Heart attacks kill more Americans than all cancers combined. Fatal heart attack victims have no symptoms until minutes before they die, hence early detection of high-risk asymptomatic individuals is needed. Even though heart attacks kill and cost more than cancers, as a nation we spend over 20 times more on screening for asymptomatic cancer than for asymptomatic atherosclerotic cardiovascular disease (ASCVD), the underlying cause of heart attacks. Currently, payers only cover screening for risk factors of ASCVD such as blood pressure and blood cholesterol. This approach tends to miss high-risk and over-treat low-risk individuals. Although treadmill stress testing with ECG is not indicated for ASCVD detection in asymptomatic individuals, it is done often, and frequently leads to misleading conclusions or unnecessary downstream diagnostic procedures. For example, former President Clinton had passed his treadmill stress tests for several years during his presidential annual checkup but had a heart attack shortly after his presidency. This common practice is a waste of our limited resources. Instead, a more accurate risk assessment using coronary artery calcium (CAC) testing is available; and has just been adopted by ACC/AHA guidelines, however payers do not cover it. CAC is measured non-invasively with a 5-minute CT-scan of the heart, and costs less than $200, whereas cancer screening with colonoscopy and mammography costs over $3000. There is an opportunity to save lives and dollars if CAC testing is covered for appropriately selected individuals. Texas has already passed HB1290 to mandate CAC coverage. Other states must step up and take actions.

Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individuals complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation.

In this clinical practice statement, we represent a summary of the current evidence and clinical applications of cardiac computed tomography (CT) in evaluation of coronary artery disease (CAD), from an expert panel organized by the American Society for Preventive Cardiology (ASPC), and appraises the current use and indications of cardiac CT in clinical practice. Cardiac CT is emerging as a front line non-invasive diagnostic test for CAD, with evidence supporting the clinical utility of cardiac CT in diagnosis and prevention. CCTA offers several advantages beyond other testing modalities, due to its ability to identify and characterize coronary stenosis severity and pathophysiological changes in coronary atherosclerosis and stenosis, aiding in early diagnosis, prognosis and management of CAD. This document further explores the emerging applications of CCTA based on functional assessment using CT derived fractional flow reserve, peri‑coronary inflammation and artificial intelligence (AI) that can provide personalized risk assessment and guide targeted treatment. We sought to provide an expert consensus based on the latest evidence and best available clinical practice guidelines regarding the role of CCTA as an essential tool in cardiovascular prevention - applicable to risk assessment and early diagnosis and management, noting potential areas for future investigation.

Background

Indocyanine green fluoroscopy has been shown to improve anastomotic leak rates in early phase trials.

Objective

We hypothesized that the use of fluoroscopy to ensure anastomotic perfusion may decrease anastomotic leak after low anterior resection.

Design

We performed a 1:1 randomized controlled parallel study. Recruitment of 450 to 1000 patients was planned over 2 years.

Settings

This was a multicenter trial.

Patients

Included patients were those undergoing resection defined as anastomosis within 10 cm of the anal verge.

Intervention

Patients underwent standard evaluation of tissue perfusion versus standard in conjunction with perfusion evaluation using indocyanine green fluoroscopy.

Main outcome measures

Primary outcome was anastomotic leak, with secondary outcomes of perfusion assessment and the rate of postoperative abscess requiring intervention.

Results

This study was concluded early because of decreasing accrual rates. A total of 25 centers recruited 347 patients, of whom 178 were randomly assigned to perfusion and 169 to standard. The groups had comparable tumor-specific and patient-specific demographics. Neoadjuvant chemoradiation was performed in 63.5% of perfusion and 65.7% of standard (p > 0.05). Mean level of anastomosis was 5.2 ± 3.1 cm in perfusion compared with 5.2 ± 3.3 cm in standard (p > 0.05). Sufficient visualization of perfusion was reported in 95.4% of patients in the perfusion group. Postoperative abscess requiring surgical management was reported in 5.7% of perfusion and 4.2% of standard (p = 0.75). Anastomotic leak was reported in 9.0% of perfusion compared with 9.6% of standard (p = 0.37). On multivariate regression analysis, there was no difference in anastomotic leak rates between perfusion and standard (OR = 0.845 (95% CI, 0.375-1.905); p = 0.34).

Limitations

The predetermined sample size to adequately reduce the risk of type II error was not achieved.

Conclusions

Successful visualization of perfusion can be achieved with indocyanine green fluoroscopy. However, no difference in anastomotic leak rates was observed between patients who underwent perfusion assessment versus standard surgical technique. In experienced hands, the addition of routine indocyanine green fluoroscopy to standard practice adds no evident clinical benefit. See Video Abstract at http://links.lww.com/DCR/B560.

