The prognostic value of visual and automatic coronary calcium -scoring from low dose CT-[15O]-water PET.

PURPOSE: Firstly, to validate automatically and visually scored coronary artery calcium (CAC) on low dose CT (LDCT) scans with a dedicated calcium scoring CT (CSCT) scan. Secondly, to assess the added value of CAC scored from LDCT scans acquired during [15O]-water-PET myocardial perfusion imaging (MPI) on prediction of major adverse cardiac events (MACE). METHODS: 572 consecutive patients with suspected coronary artery disease, who underwent [15O]-water-PET MPI with LDCT and a dedicated CSCT scan were included. In the reference CSCT scans, manual CAC scoring was performed, while LDCT scans were scored visually and automatically using deep learning approach. Subsequently, based on CAC score results from CSCT and LDCT scans, each patient's scan was assigned to one out of five cardiovascular risk groups (0; 1-100; 101-400; 401-1000; >1000) and the agreement in risk group classification between CSCT and LDCT scans was investigated. MACE was defined as a composite of all-cause death, nonfatal myocardial infarction, coronary revascularization, and unstable angina. RESULTS: The agreement in risk group classification between reference CSCT manual scoring and visual/automatic LDCT scoring from LDCT was 0.66 (95% CI: 0.62-0.70) and 0.58 (95% CI: 0.53-0.62), respectively. Based on visual and automatic CAC scoring from LDCT scans, patients with CAC>100 and CAC>400, respectively, were at increased risk of MACE, independently of ischemic information from the [15O]-water-PET scan. CONCLUSIONS: There is a moderate agreement in risk classification between visual and automatic CAC scoring from LDCT and reference CSCT scans. Visual and automatic CAC scoring from LDCT scans improve identification of patients at higher risk of MACE.

The impact of patient-reported frailty on cardiovascular outcomes in elderly patients after non-ST-acute coronary syndrome.

BACKGROUND: As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess the impact of patient-reported frailty on the treatment and prognosis of elderly early survivors of non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Frailty data were obtained from two prospective trials, POPular Age and the POPular Age Registry, which both assessed elderly NSTE-ACS patients. Frailty was assessed one month after admission with the Groningen Frailty Indicator (GFI) and was defined as a GFI-score of 4 or higher. In these early survivors of NSTE-ACS, we assessed differences in treatment and 1-year outcomes between frail and non-frail patients, considering major adverse cardiovascular events (MACE, including cardiovascular mortality, myocardial infarction, and stroke) and major bleeding. RESULTS: The total study population consisted of 2192 NSTE-ACS patients, aged ≥70 years. The GFI-score was available in 1320 patients (79 ± 5 years, 37% women), of whom 712 (54%) were considered frail. Frail patients were at higher risk for MACE than non-frail patients (9.7% vs. 5.1%, adjusted hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.01-2.43, p = 0.04), but not for major bleeding (3.7% vs. 2.8%, adjusted HR 1.23, 95% CI 0.65-2.32, p = 0.53). Cubic spline analysis showed a gradual increase of the risk for clinical outcomes with higher GFI-scores. CONCLUSIONS: In elderly NSTE-ACS patients who survived 1-month follow-up, patient-reported frailty was independently associated with a higher risk for 1-year MACE, but not with major bleeding. These findings emphasize the importance of frailty screening for risk stratification in elderly NSTE-ACS patients.

Automated cardiovascular risk categorization through AI-driven coronary calcium quantification in cardiac PET acquired attenuation correction CT.

BACKGROUND: We present an automatic method for coronary artery calcium (CAC) quantification and cardiovascular risk categorization in CT attenuation correction (CTAC) scans acquired at rest and stress during cardiac PET/CT. The method segments CAC according to visual assessment rather than the commonly used CT-number threshold. METHODS: The method decomposes an image containing CAC into a synthetic image without CAC and an image showing only CAC. Extensive evaluation was performed in a set of 98 patients, each having rest and stress CTAC scans and a dedicated calcium scoring CT (CSCT). Standard manual calcium scoring in CSCT provided the reference standard. RESULTS: The interscan reproducibility of CAC quantification computed as average absolute relative differences between CTAC and CSCT scan pairs was 75% and 85% at rest and stress using the automatic method compared to 121% and 114% using clinical calcium scoring. Agreement between automatic risk assessment in CTAC and clinical risk categorization in CSCT resulted in linearly weighted kappa of 0.65 compared to 0.40 between CTAC and CSCT using clinically used calcium scoring. CONCLUSION: The increased interscan reproducibility achieved by our method may allow routine cardiovascular risk assessment in CTAC, potentially relieving the need for dedicated CSCT.

