Hybridizing machine learning in survival analysis of cardiac PET/CT imaging.

BACKGROUND: Machine Learning (ML) allows integration of the numerous variables delivered by cardiac PET/CT, while traditional survival analysis can provide explainable prognostic estimates from a restricted number of input variables. We implemented a hybrid ML-and-survival analysis of multimodal PET/CT data to identify patients who developed myocardial infarction (MI) or death in long-term follow up. METHODS: Data from 739 intermediate risk patients who underwent coronary CT and selectively stress 15O-water-PET perfusion were analyzed for the occurrence of MI and all-cause mortality. Images were evaluated segmentally for atherosclerosis and absolute myocardial perfusion through 75 variables that were integrated through ML into an ML-CCTA and an ML-PET score. These scores were then modeled along with clinical variables through Cox regression. This hybridized model was compared against an expert interpretation-based and a calcium score-based model. RESULTS: Compared with expert- and calcium score-based models, the hybridized ML-survival model showed the highest performance (CI .81 vs .71 and .64). The strongest predictor for outcomes was the ML-CCTA score. CONCLUSION: Prognostic modeling of PET/CT data for the long-term occurrence of adverse events may be improved through ML imaging score integration and subsequent traditional survival analysis with clinical variables. This hybridization of methods offers an alternative to traditional survival modeling of conventional expert image scoring and interpretation.

Severe Acute Thrombocytopenia After Treatment with Tirofiban: A Case Series Approach.

Glycoprotein IIb/IIIa inhibitors are an adjuvant therapy for the treatment of patients with acute coronary syndromes. The main adverse reactions are bleeding and thrombocytopenia in 1-2% of cases. A 66-year-old woman arrived at the emergency department with ST-elevation MI. The catheterisation lab was busy, so she received thrombolytic therapy. Coronary angiography revealed a 90% stenosis in the middle segment of the left anterior descending artery and Thrombolysis in MI 2 flow. Subsequent percutaneous coronary intervention showed abundant thrombus and a coronary dissection and it was necessary to insert five drug-eluting stents. Non-fractionated heparin and a tirofiban infusion were used. After the percutaneous coronary intervention, she developed severe thrombocytopenia, haematuria and gingivorrhagia, for which infusion of tirofiban was suspended. In follow-up, no major bleeding or subsequent haemorrhagic complications were identified. It is crucial to distinguish between heparin-induced thrombocytopenia and thrombocytopenia caused by other drugs. A high level of suspicion should be employed in these cases.

Synthetic Attenuation Correction Maps for SPECT Imaging Using Deep Learning: A Study on Myocardial Perfusion Imaging.

(1) Background: The CT-based attenuation correction of SPECT images is essential for obtaining accurate quantitative images in cardiovascular imaging. However, there are still many SPECT cameras without associated CT scanners throughout the world, especially in developing countries. Performing additional CT scans implies troublesome planning logistics and larger radiation doses for patients, making it a suboptimal solution. Deep learning (DL) offers a revolutionary way to generate complementary images for individual patients at a large scale. Hence, we aimed to generate linear attenuation coefficient maps from SPECT emission images reconstructed without attenuation correction using deep learning. (2) Methods: A total of 384 SPECT myocardial perfusion studies that used 99mTc-sestamibi were included. A DL model based on a 2D U-Net architecture was trained using information from 312 patients. The quality of the generated synthetic attenuation correction maps (ACMs) and reconstructed emission values were evaluated using three metrics and compared to standard-of-care data using Bland-Altman plots. Finally, a quantitative evaluation of myocardial uptake was performed, followed by a semi-quantitative evaluation of myocardial perfusion. (3) Results: In a test set of 66 test patients, the ACM quality metrics were MSSIM = 0.97 ± 0.001 and NMAE = 3.08 ± 1.26 (%), and the reconstructed emission quality metrics were MSSIM = 0.99 ± 0.003 and NMAE = 0.23 ± 0.13 (%). The 95% limits of agreement (LoAs) at the voxel level for reconstructed SPECT images were: [-9.04; 9.00]%, and for the segment level, they were [-11; 10]%. The 95% LoAs for the Summed Stress Score values between the images reconstructed were [-2.8, 3.0]. When global perfusion scores were assessed, only 2 out of 66 patients showed changes in perfusion categories. (4) Conclusion: Deep learning can generate accurate attenuation correction maps from non-attenuation-corrected cardiac SPECT images. These high-quality attenuation maps are suitable for attenuation correction in myocardial perfusion SPECT imaging and could obviate the need for additional imaging in standalone SPECT scanners.

