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Objectives The aim of this analysis was to assess long-term clinical outcomes of the polymer-free Amphilimus-eluting stent (PF-AES) compared with a latest generation permanent-polymer drug-eluting stent (DES) in an all-comers population. Background PF-AES possess multiple properties improving targeted drug elution without the presence of polymers. Evaluation of long-term clinical performance of PF-AES versus latest generation permanent-polymer DES has not yet been performed in a large randomized trial introducing shortened dual-antiplatelet therapy. Methods In this physician-initiated, multicenter, randomized, all-comers trial, patients undergoing percutaneous coronary intervention with implantation of DES were enrolled. Patients were stratified for diabetes and troponin status and randomized to implantation of a permanent-polymer zotarolimus-eluting stent (PP-ZES) or a PF-AES. Dual-antiplatelet therapy duration was 12 months in troponin-positive patients and 1 month in troponin-negative patients. A noninferiority analysis was conducted to compare the 2 arms regarding target lesion failure (TLF) between 1 and 3 years. Results A total of 1,491 patients were randomized and treated. In this landmark analysis, between 1- and 3-year follow-up, TLF occurred in 35 patients (4.9%) in the PP-ZES arm and 37 PF-AES patients (5.1%). Clinical noninferiority of the PF-AES was confirmed, with a risk difference of 0.2% (upper limit 1-sided 95% CI: 2.2%; Pnoninferiority = 0.0031). Conclusions ReCre8 (Randomized “All-Comer” Evaluation of a Permanent Polymer Resolute Integrity Stent Versus a Polymer Free Cre8 Stent) is the first randomized, multicenter trial with a head-to-head comparison of PP-ZES compared with PF-AES to investigate clinical outcomes of these new-generation DES in an all-comers population with long-term follow-up. On the basis of the present results, PF-AES are clinically noninferior to PP-ZES regarding TLF between 1 and 3 years. (Randomized “All-Comer” Evaluation of a Permanent Polymer Resolute Integrity Stent Versus a Polymer Free Cre8 Stent; NCT02328898 )

Introduction Refractory angina (RA) is considered the end-stage of coronary artery disease, and often has no interventional treatment options. Coronary sinus Reducer (CSR) is a recent addition to the therapeutic arsenal, but its efficacy has only been evaluated on small populations. The RESOURCE registry provides further insights into this therapy. Methods The RESOURCE is an observational, retrospective registry that includes 658 patients with RA from 20 centers in Europe, United Kingdom and Israel. Prespecified endpoints were the amelioration of anginal symptoms evaluated with the Canadian Cardiovascular Society (CCS) score, the rates of procedural success and complications, and MACEs as composite of all-cause mortality, acute coronary syndromes, and stroke. Results At a median follow-up of 502 days (IQR 225–1091) after CSR implantation, 39.7% of patients improved by ≥2 CCS classes (primary endpoint), and 76% by ≥1 class. Procedural success was achieved in 96.7% of attempts, with 3% of procedures aborted mostly for unsuitable coronary sinus anatomy. Any complication occurred in 5.7% of procedures, but never required bailout surgery nor resulted in intra- or periprocedural death or myocardial infarction. One patient developed periprocedural stroke after inadvertent carotid artery puncture. At the last available follow-up, overall mortality and MACE were 10.4% and 14.6% respectively. At one, three and five years, mortality rate at Kaplan-Meier analysis was 4%, 13.7%, and 23.4% respectively. Conclusions CSR implantation is safe and reduces angina in patients with refractory angina.

Background: Little is known about the occurrence of unknown preexisting conduction disturbances/sinus node dysfunction (CDs/SND) in transcatheter aortic valve replacement (TAVR) patients. Preexisti...

Background Refractory angina is a growing and major health-care problem affecting millions of patients with coronary artery disease worldwide. The Coronary Sinus Reducer (CSR) is a device that may be considered for the relief of symptoms of refractory angina. It causes increased venous pressure leading to a dilatation of arterioles and reduced arterial vascular resistance in the sub-endocardium. This study describes the 5‑year Dutch experience regarding safety and efficacy of the CSR. Methods One hundred and thirty-two patients with refractory angina were treated with the CSR. The primary efficacy endpoint of the study was Canadian Cardiovascular Society (CCS) class improvement between baseline and 6‑month follow-up. The primary safety endpoint was successful CSR implantation in the absence of any device-related events. Results Eighty-five patients (67%) showed improvement of at least 1 CCS class and 43 patients (34%) of at least 2 classes. Mean CCS class improved from 3.17 ± 0.61 to 2.12 ± 1.07 after implantation (P Conclusion The CSR is a simple, safe, and effective option for most patients with refractory angina. However, approximately thirty percent of the patients showed no benefit after implantation. Future studies should focus on the exact underlying mechanisms of action and reasons for non-response to better identify patients that could benefit most from this therapy.

Background Multiple scores have been proposed to guide risk stratification after percutaneous coronary intervention. This study assessed the performance of the PRECISE-DAPT, PARIS and CREDO-Kyoto risk scores to predict post-discharge ischaemic or bleeding events. Methods A total of 1491 patients treated with latest-generation drug-eluting stent implantation were evaluated. Risk scores for post-discharge ischaemic or bleeding events were calculated and directly compared. Prognostic performance of both risk scores was assessed with calibration, Harrell’s c‑statistics net reclassification index and decision curve analyses. Results Post-discharge ischaemic events occurred in 56 patients (3.8%) and post-discharge bleeding events in 34 patients (2.3%) within the first year after the invasive procedure. C‑statistics for the PARIS ischaemic risk score was marginal (0.59, 95% confidence interval (CI) 0.51–0.68), whereas the CREDO-Kyoto ischaemic risk score was moderate (0.68, 95% CI 0.60–0.75). With regard to post-discharge bleeding events, CREDO-Kyoto displayed moderate discrimination (c-statistic 0.67, 95% CI 0.56–0.77), whereas PRECISE-DAPT (0.59, 95% CI 0.48–0.69) and PARIS (0.55, 95% CI 0.44–0.65) had a marginal discriminative capacity. Net reclassification index and decision curve analysis favoured CREDO-Kyoto-derived bleeding risk assessment. Conclusion In this contemporary all-comer population, PARIS and PRECISE-DAPT risk scores were not resilient to independent testing for post-discharge bleeding events. CREDO-Kyoto-derived risk stratification was associated with a moderate predictive capability for post-discharge ischaemic or bleeding events. Future studies are warranted to improve risk stratification with more focus on robustness and rigorous testing.

