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Сърдечно-съдовата медицина през 2022 г.: най-добрите 10 статии за спешните състояния в кардиологията и исхемичната болест на сърцето

Percutaneous coronary intervention is increasingly guided by coronary physiology and optimized using intravascular imaging. Pressure-based measurements determine the significance of a stenosis using hyperemic or nonhyperemic pressure ratios (eg, the instantaneous wave-free ratio). Intravascular ultrasound and optical coherence tomography provide cross-sectional and longitudinal detail regarding plaque composition and vessel characteristics. These facilitate lesion preparation and optimization of stent sizing and positioning. This review explores the evidence-base and practical aspects of coregistering pressure gradient assessment and intravascular imaging with angiography. We then discuss gaps in the evidence and what is needed to help integrate these techniques into clinical practice.

Smart devices are a fundamental media for acquisition, processing, storage, and transfer of digital health data. The global penetration and high frequency usage of smart devices such as smartphones and fitness monitors provide us an opportunity for incorporation into clinical trials to generate more clinically meaningful data. Reporting of angina can significantly vary between patients and also within patients at different timepoints. Furthermore, the nature of angina can lead to variation in ways patients adapt their activities of daily living and hence reporting of symptoms and quality of life. Current clinical trials investigating the effects of intervention on angina do not accurately incorporate these patient centred outcomes and considerations. Hence, methods to contemporaneously assess daily angina burden in a convenient, patient focused, and cost-effective manner are priorities for contemporary clinical trials to address. In this article, we provide our insights into the use of remote digital smart devices in clinical trials of stable coronary artery disease conducted by our research group. We discuss how our experiences from previous trials necessitated its incorporation and will provide us with important data that will inform clinical practice. We discuss the benefits and current challenges and limitations of smart device incorporation while providing our procedural workflow for how we incorporated smart devices into our clinical trials for others to consider. We hope that this approach will allow us to understand the perceptions and implications of angina on patient lives with greater granularity than previously explored.

Coronary disease carries significant morbidity and mortality globally. The pandemic of obesity and diabetes combined with an aging population have resulted in a significant proportion of patients with multivessel coronary disease, the management of which poses significant challenges. A number of advancements in coronary intervention have emerged in the last few years allowing effective percutaneous management of complex coronary disease. In this review we examine the evidence base underpinning multivessel percutaneous coronary intervention across the spectrum of stable and acute coronary syndromes.

Background: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). Methods: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. Results: The median age was 68 years, 23% of participants were women, 51% had ST-segment–elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71–1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69–1.61]). Conclusions: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search ; Unique identifier: 2019-003244-79.

Aims Coronary flow reserve (CFR) assessment has proven clinical utility, but Doppler-based methods are sensitive to noise and operator bias, limiting their clinical applicability. The objective of the study is to expand the adoption of invasive Doppler CFR, through the development of artificial intelligence (AI) algorithms to automatically quantify coronary Doppler quality and track flow velocity. Methods and results A neural network was trained on images extracted from coronary Doppler flow recordings to score signal quality and derive values for coronary flow velocity and CFR. The outputs were independently validated against expert consensus. Artificial intelligence successfully quantified Doppler signal quality, with high agreement with expert consensus (Spearman’s rho: 0.94), and within individual experts. Artificial intelligence automatically tracked flow velocity with superior numerical agreement against experts, when compared with the current console algorithm [AI flow vs. expert flow bias −1.68 cm/s, 95% confidence interval (CI) −2.13 to −1.23 cm/s, P < 0.001 with limits of agreement (LOA) −4.03 to 0.68 cm/s; console flow vs. expert flow bias −2.63 cm/s, 95% CI −3.74 to −1.52, P < 0.001, 95% LOA −8.45 to −3.19 cm/s]. Artificial intelligence yielded more precise CFR values [median absolute difference (MAD) against expert CFR: 4.0% for AI and 7.4% for console]. Artificial intelligence tracked lower-quality Doppler signals with lower variability (MAD against expert CFR 8.3% for AI and 16.7% for console). Conclusion An AI-based system, trained by experts and independently validated, could assign a quality score to Doppler traces and derive coronary flow velocity and CFR. By making Doppler CFR more automated, precise, and operator-independent, AI could expand the clinical applicability of coronary microvascular assessment.