Evolution of coronary artery calcium and absolute myocardial perfusion after percutaneous revascularization: A 3-year serial hybrid [15O]H2O PET/CT imaging study.

BACKGROUND AND AIMS: The value of serial coronary artery calcium (CAC) scores to predict changes in absolute myocardial perfusion and epicardial vasomotor function is poorly documented. This study explored the association between progression of CAC score and changes in absolute myocardial perfusion. METHODS: Fifty-three patients (26% female) with de novo single-vessel coronary artery disease underwent [15O]H2O positron emission tomography/computed tomography at 1 month (baseline), 1 year, and 3 years after complete revascularization with percutaneous coronary intervention (PCI) to assess CAC scores, hyperemic myocardial blood flow (hMBF), coronary flow reserve (CFR) and cold pressor test MBF (CPT-MBF), within the context of the VANISH trial. RESULTS: Baseline CAC score was 0 in 9%, 0.1-99.9 in 40%, 100-399.9 in 36% and ≥400 in 15% of patients, respectively. Mixed model-analysis allowed for averaging perfusion indices over all time points: hMBF (3.74 ± 0.83; 3.33 ± 0.79; 3.08 ± 0.78 and 2.44 ± 0.74 mL min-1·g-1) and CFR (3.82 ± 1.12; 3.17 ± 0.80; 3.19 ± 0.81; 2.63 ± 0.92) were lower among higher baseline CAC groups (p < 0.01; p = 0.03). However, no significant interaction was found between baseline CAC groups and time after PCI for all perfusion indices, denoting that evolution of perfusion indices over time was not significantly different between CAC groups. Furthermore, CAC progression was not correlated with evolution of hMBF (r = 0.08, p = 0.57), CFR (r = 0.09, p = 0.53) or CPT-MBF (r = 0.03, p = 0.82) during 3 years of follow-up. CONCLUSIONS: Higher baseline CAC was associated with lower hMBF and CFR. However, both baseline CAC and its progression were not associated with evolution of absolute hMBF, CFR and CPT-MBF over time, suggesting that CAC score and progression of CAC are poor indicators of change in absolute myocardial perfusion.

Incidence and outcomes of chronic total occlusion percutaneous coronary intervention in the Netherlands: data from a nationwide registry.

BACKGROUND: Patients with chronic total coronary occlusions (CTO) are at increased risk for poor clinical outcomes. We aimed to determine the incidence of CTO percutaneous coronary intervention (PCI) and to identify CTO patients at risk for cardiac events in the nationwide Netherlands Heart Registration (NHR). METHODS: We included all PCI procedures with ≥1 CTO registered in the NHR from January 2015 to December 2018, excluding acute interventions. We used multivariable logistic regression of baseline characteristics to calculate the risk for events as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Of the PCIs performed during the study period, 6.3% (8,343/133,042) were for CTOs, with the percentage increasing significantly over time from 5.9% in 2015 to 6.6% in 2018 (p < 0.001). Coronary artery bypass grafting <24 h was carried out in 0.3%, and the only significant predictor was diabetes mellitus (OR 2.97, 95% CI 1.04-8.49, p = 0.042). Myocardial infarction (MI) <30 days occurred in 0.5%, and renal insufficiency (i.e. estimated glomerular filtration rate <30 ml/min per 1.73 m2) was identified as an independent predictor (OR 4.70, 95% CI 1.07-20.61, p = 0.040). Among patients undergoing CTO-PCI, 1­year mortality was 3.7%, and independent predictors included renal insufficiency (OR 5.59, 95% CI 3.25-9.59, p < 0.001), left ventricular ejection fraction <30% (OR 3.43, 95% CI 2.00-5.90, p < 0.001), previous MI (OR 1.62, 95% CI 1.14-2.31, p = 0.007) and age (OR 1.06 per year increment, 95% CI 1.04-1.07, p < 0.001). Target-vessel revascularisation <1 year occurred in 11.3%. CONCLUSION: CTO-PCI is still infrequently performed in the Netherlands. The most important predictor of mortality after CTO-PCI was renal insufficiency. Identification of patients at risk may help improve the prognosis of CTO patients in the future.

