Publications by authors named "James P Howard"

73 Publications

Multibeat echocardiographic phase detection using deep neural networks.

Comput Biol Med 2021 Apr 6;133:104373. Epub 2021 Apr 6.

School of Computing and Engineering, University of West London, London, United Kingdom; National Heart and Lung Institute, Imperial College, London, United Kingdom.

Background: Accurate identification of end-diastolic and end-systolic frames in echocardiographic cine loops is important, yet challenging, for human experts. Manual frame selection is subject to uncertainty, affecting crucial clinical measurements, such as myocardial strain. Therefore, the ability to automatically detect frames of interest is highly desirable.

Methods: We have developed deep neural networks, trained and tested on multi-centre patient data, for the accurate identification of end-diastolic and end-systolic frames in apical four-chamber 2D multibeat cine loop recordings of arbitrary length. Seven experienced cardiologist experts independently labelled the frames of interest, thereby providing infallible annotations, allowing for observer variability measurements.

Results: When compared with the ground-truth, our model shows an average frame difference of -0.09 ± 1.10 and 0.11 ± 1.29 frames for end-diastolic and end-systolic frames, respectively. When applied to patient datasets from a different clinical site, to which the model was blind during its development, average frame differences of -1.34 ± 3.27 and -0.31 ± 3.37 frames were obtained for both frames of interest. All detection errors fall within the range of inter-observer variability: [-0.87, -5.51]±[2.29, 4.26] and [-0.97, -3.46]±[3.67, 4.68] for ED and ES events, respectively.

Conclusions: The proposed automated model can identify multiple end-systolic and end-diastolic frames in echocardiographic videos of arbitrary length with performance indistinguishable from that of human experts, but with significantly shorter processing time.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104373DOI Listing
April 2021

Meta-Analysis of Usefulness of Cerebral Embolic Protection During Transcatheter Aortic Valve Implantation.

Am J Cardiol 2021 05 5;146:69-73. Epub 2021 Feb 5.

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

One of the most feared complications of transcatheter aortic valve implantation (TAVI) is stroke, with increased mortality and disability observed in patients suffering a stroke after TAVI. There has been no significant decline in stroke rates seen over the last 5 years; attention has therefore been given to strategies for cerebral embolic protection. With the emergence of new randomized trial data, we sought to perform an updated systematic review and meta-analysis to examine the effect of cerebral embolic protection during TAVI both on clinical outcomes and on neuroimaging parameters. We performed a random-effects meta-analysis of randomized clinical trials of cerebral embolic protection during TAVI. The primary end point was the risk of stroke. The risk of stroke was not significantly different with the use of cerebral embolic protection: relative risk (RR) 0.88, 95% confidence interval (CI) 0.57 to 1.36, p = 0.566. Nor was there a significant reduction in the risk of disabling stroke, non-disabling stroke or death. There was no significant difference in total lesion volume on MRI with cerebral embolic protection: mean difference -74.94, 95% CI -174.31 to 24.4, p = 0.139. There was also not a significant difference in the number of new ischemic lesions on MRI: mean difference -2.15, 95% -5.25 to 0.96, p = 0.176, although there was significant heterogeneity for the neuroimaging outcomes. In conclusion, cerebral embolic protection during TAVI is safe but there is no evidence of a statistically significant benefit on clinical outcomes or neuroimaging parameters.
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http://dx.doi.org/10.1016/j.amjcard.2021.01.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082278PMC
May 2021

Randomized blinded placebo-controlled trials of renal sympathetic denervation for hypertension: A meta-analysis.

Cardiovasc Revasc Med 2021 Jan 30. Epub 2021 Jan 30.

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

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.
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http://dx.doi.org/10.1016/j.carrev.2021.01.031DOI Listing
January 2021

Single versus dual antiplatelet therapy after transcatheter aortic valve replacement: a meta-analysis of randomized clinical trials.

Cardiovasc Revasc Med 2021 Jan 22. Epub 2021 Jan 22.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Background: Guidelines recommend dual antiplatelet therapy (DAPT) after transcatheter aortic valve replacement (TAVR) but guidelines predate the publication of the largest randomized trial. There have been few trials in the field to date, and with a small number of total patients; pooling their results may therefore be helpful.

Methods: We systematically identified all randomized trials comparing SAPT to DAPT after TAVR. The primary endpoint was the risk of major bleeding. Secondary endpoints included all bleeding, life-threatening bleeding, stroke, myocardial infarction, death and cardiac death.

Results: Four trials, randomizing 1086 participants, were eligible (541 randomized to SAPT and 545 randomized to DAPT). The weighted mean follow-up was 9.1 months. The risk of major bleeding was significantly increased after DAPT (relative risk (RR) 2.36, 95% confidence interval (CI) 1.27 to 4.40, P = 0.007). There was a similar increased risk for all bleeding (RR 1.65, 95% CI 1.24 to 2.19, P < 0.001), although not for life-threatening bleeding (RR 1.44, 95% CI 0.74 to 2.77, P = 0.282). There were no significant differences in the risk of stroke, myocardial infarction (MI), death or cardiac death. There was no heterogeneity observed for any endpoint (I = 0.0%).