Valoracin de la irrigacin de lado izquierdo/reseccin anterior baja pilar iii un estudio aleatorizado, controlado, paralelo y multicntrico que evala los resultados de la irrigacin con pinpoint imgenes de fluorescencia cercana al infrarrojo en la reseccin anterior baja

ANTECEDENTES:Se ha demostrado que la fluoroscopia con verde de indocianina mejora las tasas de fuga anastomótica en ensayos en fases iniciales.OBJETIVO:Nuestra hipótesis es que la utilización de fluoroscopia para asegurar la irrigación anastomótica puede disminuir la fuga anastomótica luego de una resección anterior baja.DISEÑO:Realizamos un estudio paralelo, controlado, aleatorizado 1:1. Se planificó el reclutamiento de 450-1000 pacientes durante 2 años.AMBITO:Multicéntrico.PACIENTES:Pacientes sometidos a resección definida como una anastomosis dentro de los 10cm del margen anal.INTERVENCIÓN:Pacientes que se sometieron a la evaluación estándar de la irrigación tisular contra la estándar en conjunto con la valoración de la irrigación mediante fluoroscopia con verde indocianina.PRINCIPALES VARIABLES EVALUADAS:El principal resultado fue la fuga anastomótica, y los resultados secundarios fueron la evaluación de la perfusión y la tasa de absceso posoperatorio que requirió intervención.RESULTADOS:Este estudio se cerró anticipadamente debido a la disminución de las tasas de acumulación. Un total de 25 centros reclutaron a 347 pacientes, de los cuales 178 fueron, de manera aleatoria, asignados a perfusión y 169 a estándar. Los grupos tenían datos demográficos específicos del tumor y del paciente similares. Recibieron quimio-radioterapia neoadyuvante el 63,5% de la perfusión y el 65,7% del estándar (p> 0,05). La anastomosis estuvo en un nivel promedio de 5,2 + 3,1 cm en perfusión en comparación con 5,2 + 3,3 cm en estándar (p> 0,05). Se reportó una visualización suficiente de la perfusión en el 95,4% de los pacientes del grupo de perfusión. El absceso posoperatorio que requirió tratamiento quirúrgico fue de 5,7% de los perfusion y en el 4,2% del estándar (p = 0,75). Se informó fuga anastomótica en el 9,0% de la perfusión en comparación con el 9,6% del estándar (p = 0,37). En el análisis de regresión multivariante, no hubo diferencias en las tasas de fuga anastomótica entre la perfusión y el estándar (OR 0,845; IC del 95% (0,375; 1,905); p = 0,34).LIMITACIONES:No se logró el tamaño de muestra predeterminado para reducir satisfactoriamente el riesgo de error tipo II.CONCLUSIÓN:Se puede obtener una visualización adecuada de la perfusión con ICG-F. Sin embargo, no se observaron diferencias en las tasas de fuga anastomótica entre los pacientes que se sometieron a evaluación de la perfusión versus la técnica quirúrgica estándar. En manos expertas, agregar ICG-F a la rutina de la práctica estándar no agrega ningún beneficio clínico evidente. Consulte Video Resumen en http://links.lww.com/DCR/B560. (Traducción-Dr Juan Antonio Villanueva-Herrero).

Background In participants with concomitant chronic coronary disease and advanced chronic kidney disease (CKD), the effect of treatment strategies on the timing of dialysis initiation is not well characterized. Methods and Results In ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease), 777 participants with advanced CKD and moderate or severe ischemia were randomized to either an initial invasive or conservative management strategy. Herein, we compare the proportion of randomized participants with non-dialysis-requiring CKD at baseline (n=362) who initiated dialysis and compare the time to dialysis initiation between invasive versus conservative management arms. Using multivariable Cox regression analysis, we also sought to identify the effect of invasive versus conservative chronic coronary disease management strategies on dialysis initiation. At a median follow-up of 23 months (25th-75th interquartile range, 14-32 months), dialysis was initiated in 18.9% of participants (36/190) in the invasive strategy and 16.9% of participants (29/172) in the conservative strategy (P=0.22). The median time to dialysis initiation was 6.0 months (interquartile range, 3.0-16.0 months) in the invasive group and 18.2 months (interquartile range, 12.2-25.0 months) in the conservative group (P=0.004), with no difference in procedural acute kidney injury rates between the groups (7.8% versus 5.4%; P=0.26). Baseline clinical factors associated with earlier dialysis initiation were lower baseline estimated glomerular filtration rate (hazard ratio [HR] associated with 5-unit decrease, 2.08 [95% CI, 1.72-2.56]; P<0.001), diabetes (HR, 2.30 [95% CI, 1.28-4.13]; P=0.005), hypertension (HR, 7.97 [95% CI, 1.09-58.21]; P=0.041), and Hispanic ethnicity (HR, 2.34 [95% CI, 1.22-4.47]; P=0.010). Conclusions In participants with non-dialysis-requiring CKD in ISCHEMIA-CKD, randomization to an invasive chronic coronary disease management strategy (relative to a conservative chronic coronary disease management strategy) is associated with an accelerated time to initiation of maintenance dialysis for kidney failure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01985360.

