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Fulltext AI-based diagnosis of COVID-19 patients using X-ray scans with stochastic ensemble of CNNs

Arora R, Bansal V, Buckchash H, Kumar R, Sahayasheela VJ, Narayanan N, et al.

Phys Eng Sci Med, 2021 Dec;44(4):1257-1271.
PMID: 34609703 DOI: 10.1007/s13246-021-01060-9

According to the World Health Organization (WHO), novel coronavirus (COVID-19) is an infectious disease and has a significant social and economic impact. The main challenge in fighting against this disease is its scale. Due to the outbreak, medical facilities are under pressure due to case numbers. A quick diagnosis system is required to address these challenges. To this end, a stochastic deep learning model is proposed. The main idea is to constrain the deep-representations over a Gaussian prior to reinforce the discriminability in feature space. The model can work on chest X-ray or CT-scan images. It provides a fast diagnosis of COVID-19 and can scale seamlessly. The work presents a comprehensive evaluation of previously proposed approaches for X-ray based disease diagnosis. The approach works by learning a latent space over X-ray image distribution from the ensemble of state-of-the-art convolutional-nets, and then linearly regressing the predictions from an ensemble of classifiers which take the latent vector as input. We experimented with publicly available datasets having three classes: COVID-19, normal and pneumonia yielding an overall accuracy and AUC of 0.91 and 0.97, respectively. Moreover, for robust evaluation, experiments were performed on a large chest X-ray dataset to classify among Atelectasis, Effusion, Infiltration, Nodule, and Pneumonia classes. The results demonstrate that the proposed model has better understanding of the X-ray images which make the network more generic to be later used with other domains of medical image analysis.
Fulltext Association of Preterm Birth With Myocardial Fibrosis and Diastolic Dysfunction in Young Adulthood

Lewandowski AJ, Raman B, Bertagnolli M, Mohamed A, Williamson W, Pelado JL, et al.

J Am Coll Cardiol, 2021 08 17;78(7):683-692.
PMID: 34384550 DOI: 10.1016/j.jacc.2021.05.053

BACKGROUND: Preterm birth affects about 10% of live births worldwide and is associated with cardiac alterations. Animal models of preterm birth suggest that left ventricular functional impairment may be due to an up-regulation of myocardial fibrosis.
OBJECTIVES: The aim of this study was to determine whether diffuse left ventricular fibrosis is evident in young adults born preterm.
METHODS: One hundred one normotensive young adults born preterm (n = 47, mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) were included from YACHT (Young Adult Cardiovascular Health sTudy). Left ventricular structure and function were quantified by cardiovascular magnetic resonance and echocardiography. Intravenous administration of a gadolinium-based contrast agent during cardiovascular magnetic resonance was used to quantify focal myocardial fibrosis on the basis of late gadolinium enhancement and, in combination with T1 mapping, to quantify diffuse myocardial fibrosis on the basis of assessment of myocardial extracellular volume fraction.
RESULTS: Adults born preterm had smaller left ventricular end-diastolic and stroke volumes, with greater left ventricular mass and wall thickness (P < 0.001). In addition, longitudinal peak systolic strain and diastolic strain rate by both cardiovascular magnetic resonance and echocardiography, and E/A ratio measured by echocardiography, were lower in preterm-born compared to term-born adults (P < 0.05). Extracellular volume fraction was greater in preterm-born compared with term-born adults (27.81% ± 1.69% vs 25.48% ± 1.41%; P < 0.001) and was a significant mediator in the relationship between gestational age and both longitudinal peak diastolic strain rate and E/A ratio.
CONCLUSIONS: Preterm-born young adults have greater extracellular volume fraction in the left ventricle that is inversely related with gestational age and may underlie their diastolic functional impairments.
Fulltext Differing Impact of Preterm Birth on the Right and Left Atria in Adulthood

Schuermans A, den Harink T, Raman B, Smillie RW, Alsharqi M, Mohamed A, et al.

J Am Heart Assoc, 2022 Dec 06;11(23):e027305.
PMID: 36453643 DOI: 10.1161/JAHA.122.027305

Background Preterm birth affects 10% of live births and is associated with an altered left ventricular and right ventricular phenotype and increased cardiovascular disease risk in young adulthood. Because left atrial (LA) and right atrial (RA) volume and function are known independent predictors of cardiovascular outcomes, we investigated whether these were altered in preterm-born young adults. Methods and Results Preterm-born (n=200) and term-born (n=266) adults aged 18 to 39 years underwent cardiovascular magnetic resonance imaging. LA and RA maximal and minimal volumes (absolute, indexed to body surface area, and as a ratio to ventricular volumes) were obtained to study atrial morphology, while LA and RA stroke volume, strain, and strain rate were used to assess atrial function. Secondary analyses consisted of between-group comparisons based on degree of prematurity. Absolute RA volumes and RA volumes indexed to right ventricular volumes were significantly smaller in preterm-born compared with term-born adults. In addition, RA reservoir and booster strain were higher in preterm-born adults, possibly indicating functional compensation for the smaller RA volumes. LA volumes indexed to left ventricular volumes were significantly greater in preterm-born adults as compared with term-born adults, although absolute LA volumes were similar between groups. LA and RA changes were observed across gestational ages in the preterm group but were greatest in those born very-to-extremely preterm. Conclusions Preterm-born adults show changes in LA and RA structure and function, which may indicate subclinical cardiovascular disease. Further research into underlying mechanisms, opportunities for interventions, and their prognostic value is warranted.
Myocardial Disarray and Fibrosis across Hypertrophic Cardiomyopathy Stages Associate with ECG Markers of Arrhythmic Risk

Ashkir Z, Samat AHA, Ariga R, Finnigan L, Jermy S, Akhtar MA, et al.