Conclusions: DAPT after TAVR is associated with an increased risk of major bleeding and all bleeding. There is no evidence of a significant difference between DAPT or SAPT for the risks of stroke, MI, death or cardiac death. However, the total number of patients randomized is small and the duration of follow-up is short. Larger scale randomized trials with longer follow-up are required to assess for any potential differences in ischemic endpoints or mortality.
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http://dx.doi.org/10.1016/j.carrev.2021.01.016DOI Listing
January 2021

Electrocardiographic predictors of successful resynchronization of left bundle branch block by His bundle pacing.

J Cardiovasc Electrophysiol 2021 Feb 4;32(2):428-438. Epub 2021 Jan 4.

National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, UK.

Background: His bundle pacing (HBP) is an alternative to biventricular pacing (BVP) for delivering cardiac resynchronization therapy (CRT) in patients with heart failure and left bundle branch block (LBBB). It is not known whether ventricular activation times and patterns achieved by HBP are equivalent to intact conduction systems and not all patients with LBBB are resynchronized by HBP.

Objective: To compare activation times and patterns of His-CRT with BVP-CRT, LBBB and intact conduction systems.

Methods: In patients with LBBB, noninvasive epicardial mapping (ECG imaging) was performed during BVP and temporary HBP. Intrinsic activation was mapped in all subjects. Left ventricular activation times (LVAT) were measured and epicardial propagation mapping (EPM) was performed, to visualize epicardial wavefronts. Normal activation pattern and a normal LVAT range were determined from normal subjects.

Results: Forty-five patients were included, 24 with LBBB and LV impairment, and 21 with normal 12-lead ECG and LV function. In 87.5% of patients with LBBB, His-CRT successfully shortened LVAT by ≥10 ms. In 33.3%, His-CRT resulted in complete ventricular resynchronization, with activation times and patterns indistinguishable from normal subjects. EPM identified propagation discontinuity artifacts in 83% of patients with LBBB. This was the best predictor of whether successful resynchronization was achieved by HBP (logarithmic odds ratio, 2.19; 95% confidence interval, 0.07-4.31; p = .04).

Conclusion: Noninvasive electrocardiographic mapping appears to identify patients whose LBBB can be resynchronized by HBP. In contrast to BVP, His-CRT may deliver the maximum potential ventricular resynchronization, returning activation times, and patterns to those seen in normal hearts.
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http://dx.doi.org/10.1111/jce.14845DOI Listing
February 2021

Automated analysis and detection of abnormalities in transaxial anatomical cardiovascular magnetic resonance images: a proof of concept study with potential to optimize image acquisition.

Int J Cardiovasc Imaging 2021 Mar 29;37(3):1033-1042. Epub 2020 Oct 29.

Department of Computing, National Heart and Lung Institute, Imperial College London, Imperial College Healthcare NHS Trust, London, UK.

The large number of available MRI sequences means patients cannot realistically undergo them all, so the range of sequences to be acquired during a scan are protocolled based on clinical details. Adapting this to unexpected findings identified early on in the scan requires experience and vigilance. We investigated whether deep learning of the images acquired in the first few minutes of a scan could provide an automated early alert of abnormal features. Anatomy sequences from 375 CMR scans were used as a training set. From these, we annotated 1500 individual slices and used these to train a convolutional neural network to perform automatic segmentation of the cardiac chambers, great vessels and any pleural effusions. 200 scans were used as a testing set. The system then assembled a 3D model of the thorax from which it made clinical measurements to identify important abnormalities. The system was successful in segmenting the anatomy slices (Dice 0.910) and identified multiple features which may guide further image acquisition. Diagnostic accuracy was 90.5% and 85.5% for left and right ventricular dilatation, 85% for left ventricular hypertrophy and 94.4% for ascending aorta dilatation. The area under ROC curve for diagnosing pleural effusions was 0.91. We present proof-of-concept that a neural network can segment and derive accurate clinical measurements from a 3D model of the thorax made from transaxial anatomy images acquired in the first few minutes of a scan. This early information could lead to dynamic adaptive scanning protocols, and by focusing scanner time appropriately and prioritizing cases for supervision and early reporting, improve patient experience and efficiency.
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http://dx.doi.org/10.1007/s10554-020-02050-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969571PMC
March 2021

Discriminating electrocardiographic responses to His-bundle pacing using machine learning.

Cardiovasc Digit Health J 2020 Jul-Aug;1(1):11-20

National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, United Kingdom.

Background: His-bundle pacing (HBP) has emerged as an alternative to conventional ventricular pacing because of its ability to deliver physiological ventricular activation. Pacing at the His bundle produces different electrocardiographic (ECG) responses: selective His-bundle pacing (S-HBP), non-selective His bundle pacing (NS-HBP), and myocardium-only capture (MOC). These 3 capture types must be distinguished from each other, which can be challenging and time-consuming even for experts.