BACKGROUND: Ischemia with nonobstructive coronary arteries (INOCA) is common clinically, particularly among women, but its prevalence among patients with at least moderate ischemia and the relationship between ischemia severity and non-obstructive atherosclerosis severity are unknown. OBJECTIVES: The authors investigated predictors of INOCA in enrolled, nonrandomized participants in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), sex differences, and the relationship between ischemia and atherosclerosis in patients with INOCA. METHODS: Core laboratories independently reviewed screening noninvasive stress test results (nuclear imaging, echocardiography, magnetic resonance imaging or nonimaging exercise tolerance testing), and coronary computed tomography angiography (CCTA), blinded to results of the screening test. INOCA was defined as all stenoses <50% on CCTA in a patient with moderate or severe ischemia on stress testing. INOCA patients, who were excluded from randomization, were compared with randomized participants with ≥50% stenosis in ≥1 vessel and moderate or severe ischemia. RESULTS: Among 3,612 participants with core laboratory-confirmed moderate or severe ischemia and interpretable CCTA, 476 (13%) had INOCA. Patients with INOCA were younger, were predominantly female, and had fewer atherosclerosis risk factors. For each stress testing modality, the extent of ischemia tended to be less among patients with INOCA, particularly with nuclear imaging. There was no significant relationship between severity of ischemia and extent or severity of nonobstructive atherosclerosis on CCTA. On multivariable analysis, female sex was independently associated with INOCA (odds ratio: 4.2 [95% CI: 3.4-5.2]). CONCLUSIONS: Among participants enrolled in ISCHEMIA with core laboratory-confirmed moderate or severe ischemia, the prevalence of INOCA was 13%. Severity of ischemia was not associated with severity of nonobstructive atherosclerosis. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Objectives

This study aimed to examine the concordance of coronary computed tomographic angiography (CCTA) assessment of coronary anatomy and invasive coronary angiography (ICA) as the reference standard in patients enrolled in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches).

Background

Performance of CCTA compared with ICA has not been assessed in patients with very high burdens of stress-induced ischemia and a high likelihood of anatomically significant coronary artery disease (CAD). A blinded CCTA was performed after enrollment to exclude patients with left main (LM) disease or no obstructive CAD before randomization to an initial conservative or invasive strategy, the latter guided by ICA and optimal revascularization.

Methods

Rates of concordance were calculated on a per-patient basis in patients randomized to the invasive strategy. Anatomic significance was defined as ≥50% diameter stenosis (DS) for both modalities. Sensitivity analyses using a threshold of ≥70% DS for CCTA or considering only CCTA images of good-to-excellent quality were performed.

Results

In 1,728 patients identified by CCTA as having no LM disease ≥50% and at least single-vessel CAD, ICA confirmed 97.1% without LM disease ≥50%, 92.2% with at least single-vessel CAD and no LM disease ≥50%, and only 4.9% without anatomically significant CAD. Results using a ≥70% DS threshold or only CCTA of good-to-excellent quality showed similar overall performance.

Conclusions

CCTA before randomization in ISCHEMIA demonstrated high concordance with subsequent ICA for identification of patients with angiographically significant disease without LM disease.

