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Background: Fractional flow reserve (FFR) has emerged as the invasive gold standard for assessing vessel-specific ischemia. However, FFR measurements are influenced by the hydrostatic effect, which might adversely impact the assessment of ischemia., Aims: This study aimed to investigate the impact of hydrostatic pressure on FFR measurements by correcting for the height and comparing FFR with [ 15 O]H 2 O positron emission tomography (PET)-derived relative flow reserve (RFR)., Methods: The 206 patients were included in this analysis. Patients underwent coronary computed tomography angiography (CCTA), [ 15 O]H 2 O PET, and invasive coronary angiography with routine FFR in every epicardial artery. Height differences between the aortic guiding catheter and distal pressure sensor were quantified on CCTA images. An FFR ≤ 0.80 was considered significant., Results: The study found a reclassification in 7% of the coronary arteries. Notably, 11% of left anterior descending (LAD) arteries were reclassified from hemodynamically significant to nonsignificant. Conversely, 6% of left circumflex (Cx) arteries were reclassified from nonsignificant to significant. After correcting for the hydrostatic pressure effect, the correlation between FFR and PET-derived RFR increased significantly from r = 0.720 to r = 0.786 (p = 0.009). The average magnitude of correction was +0.05 FFR units in the LAD, -0.03 in the Cx, and -0.02 in the right coronary artery., Conclusion: Hydrostatic pressure has a small but clinically relevant influence on FFR measurements obtained with a pressure wire. Correcting for this hydrostatic error significantly enhances the correlation between FFR and PET-derived RFR., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Importance: An upper-extremity approach for secondary access during transfemoral transcatheter aortic valve implantation (TAVI) may reduce clinically relevant secondary access site-related bleeding., Objective: To investigate the safety and efficacy of an upper-extremity approach compared with a lower-extremity approach in patients undergoing TAVI., Design, Setting, and Participants: The TAVI XS trial was a randomized clinical trial performed between November 28, 2022, and November 15, 2023, with a 30-day follow-up, in 4 TAVI centers in the Netherlands. Eligibility was determined first, and only those patients with severe aortic stenosis and no contraindication for upper- or lower-extremity secondary access were informed about the study and asked to participate., Intervention: Participants were randomized 1:1 between the upper-extremity approach (radial artery diagnostic access and upper-arm vein for temporary pacing lead placement) and lower-extremity approach (femoral artery diagnostic access and femoral vein for temporary pacing lead placement) for secondary access during TAVI., Main Outcomes and Measures: Primary end point was clinically relevant bleeding (Bleeding Academic Research Consortium type 2, 3, or 5) of the randomized secondary access. Secondary end points included any clinically relevant bleeding, time to mobilization, duration of hospitalization, secondary access failure, and procedural time., Results: Of a total of 324 eligible patients, 238 patients undergoing transfemoral TAVI (mean [SD] age, 79.4 [6.5] years; 150 male [63.0%]; median European System for Cardiac Operative Risk Evaluation II score, 2.2% [IQR, 1.5%-3.5%]) were included. The primary end point occurred in 5 of 119 patients (4.2%) in the upper-extremity group and 16 of 119 (13.4%) in the lower-extremity group (odds ratio [OR], 0.28 [95% CI, 0.10-0.80]; P = .01). Incidence of any clinically relevant bleeding was decreased in the upper-extremity group (25 of 119 [21.0%] vs 41 of 119 [34.5%] patients; OR, 0.51 [95% CI, 0.28-0.91]; P = .02). There was no difference in time to mobilization or duration of hospitalization. Secondary access failure (14 of 119 [11.8%] vs 1 of 119 [0.8%] patients; OR, 15.73 [95% CI, 2.03-121.69]; P = .001) and procedural time (60.0 [IQR, 39.0-88.0; 95% CI, 53.0-70.0] vs 48.0 [IQR, 34.0-64.0; 95% CI, 40.0-55.0] minutes; P = .002) were higher in the upper-extremity cohort., Conclusion and Relevance: In this randomized clinical trial of patients undergoing transfemoral TAVI, the upper-extremity approach for secondary access was associated with less clinically relevant access site-related bleeding compared with the conventional lower-extremity approach and should be considered to reduce periprocedural bleeding complications., Trial Registration: ClinicalTrials.gov Identifier: NCT05672823.

