Prognostic value of left ventricular mass measured on coronary computed tomography angiography.

BACKGROUND: Left ventricular (LV) mass is a well-established prognostic indicator for cardiovascular risk. Measurement of LV mass on coronary computed tomography angiography (CCTA) is considered optional. We aimed to assess for associations between LV mass measured on CCTA with all-cause mortality (ACM) risk and to determine age- and sex-specific distributions. METHODS: We evaluated patients without known coronary artery disease (CAD) who underwent CCTA at a single center. We assessed age- and sex-specific distributions (10th, 25th, 50th, 75th, and 90th percentiles) of LV mass index. ACM, the primary endpoint, was recorded over a median period of 5.1 [interquartile range: 1.4-8.4] years. The association between LV mass and mortality risk was assessed using multivariable Cox models adjusted for age, sex, medical history, coronary artery calcium (CAC) score and CCTA stenosis. RESULTS: 4187 patients (mean age: 61.9 â€‹± â€‹11.7, 63 â€‹% male) were included. Male sex, African American ethnicity, Hypertension, CAC>400, and smoking were independent predictors of increased LV mass index. During the median 5.1 years of study follow, 265 (6.3 â€‹%) deaths occurred. Increased LV mass index percentiles were associated with increased risk of ACM. The addition of LV mass index percentiles improved discrimination and reclassification for mortality prediction over a model with age, sex, conventional risk factors, CAC score and CCTA stenosis severity (X2 improvement: 22.68, NRI: 28 â€‹%, both p â€‹< â€‹0.001). CONCLUSION: In a large sample of patients without known CAD who underwent CCTA, increased LV mass index provided independent and incremental prognostic value for all-cause mortality. Assessment of LV mass by CCTA, considering age and gender distribution, can be utilized clinically to identify patients with high myocardial mass.

AI for Multistructure Incidental Findings and Mortality Prediction at Chest CT in Lung Cancer Screening.

Background Incidental extrapulmonary findings are commonly detected on chest CT scans and can be clinically important. Purpose To integrate artificial intelligence (AI)-based segmentation for multiple structures, coronary artery calcium (CAC), and epicardial adipose tissue with automated feature extraction methods and machine learning to detect extrapulmonary abnormalities and predict all-cause mortality (ACM) in a large multicenter cohort. Materials and Methods In this post hoc analysis, baseline chest CT scans in patients enrolled in the National Lung Screening Trial (NLST) from August 2002 to September 2007 were included from 33 participating sites. Per scan, 32 structures were segmented with a multistructure model. For each structure, 15 clinically interpretable radiomic features were quantified. Four general codes describing abnormalities reported by NLST radiologists were applied to identify extrapulmonary significant incidental findings on the CT scans. Death at 2-year and 10-year follow-up and the presence of extrapulmonary significant incidental findings were predicted with ensemble AI models, and individualized structure risk scores were evaluated. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the performance of the models for prediction of ACM and extrapulmonary significant incidental findings. The Pearson χ2 test and Kruskal-Wallis rank sum test were used for statistical analyses. Results A total of 24 401 participants (median age, 61 years [IQR, 57-65 years]; 14 468 male) were included. In 3880 of 24 401 participants (16%), 4283 extrapulmonary significant incidental findings were reported. During the 10-year follow-up, 3389 of 24 401 participants (14%) died. CAC had the highest feature importance for predicting the three study end points. The 10-year ACM model demonstrated the best AUC performance (0.72; per-year mortality of 2.6% above and 0.8% below the risk threshold), followed by 2-year ACM (0.71; per-year mortality of 1.13% above and 0.3% below the risk threshold) and prediction of extrapulmonary significant incidental findings (0.70; probability of occurrence of 25.4% above and 9.6% below the threshold). Conclusion A fully automated AI model indicated extrapulmonary structures at risk on chest CT scans and predicted ACM with explanations. ClinicalTrials.gov Identifier: NCT00047385 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Yanagawa and Hata in this issue.