A computed tomography algorithm for crossing coronary chronic total occlusions: riding on the wave of the proximal cap and distal vessel segment.

With wider adoption of coronary computed tomography angiography (coronary CTA), chronic total occlusions (CTOs) are being increasingly identified and characterised by non-invasive angiography. In particular, the ability of coronary CTA to clearly delineate atherosclerotic plaque, as well as to display three-dimensional vessel trajectories, has garnered particular attention in the context of preprocedural planning and periprocedural guidance of CTO percutaneous coronary intervention (PCI). Single CTO features and combined scoring systems derived from CTA (mostly exceeding the diagnostic performance of the angiographic J­CTO score) have been used to predict time-efficient guidewire crossing, and thus grade the CTO difficulty level prior to PCI. In addition, the introduction of three-dimensional CTA/fluoroscopy co-registration for periprocedural navigation during CTO PCI offers the unprecedented opportunity to resolve proximal cap ambiguity and clearly visualise the distal CTO segment, thereby potentially influencing CTO PCI strategies and techniques. In this review, the potential advantages of non-invasive evaluation of CTO by coronary CTA are described, and a CTA-based hybrid algorithm is introduced for further enhancing the efficiency of CTO PCI. Further studies are clearly needed to verify the proposed approach. However, several luminary operators have already implemented coronary CTA for planning and periprocedural guidance of CTO interventions using the hybrid algorithm.

Coronary computed tomography angiography and [15O]H2O positron emission tomography perfusion imaging for the assessment of coronary artery disease.

Determining the anatomic severity and extent of coronary artery disease (CAD) by means of coronary computed tomography angiography (CCTA) and its effect on perfusion using myocardial perfusion imaging (MPI) form the pillars of the non-invasive imaging assessment of CAD. This review will 1) focus on CCTA and [15O]H2O positron emission tomography MPI as stand-alone imaging modalities and their combined use for detecting CAD, 2) highlight some of the lessons learned from the PACIFIC trial (Comparison of Coronary CT Angiography, SPECT, PET, and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve (FFR) (NCT01521468)), and 3) discuss the use of [15O]H2O PET MPI in the clinical work-up of patients with a chronic coronary total occlusion (CTO).

Impact of scan quality on the diagnostic performance of CCTA, SPECT, and PET for diagnosing myocardial ischemia defined by fractional flow reserve.

BACKGROUND: Scan quality can have a significant effect on the diagnostic performance of non-invasive imaging techniques. However, the extent of its influence has scarcely been investigated in a head-to-head manner. METHODS: Two-hundred and eight patients underwent CCTA, SPECT, and PET prior to invasive fractional flow reserve measurements. Scan quality was classified as either good, moderate, or poor. RESULTS: Distribution of good, moderate, and poor quality scans was; CCTA; 66%, 22%, 13%; SPECT; 52%, 38%, 9%; PET; 86%, 13%, 1%. Good quality CCTA scans possessed a higher specificity (75% vs. 31%, p = 0.001), positive predictive value (PPV, 71% vs. 51%, p = 0.050), and accuracy (80% vs. 60%, p = 0.009) compared to moderate quality scans, while sensitivity (94%) and negative predictive value (NPV, 88%) were similar to moderate and poor quality scans. Sensitivity (76%), NPV (84%), and accuracy (85%) of good quality SPECT scans was superior to those of moderate (41% p = 0.001, 56% p = 0.010, 70% p = 0.010) and poor quality (30% p = 0.003, 65% p = 0.069, 63% p = 0.038). Specificity (92%) and PPV (87%) of good quality SPECT scans did not differ from scans of diminished quality. Good quality PET scans exhibited high sensitivity (84%), specificity (86%), NPV (88%), PPV (81%) and accuracy (85%), which was comparable to scans of lesser quality. Good quality CCTA, SPECT, and PET scans demonstrated a similar diagnostic accuracy (p = 0.247). CONCLUSION: Diagnostic performance of CCTA, and SPECT is hampered by scan quality, while the diagnostic value of PET is not affected. Good quality CCTA, SPECT, and PET scans possess a high diagnostic accuracy.