BACKGROUND: Patients hospitalised with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate efficacy of an acute coronary syndrome regimen in patients hospitalised with COVID-19 and coronary disease risk factors. PATIENTS/METHODS: A randomised controlled open-label trial across acute hospitals (UK and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28-days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, death). RESULTS: 320 patients from 9 centres were randomised. The trial terminated early due to low recruitment. At 30 days there was no significant difference in mortality (intervention: 11.5% vs control: 15%, unadjusted OR 0.73, 95%CI 0.38 to 1.41, p=0.355). Significant bleeds were infrequent and not significantly different between the arms (intervention: 1.9% vs control 1.9%, p>0.999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR 1.46, 95% CrI 0.88 to 2.37, Pr(Beta>0)=93%; adjusted OR 1.50, 95% CrI 0.91 to 2.45, Pr(Beta>0)=95%) and median time to discharge home was two days shorter (95% CrI -4 to 0, 2% probability that it was worse). CONCLUSIONS: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

There have been no studies comparing clinical outcomes of physiology-guided revascularization in patients with unprotected left main coronary disease (ULMD) between percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG). The aim of this study was to assess the long-term clinical outcomes between PCI and CABG of patients with physiologically significant ULMD. From an international multicenter registry of ULMD patients interrogated with instantaneous wave-free ratio (iFR), we analyzed data from 151 patients (85 PCI vs. 66 CABG) who underwent revascularization according to the cutoff value of iFR ≤ 0.89. Propensity score matching was employed to adjust for baseline clinical characteristics. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were the individual components of the primary endpoint. Mean age was 66.6 (± 9.2) years, 79.2% male. Mean SYNTAX score was 22.6 (± 8.4) and median iFR was 0.83 (IQR 0.74–0.87). After performing propensity score matching analysis, 48 patients treated with CABG were matched to those who underwent PCI. At a median follow-up period of 2.8 years, the primary endpoint occurred in 8.3% in PCI group and 20.8% in CABG group, respectively (HR 3.80; 95% CI 1.04–13.9; p = 0.043). There was no difference in each component of the primary event (p > 0.05 for all). Within the present study, iFR-guided PCI was associated with lower cardiovascular events rate in patients with ULMD and intermediate SYNTAX score, as compared to CABG. Graphical abstract State-of-the-art PCI vs. CABG for ULMD. Study design and primary endpoint in patients with physiologically significant ULMD. MACE was defined as the composite of all-cause death, non-fatal myocardial infarction, and target lesion revascularization. The blue line denotes the PCI arm, and the red line denotes the CABG arm. PCI was associated with significantly lower risk of MACE than CABG. CABG: coronary artery bypass grafting; iFR: instantaneous wave-free ratio; MACE: major adverse cardiovascular events; PCI: percutaneous coronary intervention; ULMD: unprotected left main coronary artery disease.

Aims Oxygen-pulse morphology and gas exchange analysis measured during cardiopulmonary exercise testing (CPET) has been associated with myocardial ischaemia. The aim of this analysis was to examine the relationship between CPET parameters, myocardial ischaemia and anginal symptoms in patients with chronic coronary syndrome and to determine the ability of these parameters to predict the placebo-controlled response to percutaneous coronary intervention (PCI). Methods and results Patients with severe single-vessel coronary artery disease (CAD) were randomized 1:1 to PCI or placebo in the ORBITA trial. Subjects underwent pre-randomization treadmill CPET, dobutamine stress echocardiography (DSE) and symptom assessment. These assessments were repeated at the end of a 6-week blinded follow-up period. A total of 195 patients with CPET data were randomized (102 PCI, 93 placebo). Patients in whom an oxygen-pulse plateau was observed during CPET had higher (more ischaemic) DSE score [+0.82 segments; 95% confidence interval (CI): 0.40 to 1.25, P = 0.0068] and lower fractional flow reserve (−0.07; 95% CI: −0.12 to −0.02, P = 0.011) compared with those without. At lower (more abnormal) oxygen-pulse slopes, there was a larger improvement of the placebo-controlled effect of PCI on DSE score [oxygen-pulse plateau presence (Pinteraction = 0.026) and oxygen-pulse gradient (Pinteraction = 0.023)] and Seattle angina physical-limitation score [oxygen-pulse plateau presence (Pinteraction = 0.037)]. Impaired peak VO2, VE/VCO2 slope, peak oxygen-pulse, and oxygen uptake efficacy slope was significantly associated with higher symptom burden but did not relate to severity of ischaemia or predict response to PCI. Conclusion Although selected CPET parameters relate to severity of angina symptoms and quality of life, only an oxygen-pulse plateau detects the severity of myocardial ischaemia and predicts the placebo-controlled efficacy of PCI in patients with single-vessel CAD.