Deep Learning-Enabled Quantification of 99mTc-Pyrophosphate SPECT/CT for Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR CA) is increasingly recognized as a cause of heart failure in older patients, with 99mTc-pyrophosphate imaging frequently used to establish the diagnosis. Visual interpretation of SPECT images is the gold standard for interpretation but is inherently subjective. Manual quantitation of SPECT myocardial 99mTc-pyrophosphate activity is time-consuming and not performed clinically. We evaluated a deep learning approach for fully automated volumetric quantitation of 99mTc-pyrophosphate using segmentation of coregistered anatomic structures from CT attenuation maps. Methods: Patients who underwent SPECT/CT 99mTc-pyrophosphate imaging for suspected ATTR CA were included. Diagnosis of ATTR CA was determined using standard criteria. Cardiac chambers and myocardium were segmented from CT attenuation maps using a foundational deep learning model and then applied to attenuation-corrected SPECT images to quantify radiotracer activity. We evaluated the diagnostic accuracy of target-to-background ratio (TBR), cardiac pyrophosphate activity (CPA), and volume of involvement (VOI) using the area under the receiver operating characteristic curve (AUC). We then evaluated associations with the composite outcome of cardiovascular death or heart failure hospitalization. Results: In total, 299 patients were included (median age, 76 y), with ATTR CA diagnosed in 83 (27.8%) patients. CPA (AUC, 0.989; 95% CI, 0.974-1.00) and VOI (AUC, 0.988; 95% CI, 0.973-1.00) had the highest prediction performance for ATTR CA. The next highest AUC was for TBR (AUC, 0.979; 95% CI, 0.964-0.995). The AUC for CPA was significantly higher than that for heart-to-contralateral ratio (AUC, 0.975; 95% CI, 0.952-0.998; P = 0.046). Twenty-three patients with ATTR CA experienced cardiovascular death or heart failure hospitalization. All methods for establishing TBR, CPA, and VOI were associated with an increased risk of events after adjustment for age, with hazard ratios ranging from 1.41 to 1.84 per SD increase. Conclusion: Deep learning segmentation of coregistered CT attenuation maps is not affected by the pattern of radiotracer uptake and allows for fully automatic quantification of hot-spot SPECT imaging such as 99mTc-pyrophosphate. This approach can be used to accurately identify patients with ATTR CA and may play a role in risk prediction.

Stress Perfusion Cardiac Magnetic Resonance vs SPECT Imaging for Detection of Coronary Artery Disease.

BACKGROUND: GadaCAD2 was 1 of 2 international, multicenter, prospective, Phase 3 clinical trials that led to U.S. Food and Drug Administration approval of gadobutrol to assess myocardial perfusion and late gadolinium enhancement (LGE) in adults with known or suspected coronary artery disease (CAD). OBJECTIVES: A prespecified secondary objective was to determine if stress perfusion cardiovascular magnetic resonance (CMR) was noninferior to single-photon emission computed tomography (SPECT) for detecting significant CAD and for excluding significant CAD. METHODS: Participants with known or suspected CAD underwent a research rest and stress perfusion CMR that was compared with a gated SPECT performed using standard clinical protocols. For CMR, adenosine or regadenoson served as vasodilators. The total dose of gadobutrol was 0.1 mmol/kg body weight. The standard of reference was a 70% stenosis defined by quantitative coronary angiography (QCA). A negative coronary computed tomography angiography could exclude CAD. Analysis was per patient. CMR, SPECT, and QCA were evaluated by independent central core lab readers blinded to clinical information. RESULTS: Participants were predominantly male (61.4% male; mean age 58.9 ± 10.2 years) and were recruited from the United States (75.0%), Australia (14.7%), Singapore (5.7%), and Canada (4.6%). The prevalence of significant CAD was 24.5% (n = 72 of 294). Stress perfusion CMR was statistically superior to gated SPECT for specificity (P = 0.002), area under the receiver operating characteristic curve (P < 0.001), accuracy (P = 0.003), positive predictive value (P < 0.001), and negative predictive value (P = 0.041). The sensitivity of CMR for a 70% QCA stenosis was noninferior and nonsuperior to gated SPECT. CONCLUSIONS: Vasodilator stress perfusion CMR, as performed with gadobutrol 0.1 mmol/kg body weight, had superior diagnostic accuracy for diagnosis and exclusion of significant CAD vs gated SPECT.