Non-culprit coronary artery lesions are commonly present in patients presenting with an acute coronary syndrome (ACS). Additional stenting of non-culprit lesions in addition to the culprit lesion intends to prevent secondary events caused by these lesions. At the same time, multiple trials have demonstrated the potential of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in reducing plaque size and changing plaque composition of non-culprit lesions. Whether intensive low-density lipoprotein cholesterol (LDL-C) reduction with PCSK9 inhibitor evolocumab improves non-culprit vessel hemodynamics, reduces the risk of plaque rupture of important non-culprit lesions, and might obviate the need for additional stenting has not been investigated. The "Functional Improvement of non-infarcT related coronary artery stenosis by Extensive LDL-C Reduction with a PCSK9 Antibody" (FITTER) trial is a multi-center, randomized, double-blind, placebo-controlled clinical trial for patients presenting with ACS and multivessel disease (MVD). After treatment of the culprit lesion, fractional flow reserve (FFR) is performed in non-culprit vessels amenable for percutaneous coronary intervention (PCI). Coronary intervention in patients with hemodynamically important non-critical lesions (FFR: 0.67-0.85) is staged after baseline imaging using near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS). Eligible patients are randomized and treated for 12 weeks with either evolocumab or placebo, in addition to high-intensity statin therapy. Follow-up angiography with repeat FFR and IVUS-NIRS is scheduled at 12 weeks. Staged PCI is performed at the operator's discretion.The FITTER trial is the first study to evaluate the effect of maximal LDL-C reduction by the PCSK9 inhibitor evolocumab on invasively measured FFR, plaque size, and plaque composition in hemodynamically important non-culprit lesions, during a treatment period of just 12 weeks after an ACS. Currently, all patients have been included (August 2023) and data analysis is ongoing., Trial Registration Number: clinicaltrials.gov NCT04141579., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert-Jan M van Geuns reports financial support and equipment, drugs, or supplies were provided by Amgen Inc. Robert-Jan M van Geuns reports financial support and equipment, drugs, or supplies were provided by 10.13039/100018503Infraredx Inc. Robert-Jan M van Geuns reports financial support was provided by HealthHolland. Pieter C Smits reports a relationship with Abbott Vascular Inc that includes: funding grants and speaking and lecture fees. Pieter C Smits reports a relationship with Shanghai MicroPort Medical Group Co Ltd that includes: funding grants and speaking and lecture fees. Pieter C Smits reports a relationship with SMT that includes: funding grants and speaking and lecture fees. Pieter C Smits reports a relationship with Terumo Medical Corporation that includes: speaking and lecture fees. Robert A Byrne reports a relationship with Abbott Vascular Inc that includes: funding grants. Robert A Byrne reports a relationship with Biosensors that includes: funding grants. Robert A Byrne reports a relationship with 10.13039/100008497Boston Scientific Corporation that includes: funding grants. Robert A Byrne reports a relationship with Translumina GmbH that includes: funding grants. Niels van Royen reports a relationship with BIOTRONIK Inc that includes: funding grants. Niels van Royen reports a relationship with Abbott Vascular Inc that includes: funding grants and speaking and lecture fees. Niels van Royen reports a relationship with Medtronic Inc that includes: funding grants. Niels van Royen reports a relationship with Philips that includes: funding grants. Niels van Royen reports a relationship with Rainmed that includes: speaking and lecture fees. Niels van Royen reports a relationship with Shanghai MicroPort Medical Group Co Ltd that includes: speaking and lecture fees. Niels van Royen reports a relationship with Bayer AG that includes: speaking and lecture fees. Robert-Jan M van Geuns reports a relationship with Abbott Vascular Inc that includes: speaking and lecture fees. Robert-Jan M van Geuns reports a relationship with AstraZeneca that includes: funding grants and speaking and lecture fees. Robert-Jan M van Geuns reports a relationship with Sanofi that includes: funding grants and speaking and lecture fees. Robert-Jan M van Geuns reports a relationship with Amgen Inc that includes: funding grants and speaking and lecture fees. Robert-Jan M van Geuns reports a relationship with 10.13039/100018503Infraredx Inc that includes: funding grants and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes., Methods: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI., Results: A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 0.87±0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65 [95% CI, 0.61-0.69]; P <0.001) and demonstrated excellent predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79-0.84]; P <0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 0.54 [95% CI, 0.50-0.57]). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared with those with focal disease (odds ratio, 1.71 [95% CI, 1.00-2.97])., Conclusions: Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789317., Competing Interests: Dr Collet reports receiving research grants from Biosensors, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; consultancy fees from HeartFlow, OpSens Medical, Abbott Vascular, and Philips Volcano; and has patents pending on diagnostic methods for coronary artery disease. Dr Munhoz reports a research grant provided by the CardioPath PhD programme and speaker fees from Abbott Vascular. Dr Mizukami reports receiving research grants from Boston Scientific and speaker fees from Abbott Vascular, CathWorks, and Boston Scientific. Dr Matsuo has received consulting fees from Kaneka and Zeon and speaker’s fees from Abbott Medical Japan, Boston Scientific, Philips, and Amgen. Dr Ko has received consulting fees from Canon Medical, Abbott, and Medtronic. Dr Biscaglia received research grants provided by Sahajanand Medical Technologies, Medis Medical Imaging, Eukon Srl, Siemens Healthineers, General Electric Healthcare, and Insight Lifetech. Dr Engstrøm reports speaker and advisory board fees from Abbott, Boston Scientific, and Novo Nordisk. Dr Leone reports receiving consultancy fees from Abbott and honoraria for sponsored symposia from Abbott, Medtronic, and Abiomed. Dr Fearon receives institutional research support from Abbott, Boston Scientific, and Medtronic and has consulting relationships with CathWorks and Siemens and stock options from HeartFlow. Dr Christiansen has received consulting fees from Abbott Medical Denmark A/S. Dr Yong has received minor honoraria from Abbott Vascular and research grants from Abbott Vascular and Philips. Dr Escaned is supported by the Intensification of Research Activity project INT22/00088 from the Spanish Instituto de Salud Carlos III and received speaker and advisory board member fees from Abbott and Philips. Dr Storozhenko reports a grant provided by the EAPCI Fellowship Programme. Dr West is an employee of Abbott Vascular. Dr De Potter is a paid consultant for Biosense Webster and receives grant support (institutional) and consultancy fees (institutional) from Abbott. Dr Berry receives research funding from the British Heart Foundation (grants RE/18/6134217, BHF/FS/17/26/32744, and PG/19/28/34310) and is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Coroventis Research, GlaxoSmithKline, HeartFlow, Menarini, Novartis, Servier, Siemens Healthcare, and Valo Health. Dr Collison has received consulting fees from Abbott. Dr Johnson has received consultancy or speaker fees from Abbott Vascular, Boston Scientific, Medtronic, Shockwave, and Terumo, and research grants from Abbott Vascular. Dr Amano reports receiving lecture fees from Astellas Pharma, Astra Zeneca, Bayer, Daiichi Sankyo, and Bristol Myers Squibb. Dr Perera has received research grant support from Abbott Vascular, HeartFlow, and Philips. Dr Jeremias has received consulting fees from Canon Medical, Artrya Medical, and Boston Scientific. Dr Ali reports institutional grant support from Abbott, Abiomed, Acist, Amgen, Boston Scientific, CathWorks, Canon Medical, Conavi, HeartFlow, Inari, Medtronic, the US National Institutes of Health, Nipro, OpSens Medical, Medis, Philips, Shockwave, Siemens, SpectraWAVE, and Teleflex; consulting fees from Abiomed, Astra Zeneca, Boston Scientific, CathWorks, OpSens Medical, Philips, and Shockwave; and equity in Elucid, Lifelink, SpectraWAVE, Shockwave, and VitalConnect. Dr Pijls has received research grants from Abbott and Hexacath; consultancy fees from Abbott, GE, Philips, and HeartFlow; and has equity in General Electric, Philips, and HeartFlow. Dr De Bruyne reports receiving consultancy fees from Boston Scientific and Abbott and research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular. Dr Johnson received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; has received significant institutional research support from St Jude Medical (CONTRAST [Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology?; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02184117]) and Philips Volcano (DEFINE-FLOW [Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02328820]) for other studies using intracoronary pressure and flow sensors; has an institutional licensing agreement with Boston Scientific for the smart-minimum FFR algorithm (now commercialized under 510[k] K191008); and has patents pending on diagnostic methods for quantifying aortic stenosis and TAVI physiology and on methods to correct pressure tracings from fluid-filled catheters.

Background: During transcatheter aortic valve implantation (TAVI), secondary access is required for angiographic guidance and temporary pacing. The most commonly used secondary access sites are the femoral artery (angiographic guidance) and the femoral vein (temporary pacing). An upper extremity approach using the radial artery and an upper arm vein instead of the lower extremity approach using the femoral artery and femoral vein may reduce clinically relevant secondary access site-related bleeding complications, but robust evidence is lacking., Trial Design: The TAVI XS trial is a multicentre, randomised, open-label clinical trial with blinded evaluation of endpoints. A total of 238 patients undergoing transfemoral TAVI will be included. The primary endpoint is the incidence of clinically relevant bleeding (i.e. Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding) of the randomised secondary access site (either diagnostic or pacemaker access, or both) within 30 days after TAVI. Secondary endpoints include time to mobilisation after TAVI, duration of hospitalisation, any BARC type 2, 3 or 5 bleeding, and early safety at 30 days according to Valve Academic Research Consortium‑3 criteria., Conclusion: The TAVI XS trial is the first randomised trial comparing an upper extremity approach to a lower extremity approach with regard to clinically relevant secondary access site-related bleeding complications. The results of this trial will provide important insights into the safety and efficacy of an upper extremity approach in patients undergoing transfemoral TAVI., (© 2024. The Author(s).)