Multi-task Deep Learning of Myocardial Blood Flow and Cardiovascular Risk Traits from PET Myocardial Perfusion Imaging.

BACKGROUND: Advanced cardiac imaging with positron emission tomography (PET) is a powerful tool for the evaluation of known or suspected cardiovascular disease. Deep learning (DL) offers the possibility to abstract highly complex patterns to optimize classification and prediction tasks. METHODS AND RESULTS: We utilized DL models with a multi-task learning approach to identify an impaired myocardial flow reserve (MFR <2.0 ml/g/min) as well as to classify cardiovascular risk traits (factors), namely sex, diabetes, arterial hypertension, dyslipidemia and smoking at the individual-patient level from PET myocardial perfusion polar maps using transfer learning. Performance was assessed on a hold-out test set through the area under receiver operating curve (AUC). DL achieved the highest AUC of 0.94 [0.87-0.98] in classifying an impaired MFR in reserve perfusion polar maps. Fine-tuned DL for the classification of cardiovascular risk factors yielded the highest performance in the identification of sex from stress polar maps (AUC = 0.81 [0.73, 0.88]). Identification of smoking achieved an AUC = 0.71 [0.58, 0.85] from the analysis of rest polar maps. The identification of dyslipidemia and arterial hypertension showed poor performance and was not statistically significant. CONCLUSION: Multi-task DL for the evaluation of quantitative PET myocardial perfusion polar maps is able to identify an impaired MFR as well as cardiovascular risk traits such as sex, smoking and possibly diabetes at the individual-patient level.

Myocardial perfusion quantification with Rb-82 PET: good interobserver agreement of Carimas software on global, regional, and segmental levels.

PURPOSE: To estimate the interobserver agreement of the Carimas software package (SP) on global, regional, and segmental levels for the most widely used myocardial perfusion PET tracer-Rb-82. MATERIALS AND METHODS: Rest and stress Rb-82 PET scans of 48 patients with suspected or known coronary artery disease (CAD) were analyzed in four centers using the Carimas SP. We considered values to agree if they simultaneously had an intraclass correlation coefficient (ICC) > 0.75 and a difference < 20% of the median across all observers. RESULTS: The median values on the segmental level were 1.08 mL/min/g for rest myocardial blood flow (MBF), 2.24 mL/min/g for stress MBF, and 2.17 for myocardial flow reserve (MFR). For the rest MBF and MFR, all the values at all the levels fulfilled were in excellent agreement. For stress MBF, at the global and regional levels, all the 24 comparisons showed excellent agreement. Only 1 out of 102 segmental comparisons (seg. 14) was over the adequate agreement limit-23.5% of the median value (ICC = 0.95). CONCLUSION: Interobserver agreement for Rb-82 PET myocardial perfusion quantification analyzed with Carimas is good at any LV segmentation level-global, regional, and segmental. It is good for all the estimates-rest MBF, stress MBF, and MFR.

Artificial Intelligence to Improve Risk Prediction with Nuclear Cardiac Studies.

PURPOSE OF REVIEW: As machine learning-based artificial intelligence (AI) continues to revolutionize the way in which we analyze data, the field of nuclear cardiology provides fertile ground for the implementation of these complex analytics. This review summarizes and discusses the principles regarding nuclear cardiology techniques and AI, and the current evidence regarding its performance and contribution to the improvement of risk prediction in cardiovascular disease. There is a growing body of evidence on the experimentation with and implementation of machine learning-based AI on nuclear cardiology studies both concerning SPECT and PET technology for the improvement of risk-of-disease (classification of disease) and risk-of-events (prediction of adverse events) estimations. These publications still report objective divergence in methods either utilizing statistical machine learning approaches or deep learning with varying architectures, dataset sizes, and performance. Recent efforts have been placed into bringing standardization and quality to the experimentation and application of machine learning-based AI in cardiovascular imaging to generate standards in data harmonization and analysis through AI. Machine learning-based AI offers the possibility to improve risk evaluation in cardiovascular disease through its implementation on cardiac nuclear studies. AI in improving risk evaluation in nuclear cardiology. * Based on the 2019 ESC guidelines.