Eur Heart J Cardiovasc Imaging, 2024 Oct 17.
PMID: 39417278 DOI: 10.1093/ehjci/jeae260

BACKGROUND: Myocardial disarray, an early feature of hypertrophic cardiomyopathy (HCM) and a substrate for ventricular arrhythmia, is poorly characterised in prehypertrophic sarcomeric variant carriers (SARC+LVH-).
OBJECTIVES: Using diffusion tensor cardiac magnetic resonance (DT-CMR) we assessed myocardial disarray and fibrosis in both SARC+LVH- and HCM patients and evaluated the relationship between microstructural alterations and electrocardiographic (ECG) parameters associated with arrhythmic risk.
METHODS: Sixty-two individuals (24 SARC+LVH-, 24 HCM and 14 matched controls) were evaluated with multiparametric CMR including stimulated echo acquisition mode (STEAM) DT-CMR, and blinded quantitative 12-lead ECG analysis.
RESULTS: Mean diastolic fractional anisotropy (FA) was reduced in HCM compared to SARC+LVH- and controls (0.49±0.05 vs 0.52±0.04 vs 0.53±0.04, p=0.009), even after adjustment for differences in extracellular volume (ECV) (p=0.038). Both HCM and SARC+LVH- had segments with significantly reduced FA relative to controls (54% vs 25% vs 0%, p=0.002). Multiple repolarization parameters were prolonged in HCM and SARC+LVH-, with corrected JT interval (JTc) being most significant (354±42ms vs 356±26ms vs 314±26ms, p=0.002). Among SARC+LVH-, JTc duration correlated negatively with mean FA (r=-0.6, p=0.002). In HCM, the JTc interval showed a stronger association with ECV (r=0.6 p=0.019) than FA (r=-0.1 p=0.72). JTc discriminated SARC+LVH- from controls (Area-under-the-receiver-operator-curve 0.88, CI 0.76-1.00, p<0.001), and in HCM correlated with the ESC HCM sudden cardiac death risk score (r=0.5, p=0.014).
CONCLUSION: Low diastolic FA, suggestive of myocardial disarray, is present in both SARC+LVH- and HCM. Low FA and raised ECV were associated with repolarization prolongation. Myocardial disarray assessment using DT-CMR and repolarization parameters such as the JTc interval demonstrate significant potential as markers of disease activity in HCM.
Fulltext The interplay between metabolic alterations, diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study

Mahmod M, Pal N, Rayner J, Holloway C, Raman B, Dass S, et al.

J Cardiovasc Magn Reson, 2018 12 24;20(1):88.
PMID: 30580760 DOI: 10.1186/s12968-018-0511-6

BACKGROUND: Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.
METHODS: Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent 1H-cardiovascular magnetic resonance spectroscopy (1H-CMRS) to measure MTG (lipid/water, %), 31P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.
RESULTS: When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45 ± 0.25% vs. 0.64 ± 0.16%, p = 0.009) and reduced PCr/ATP (1.60 ± 0.09 vs. 2.00 ± 0.10, p = 0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO2 max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO2 max.
CONCLUSIONS: Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.
Fulltext Safety and Efficacy of Metabolic Modulation With Ninerafaxstat in Patients With Nonobstructive Hypertrophic Cardiomyopathy

Maron MS, Mahmod M, Abd Samat AH, Choudhury L, Massera D, Phelan DMJ, et al.

J Am Coll Cardiol, 2024 May 28;83(21):2037-2048.
PMID: 38599256 DOI: 10.1016/j.jacc.2024.03.387

BACKGROUND: In nonobstructive hypertrophic cardiomyopathy (nHCM), there are no approved medical therapies. Impaired myocardial energetics is a potential cause of symptoms and exercise limitation. Ninerafaxstat, a novel cardiac mitotrope, enhances cardiac energetics.
OBJECTIVES: This study sought to evaluate the safety and efficacy of ninerafaxstat in nHCM.
METHODS: Patients with hypertrophic cardiomyopathy and left ventricular outflow tract gradient <30 mm Hg, ejection fraction ≥50%, and peak oxygen consumption <80% predicted were randomized to ninerafaxstat 200 mg twice daily or placebo (1:1) for 12 weeks. The primary endpoint was safety and tolerability, with efficacy outcomes also assessed as secondary endpoints.
RESULTS: A total of 67 patients with nHCM were enrolled at 12 centers (57 ± 11.8 years of age; 55% women). Serious adverse events occurred in 11.8% (n = 4 of 34) in the ninerafaxstat group and 6.1% (n = 2 of 33) of patients in the placebo group. From baseline to 12 weeks, ninerafaxstat was associated with significantly better VE/Vco2 (ventilatory efficiency) slope compared with placebo with a least-squares (LS) mean difference between the groups of -2.1 (95% CI: -3.6 to -0.6; P = 0.006), with no significant difference in peak VO2 (P = 0.90). The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score was directionally, though not significantly, improved with ninerafaxstat vs placebo (LS mean 3.2; 95% CI: -2.9 to 9.2; P = 0.30); however, it was statistically significant when analyzed post hoc in the 35 patients with baseline Kansas City Cardiomyopathy Questionnaire Clinical Summary Score ≤80 (LS mean 9.4; 95% CI: 0.3-18.5; P = 0.04).
CONCLUSIONS: In symptomatic nHCM, novel drug therapy targeting myocardial energetics was safe and well tolerated and associated with better exercise performance and health status among those most symptomatically limited. The findings support assessing ninerafaxstat in a phase 3 study.