Objective: The purpose of this study was to use artificial intelligence (AI) in the form of supervised machine learning using a convolutional neural network (CNN) to automate HBP ECG interpretation.

Methods: We identified patients who had undergone HBP and extracted raw 12-lead ECG data during S-HBP, NS-HBP, and MOC. A CNN was trained, using 3-fold cross-validation, on 75% of the segmented QRS complexes labeled with their capture type. The remaining 25% was kept aside as a testing dataset.

Results: The CNN was trained with 1297 QRS complexes from 59 patients. Cohen kappa for the neural network's performance on the 17-patient testing set was 0.59 (95% confidence interval 0.30 to 0.88; <.0001), with an overall accuracy of 75%. The CNN's accuracy in the 17-patient testing set was 67% for S-HBP, 71% for NS-HBP, and 84% for MOC.

Conclusion: We demonstrated proof of concept that a neural network can be trained to automate discrimination between HBP ECG responses. When a larger dataset is trained to higher accuracy, automated AI ECG analysis could facilitate HBP implantation and follow-up and prevent complications resulting from incorrect HBP ECG analysis.
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http://dx.doi.org/10.1016/j.cvdhj.2020.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484933PMC
September 2020

Drug-Eluting Stents Versus Bypass Surgery for Left Main Disease: An Updated Meta-Analysis of Randomized Controlled Trials With Long-Term Follow-Up.

Am J Cardiol 2020 10 30;132:168-172. Epub 2020 Jun 30.

The Cardiovascular Research Foundation, New York, New York; Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, New York.

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http://dx.doi.org/10.1016/j.amjcard.2020.06.059DOI Listing
October 2020

Bias, heterogeneity, and uncertainty in meta-analysis.

Eur Heart J 2020 07;41(28):2712

National Heart and Lung Institute, Imperial College London, Du Cane Road, London W12 0HS, UK.

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http://dx.doi.org/10.1093/eurheartj/ehaa394DOI Listing
July 2020

Artificial Intelligence, Data Sensors and Interconnectivity: Future Opportunities for Heart Failure.

Card Fail Rev 2020 Mar 12;6:e11. Epub 2020 May 12.

Imperial Centre for Cardiac Engineering, National Heart and Lung Institute, Imperial College London, UK.

A higher proportion of patients with heart failure have benefitted from a wide and expanding variety of sensor-enabled implantable devices than any other patient group. These patients can now also take advantage of the ever-increasing availability and affordability of consumer electronics. Wearable, on- and near-body sensor technologies, much like implantable devices, generate massive amounts of data. The connectivity of all these devices has created opportunities for pooling data from multiple sensors - so-called interconnectivity - and for artificial intelligence to provide new diagnostic, triage, risk-stratification and disease management insights for the delivery of better, more personalised and cost-effective healthcare. Artificial intelligence is also bringing important and previously inaccessible insights from our conventional cardiac investigations. The aim of this article is to review the convergence of artificial intelligence, sensor technologies and interconnectivity and the way in which this combination is set to change the care of patients with heart failure.
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http://dx.doi.org/10.15420/cfr.2019.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265101PMC
March 2020

Complete Revascularization by Percutaneous Coronary Intervention for Patients With ST-Segment-Elevation Myocardial Infarction and Multivessel Coronary Artery Disease: An Updated Meta-Analysis of Randomized Trials.

J Am Heart Assoc 2020 06 1;9(12):e015263. Epub 2020 Jun 1.

Columbia University Medical Center/New York-Presbyterian Hospital New York NY.

Background For patients with ST-segment-elevation myocardial infarction (STEMI) and multivessel coronary artery disease, the optimal treatment of the non-infarct-related artery has been controversial. This up-to-date meta-analysis focusing on individual clinical end points was performed to further evaluate the benefit of complete revascularization with percutaneous coronary intervention for patients with STEMI and multivessel coronary artery disease. Methods and Results We systematically identified all randomized trials comparing complete revascularization with percutaneous coronary intervention to culprit-only revascularization for multivessel disease in STEMI and performed a random-effects meta-analysis. The primary efficacy end point was cardiovascular death analyzed on an intention-to-treat basis. Secondary end points included all-cause mortality, myocardial infarction, and unplanned revascularization. Ten studies (7542 patients) were included: 3664 patients were randomized to complete revascularization and 3878 to culprit-only revascularization. Across all patients, complete revascularization was superior to culprit-only revascularization for reduction in the risk of cardiovascular death (relative risk [RR], 0.68; 95% CI, 0.47-0.98; =0.037; I=21.8%) and reduction in the risk of myocardial infarction (RR, 0.65; 95% CI, 0.54-0.79; <0.0001; I=0.0%). Complete revascularization also significantly reduced the risk of unplanned revascularization (RR, 0.37; 95% CI, 0.28-0.51; <0.0001; I=64.7%). The difference in all-cause mortality with percutaneous coronary intervention was not statistically significant (RR, 0.85; 95% CI, 0.69-1.04; =0.108; I=0.0%). Conclusions For patients with STEMI and multivessel disease, complete revascularization with percutaneous coronary intervention significantly improves hard clinical outcomes including cardiovascular death and myocardial infarction. These data have implications for clinical practice guidelines regarding recommendations for complete revascularization following STEMI.
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http://dx.doi.org/10.1161/JAHA.119.015263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429036PMC
June 2020

Inter-observer differences in interpretation of coronary pressure-wire pullback data by non-expert interventional cardiologists.