Purpose: Cardiac resynchronisation therapy (CRT) improves left ventricular (LV) function acutely, with further improvements and reverse remodelling during chronic CRT. The current study investigated the relation between acute improvement of LV systolic function, acute mechanical recoordination, and long-term reverse remodelling after CRT. Methods: In 35 patients, LV speckle tracking longitudinal strain, LV volumes & ejection fraction (LVEF) were assessed by echocardiography before, acutely within three days, and 6 months after CRT. A subgroup of 25 patients underwent invasive assessment of the maximal rate of LV pressure rise (dP/dtmax,) during CRT-implantation. The acute change in dP/dtmax, LVEF, systolic discoordination (internal stretch fraction [ISF] and LV systolic rebound stretch [SRSlv]) and systolic dyssynchrony (standard deviation of peak strain times [2DS-SD18]) was studied, and their association with long-term reverse remodelling were determined. Results: CRT induced acute and ongoing recoordination (ISF from 45 ± 18 to 27 ± 11 and 23 ± 12%, p max 668 ± 185 vs. 817 ± 198 mmHg/s, p Conclusion: Long-term reverse remodelling after CRT is likely determined by (acute) recoordination rather than by acute hemodynamic improvements. Discoordination may therefore be a more important CRT-substrate that can be assessed and, acutely restored.

Objective We sought to determine the incidence, angiographic predictors, and impact of stent thrombosis (ST). Background Given the high mortality after ST, this study emphasises the importance of ongoing efforts to identify angiographic predictors of ST. Methods All consecutive patients with angiographically confirmed ST between 2010 and 2016 were 1:4 matched for (1) percutaneous coronary intervention (PCI) indication and (2) index date ±6 weeks to randomly selected controls. Index PCI angiograms were reassessed by two independent cardiologists. A multivariable conditional logistic regression model was built to identify independent predictors of ST. Results Of 6,545 consecutive patients undergoing PCI, 55 patients [0.84%, 95% confidence interval (CI) 0.63–1.10%] presented with definite ST. Multivariable logistic regression identified dual antiplatelet therapy (DAPT) non-use as the strongest predictor of ST (odds ratio (OR) 10.9, 95% CI 2.47–48.5, p

Background: Polymer-free amphilimus-eluting stents (PF-AES) represent a novel elution technology in the current era of drug-eluting stents. The clinical safety and efficacy of PF-AES as compared with latest-generation permanent-polymer zotarolimus-eluting stents (PP-ZES) have not yet been investigated in a large randomized trial. Methods: In this physician-initiated, prospective, multicenter, randomized, noninferiority trial, an all-comers population requiring percutaneous coronary intervention was enrolled across 3 European sites. Randomization (1:1 ratio) to PP-ZES or PF-AES was performed after stratification for troponin status and diabetes mellitus. In both treatment arms, troponin-positive patients were planned for 12-month dual antiplatelet therapy, whereas troponin-negative patients were planned for 1-month dual antiplatelet therapy. Outcome assessors were blinded to the allocated treatment. The device-oriented primary end point of target-lesion failure was defined as cardiac death, target-vessel myocardial infarction, or target-lesion revascularization at 12-months as analyzed by modified intention-to-treat (80% power, and a 3.5% noninferiority margin). Results: In total, 1502 patients were randomized and 1491 treated with the assigned stent and available for follow-up. The primary end point occurred in 42 (5.6%) of the 744 patients receiving PP-ZES versus 46 (6.2%) of the 747 patients receiving PF-AES. PF-AES were clinically noninferior to PP-ZES (risk difference, 0.5%; upper limit 1-sided 95% confidence interval, 2.6%; P noninferiority =0.0086). Cardiac death occurred in 10 (1.3%) versus 10 patients (1.3%; P value for difference, 1.00), target-vessel myocardial infarction occurred in 18 (2.4%) versus 17 patients (2.3%; P value for difference, 0.87), and target-lesion revascularization occurred in 22 (2.9%) versus 20 patients (2.6%; P value for difference, 0.75) for PF-AES as compared with PP-ZES. Overall, definite or probable stent thrombosis occurred in 1.0%. Conclusions: PF-AES were noninferior to PP-ZES regarding target-lesion failure at 12 months. Findings regarding the secondary end point and prespecified subgroups were generally consistent with that of the primary end point. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02328898.

