Publications by authors named "Stephen P Hoole"

107 Publications

Coronary imaging of cardiac allograft vasculopathy predicts current and future deterioration of left ventricular function in patients with orthotopic heart transplantation.

Clin Transplant 2021 Nov 1:e14523. Epub 2021 Nov 1.

Department of Interventional Cardiology, Cambridge Biomedical Campus, Royal Papworth Hospital, Cambridge, UK.

Background: Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) improve sensitivity of cardiac allograft vasculopathy (CAV) detection compared to invasive coronary angiography (ICA), but their ability to predict clinical events is unknown. We determined whether severe CAV detected with ICA, IVUS, or OCT correlates with graft function.

Methods: Comparison of specific vessel parameters between IVUS and OCT on 20 patients attending for angiography 12-24 months post-orthotopic heart transplant. Serial left ventricular ejection fraction (EF) was recorded prospectively.

Results: Analyzing 55 coronary arteries, OCT and IVUS correlated well for vessel CAV characteristics. A mean intimal thickness (MIT)  > .25 mm had a sensitivity of 86.7% and specificity of 74.3% at detecting Stanford grade 4 CAV. Those with angiographically evident CAV had significant reduction in graft EF over 7.3 years follow-up (median ΔEF -2% vs +1.5%, P = .03). Patients with MIT  > .25 mm in at least one vessel had a lower median EF at time of surveillance (57% vs 62%, P = .014). Two MACEs were noted.

Conclusion: Imaging with OCT correlates well with IVUS for CAV detection. Combined angiography and OCT to screen for CAV within 12-24 months of transplant predicts concurrent and future deterioration in graft function.
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http://dx.doi.org/10.1111/ctr.14523DOI Listing
November 2021

Trans-myocardial blood Interleukin-6 levels relate to intracoronary imaging defined features of plaque vulnerability and predict procedure-induced myocardial infarction.

Cardiovasc Revasc Med 2021 Oct 14. Epub 2021 Oct 14.

Interventional Cardiology, Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK. Electronic address:

Background: Intravascular imaging has defined various vulnerable plaque (VP) phenotypes that predict future clinical events. Atherosclerosis is an inflammatory process and inflammation, measured by systemic biomarkers can also predict events and anti-inflammatory therapy is beneficial. We were interested to assess the relationship between plaque phenotypes and key inflammatory biomarkers, measured close to the coronary.

Methods: Ninety-two patients scheduled for elective percutaneous coronary intervention (PCI) underwent virtual histology intravascular ultrasound, optical coherence tomography, pressure wire and blood sampling from the guide catheter (GC), coronary sinus (CS) to determine trans-myocardial gradient (TMG = CS-GC) and from peripheral blood. Procedure related troponin release was assessed at 6-hours post-PCI from peripheral venous blood. Biomarker data were analysed and compared with coronary data.

Results: Interleukin (IL)-6 was associated with increased levels of tumour necrosis factor (TNF)-α and C-reactive protein (CRP) and the pre-PCI IL-6 TMG correlated with plaque features of vulnerability: plaque burden - PB (r = 0.253, p = 0.04) and minimal lumen area - MLA (r = -0.438, p = 0.007), although no relationship existed for thin-capped fibroatheroma defined by either imaging modality. Peripheral IL-6 levels had no correlation with post PCI troponin, although the pre-PCI IL-6 TMG was related (r = 0.334, p = 0.006), as was PB (r = 0.27, p = 0.029).

Conclusion: IL-6 TMG pre-PCI correlates with plaque burden and MLA that have been shown to predict future clinical events and is correlated with post-PCI troponin release. These associations were not apparent from peripheral blood and suggest that local coronary biomarker signatures may help further define vulnerability and risk.
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http://dx.doi.org/10.1016/j.carrev.2021.10.006DOI Listing
October 2021

Pericoronary and periaortic adipose tissue density are associated with inflammatory disease activity in Takayasu arteritis and atherosclerosis.

Eur Heart J Open 2021 Sep 6;1(2):oeab019. Epub 2021 Aug 6.

Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK.

Aims: To examine pericoronary adipose tissue (PCAT) and periaortic adipose tissue (PAAT) density on coronary computed tomography angiography for assessing arterial inflammation in Takayasu arteritis (TAK) and atherosclerosis.

Methods And Results: PCAT and PAAT density was measured in coronary ( = 1016) and aortic ( = 108) segments from 108 subjects [TAK + coronary artery disease (CAD), = 36; TAK, = 18; atherosclerotic CAD, = 32; matched controls, = 22]. Median PCAT and PAAT densities varied between groups (mPCAT: < 0.0001; PAAT: = 0.0002). PCAT density was 7.01 ± standard error of the mean (SEM) 1.78 Hounsfield Unit (HU) higher in coronary segments from TAK + CAD patients than stable CAD patients ( = 0.0002), and 8.20 ± SEM 2.04 HU higher in TAK patients without CAD than controls ( = 0.0001). mPCAT density was correlated with Indian Takayasu Clinical Activity Score ( = 0.43, = 0.001) and C-reactive protein ( = 0.41, < 0.0001) and was higher in active vs. inactive TAK ( = 0.002). mPCAT density above -74 HU had 100% sensitivity and 95% specificity for differentiating active TAK from controls [area under the curve = 0.99 (95% confidence interval 0.97-1)]. The association of PCAT density and coronary arterial inflammation measured by Ga-DOTATATE positron emission tomography (PET) equated to an increase of 2.44 ± SEM 0.77 HU in PCAT density for each unit increase in Ga-DOTATATE maximum tissue-to-blood ratio ( = 0.002). These findings remained in multivariable sensitivity analyses adjusted for potential confounders.

Conclusions: PCAT and PAAT density are higher in TAK than atherosclerotic CAD or controls and are associated with clinical, biochemical, and PET markers of inflammation. Owing to excellent diagnostic accuracy, PCAT density could be useful as a clinical adjunct for assessing disease activity in TAK.
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http://dx.doi.org/10.1093/ehjopen/oeab019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508012PMC
September 2021

Five-year outcomes after state-of-the-art percutaneous coronary revascularization in patients with de novo three-vessel disease: final results of the SYNTAX II study.

Eur Heart J 2021 Oct 7. Epub 2021 Oct 7.

Manchester Heart Centre, Manchester Royal Infirmary, Central Manchester University Hospitals, Oxford Rd, Manchester M13 9WL, UK.

Aims: The SYNTAX II study evaluated the impact of advances in percutaneous coronary intervention (PCI), integrated into a single revascularization strategy, on outcomes of patients with de novo three-vessel disease. The study employed decision-making utilizing the SYNTAX score II, use of coronary physiology, thin-strut biodegradable polymer drug-eluting stents, intravascular ultrasound, enhanced treatments of chronic total occlusions, and optimized medical therapy. Patients treated with this approach were compared with predefined patients from the SYNTAX I trial.