Impact of Complete Revascularization in the ISCHEMIA Trial.

BACKGROUND: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients undergoing an invasive (INV) compared with a conservative (CON) management strategy has not been reported. OBJECTIVES: Among patients with chronic coronary disease without prior coronary artery bypass grafting randomized to INV vs CON management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, we examined the following: 1) the outcomes of ACR and FCR compared with incomplete revascularization; and 2) the potential impact of achieving CR in all INV patients compared with CON management. METHODS: ACR and FCR in the INV group were assessed at an independent core laboratory. Multivariable-adjusted outcomes of CR were examined in INV patients. Inverse probability weighted modeling was then performed to estimate the treatment effect had CR been achieved in all INV patients compared with CON management. RESULTS: ACR and FCR were achieved in 43.4% and 58.4% of 1,824 INV patients. ACR was associated with reduced 4-year rates of cardiovascular death or MI compared with incomplete revascularization. By inverse probability weighted modeling, ACR in all 2,296 INV patients compared with 2,498 CON patients was associated with a lower 4-year rate of cardiovascular death or MI (difference -3.5; 95% CI: -7.2% to 0.0%). In comparison, the event rate difference of cardiovascular death or MI for INV minus CON in the overall ISCHEMIA trial was -2.4%. Results were similar but less pronounced with FCR. CONCLUSIONS: The outcomes of an INV strategy may be improved if CR (especially ACR) is achieved. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Impact of statins based on high-risk plaque features on coronary plaque progression in mild stenosis lesions: results from the PARADIGM study.

AIMS: To investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA). METHODS AND RESULTS: We analyzed mild stenosis (25-49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02-3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09-2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07-2.22; P = 0.020). CONCLUSION: In mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

Latent Coronary Plaque Morphology From Computed Tomography Angiography, Molecular Disease Activity on Positron Emission Tomography, and Clinical Outcomes.

BACKGROUND: Assessments of coronary disease activity with 18F-sodium fluoride positron emission tomography and radiomics-based precision coronary plaque phenotyping derived from coronary computed tomography angiography may enhance risk stratification in patients with coronary artery disease. We sought to investigate whether the prognostic information provided by these 2 approaches is complementary in the prediction of myocardial infarction. METHODS: Patients with known coronary artery disease underwent coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography on a hybrid positron emission tomography/computed tomography scanner. Coronary 18F-NaF uptake was determined by the coronary microcalcification activity. We performed quantitative plaque analysis of coronary computed tomography angiography datasets and extracted 1103 radiomic features for each plaque. Using weighted correlation network analysis, we derived latent morphological features of coronary lesions which were aggregated to patient-level radiomics nomograms to predict myocardial infarction. RESULTS: Among 260 patients with established coronary artery disease (age, 65±9 years; 83% men), 179 (69%) participants showed increased coronary 18F-NaF activity (coronary microcalcification activity>0). Over 53 (40-59) months of follow-up, 18 patients had a myocardial infarction. Using weighted correlation network analysis, we derived 15 distinct eigen radiomic features representing latent morphological coronary plaque patterns in an unsupervised fashion. Following adjustments for calcified, noncalcified, and low-density noncalcified plaque volumes and 18F-NaF coronary microcalcification activity, 4 radiomic features remained independent predictors of myocardial infarction (hazard ratio, 1.46 [95% CI, 1.03-2.08]; P=0.03; hazard ratio, 1.62 [95% CI, 1.04-2.54]; P=0.02; hazard ratio, 1.49 [95% CI, 1.07-2.06]; P=0.01; and hazard ratio, 1.50 (95% CI, 1.05-2.13); P=0.02). CONCLUSIONS: In patients with established coronary artery disease, latent coronary plaque morphological features, quantitative plaque volumes, and disease activity on 18F-sodium fluoride positron emission tomography are additive predictors of myocardial infarction.

RNAi-mediated rheostat for dynamic control of AAV-delivered transgenes.