Prophylactic veno-arterial extracorporeal membrane oxygenation in patients undergoing high-risk percutaneous coronary intervention.

PURPOSE: Complex high-risk percutaneous coronary intervention (PCI) is challenging and frequently accompanied by haemodynamic instability. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide cardiopulmonary support in high-risk PCI. However, the outcome is unclear. METHODS: A two-centre, retrospective study was performed of all patients undergoing high-risk PCI and receiving VA-ECMO for cardiopulmonary support. RESULTS: A total of 14 patients (92% male, median age 69 (53-83) years), of whom 50% had previous coronary artery disease in the form of a coronary artery bypass graft (36%) and a PCI (14%) underwent high-risk PCI and received VA-ECMO support. The main target lesion was a left main coronary artery in 78%, a left anterior descending artery in 14%, a right coronary artery in 7%, and 71% underwent multi-vessel PCI in addition to main target vessel PCI. The median SYNTAX score was 27.2 (8-42.5) and in 64% (9/14) there was a chronic total occlusion. Left ventricular function was mildly impaired in 7% (1/14), moderately impaired in 14% (2/14) and severely impaired in 64% (9/14). Cannulation was femoral-femoral in all patients. Median ECMO run was 2.57 h (1-4). Survival was 93% (13/14). One patient died during hospitalisation due to refractory cardiac failure. All other patients survived to discharge. Complications occurred in 14% (2/14), with one patient developing a transient ischaemic attack post-ECMO and one patient developing a thrombus in the femoral vein used for ECMO cannulation. CONCLUSION: VA-ECMO in high-risk PCI is feasible with a good outcome. It can be successfully used for cardiopulmonary support in selected patients.

Data on the impact of scan quality on the diagnostic performance of CCTA, SPECT, and PET for diagnosing myocardial ischemia defined by fractional flow reserve on a per vessel level.

Scan quality directly impacts the diagnostic performance of non-invasive imaging modalities as reported in a substudy of the PACIFC-trial: "Impact of Scan Quality on the Diagnostic Performance of CCTA, SPECT, and PET for Diagnosing Myocardial Ischemia Defined by Fractional Flow Reserve" [1]. This Data-in-Brief paper supplements the hereinabove mentioned article by presenting the diagnostic performance of CCTA, SPECT, and PET on a per vessel level for the detection of hemodynamic significant coronary artery disease (CAD) when stratified according to scan quality and vascular territory.

The association of coronary lumen volume to left ventricle mass ratio with myocardial blood flow and fractional flow reserve.

BACKGROUND: A diminished coronary lumen volume to left ventricle mass ratio (V/M) derived from coronary computed tomography angiography (CCTA) has been proposed as factor contributing to impaired myocardial blood flow (MBF) even in the absence of obstructive disease on invasive coronary angiography (ICA). METHODS: Patients underwent CCTA, and positron emission tomography (PET) prior to ICA. Matched global V/M, global, and vessel specific hyperaemic MBF (hMBF), coronary flow reserve (CFR), and, FFR were available for 431 vessels in 152 patients. The median V/M (20.71 mm3/g) was used to divide the population into patients with either a low V/M or a high V/M. RESULTS: Overall, a higher percentage of vessels with an abnormal hMBF and FFR (34% vs. 19%, p = 0.009 and 20% vs. 9%, p = 0.004), as well as a lower FFR (0.93 [interquartile range: 0.85-0.97] vs. 0.95 [0.89-0.98], p = 0.016) values were observed in the low V/M group. V/M was weakly associated with vessel specific hMBF (R = 0.148, p = 0.027), and FFR (R = 0.156, p < 0.001). Among vessels with non-obstructive CAD on ICA (361 vessels), no association between V/M and vessel specific hMBF nor CFR was noted. However, in the absence of obstructive CAD, V/M was associated with (R = 0.081, p = 0.027), and independently predictive for FFR (p = 0.047). CONCLUSION: Overall, an abnormal vessel specific hMBF and FFR were more prevalent in patients with a low V/M compared to those with a high V/M. Furthermore, V/M was weakly associated with vessel specific hMBF and FFR. In the absence of obstructive CAD on ICA, V/M was weakly associated with notwithstanding independently predictive for FFR.