Background: Fluid-filled pressure guidewires are unaffected by the previously inevitable hydrostatic pressure gradient (HPG). This study aimed to compare simultaneous pressure measurements with fluid-filled and sensor-tipped pressure guidewires., Methods: Fifty patients underwent fractional flow reserve (FFR) and P d /P a measurement with a fluid-filled and a sensor-tipped pressure guidewire simultaneously. To assess maneuverability, patients were randomized with respect to which pressure guidewire was used to cross the lesion first. Lateral fluoroscopy was used to estimate height difference between catheter tip and distal wire position (and thus HPG). Agreement between pressure measurements was studied., Results: Measurements were performed in LM (4% (n = 2)), LAD (44% (n = 22)), LCX (26% (n = 13)), and RCA (26% (n = 13)). Simultaneous pressure measurements showed excellent agreement (mean FFR difference - 0.01 ± 0.03 (r = 0.959, p < 0.001), mean P d /P a difference - 0.01 ± 0.04 (r = 0.929, p < 0.001)). FFR was ≤0.80 in 42.6% (n = 20) with fluid-filled FFR measurements versus 46.8% (n = 22) by sensor-tipped FFR measurements. Mean height difference was 15 ± 34 mm, and strongly dependent on the coronary artery (LAD 45 ± 10 mm, LCX -23 ± 16 mm, RCA -13 ± 17 mm). There was a strong correlation between height difference and difference in pressure ratios between sensor-tipped and fluid-filled pressure guidewires (FFR r = -0.850, p < 0.001; P d /P a r = -0.641, p < 0.001). Largest FFR differences were present in the LAD (-0.04 ± 0.02). After HPG correction, mean difference between HPG-corrected sensor-tipped FFR and fluid-filled FFR was 0.00 ± 0.02, mean P d /P a difference was 0.01 ± 0.03., Conclusions: This study shows excellent overall correlation between FFR and P d /P a measurements with both pressure guidewires. Differences measured with fluid-filled and sensor-tipped pressure guidewires are vessel-specific and attributable to hydrostatic pressure gradients (NCT04802681)., Competing Interests: Declaration of competing interest PT received research grants from Cavis Technologies AB, Biosensors, OpSens Medical and lecture fees from Medtronic. NvR received personal fees from Abbott, Rainmed, Microport and Bayer and received research grants from Philips, Biotronik, Abbott, and Medtronic. EH is a former employee of Cavis Technologies AB. The other authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

A 25-year-old male with neurofibromatosis type 1 presented with acute ST-segment elevation myocardial infarction. Coronary imaging revealed an aberrant right coronary anatomy, ectatic coronary arteries, and significant stenosis. Based on previous literature and clinical presentation, this case highlights the potential role of neurofibromatosis in the pathogenesis of coronary artery disease., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background The femoral vein is commonly used as a pacemaker access site during transcatheter aortic valve replacement (TAVR). Using an upper arm vein as an alternative access site potentially causes fewer bleeding complications and shorter time to mobilization. We aimed to assess the safety and efficacy of an upper arm vein as a temporary pacemaker access site during TAVR. Methods We evaluated all patients undergoing TAVR in our center between January 2020 and January 2023. Upper arm, femoral, and jugular vein pacemaker access was used in 255 (45.8%), 191 (34.3%), and 111 (19.9%) patients, respectively. Clinical outcomes were analyzed according to pacemaker access in the overall population and in a propensity-matched population involving 165 upper arm and 165 femoral vein patients. Primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 pacemaker access site-related bleeding. Results In the overall population, primary endpoint was lowest for upper arm, followed by femoral and jugular vein access (2.4% vs. 5.8% vs. 10.8%, p = 0.003). Time to mobilization was significantly longer ( p < 0.001) in the jugular cohort compared with the other cohorts. In the propensity-matched cohort, primary endpoint showed a trend toward lower occurrence in the upper arm compared with the femoral cohort (2.4% vs. 6.1%, p = 0.10). Time to mobilization was significantly shorter (480 vs. 1140 min, p < 0.001) in the upper arm cohort, with a comparable skin-to-skin time (83 vs. 85 min, p = 0.75). Cross-over from upper arm pacemaker access was required in 17 patients (6.3% of attempted cases via an upper arm vein). Conclusions Using an upper arm vein as a temporary pacemaker access site is safe and feasible. Its use might be associated with fewer bleeding complications and shorter time to mobilization compared with the femoral vein.

Objectives: This study evaluates clinical outcomes after implementing a liberal post-dilatation strategy during PCI., Background: Post-dilatation after percutaneous coronary intervention (PCI) is performed to achieve optimal stent expansion and reduce complications. However, its prognostic effects are unclear and conflicting., Methods: This study is a pre-post-intervention analysis of two cohorts, before (2015-2017) and after (2018-2020) implementation of a liberal post-dilatation strategy. The primary end point consisted of major adverse cardiovascular events (MACE) at 30 days. Secondary end points consisted of the individual components of the primary end point as well as 1 year mortality and target vessel revascularization., Results: A total of 10,153 patients were included: 5,383 in the pre-cohort and 4,770 in the post-cohort. The 30-day MACE was 5.00% in the pre-cohort and 4.09% in the post-cohort (p = 0.008; OR 0.75 (CI 0.61-0.93)). There was a significant difference between the pre- and post-cohort in 30-day mortality, respectively, 2.91% and 2.25% (p = .01; OR 0.70 (CI 0.53-0.93)), and MI at 30 days, 1.17% versus 0.59% (p = .003; OR 0.49 (CI 0.31-0.78)). At 1 year, there was a significant difference in mortality between the pre-cohort, 5.84%, and post-cohort, 5.19% (p = .02; OR 0.79 (CI 0.66-0.96))., Conclusions: A liberal post-dilatation strategy after PCI was associated with a significant decrease in 30-day MACE, 30-day MI, 30-day mortality, and 1-year mortality. Future studies are warranted to validate the causality between post-dilatation and improvement of clinical outcomes., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Introduction: Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum., Aim: The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR., Methods: This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least 1 lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events., Results: Recruitment is ongoing and is expected to be completed in the second half of 2023., Conclusion: This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the preprocedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes., Competing Interests: Disclosures AML reports receiving consultancy fees from Abbott and honoraria for sponsored symposiums from Abbott, Medtronic and Abiomed. DM report a research grant provided by the Cardiopath PhD program and speaker fees from Abbott Vascular. BDB reports receiving consultancy fees from Boston Scientific and Abbott and research grants from Coroventis Research, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc. and Abbott Vascular. CC reports receiving research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc. and Abbott Vascular; and consultancy fees from Heart Flow Inc, Opsens, Abbott Vascular and Philips Volcano. BK has received consulting fees from Canon Medical, Abbott and Medtronic. AI has received consulting fees from Canon, Artrya Medical and Boston Scientific. TWJ has received consultancy/speaker fees from Abbott Vascular, Boston Scientific, Medtronic, Shockwave, Terumo and research grants from Abbott Vascular. NPJ received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; has received significant institutional research support from St. Jude Medical (CONTRAST, NCT02184117) and Philips Volcano Corporation (DEFINE-FLOW, NCT02328820) for other studies using intracoronary pressure and flow sensors; has an institutional licensing agreement with Boston Scientific for the smart-minimum FFR algorithm (now commercialized under 510(k) K191008); and has patents pending on diagnostic methods for quantifying aortic stenosis and TAVI physiology, and on methods to correct pressure tracings from fluid-filled catheters. SB received research grants provided by Sahajanand Medical Technologies Ltd (SMT), Medis Medical Imaging Systems, Eukon S.r.l., Siemens Healthineers, General Electric (GE) Healthcare, and Insight Lifetech. EHC has received consulting fees from Abbott Medical Denmark A/S. CB receives research funding from the British Heart Foundation (RE/18/6134217, BHF/FS/17/26/32744, PG/19/28/34310). Colin Berry is employed by the University of Glasgow which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Coroventis, GSK, HeartFlow, Menarini, Novartis, Servier, Siemens Healthcare, and Valo Health. WFF receives institutional research support from Abbot, Boston, and Medtronic and has consulting relationships with CathWorks and Siemens and stock options with HeartFlow. TE reports speakers and advisory board fees from Abbott, Boston and Novo Nordisk. AY has received minor honoraria from Abbott Vascular, and research grants from Abbott Vascular and Philips. DC has received consulting fees from Abbott. TS reports a grant provided by the EAPCI Fellowship Programme., (Copyright © 2023 Elsevier Inc. All rights reserved.)