Methods And Results: SYNTAX II was a multicentre, single-arm, open-label study of patients requiring revascularization who demonstrated clinical equipoise for treatment with either coronary artery bypass grafting (CABG) or PCI, predicted by the SYNTAX score II. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which included any revascularization. The comparators were a matched PCI cohort trial and a matched CABG cohort, both from the SYNTAX I trial. At 5 years, MACCE rate in SYNTAX II was significantly lower than in the SYNTAX I PCI cohort (21.5% vs. 36.4%, P < 0.001). This reflected lower rates of revascularization (13.8% vs. 23.8%, P < 0.001), and myocardial infarction (MI) (2.7% vs. 10.4%, P < 0.001), consisting of both procedural MI (0.2% vs. 3.8%, P < 0.001) and spontaneous MI (2.3% vs. 6.9%, P = 0.004). All-cause mortality was lower in SYNTAX II (8.1% vs. 13.8%, P = 0.013) reflecting a lower rate of cardiac death (2.8% vs. 8.4%, P < 0.001). Major adverse cardiac and cerebrovascular events' outcomes at 5 years among patients in SYNTAX II and predefined patients in the SYNTAX I CABG cohort were similar (21.5% vs. 24.6%, P = 0.35).

Conclusions: Use of the SYNTAX II PCI strategy in patients with de novo three-vessel disease led to improved and durable clinical results when compared to predefined patients treated with PCI in the original SYNTAX I trial. A predefined exploratory analysis found no significant difference in MACCE between SYNTAX II PCI and matched SYNTAX I CABG patients at 5-year follow-up.
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http://dx.doi.org/10.1093/eurheartj/ehab703DOI Listing
October 2021

Current strategies for managing chronic thromboembolic pulmonary hypertension: results of the worldwide prospective CTEPH Registry.

ERJ Open Res 2021 Jul 16;7(3). Epub 2021 Aug 16.

Royal Papworth Hospital, Cambridge, UK.

Background: Pulmonary endarterectomy (PEA), pulmonary arterial hypertension (PAH) therapy and balloon pulmonary angioplasty (BPA) are currently accepted therapies for chronic thromboembolic pulmonary hypertension (CTEPH). This international CTEPH Registry identifies clinical characteristics of patients, diagnostic algorithms and treatment decisions in a global context.

Methods: 1010 newly diagnosed consecutive patients were included in the registry between February 2015 and September 2016. Diagnosis was confirmed by right heart catheterisation, ventilation-perfusion lung scan, computerised pulmonary angiography and/or invasive pulmonary angiography after at least 3 months on anticoagulation.

Results: Overall, 649 patients (64.3%) were considered for PEA, 193 (19.1%) for BPA, 20 (2.0%) for both PEA and BPA, and 148 (14.7%) for PAH therapy only. Reasons for PEA inoperability were technical inaccessibility (n=235), comorbidities (n=63) and patient refusal (n=44). In Europe and America and other countries (AAO), 72% of patients were deemed suitable for PEA, whereas in Japan, 70% of patients were offered BPA as first choice. Sex was evenly balanced, except in Japan where 75% of patients were female. A history of acute pulmonary embolism was reported for 65.6% of patients. At least one PAH therapy was initiated in 35.8% of patients (26.2% of PEA candidates, 54.5% of BPA candidates and 54.1% of those not eligible for either PEA or BPA). At the time of analysis, 39 patients (3.9%) had died of pulmonary hypertension-related causes (3.5% after PEA and 1.8% after BPA).

Conclusions: The registry revealed noticeable differences in patient characteristics (rates of pulmonary embolism and sex) and therapeutic approaches in Japan compared with Europe and AAO.
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http://dx.doi.org/10.1183/23120541.00850-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365143PMC
July 2021

Serial right heart catheter assessment between balloon pulmonary angioplasty sessions identify procedural factors that influence response to treatment.

J Heart Lung Transplant 2021 10 1;40(10):1223-1234. Epub 2021 Jul 1.

Department of Cardiology, Royal Papworth Hospital, Cambridge, UK. Electronic address:

Background: Balloon pulmonary angioplasty (BPA) is delivered as a series of treatments for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) however, there is little published data on the procedural determinants of outcome.

Methods: Pre- and post-BPA clinical and hemodynamic data, as well as serial hemodynamic and procedural data at each BPA session were evaluated to determine patient and procedure-related factors that influence hemodynamic response.

Results: Per procedure data from 210 procedures in 84 patients and per patient data from 182 procedures in 63 patients with completed treatment and 3-month follow-up were analyzed. A median of 3 (range 1-6) BPA procedures treating a median of 2 segments per procedure (range 1-3) were performed per patient with a median interval between procedures of 42 (range 5-491) days. Clinical outcome correlated with hemodynamic change (pulmonary vascular resistance [ΔPVR] vs Cambridge Pulmonary Hypertension Outcome Review [CAMPHOR] symptom score: p < 0.001, Pearson's r = 0.48, n = 49). Responders to BPA had more severe disease at baseline and 37.5 % of non-responders were post-PEA. There was a dose-response relationship between per procedure and total number of segments treated and hemodynamic improvement (ΔPVR: 1 segment: -0.9%, 2: -14.5%, 3 or more: -16.1%, p < 0.001). Treating totally occluded vessels had a greater hemodynamic effect (mean pulmonary artery pressure [ΔmPAP]: sessions with occlusion: -8.0%, without occlusion treated: -3.2%, p < 0.05) without an increased complication rate.

Conclusions: The magnitude of clinical benefit is related to the hemodynamic effect of BPA which in turn is related to the number of segments treated and lesion severity. Patients who were post-PEA were less likely to respond to BPA.
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http://dx.doi.org/10.1016/j.healun.2021.06.011DOI Listing
October 2021

Adenosine-Induced Coronary Steal Is Observed in Patients Presenting With ST-Segment-Elevation Myocardial Infarction.

J Am Heart Assoc 2021 07 30;10(13):e019899. Epub 2021 Jun 30.

Department of Interventional Cardiology Royal Papworth Hospital Cambridge United Kingdom.