Objectives The purpose of this analysis was to compare target-lesion failure (TLF) of a permanent polymer zotarolimus-eluting stent (PP-ZES) versus a polymer-free amphilimus-eluting stent (PF-AES) in diabetics. Background The improvement of outcomes with new-generation drug-eluting stent as seen in the general population is less pronounced among diabetics. The PF-AES introduces an elution-technology with potential enhanced performance in diabetics. Methods In this subanalysis of the ReCre8 trial, patients were randomized to either a PP-ZES or PF-AES after stratification for diabetes and troponin status. The primary device-oriented endpoint was TLF, a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization. Results In the ReCre8 trial, 304 (20%) patients were diabetic and 96 (6%) had insulin-dependent diabetes mellitus. There was no statistically significant difference between the two study arms regarding the primary endpoint (PP-ZES 7.2% vs. PF-AES 4.0%; p = .21), although the composite of net adverse clinical events was higher in the PP-ZES arm (15.7 vs. 8.0%; p = .035). Stent thrombosis was low in both groups with no cases in the PP-ZES arm and 1 case in the PF-AES arm (p = .32). Regarding insulin-treated diabetics, TLF was higher in the PP-ZES arm (14.9 vs. 2.1%; p = .022). Conclusions Diabetics could potentially benefit from a dedicated stent, releasing sirolimus with a lipophilic carrier (amphilimus-formulation). Future trials should confirm the potential benefit of a PF-AES in this population.

Objectives: To compare the outcomes of transfemoral ACURATE neo (NEO) and Sapien 3 (S3) patients in terms of device success and clinical safety outcomes using a propensity score analysis. Background: Differences in clinical outcomes between the latest-generation balloon-expandable S3 and self-expanding NEO in a “real-world transfemoral TAVI population” are still unclear. Methods: We compared up to 6 months clinical outcomes using a propensity score analysis (inverse probability of treatment weighting [IPTW]) to account for differences in baseline characteristics. Results: A total of 345 patients underwent transfemoral transcatheter aortic valve implantation (TAVI) with either NEO or S3 at two centers in the Netherlands. Composite device success and early safety endpoints were comparable between NEO and S3 (Device success: IPTW-adjusted OR: 0.35 [95% CI: 0.12–1.18], and early safety: IPTW-adjusted OR: 0.51 [95% CI: 0.19–1.38]). Six-months mortality was 5.3 versus 3.6%, stroke was 2.8 versus 3.3%, and pacemaker rate was 6.1 versus 8.6%, respectively with p = NS. Mean aortic gradient was lower in the NEO group (5.72 ± 2.47 vs. 9.05 ± 3.48; p =

Coronary sinus Reducer (CSR) implantation is currently recommended to relieve angina in patients with refractory symptoms despite optimal medical therapy and maximally achievable revascularization. The impact of diabetes mellitus on outcome after CSR implantation is at present unknown. We aimed to explore the impact of CSR in refractory angina patients with diabetes mellitus. Data from consecutive patients undergoing CSR implantation at four different centres between 2014 and 2018 were included. Patients were divided according to the presence or absence of diabetes mellitus. Primary objective of this analysis was to evaluate the clinical response to CSR implantation defined as an improvement of ≥ 1 classes of the Canadian Cardiovascular Society (CCS) Classification. A total of 219 patients were included, 116 (53%) of whom had diabetes mellitus. The median age of the population was 69 years and 167 patients (76%) were male. There were no significant differences between groups of patients with and without diabetes mellitus with respect to CCS class at baseline (p value = 0.32) and at follow-up (p = 0.75). Over a median follow-up of 393 [224–1004] days, 84 (72%) of the patients with diabetes mellitus met the primary outcome, similarly to those without diabetes mellitus (p = 0.28). Fifty-three patients (24%) did not have an improvement in CCS class and no one experienced worsening of angina. CSR implantation was equally effective in improving angina symptoms among patients with refractory angina and diabetes mellitus compared to patients without diabetes mellitus.

Objectives We hypothesized that some coronary sinus (CS) anatomies allow a more straightforward CS Reducer (CSR) implantation. Background Recent decades have seen a rise in patients with chronic angina. When complete revascularization and maximal medical therapy fail to reduce symptoms, CSR has become a new therapeutic option. Methods We identified a classical C-shape-a near horizontal course of the proximal portion of a circular CS-in a retrospective analysis of 47 CSR implantations and compared the procedural time, fluoroscopic time, contrast use, presence of valves or bifurcations and procedural complications with the non-C-shape CS anatomy. Results We found a significant difference in procedural (20.0 [19.0-24.7] min vs. 24.5 [20.7-51.0] min; p = .028 and fluoroscopic time (9.5 [7.5-14.5] min vs. 11.0 [7.9-30.0] min; p = .016). There was no significant difference in contrast use. The presence of bifurcations or valves along the CS course did not influence the procedural timings. Conclusion This study is the first systematic evaluation of CS anatomy and its procedural implications. We identified a favorable C-shape anatomy which allows for a more straightforward implantation. Operators should be aware of the different implications of CS anatomy, their influence on guiding catheter stability and overall procedure complexity.

Background: Currently, 2 third-generation transcatheter valves, 29-mm Sapien-3 and 34-mm Evolut-R (ER), are indicated for large sized aortic annuli. We analyzed short and 1-year performance of these valves in patients with large (area ≥575 mm 2 or perimeter ≥85 mm) and extra-large (≥683 mm 2 or ≥94.2 mm) aortic annuli undergoing transcatheter aortic valve replacement. Methods: A total of 833 patients across 12 centers with symptomatic aortic stenosis and large aortic annuli underwent transcatheter aortic valve replacement with 29-mm Sapien-3 (n=640) or 34-mm ER (n=193). Clinical, anatomic, and procedural characteristics were collected, and Valve Academic Research Consortium-2 outcomes were reported. Results: Median aortic annulus area and perimeter were 617 mm 2 (591–657) and 89.1 mm (87.0–92.1), respectively (704 mm 2 [689–743] and 96.0 mm [94.5–97.9] in the subgroup of 124 patients with extra-large annuli). Overall device success was 94.3% (Sapien-3, 95.8% and ER, 89.3%; P =0.001), with a higher rate of significant paravalvular leak ( P =0.004), second valve implantation ( P =0.013), and valve embolization ( P =0.009) in the ER group. Thirty-day and 1-year mortality was 2.4% and 9.2%, respectively, without differences between groups. Valve hemodynamics were excellent (mean gradient, 8.8±3.6 mm Hg; 3.3% rate of moderate-severe paravalvular leak) in the extra-large annulus, without differences compared with the large annulus group. Conclusions: In patients with large and extra-large aortic annuli, transcatheter aortic valve replacement using 29-mm Sapien-3 and 34-mm ER is safe and feasible. Observed differences in clinical outcomes and hemodynamic performance may guide valve choice in this cohort of patients undergoing transcatheter aortic valve replacement.