Genomic insights in ascending aortic size and distensibility.

BACKGROUND: Alterations in the anatomic and biomechanical properties of the ascending aorta (AAo) can give rise to various vascular pathologies. The aim of the current study is to gain additional insights in the biology of the AAo size and function. METHODS: We developed an AI based analysis pipeline for the segmentation of the AAo, and the extraction of AAO parameters. We then performed genome-wide association studies of AAo maximum area, AAo minimum area and AAo distensibility in up to 37,910 individuals from the UK Biobank. Variants that were significantly associated with AAo phenotypes were used as instrumental variables in Mendelian randomization analyses to investigate potential causal relationships with coronary artery disease, myocardial infarction, stroke and aneurysms. FINDINGS: Genome-wide association studies revealed a total of 107 SNPs in 78 loci. We annotated 101 candidate genes involved in various biological processes, including connective tissue development (THSD4 and COL6A3). Mendelian randomization analyses showed a causal association with aneurysm development, but not with other vascular diseases. INTERPRETATION: We identified 78 loci that provide insights into mechanisms underlying AAo size and function in the general population and provide genetic evidence for their role in aortic aneurysm development.

Prehospital risk stratification in patients with chest pain.

OBJECTIVES: The History, ECG, Age, Risk Factors and Troponin (HEART) Score is a decision support tool applied by physicians in the emergency department developed to risk stratify low-risk patients presenting with chest pain. We assessed the potential value of this tool in prehospital setting, when applied by emergency medical services (EMS), and derived and validated a tool adapted to the prehospital setting in order to determine if it could assist with decisions regarding conveyance to a hospital. METHODS: In 2017, EMS personnel prospectively determined the HEART Score, including point-of-care (POC) troponin measurements, in patients presenting with chest pain, in the north of the Netherlands. The primary endpoint was a major adverse cardiac event (MACE), consisting of acute myocardial infarction or death, within 3 days. The components of the HEART Score were evaluated for their discriminatory value, cut-offs were calibrated for the prehospital setting and sex was substituted for cardiac risk factors to develop a prehospital HEART (preHEART) Score. This score was validated in an independent prospective cohort of 435 patients in 2018. RESULTS: Among 1208 patients prospectively recruited in the first cohort, 123 patients (10.2%) developed a MACE. The HEART Score had a negative predictive value (NPV) of 98.4% (96.4-99.3), a positive predictive value (PPV) of 35.5% (31.8-39.3) and an area under the receiver operating characteristic curve (AUC) of 0.81 (0.78-0.85). The preHEART Score had an NPV of 99.3% (98.1-99.8), a PPV of 49.4% (42.0-56.9) and an AUC of 0.85 (0.82-0.88), outperforming the HEART Score or POC troponin measurements on their own. Similar results were found in a validation cohort. CONCLUSIONS: The HEART Score can be used in the prehospital setting to assist with conveyance decisions and choice of hospitals; however, the preHEART Score outperforms both the HEART Score and single POC troponin measurements when applied by EMS personnel in the prehospital setting.

Position paper of the EACVI and EANM on artificial intelligence applications in multimodality cardiovascular imaging using SPECT/CT, PET/CT, and cardiac CT.

In daily clinical practice, clinicians integrate available data to ascertain the diagnostic and prognostic probability of a disease or clinical outcome for their patients. For patients with suspected or known cardiovascular disease, several anatomical and functional imaging techniques are commonly performed to aid this endeavor, including coronary computed tomography angiography (CCTA) and nuclear cardiology imaging. Continuous improvement in positron emission tomography (PET), single-photon emission computed tomography (SPECT), and CT hardware and software has resulted in improved diagnostic performance and wide implementation of these imaging techniques in daily clinical practice. However, the human ability to interpret, quantify, and integrate these data sets is limited. The identification of novel markers and application of machine learning (ML) algorithms, including deep learning (DL) to cardiovascular imaging techniques will further improve diagnosis and prognostication for patients with cardiovascular diseases. The goal of this position paper of the European Association of Nuclear Medicine (EANM) and the European Association of Cardiovascular Imaging (EACVI) is to provide an overview of the general concepts behind modern machine learning-based artificial intelligence, highlights currently prefered methods, practices, and computational models, and proposes new strategies to support the clinical application of ML in the field of cardiovascular imaging using nuclear cardiology (hybrid) and CT techniques.