Background Adenosine is used to treat no-reflow in the infarct-related artery (IRA) during ST-segment-elevation myocardial infarction intervention. However, the physiological effect of adenosine in the IRA is variable. Coronary steal-a reduction of blood flow to the distal coronary bed-can occur in response to adenosine and this is facilitated by collaterals. We investigated the effects of adenosine on coronary flow reserve (CFR) in patients presenting with ST-segment-elevation myocardial infarction to better understand the physiological mechanism underpinning the variable response to adenosine. Methods and Results Pressure-wire assessment of the IRA after percutaneous coronary intervention was performed in 93 patients presenting with ST-segment-elevation myocardial infarction to calculate index of microvascular resistance, CFR, and collateral flow index by pressure. Modified collateral Rentrop grade to the IRA was recorded, as was microvascular obstruction by cardiac magnetic resonance imaging. Coronary steal (CFR <0.9), no change in flow (CFR=0.9-1.1), and hyperemic flow (CFR >1.1) after adenosine occurred in 19 (20%), 15 (16%), and 59 (63%) patients, respectively. Patients with coronary steal had higher modified Rentrop score to the IRA (1 [0, 1.75] versus 0 [0, 1], <0.001) and a higher collateral flow index by pressure (0.25±0.10 versus 0.15±0.10, =0.004) than the hyperemic group. The coronary steal group also had significantly higher index of microvascular resistance (61.68 [28.13, 87.04] versus 23.93 [14.67, 37.00], =0.006) and had more disease (stenosis >50%) in the donor arteries (52.63% versus 22.03%, =0.02) than the hyperemic group. Conclusions Adenosine-induced coronary steal may be responsible for a reduction in coronary flow reserve in a proportion of patients presenting with ST-segment-elevation myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03145194. URL: https://www.isrctn.com; Unique identifier: ISRCTN3176727.
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http://dx.doi.org/10.1161/JAHA.120.019899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403291PMC
July 2021

Myocardial stress perfusion in asymptomatic patients: the silent ischemia makes the loudest sound.

Eur Radiol 2021 Aug 29;31(8):6169-6171. Epub 2021 May 29.

Royal Papworth Hospital, Cambridge, UK.

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http://dx.doi.org/10.1007/s00330-021-08082-7DOI Listing
August 2021

International Prospective Registry of Acute Coronary Syndromes in Patients With COVID-19.

J Am Coll Cardiol 2021 05;77(20):2466-2476

Cardiovascular Department, Manzoni Hospital, Lecco, Italy.

Background: Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear.

Objectives: The purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre-COVID-19 cohorts.

Methods: From March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re-myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre-COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019).

Results: In 144 ST-segment elevation myocardial infarction (STEMI) and 121 non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001).

Conclusions: In this multicenter international registry, COVID-19-positive ACS patients presented later and had increased in-hospital mortality compared with a pre-COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.
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http://dx.doi.org/10.1016/j.jacc.2021.03.309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128002PMC
May 2021

Risks and benefits of percutaneous coronary intervention in spontaneous coronary artery dissection.

Heart 2021 09 18;107(17):1398-1406. Epub 2021 May 18.

Department of Cardiovascular Sciences and NIHR Biomedical Research Centre, University of Leicester, Leicester, Leicestershire, UK

Objective: To investigate percutaneous coronary intervention (PCI) practice in an international cohort of patients with spontaneous coronary artery dissection (SCAD). To explore factors associated with complications and study angiographic and longer term outcomes.

Methods: SCAD patients (n=215, 94% female) who underwent PCI from three national cohort studies were investigated and compared with a matched cohort of conservatively managed SCAD patients (n=221).

Results: SCAD-PCI patients were high risk at presentation with only 8.8% undergoing PCI outside the context of ST-elevation myocardial infarction/cardiac arrest, thrombolysis in myocardial infarction (TIMI) 0/1 flow or proximal dissections. PCI complications occurred in 38.6% (83/215), with 13.0% (28/215) serious complications. PCI-related complications were associated with more extensive dissections (multiple vs single American Heart Association coronary segments, OR 1.9 (95% CI: 1.06-3.39),p=0.030), more proximal dissections (proximal diameter per mm, OR 2.25 (1.38-3.67), p=0.001) and dissections with no contrast penetration of the false lumen (Yip-Saw 2 versus 1, OR 2.89 (1.12-7.43), p=0.028). SCAD-PCI involved long lengths of stent (median 46mm, IQR: 29-61mm). Despite these risks, SCAD-PCI led to angiographic improvements in those with reduced TIMI flow in 84.3% (118/140). Worsening TIMI flow was only seen in 7.0% (15/215) of SCAD-PCI patients. Post-PCI major adverse cardiovascular and cerebrovascular events (MACCE) and left ventricular function outcomes were favourable.

Conclusion: While a conservative approach to revascularisation is favoured, SCAD cases with higher risk presentations may require PCI. SCAD-PCI is associated with longer stent lengths and a higher risk of complications but leads to overall improvements in coronary flow and good medium-term outcomes in patients.
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http://dx.doi.org/10.1136/heartjnl-2020-318914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372386PMC
September 2021

Outcomes following PCI in CABG candidates during the COVID-19 pandemic: The prospective multicentre UK-ReVasc registry.

Catheter Cardiovasc Interv 2021 May 4. Epub 2021 May 4.

Department of Cardiovascular Sciences and the NIHR Leicester Biomedical Research Centre, Glenfield Hospital, University of Leicester, Leicester, UK.

Objectives: To describe outcomes following percutaneous coronary intervention (PCI) in patients who would usually have undergone coronary artery bypass grafting (CABG).

Background: In the United Kingdom, cardiac surgery for coronary artery disease (CAD) was dramatically reduced during the first wave of the COVID-19 pandemic. Many patients with "surgical disease" instead underwent PCI.

Methods: Between 1 March 2020 and 31 July 2020, 215 patients with recognized "surgical" CAD who underwent PCI were enrolled in the prospective UK-ReVasc Registry (ReVR). 30-day major cardiovascular event outcomes were collected. Findings in ReVR patients were directly compared to reference PCI and isolated CABG pre-COVID-19 data from British Cardiovascular Intervention Society (BCIS) and National Cardiac Audit Programme (NCAP) databases.

Results: ReVR patients had higher incidence of diabetes (34.4% vs 26.4%, P = .008), multi-vessel disease with left main stem disease (51.4% vs 3.0%, P < .001) and left anterior descending artery involvement (94.8% vs 67.2%, P < .001) compared to BCIS data. SYNTAX Score in ReVR was high (mean 28.0). Increased use of transradial access (93.3% vs 88.6%, P = .03), intracoronary imaging (43.6% vs 14.4%, P < .001) and calcium modification (23.6% vs 3.5%, P < .001) was observed. No difference in in-hospital mortality was demonstrated compared to PCI and CABG data (ReVR 1.4% vs BCIS 0.7%, P = .19; vs NCAP 1.0%, P = .48). Inpatient stay was half compared to CABG (3.0 vs 6.0 days). Low-event rates in ReVR were maintained to 30-day follow-up.

Conclusions: PCI undertaken using contemporary techniques produces excellent short-term results in patients who would be otherwise CABG candidates. Longer-term follow-up is essential to determine whether these outcomes are maintained over time.
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http://dx.doi.org/10.1002/ccd.29702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239910PMC
May 2021

GLP-1 vasodilatation in humans with coronary artery disease is not adenosine mediated.