Cardiovasc Interv Ther 2020 May 19. Epub 2020 May 19.

Hammersmith Hospital, Imperial College London, London, UK.

The physiological pattern of coronary artery disease as determined by pressure-wire (PW)-pullback is important for decision-making of revascularization and risk stratification of patients. However, it remains unclear whether inter-observer differences in interpreting PW-pullback data are subject to the expertise of physicians. This study sought to investigate the subjectivity of this assessment among non-experts. Expert interventional cardiologists classified 545 PW-pullback traces into physiologically focal or physiologically diffuse disease pattern. Defining expert-consensus as the reference standard, we evaluated ten non-expert doctors' classification performance. Observers were stratified equally by two ways: (i) years of experience as interventional cardiologists (middle-level vs. junior-level) and (ii) volume of institutions where they belonged to (high-volume center vs. low-volume center). When judged against the expert-consensus, the agreement of non-expert observers in assessing physiological pattern of disease (focal or diffuse) ranged from 69.1 to 85.0% (p for heterogeneity < 0.0001). There was no evidence for a moderating effect of years of experience; the pooled accuracy of middle-level doctors was 78.8% (95% confidential interval [CI] 72.8-84.7%) vs. 79.1% for junior-level doctors (95% CI 75.9-82.2%, p = 0.95 for difference). On the other hand, we observed a significant moderating effect of center volume. Accuracy across non-experts in high-volume centers was 82.7% (95% CI 80.3-85.1%) vs. 75.1% for low-volume centers (95% CI 71.9-78.3%, p = 0.0002 for difference). Interpretation of PW-pullback by non-expert interventional cardiologists was considerably subjective.
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http://dx.doi.org/10.1007/s12928-020-00673-3DOI Listing
May 2020

Safety of Revascularization Deferral of Left Main Stenosis Based on Instantaneous Wave-Free Ratio Evaluation.

JACC Cardiovasc Interv 2020 07 13;13(14):1655-1664. Epub 2020 May 13.

Cardiovascular Science, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom. Electronic address:

Objectives: The aim of this study was to assess the long-term clinical outcomes of patients with left main coronary artery (LM) stenosis in whom treatment strategy was based on the instantaneous wave-free ratio (iFR).

Background: The overall safety of iFR to guide revascularization decision making in patients with stable coronary artery disease has been established. However, no study has examined the safety of deferral of revascularization of LM disease on the basis of iFR.

Methods: This multicenter observational study included 314 patients in whom LM stenosis was deferred (n = 163 [51.9%]) or revascularized (n = 151 [48.1%]) according to the iFR cutoff ≤0.89. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were each individual component of the primary endpoint and also cardiac death.

Results: At a median follow-up period of 30 months, the primary endpoint occurred in 15 patients (9.2%) in the deferred group and 22 patients (14.6%) in the revascularized group (hazard ratio: 1.45; 95% confidence interval: 0.75 to 2.81; p = 0.26), indicating no evidence of a significant difference between the 2 groups. For the secondary endpoints, findings in the iFR-based deferral and revascularization groups were as follows: all-cause death, 3.7% versus 4.6%; cardiac death, 1.2% versus 2.0%; nonfatal myocardial infarction, 2.5% versus 5.3%; and target lesion revascularization, 4.3% versus 5.3% (p > 0.05 for all).

Conclusions: Deferral of revascularization of LM stenosis on the basis of iFR appears to be safe, with similar long-term outcomes to those in patients in whom LM revascularization was performed according to iFR values.
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http://dx.doi.org/10.1016/j.jcin.2020.02.035DOI Listing
July 2020

Difference in functional assessment of individual stenosis severity in serial coronary lesions between resting and hyperemic pressure-wire pullback: Insights from the GIFT registry.

Int J Cardiol 2020 08 3;312:10-15. Epub 2020 May 3.

Cardiovascular Science, Imperial College London, Hammersmith Hospital, London, United Kingdom.

Background: Identifying the individual hemodynamic significance of tandem coronary artery lesions can be complicated by the crosstalk phenomenon which occurs between serial stenoses under hyperemic conditions. Physiological assessments performed under resting conditions are considered to be, theoretically, less affected by the hemodynamic interaction between serial coronary stenoses. The purpose of this study was to assess whether pressure-wire (PW) pullback measurements at rest and during hyperemia provided different information as to which stenosis appeared to be most functionally significant.

Methods: In consecutive patients with angiographically discrete serial lesions, physiological lesion predominance (i.e. proximal or distal) was defined according to the pressure gradient along the vessels on PW-pullback trace. We used instantaneous wave-free ratio (iFR) based assessment as the reference standard and compared fractional flow reserve (FFR) based and hyperemic-iFR based lesion predominance.