Improving patient identification for advanced cardiac imaging through machine learning-integration of clinical and coronary CT angiography data.

BACKGROUND: Standard computed tomography angiography (CTA) outputs a myriad of interrelated variables in the evaluation of suspected coronary artery disease (CAD). But an important proportion of obstructive lesions does not cause significant myocardial ischemia. Nowadays, machine learning (ML) allows integration of numerous variables through complex interdependencies that optimize classification and prediction at the individual level. We evaluated ML performance in integrating CTA and clinical variables to identify patients that demonstrate myocardial ischemia through PET and those who ultimately underwent early revascularization. METHODS AND RESULTS: 830 patients with CTA and selective PET were analyzed. Nine clinical and 58 CTA variables were integrated through ensemble-boosting ML to identify patients with ischemia and those who underwent early revascularization. ML performance was compared against expert CTA interpretation, calcium score and clinical variables. While ML using all CTA variables achieved an AUC = 0.85, it was outperformed by expert CTA interpretation (AUC = 0.87, p < 0.01 for comparison), comparable to ML integration of CTA variables with clinical variables. However, the best performance was achieved by ML integration of expert CTA interpretation and clinical variables for both dependent variables (AUCs = 0.91 and 0.90, p < 0.001). CONCLUSIONS: Machine learning integration of diagnostic CTA and clinical data may improve identification of patients with myocardial ischemia and those requiring early revascularization at the individual level. This could potentially aid in sparing the need for subsequent advanced imaging and better identifying patients in ultimate need for revascularization. While ML integrating all CTA variables did not outperform expert CTA interpretation, ML data integration from different sources consistently improves diagnostic performance.

Genome-Wide Association Study and Identification of a Protective Missense Variant on Lipoprotein(a) Concentration: Protective Missense Variant on Lipoprotein(a) Concentration-Brief Report.

[Figure: see text].

Uncertainty estimation for deep learning-based automated analysis of 12-lead electrocardiograms.

Aims: Automated interpretation of electrocardiograms (ECGs) using deep neural networks (DNNs) has gained much attention recently. While the initial results have been encouraging, limited attention has been paid to whether such results can be trusted, which is paramount for their clinical implementation. This study aims to systematically investigate uncertainty estimation techniques for automated classification of ECGs using DNNs and to gain insight into its utility through a clinical simulation. Methods and results: On a total of 526 656 ECGs from three different datasets, six different methods for estimation of aleatoric and epistemic uncertainty were systematically investigated. The methods were evaluated based on ranking, calibration, and robustness against out-of-distribution data. Furthermore, a clinical simulation was performed where increasing uncertainty thresholds were applied to achieve a clinically acceptable performance. Finally, the correspondence between the uncertainty of ECGs and the lack of interpretational agreement between cardiologists was estimated. Results demonstrated the largest benefit when modelling both epistemic and aleatoric uncertainty. Notably, the combination of variational inference with Bayesian decomposition and ensemble with auxiliary output outperformed the other methods. The clinical simulation showed that the accuracy of the algorithm increased as uncertain predictions were referred to the physician. Moreover, high uncertainty in DNN-based ECG classification strongly corresponded with a lower diagnostic agreement in cardiologist's interpretation (P < 0.001). Conclusion: Uncertainty estimation is warranted in automated DNN-based ECG classification and its accurate estimation enables intermediate quality control in the clinical implementation of deep learning. This is an important step towards the clinical applicability of automated ECG diagnosis using DNNs.

Validation of the European Society of Cardiology pre-test probability model for obstructive coronary artery disease.