BMC Cardiovasc Disord 2021 05 1;21(1):223. Epub 2021 May 1.

Department of Interventional Cardiology, Royal Papworth Hospital, Papworth Road, Cambridge Biomedical Campus, Cambridge, CB2 0AY, UK.

Background: Incretin therapies appear to provide cardioprotection and improve cardiovascular outcomes in patients with diabetes, but the mechanism of this effect remains elusive. We have previously shown that glucagon-like peptide (GLP)-1 is a coronary vasodilator and we sought to investigate if this is an adenosine-mediated effect.

Methods: We recruited 41 patients having percutaneous coronary intervention (PCI) for stable angina and allocated them into four groups administering a specific study-related infusion following successful PCI: GLP-1 infusion (Group G) (n = 10); Placebo, normal saline infusion (Group P) (n = 11); GLP-1 + Theophylline infusion (Group GT) (n = 10); and Theophylline infusion (Group T) (n = 10). A pressure wire assessment of coronary distal pressure and flow velocity (thermodilution transit time-Tmn) at rest and hyperaemia was performed after PCI and repeated following the study infusion to derive basal and index of microvascular resistance (BMR and IMR).

Results: There were no significant differences in the demographics of patients recruited to our study. Most of the patients were not diabetic. GLP-1 caused significant reduction of resting Tmn that was not attenuated by theophylline: mean delta Tmn (SD) group G - 0.23 s (0.27) versus group GT - 0.18 s (0.37), p = 0.65. Theophylline alone (group T) did not significantly alter resting flow velocity compared to group GT: delta Tmn in group T 0.04 s (0.15), p = 0.30. The resulting decrease in BMR observed in group G persisted in group GT: - 20.83 mmHg s (24.54 vs. - 21.20 mmHg s (30.41), p = 0.97. GLP-1 did not increase circulating adenosine levels in group GT more than group T: delta median adenosine - 2.0 ng/ml (- 117.1, 14.8) versus - 0.5 ng/ml (- 19.6, 9.4); p = 0.60.

Conclusion: The vasodilatory effect of GLP-1 is not abolished by theophylline and GLP-1 does not increase adenosine levels, indicating an adenosine-independent mechanism of GLP-1 coronary vasodilatation.

Trial Registration: The local research ethics committee approved the study (National Research Ethics Service-NRES Committee, East of England): REC reference 14/EE/0018. The study was performed according to institutional guidelines, was registered on http://www.clinicaltrials.gov (unique identifier: NCT03502083) and the study conformed to the principles outlined in the Declaration of Helsinki.
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http://dx.doi.org/10.1186/s12872-021-02030-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088691PMC
May 2021

Rituximab in Patients with Acute ST-elevation Myocardial Infarction (RITA-MI): an Experimental Medicine Safety Study.

Cardiovasc Res 2021 Mar 30. Epub 2021 Mar 30.

Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, UK.

Aims: In pre-clinical models of acute myocardial infarction (MI), mature B cells mobilise inflammatory monocytes into the heart, leading to increased infarct size and deterioration of cardiac function, whilst anti-CD20 antibody mediated depletion of B cells limits myocardial injury and improves cardiac function. Rituximab is a monoclonal anti-CD20 antibody targeted against human B cells. However, its use in cardiovascular disease is untested and is currently contraindicated. Therefore, we assessed the safety, feasibility and pharmacodynamic effect of rituximab given to patients with acute ST elevation MI (STEMI).

Methods And Results: RITA-MI was a prospective, open-label, dose-escalation, single-arm, phase 1/2a clinical trial, which tested rituximab administered as a single intravenous dose in patients with STEMI within 48 hours of symptom onset. Four escalating doses (200, 500, 700 and 1000 mg) were used. The primary endpoint was safety, whilst secondary endpoints were changes in circulating immune cell subsets including B cells, and cardiac and inflammatory biomarkers. [NCT : 03072199]. A total of 24 patients were dosed. Rituximab appeared well tolerated. Seven serious adverse events were reported, none of which were assessed as being related to the rituximab infusion. Rituximab caused a mean 96.3% (95% CI 93.8-98.8%) depletion of circulating B cells within 30 mins of starting the infusion. Maximal B cell depletion was seen at day 6, which was significantly lower than baseline for all doses (p < 0.001). B cell repopulation at 6 months was dose-dependent, with modulation of returning B cell subsets. Immunoglobulin (IgG, IgM and IgA) levels were not affected during the 6 months of follow-up.

Conclusions: A single infusion of rituximab appears safe when given in the acute STEMI setting and substantially alters circulating B cell subsets. We provide important new insight into the feasibility and pharmacodynamics of rituximab in acute STEMI, which will inform further clinical translation of this potential therapy.

Clinical Trial Registration: NCT03072199 at https://www.clinicaltrials.gov/.

Translational Perspective: Selective depletion of B cells using anti-CD20 antibody has been shown to be beneficial in various pre-clinical models of myocardial infarction with additional supportive clinical observational data. Our research provides the first translational step in using this strategy in patients. We found rituximab to be safe and effective in rapidly and profoundly depleting B cells in patients after an acute myocardial infarction. This work has directly led to the funding and setup of a multi-centre, international, randomised, double-blind, placebo-controlled, phase 2 b clinical trial which should give us an indication of this strategy's clinical efficacy.
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http://dx.doi.org/10.1093/cvr/cvab113DOI Listing
March 2021

Balloon Pulmonary Angioplasty: State of the Art.

Interv Cardiol 2020 Apr 15;16:e02. Epub 2021 Feb 15.

Royal Papworth Hospital Cambridge, UK.

Balloon pulmonary angioplasty (BPA) is a novel technique for the treatment of chronic thromboembolic pulmonary hypertension. While cardiologists need no introduction to the concept of balloon angioplasty, BPA has its own particular challenges. This article aims to provide the reader with an overview of BPA, starting with an introduction to chronic thromboembolic disease (CTED), the standard management of chronic thromboembolic pulmonary hypertension (CTEPH), technical challenges faced when performing BPA and the evidence base supporting its use. The second part of the article will focus on the future of BPA, in particular the areas where research is required to establish an evidence base to justify the role of BPA in CTEPH and CTED treatment.
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http://dx.doi.org/10.15420/icr.2020.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903587PMC
April 2020

COVID-19 patient with coronary thrombosis supported with ECMO and Impella 5.0 ventricular assist device: a case report.

Eur Heart J Case Rep 2020 Dec 20;4(6):1-6. Epub 2020 Nov 20.

Royal Papworth Hospital, Cambridge CB2 0AY, UK.

Background: COVID-19 can present with cardiovascular complications.