Automated SPECT analysis compared with expert visual scoring for the detection of FFR-defined coronary artery disease.

PURPOSE: Traditionally, interpretation of myocardial perfusion imaging (MPI) is based on visual assessment. Computer-based automated analysis might be a simple alternative obviating the need for extensive reading experience. Therefore, the aim of the present study was to compare the diagnostic performance of automated analysis with that of expert visual reading for the detection of obstructive coronary artery disease (CAD). METHODS: 206 Patients (64% men, age 58.2 ± 8.7 years) with suspected CAD were included prospectively. All patients underwent 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) and invasive coronary angiography with fractional flow reserve (FFR) measurements. Non-corrected (NC) and attenuation-corrected (AC) SPECT images were analyzed both visually as well as automatically by commercially available SPECT software. Automated analysis comprised a segmental summed stress score (SSS), summed difference score (SDS), stress total perfusion deficit (S-TPD), and ischemic total perfusion deficit (I-TPD), representing the extent and severity of hypoperfused myocardium. Subsequently, software was optimized with an institutional normal database and thresholds. Diagnostic performances of automated and visual analysis were compared taking FFR as a reference. RESULTS: Sensitivity did not differ significantly between visual reading and most automated scoring parameters, except for SDS, which was significantly higher than visual assessment (p < 0.001). Specificity, however, was significantly higher for visual reading than for any of the automated scores (p < 0.001 for all). Diagnostic accuracy was significantly higher for visual scoring (77.2%) than for all NC images scores (p < 0.05), but not compared with SSS AC and S-TPD AC (69.8% and 71.2%, p = 0.063 and p = 0.134). After optimization of the automated software, diagnostic accuracies were similar for visual (73.8%) and automated analysis. Among the automated parameters, S-TPD AC showed the highest accuracy (73.5%). CONCLUSION: Automated analysis of myocardial perfusion SPECT can be as accurate as visual interpretation by an expert reader in detecting significant CAD defined by FFR.

Incremental diagnostic value of epicardial adipose tissue for the detection of functionally relevant coronary artery disease.

BACKGROUND AND AIM: To determine the incremental diagnostic value of epicardial adipose tissue (EAT) volume in addition to the coronary artery calcium (CAC) score for detecting hemodynamic significant coronary artery disease (CAD). METHODS AND RESULTS: 122 patients (mean age 61 ± 10 years, 61% male) without a previous cardiac history underwent a non-contrast CT scan for calcium scoring and EAT volume measurements. Subsequently all patients underwent invasive coronary angiography (ICA) in conjunction with fractional flow reserve (FFR) measurements. A stenosis >90% and/or a FFR ≤0.80 were considered significant. Mean EAT volume and CACscore were 128 ± 51 cm(3) and 418 ± 704, respectively. The correlation between EAT volume and the CACscore was poor (r = 0.11, p = 0.24). Male gender (odds ratio [OR] 2.86, p = 0.01), CACscore ([cut-off value 100] OR 3.31, p = 0.003, and EAT volume ([cut-off value 92 cm(3)] OR 4.28, p = 0.01) were associated with flow-limiting disease. The multivariate model revealed that only male gender (OR 2.50, p = 0.045), CAC score (OR 3.60, p = 0.005), and EAT volume (OR 4.95, p = 0.02) were independent predictors of myocardial ischemia. Using the cut-off values of 100 (CAC score) and 92 cm(3) (EAT volume), sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for detecting functionally relevant CAD as indicated by FFR were 71, 57, 77, 50 and 63% and 91, 29, 85, 44 and 52% for the CACscore and EAT volume, respectively. Adding EAT volume to the CAC score and cardiovascular risk factors did not enhance diagnostic performance for the detection of significant CAD (p = 0.57). CONCLUSION: EAT volume measurements have no diagnostic value beyond calcium scoring and cardiovascular risk factors in the detection of hemodynamic significant CAD.