Results: Eighty-eight vessels (70 patients, mean age 70.3 ± 9.4 years, 80% male) were included in this study. Median iFR, FFR and hyperemic-iFR were 0.85 (interquartile range [IQR]: 0.74 to 0.91), 0.73 (IQR: 0.65 to 0.80) and 0.60 (IQR: 0.49 to 0.71), respectively. When judged against iFR-pullback based physiological assessment, lesion predominance changed in 22.7% (20/88) in FFR and in 20.5% (18/88) in hyperemic-iFR, respectively. There was no statistical difference between FFR and hyperemic-iFR for the impact on these changes (p = 0.77).

Conclusions: In serial coronary lesions, hyperemic PW-pullback disagreed with resting PW-pullback on the lesion-specific identification of ischemia in approximately 20% of cases, either in whole cardiac cycle or in wave-free period.
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http://dx.doi.org/10.1016/j.ijcard.2020.05.001DOI Listing
August 2020

Beta-blocker efficacy across different cardiovascular indications: an umbrella review and meta-analytic assessment.

BMC Med 2020 05 5;18(1):103. Epub 2020 May 5.

University of Birmingham Institute of Cardiovascular Sciences, Medical School, Birmingham, B15 2TT, UK.

Background: Beta-blockers are widely used for many cardiovascular conditions; however, their efficacy in contemporary clinical practice remains uncertain.

Methods: We performed a prospectively designed, umbrella review of meta-analyses of randomised controlled trials (RCTs) investigating the evidence of beta-blockers in the contemporary management of coronary artery disease (CAD), heart failure (HF), patients undergoing surgery or hypertension (registration: PROSPERO CRD42016038375). We searched MEDLINE, EMBASE and the Cochrane Library from inception until December 2018. Outcomes were analysed as beta-blockers versus control for all-cause mortality, myocardial infarction (MI), incident HF or stroke. Two independent investigators abstracted the data, assessed the quality of the evidence and rated the certainty of evidence.

Results: We identified 98 meta-analyses, including 284 unique RCTs and 1,617,523 patient-years of follow-up. In CAD, 12 meta-analyses (93 RCTs, 103,481 patients) showed that beta-blockers reduced mortality in analyses before routine reperfusion, but there was a lack of benefit in contemporary studies where ≥ 50% of patients received thrombolytics or intervention. Beta-blockers reduced incident MI at the expense of increased HF. In HF with reduced ejection fraction, 34 meta-analyses (66 RCTs, 35,383 patients) demonstrated a reduction in mortality and HF hospitalisation with beta-blockers in sinus rhythm, but not in atrial fibrillation. In patients undergoing surgery, 23 meta-analyses (89 RCTs, 19,211 patients) showed no effect of beta-blockers on mortality for cardiac surgery, but increased mortality in non-cardiac surgery. In non-cardiac surgery, beta-blockers reduced MI after surgery but increased the risk of stroke. In hypertension, 27 meta-analyses (36 RCTs, 260,549 patients) identified no benefit versus placebo, but beta-blockers were inferior to other agents for preventing mortality and stroke.

Conclusions: Beta-blockers substantially reduce mortality in HF patients in sinus rhythm, but for other conditions, clinicians need to weigh up both benefit and potential risk.
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http://dx.doi.org/10.1186/s12916-020-01564-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199339PMC
May 2020

Per-Vessel Level Analysis of Fractional Flow Reserve and Instantaneous Wave-Free Ratio Discordance - Insights From the AJIP Registry.

Circ J 2020 05 22;84(6):1034-1038. Epub 2020 Apr 22.

Cardiovascular Science, Imperial College London.

Background: The per-vessel level impact of physiological pattern of disease on the discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) has not been clarified.Methods and Results:Using the AJIP registry, vessels with FFR/iFR discordance (133/671 [19.8%]) were analyzed. In the left anterior descending artery (LAD), physiologically diffuse disease, as assessed by pressure-wire pullback, was associated with FFR-/iFR+ (83.3% [40/48]), while physiologically focal disease was associated with FFR+/iFR- (57.4% [31/54]), significantly (P<0.0001). These differences were not significant in non-LAD (P=0.17).

Conclusions: The impact of physiological pattern of disease on FFR/iFR discordance is more pronounced in the LAD.
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http://dx.doi.org/10.1253/circj.CJ-19-0785DOI Listing
May 2020

An optimisation-based iterative approach for speckle tracking echocardiography.

Med Biol Eng Comput 2020 Jun 7;58(6):1309-1323. Epub 2020 Apr 7.

National Heart and Lung Institute, Imperial College London, London, UK.