When measuring hyperemic and nonhyperemic pressure ratios with traditional sensor-tipped wires, the inevitable hydrostatic pressure gradient (HPG) may influence treatment decisions. This study aimed to simulate and analyze the effect of a hydrostatic pressure gradient on different indices of functional lesion severity. A hypothetical P d -P a height difference and subsequent hydrostatic pressure gradient based on previous literature was applied to the pressure measurements from the CONTRAST study. The effect on three indices of functional lesion severity (FFR, P d /P a , and dPR) was assessed and possible reclassifications in functional significance by the different indices were analyzed. In 602 pressure tracings, simulated hydrostatic pressure gradients led to an absolute change in P d of 3.18 ± 1.30 mmHg, resulting in an overall increase in FFR, P d /P a, and dPR of 0.02 ± 0.04 for all indices ( P = 0.69). Reclassification due to the hydrostatic pressure gradient when using dichotomous cutoff values occurred in 13.4, 22.3, and 20.6% for FFR, P d /P a , and dPR, respectively. The effect of hydrostatic pressure gradient correction differed among the coronary arteries and was most pronounced in the left anterior descending. When considering the gray zone for the different functional indices, the hydrostatic pressure gradient resulted in reclassification in only one patient out of the complete patient population (1/602; 0.17%). The hydrostatic pressure gradient can influence functional lesion assessment when using dichotomous cutoff values. When taking the gray zone into account, its effect is limited. NEW & NOTEWORTHY This study systematically simulated the effect of hydrostatic pressure gradients (HPG) on real-world hyperemic and nonhyperemic pressure ratios, showing correction for HPG leads to reclassification in functional significance from 13.4 to 22.3% for different functional indices. This was most pronounced in nonhyperemic pressure ratios. A new pressure guidewire (Wirecath) is unaffected by HPG. The ongoing PW-COMPARE study (NCT04802681) prospectively analyzes the magnitude and importance of HPG by simultaneous FFR measurements.

Objectives: To identify angiographic predictors of aberrant left circumflex artery (LCx) by comparing left main (LM) length and bifurcation angle between patients with aberrant LCx and normal anatomy., Background: Failure to recognize aberrant LCx during a cardiac catheterization may hamper correct diagnosis, delay intervention in acute coronary syndromes, and result in increased contrast volume, radiation exposure, and infarct size., Methods: We retrospectively analyzed angiograms of aberrant LCx patients and normal anatomy matched controls, in three-participating centers. LM-length, bifurcation angle between the left anterior descending (LAD) and the first non-LAD branch of the LM, and procedural data were compared., Results: Between 2003 and 2020, 136 patients with aberrant LCx and 135 controls were identified. More catheters (2.4 ± 0.6 vs. 2.2 ± 0.9, p = 0.009), larger contrast volumes (169 ± 94 ml vs. 129 ± 68 ml, p < 0.0005), and prolonged fluoroscopy time (652.9 ± 623.7 s vs. 393.1 ± 332.1 s, p < 0.0005), were required in the aberrant LCx-group compared with controls. Patients with aberrant LCx had a longer LM-length and a more acute bifurcation angle, both in caudal and cranial views, compared with controls (24.7 ± 8.1 vs. 10.8 ± 4.5 mm, p < 0.0005 and 26.7 ± 7.4 vs. 12 ± 5.5 mm, p < 0.0005, respectively, and 45.2° ± 12° vs. 88.8° ± 23°, p < 0.0005 and 51.9° ± 21° vs. 68.2° ± 28.3°, p < 0.0005, respectively). In ROC analysis, LM-length showed the best diagnostic accuracy for detecting aberrant LCx. In multiple logistic regression analysis, a cranially measured LM-length > 17.7 mm was associated with a 5.3 times greater probability of predicting aberrant LCx [95% CI (3.4-8.1), p < 0.0001]., Conclusions: Our study suggests that a long LM-length and an acute bifurcation angle can indicate the presence of aberrant LCx. We present a practical algorithm for its rapid identification., (© 2022 Wiley Periodicals LLC.)

Objectives: It is unknown whether computed tomographic coronary angiography (CTCA) can be used to perform ultraselective invasive coronary angiography (ICA) by only visualizing the abnormal coronary artery on CTCA and defer visualization of the normal contralateral coronary artery. This study assessed the accuracy of CTCA in patients with coronary artery disease (CAD) on CTCA limited to either the left (LCA) or right coronary artery (RCA) in predicting a contralateral coronary artery without abnormalities on CTCA determined to be normal by ICA., Methods: This retrospective analysis included patients with CAD limited to the LCA or RCA on CTCA. Primary endpoint was the accuracy of CTCA to predict a contralateral coronary artery without abnormalities on CTCA to be normal by ICA. Secondary endpoints were potential reductions in procedure time and radiation exposure if an ultraselective ICA approach would be used compared to standard ICA., Results: In total, 202 patients were included. CTCA was correct in predicting a normal contralateral coronary artery in 201 of the 202 patients (99.5%). Deferring ICA of the normal contralateral coronary artery on CTCA resulted in a potential reduction in procedure time and dose area product of 4.22 ± 2.67 minutes (61 ± 16% reduction) and 1501 ± 1304 mGy•cm² (29 ± 13% reduction)., Conclusions: In this retrospective study, CTCA was extremely accurate in predicting a normal contralateral coronary artery in patients with LCA- or RCA-limited CAD on CTCA. A potential CTCA-guided ultraselective ICA approach was feasible and would have led to a considerable decrease in procedure time and radiation exposure.

Introduction: To date there are no recommendations on how to treat patients with an FFR positive but diffusely diseased left anterior descending coronary artery (LAD). Benefit of coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) is not so evident due to doubts regarding longevity and patency., Methods: This retrospective single-center study assessed clinical outcomes in patients presenting with symptomatic single vessel coronary artery disease of a diffusely diseased, hemodynamically significant LAD treated by coronary artery bypass grafting (CABG) or optimal medical therapy (OMT) between 2015 and 2020. Primary outcome of this study was the composite endpoint of all-cause mortality, myocardial infarction and repeat revascularization during 2-year follow-up. Secondary endpoints consisted of the individual components of the primary endpoint. Change in angina severity grade based on the Canadian Cardiovascular Society (CCS) class between baseline and 2-year follow-up was assessed., Results: Fifty-nine patients were included of which 25 patients underwent CABG and 34 patients were treated by OMT. There was a statistically significant difference in FFR value at baseline between the treatment groups (CABG 0.70 ± 0.04; OMT 0.75 ± 0.04; p < 0.001). After 2-year follow-up, there were no statistically significant differences with regard to the primary endpoint (CABG 16% (n = 4); OMT 17.6% (n = 6); p = 1.00) and secondary endpoints between the groups over 2-year follow-up., Conclusion: In patients with hemodynamically significant diffuse single vessel coronary artery disease of the left anterior descending, there was no difference between OMT and CABG in terms of mortality, myocardial infarction, revascularization and symptom reduction after two years of follow-up., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: We aimed to determine the safety and efficacy of the Allegra transcatheter heart valve (THV) for the treatment of severe aortic valve stenosis in a large patient population treated under real-world conditions., Background: The Allegra is a novel self-expanding THV with supra-annular bovine leaflets. The valve is available in three different sizes (23, 27, and 31 mm), all are delivered through an 18F sheath., Methods: Consecutive patients undergoing TAVR with the Allegra THV were enrolled in a multicenter-registry. Data were collected throughout initial hospital-stay and at 30-day follow-up. Clinical endpoints were defined according to the updated definitions of the Valve-Academic-Research-Consortium., Results: This registry included 255 patients (mean age 83 ± 6 years, 48% women) from four European centers. Median European System for Cardiac Operative Risk Evaluation II score (EuroSCORE II) was 3.3% (IQR 1.9-5.8%). Acute device success was 95.7%. The remaining 11 patients had either moderate paravalvular regurgitation immediately after the procedure (7 patients) or the device could not be optimal positioned requiring implantation of a second THV (4 patients). Major vascular complications and major/life-threatening bleedings occurred in 10 (3.9%) and 12 (4.7%) patients, respectively. At 30 day follow-up, mean effective orifice area was 2.2 ± 0.5 cm 2 , mean gradient was 6.9 ± 3.8 mmHg, 7 (3.3%) patients had more than mild paravalvular leakage, 3 patients (1.2%) had died, 6 patients (2.4%) had a stroke and 30 (12.8%) patients had required implantation of a new permanent pacemaker., Conclusions: Transfemoral implantation of the Allegra THV resulted in favorable clinical and echocardiographic outcomes during hospitalization and short-term follow up., (© 2021 Wiley Periodicals LLC.)

Objectives: This study aimed to prospectively investigate intra-aortic balloon pump counterpulsation (IABP) support in large myocardial infarction complicated by persistent ischemia after primary percutaneous coronary intervention (PCI)., Background: Use of IABP is suggested to be effective by increasing diastolic aortic pressure, thereby improving coronary blood flow. This can only be expected with exhausted coronary autoregulation, typical in acute myocardial infarction complicated by persistent ischemia. In this situation, augmented diastolic pressure is expected to increase myocardial oxygenation., Methods: One hundred patients with large STEMI complicated by persistent ischemia after primary PCI were randomized to treatment with or without IABP therapy on top of standard care. IABP support was initiated following primary PCI, immediately after inclusion. Primary end point was all-cause mortality, need for (additional) mechanical hemodynamic support, or readmission for heart failure within 6 months., Results: Mean age was 63 ± 10 years, 76% were male. Mean systolic and diastolic blood pressure were 120 ± 25 mmHg and 73 ± 17 mmHg. Mean heart rate was 75 ± 18 mmHg. Before PCI, mean summed ST-deviation was 21 ± 8 mm with only minimal ST-resolution after PCI. One patient in the IABP group reached the primary end point versus four patients in the control group (2% vs. 8%; p = 0.16). After primary PCI, resolution of ST-deviation was significantly more pronounced in the IABP group (73 ± 17%) compared to the control group (56 ± 26%; p < 0.01)., Conclusions: In this pilot study, in patients with large STEMI and persistent ischemia after primary PCI, use of IABP showed a nonsignificant decrease in mortality, necessity for (additional) mechanical hemodynamic support or readmission for heart failure at 6 months, and resulted in more rapid ST-resolution., (© 2019 Wiley Periodicals, Inc.)