Introduction Transcatheter aortic valve implantation (TAVI) is a safe and effective treatment for inoperable, intermediate- or high-risk patients with severe symptomatic aortic stenosis and has been associated with excellent clinical outcomes. A clinically relevant remaining problem is aortic regurgitation (AR) post-TAVI, which is associated with increased mortality. Therefore, we conducted a prospective randomised trial to assess the safety and efficacy of a first-generation self-expandable valve (SEV; CoreValve) and a third-generation balloon-expandable valve (BEV; Sapien 3) with respect to clinical outcomes and AR as determined quantitatively by magnetic resonance imaging (MRI). Methods The ELECT study was an investigator-initiated, single-centre trial involving patients with severe symptomatic aortic stenosis and with a clinical indication for transfemoral TAVI. Fifty-six patients were randomly assigned to the BEV or SEV group. Results AR determined quantitatively by MRI was lower in the BEV than in the SEV group [regurgitant fraction: 1.1% (0–8.0) vs 8.7% (3.0–14.8) for SEV; p = 0.01]. Secondary endpoints according to the criteria of the Second Valve Academic Research Consortium (VARC-2) showed BEV to have better early safety [0 (0%) vs 8 (30%); p = 0.002] at 30 days and a lower risk of stroke [0 (0%) vs 5 (21%); p = 0.01], major adverse cardiac and cerebrovascular events [0 (0%) vs 10 (38%); p p = 0.02] in the 1st year compared with SEV. Conclusions The use of the latest generation of BEV was associated with less AR as quantitatively assessed by MRI. Although the use of MRI to quantify AR is not feasible in daily clinical practice, it should be considered as a surrogate endpoint for clinical outcomes in comparative studies of valves for TAVI. ClinicalTrials.gov number NCT01982032.

AIMS: The coronary sinus Reducer is a percutaneous device proven to improve angina symptoms in refractory angina (RA). We evaluated its potential cost-effectiveness and impact on the healthcare resource use. METHODS AND RESULTS: Angina-related healthcare resource usage and quality-of-life data were collected for 215 consecutive RA patients undergoing Reducer implantation in Belgium, the Netherlands, and Italy. Costs were assessed from each country's healthcare system perspective. Data from the date of RA diagnosis to Reducer implantation [Standard-of-Care (SoC)-period] and from Reducer implantation to follow-up (Reducer-period) were compared: during Reducer-period, a significant reduction in angina-driven hospitalizations, outpatient visits, coronary angiograms, and percutaneous coronary interventions per patient-year was observed, translating into significantly reduced costs per patient-year. To assess cost-effectiveness, costs and utilities of 1-year SoC were compared with those of 1-year Reducer-period. Assumptions on Reducer efficacy duration were further explored with modelled projections. Reducer was associated with higher quality-adjusted life years (QALYs: 0.665 vs. 0.580, P

The coronary sinus reducer (CSR) has been introduced as therapy for patients with refractory angina with no other treatment options. Aim of this study is to investigate the efficacy of the CSR in patients with refractory angina and presence of coronary chronic total occlusions (CTO). In this multicentre, international retrospective study, patients undergoing CSR implantation were screened and divided in 2 groups according to the presence/absence of CTO lesions. Baseline and clinical characteristics were analyzed in the 2 groups. Primary-outcome consisted of the variation in Canadian Cardiovascular Society (CCS) class at 6-month follow-up. Between January 2014 and December 2018, 205 patients with refractory angina were consecutively treated with the study device in the participating centers, 103 (50.2%) of which had a CTO lesion at coronary angiogram and formed the CTO-group. Baseline characteristics of the study population were well balanced between the 2 groups. CSR was successfully implanted in all cases. Baseline CCS class was 3 ± 0.5 in the CTO-group versus 3.1 ± 0.6 in the non-CTO group (p = 0.45), and improved at follow-up to 1.6 ± 0.9 versus 2 ± 1.1 respectively (p0.01), with a significantly higher improvement in CCS class in the CTO-group (1.4 ± 0.9 vs 1.1 ± 1 respectively, p = 0.01). Any improvement in CCS class was registered in 79 (80.6%) CTO-patients, while a significantly lower percentage (65 patients, 66.3%) of the non-CTO patients reported benefits in CCS class (p = 0.03). In conclusions, patients suffering from refractory angina with non-revascularized CTO lesions have a better response to CSR implantation than patients without CTOs. CSR implantation should be considered a valid complementary therapy to CTO-PCI in these patients.