Speckle tracking is the most prominent technique used to estimate the regional movement of the heart based on echocardiograms. In this study, we propose an optimised-based block matching algorithm to perform speckle tracking iteratively. The proposed technique was evaluated using a publicly available synthetic echocardiographic dataset with known ground-truth from several major vendors and for healthy/ischaemic cases. The results were compared with the results from the classic (standard) two-dimensional block matching. The proposed method presented an average displacement error of 0.57 pixels, while classic block matching provided an average error of 1.15 pixels. When estimating the segmental/regional longitudinal strain in healthy cases, the proposed method, with an average of 0.32 ± 0.53, outperformed the classic counterpart, with an average of 3.43 ± 2.84. A similar superior performance was observed in ischaemic cases. This method does not require any additional ad hoc filtering process. Therefore, it can potentially help to reduce the variability in the strain measurements caused by various post-processing techniques applied by different implementations of the speckle tracking. Graphical Abstract Standard block matching versus proposed iterative block matching approach.
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http://dx.doi.org/10.1007/s11517-020-02142-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211789PMC
June 2020

Improving ultrasound video classification: an evaluation of novel deep learning methods in echocardiography.

J Med Artif Intell 2020 Mar;3

National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, UK.

Echocardiography is the commonest medical ultrasound examination, but automated interpretation is challenging and hinges on correct recognition of the 'view' (imaging plane and orientation). Current state-of-the-art methods for identifying the view computationally involve 2-dimensional convolutional neural networks (CNNs), but these merely classify individual frames of a video in isolation, and ignore information describing the movement of structures throughout the cardiac cycle. Here we explore the efficacy of novel CNN architectures, including time-distributed networks and two-stream networks, which are inspired by advances in human action recognition. We demonstrate that these new architectures more than halve the error rate of traditional CNNs from 8.1% to 3.9%. These advances in accuracy may be due to these networks' ability to track the movement of specific structures such as heart valves throughout the cardiac cycle. Finally, we show the accuracies of these new state-of-the-art networks are approaching expert agreement (3.6% discordance), with a similar pattern of discordance between views.
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http://dx.doi.org/10.21037/jmai.2019.10.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100611PMC
March 2020

Mortality after drug-eluting stents vs. coronary artery bypass grafting for left main coronary artery disease: a meta-analysis of randomized controlled trials.

Eur Heart J 2020 09;41(34):3228-3235

Center for Interventional Vascular Therapy, Columbia University Medical Center, NewYork-Presbyterian Hospital, 161 Fort Washington Avenue, New York, NY 10032, USA.

Aims: The optimal method of revascularization for patients with left main coronary artery disease (LMCAD) is controversial. Coronary artery bypass graft surgery (CABG) has traditionally been considered the gold standard therapy, and recent randomized trials comparing CABG with percutaneous coronary intervention (PCI) with drug-eluting stents (DES) have reported conflicting outcomes. We, therefore, performed a systematic review and updated meta-analysis comparing CABG to PCI with DES for the treatment of LMCAD.

Methods And Results: We systematically identified all randomized trials comparing PCI with DES vs. CABG in patients with LMCAD. The primary efficacy endpoint was all-cause mortality. Secondary endpoints included cardiac death, myocardial infarction (MI), stroke, and unplanned revascularization. All analyses were by intention-to-treat. There were five eligible trials in which 4612 patients were randomized. The weighted mean follow-up duration was 67.1 months. There were no significant differences between PCI and CABG for the risk of all-cause mortality [relative risk (RR) 1.03, 95% confidence interval (CI) 0.81-1.32; P = 0.779] or cardiac death (RR 1.03, 95% CI 0.79-1.34; P = 0.817). There were also no significant differences in the risk of stroke (RR 0.74, 95% CI 0.35-1.50; P = 0.400) or MI (RR 1.22, 95% CI 0.96-1.56; P = 0.110). Percutaneous coronary intervention was associated with an increased risk of unplanned revascularization (RR 1.73, 95% CI 1.49-2.02; P < 0.001).

Conclusion: The totality of randomized clinical trial evidence demonstrated similar long-term mortality after PCI with DES compared with CABG in patients with LMCAD. Nor were there significant differences in cardiac death, stroke, or MI between PCI and CABG. Unplanned revascularization procedures were less common after CABG compared with PCI. These findings may inform clinical decision-making between cardiologists, surgeons, and patients with LMCAD.
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http://dx.doi.org/10.1093/eurheartj/ehaa135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557472PMC
September 2020

Long-Term Effects of Transcatheter Aortic Valve Implantation on Coronary Hemodynamics in Patients With Concomitant Coronary Artery Disease and Severe Aortic Stenosis.

J Am Heart Assoc 2020 03 27;9(5):e015133. Epub 2020 Feb 27.

Heart Centre Amsterdam UMC Amsterdam the Netherlands.

