Deep Learning in Cardiology

The medical field is creating large amount of data that physicians are unable to decipher and use efficiently. Moreover, rule-based expert systems are inefficient in solving complicated medical tasks or for creating insights using big data. Deep learning has emerged as a more accurate and effective technology in a wide range of medical problems such as diagnosis, prediction and intervention. Deep learning is a representation learning method that consists of layers that transform the data non-linearly, thus, revealing hierarchical relationships and structures. In this review we survey deep learning application papers that use structured data, signal and imaging modalities from cardiology. We discuss the advantages and limitations of applying deep learning in cardiology that also apply in medicine in general, while proposing certain directions as the most viable for clinical use.Comment: 27 pages, 2 figures, 10 table

Fractional flow reserve-guided management in stable coronary disease and acute myocardial infarction: recent developments

Coronary artery disease (CAD) is a leading global cause of morbidity and mortality, and improvements in the diagnosis and treatment of CAD can reduce the health and economic burden of this condition. Fractional flow reserve (FFR) is an evidence-based diagnostic test of the physiological significance of a coronary artery stenosis. Fractional flow reserve is a pressure-derived index of the maximal achievable myocardial blood flow in the presence of an epicardial coronary stenosis as a ratio to maximum achievable flow if that artery were normal. When compared with standard angiography-guided management, FFR disclosure is impactful on the decision for revascularization and clinical outcomes. In this article, we review recent developments with FFR in patients with stable CAD and recent myocardial infarction. Specifically, we review novel developments in our understanding of CAD pathophysiology, diagnostic applications, prognostic studies, clinical trials, and clinical guidelines

Estimation of ejection fraction with ventriculography versus echocardiography in patients referred for cardiac surgery

Abstract: Aim: The aim of this study was to compare the estimation of ejection fraction (EF) by ventricuography (VG) and echocardiography (ECHO) in patients referred for surgery and to validate the results by comparison with other published data. Methods: One hundred patients who underwent VG prior to surgery were subjected to a trans-thoracic ECHO. Radiographers calculated the EF by tracing the outer border of the ventriculogram during systole and diastole. A single cardiologist, who was blinded to the angiogram result, measured EF during trans-thoracic ECHO using the biplane Simpson’s method. Results: EF was significantly higher by VG versus ECHO for the whole group (67.9±13.2 vs 55.7±8.5, p=0.000). In 81 patients the EF estimated at VG was higher than that calculated at ECHO (71.7±10.2 vs 55.9±7.2, p=0.000). In 19 patients the EF estimated at VG was lower than that calculated at ECHO, but the difference was not significant (51.8±12.9 by VG vs 55.4±12.8, p=0.387). In 13 patients, with an EF less than 50% on VG, the correlation with ECHO was very good (42.0±9.0 vs 42.0±8.3, p=0.995). Two patients with an EF fraction under 30% had similar measurements by VG and ECHO. The EF range as measured by ECHO was consistent with published data. Conclusion: Ventriculography overestimates EF when compared with ECHO. When EF is less than 50% on VG, ECHO findings were similar. The value of ventriculography in patients referred for cardiac surgery is now being brought into question when ECHO, a better and less invasive test that measures EF, is available.peer-reviewe

Clinical risk factors and atherosclerotic plaque extent to define risk for major events in patients without obstructive coronary artery disease: the long-term coronary computed tomography angiography CONFIRM registry.

AimsIn patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent.Methods and resultsPatients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3-4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3-2.2) and 1.4 (95% CI 1.1-1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004).ConclusionAmong patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both

Estimation of coronary artery hyperemic blood flow based on arterial lumen volume using angiographic images