Pronounced echocardiographically measured mechanical dyssynchrony is a positive predictor of response to cardiac resynchronization therapy (CRT), whereas right ventricular (RV) dysfunction is a negative predictor. The aim of this study was to investigate how RV dysfunction influences the association between mechanical dyssynchrony and left ventricular (LV) volumetric remodeling following CRT.One hundred twenty-two CRT candidates (mean LV ejection fraction, 19 ± 6%; mean QRS width, 168 ± 21 msec) were prospectively enrolled and underwent echocardiography before and 6 months after CRT. Volumetric remodeling was defined as percentage reduction in LV end-systolic volume. RV dysfunction was defined as RV fractional area change 35%. Mechanical dyssynchrony was assessed as time to peak strain between the septum and LV lateral wall, interventricular mechanical delay, and septal systolic rebound stretch. Simulations of heart failure with an LV conduction delay in the CircAdapt computer model were used to investigate how LV and RV myocardial contractility influence LV dyssynchrony and acute CRT response.In the entire patient cohort, higher baseline septal systolic rebound stretch, time to peak strain between the septum and LV lateral wall, and interventricular mechanical delay were all associated with LV volumetric remodeling in univariate analysis (R = 0.599, R = 0.421, and R = 0.410, respectively, P .01 for all). The association between septal systolic rebound stretch and LV volumetric remodeling was even stronger in patients without RV dysfunction (R = 0.648, P .01). However, none of the mechanical dyssynchrony parameters were associated with LV remodeling in the RV dysfunction subgroup. The computer simulations showed that low RV contractility reduced CRT response but hardly affected mechanical dyssynchrony. In contrast, LV contractility changes had congruent effects on mechanical dyssynchrony and CRT response.Mechanical dyssynchrony parameters do not reflect the negative impact of reduced RV contractility on CRT response. Echocardiographic prediction of CRT response should therefore include parameters of mechanical dyssynchrony and RV function.

Background: Myocardial perfusion imaging (MPI) is an accurate noninvasive test for patients with suspected obstructive coronary artery disease (CAD) and coronary artery calcium (CAC) score is known to be a powerful predictor of cardiovascular events. Collection of CAC scores simultaneously with MPI is unexplored. Aim: We aimed to investigate whether automatically derived CAC scores during myocardial perfusion imaging would further improve the diagnostic accuracy of MPI to detect obstructive CAD. Methods: We analyzed 150 consecutive patients without a history of coronary revascularization with suspected obstructive CAD who were referred for 82Rb PET/CT and available coronary angiographic data. Myocardial perfusion was evaluated both semi quantitatively as well as quantitatively according to the European guidelines. CAC scores were automatically derived from the low-dose attenuation correction CT scans using previously developed software based on deep learning. Obstructive CAD was defined as stenosis >70% (or >50% in the left main coronary artery) and/or fractional flow reserve (FFR) ≤0.80. Results: In total 58% of patients had obstructive CAD of which seventy-four percent were male. Addition of CAC scores to MPI and clinical predictors significantly improved the diagnostic accuracy of MPI to detect obstructive CAD. The area under the curve (AUC) increased from 0.87 to 0.91 (p: 0.025). Sensitivity and specificity analysis showed an incremental decrease in false negative tests with our MPI + CAC approach (n = 14 to n = 4), as a consequence an increase in false positive tests was seen (n = 11 to n = 28). Conclusion: CAC scores collected simultaneously with MPI improve the detection of obstructive coronary artery disease in patients without a history of coronary revascularization. Keywords: Coronary artery calcium, Obstructive coronary artery disease, Myocardial perfusion imaging, Deep learning, Cardiovascular imaging

Background Polymer‐free amphilimus‐eluting stents (PF‐AES) represent a novel elution‐technology in coronary stenting. We aimed to assess 1‐year clinical outcomes of PF‐AES as compared to latest‐generation permanent polymer zotarolimus‐eluting stents (PP‐ZES) in a real‐world all‐comers setting. Methods A prospective registry of patients treated with either PF‐AES or PP‐ZES between 2014 and 2016 was conducted. The primary outcome was defined as major adverse cardiac and cerebrovascular events (MACCE), and the secondary outcome was defined as target‐lesion failure (TLF) at 1 year. To account for measured confounders, a propensity‐score adjusted Cox proportional‐hazard model was built to evaluate clinical outcomes. Results A total of 734 consecutive patients with 1,269 DES implantations were enrolled. The population was characterized by 28% diabetes, 24% ST‐segment elevation myocardial infarction, and a high number of complex lesions (69%). The rate of MACCE was 11.5% for PF‐AES and 13.6% for PP‐ZES, plog‐rank = 0.11. TLF was numerically lower in PF‐AES as compared to PP‐ZES (5.4 vs. 6.1%, plog‐rank = 0.68). After propensity‐score adjustment, PF‐AES showed a trend toward a lower rate of MACCE and a favorable rate of TLF as compared to PP‐ZES (HR 0.70; 95%CI 0.45 to 1.10, P = 0.12; and HR 0.88; 95%CI 0.47 to 1.65, P = 0.68, respectively). Rates of definite ST were low (0.8 vs. 0.3%, plog‐rank = 0.62). Conclusions Our study suggests that implantation of PF‐AES was safe and effective in real‐world patients, with low‐rates of MACCE and TLF at 1 year. Our data needs to be confirmed by a large trial to evaluate the clinical outcomes of this novel polymer‐free, eluting‐technology used in PF‐AES.

IntroductionAnatomic stenosis evaluation on coronary CT angiography (CCTA) lacks specificity in indicating the functional significance of a stenosis. Recent developments in CT techniques (including dual-layer spectral detector CT [SDCT] and static stress CT perfusion [CTP]) and image analyses (including fractional flow reserve [FFR] derived from CCTA images [FFRCT] and deep learning analysis [DL]) are potential strategies to increase the specificity of CCTA by combining both anatomical and functional information in one investigation. The aim of the current study is to assess the diagnostic performance of (combinations of) SDCT, CTP, FFRCTand DL for the identification of functionally significant coronary artery stenosis.Methods and analysisSeventy-five patients aged 18 years and older with stable angina and known coronary artery disease and scheduled to undergo clinically indicated invasive FFR will be enrolled. All subjects will undergo the following SDCT scans: coronary calcium scoring, static stress CTP, rest CCTA and if indicated (history of myocardial infarction) a delayed enhancement acquisition. Invasive FFR of ≤0.80, measured within 30 days after the SDCT scans, will be used as reference to indicate a functionally significant stenosis. The primary study endpoint is the diagnostic performance of SDCT (including CTP) for the identification of functionally significant coronary artery stenosis. Secondary study endpoint is the diagnostic performance of SDCT, CTP, FFRCTand DL separately and combined for the identification of functionally significant coronary artery stenosis.Ethics and disseminationEthical approval was obtained. All subjects will provide written informed consent. Study findings will be disseminated through peer-reviewed conference presentations and journal publications.Trial registration numberNCT03139006; Pre-results.