Adeno-associated virus (AAV)-based gene therapy could be facilitated by the development of molecular switches to control the magnitude and timing of expression of therapeutic transgenes. RNA interference (RNAi)-based approaches hold unique potential as a clinically proven modality to pharmacologically regulate AAV gene dosage in a sequence-specific manner. We present a generalizable RNAi-based rheostat wherein hepatocyte-directed AAV transgene expression is silenced using the clinically validated modality of chemically modified small interfering RNA (siRNA) conjugates or vectorized co-expression of short hairpin RNA (shRNA). For transgene induction, we employ REVERSIR technology, a synthetic high-affinity oligonucleotide complementary to the siRNA or shRNA guide strand to reverse RNAi activity and rapidly recover transgene expression. For potential clinical development, we report potent and specific siRNA sequences that may allow selective regulation of transgenes while minimizing unintended off-target effects. Our results establish a conceptual framework for RNAi-based regulatory switches with potential for infrequent dosing in clinical settings to dynamically modulate expression of virally-delivered gene therapies.

Assessment of lifestyle "vital signs" in healthcare settings.

Unhealthy lifestyles, such as maintenance of poor diets and physical inactivity, are a powerful driver of disease-producing risk factors and chronic illnesses. This has led to an increasing call to assess adverse lifestyle factors in healthcare settings. This approach could be aided by designating health-related lifestyle factors as "vital signs" that can be recorded during patient visits. Just such an approach has been used for assessing patients' smoking habits since the 1990s. In this review, we assess the rationale for addressing six other health-related lifestyle factors, beyond smoking, in patient care settings: physical activity (PA), sedentary behavior (SB), participation in muscle strengthening exercises, mobility limitations, diet, and sleep quality. For each domain, we evaluate the evidence that supports currently proposed ultra-short screening tools. Our analysis indicates strong medical evidence to support the use of one to two-item screening questions for assessing patients' PA, SB, muscle strengthening activities, and presence of "pre-clinical" mobility limitations. We also present a theoretical basis for measuring patients' diet quality through use of an ultrashort dietary screen, based on evaluation of healthy food intake (fruits/vegetables) and unhealthy food intake (high consumption of highly processed meats and/or consumption of sugary foods and beverages) and a proposed evaluation of sleep quality using a single-item screener. The result is a 10-item lifestyle questionnaire that is based on patient self-report. As such, this questionnaire has the potential to be employed as a practical tool for assessing health behaviors in clinical care settings without impairing the normal workflow of healthcare providers.

Relationship between impaired myocardial blood flow by positron emission tomography and low-attenuation plaque burden and pericoronary adipose tissue attenuation from coronary computed tomography: From the prospective PACIFIC trial.

BACKGROUND: Positron emission tomography (PET) is the clinical gold standard for quantifying myocardial blood flow (MBF). Pericoronary adipose tissue (PCAT) attenuation may detect vascular inflammation indirectly. We examined the relationship between MBF by PET and plaque burden and PCAT on coronary CT angiography (CCTA). METHODS: This post hoc analysis of the PACIFIC trial included 208 patients with suspected coronary artery disease (CAD) who underwent [15O]H2O PET and CCTA. Low-attenuation plaque (LAP, < 30HU), non-calcified plaque (NCP), and PCAT attenuation were measured by CCTA. RESULTS: In 582 vessels, 211 (36.3%) had impaired per-vessel hyperemic MBF (≤ 2.30 mL/min/g). In multivariable analysis, LAP burden was independently and consistently associated with impaired hyperemic MBF (P = 0.016); over NCP burden (P = 0.997). Addition of LAP burden improved predictive performance for impaired hyperemic MBF from a model with CAD severity and calcified plaque burden (P < 0.001). There was no correlation between PCAT attenuation and hyperemic MBF (r = - 0.11), and PCAT attenuation was not associated with impaired hyperemic MBF in univariable or multivariable analysis of all vessels (P > 0.1). CONCLUSION: In patients with stable CAD, LAP burden was independently associated with impaired hyperemic MBF and a stronger predictor of impaired hyperemic MBF than NCP burden. There was no association between PCAT attenuation and hyperemic MBF.

Comparison of Clinical Guidelines for Authorization of MRI in the Evaluation of Neck Pain and Cervical Radiculopathy in the United States.