The impact of obesity on the relationship between epicardial adipose tissue, left ventricular mass and coronary microvascular function.

PURPOSE: Epicardial adipose tissue (EAT) has been linked to coronary artery disease (CAD) and coronary microvascular dysfunction. However, its injurious effect may also impact the underlying myocardium. This study aimed to determine the impact of obesity on the quantitative relationship between left ventricular mass (LVM), EAT and coronary microvascular function. METHODS: A total of 208 (94 men, 45 %) patients evaluated for CAD but free of coronary obstructions underwent quantitative [(15)O]H2O hybrid positron emission tomography (PET)/CT imaging. Coronary microvascular resistance (CMVR) was calculated as the ratio of mean arterial pressure to hyperaemic myocardial blood flow. RESULTS: Obese patients [body mass index (BMI) > 25, n = 133, 64 % of total] had more EAT (125.3 ± 47.6 vs 93.5 ± 42.1 cc, p < 0.001), a higher LVM (130.1 ± 30.4 vs 114.2 ± 29.3 g, p < 0.001) and an increased CMVR (26.6 ± 9.1 vs 22.3 ± 8.6 mmHg×ml(-1)×min(-1)×g(-1), p < 0.01) as compared to nonobese patients. Male gender (ß = 40.7, p < 0.001), BMI (ß = 1.61, p < 0.001), smoking (ß = 6.29, p = 0.03) and EAT volume (ß = 0.10, p < 0.01) were identified as independent predictors of LVM. When grouped according to BMI status, EAT was only independently associated with LVM in nonobese patients. LVM, hypercholesterolaemia and coronary artery calcium score were independent predictors of CMVR. CONCLUSION: EAT volume is associated with LVM independently of BMI and might therefore be a better predictor of cardiovascular risk than BMI. However, EAT volume was not related to coronary microvascular function after adjustments for LVM and traditional risk factors.

ENerGetIcs in hypertrophic cardiomyopathy: traNslation between MRI, PET and cardiac myofilament function (ENGINE study).

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart disease mostly due to mutations in genes encoding sarcomeric proteins. HCM is characterised by asymmetric hypertrophy of the left ventricle (LV) in the absence of another cardiac or systemic disease. At present it lacks specific treatment to prevent or reverse cardiac dysfunction and hypertrophy in mutation carriers and HCM patients. Previous studies have indicated that sarcomere mutations increase energetic costs of cardiac contraction and cause myocardial dysfunction and hypertrophy. By using a translational approach, we aim to determine to what extent disturbances of myocardial energy metabolism underlie disease progression in HCM. METHODS: Hypertrophic obstructive cardiomyopathy (HOCM) patients and aortic valve stenosis (AVS) patients will undergo a positron emission tomography (PET) with acetate and cardiovascular magnetic resonance imaging (CMR) with tissue tagging before and 4 months after myectomy surgery or aortic valve replacement + septal biopsy. Myectomy tissue or septal biopsy will be used to determine efficiency of sarcomere contraction in-vitro, and results will be compared with in-vivo cardiac performance. Healthy subjects and non-hypertrophic HCM mutation carriers will serve as a control group. ENDPOINTS: Our study will reveal whether perturbations in cardiac energetics deteriorate during disease progression in HCM and whether these changes are attributed to cardiac remodelling or the presence of a sarcomere mutation per se. In-vitro studies in hypertrophied cardiac muscle from HOCM and AVS patients will establish whether sarcomere mutations increase ATP consumption of sarcomeres in human myocardium. Our follow-up imaging study in HOCM and AVS patients will reveal whether impaired cardiac energetics are restored by cardiac surgery.