Polymer-free amphilimus-eluting stents (PF-AES) represent a novel elution technology in the current era of drug-eluting stents. The clinical safety and efficacy of PF-AES as compared with latest-generation permanent-polymer zotarolimus-eluting stents (PP-ZES) have not yet been investigated in a large randomized trial.In this physician-initiated, prospective, multicenter, randomized, noninferiority trial, an all-comers population requiring percutaneous coronary intervention was enrolled across 3 European sites. Randomization (1:1 ratio) to PP-ZES or PF-AES was performed after stratification for troponin status and diabetes mellitus. In both treatment arms, troponin-positive patients were planned for 12-month dual antiplatelet therapy, whereas troponin-negative patients were planned for 1-month dual antiplatelet therapy. Outcome assessors were blinded to the allocated treatment. The device-oriented primary end point of target-lesion failure was defined as cardiac death, target-vessel myocardial infarction, or target-lesion revascularization at 12-months as analyzed by modified intention-to-treat (80% power, and a 3.5% noninferiority margin).In total, 1502 patients were randomized and 1491 treated with the assigned stent and available for follow-up. The primary end point occurred in 42 (5.6%) of the 744 patients receiving PP-ZES versus 46 (6.2%) of the 747 patients receiving PF-AES. PF-AES were clinically noninferior to PP-ZES (risk difference, 0.5%; upper limit 1-sided 95% confidence interval, 2.6%; PPF-AES were noninferior to PP-ZES regarding target-lesion failure at 12 months. Findings regarding the secondary end point and prespecified subgroups were generally consistent with that of the primary end point.URL: https://www.clinicaltrials.gov . Unique identifier: NCT02328898.

A 62-year old male underwent treatment of a bifurcation lesion in the left anterior descending coronary artery using provisional stenting with a jailed wire technique. Severe longitudinal stent deformation and unravelment of the stent part proximal of the bifurcation occurred when we tried to pull the jailed wire from the side branch. The described case poses a caution on the use of this specific stent(-design) in bifurcation lesions.

Introduction Predicting reverse remodeling after cardiac resynchronization therapy (CRT) remains challenging and different etiologies of heart failure might hamper identification of predictors. Objective Assess the incremental value of mechanical dyssynchrony besides electrical dyssynchrony for predicting CRT response. Methods 227 patients (51% ischemic) received CRT. Response was defined as ≥ 15% left ventricular end systolic volume decrease after six months. Prediction models were developed comprising clinical parameters and electrical dyssynchrony (Model A), subsequently complemented with mechanical dyssynchrony (Model B). Models were compared by area under the receiver-operating curve (AUC), net reclassification index (NRI) and integrated discrimination improvement (IDI) for the complete cohort, ischemic (ICM) and non-ischemic (NICM) subpopulations. Results Model B performed significantly better than Model A supported by AUC, NRI and IDI. Furthermore, model B significantly better predicted response for NICM than ICM. Conclusion Electrical dyssynchrony and mechanical dyssynchrony are essential to predict CRT response. Nevertheless, response prediction for ICM remains challenging.

Background— The power of echocardiographic dyssynchrony indices to predict response to cardiac resynchronization therapy (CRT) appears to vary between indices and between studies. We investigated whether the variability of predictive power between the dyssynchrony indices can be explained by differences in their operational definitions. Methods and Results— In 132 CRT-candidates (left ventricular [LV] ejection fraction, 19 ± 6%; QRS width, 170 ± 22 ms), 4 mechanical dyssynchrony indices (septal systolic rebound stretch [SRSsept], interventricular mechanical dyssynchrony [IVMD], septal-to-lateral peak shortening delay [Strain-SL], and septal-to-posterior wall motion delay [SPWMD]) were quantified at baseline. CRT response was quantified as 6-month percent change of LV end-systolic volume. Multiscale computer simulations of cardiac mechanics and hemodynamics were used to assess the relationships between dyssynchrony indices and CRT response within wide ranges of dyssynchrony of LV activation and reduced contractility. In patients, SRSsept showed best correlation with CRT response followed by IVMD, Strain-SL, and SPWMD ( R =−0.56, −0.50, −0.48, and −0.39, respectively; all P Conclusions— The power to predict CRT response differs between indices of mechanical dyssynchrony. SRSsept and IVMD better represent LV dyssynchrony amenable to CRT and better predict CRT response than the indices assessing time-to-peak deformation or motion.

Septal rebound stretch (SRSsept) is a distinctive characteristic of discoordination-related mechanical inefficiency. We assessed how intermediate- and long-term outcome after cardiac resynchronization therapy (CRT) relate to baseline SRSsept.A total of 101 patients (age 65 ± 11 years, 69 men, 18 New York Heart Association (NYHA) class IV, QRS 173 ± 23 ms) scheduled for CRT underwent clinical assessment, echocardiography, and brain-type natriuretic peptide (BNP) measurements before and 6.4 ± 2.3 months after CRT. Baseline SRSsept (all systolic stretch after initial shortening in the septum) was quantified by speckle tracking echocardiography. Primary composite end point was death, urgent cardiac transplantation, or left ventricular assist device implantation at the end of the study. Secondary end points were intermediate-term (6 months) response, quantified as decreases in left ventricular end-systolic volume (ΔLVESV) and BNP (ΔBNP). After a mean clinical follow-up of 15.6 ± 9.0 months; 23 patients had reached the primary end point. Baseline SRSsept (hazard ratio [HR] 0.742; 95% confidence intervals [CI] 0.601-0.916, P.01]) was independently associated with a better outcome and NYHA class (HR 5.786: 95% CI 2.341-14.299, P.001) with a worse outcome. Contrary to baseline NYHA class, baseline SRSsept was an independent predictor of both ΔLVESV (beta 0.53; P.001) and ΔBNP (beta 0.29; P.01). Intermediate-term ΔLVESV and ΔBNP were associated with a favorable long-term outcome.SRSsept at baseline is a strong, independent predictor of long-term prognosis after CRT and of improvements in left ventricular remodeling and neurohormonal activation at intermediate term.