Coronary artery disease (CAD), the most common manifestation of cardiovascular disease, remains the most common cause of mortality in the United States. Risk assessment is key for primary prevention of coronary events and coronary artery calcium (CAC) scoring using computed tomography (CT) is one such non-invasive tool. Despite the proven clinical value of CAC, the current clinical practice implementation for CAC has limitations such as the lack of insurance coverage for the test, need for capital-intensive CT machines, specialized imaging protocols, and accredited 3D imaging labs for analysis (including personnel and software). Perhaps the greatest gap is the millions of patients who undergo routine chest CT exams and demonstrate coronary artery calcification, but their presence is not often reported or quantitation is not feasible. We present two deep learning models that automate CAC scoring demonstrating advantages in automated scoring for both dedicated gated coronary CT exams and routine non-gated chest CTs performed for other reasons to allow opportunistic screening. First, we trained a gated coronary CT model for CAC scoring that showed near perfect agreement (mean difference in scores = -2.86; Cohen's Kappa = 0.89, P < 0.0001) with current conventional manual scoring on a retrospective dataset of 79 patients and was found to perform the task faster (average time for automated CAC scoring using a graphics processing unit (GPU) was 3.5 ± 2.1 s vs. 261 s for manual scoring) in a prospective trial of 55 patients with little difference in scores compared to three technologists (mean difference in scores = 3.24, 5.12, and 5.48, respectively). Then using CAC scores from paired gated coronary CT as a reference standard, we trained a deep learning model on our internal data and a cohort from the Multi-Ethnic Study of Atherosclerosis (MESA) study (total training n = 341, Stanford test n = 42, MESA test n = 46) to perform CAC scoring on routine non-gated chest CT exams with validation on external datasets (total n = 303) obtained from four geographically disparate health systems. On identifying patients with any CAC (i.e., CAC ≥ 1), sensitivity and PPV was high across all datasets (ranges: 80-100% and 87-100%, respectively). For CAC ≥ 100 on routine non-gated chest CTs, which is the latest recommended threshold to initiate statin therapy, our model showed sensitivities of 71-94% and positive predictive values in the range of 88-100% across all the sites. Adoption of this model could allow more patients to be screened with CAC scoring, potentially allowing opportunistic early preventive interventions.

Coronary artery calcium (CAC) scans contain valuable information beyond the Agatston Score which is currently reported for predicting coronary heart disease (CHD) only. We examined whether new artificial intelligence (AI) applied to CAC scans can predict non-CHD events, including heart failure, atrial fibrillation, and stroke. We applied AI-enabled automated cardiac chambers volumetry and calcified plaque characterization to CAC scans (AI-CAC) of 5830 asymptomatic individuals (52.2% women, age 61.7 ± 10.2 years) in the multi-ethnic study of atherosclerosis during 15 years of follow-up, 1773 CVD events accrued. The AUC at 1-, 5-, 10-, and 15-year follow-up for AI-CAC vs. Agatston score was (0.784 vs. 0.701), (0.771 vs. 0.709), (0.789 vs. 0.712) and (0.816 vs. 0.729) (p < 0.0001 for all), respectively. AI-CAC plaque characteristics, including number, location, density, plus number of vessels, significantly improved CHD prediction in the CAC 1-100 cohort vs. Agatston Score. AI-CAC significantly improved the Agatston score for predicting all CVD events.

Background

In the ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), an initial invasive strategy did not significantly reduce rates of cardiovascular events or all-cause mortality in comparison with a conservative strategy in patients with stable ischemic heart disease and moderate/severe myocardial ischemia. The most frequent component of composite cardiovascular end points was myocardial infarction (MI).

Methods

ISCHEMIA prespecified that the primary and major secondary composite end points of the trial be analyzed using 2 MI definitions. For procedural MI, the primary MI definition used creatine kinase-MB as the preferred biomarker, whereas the secondary definition used cardiac troponin. Procedural thresholds were >5 times the upper reference level for percutaneous coronary intervention and >10 times for coronary artery bypass grafting. Procedural MI definitions included (1) a category of elevated biomarker only events with much higher biomarker thresholds, (2) new ST-segment depression of ≥1 mm for the primary and ≥0.5 mm for the secondary definition, and (3) new coronary dissections >National Heart, Lung, and Blood Institute grade 3. We compared MI type, frequency, and prognosis by treatment assignment using both MI definitions.

Results

Procedural MIs accounted for 20.1% of all MI events with the primary definition and 40.6% of all MI events with the secondary definition. Four-year MI rates in patients undergoing revascularization were more frequent with the invasive versus conservative strategy using the primary (2.7% versus 1.1%; adjusted hazard ratio [HR], 2.98 [95% CI, 1.87-4.73]) and secondary (8.2% versus 2.0%; adjusted HR, 5.04 [95% CI, 3.64-6.97]) MI definitions. Type 1 MIs were less frequent with the invasive versus conservative strategy using the primary (3.40% versus 6.89%; adjusted HR, 0.53 [95% CI, 0.41-0.69]; P<0.0001) and secondary (3.48% versus 6.89%; adjusted HR, 0.53 [95% CI, 0.41-0.69]; P<0.0001) definitions. The risk of subsequent cardiovascular death was higher after a type 1 MI than after no MI using the primary (adjusted HR, 3.38 [95% CI, 2.03-5.61]; P<0.001) or secondary MI definition (adjusted HR, 3.52 [2.11-5.88]; P<0.001).

Conclusions

In ISCHEMIA, type 1 MI events using the primary and secondary definitions during 5-year follow-up were more frequent with an initial conservative strategy and associated with subsequent cardiovascular death. Procedural MI rates were greater in the invasive strategy and with the use of the secondary MI definition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.