Background As younger patients are being considered for transcatheter aortic valve implantation (TAVI), the assessment and treatment of concomitant coronary artery disease is taking on increased importance. Methods and Results Thirteen contemporary lower-risk patients with TAVI with severe aortic stenosis (AS) and moderate-severe coronary lesions were included. Patients underwent assessment of coronary hemodynamics in the presence of severe AS (pre-TAVI), in the absence of severe AS (immediately post-TAVI), and at longer-term follow-up (6 months post-TAVI). Fractional flow reserve decreased from 0.85 (0.76-0.88) pre-TAVI to 0.79 (0.74-0.83) post-TAVI, and then to 0.71 (0.65-0.77) at 6-month follow-up (<0.001 for all comparisons). Conversely, instantaneous wave-free ratio was not significantly different: 0.82 (0.80-0.90) pre-TAVI, 0.83 (0.77-0.88) post-TAVI, and 0.83 (0.73-0.89) at 6 months (=0.735). These changes are explained by the underlying coronary flow. Hyperemic whole-cycle coronary flow (fractional flow reserve flow) increased from 26.36 cm/s (23.82-31.82 cm/s) pre-TAVI to 30.78 cm/s (29.70-34.68 cm/s) post-TAVI (=0.012), to 40.20 cm/s (32.14-50.00 cm/s) at 6-month follow-up (<0.001 for both comparisons). Resting flow during the wave-free period of diastole was not significantly different: 25.48 cm/s (21.12-33.65 cm/s) pre-TAVI, 24.54 cm/s (20.74-27.88 cm/s) post-TAVI, and 25.89 cm/s (22.57-28.96 cm/s) at 6 months (=0.500). Conclusions TAVI acutely improves whole-cycle hyperemic coronary flow, with ongoing sustained improvements at longer-term follow-up. This enhanced response to hyperemic stimuli appears to make fractional flow reserve assessment less suitable for patients with severe AS. Conversely, resting diastolic flow is not significantly influenced by the presence of severe AS. Resting indices of coronary stenosis severity, therefore, appear to be more appropriate for this patient population, although large-scale prospective randomized trials will be required to determine the role of coronary physiology in patients with severe AS.
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http://dx.doi.org/10.1161/JAHA.119.015133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335578PMC
March 2020

Effects of Percutaneous Coronary Intervention on Death and Myocardial Infarction Stratified by Stable and Unstable Coronary Artery Disease: A Meta-Analysis of Randomized Controlled Trials.

Circ Cardiovasc Qual Outcomes 2020 02 17;13(2):e006363. Epub 2020 Feb 17.

Imperial College London, United Kingdom (L.C., J.H., C.R., A.N.N., C.K., D.M.,M.F., M.S.-S., G.C., S.S., R.A.-L., D.P.F., Y.A.).

Background: In patients presenting with ST-segment-elevation myocardial infarction, percutaneous coronary intervention (PCI) reduces mortality when compared with fibrinolysis. In other forms of coronary artery disease (CAD), however, it has been controversial whether PCI reduces mortality. In this meta-analysis, we examine the benefits of PCI in (1) patients post-myocardial infarction (MI) who did not receive immediate revascularization; (2) patients who have undergone primary PCI for ST-segment-elevation myocardial infarction but have residual coronary lesions; (3) patients who have suffered a non-ST-segment-elevation acute coronary syndrome; and (4) patients with truly stable CAD with no recent infarct. This analysis includes data from the recently presented International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) and Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI (COMPLETE) trials.

Methods And Results: We systematically identified all randomized trials of PCI on a background of medical therapy for the treatment of CAD. The ISCHEMIA trial, presented in November 2019, was eligible for inclusion. Data were combined using a random-effects meta-analysis. The primary end point was all-cause mortality. Forty-six trials, including 37 757 patients, were eligible. In the 3 unstable scenarios, PCI had the following effects on mortality: unrevascularized post-MI relative risk (RR) 0.68 (95% CI, 0.45-1.03); =0.07; multivessel disease following ST-segment-elevation myocardial infarction (RR, 0.84 [95% CI, 0.69-1.04]; =0.11); non-ST-segment-elevation acute coronary syndrome (RR, 0.84 [95% CI, 0.72-0.97]; =0.02). Overall, in these unstable scenarios PCI was associated with a significant reduction in mortality (RR, 0.84 [95% CI, 0.75-0.93]; =0.02). In unstable CAD, PCI also reduced cardiac death (RR, 0.69 [95% CI, 0.53-0.90]; =0.007) and MI (RR, 0.74 [95% CI, 0.62-0.90]; =0.002). For stable CAD, PCI did not reduce mortality (RR, 0.98 [95% CI, 0.87-1.11]), cardiac death (RR, 0.89 [95% CI, 0.71-1.12]; =0.33), or MI (RR, 0.96 [95% CI, 0.86-1.08]; =0.54).

Conclusions: PCI prevents death, cardiac death, and MI in patients with unstable CAD. For patients with stable CAD, PCI shows no evidence of an effect on any of these outcomes.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.119.006363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034389PMC
February 2020

Interference Between Pressure-Wire and Deployed Coronary Stents: Insights from a Bench Test.

Cardiovasc Revasc Med 2020 06 27;21(6):765-770. Epub 2019 Oct 27.

Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.

Background: While several complications related to pressure-wire (PW) have been reported, mechanistic justification has not always been offered. Furthermore, interference between a PW and a protruding side-branch stent has not been previously reported. The purpose of this study was to evaluate interference between PW-pullback from a main-branch with a protruded ostial stent deployed in a side-branch.