In this article, we provide a historical view of key aspects of British Cardiovascular Society (BCS) influence in clinical trials of ischaemic heart disease (IHD) followed by key research and developments, notable publications and future perspectives. We discuss the role of the BCS and its members. The scope of this article covers clinical trials in stable IHD and acute coronary syndromes, including interventions relating to diagnosis, treatment and management. We discuss the role of the BCS in supporting the original RITA trials. We highlight the changing face of angina and its management providing contemporary and future insights into microvascular disease, ischaemic symptoms with no obstructive coronary arteries and, relatedly, myocardial infarction with no obstructive coronary arteries. The article is presented as a brief overview of the BCS in IHD research, relationships with stakeholders, patient and public involvement and clinical trials from the perspective of past, present and future possibilities.

Background: Retrievable stents and aspiration catheters have been developed to provide more effective arterial recanalisation in acute ischaemic stroke. Aims: The aim of this analysis was to test the effect of mechanical thrombectomy on mortality and longterm neurological outcome in patients presenting with acute large-vessel anterior circulation ischaemic stroke. Methods: A structured search identified randomised controlled trials of thrombectomy (using a retrievable stent or aspiration catheter) versus control on a background of medical therapy which included intravenous thrombolysis if appropriate. The primary endpoint was disability at 90-day follow-up as assessed by the modified Rankin scale (mRS). Secondary endpoints included all-cause mortality and symptomatic intracranial haemorrhage. A Bayesian mixed-effects model was used for analysis. Results: Twelve (12) trials met the inclusion criteria, comprising a total of 1,276 patients randomised to thrombectomy and 1,282 patients to control. Randomisation to thrombectomy significantly reduced disability at 90 days (OR 0.52, 95% credible interval 0.46 to 0.61, probability(control better)2 (OR 0.44, CrI 0.37 to 0.52, pr

Item does not contain fulltext BACKGROUND: Coronary blood flow in humans is known to be predominantly diastolic. Small studies in animals and humans suggest that this is less pronounced or even reversed in the right coronary artery (RCA). AIMS: This study aimed to characterise the phasic patterns of coronary flow in the left versus right coronary arteries of patients undergoing invasive physiological assessment. METHODS: We analysed data from the Iberian-Dutch-English Collaborators (IDEAL) study. A total of 482 simultaneous pressure and flow measurements from 301 patients were included in our analysis. RESULTS: On average, coronary flow was higher in diastole both at rest and during hyperaemia in both the RCA and LCA (mean diastolic-to-systolic velocity ratio [DSVR] was, respectively, 1.85±0.70, 1.76±0.58, 1.53±0.34 and 1.58±0.43 for LCA(rest), LCA(hyp), RCA(rest) and RCA(hyp), p

Background The efficacy of renal denervation has been controversial, but the procedure has now undergone several placebo-controlled trials. New placebo-controlled trial data has recently emerged, with longer follow-up of one trial and the full report of another trial (which constitutes 27% of the total placebo-controlled trial data). We therefore sought to evaluate the effect of renal denervation on ambulatory and office blood pressures in patients with hypertension. Methods We systematically identified all blinded placebo-controlled randomized trials of catheter-based renal denervation for hypertension. The primary efficacy outcome was ambulatory systolic blood pressure change relative to placebo. A random-effects meta-analysis was performed. Results 6 studies randomizing 1232 patients were eligible. 713 patients were randomized to renal denervation and 519 to placebo. Renal denervation significantly reduced ambulatory systolic blood pressure (−3.52 mmHg; 95% CI −4.94 to −2.09; p < 0.0001), ambulatory diastolic blood pressure (−1.93 mmHg; 95% CI −3.04 to −0.83, p = 0.0006), office systolic blood pressure size (−5.10 mmHg; 95% CI −7.31 to −2.90, p < 0.0001) and office diastolic pressure (effect size −3.11 mmHg; 95% CI −4.43 to −1.78, p < 0.0001). Adverse events were rare and not more common with denervation. Conclusions The totality of blinded, randomized placebo-controlled data shows that renal denervation is safe and provides genuine reduction in blood pressure for at least 6 months post-procedure. If this effect continues in the long term, renal denervation might provide a life-long 10% relative risk reduction in major adverse cardiac events and 7.5% relative risk reduction in all-cause mortality.