Aims The aim of this study was to investigate (i) the baseline patterns of segmental peak myocardial strain (PMS) in heart failure (HF) patients with ventricular conduction delay, (ii) changes in patterns of segmental PMS induced by cardiac resynchronization therapy (CRT), and (iii) whether they differ between CRT responders and non-responders. Methods and results Segmental and global longitudinal (L-) and radial (R-) PMS measurements derived from speckle tracking were prospectively obtained in 85 HF patients with intraventricular conduction delay before and 6 months after CRT device implantation and in 30 healthy subjects. Segmental strain analysis in HF patients showed pronounced heterogeneity both in longitudinal and in radial directions with the lowest amplitudes in the septum and the highest amplitudes in the lateral and posterior walls. After CRT, 60% of the patients were responders (≥15% reduction in end-systolic volume). Before CRT, responders showed higher global R-PMS than non-responders (19.5 ± 13.4 vs.13.1 ± 4.8%, respectively; P = 0.04) despite similar global L-PMS. After CRT, responders showed an increase in L-PMS in most segments and a homogeneous increase in R-PMS, leading to a more uniform pattern of strain and an improved global L-PMS and R-PMS. In contrast, in non-responders, the gain in L-PMS and R-PMS in septal segments was completely offset by a decrease in posterolateral segments, failing to decrease segmental heterogeneity and to increase global L-PMS and R-PMS. Conclusion Heart failure patients with ventricular conduction delay show pronounced heterogeneous patterns of segmental PMS, which can be reversed by CRT.

Aims Optimal left ventricular (LV) lead position improves the response to cardiac resynchronization therapy (CRT). However, in some patients it is not possible to position the LV lead at an optimal pacing site. The aim of this study was to determine whether optimization of the pacing settings atrioventricular delay (AVD) and interventricular delay (VVD) can compensate for a non-optimal LV pacing site. Methods and results In 16 patients with heart failure [New York Heart Association class III (13) or IV (3), median QRS duration of 172 ms and median LV ejection fraction of 20%] the acute haemodynamic effect of biventricular pacing was assessed at ≥2 pacing sites by the increase in maximum rate of LV pressure rise (%d P /d t max). At each site the AVD and VVD were optimized. Biventricular pacing with nominal settings at a non-optimal LV pacing site improved d P /d t max by 12.8% (−0.5 to 23.2%). This could be further improved by 6.5 percentage points (1.2–13.9) by optimization of pacing settings ( P = 0.001) and by 9.9 percentage points (3.7–13.3, P = 0.004) by optimization of pacing site. Optimization of the LV pacing site and pacing settings together improved %d P /d t max by 16.2 per cent points (10.0–21.8, P < 0.001). Conclusion Optimization of the AVD and VVD can partly compensate for a non-optimal LV pacing site. However, a combination of an optimal LV pacing site and optimized pacing settings gives the best acute haemodynamic response.

Background: Recent, conflicting results about the use of tissue Doppler imaging derived (TDI-) asynchrony indices to predict reverse remodelling after cardiac resynchronisation therapy (CRT) have raised questions about their physiological meaning and methodological limitations. Methods: In 41 patients, baseline TDI-derived septal to lateral delays of peak velocities (TDI-SL), standard deviation of peak velocities over 12 segments (Ts-SD), and peak 2D longitudinal strain (strain-SL) were compared with volumetric response (reduction in end-systolic volume of ≥ 15%) after at least 6 months of CRT. Timing of peak TDI velocities was compared to timing of 2DS velocities and strain-SL. Influence of sample position, transverse motion, and interobserver inconsistency of the chosen peak velocities was assessed. Diagnostic accuracy of TDI-based delays was compared to accuracy of visual and 2D strain-based assessment. Results: After 7.0±3.2 months of CRT, 24 patients were classified as responders. TDI-SL and Ts-SD were similar between responders and nonresponders at baseline, did not predict response, and were unaffected by CRT. Visual asynchrony scoring and strain-SL were better predictors of response than TDI-SL and Ts-SD. TDI measurements were highly susceptible to sample location and transverse motion components and poorly correlated with the timing of longitudinal contraction. There was a considerably poor agreement between observers with regard to scoring of TDI-SL and Ts-SD. Conclusion: TDI-based measurements of asynchrony do not appear robust predictors of volume response to CRT.

A 55-year-old woman with dilated cardiomyopathy and rate-dependent left bundle branch block had a cardiac resynchronisation therapy (CRT) device implanted. During implantation, the maximum rate of left ventricular pressure rise (dP/dt(max)) was measured invasively. This case presents a description of the acute negative effect of a left bundle branch block on dP/dt(max), and the different effect of CRT on left ventricular haemodynamic function in the presence and absence of a left bundle branch block.

In this article we present the myocardial deformation imaging (MDI) studies of three daughters of a man with hypertrophic cardiomyopathy (HCM) who died suddenly. The daughters had been referred for genetic counselling several months earlier. We demonstrate that, despite the absence of conventional two-dimensional echo characteristics of HCM, MDI accurately and easily demonstrated the presence of the disease in the two daughters with the genetic disorder. (Neth Heart J 2010;18:552-4.).