Background: Pressure measurement for the duration of the wave-free period (WFP) is considered essential for resting-state physiological assessment of coronary stenosis severity using the instantaneous wave-free ratio (iFR)., Objectives: The aim of this study was to compare other diastolic resting indexes to iFR., Methods: In the population of the VERIFY2 (Pd/Pa vs iFR in an Unselected Population Referred for Invasive Angiography) study, iFR calculated by proprietary software (Volcano Harvest, Volcano Corporation, Rancho Cordova, California) was compared with the ratio of resting distal coronary pressure and aortic pressure during the complete duration of diastole (dPR), 25% to 75% of diastole (dPR 25-75 ), and midpoint of diastole (dPR mid ), along with Matlab calculated iFR (iFR matlab ) and iFR-like indexes shortening the length of the WFP by 50 and 100 ms (iFR -50ms and iFR -100ms ), respectively. Mutual differences, Spearman correlations, area under the curve values from receiver-operating characteristic analyses, and diagnostic performance with respect to iFR and fractional flow reserve (FFR) were calculated for all indexes., Results: Median iFR in 197 patients with 257 vessels was 0.91 with an interquartile range of 0.87 to 0.95. The mutual differences (± SD) with iFR were 0.006 ± 0.011 (dPR), 0.001 ± 0.007 (dPR 25-75 ), 0.001 ± 0.008 (dPR mid ), 0.005 ± 0.009 (iFR matlab ), 0.003 ± 0.008 (iFR -50ms ), and 0.001 ± 0.009 (iFR -100ms ). Correlations for all indexes with iFR were >0.99 (p < 0.001 for all). Area under the curve values for predicting iFR were >0.99 for all indexes as well. Diagnostic accuracy compared with FFR was 76% to 77% for all indexes including iFR., Conclusions: All diastolic resting indexes tested were identical to iFR, both numerically and with respect to their agreement with FFR. A numerically equal value to iFR can be determined without restriction to the WFP. Cutoff values, guidelines, and clinical recommendations for iFR can therefore be extended to these other indexes. (Pd/Pa vs iFR in an Unselected Population Referred for Invasive Angiography [VERIFY2]; NCT02377310)., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Hypothermia reduces reperfusion injury and infarct size in animal models of acute myocardial infarction if started before reperfusion. Human studies have not confirmed benefit, probably due to insufficient myocardial cooling and adverse systemic effects. This study sought to assess the safety and feasibility of a novel method for selective, sensor-monitored intracoronary hypothermia., Methods and Results: Ten patients undergoing primary percutaneous coronary intervention (PPCI) were included. Saline at room temperature was administered distal to the culprit lesion through an inflated overthe- wire balloon (OTWB) in order to cool the endangered myocardium for 10 minutes (occlusion phase). Next, the OTWB was deflated and cooling continued with saline at 4°C for another 10 minutes (reperfusion phase). A sensor-tipped temperature wire in the distal coronary artery allowed titration of the infusion rate to achieve the desired coronary temperature (6°C below body temperature). Target coronary temperature was achieved within 27 seconds (median; IQR 21-46). Except for two patients with inferior wall infarction experiencing transient conduction disturbances, no side effects occurred. Systemic temperature remained unchanged. Finally, PPCI was performed as per routine., Conclusions: Selective hypothermia of the infarct area by intracoronary infusion of saline provides a novel method to reduce coronary temperature quickly and guarantee local myocardial hypothermia. In anterior wall myocardial infarctions, the protocol appeared safe, without serious haemodynamic or systemic side effects. In inferior wall myocardial infarctions, transient conduction abnormalities of short duration occurred. Potentially, selective intracoronary delivery of hypothermia could attenuate reperfusion injury caused by traditional PPCI.

Because current reperfusion strategies in acute myocardial infarction (AMI) seem to be exhausted in terms of additional mortality benefit, there remains a need for new methods to attenuate reperfusion injury and, thereby, further reduce myocardial infarct size and improve long-term survival. Therapeutic hypothermia (32-35°C) diminishes reperfusion injury and reduces infarct size in a variety of animal models of AMI if provided before reperfusion. In human studies this reduction has not been confirmed so far, most likely because systemic cooling acts slowly, and therefore, the target temperature is not reached in time or at all in a substantial number of patients. Furthermore, systemic cooling can cause adverse effects such as severe shivering, volume overload, and an enhanced adrenergic state. In most randomized clinical trials, however, subgroups of patients with anterior myocardial infarction that reached the target temperature before reperfusion did show a reduction in infarct size. To transform therapeutic hypothermia into a clinically feasible treatment for AMI, its method must be modified. An ideal technique should be quick enough to achieve sufficient myocardial hypothermia before reperfusion, without significant delay and without the adverse effects of systemic cooling. In this review, we propose a novel, potentially feasible method of selective intracoronary hypothermia to overcome the problems encountered with prior techniques.

Hypothermia may attenuate reperfusion injury and thereby improve acute myocardial infarction therapy. Systemic cooling trials failed to reduce infarct size, perhaps because the target temperature was not reached fast enough. The use of selective intracoronary hypothermia combined with intracoronary temperature monitoring allows for titrating to target temperature and optimizing the cooling rate. We aimed to the test the feasibility of intracoronary cooling for controlled, selective myocardial hypothermia in an isolated beating pig heart. In five porcine hearts the left anterior descending artery (LAD) was occluded by an over-the-wire balloon (OTWB). After occlusion, saline at 22°C was infused through the OTWB lumen for 5 minutes into the infarct area at a rate of 30 ml/min. Thereafter the balloon was deflated but infusion continued with saline at 4°C for 5 minutes. Distal coronary temperature was continuously monitored by a pressure/temperature guidewire. Myocardial temperature at several locations in the infarct and control areas was recorded using needle thermistors. In the occlusion phase, coronary temperature decreased by 11.4°C (range 9.4-12.5°C). Myocardial temperature throughout the infarct area decreased by 5.1°C (range 1.8-8.1°C) within three minutes. During the reperfusion phase, coronary temperature decreased by 6.2°C (range 4.1-10.3°C) and myocardial temperature decreased by 4.5°C (range 1.5-7.4°C). Myocardial temperature outside the infarct area was not affected. In the isolated beating pig heart with acute occlusion of the LAD, we were able to rapidly "induce, maintain, and control" a stable intracoronary and myocardial target temperature of at least 4°C below body temperature without side effects and using standard PCI equipment, justifying further studies of this technique in humans.

Aims: Percutaneous coronary intervention (PCI) of bifurcation lesions can be performed using various techniques. The aim of this study was to analyse the outcome of various techniques of bifurcation stenting in all patients undergoing bifurcation stenting at one large intervention centre in 2013, taking into account that more complex lesions might more often warrant a two-stent technique., Methods and Results: This retrospective study included 260 consecutive patients who underwent non-primary PCI of a bifurcation lesion at the Catharina Hospital, Eindhoven, in 2013. Patients were classified into two groups: one-stent technique (provisional stenting), and two-stent techniques (culotte, crush and T‑stenting). The primary endpoint was the rate of restenosis at 1 year. The secondary endpoints were procedural complications (side branch occlusion, periprocedural infarction, and death) and major adverse cardiac events (MACE) at 1 year. Periprocedural complications occurred in 15 patients (5.8 %) with no difference between the groups (p = 0.27). After 1 year, restenosis occurred in 3.2 % of the patients in the one-stent technique group and 7.3 % in the two-stent technique group (p = 0.20). MACE at 1 year did not differ between the groups at 11.9 % and 12.2 % respectively (p = 1.00)., Conclusions: This study shows that there is no significant difference between restenosis rate, or any other outcome parameter, with the different techniques of bifurcation stenting. Since provisional stenting is the simplest, most straightforward and cheapest approach, if technically feasible this technique has our preference as the initial approach, and an upgrade can be considered if the result is insufficient., Competing Interests: S.J.L. Leus, E. van Hagen, F.M. Zimmermann, L.X. van Nunen, M. van ‘t Veer, J. Koolen and N.H.J. Pijls declare that they have no competing interest.