The purpose of this study is to develop a method to estimate the hyperemic blood flow in a coronary artery using the sum of the distal lumen volumes in a swine animal model. The limitations of visually assessing coronary artery disease are well known. These limitations are particularly important in intermediate coronary lesions where it is difficult to determine whether a particular lesion is the cause of ischemia. Therefore, a functional measure of stenosis severity is needed using angiographic image data. Coronary arteriography was performed in 10 swine (Yorkshire, 25–35 kg) after power injection of contrast material into the left main coronary artery. A densitometry technique was used to quantify regional flow and lumen volume in vivo after inducing hyperemia. Additionally, 3 swine hearts were casted and imaged post-mortem using cone-beam CT to obtain the lumen volume and the arterial length of corresponding coronary arteries. Using densitometry, the results showed that the stem hyperemic flow (Q) and the associated crown lumen volume (V) were related by Q = 159.08 V3/4 (r = 0.98, SEE = 10.59 ml/min). The stem hyperemic flow and the associated crown length (L) using cone-beam CT were related by Q = 2.89 L (r = 0.99, SEE = 8.72 ml/min). These results indicate that measured arterial branch lengths or lumen volumes can potentially be used to predict the expected hyperemic flow in an arterial tree. This, in conjunction with measured hyperemic flow in the presence of a stenosis, could be used to predict fractional flow reserve based entirely on angiographic data

Association of PET-measured myocardial flow reserve with echocardiography-estimated pulmonary artery systolic pressure in patients with hypertrophic cardiomyopathy

BackgroundPulmonary hypertension (PH) is a known complication of HCM and is a strong predictor of mortality. We aim to investigate the relationship between microvascular dysfunction measured by quantitative PET and PH in HCM patients.MethodsEighty-nine symptomatic HCM patients were included in the study. Each patient underwent two 20-min 13N-NH3 dynamic PET scans for rest and stress conditions, respectively. A 2-tissue irreversible compartmental model was used to fit the segments time activity curves for estimating segmental and global myocardial blood flow (MBF) and myocardial flow reserve (MFR). Echocardiographic derived PASP was utilized to estimate PH.ResultsPatients were categorized into two groups across PASP: PH (PASP > 36 mmHg) and no-PH (PASP ≤ 36 mmHg). patients with PH had larger left atrium, ratio of higher inflow early diastole (E) and atrial contraction (A) waves, E/A, and ratio of inflow and peak early diastolic waves, E/e', significantly reduced global stress MBF (1.85 ± 0.52 vs. 2.13 ± 0.56 ml/min/g; p = 0.024) and MFR (2.21 ± 0.57 vs. 2.62 ± 0.75; p = 0.005), while the MBFs at rest between the two groups were similar. There were significant negative correlations between global stress MBF/MFR and PASP (stress MBF: r = -0.23, p = 0.03; MFR: r = -0.32, p = 0.002); for regional MBF and MFR measurements, the highest linear correlation coefficients were observed in the septal wall (stress MBF: r = -0.27, p = 0.01; MFR: r = -0.31, p = 0.003). Global MFR was identified to be independent predictor for PH in multivariate regression analysis.ConclusionEchocardiography-derived PASP is negatively correlated with global MFR measured by 13N-NH3 dynamic PET. Global MFR is suggested to be an index of PH in HCM patients.</div

Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

<div><p>Background</p><p>Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.</p><p>Methodology</p><p>497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.</p><p>Principal Findings</p><p>Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).</p><p>Significance</p><p>These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.</p></div

Noninvasive physiologic assessment of coronary stenoses using cardiac CT

Coronary CT angiography (CCTA) has become an important non-invasive imaging modality in the diagnosis of coronary artery disease (CAD). CCTA enables accurate evaluation of coronary artery stenosis. However, CCTA provides limited information on the physiological significance of stenotic lesions. A noninvasive ‘one-stop-shop’ diagnostic test that can provide both anatomical and functional significance of stenotic lesions would be beneficial in the diagnosis and management of CAD. Recently, with the introduction of novel techniques such as myocardial CT perfusion, CT-derived fractional flow reserve (FFRCT), and transluminal attenuation gradient (TAG), CCTA has emerged as a non-invasive method for the assessment of both anatomy of coronary lesions and its physiological consequences during a single study. This review provides an overview of the current status of new CT techniques for the physiologic assessments of CAD