Сърдечно-съдовата медицина през 2022 г.: най-добрите 10 статии за спешните състояния в кардиологията и исхемичната болест на сърцето The year in cardiovascular medicine 2022: the top 10 papers in acute cardiac care and ischaemic heart disease

The main aims of therapy in chronic stable angina are to reduce the risk of myocardial infarction and death and improve symptoms and quality of life (QoL). Unblinded trials have shown that revascularization does not reduce the risk of myocardial infarction or death but does appear to improve symptoms. However, symptoms are susceptible to the placebo effect which can bias therapies to appear more effective than they are. To assess the true physical impact of a treatment on symptoms, placebo-controlled trials with patients and medical and research teams blinded to treatment allocation are necessary. Symptoms and QoL can be reported directly by the patient or indirectly by the physician. Patient-reported outcome measures in angina trials can include angina frequency, frequency of nitrate use, exercise capacity, and questionnaires such as the Seattle Angina Questionnaire (SAQ) and the generic EuroQOL-5D-5L (EQ-5D-5L) QoL questionnaire. Physician-assessed outcome measures include Canadian Cardiovascular Society Class. The Objective Randomised Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) trial was the first blinded placebo-controlled study investigating the role of percutaneous coronary intervention (PCI) in chronic stable angina. The trial showed a smaller than expected and not statistically significant effect of placebo-controlled PCI on the primary endpoint of change in exercise time at 6 weeks follow-up in single-vessel coronary artery disease. There was also no significant placebo-controlled treatment effect of PCI for the prespecified secondary endpoints of SAQ or EQ-5D-5L, although PCI did result in 20% more patients becoming free from angina than placebo in a non-prespecified secondary analysis. ORBITA has demonstrated the need for symptomatic and QoL effects of PCI to be studied using placebo control. Here, we describe ways of measuring QoL, the impact of the unblinded and blinded trials to date, what we have learned from ORBITA, and what is next for this common and complex condition.

This review article summarizes key landmark trials that have shaped understanding of the role of percutaneous coronary intervention (PCI) in stable coronary artery disease (CAD). The relationship between stenosis, ischemia, and angina is more complex than first imagined. Anginal relief remains the primary indication for PCI in stable CAD. The first placebo-controlled PCI trial showed a surprisingly small effect size, suggesting a significant placebo effect. PCI in stable CAD has not been shown to improve mortality or overall myocardial infarction rates, even in the presence of significant ischemia. Rather, risk reduction medical therapy remains the main intervention for improving outcomes.

Ischemia and no obstructive coronary arteries (INOCA) is a common clinical presentation, with a variety of causes that are often not fully investigated in routine clinical practice. The goal of our study was to characterize a real-world population of patients with INOCA, with a deeper focus on symptoms and stress test findings. The study population consisted of 435 patients who underwent diagnostic coronary angiography for anginal symptoms and/or evidence of myocardial ischemia at non-invasive imaging. In all patients angiography demonstrated nonobstructive coronary artery disease (CAD, less than 30% luminal diameter stenosis or fractional flow reserve > 0.8 and/or instantaneous wave-free ratio > 0.89). Fifty-four percent of the patients were women. Atypical clinical presentation was more common in women (59.5 vs. 49.5%, p = 0.037). Women were more likely to have normal coronary arteries than men (41.8 vs. 16.2%, p

AIMS: The aim of this study was to assess the acute performance of the 95 µm ArterioSorb oriented poly L-lactic acid (PLLA) scaffold in comparison with the XIENCE metallic drug-eluting stent (DES) in porcine coronary arteries. METHODS AND RESULTS: In 15 non-atherosclerotic Yucatan mini pigs, the ArterioSorb (3.0/14 mm) and XIENCE (3.0/15 mm) were implanted in 25 and 15 vessels, respectively. Acute performance was evaluated by using quantitative coronary angiography (QCA) and optical coherence tomography (OCT). Following three-dimensional reconstruction of the coronary arteries, endothelial shear stress (ESS) was quantified using non-Newtonian steady-flow simulation. Acute recoil measured by QCA was comparable in the two arms. Post-procedural flow and scaffold/stent area by OCT did not differ between the two devices. ESS post procedure was comparable between ArterioSorb and XIENCE (2.21±1.97 vs 2.25±1.71 Pa, p=0.314). CONCLUSIONS: Acute recoil, luminal dimensions and ESS in the ArterioSorb oriented PLLA scaffold with thin struts of 95 µm were comparable to those in the XIENCE metallic DES.