Case Summary: We present a case report of a 43-year-old previously fit patient who suffered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with thrombosis of the coronary arteries causing acute myocardial infarction. These were treated with coronary stenting during which the patient suffered cardiac arrest. He was supported with automated chest compressions followed by peripheral veno-arterial extracorporeal membrane oxygenation (VA ECMO). No immediate recovery of the myocardial function was observed and, after insufficient venting of the left ventricle was diagnosed, an Impella 5 pump was implanted. The cardiovascular function recovered sufficiently and ECMO was explanted and inotropic infusions discontinued. Due to SARS-CoV-2 pulmonary infection, hypoxia became resistant to conventional mechanical ventilation and the patient was nursed prone overnight. After initial recovery of respiratory function, the patient received a tracheostomy and was allowed to wake up. Following a short period of agitation his neurological function recovered completely. During the third week of recovery, progressive multisystem dysfunction, possibly related to COVID-19, developed into multiorgan failure, and the patient died.

Discussion: We believe that this is the first case report of coronary thrombosis related to COVID-19. Despite the negative outcome in this patient, we suggest that complex patients may in the future benefit from advanced cardiovascular support, and may even be nursed safely in the prone position with Impella devices.
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http://dx.doi.org/10.1093/ehjcr/ytaa342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717226PMC
December 2020

Non-hyperaemic pressure ratios to guide percutaneous coronary intervention.

Open Heart 2020 10;7(2)

Monash Cardiovascular Research Centre and MonashHeart, Monash University and Monash Health, Melbourne, Victoria, Australia.

The use of fractional flow reserve (FFR) in guiding revascularisation improves patient outcomes and has been well-established in clinical guidelines. Despite this, the uptake of FFR has been limited, likely attributable to the perceived increase in procedural time and use of hyperaemic agents that can cause patient discomfort. This has led to the development of instantaneous wave-free ratio (iFR), an alternative non-hyperaemic pressure ratio (NHPR). Since its inception, the use of iFR has been supported by an increasing body of evidence and is now guideline recommended. More recently, other commercially available NHPRs including diastolic hyperaemia-free ratio and resting full-cycle ratio have emerged. Studies have demonstrated that these indices, in addition to mean distal coronary artery pressure to mean aortic pressure ratio, are mathematically analogous (with specific nuances) to iFR. Additionally, there is increasing data demonstrating the equivalent diagnostic performance of alternative NHPRs in comparison with iFR and FFR. These NHPRs are now integral within most current pressure wire systems and are commonly available in the catheter laboratory. It is therefore key to understand the fundamental differences and evidence for NHPRs to guide appropriate clinical decision-making.
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http://dx.doi.org/10.1136/openhrt-2020-001308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534727PMC
October 2020

Coronary artery dissection following radiofrequency ablation for atrial fibrillation: Case report and review of the literature.

Catheter Cardiovasc Interv 2021 02 5;97(2):287-291. Epub 2020 Aug 5.

Royal Papworth Hospital, Cambridge Biomedical Campus, Cambridge, UK.

Coronary artery injury following catheter ablation for cardiac arrhythmias is very rare. We present a case of left circumflex (LCx) coronary artery dissection causing inferoposterior ST-elevation myocardial infarction following radiofrequency (RF) ablation for atrial fibrillation (AF) in a 39-year-old male with no cardiovascular risk factors. This was confirmed on coronary angiography and intracoronary vascular ultrasound (IVUS). The likely etiology is thermal injury during RF ablation for AF, due to the close proximity of the left atrial appendage and left pulmonary veins to the LCx. He was successfully treated with primary percutaneous coronary intervention with good outcome. This is, to our knowledge, the first reported case of proven acute coronary dissection secondary to RF ablation for AF reported in the literature, and highlights the importance of considering this as a mechanism for coronary occlusion in these patients.
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http://dx.doi.org/10.1002/ccd.29183DOI Listing
February 2021

Recent advances in percutaneous coronary intervention.

Heart 2020 09 10;106(18):1380-1386. Epub 2020 Jun 10.

Interventional Cardiology, Royal Papworth Hospital NHS Foundation Trust, Cambridge, Cambridgeshire, UK.

Percutaneous coronary intervention (PCI) continues to advance at pace with an ever-broadening indication. In this article we will review the recent technological advances in PCI that have enabled more complex coronary disease to be treated. The choice of revascularisation strategy must take into account the evidence-just because we can treat by PCI does not necessarily mean we should. When PCI is indicated, a safe, precision PCI approach guided by physiology, imaging and optimal lesion preparation should be the goal to obtain complete revascularisation and a durable long-term result. When these standards are adhered to, the outcomes can be excellent, in even complex coronary disease. We provide contemporary trial evidence to justify PCI and treatment algorithms that ensure optimal revascularisation decision making to achieve the best patient outcomes.
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http://dx.doi.org/10.1136/heartjnl-2019-315707DOI Listing
September 2020

Chronic thromboembolic pulmonary hypertension: interventional approaches.

Heart 2020 10 13;106(19):1525-1531. Epub 2020 May 13.

Department of Cardiothoracic Surgery, Royal Papworth Hospital NHS Foundation Trust, Cambridge, Cambridgeshire, UK.

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http://dx.doi.org/10.1136/heartjnl-2019-316291DOI Listing
October 2020

Balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension: the UK experience.

Open Heart 2020 27;7(1):e001144. Epub 2020 Feb 27.

Pulmonary Vascular Disease Unit, Royal Papworth Hospital NHS foundation Trust, Cambridge, Cambridgeshire, United Kingdom.

Objective: Inoperable chronic thromboembolic pulmonary hypertension (CTEPH) managed medically has a poor prognosis. Balloon pulmonary angioplasty (BPA) offers a new treatment for inoperable patients. The national BPA service for the UK opened in October 2015 and we now describe the treatment of our initial patient cohort.

Methods: Thirty consecutive, inoperable, anatomically suitable, symptomatic patients on stable medical therapy for CTEPH were identified and offered BPA. They initially underwent baseline investigations including Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) quality of life (QoL) questionnaire, cardiopulmonary exercise test, 6 min walk distance (6MWD), transthoracic echocardiography, N-terminal probrain natriuretic peptide (NT pro-BNP) and right heart catheterisation. Serial BPA sessions were then performed and after completion, the treatment effect was gauged by comparing the same investigations at 3 months follow-up.

Results: A median of 3 (IQR 1-6) BPA sessions per patient resulted in a significant improvement in functional status (WHO functional class ≥3: 24 vs 4, p<0.0001) and QoL (CAMPHOR symptom score: 8.7±5.4 vs 5.6±6.1, p=0.0005) with reductions in pulmonary pressures (mean pulmonary artery pressure: 44.7±11.0 vs 34.4±8.3 mm Hg, p<0.0001) and resistance (pulmonary vascular resistance: 663±281 vs 436±196 dyn.s.cm, p<0.0001). Exercise capacity improved (minute ventilation/carbon dioxide production: 55.3±12.2 vs 45.0±7.8, p=0.03 and 6MWD: 366±107 vs 440±94 m, p<0.0001) and there was reduction in right ventricular (RV) stretch (NT pro-BNP: 442 (IQR 168-1607) vs 202 (IQR 105-447) pg/mL, p<0.0001) and dimensions (mid RV diameter: 4.4±1.0 vs 3.8±0.7 cm, p=0.002). There were no deaths or life-threatening complications and the mild-moderate per-procedure complication rate was 10.5%.

Conclusions: BPA is safe and improves the functional status, QoL, pulmonary haemodynamics and RV dimensions of patients with inoperable CTEPH.
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http://dx.doi.org/10.1136/openhrt-2019-001144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046957PMC
June 2020

Chronic infarct size after spontaneous coronary artery dissection: implications for pathophysiology and clinical management.

Eur Heart J 2020 06;41(23):2197-2205

Department of Cardiovascular Sciences, NIHR Leicester Biomedical Research Centre, University of Leicester, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.

Aims: To report the extent and distribution of myocardial injury and its impact on left ventricular systolic function with cardiac magnetic resonance imaging (CMR) following spontaneous coronary artery dissection (SCAD) and to investigate predictors of myocardial injury.

Methods And Results: One hundred and fifty-eight angiographically confirmed SCAD-survivors (98% female) were phenotyped by CMR and compared in a case-control study with 59 (97% female) healthy controls (44.5 ± 8.4 vs. 45.0 ± 9.1 years). Spontaneous coronary artery dissection presentation was with non-ST-elevation myocardial infarction in 95 (60.3%), ST-elevation myocardial infarction (STEMI) in 52 (32.7%), and cardiac arrest in 11 (6.9%). Left ventricular function in SCAD-survivors was generally well preserved with small reductions in ejection fraction (57 ± 7.2% vs. 60 ± 4.9%, P < 0.01) and increases in left ventricular dimensions (end-diastolic volume: 85 ± 14 mL/m2 vs. 80 ± 11 mL/m2, P < 0.05; end-systolic volume: 37 ± 11 mL/m2 vs. 32 ± 7 mL/m2, P <0.01) compared to healthy controls. Infarcts were small with few large infarcts (median 4.06%; range 0-30.9%) and 39% having no detectable late gadolinium enhancement (LGE). Female SCAD patients presenting with STEMI had similar sized infarcts to female Type-1 STEMI patients age <75 years. Multivariate modelling demonstrated STEMI at presentation, initial TIMI 0/1 flow, multivessel SCAD, and a Beighton score >4 were associated with larger infarcts [>10% left ventricular (LV) mass].

Conclusion: The majority of patients presenting with SCAD have no or small infarctions and preserved ejection fraction. Patients presenting with STEMI, TIMI 0/1 flow, multivessel SCAD and those with features of connective tissue disorders are more likely to have larger infarcts.
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http://dx.doi.org/10.1093/eurheartj/ehz895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299635PMC
June 2020

Ascertainment of Silent Myocardial Infarction in Patients Undergoing Percutaneous Coronary Intervention (from the GLOBAL LEADERS Trial).

Am J Cardiol 2019 12 26;124(12):1833-1840. Epub 2019 Sep 26.

Department of Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; Cardialysis B.V., Rotterdam, the Netherlands.

Q-wave myocardial infarction (QWMI) comprises 2 entities. First, a clinically evident MI, which can occur spontaneously or be related to a coronary procedure. Second, silent MI which is incidentally detected on serial electrocardiographic (ECG) assessment. The prevalence of silent MI after percutaneous coronary intervention (PCI) in the drug-eluting stent era has not been fully investigated. The GLOBAL LEADERS is an all-comers multicenter trial which randomized 15,991 patients who underwent PCI to 2 antiplatelet treatment strategies. The primary end point was a composite of all-cause death or nonfatal new QWMI at 2-years follow-up. ECGs were collected at discharge, 3-month and 2-year visits, and analyzed by an independent ECG core laboratory following the Minnesota code. All new QWMI were further reviewed by a blinded independent cardiologist to identify a potential clinical correlate by reviewing clinical information. Of 15,968 participants, ECG information was complete in 14,829 (92.9%) at 2 years. A new QWMI was confirmed in 186 (1.16%) patients. Transient new Q-waves were observed in 28.5% (53 of 186) of them during the follow-up. The majority of new QWMI (78%, 146 of 186) were classified as silent MI due to the absence of a clinical correlate. Silent MI accounted for 22.1% (146 of 660) of all MI events. The prevalence of silent MI did not differ significantly between treatment strategies (experimental vs reference: 0.88% vs 0.98%, p = 0.5027). In conclusion, we document the prevalence of silent MI in an all-comers population undergoing PCI in this large-scale randomized trial.
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http://dx.doi.org/10.1016/j.amjcard.2019.08.049DOI Listing
December 2019

Diagnosis of patients with angina and non-obstructive coronary disease in the catheter laboratory.

Heart 2019 10 31;105(20):1536-1542. Epub 2019 Jul 31.

The BHF Centre of Excellence and the NIHR Biomedical Research Centre at the School of Cardiovascular Medicine and Sciences, King's College London, London, UK.

Around 40% of all patients undergoing angiography are found to have normal coronary arteries or non-obstructive coronary artery disease (NOCAD). Despite the high prevalence, this is a group who rarely receive a definitive diagnosis, are frequently labelled and managed inappropriately and by and large, continue to remain symptomatic. Half of this group will have coronary microvascular dysfunction (CMD), associated with a higher rate of major adverse cardiovascular events; identifying CMD represents a therapeutic target of unmet need. As the pressure wire has revolutionised our ability to interrogate epicardial coronary disease during the time of angiography, measuring flow can similarly classify NOCAD during a single procedure. Assessment of flow is a function that is already integral to some pressure wires and furthermore, the familiarity and usage of the combined Doppler and pressure wire is rapidly increasing-these are techniques that readily lend themselves to the skillset of a practising interventional cardiologist. We present a structured algorithm designed for cardiologists who frequently encounter NOCAD in the catheter laboratory, identifying specific disease phenotypes within this heterogeneous population with linked therapy. This review paper clearly explains the rationale for this algorithm and outlines its applicability to routine clinical practice and also, the importance of phenotyping for future research. Ultimately, personalised therapy could improve outcomes for both patients and healthcare providers; while these approaches in turn will need robust evaluation to ensure that they improve both clinical outcomes and health economic benefits, this proposal will provide a framework for future trials and evaluations.
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http://dx.doi.org/10.1136/heartjnl-2019-315042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774766PMC
October 2019

The role of Glucagon-Like Peptide 1 Loading on periprocedural myocardial infarction During elective PCI (GOLD-PCI study): A randomized, placebo-controlled trial.

Am Heart J 2019 09 9;215:41-51. Epub 2019 Jun 9.

Department of Cardiology, Royal Papworth Hospital, Cambridge, United Kingdom; Department of Cardiovascular Medicine, University of Cambridge, United Kingdom. Electronic address:

Background: The incretin hormone glucagon-like peptide 1 (GLP-1) has been shown to protect against lethal ischemia-reperfusion injury in animal models and against nonlethal ischemia reperfusion injury in humans. Furthermore, GLP-1 receptor agonists have been shown to reduce major adverse cardiovascular and cerebrovascular events (MACCE) in large-scale studies. We sought to investigate whether GLP-1 reduced percutaneous coronary intervention (PCI)-associated myocardial infarction (PMI) during elective PCI.

Methods: The study was a randomized, double-blind controlled trial in which patients undergoing elective PCI received an intravenous infusion of either GLP-1 at 1.2 pmol/kg/min or matched 0.9% saline placebo before and during the procedure. Randomization was performed in 1:1 fashion, with stratification for diabetes mellitus. Six-hour cardiac troponin I (cTnI) was measured with a primary end point of PMI defined as rise ≫×5 upper limit of normal (280 ng/L). Secondary end points included cTnI rise and MACCE at 12 months.

Results: A total of 192 patients were randomized with 152 (79%) male and a mean age of 68.1 ± 8.9 years. No significant differences in patient demographics were noted between the groups. There was no difference in the rate of PMI between GLP-1 and placebo (9 [9.8%] vs 8 [8.3%], P = 1.0) or in the secondary end points of difference in median cTnI between groups (9.5 [0-88.5] vs 20 [0-58.5] ng/L, P = .25) and MACCE at 12 months (7 [7.3%] vs 9 [9.4%], P = .61).

Conclusions: In this randomized, placebo-controlled trial, GLP-1 did not reduce the low incidence of PMI or abrogate biomarker rise during elective PCI, nor did it influence the 12-month MACCE rate which also remained low.

Clinical Trial Registration: Clinicaltrials.gov Number: NCT02127996https://clinicaltrials.gov/ct2/show/NCT02127996.
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http://dx.doi.org/10.1016/j.ahj.2019.05.013DOI Listing
September 2019

DNA Damage and Repair in Patients With Coronary Artery Disease: Correlation With Plaque Morphology Using Optical Coherence Tomography (DECODE Study).

Cardiovasc Revasc Med 2019 Sep 23;20(9):812-818. Epub 2019 May 23.

Coronary Research Group, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Faculty of Medicine, University of Southampton, Southampton, UK. Electronic address:

Objective: The aim of this study was to examine DNA ligase activity and expression of DNA damage response pathway (DDR) genes in patients with stable angina (SA) and non-ST elevation myocardial infarction (NSTEMI) and determine whether they correlate with plaque morphology.

Background: Patients with coronary artery disease (CAD) have evidence of deoxyribonucleic acid (DNA) damage in peripheral blood mononuclear cells (PBMCs). It is unclear whether this represents excess damage or defective DNA repair activity.

Methods: DNA ligase activity and the expression of 22 DDR genes were measured in PBMCs of patients (both SA (n = 47) and NSTEMI (n = 42)) and in age and gender-matched controls (n = 35). Target lesion anatomical assessment was undertaken with frequency domain optical coherent tomography.

Results: DNA ligase activity was different across the three groups of patients (control = 119 ± 53, NSTEMI = 115.6 ± 85.1, SA = 81 ± 55.7 units/g of nuclear protein; ANOVA p = 0.023). Pair wise comparison demonstrated that this significance is due to differences between the control and SA patients (p = 0.046). Genes involved in double strand break repair and nucleotide excision repair pathways were differentially expressed in patients with SA and NSTEMI. In SA patients, fibrocalcific plaques were strongly associated with GTSE1, DDB1, MLH3 and ERCC1 expression. By contrast, in NSTEMI patients the strongest association was observed between fibrous plaques and ATM and XPA expression.

Conclusion: PBMCs from patients with CAD exhibit differences in DNA ligase activity and expression of DDR genes. Expression levels of certain DDR genes are strongly associated with plaque morphology and may play a role in plaque development and progression. Trial Registration Number URL: www.Clinicaltrials.gov; NCT02335086.
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http://dx.doi.org/10.1016/j.carrev.2019.04.028DOI Listing
September 2019

Glucagon-Like Peptide-1-Mediated Cardioprotection Does Not Reduce Right Ventricular Stunning and Cumulative Ischemic Dysfunction After Coronary Balloon Occlusion.

JACC Basic Transl Sci 2019 Apr 29;4(2):222-233. Epub 2019 Apr 29.

Department of Interventional Cardiology, Royal Papworth Hospital, Cambridge, United Kingdom.

Stunning and cumulative ischemic dysfunction occur in the left ventricle with coronary balloon occlusion. Glucagon-like peptide (GLP)-1 protects the left ventricle against this dysfunction. This study used a conductance catheter method to evaluate whether the right ventricle (RV) developed similar dysfunction during right coronary artery balloon occlusion and whether GLP-1 was protective. In this study, the RV underwent significant stunning and cumulative ischemic dysfunction with right coronary artery balloon occlusion. However, GLP-1 did not protect the RV against this dysfunction when infused after balloon occlusion.
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http://dx.doi.org/10.1016/j.jacbts.2018.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488814PMC
April 2019

Fractional flow reserve in acute coronary syndrome: a meta-analysis and systematic review.

Open Heart 2019;6(1):e000934. Epub 2019 Jan 13.

Department of Interventional Cardiology, Royal Papworth Hospital, Cambridge, UK.

Background: The utility of fractional flow reserve (FFR) to guide revascularisation in the management of acute coronary syndrome (ACS) remains unclear.

Objective: This study aims to compare the clinical outcomes of patients following FFR-guided revascularisation for either ACS or stable angina (SA) and in particular focuses on the outcome of those with deferred revascularisation after FFR.

Methods: A meta-analysis of existing literature was performed. Outcomes including the rate of major adverse cardiovascular events (MACE), recurrent myocardial infarction (MI), mortality and unplanned revascularisation were analysed.

Results: A review of 937 records yielded 9 studies comparing 5457 patients, which were included in the analyses. Patients with ACS had a higher rate of recurrent MI (OR 1.81, p=0.02) and a strong trend towards more MACE and all-cause mortality compared with patients with SA when treated by an FFR-guided revascularisation strategy. Deferral of invasive therapy on the basis of FFR led to a higher rate of MACE (17.6% vs 7.3 %; p=0.004), recurrent MI (5.3% vs 1.5%, p=0.001) and target vessel revascularisation (16.4% vs 5.6 %; p=0.02) in patients with ACS, and a strong trend towards a higher cardiovascular mortality at follow-up when compared with patients with SA.

Conclusion: The event rate in patients with ACS is much higher than SA despite following an FFR-guided revascularisation strategy. Deferring revascularisation does not appear to be as safe for ACS as it is for SA using contemporary FFR cut-offs validated in SA. Refinement of the therapeutic strategy for patients with ACS with multivessel disease is needed to redress the balance.
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http://dx.doi.org/10.1136/openhrt-2018-000934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350698PMC
February 2021

Long-Term Durability of Transcatheter Aortic Valve Prostheses.

J Am Coll Cardiol 2019 02;73(5):537-545

Department of Cardiology, Royal Victoria Hospital, Belfast, United Kingdom.

Background: Very little is known about long-term valve durability after transcatheter aortic valve replacement (TAVR).

Objectives: This study sought to evaluate the incidence of structural valve degeneration (SVD) 5 to 10 years post-procedure.

Methods: Demographic, procedural, and in-hospital outcome data on patients who underwent TAVR from 2007 to 2011 were obtained from the U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) registry. Patients in whom echocardiographic data were available both at baseline and ≥5 years post-TAVR were included. Hemodynamic SVD was determined according to European task force committee guidelines.

Results: A total of 241 patients (79.3 ± 7.5 years of age; 46% female) with paired post-procedure and late echocardiographic follow-up (median 5.8 years, range 5 to 10 years) were included. A total of 149 patients (64%) were treated with a self-expandable valve and 80 (34.7%) with a balloon-expandable valve. Peak aortic valve gradient at follow-up was lower than post-procedure (17.1 vs. 19.1 mm Hg; p = 0.002). More patients had none/trivial aortic regurgitation (AR) (47.5% vs. 33%), and fewer had mild AR (42.5% vs. 57%) at follow-up (p = 0.02). There was 1 case (0.4%) of severe SVD 5.3 years after implantation (new severe AR). There were 21 cases (8.7%) of moderate SVD (mean 6.1 years post-implantation; range 4.9 to 8.6 years). Twelve of these (57%) were due to new AR and 9 (43%) to restenosis.

Conclusions: Long-term transcatheter aortic valve function is excellent. In the authors' study, 91% of patients remained free of SVD between 5 and 10 years post-implantation. The incidence of severe SVD was <1%. Moderate SVD occurred in 1 in 12 patients.
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http://dx.doi.org/10.1016/j.jacc.2018.10.078DOI Listing
February 2019

Effects of Acute GLP-1 Infusion on Pulmonary and Systemic Hemodynamics in Patients With Heart Failure: A Pilot Study.

Clin Ther 2019 01 28;41(1):118-127.e0. Epub 2018 Dec 28.

Department of Interventional Cardiology, Royal Papworth Hospital NHS Foundation Trust, Cambridge, United Kingdom. Electronic address:

Purpose: Cardiovascular-safety studies assessing glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase 4 inhibitors have provided inconsistent data on the risk for developing heart failure. Animal studies have shown that GLP-1 is a vasodilator; if confirmed in humans, this may ameliorate heart failure symptoms.

Methods: In a single-center, observational pilot study, we recruited 10 patients with advanced heart failure undergoing right heart catheterization, and we recorded pulmonary hemodynamic measures, including cardiac output calculated by thermodilution and the indirect Fick method before and after a 15-minute continuous infusion of native GLP-1 (7-36) NH.

Findings: There was a neutral effect of GLP-1 on all pressure and hemodynamics indices as derived by cardiac output calculated by thermodilution. However, there was a small but consistent reduction in cardiac output as calculated by the indirect Fick method after GLP-1 infusion (baseline, 4.0 [1.1] L/min vs GLP-1, 3.6 [0.9] L/min; P = 0.003), driven by a consistent reduction in mixed venous oxygen saturation after GLP-1 infusion (baseline, 62.2% [7.0%] vs GLP-1, 59.3% [6.8%]; P < 0.001), whereas arterial saturation remained constant (baseline, 96.8% [3.3%] vs GLP-1, 97.0% [3.2%]; P = 0.34). This resulted in an increase in systemic vascular resistance by Fick (baseline, 1285 [228] dyn · s/cm vs GLP-1, 1562 [247] dyn · s/cm; P = 0.001).

Implications: Acute infusion of GLP-1 has a neutral hemodynamic effect, when assessed by thermodilution, in patients with heart failure. However, GLP-1 reduces mixed venous oxygen saturation. ClinicalTrials.gov identifier: NCT02129179.
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http://dx.doi.org/10.1016/j.clinthera.2018.11.013DOI Listing
January 2019

GLP-1 Is a Coronary Artery Vasodilator in Humans.

J Am Heart Assoc 2018 11;7(22):e010321

3 Department of Interventional Cardiology Royal Papworth Hospital NHS Foundation Trust Cambridge United Kingdom.

Background The mechanism underlying the beneficial cardiovascular effects of the incretin GLP-1 (glucagon-like peptide 1) and its analogues in humans is elusive. We hypothesized that activating receptors located on vascular smooth muscle cells to induce either peripheral or coronary vasodilatation mediates the cardiovascular effect of GLP -1. Methods and Results Ten stable patients with angina awaiting left anterior descending artery stenting underwent forearm blood flow measurement using forearm plethysmography and post-percutaneous coronary intervention coronary blood flow measurement using a pressure-flow wire before and after peripheral GLP -1 administration. Coronary sinus and artery bloods were sampled for GLP -1 levels. A further 11 control patients received saline rather than GLP -1 in the coronary blood flow protocol. GLP -1 receptor (GLP-1R) expression was assessed by immunohistochemistry using a specific GLP -1R monoclonal antibody in human tissue to inform the physiological studies. There was no effect of GLP -1 on absolute forearm blood flow or forearm blood flow ratio after GLP -1, systemic hemodynamics were not affected, and no binding of GLP -1R monoclonal antibody was detected in vascular tissue. GLP -1 reduced resting coronary transit time (mean [ SD ], 0.87 [0.39] versus 0.63 [0.27] seconds; P=0.02) and basal microcirculatory resistance (mean [ SD ], 76.3 [37.9] versus 55.4 [30.4] mm Hg/s; P=0.02), whereas in controls, there was an increase in transit time (mean [SD], 0.48 [0.24] versus 0.83 [0.41] seconds; P<0.001) and basal microcirculatory resistance (mean [SD], 45.9 [34.7] versus 66.7 [37.2] mm Hg/s; P=0.02). GLP -1R monoclonal antibody binding was confirmed in ventricular tissue but not in vascular tissue, and transmyocardial GLP -1 extraction was observed. Conclusions GLP -1 causes coronary microvascular dilation and increased flow but does not influence peripheral tone. GLP -1R immunohistochemistry suggests that GLP -1 coronary vasodilatation is indirectly mediated by ventricular-coronary cross talk.
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http://dx.doi.org/10.1161/JAHA.118.010321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404441PMC
November 2018
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