Myocardial perfusion in heart disease

Heart disease: Coronary heart disease is a major cause of mortality and morbidity in the UK and globally. It is managed with medical therapy and coronary revascularisation to reduce symptoms and reduce risk of major adverse cardiovascular events. When patients present with chest pain, it is important to risk stratify those that would most benefit from invasive coronary assessment and those that can be managed with medical therapy alone. Myocardial perfusion techniques have been developed in order to do this. Cardiovascular magnetic resonance (CMR) with stress perfusion: CMR allows the non-invasive assessment of coronary artery disease (CAD). Under conditions of vasodilator stress, a gadolinium based contrast agent is injected and during the first pass through the left ventricle, perfusion defects can be observed. There is a strong evidence base for perfusion CMR but the technique is qualitative, relies on experienced operators and potentially misses globally low perfusion such as in cases of “balanced” ischaemia. Quantitative perfusion CMR: In contrast, quantitative perfusion techniques allow the calculation of myocardial blood flow (MBF). It is more objective, less reliant on the expert observer and can give additional insights into microvascular disease and cardiomyopathy. As well as being less subjective, quantitative perfusion has other advantages for example it allows full assessment of ischaemic burden and may contain prognostic information that could be used to risk stratify and improve patient care. However, quantitative perfusion has been outside the realm of routine clinical practice due to difficulties in acquiring suitable data for full quantification and the laborious nature of analysing it. Perfusion mapping: Peter Kellman, Hui Xue and colleagues at the National Institutes for Health, USA developed the “perfusion mapping” technique to address these limitations. Perfusion maps are generated automatically and inline during the CMR scan and each voxel encodes myocardial blood flow. This allows the instant quantification of MBF without complex acquisition techniques and post processing. In this thesis I have taken perfusion mapping and deployed in the real-world at a scale an order of magnitude higher than prior quantitative perfusion studies, developing the evidence base for routine clinical use across a broad range of diseases and scenarios: In coronary artery disease: I have shown that perfusion mapping is accurate to detect coronary artery stenosis as defined by 3D quantitative coronary angiography in a single centre, 50 patient study. Transmural and subendocardial perfusion are particularly sensitive to detect coronary stenoses with performances similar to expert readers. There is a high sensitivity and high negative predictive value making perfusion mapping a good “rule-out” test for coronary disease. Quantitative perfusion and prognosis: I investigated whether stress MBF and myocardial perfusion reserve (MPR) calculated by perfusion mapping would encode prognostic information in a 1049 patient multi-centre study over a mean follow up time of 605 days. Both stress MBF and MPR were independently associated with death and major adverse cardiovascular events (MACE). The hazard ratio for MACE was 2.14 for each 1ml/g/min decrease in stress MBF and 1.74 for each unit decrease in MPR. This work can now be taken forward with prospective studies in order to better risk stratify patients, including those without perfusion defects on clinical read. Reference ranges and non-obstructive coronary disease: I sought to determine the factors that contribute to perfusion in a multi-centre registry study. In patients with no obstructive coronary artery disease, stress MBF was reduced with age, diabetes, left ventricular hypertrophy (LVH) and the use of beta blockers. Rest MBF was influenced by sex (higher in females) and reduced with beta blockers. This study suggests patient factors beyond coronary artery disease (and therefore likely microvascular disease) should also be considered when interpreting quantitative perfusion studies. In cardiomyopathy: I also investigated myocardial perfusion in cardiomyopathy looking at Fabry disease as an example disease. In a prospective, observational, single centre study of 44 patients and 27 controls I found Fabry patients had reduced perfusion (and therefore likely microvascular dysfunction), particularly in the subendocardium and was associated with left ventricular hypertrophy (LVH), glycophospholipid storage and scar. Perfusion was reduced even in patients without LVH suggesting it is an early disease marker. In conclusion, in this thesis, I have developed an evidence base for quantitative perfusion CMR and demonstrated how it can be integrated into routine clinical care. Perfusion mapping is accurate for detecting coronary artery stenosis and encodes prognostic information. Further work in this area could enable patients to be risk stratified based on their myocardial perfusion in order to reduce the morbidity and mortality associated with epicardial and microvascular coronary artery disease. Following on from this work, two further British Heart Foundation Clinical Research Training Fellowships have been awarded to further investigate quantitative perfusion in patients following surgical revascularisation of coronary disease and in patients with hypertrophic cardiomyopathy