Aims: The aim of this study is to validate a novel monorail infusion catheter for thermodilution-based quantitative coronary flow measurements., Methods and Results: Based on the principles of thermodilution, volumetric coronary flow can be determined from the flow rate of a continuous saline infusion, the temperature of saline when it enters the coronary artery, and the temperature of the blood mixed with the saline in the distal part of the coronary artery. In an in vitro set-up of the systemic and coronary circulation at body temperature, coronary flow values were varied from 50-300 ml/min in steps of 50 ml/min. At each coronary flow value, thermodilution-based measurements were performed at infusion rates of 15, 20, and 30 ml/min. Temperatures and pressures were simultaneously measured with a pressure/temperature sensor-tipped guidewire. Agreement of the calculated flow and the measured flow as well as repeatability were assessed. A total of five catheters were tested, with a total of 180 measurements. A strong correlation (ρ=0.976, p<0.0001) and a difference of -6.5±15.5 ml/min were found between measured and calculated flow. The difference between two repeated measures was 0.2%±8.0%., Conclusions: This novel infusion catheter used in combination with a pressure/temperature sensor-tipped guidewire allows accurate and repeatable absolute coronary flow measurements. This opens a window to a better understanding of the coronary microcirculation.

Background: In ST-elevation myocardial infarction (STEMI), reduction in time to reperfusion of the occluded coronary artery reduces infarct size. In animal models, an additional reduction of infarct size was observed when hypothermia was induced before reperfusion, despite a longer ischemic time. However, several human studies did not corroborate this positive effect, which is believed to be in part due to the inability of systemic induced hypothermia to induce sufficient decrease of local myocardial temperature before reperfusion. Providing rapid local myocardial hypothermia by intracoronary infusion of saline before reperfusion in patients with STEMI may overcome this problem. In this study, we evaluate the safety and feasibility of providing rapid intracoronary myocardial hypothermia in patients undergoing intracoronary blood flow measurements based on thermodilution with continuous infusion of saline at room temperature., Methods and Results: In 53 patients with stable angina (SA) and 20 patients with STEMI, a total of 215 measurements were performed. The measurements consisted of continuous selective intracoronary infusion of saline at room temperature with rates between 10 ml/min and 30 ml/min. Temperature changes compared to initial blood temperature (Tb ) were measured at the tip of the infusion catheter (Ti ) and distally in the coronary artery (Td ). In patients with SA, Ti was -5.65 ± 1.41°C (range -9.27 to -2.28) and Td was -0.78 ± 0.51°C (range -3.27 to -0.23°C). In patients with STEMI, Ti was -7.45 ± 0.51°C (range -8.21 to -6.56) and Td was -1.37 ± 0.82°C (range -4.62 to -0.74°C). In all patients, steady-state intracoronary hypothermia was achieved within 15 sec and could be maintained without noticeable complications., Conclusion: This study demonstrates the safety and feasibility of inducing intracoronary hypothermia by selective infusion of saline at room temperature in patients with SA and STEMI. Steady-state hypothermia could be achieved and maintained quickly, easily, and safely using common PCI techniques. Therefore, our findings warrant further studies to the use of intracoronary hypothermia to enhance myocardial salvage in acute myocardial infarction., (© 2015 Wiley Periodicals, Inc.)

Intra-aortic balloon pump (IABP) counterpulsation is the most widely used mechanical circulatory support device because of its ease of use, low complication rate, and fast manner of insertion. Its benefit is still subject of debate, and a considerable gap exists between guidelines and clinical practice. Retrospective nonrandomized studies and animal experiments show benefits of IABP therapy. However, recent large randomized trials do not show benefit of IABP therapy, which has led to a downgrading in the guidelines. In our view, this dichotomy between trials and practice might be the result of insufficient understanding of the prerequisites needed for effective IABP therapy, that is, exhausted autoregulation, and of not including the right patient population in trials. The population included in recent large randomized trials has been heterogeneous, also including patients in whom benefit of IABP could not be expected. The clinical condition in which most benefit is expected, that is persistent ischemia in acute ST-elevation myocardial infarction, is discussed in this review. In conclusion, this review aims to explain the physiological principles needed for effective IABP therapy, to reflect critically on the large randomized trials, and to solve some of the controversies in this field., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: Stenting an angiographically intermediate but functionally non-significant stenosis is controversial. Nevertheless, it has been questioned if deferral of a functionally non-significant lesion on the basis of fractional flow reserve (FFR) measurement, is safe, especially on the long term. Five-year follow-up of the DEFER trial showed that outcome after deferral of percutaneous coronary intervention (PCI) of an intermediate coronary stenosis based on FFR ≥ 0.75 is excellent and was not improved by stenting. The aim of this study was to investigate the validity of this position on the very long term., Methods and Results: In 325 patients scheduled for PCI of an intermediate stenosis, FFR was measured just before the planned intervention. If FFR was ≥0.75, patients were randomly assigned to deferral (Defer group; n = 91) or performance (Perform group; n = 90) of PCI. If FFR was <0.75, PCI was performed as planned (Reference group; n = 144). Clinical follow-up was 15 years. There were no differences in baseline clinical characteristics between the randomized groups. Complete 15-year follow-up was obtained in 92% of patients. After 15 years of follow-up, the rate of death was not different between the three groups: 33.0% in the Defer group, 31.1% in the Perform group, and 36.1% in the Reference group (Defer vs. Perform, RR 1.06, 95% CI: 0.69-1.62, P = 0.79). The rate of myocardial infarction was significantly lower in the Defer group (2.2%) compared with the Perform group (10.0%), RR 0.22, 95% CI: 0.05-0.99, P = 0.03., Conclusion: Deferral of PCI of a functionally non-significant stenosis is associated with a favourable very long-term follow-up without signs of late 'catch-up' phenomenon., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: The aim of this study was to compare the hyperaemic effect of a single bolus regadenoson injection to a central venous adenosine infusion for inducing hyperaemia in the measurement of fractional flow reserve (FFR)., Methods and Results: One hundred patients scheduled for FFR measurement were enrolled. FFR was first measured by IV adenosine (140 µg/kg/min), thereafter by IV bolus regadenoson injection (400 µg), followed by another measurement by IV adenosine and bolus injection of regadenoson. The regadenoson injections were randomised to central or peripheral intravenous. Hyperaemic response and duration of steady state maximum hyperaemia were studied, central versus peripheral venous regadenoson injections were compared, and safety and reproducibility of repeated injections were investigated. Mean age was 66±8 years, 75% of the patients were male. The target stenosis was located in the LM, LAD, LCX, and RCA in 7%, 54%, 20% and 19%, respectively. There was no difference in FFR measured by adenosine or by regadenoson (ΔFFR=0.00±0.01, r=0.994, p<0.001). Duration of maximum hyperaemia after regadenoson was variable (10-600 s). No serious side effects of either drug were observed., Conclusions: Maximum coronary hyperaemia can be achieved easily, rapidly, and safely by one single intravenous bolus of regadenoson administered either centrally or peripherally. Repeated regadenoson injections are safe. The hyperaemic plateau is variable. Clinical Trial Registration: http://clinicaltrials.gov/ct2/ show/study/NCT01809743?term=NCT01809743&rank=1 (ClinicalTrials.gov Identifier: NCT01809743).