AIMS: Estimation of pre-test probability (PTP) of disease in patients with suspected coronary artery disease (CAD) is a common challenge. Due to decreasing prevalence of obstructive CAD in patients referred for diagnostic testing, the European Society of Cardiology suggested a new PTP (2019-ESC-PTP) model. The aim of this study was to validate that model. METHODS AND RESULTS: Symptomatic patients referred for coronary computed tomography angiography (CTA) due to suspected CAD in a geographical uptake area of 3.3 million inhabitants were included. The reference standard was a combined endpoint of CTA and invasive coronary angiography (ICA) with obstructive CAD defined at ICA as a ≥50% diameter stenosis or fractional flow reserve ≤0.80 when performed. The 2019-ESC-PTP, 2013-ESC-PTP, and CAD Consortium basic PTP scores were calculated based on age, sex, and symptoms. Of the 42 328 identified patients, coronary stenosis was detected in 8.8% using the combined endpoint. The 2019-ESC-PTP and CAD Consortium basic scores classified substantially more patients into the low PTP groups (PTP < 15%) than did the 2013-ESC-PTP (64% and 65% vs. 16%, P < 0.001). Using the combined endpoint as reference, calibration of the 2019-ESC-PTP model was superior to the 2013-ESC-PTP and CAD Consortium basic score. CONCLUSION: The new 2019-ESC-PTP model is well calibrated and superior to the previously recommended models in predicting obstructive stenosis detected by a combined endpoint of CTA and ICA.

Change in abdominal, but not femoral subcutaneous fat CT-radiodensity is associated with improved metabolic profile after bariatric surgery.

BACKGROUND AND AIMS: Computed tomography (CT)-derived adipose tissue radiodensity represents a potential noninvasive surrogate marker for lipid deposition and obesity-related metabolic disease risk. We studied the effects of bariatric surgery on CT-derived adipose radiodensities in abdominal and femoral areas and their relationships to circulating metabolites in morbidly obese patients. METHODS AND RESULTS: We examined 23 morbidly obese women who underwent CT imaging before and 6 months after bariatric surgery. Fifteen healthy non-obese women served as controls. Radiodensities of the abdominal subcutaneous (SAT) and visceral adipose tissue (VAT), and the femoral SAT, adipose tissue masses were measured in all participants. Circulating metabolites were measured by NMR. At baseline, radiodensities of abdominal fat depots were lower in the obese patients as compared to the controls. Surprisingly, radiodensity of femoral SAT was higher in the obese as compared to the controls. In the abdominal SAT depot, radiodensity strongly correlated with SAT mass (r = -0.72, p < 0.001). After surgery, the radiodensities of abdominal fat increased significantly (both p < 0.01), while femoral SAT radiodensity remained unchanged. Circulating ApoB/ApoA-I, leucine, valine, and GlycA decreased, while glycine levels significantly increased as compared to pre-surgical values (all p < 0.05). The increase in abdominal fat radiodensity correlated negatively with the decreased levels of ApoB/ApoA-I ratio, leucine and GlycA (all p < 0.05). The increase in abdominal SAT density was significantly correlated with the decrease in the fat depot mass (r = -0.66, p = 0.002). CONCLUSION: Higher lipid content in abdominal fat depots, and lower content in femoral subcutaneous fat, constitute prominent pathophysiological features in morbid obesity. Further studies are needed to clarify the role of non-abdominal subcutaneous fat in the pathogenesis of obesity. CLINICAL TRIAL REGISTRATION NUMBER: NCT01373892.

On stethoscopes, patient records, artificial intelligence, and zettabytes: A glimpse into the future of digital medicine in Mexico.

Science and technology are modifying medicine at a dizzying pace. Although access in our country to the benefits of innovations in the area of devices, data storage and artificial intelligence are still very restricted, the advance of digital medicine offers the opportunity to solve some of the biggest problems faced by medical practice and public health in Mexico. The potential areas where digital medicine can be disruptive are accessibility to quality medical care, centralization of specialties in large cities, dehumanization of medical treatment, lack of resources to access evidence-supported treatments, and among others. This review presents some of the advances that are guiding the new revolution in medicine, discusses the potential barriers to implementation, and suggest crucial elements for the path of incorporation of digital medicine in Mexico.

La ciencia y la tecnología han modificado la medicina a un ritmo vertiginoso. Si bien el acceso en México a los beneficios de las innovaciones en el área de dispositivos, almacenamiento de datos e inteligencia artificial aún es muy restringido, el avance de la medicina digital ofrece la oportunidad de solventar algunos de los problemas más grandes que enfrenta la práctica médica y la salud pública en este país. Las potenciales áreas en las que la medicina digital puede resultar innovadora son la accesibilidad a cuidados médicos de calidad, la centralización de las especialidades en grandes urbes, la deshumanización del trato médico, la falta de recursos para acceder a tratamientos avalados por evidencia, entre otros. Esta revisión presenta algunos de los avances que guían la nueva revolución en la medicina, revisa el potencial y las posibles barreras para su aplicación, además de sugerir elementos cruciales para el trayecto de incorporación de la medicina digital en México.

Sex-Based Differences in Unrecognized Myocardial Infarction.

Background Myocardial infarction is an important cause of morbidity and mortality in both men and women. Atypical or the absence of symptoms, more prevalent among women, may contribute to unrecognized myocardial infarctions and missed opportunities for preventive therapies. The aim of this research is to investigate sex-based differences of undiagnosed myocardial infarction in the general population. Methods and Results In the Lifelines Cohort Study, all individuals ≥18 years with a normal baseline ECG were followed from baseline visit till first follow-up visit (≈5 years, n=97 203). Individuals with infarct-related changes between baseline and follow-up ECGs were identified. The age- and sex-specific incidence rates were calculated and sex-specific cardiac symptoms and predictors of unrecognized myocardial infarction were determined. Follow-up ECG was available after a median of 3.8 (25th and 75th percentile: 3.0-4.6) years. During follow-up, 198 women experienced myocardial infarction (incidence rate 1.92 per 1000 persons-years) compared with 365 men (incidence rate 3.30; P<0.001 versus women). In 59 (30%) women, myocardial infarction was unrecognized compared with 60 (16%) men (P<0.001 versus women). Individuals with unrecognized myocardial infarction less often reported specific cardiac symptoms compared with individuals with recognized myocardial infarction. Predictors of unrecognized myocardial infarction were mainly hypertension, smoking, and higher blood glucose level. Conclusions A substantial proportion of myocardial infarctions are unrecognized, especially in women. Opportunities for secondary preventive therapies remain underutilized if myocardial infarction is unrecognized.

On stethoscopes, patient records, artificial intelligence, and zettabytes: A glimpse into the future of digital medicine in Mexico / Sobre estetoscopios, expedientes clínicos, inteligencia artificial y zettabytes: una mirada al futuro de la medicina digital en México

Abstract Science and technology are modifying medicine at a dizzying pace. Although access in our country to the benefits of innovations in the area of devices, data storage and artificial intelligence are still very restricted, the advance of digital medicine offers the opportunity to solve some of the biggest problems faced by medical practice and public health in Mexico. The potential areas where digital medicine can be disruptive are accessibility to quality medical care, centralization of specialties in large cities, dehumanization of medical treatment, lack of resources to access evidence-supported treatments, and among others. This review presents some of the advances that are guiding the new revolution in medicine, discusses the potential barriers to implementation, and suggest crucial elements for the path of incorporation of digital medicine in Mexico.

Resumen La ciencia y la tecnología han modificado la medicina a un ritmo vertiginoso. Si bien el acceso en México a los beneficios de las innovaciones en el área de dispositivos, almacenamiento de datos e inteligencia artificial aún es muy restringido, el avance de la medicina digital ofrece la oportunidad de solventar algunos de los problemas más grandes que enfrenta la práctica médica y la salud pública en este país. Las potenciales áreas en las que la medicina digital puede resultar innovadora son la accesibilidad a cuidados médicos de calidad, la centralización de las especialidades en grandes urbes, la deshumanización del trato médico, la falta de recursos para acceder a tratamientos avalados por evidencia, entre otros. Esta revisión presenta algunos de los avances que guían la nueva revolución en la medicina, revisa el potencial y las posibles barreras para su aplicación, además de sugerir elementos cruciales para el trayecto de incorporación de la medicina digital en México.