Methods: In a polyurethane bifurcation vessel model, PW-pullback was performed in a main-branch following protruded ostial stenting in a side-branch. Tested PWs included PressureWire X, Comet, OptoWire, and Verrata. For each PW, pullback was performed through the same proximal cell of the protruded stent 20 times. Interference during PW-pullback was objectively analyzed with a fiberscope placed at the distal main-branch and classified into 3 grades according to the interaction with stent strut.

Results: There were significant differences in the rate of interference between the PWs. No-interference, interference without strut traction, and interference with strut traction (i.e. stent deformation) were observed as follows: 17/20, 3/20, and 0/20 in PressureWire X; 19/20, 1/20, and 0/20 in Comet; 8/20, 10/20, and 2/20 in OptoWire; and 13/20, 2/20, and 5/20 in Verrata, respectively (p for any differences: <0.001). Visually identifiable major stent deformation was observed once in OptoWire due to the deep concave sensor window and twice in Verrata due to the proximal gap between the sensor and coiled-wire.

Conclusions: PW-pullback in the main-branch after side-branch ostial stenting should be carefully performed to avoid stent deformation. Consideration on the specific mechanical features of the PW is also essential.
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http://dx.doi.org/10.1016/j.carrev.2019.10.026DOI Listing
June 2020

Determining the Predominant Lesion in Patients With Severe Aortic Stenosis and Coronary Stenoses: A Multicenter Study Using Intracoronary Pressure and Flow.

Circ Cardiovasc Interv 2019 12 22;12(12):e008263. Epub 2019 Nov 22.

National Heart and Lung Institute, Hammersmith Hospital, Imperial College London, United Kingdom (Y.A., J.P.H., C.C., C.R., R.A.-L., R.P., T.W., D.F., J.M., P.S., S.S.).

Background: Patients with severe aortic stenosis (AS) often have coronary artery disease. Both the aortic valve and the coronary disease influence the blood flow to the myocardium and its ability to respond to stress; leading to exertional symptoms. In this study, we aim to quantify the effect of severe AS on the coronary microcirculation and determine if this is influenced by any concomitant coronary disease. We then compare this to the effect of coronary stenoses on the coronary microcirculation.

Methods: Group 1: 55 patients with severe AS and intermediate coronary stenoses treated with transcatheter aortic valve implantation (TAVI) were included. Group 2: 85 patients with intermediate coronary stenoses and no AS treated with percutaneous coronary intervention were included. Coronary pressure and flow were measured at rest and during hyperemia in both groups, before and after TAVI (group 1) and before and after percutaneous coronary intervention (group 2).

Results: Microvascular resistance over the wave-free period of diastole increased significantly post-TAVI (pre-TAVI, 2.71±1.4 mm Hg·cm·s versus post-TAVI 3.04±1.6 mm Hg·cm·s [=0.03]). Microvascular reserve over the wave-free period of diastole significantly improved post-TAVI (pre-TAVI 1.88±1.0 versus post-TAVI 2.09±0.8 [=0.003]); this was independent of the severity of the underlying coronary stenosis. The change in microvascular resistance post-TAVI was equivalent to that produced by stenting a coronary lesion with an instantaneous wave-free ratio of ≤0.74.

Conclusions: TAVI improves microcirculatory function regardless of the severity of underlying coronary disease. TAVI for severe AS produces a coronary hemodynamic improvement equivalent to the hemodynamic benefit of stenting coronary stenoses with instantaneous wave-free ratio values <0.74. Future trials of physiology-guided revascularization in severe AS may consider using this value to guide treatment of concomitant coronary artery disease.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924937PMC
December 2019

Dobutamine Stress Echocardiography Ischemia as a Predictor of the Placebo-Controlled Efficacy of Percutaneous Coronary Intervention in Stable Coronary Artery Disease: The Stress Echocardiography-Stratified Analysis of ORBITA.

Circulation 2019 12 11;140(24):1971-1980. Epub 2019 Nov 11.

Imperial College Healthcare NHS Trust, London, UK (R.K.A-L., M.J.S.-S., J.P.H., A.N.N., C.R., S.S., S.N., R.P., I.M., C.C., Y.A., H.S., R.A., G.C., G.K., J.M., J.E.D., D.P.F.).

Background: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina).

Methods: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling.

Results: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (=0.116), physical limitation (=0.461), quality of life (=0.689), EuroQOL 5 quality-of-life score (=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (=0.693), and treadmill exercise time (=0.426).

Conclusions: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.042918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903430PMC
December 2019

Editorial commentary: Renal denervation: The three stages of academic grief.

Authors:
James P Howard

Trends Cardiovasc Med 2020 05 22;30(4):196-197. Epub 2019 Oct 22.

Department of Cardiology, National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.tcm.2019.05.014DOI Listing
May 2020

Artificial Intelligence for Aortic Pressure Waveform Analysis During Coronary Angiography: Machine Learning for Patient Safety.

JACC Cardiovasc Interv 2019 10 25;12(20):2093-2101. Epub 2019 Sep 25.

Department of Cardiology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jcin.2019.06.036DOI Listing
October 2019