enrolled. Procedural and follow-up data were collected. Learning curve effects were analysed by operator ablation experience and primary ablation modality. In total, 1233 patients (61% male, mean age 66 ± 11years, 60% paroxysmal AF) were treated by 42 operators. In 169 patients (14%), additional lesions outside the PVs were performed, most commonly at the posterior wall (n = 127). Median procedure and fluoroscopy times were 58 (interquartile range: 40-87) and 14 (9-21) min, respectively, with no differences due to operator experience. Major complications occurred in 21/1233 procedures (1.7%) including pericardial tamponade (14; 1.1%) and transient ischaemic attack or stroke (n = 7; 0.6%), of which one was fatal. Prior cryoballoon users had less complication. At a median follow-up of 365 (323-386) days, the Kaplan-Meier estimate of arrhythmia-free survival was 74% (80% for paroxysmal and 66% for persistent AF). Freedom from arrhythmia was not influenced by operator experience. In 149 (12%) patients, a repeat procedure was performed due to AF recurrence and 418/584 (72%) PVs were durably isolated. The EU-PORIA registry demonstrates a high single-procedure success rate with an excellent safety profile and short procedure times in a real-world, all-comer AF patient population.

Comprehensive Assessment of Myocardial Ischemia Mechanisms in the Catheterization Laboratory: Design and Rationale of the Advanced Invasive Diagnosis Strategy for Patients with Stable Coronary Syndromes Undergoing Coronary ANGIOgraphy - the AID-ANGIO Study

BackgroundThe diagnostic yield of invasive coronary angiography (ICA) to identify obstructive coronary artery disease in the context of chronic coronary syndromes (CCS) is very low. Furthermore, myocardial ischemia may have a non-obstructive origin, which cannot be detected by ICA. MethodsAID-ANGIO is an observational, prospective, single-cohort, multicenter study, intended to evaluate the diagnostic yield of adopting a hierarchical strategy to assess obstructive and non-obstructive causes of myocardial ischemia in an all-comers population of patients with CCS at the time of ICA. The primary endpoint will investigate the additional diagnostic value of such strategy over angiography alone regarding the identification of ischemia-generating mechanisms. SummaryAn estimated sample of consecutive 260 patients with CCS referred by their clinicians to ICA, will be enrolled. In a stepwise manner, a conventional ICA will be performed as the initial diagnostic tool. Those patients with severe-grade stenosis will not undergo further assessment and an obstructive origin for myocardial ischemia will be assumed. Subsequently, the remainder with intermediate-grade stenosis will be assessed with pressure guidewires. Those with a negative result from physiological evaluation and those without epicardial coronary stenosis will be further studied for ischemia of non-obstructive origin, including microvascular dysfunction and vasomotor disorders.The study will be conducted in two steps. Firstly, ICA images will be displayed to patient's referring clinicians, who will be asked to identify the existent epicardial stenosis, their angiographic severity and probable physiological relevance, together with a tentative therapeutic approach. Then, the diagnostic algorithm will continue to be applied and, considering the whole gathered information, a definite therapeutic plan will be consensually established by the interventional cardiologist and patient's referring clinicians. ConclusionThe AID-ANGIO study will assess the additional diagnostic yield of a hierarchical strategy over ICA alone to identify ischemia-generating mechanisms in patients with CCS and its impact on therapeutic approach. Positive results of the study might support a streamlined invasive diagnostic process for patients with CCS.

Late recurrence of atrial fibrillation and flutter in patients referred for elective electrical cardioversion.

Aim The primary aim was to ascertain long-term rates of atrial fibrillation (AF) recurrence in this all-comer patient population undergoing elective electrical cardioversion (DCR). Secondary aims included procedural DCR success, clinical predictors of long-term maintenance of sinus rhythm (SR) and AF related hospitalizations.Material and Methods A retrospective cohort study was conducted. Consecutive patients (n=316) undergoing elective DCR were included.Results Successful immediate reversion to SR was attained in 266 (84 %) of patients. 224 (84 %) patients were followed up for a median period of 3.5 years (IQR 2.7-4.3). Most patients (150 [67 %]) had recurrence of AF / flutter at a median time of 240 days. Clinical predictors of AF recurrence included a history of AF (HR 0.63, p=0.038) and a dilated left atrium (HR 4.13, p=0.048). Maintenance of SR was associated with fewer unplanned hospitalizations for AF (HR 3.25, p<0.01).Conclusion There was high procedural success post DCR. However, long-term rates of AF recurrence were high, and AF recurrences were associated with increased hospitalizations. These findings underscore the importance of clinical vigilance and multi-modal management as part of a comprehensive and effective rhythm control strategy.

Three years performance of Biodegradable Polymer Sirolimus Eluting Stent in all comer patients undergoing Percutaneous Coronary Intervention.

Introduction: Contemporary evidence suggest the comparable performance of biodegradable polymer sirolimus eluting stents (BPSES) with that of second generation durable polymer drug eluting stents. This study was done to evaluate the performance of BPSES in all comer patients undergoing percutaneous intervention (PCI) in real world setting over a period of three years. Materials & Methods: This was a prospective observational study, wherein all comer consecutive patients undergoing PCI with BPSES (Yukon Choice Elite stent by Translumina Therapeutics, India) were enrolled and followed up for 3 years. The study's primary endpoint was the Device Oriented Composite Endpoint (DOCE), which included cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization (TLR); the co-primary endpoint was the Patient-Oriented Composite Endpoint (POCE), which included all-cause mortality, any MI , and any repeat revascularization and the secondary endpoint was definite or probable stent thrombosis (DST & PST). Results: 301 patients with 502 lesions were treated with 485 BP-SES. Mean age of the study cohort was 61.6± 9.3 yrs and males were 79.1%. 18.6% patients were diabetic, 29.6% had ejection fraction less than 40% and 73.1% patients presented with acute coronary syndrome (ACS). Majority of the patient had triple vessel disease (TVD) (51.8%), multivessel PCI was done in 15.6% and complex PCI in 26.2% patients. A mean of 1.6 ±0.8 stents per patient with mean diameter 3.0 ± 0.3 mm and mean length of 27.2 ± 0.8 mm were placed. DOCE & POCE occurred in 7.9% (cardiac death-4.8%, TLR-2.6% & target vessel MI-0.4%) and 12.8% (All deaths-9.7%, any MI- 0.4% and any revascularisation-2.6%) patients respectively at three years follow-up. DST & PST rate was 0.9% and 0.4% respectively in the study cohort. All the cases of stent thrombosis occurred within 30 days. Kaplan Meier analysis revealed that diabetes mellitus, low ejection fraction (EF), acute coronary syndrome (ACS), long stents and complex intervention had no impact on occurrence of DOCE & POCE while using BP-SES in all-comer patient population. Conclusion: Present study showed favourable long term safety and efficacy profile of BP-SES for all-comer patients undergoing PCI.

Comparison of the prevalence of SARS-CoV-2 nucleoprotein antibodies in healthcare workers and an unselected adult and paediatric all-comer patient population: insights from a longitudinal study of healthcare workers and concurrent serial cross-sectional studies of patients at an academic medical centre in Austria

ObjectivesThis study aimed to estimate and compare the prevalence of the virus-specific antibodies against the SARS-CoV-2 nucleoprotein antigen (anti-SARS-CoV-2 N) in healthcare workers and an all-comer paediatric and adult patient...

Anticoagulation for Atrial Fibrillation in Acute Coronary Syndrome Survivors Reduces Major Cardiovascular Events and Mortality.

The prevalence of atrial fibrillation (AF) in acute coronary syndrome (ACS) patients is increasing. Data on outcomes of anticoagulation in ACS patients with AF are lacking. The aim of our study was to investigate the prevalence of stroke, myocardial infarction, bleeding complications, and all-cause mortality in this population. PL-ACS and AMI-PL registries gather an all-comer population of ACS patients in Poland, exceeding half a million records. We have selected ACS survivors with concomitant AF on admission, divided them into subgroups with regard to the administered anticoagulation, and followed up with them for a 12-month period ( n = 13,973). Subsequently, groups were propensity score matched for age, sex, ejection fraction, diabetes, heart failure, renal impairment, and type of ACS. The study population was divided with regard to the administration of anticoagulation. Anticoagulation was prescribed in 2,466 patients (17.6%). The (D)OAC+ patients were younger; however, comorbidities were more prevalent in this group. The 12-month follow-up showed that the (D)OAC+ patients had significantly lower rates of all-cause mortality, myocardial infarction, and ischemic stroke, with no significant increase in bleeding events. After matching, the study groups consisted of 2,194 patients each and showed no differences in baseline characteristics. The outcomes of the 12-month observation were similar to the findings before matching. This all-comer national registry analysis shows that the use of guideline-recommended therapy and anticoagulation in ACS survivors with AF is associated with a lower rate of all-cause mortality, recurrent myocardial infarction, and ischemic stroke.

High bleeding risk in patients undergoing percutaneous coronary intervention with drug-eluting stent implantation: ReCre8 subanalysis

ObjectivesIn an all-comers cohort undergoing percutaneous coronary intervention (PCI), we aimed to assess prevalence of high bleeding risk (HBR) patients and impact of HBR and dual antiplatelet therapy (DAPT) on clinical events. BackgroundHBR represents a complex subgroup of patients undergoing PCI. MethodsIn the ReCre8 trial, patients undergoing PCI were stratified for troponin status and diabetes and randomized to a permanent polymer zotarolimus-eluting- or polymer-free amphilimus-eluting stent. Patients were treated with 12 months (troponin-positive) or one month (troponin-negative) of DAPT. We evaluated clinical outcomes in patients with and without HBR according to the Academic Research Consortium for High Bleeding Risk criteria. ResultsFrom a total of 1488 patients included in this subanalysis, 406 patients (27.3 %) were identified as being at HBR. Among HBR patients, target-lesion failure (TLF) was similar after one year yet was higher after three years (13.3 % vs. 9.1 %; p = 0.013), compared to non-HBR patients. There was no difference in Bleeding Academic Research Consortium (BARC) 3 to 5 bleeding, however BARC 2 to 5 bleeding was higher after three years with 4.9 % vs. 3.0 % (p = 0.037). There were no differences between troponin-positive (12-months DAPT) and -negative (1-month DAPT) HBR patients with respect to ischemic and bleeding outcomes. ConclusionsIn this all-comers population of PCI patients, a higher TLF rate among HBR patients at long-term follow-up was found, underlining the complexities involving treatment of HBR patients. We did not observe statistically significant differences in BARC 3 to 5 bleeding between HBR and non-HBR patients regardless of DAPT duration. Clinical trial registrationURL: http://www.clinicaltrials.gov, unique identifier: NCT02328898.

Telomere Shortening in Hypertensive Heart Disease Depends on Oxidative DNA Damage and Predicts Impaired Recovery of Cardiac Function in Heart Failure.

Heart failure (HF) coincides with cardiomyocyte telomere shortening. Arterial hypertension is the most prominent risk factor for HF. Both HF and arterial hypertension are associated with dysregulation of the neurohormonal axis. How neurohormonal activation is linked to telomere shortening in the pathogenesis of HF is incompletely understood. Cardiomyocyte telomere length was assessed in a mouse model of hypertensive HF induced by excess neurohormonal activation (AngII [angiotensin II] infusion, high salt diet, and uninephrectomy), in AngII-stimulated cardiomyocytes and in endomyocardial biopsies from patients with HF. Superoxide production, expression of NOX2 (NADPH oxidase 2) and PRDX1 (peroxiredoxin 1) and HDAC6 (histone deacetylase 6) activity were assessed. Telomere shortening occurred in vitro and in vivo, correlating with both left ventricular (LV) dilatation and LV systolic function impairment. Telomere shortening coincided with increased superoxide production, increased NOX2 expression, increased HDAC6 activity, loss of the telomere-specific antioxidant PRDX1, and increased oxidative DNA-damage. NOX2 knockout prevented PRDX1 depletion, DNA-damage and telomere shortening confirming this enzyme as a critical source of reactive oxygen species. Cotreatment with the NOX inhibitor apocynin ameliorated hypertensive HF and telomere shortening. Similarly, treatment with the HDAC6 inhibitor tubastatin A, which increases PRDX1 bioavailability, prevented telomere shortening in adult cardiomyocytes. To explore the clinical relevance of our findings, we examined endomyocardial biopsies from an all-comer population of patients with HF with reduced ejection fraction. Here, cardiomyocyte telomere length predicted the recovery of cardiac function. Cardiomyocyte telomere shortening and oxidative damage in heart failure with reduced ejection fraction induced by excess neurohormonal activation depends on NOX2-derived superoxide and may help to stratify HF therapy.

0480 Reduction in health care-related costs after initiation of treatment with a prescription digital therapeutic for chronic insomnia: two-year follow up analysis of health care claims data

Abstract Introduction The objective of this study was to evaluate the effectiveness of the first FDA-authorized prescription digital therapeutic (PDT) for adults with chronic insomnia that delivers evidence-based treatment (Somryst, previously called SHUTi). FDA considers PDTs to be prescription-only neurobehavioral devices that provide a computerized version of condition-specific behavioral therapy as an adjunct to clinician supervised outpatient treatment. Methods A pre/post multi-payer analysis of claims data was conducted, comparing two-year pre- and post-index healthcare resource utilization (HCRU) in an all-comer population of patients with self-identified sleep problems across the United States who activated the PDT between February 1, 2012 and December 31, 2018 (Index). HCRU categories assessed were: hospitalizations, treat-and-release emergency department (ED) visits, ambulatory surgical center (ASC) visits, hospital outpatient department (HOPD) visits, office visits, number of sleep medication prescriptions, and associated health care costs. Costs were estimated by multiplying HCRU by published average costs for each medical resource. Results 252 patients initiating the PDT were analyzed (mean age 54.2 years, 57.5% female). Compared to the pre-index period, post-index events were reduced for ED (-56.2%; P=0.001), hospitalizations (-20.9%; P=0.4), sleep medication use (-8.9%; P=0. 0.377), HOPD (-8.3%; P=0.522), and ASC (-6.7%; P=0.695). Post-index events were slightly increased for office visits (+0.7%; P=0.891). Total estimated two-year cost savings associated with the reduced rates of all services except office visits was $494,634, or $1,963 per patient. Conclusion In a real-world cohort of patients with self-identified sleep problems, treatment with a PDT delivering digital CBT-I was associated with clinically meaningful net reductions in health-related services and associated costs. Support (If Any) This analysis was funded by Pear Therapeutics, Inc.

E-9 | Prospective Evaluation of Ultrathin-strut Biodegradable Polymer-coated Sirolimus-eluting Stents in an All-comers Patient Population: Slovakia Registry with a Subgroup Analysis

Thicker struts affording a smaller minimum in-stent diameter are known predictors of restenosis in coronary stents. The Slovakia Registry aimed to assess safety and efficacy of the ultrathin (60 μm) biodegradable polymer-coated Supraflex sirolimus-eluting stents (SES) (Sahajanand Medical Technologies Ltd., Surat, India), in an all-comers population with a subgroup of diabetic patients.

Prediction of 3-year all-cause and cardiovascular cause mortality in a prospective percutaneous coronary intervention registry: Machine learning model outperforms conventional clinical risk scores

Background and aimsMachine learning (ML) models have been proposed as a prognostic clinical tool and superiority over clinical risk scores is yet to be established. Our aim was to analyse the performance of predicting 3-year all-cause- and cardiovascular cause mortality using ML techniques and compare it with clinical scores in a percutaneous coronary intervention (PCI) population. MethodsAn all-comers patient population treated by PCI in a tertiary cardiovascular centre that have been included prospectively in the local registry between January 2016–December 2017 was analysed. The ML model was trained to predict 3-year mortality and prediction performance was compared with that of GRACE, ACEF, SYNTAX II 2020 and TIMI scores. ResultsA total number of 2242 patients were included with 12.1% and 14.9% 3-year cardiovascular and -all-cause mortality, respectively. The area under receiver operator characteristic curve for the ML model was higher than that of GRACE, ACEF, SYNTAX II and TIMI scores: 0.886 vs. 0.797, 0.792, 0.757 and 0.696 for 3-year cardiovascular- and 0.854 vs. 0.762, 0.764, 0.730 and 0.691 for 3-year all-cause mortality prediction, respectively (all p ≤ 0.001). Similarly, the area under precision-recall curve for the ML model was higher than that of GRACE, ACEF, SYNTAX II and TIMI scores: 0.729 vs. 0.474, 0.469, 0.365 and 0.389 for 3-year cardiovascular- and 0.718 vs. 0.483, 0.466, 0.388 and 0.395 for 3-year all-cause mortality prediction, respectively (all p ≤ 0.001). ConclusionThe ML model was superior in predicting 3-year cardiovascular- and all-cause mortality when compared to clinical scores in a prospective PCI registry.

Risk-related short-term clinical outcomes after transcatheter aortic valve implantation and their impact on early mortality: an analysis of claims-based data from Germany

ObjectivesWe aimed to define and assess risk-specific adverse outcomes after transcatheter aortic valve implantation (TAVI) in an all-comers patient population based on German administrative claims data.MethodsAdministrative claims data of patients undergoing transvascular TAVI between 2017 and 2019 derived from the largest provider of statutory health-care insurance in Germany were used. Patients’ risk profile was assessed using the established Hospital Frailty Risk (HFR) score and 30-day adverse events were evaluated. Multivariable logistic regression models were applied to investigate the relation of patients’ risk factors to clinical outcomes and, subsequently, of clinical outcomes to mortality.ResultsA total of 21,430 patients were included in the analysis. Of those, 51% were categorized as low-, 37% as intermediate-, and 12% as high-risk TAVI patients according to HFR score. Whereas low-risk TAVI patients showed low rates of periprocedural adverse events, TAVI patients at intermediate or high risk suffered from worse outcomes. An increase in HFR score was associated with an increased risk for all adverse outcome measures. The strongest association of patients’ risk profile and outcome was present for cerebrovascular events and acute renal failure after TAVI. Independent of patients’ risk, the latter showed the strongest relation with early mortality after TAVI.ConclusionsDifferentiated outcomes after TAVI can be assessed using claims-based data and are highly dependent on patients’ risk profile. The present study might be of use to define risk-adjusted outcome margins for TAVI patients in Germany on the basis of health-insurance data.Graphical abstract