The American College of Radiology has published appropriateness criteria to help guide when to use MRI. Many health insurance carriers use proprietary clinical guidelines for prior authorization of imaging studies. The purpose of this study was to compare the specific criteria in those guidelines, for neck pain both with and without radicular symptoms. An online search was conducted to identify the guidelines for authorization of cervical spine MRI used by the largest commercial insurance carriers in the United States by market share. Guidelines were analyzed for neck pain with and without radiculopathy. Cervical trauma, myelopathy, infection, neoplasm, multiple sclerosis, and postprocedural care were excluded. The remaining criteria were broken down into categories including clinical symptoms, conservative therapy, other required radiologic studies, and clinical re-evaluation. Individual criteria within each of the categories were compared. After evaluation of the top 56 insurance companies in the United States, 30 companies using four main utilization management companies remained for analysis. After direct comparison of publicly available guidelines documents, notable discrepancies existed between the four companies in all subcategories analyzed. In addition, varying amounts of evidence-based literature was identified to support criteria requirements for prior authorization. This study demonstrates that the guidelines used by private health insurance companies for cervical MRI authorization in the setting of neck pain with and without cervical radiculopathy are inconsistent and use objective measures that have not been validated in the literature. We think this warrants additional scrutiny and investigation.

Glycemic control is independently associated with rapid progression of coronary atherosclerosis in the absence of a baseline coronary plaque burden: a retrospective case-control study from the PARADIGM registry.

BACKGROUND: The baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images. METHODS: A total of 402 patients (mean age: 57.6 ± 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of ≥ 1.0%/year in the percentage atheroma volume (PAV). RESULTS: During a median inter-scan period of 3.6 years (interquartile range: 2.7-5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (≥ 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (ß: 0.098, 95% confidence interval [CI]: 0.048-0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574-0.999]; P = 0.017). CONCLUSION: In this retrospective case-control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

Comparison of Outcomes of Invasive or Conservative Management of Chronic Coronary Disease in Four Randomized Controlled Trials.

Revascularization and medical therapy for chronic coronary disease have both evolved significantly over the last 50 years. A total of 4 contemporary randomized controlled trials- Clinical Outcomes Utilizing Revascularization and Aggressive drug Evaluation (COURAGE), Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D), Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 (FAME 2), and International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA)-have assessed the incremental benefit of revascularization when added to secondary prevention with intensive pharmacologic and lifestyle intervention. We reviewed these 4 seminal studies with the objective of marshaling evidence to better frame how these results should apply to clinical decision making. These studies differed in study design, end points, intensity of treatment, and revascularization techniques. Nevertheless, they all demonstrate similar rates of "hard" clinical events with invasive and conservative management, and varying degrees of benefit in angina-related quality of life with revascularization. In conclusion, although controversy persists concerning the role of revascularization because of differing interpretations of the clinical trial evidence, we contend that instead of being competing management strategies, invasive and conservative approaches are complementary.

Association between hypercholesterolemia and mortality risk among patients referred for cardiac imaging test: Evidence of a "cholesterol paradox?"

AIM: Some observational studies have observed a lower, rather than higher, mortality rate in association with hypercholesterolemia during follow-up of patients after cardiac stress testing. We aim to assess the relationship of hypercholesterolemia and other CAD risk factors to mortality across a wide spectrum of patients referred for various cardiac tests. METHODS AND RESULTS: We identified four cardiac cohorts: 64,357 patients undergoing coronary artery calcium (CAC) scanning, 10,814 patients undergoing coronary CT angiography (CCTA), 31,411 patients without known CAD undergoing stress/rest single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and 5051 patients with known CAD undergoing stress/rest SPECT-MPI. Each cohort was followed for all-cause mortality using risk-adjusted Cox models. We pooled the hazard ratios between cohorts with a random effects model. Baseline risk varied markedly among cohorts, from an annualized mortality rate of 0.31%/year in CAC patients to 3.63%/year among SPECT-MPI patients with known CAD. Hypertension, diabetes, and smoking were each associated with increased mortality in each patient cohort (pooled hazard ratio[95% CI]: 1.38[1.33-1.44], 1.88[1.76-2.00], and 1.67[1.48-1.86], respectively). By contrast, hypercholesterolemia was associated with decreased rather than increased mortality (pooled hazard ratio[95% CI]: 0.71[0.58-0.84]). Analysis of serum lipids among 7744 patients undergoing CAC or CCTA scanning revealed an inverse relationship between LDL cholesterol and mortality. CONCLUSIONS: Among a broad spectrum of patients referred for a variety of cardiac tests and ranging from low to high clinical risk, hypercholesterolemia was not associated with increased mortality risk. Our findings suggest that hypercholesterolemia may be sensitive to confounding by other clinical factors and post-test treatment changes in patient populations.