Transcatheter aortic valve replacement (TAVR) is the treatment of choice for patients with severe aortic stenosis who are at a moderate or higher surgical risk. Stroke is a recognised and serious complication of TAVR, and it is important to identify patients at higher stroke risk. This study aims to discover if aortic valve calcium score calculated from pre-TAVR computed tomography is associated with acute stroke in TAVR patients.We conducted a retrospective, observational cohort study of 433 consecutive patients undergoing TAVR between January 2017 and December 2019 at the Hammersmith Hospital.This cohort had a median age of 83 years (interquartile range, 78-87), and 52.7% were male. Fifty-two patients (12.0%) had a history of previous stroke or transient ischemic attack. Median aortic valve calcium score was 2145 (interquartile range, 1427-3247) Agatston units. Twenty-two patients had a stroke up to the time of discharge (5.1%). In a logistic regression model, aortic valve calcium score was significantly associated with acute stroke (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.01-1.53;Aortic valve calcium score from pre-TAVR computed tomography is an independent risk factor for acute stroke in the TAVR population. This is an additional clinical value of the pre-TAVR aortic valve calcium score and should be considered when discussing periprocedural stroke risk.

Percutaneous coronary intervention (PCI) is frequently performed for stable angina. However, the first blinded trial, ORBITA, did not show a placebo-controlled increment in exercise time in patients with single-vessel disease, at 6 weeks, on maximal antianginal therapy. ORBITA-2 will assess the placebo-controlled efficacy of PCI on angina frequency in patients with single- or multivessel disease, at 12 weeks, on no antianginal therapy. ORBITA-2 is a double-blind placebo-controlled trial randomising participants with (i) angina at presentation, (ii) documented angina during the 2-week pre-randomisation symptom assessment phase, (iii) objective evidence of ischaemia, (iv) single- or multivessel disease, and (v) clinical eligibility for PCI. At enrolment, antianginals will be stopped, and angina questionnaires completed. Participants will record their symptoms on a smartphone application daily throughout the trial and will undergo exercise treadmill testing and stress echocardiography at pre-randomisation. They will then undergo coronary angiography with unblinded invasive physiology assessment. Eligible participants will then be sedated to a deep level of conscious sedation and randomised 1:1 between PCI and placebo. After the 12-week blinded follow-up period, they will return for questionnaires, exercise testing and stress echocardiography assessment. If angina becomes intolerable, antianginals will be introduced using a prespecified medication protocol. The primary outcome is an angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include exercise treadmill time, angina frequency, angina severity and quality of life. Trial registration: ClinicalTrials.gov: NCT03742050.

Background The placebo effect is a well described phenomenon in blinded studies evaluating anti-anginal therapeutics, although its impact on clinical research metrics remains unknown. We conducted a systematic review and meta-analysis to quantify the impact of placebo on endpoints of symptoms, life-quality and functional outcomes in randomized placebo-controlled trials (RCTs) of symptomatic stable coronary artery disease. Methods We systematically reviewed MEDLINE, EMBASE, and the Cochrane database for double-blind RCTs of anti-angina therapeutics. Patients randomized to the placebo-arm were the study population. Main outcomes were the changes in exercise performance (exercise treadmill test [ETT] parameters), quality of life (Seattle Angina Questionnaire domains), symptoms (Canadian Cardiovascular Society angina class) and drug usage (nitroglycerin tabs/week) between baseline and following placebo. The primary outcome was ETT total duration time. Data were pooled with a random effect model. Results Seventy-eight RCTs (83% drug-controlled, 17% procedure-controlled) were included encompassing 4,925 patients randomized to placebo. ETT total duration time was significantly improved following placebo as compared to baseline (mean [95% confidence interval]: 29.2 [20.6-37.8] seconds) with evidence of high heterogeneity (I 2 = 98%) At subgroup analysis, crossover design was associated with a smaller placebo effect on ETT performance than parallel study design (p for interaction=0.001). A significant placebo effect was observed for all secondary outcomes with overall high heterogeneity. Conclusion A substantial placebo effect was present in angina RCTs across a variety of functional and life-quality metrics. High variability in placebo effect size was present, mostly unexplained by differences in study and patient characteristics (PROSPERO CRD42019132797).