Background: In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up., Methods: The FAME study was a multicentre trial done in Belgium, Denmark, Germany, the Netherlands, Sweden, the UK, and the USA. Patients (aged ≥ 18 years) with multivessel coronary artery disease were randomly assigned to undergo angiography-guided PCI or FFR-guided PCI. Before randomisation, stenoses requiring PCI were identified on the angiogram. Patients allocated to angiography-guided PCI had revascularisation of all identified stenoses. Patients allocated to FFR-guided PCI had FFR measurements of all stenotic arteries and PCI was done only if FFR was 0·80 or less. No one was masked to treatment assignment. The primary endpoint was major adverse cardiac events at 1 year, and the data for the 5-year follow-up are reported here. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267774., Findings: After 5 years, major adverse cardiac events occurred in 31% of patients (154 of 496) in the angiography-guided group versus 28% (143 of 509 patients) in the FFR-guided group (relative risk 0·91, 95% CI 0·75-1·10; p=0·31). The number of stents placed per patient was significantly higher in the angiography-guided group than in the FFR-guided group (mean 2·7 [SD 1·2] vs 1·9 [1·3], p<0·0001)., Interpretation: The results confirm the long-term safety of FFR-guided PCI in patients with multivessel disease. A strategy of FFR-guided PCI resulted in a significant decrease of major adverse cardiac events for up to 2 years after the index procedure. From 2 years to 5 years, the risks for both groups developed similarly. This clinical outcome in the FFR-guided group was achieved with a lower number of stented arteries and less resource use. These results indicate that FFR guidance of multivessel PCI should be the standard of care in most patients., Funding: St Jude Medical, Friends of the Heart Foundation, and Medtronic., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The blood pressure changes induced by the intra-aortic balloon pump (IABP) are expected to create clinical improvement in terms of coronary perfusion and myocardial oxygen consumption. However, the measured effects reported in literature are inconsistent. The aim of this study was to investigate the influence of ischemia on IABP efficacy in healthy hearts and in shock. Twelve slaughterhouse porcine hearts (hearts 1-12) were connected to an external circulatory system, while physiologic cardiac performance was restored. Different clinical scenarios, ranging from healthy to cardiogenic shock, were simulated by step-wise administration of negative inotropic drugs. In hearts 7-12, severe global myocardial ischemia superimposed upon the decreased contractile states was created. IABP support was applied in all hearts under all conditions. Without ischemia, the IABP induced a mild increase in coronary blood flow and cardiac output. These effects were strongly augmented in the presence of persisting ischemia, where coronary blood flow increased by 49 ± 24% (P < 0.01) and cardiac output by 17 ± 6% (P < 0.01) in case of severe pump failure. As expected, myocardial oxygen consumption increased in case of ischemia (21 ± 17%; P < 0.01), while it slightly decreased without (-3 ± 6%; P < 0.01). In case of progressive pump failure due to persistent myocardial ischemia, the IABP increased hyperemic coronary blood flow and cardiac output significantly, and reversed the progressive hemodynamic deterioration within minutes. This suggests that IABP therapy in acute myocardial infarction is most effective in patients with viable myocardium, suffering from persistent myocardial ischemia, despite adequate epicardial reperfusion., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Aims: This substudy investigated IABP support in large STEMI complicated by persistent ischaemia within the original CRISP-AMI trial., Methods and Results: Patients were included if the ECG at admission showed summed ST deviation (ST-D) ≥15 mm and the ECG post PCI showed poor ST resolution (<50%). Endpoints evaluated were all-cause mortality at six months and the composite endpoint of death, cardiogenic shock or new or worsening heart failure at six months. One hundred and forty-nine patients had ST-D ≥15 mm (mean ST-D 24±8 mm). Of these patients, 36 (24%) showed poor ST resolution (15 patients in the IABP group; 21 patients in the control group). Mean age was 55±11 years, 89% were male. Mean systolic and diastolic blood pressures were 135±31 mmHg and 83±22 mmHg, respectively. The left anterior descending coronary artery was the infarct-related artery in all cases, primary PCI was successful in 94%. At six months, zero patients in the IABP group died versus five patients in the control group (0% versus 24%; p=0.046). There was a trend towards statistical significance in the composite endpoint (one patient [7%] versus seven patients [33%]; p=0.06)., Conclusions: In this substudy, use of IABP was associated with decreased six-month mortality in large STEMI complicated by persistent ischaemia after PCI.

Background: Recent evidence questions the role of intra-aortic balloon counterpulsation (IABP) in the treatment of acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). An area of increasing interest is the use of IABP for persistent ischaemia (PI). We analysed the use of IABP in patients with AMI complicated by CS or PI., Methods: From 2008 to 2010, a total of 4076 patients were admitted to our hospital for primary percutaneous coronary intervention (PCI) for AMI. Out of those, 239 patients received an IABP either because of CS or because of PI. Characteristics and outcome of those patients are investigated., Results: The mean age of the study population was 64 ± 11 years; 75 % were male patients. Of the patients, 63 % had CS and 37 % had PI. Patients with CS had a 30-day mortality rate of 36 %; 1-year mortality was 41 %. Patients with PI had a 30-day mortality rate of 7 %; 1-year mortality was 11 %., Conclusions: Mortality in patients admitted for primary PCI because of AMI complicated by CS is high despite IABP use. Outcome in patients treated with IABP for PI is favourable and mandates further prospective studies.

Cornerstones in the treatment of coronary artery disease (CAD) are medical therapy and coronary revascularization. In acute settings (ST-elevation myocardial infarction and non-ST-elevation myocardial infarction), percutaneous coronary intervention (PCI) has proven to improve prognosis. The optimal treatment of stable CAD is subject to great controversy. By using fractional flow reserve to guide PCI, it is possible to stent only those lesions that induce myocardial ischemia. This review aims to reflect on the use of FFR-guided PCI in stable CAD.

Because of the large number of interaction factors involved, the effects of the intra-aortic balloon pump (IABP) have not been investigated deeply. To enhance its clinical efficiency and to better define indications for use, advanced models are required to test the interaction between the IABP and the cardiovascular system. A patient with mild blood pressure depression and a lowered cardiac output is modeled in a lumped parameter computational model, developed with physiologically representative elements for relevant components of circulation and device. IABP support is applied, and the moments of balloon inflation and deflation are varied around their conventional timing modes. For validation purposes, timing is adapted within acceptable ranges in ten patients undergoing IABP therapy for typical clinical indications. In both model and patients, the IABP induces a diastolic blood pressure augmentation as well as a systolic reduction in afterload. The support capabilities of the IABP benefit the most when the balloon is deflated simultaneously with ventricular contraction, whereas inflation before onset of diastole unconditionally interferes with ejection. The physiologic response makes the model an excellent tool for testing the interaction between the IABP and the cardiovascular system, and how alterations of specific IABP parameters (i.e., timing) affect this coupling.