Reduced myocardial perfusion is common among subjects with ischemia and no obstructive coronary artery disease and heart failure with preserved ejection fraction: a report from the WISE-CVD continuation study.

Aim: Women with evidence of ischemia and no obstructive coronary artery disease (INOCA) have an increased risk of major adverse cardiac events, including heart failure with preserved ejection fraction (HFpEF). To investigate potential links between INOCA and HFpEF, we examined pathophysiological findings present in both INOCA and HFpEF. Methods: We performed adenosine stress cardiac magnetic resonance imaging (CMRI) in 56 participants, including 35 women with suspected INOCA, 13 women with HFpEF, and 8 reference control women. Myocardial perfusion imaging was performed at rest and with vasodilator stress with intravenous adenosine. Myocardial perfusion reserve index was quantified as the ratio of the upslope of increase in myocardial contrast at stress vs. rest. All CMRI measures were quantified using CVI42 software (Circle Cardiovascular Imaging Inc). Statistical analysis was performed using linear regression models, Fisher's exact tests, ANOVA, or Kruskal-Wallis tests. Results: Age (P = 0.007), Body surface area (0.05) were higher in the HFpEF group. Left ventricular ejection fraction (P = 0.02) was lower among the INOCA and HFpEF groups than reference controls after age adjustment. In addition, there was a graded reduction in myocardial perfusion reserve index in HFpEF vs. INOCA vs. reference controls (1.5 ± 0.3, 1.8 ± 0.3, 1.9 ± 0.3, P = 0.02), which was attenuated with age-adjustment. Conclusion: Reduced myocardial perfusion reserve appears to be a common pathophysiologic feature in INOCA and HFpEF patients.

Cardiac microstructural alterations in immune-inflammatory myocardial disease: a retrospective case-control study.

BACKGROUND: Immune-inflammatory myocardial disease contributes to multiple chronic cardiac processes, but access to non-invasive screening is limited. We have previously developed a method of echocardiographic texture analysis, called the high-spectrum signal intensity coefficient (HS-SIC) which assesses myocardial microstructure and previously associated with myocardial fibrosis. We aimed to determine whether this echocardiographic texture analysis of cardiac microstructure can identify inflammatory cardiac disease in the clinical setting. METHODS: We conducted a retrospective case-control study of 318 patients with distinct clinical myocardial pathologies and 20 healthy controls. Populations included myocarditis, atypical chest pain/palpitations, STEMI, severe aortic stenosis, acute COVID infection, amyloidosis, and cardiac transplantation with acute rejection, without current rejection but with prior rejection, and with no history of rejection. We assessed the HS-SIC's ability to differentiate between a broader diversity of clinical groups and healthy controls. We used Kruskal-Wallis tests to compare HS-SIC values measured in each of the clinical populations with those in the healthy control group and compared HS-SIC values between the subgroups of cardiac transplantation rejection status. RESULTS: For the total sample of N = 338, the mean age was 49.6 ± 20.9 years and 50% were women. The mean ± standard error of the mean of HS-SIC were: 0.668 ± 0.074 for controls, 0.552 ± 0.049 for atypical chest pain/palpitations, 0.425 ± 0.058 for myocarditis, 0.881 ± 0.129 for STEMI, 1.116 ± 0.196 for severe aortic stenosis, 0.904 ± 0.116 for acute COVID, and 0.698 ± 0.103 for amyloidosis. Among cardiac transplant recipients, HS-SIC values were 0.478 ± 0.999 for active rejection, 0.594 ± 0.091 for prior rejection, and 1.191 ± 0.442 for never rejection. We observed significant differences in HS-SIC between controls and myocarditis (P = 0.0014), active rejection (P = 0.0076), and atypical chest pain or palpitations (P = 0.0014); as well as between transplant patients with active rejection and those without current or prior rejection (P = 0.031). CONCLUSIONS: An echocardiographic method can be used to characterize tissue signatures of microstructural changes across a spectrum of cardiac disease including immune-inflammatory conditions.