Objectives-\ud Adenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis.\ud Methods-\ud Twenty-three patients (mean age, 60.6 ± 8.1 years) with CCS and single-vessel coronary stenosis underwent cardiac catheterization. Continuous trans-stenotic coronary pressure-flow measurements were performed during: i) IV adenosine hyperemia, and ii) physical exercise using a catheter-table-mounted supine ergometer. Systemic, coronary and microcirculatory hemodynamic responses were compared between IV adenosine and exercise stimuli.\ud Results-\ud Mean stenosis diameter was 74.6% ± 10.4. Median (interquartile range) FFR was 0.54 (0.44–0.72). At adenosine hyperemia versus exercise stress, mean aortic pressure (Pa, 91 ± 16 mmHg vs 99 ± 15 mmHg, p < 0.0001), distal coronary pressure (Pd, 58 ± 21 mmHg vs 69 ± 24 mmHg, p < 0.0001), trans-stenotic pressure ratio (Pd/Pa, 0.63 ± 0.18 vs 0.69 ± 0.19, p < 0.0001), microvascular resistance (MR, 2.9 ± 2.2 mmHg.cm−1.sec−1 vs 4.2 ± 1.7 mmHg.cm−1.sec−1, p = 0.001), heart rate (HR, 80 ± 15 bpm vs 85 ± 21 bpm, p = 0.02) and rate-pressure product (RPP, 7522 ± 2335 vs 9077 ± 3200, p = 0.0001) were all lower. Conversely, coronary flow velocity (APV, 23.7 ± 9.5 cm/s vs 18.5 ± 6.8 cm/s, p = 0.02) was higher. Additionally, temporal changes in Pa, Pd, Pd/Pa, MR, HR, RPP and APV during IV adenosine hyperemia versus exercise were all significantly different (p < 0.05 for all).\ud Conclusions-\ud In patients with CCS and coronary stenosis, invasive hemodynamic responses differed markedly between IV adenosine hyperemia versus physical exercise stress. These differences were observed across systemic, coronary and microcirculatory hemodynamics.

Background We sought to investigate sex-specific differences in authorship of cardiovascular research over the past decade. Methods and Results All 387 463 cardiovascular publications between 2010 and 2019 were retrieved from Web of Science. Articles increased from 19 960 to 29 604 articles per year (

Aim: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) forms a significant component of oxidised LDL. The effects of exercise on levels of MDA-LDL and anti-MDA-LDL antibodies are not well-understood. Furthermore, it is not known whether these can be modified in patients with coronary artery disease by percutaneous coronary intervention (PCI).Methods: The Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina (ORBITA) trial was the first blinded, multi-centre randomised trial of PCI vs. placebo procedure for angina relief. Serum samples were available at four time-points: pre-randomisation pre- (P1) and post- (P2) exercise and post-randomisation (6-weeks following the PCI or placebo procedure), pre- (P3) and post- (P4) exercise. ELISAs were performed using laboratory-developed assays for MDA-LDL (adjusted for Apolipoprotein B) and anti-MDA-LDL antibodies.Results: One hundred ninety-six of the 200 patients (age 66.1 [SD 8.99] years, 28% female) with severe single vessel coronary artery disease suitable for PCI enrolled in the ORBITA trial had blood available for analysis. With exercise at pre-randomisation (P2–P1) there was no significant change in adjusted MDA-LDL (−0.001, 95% CI −0.004 to 0.001; p = 0.287); however, IgG and IgM anti-MDA-LDL significantly declined (−0.022, 95% CI −0.029 to −0.014, p < 0.0001; −0.016, 95% CI −0.024 to −0.008, p = 0.0002, respectively). PCI did not have a significant impact on either the pre-exercise values (P3 controlling for P1) of MDA-LDL (p = 0.102), IgG (p = 0.444) or IgM anti-MDA-LDL (p = 0.909). Nor did PCI impact the exercise induced changes in these markers (P4 controlling for P1, P2, and P3) for MDA-LDL (p = 0.605), IgG (p = 0.725) or IgM anti-MDA-LDL (p = 0.171). Pre-randomisation ischaemia on stress echo did not impact these interactions.Conclusions: Exercise results in an acute reduction in anti-oxLDL antibodies in patients with severe single vessel coronary disease, possibly indicating an induction in homoeostatic clearance via the innate immune system. However, PCI did not ameliorate this effect.

During viral pandemics, filtering facepiece (FFP) masks together with eye protection form the essential components of personal protective equipment (PPE) for healthcare workers. There remain concerns regarding insufficient global supply and imperfect protection offered by currently available PPE strategies. A range of full-face snorkel masks were adapted to accept high grade medical respiratory filters using bespoke-designed 3D-printed connectors. We compared the protection offered by the snorkel to that of standard PPE using a placebo-controlled respirator filtering test as well as a fluorescent droplet deposition experiment. Out of the 56 subjects tested, 42 (75%) passed filtering testing with the snorkel mask compared to 31 (55%) with a FFP3 respirator mask (p = 0.003). Amongst the 43 subjects who were not excluded following a placebo control, 85% passed filtering testing with the snorkel versus to 68% with a FFP3 mask (p = 0.008). Following front and lateral spray of fluorescence liquid particles, the snorkel mask also provided superior protection against droplet deposition within the subject's face, when compared to a standard PPE combination of FFP3 masks and eye protection (3.19x108 versus 6.81x108 fluorescence units, p0.001). The 3D printable adaptors are available for free download online at https://www.ImperialHackspace.com/COVID-19-Snorkel-Respirator-Project/.Full-face snorkel masks adapted as particulate respirators performed better than a standard PPE combination of FFP3 mask and eye protection against aerosol inhalation and droplet deposition. This adaptation is therefore a promising PPE solution for healthcare workers during highly contagious viral outbreaks.

Supplemental Digital Content is available in the text., Background: Physiological assessment with pressure wire pullback can characterize coronary artery disease (CAD) with a focal or diffuse pattern. However, the clinical relevance of this distinction is unknown. We use data from the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) to test if the pattern of CAD predicts the placebo-controlled efficacy of percutaneous coronary intervention (PCI) on stress echocardiography ischemia and symptom end points. Methods: One hundred sixty-four patients in ORBITA underwent blinded instantaneous wave-free ratio (iFR) pullback assessment before randomization. Focal disease was defined as a ≥0.03 iFR unit drop within 15 mm, rather than over a longer distance. Analyses were performed using regression modeling. Results: In the PCI arm (n=85), 48 were focal and 37 were diffuse. In the placebo arm (n=79), 35 were focal and 44 were diffuse. Focal stenoses were associated with significantly lower fractional flow reserve (FFR) and iFR values than diffusely diseased vessels (mean FFR and iFR, focal 0.60±0.15 and 0.65±0.24, diffuse 0.78±0.10 and 0.88±0.08, respectively, P

Item does not contain fulltext OBJECTIVES: This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies. BACKGROUND: An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes. METHODS: This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. RESULTS: Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 +/- 0.51 vs. 0.43 +/- 0.59; p < 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p < 0.001). There was no difference in mean iFR value according to sex (0.91 +/- 0.09 vs. 0.91 +/- 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 +/- 0.09 vs. 0.85 +/- 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919). CONCLUSIONS: An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038).

Objectives: This study developed a neural network to perform automated pressure waveform analysis and allow real-time accurate identification of damping. Background: Damping of aortic pressure during coronary angiography must be identified to avoid serious complications and make accurate coronary physiology measurements. There are currently no automated methods to do this, and so identification of damping requires constant monitoring, which is prone to human error. Methods: The neural network was trained and tested versus core laboratory expert opinions derived from 2 separate datasets. A total of 5,709 aortic pressure waveforms of individual heart beats were extracted and classified. The study developed a recurrent convolutional neural network to classify beats as either normal, showing damping, or artifactual. Accuracies were reported using the opinions of 2 independent core laboratories. Results: The neural network was 99.4% accurate (95% confidence interval: 98.8% to 99.6%) at classifying beats from the testing dataset when judged against the opinions of the internal core laboratory. It was 98.7% accurate (95% confidence interval: 98.0% to 99.2%) when judged against the opinions of an external core laboratory not involved in neural network training. The neural network was 100% sensitive, with no beats classified as damped misclassified, with a specificity of 99.8%. The positive predictive and negative predictive values were 98.1% and 99.5%. The 2 core laboratories agreed more closely with the neural network than with each other. Conclusions: Arterial waveform analysis using neural networks allows rapid and accurate identification of damping. This demonstrates how machine learning can assist with patient safety and the quality control of procedures.