Background— Response to cardiac resynchronization therapy depends both on dyssynchrony and (regional) contractility. We hypothesized that septal deformation can be used to infer integrated information on dyssynchrony and regional contractility, and thereby predict cardiac resynchronization therapy response. Methods and Results— In 132 cardiac resynchronization therapy candidates with left bundle branch block (LBBB)-like electrocardiogram morphology (left ventricular ejection fraction 19±6%; QRS width 170±23 ms), longitudinal septal strain was assessed by speckle tracking echocardiography. To investigate the effects of dyssynchronous activation and differences in septal and left ventricular free wall contractility on septal deformation pattern, we used the CircAdapt computer model of the human heart and circulation. In the patients, 3 characteristic septal deformation patterns were identified: LBBB-1=double-peaked systolic shortening (n=28); LBBB-2=early systolic shortening followed by prominent systolic stretching (n=34); and LBBB-3=pseudonormal shortening with less pronounced late systolic stretch (n=70). LBBB-3 revealed more scar (2 [2–5] segments) compared with LBBB-1 and LBBB-2 (both 0 [0–1], P Conclusions— A double-peaked systolic septal deformation pattern is characteristic for LBBB and results from intraventricular dyssynchrony. Abnormal contractility modifies this pattern. A computer model can be helpful in understanding septal deformation and predicting cardiac resynchronization therapy response.

Echocardiography plays an important role in patient assessment before cardiac resynchronization therapy (CRT) and can monitor many of its mechanical effects in heart failure patients. Encouraged by the highly variable individual response observed in the major CRT trials, echocardiography-based measurements of mechanical dyssynchrony have been extensively investigated with the aim of improving response prediction and CRT delivery. Despite recent setbacks, these techniques have continued to develop in order to overcome some of their initial flaws and limitations. This review discusses the concepts and rationale of the available echocardiographic techniques, highlighting newer quantification methods and discussing some of the unsolved issues that need to be addressed.

Pacing experiments in healthy animal hearts have suggested a larger detrimental effect of septal compared to free wall preexcitation. We investigated the intrinsic relation among the site of electrical preexcitation, mechanical dyssynchrony, and dysfunction in human patients. In 33 patients with Wolff-Parkinson-White (WPW) syndrome and 18 controls, regional myocardial deformation was assessed by speckle tracking mapping (ST-Map) to assess the preexcitation site, shortening sequences and dyssynchrony, and the extent of local and global ejecting shortening. The ST-Map data in patients with accessory atrioventricular pathways correctly diagnosed as located in the interventricular septum (IVS) (n = 11) or left ventricular free wall (LFW) (n = 12) were compared to the corresponding control values. A local ejecting shortening of2 SD of the control values identified hypokinetic segments. The localization of the atrioventricular pathways by ST-Map matched with the invasive electrophysiology findings in 23 of 33 patients and was one segment different in 5 of 33 patients. In both WPW-IVS and WPW-LFW, local ejecting shortening was impaired at the preexcitation site (p0.01). However, at similar electrical and mechanical dyssynchrony, WPW-IVS had more extensive hypokinesia than did WPW-LFW (3.6 +/- 0.9 vs 1.8 +/- 1.3 segments, p0.01). Compared to controls, the left ventricular function was significantly reduced only in WPW-IVS (global ejecting shortening 17 +/- 2% vs 19 +/- 2%, p = 0.01; ejection fraction 55 +/- 5% vs 59 +/- 3%, p = 0.02). In conclusion, preexcitation is associated with local hypokinesia, which at comparable preexcitation is more extensive in WPW-IVS than in WPW-LFW and could adversely affect ventricular function. ST-Map might have a future role in detecting and guiding treatment of septal pathways with significant mechanical effects.

Aims To develop a novel myocardial deformation index that is highly sensitive to the effect of cardiac resynchronization therapy (CRT) and that can be used to predict response to CRT. Methods and results Before and 6.5 ± 2.3 months after implantation of a CRT device, longitudinal shortening and stretch were timed and quantified by speckle tracking echocardiography in a cohort of 62 patients. Distinction was made between systolic total stretch (STS; all systolic stretch) and systolic rebound stretch (SRS; only systolic stretch following initial shortening). Systolic total stretch and SRS could be measured in all wall segments in 41 of 62 patients. Septal SRS quantification was possible in all 62 patients and was performed by a blinded observer. Cardiac resynchronization therapy reduced STS (−55 ± 30%) but reduced SRS (−77 ± 21%) significantly more (P < 0.01). The largest amount of baseline SRS and the largest reductions in SRS (−90 ± 22%) were found in the septum. Reductions in local SRS were paralleled by increases in local systolic shortening that were twice as large (r = 0.79), thereby strongly improving septal function. Baseline values of septal SRS correlated with reductions in left ventricular end-systolic volume index (ΔLVESVi; r = 0.62) and brain-type natriuretic peptide (BNP) (Δlog10BNP; r = 0.57). Septal SRS was an independent predictor of CRT response in linear regression analysis and predicted ΔLVESVi of ≥15% with a sensitivity and specificity of 81% at ROC analysis (areas under the curve 0.89 ± 0.04). Conclusion Septal rebound stretch appears to be a sensitive and practical diagnostic criterion to quantify the functional substrate amenable to CRT and to predict response.

In a recent issue of the Journal, Duckett et al. ([1][1]) published a study indicating that the acute hemodynamic response ([AHR], assessed by LVdP/dtmax, the maximum rate of rise of left ventricular pressure) predicts reverse remodeling ([RR], which is the decrease in left ventricular end-systolic