Is the Use of Intraoperative 3D Navigation for Thoracolumbar Spine Surgery a Risk Factor for Post-Operative Infection?

Pedicle screw fixation is a technique used to provide rigid fixation in thoracolumbar spine surgery. Safe intraosseous placement of pedicle screws is necessary to provide optimal fixation as well as to avoid damage to adjacent anatomic structures. Despite the wide variety of techniques available, none thus far has been able to fully eliminate the risk of malpositioned screws. Intraoperative 3-dimensional navigation (I3DN) was developed to improve accuracy in the placement of pedicle screws. To our knowledge, no previous studies have investigated whether infection rates are higher with I3DN. A single-institution, retrospective study of patients age > 18 undergoing thoracolumbar fusion and instrumentation was carried out and use of I3DN was recorded. The I3DN group had a significantly greater rate of return to the operating room for culture-positive incision and drainage (17 (4.1%) vs. 1 (0.6%), p = 0.025). In multivariate analysis, the use of I3DM did not reach significance with an OR of 6.49 (0.84−50.02, p = 0.073). Post-operative infections are multifactorial and potential infection risks associated with I3DN need to be weighed against the safety benefits of improved accuracy of pedicle screw positioning.

Pericoronary Adipose Tissue Attenuation, Low-Attenuation Plaque Burden, and 5-Year Risk of Myocardial Infarction.

BACKGROUND: Pericoronary adipose tissue (PCAT) attenuation and low-attenuation noncalcified plaque (LAP) burden can both predict outcomes. OBJECTIVES: This study sought to assess the relative and additive values of PCAT attenuation and LAP to predict future risk of myocardial infarction. METHODS: In a post hoc analysis of the multicenter SCOT-HEART (Scottish Computed Tomography of the Heart) trial, the authors investigated the relationships between the future risk of fatal or nonfatal myocardial infarction and PCAT attenuation measured from coronary computed tomography angiography (CTA) using multivariable Cox regression models including plaque burden, obstructive coronary disease, and cardiac risk score (incorporating age, sex, diabetes, smoking, hypertension, hyperlipidemia, and family history). RESULTS: In 1,697 evaluable participants (age: 58 ± 10 years), there were 37 myocardial infarctions after a median follow-up of 4.7 years. Mean PCAT was -76 ± 8 HU and median LAP burden was 4.20% (IQR: 0%-6.86%). PCAT attenuation of the right coronary artery (RCA) was predictive of myocardial infarction (HR: 1.55; P = 0.017, per 1 SD increment) with an optimum threshold of -70.5 HU (HR: 2.45; P = 0.01). In multivariable analysis, adding PCAT-RCA of ≥-70.5 HU to an LAP burden of >4% (the optimum threshold for future myocardial infarction; HR: 4.87; P < 0.0001) led to improved prediction of future myocardial infarction (HR: 11.7; P < 0.0001). LAP burden showed higher area under the curve compared to PCAT attenuation for the prediction of myocardial infarction (AUC = 0.71 [95% CI: 0.62-0.80] vs AUC = 0.64 [95% CI: 0.54-0.74]; P < 0.001), with increased area under the curve when the 2 metrics are combined (AUC = 0.75 [95% CI: 0.65-0.85]; P = 0.037). CONCLUSION: Coronary CTA-defined LAP burden and PCAT attenuation have marked and complementary predictive value for the risk of fatal or nonfatal myocardial infarction.

Bypass Grafting and Native Coronary Artery Disease Activity.

OBJECTIVES: The aim of this study was to describe the potential of 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression. BACKGROUND: As well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis. METHODS: Patients with established coronary artery disease underwent baseline 18F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on 18F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery. RESULTS: Among 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no 18F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting. CONCLUSIONS: Native coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy.