Low-Density Lipoprotein Cholesterol Is Predominantly Associated With Atherosclerotic Cardiovascular Disease Events in Patients With Evidence of Coronary Atherosclerosis: The Western Denmark Heart Registry.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, a sizable proportion of middle-aged individuals with elevated LDL-C level have not developed coronary atherosclerosis as assessed by coronary artery calcification (CAC). Whether presence of CAC modifies the association of LDL-C with ASCVD risk is unknown. We evaluated the association of LDL-C with future ASCVD events in patients with and without CAC. METHODS: The study included 23 132 consecutive symptomatic patients evaluated for coronary artery disease using coronary computed tomography angiography (CTA) from the Western Denmark Heart Registry, a seminational, multicenter-based registry with longitudinal registration of patient and procedure data. We assessed the association of LDL-C level obtained before CTA with ASCVD (myocardial infarction and ischemic stroke) events occurring during follow-up stratified by CAC>0 versus CAC=0 using Cox regression models adjusted for baseline characteristics. Outcomes were identified through linkage among national registries covering all hospitals in Denmark. We replicated our results in the National Heart, Lung, and Blood Institute-funded Multi-Ethnic Study of Atherosclerosis. RESULTS: During a median follow-up of 4.3 years, 552 patients experienced a first ASCVD event. In the overall population, LDL-C (per 38.7 mg/dL increase) was associated with ASCVD events occurring during follow-up (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04-1.24]). When stratified by the presence or absence of baseline CAC, LDL-C was only associated with ASCVD in the 10 792/23 132 patients (47%) with CAC>0 (aHR, 1.18 [95% CI, 1.06-1.31]); no association was observed among the 12 340/23 132 patients (53%) with CAC=0 (aHR, 1.02 [95% CI, 0.87-1.18]). Similarly, a very high LDL-C level (>193 mg/dL) versus LDL-C <116 mg/dL was associated with ASCVD in patients with CAC>0 (aHR, 2.42 [95% CI, 1.59-3.67]) but not in those without CAC (aHR, 0.92 [0.48-1.79]). In patients with CAC=0, diabetes, current smoking, and low high-density lipoprotein cholesterol levels were associated with future ASCVD events. The principal findings were replicated in the Multi-Ethnic Study of Atherosclerosis. CONCLUSIONS: LDL-C appears to be almost exclusively associated with ASCVD events over ≈5 years of follow-up in middle-aged individuals with versus without evidence of coronary atherosclerosis. This information is valuable for individualized risk assessment among middle-aged people with or without coronary atherosclerosis.

Randomized comparison of TAVI valves: The Compare-TAVI trial.

INTRODUCTION: Based on technical advancements and clinical evidence, transcatheter aortic valve implantation (TAVI) has been widely adopted. New generation TAVI valve platforms are continually being developed. Ideally, new valves should be superior or at least non-inferior regarding efficacy and safety, when compared to best-in-practice contemporary TAVI valves. METHODS AND ANALYSIS: The Compare-TAVI trial (ClinicalTrials.gov NCT04443023) was launched in 2020, to perform a 1:1 randomized comparison of new vs contemporary TAVI valves, preferably in all comers. Consecutive cohorts will be launched with sample sizes depending on the choice of interim analyses, expected event rates, and chosen superiority or non-inferiority margins. Enrollment has just been finalized in cohort B, comparing the Sapien 3/Sapien 3 Ultra Transcatheter Heart Valve (THV) series (Edwards Lifesciences, Irvine, California, USA) and the Myval/Myval Octacor THV series (Meril Life Sciences Pvt. Ltd., Vapi, Gujarat, India) balloon expandable valves. This non-inferiority study was aimed to include 1062 patients. The 1-year composite safety and efficacy endpoint comprises death, stroke, moderate-severe aortic regurgitation, and moderate-severe valve deterioration. Patients will be followed until withdrawal of consent, death, or completion of 10-year follow-up, whichever comes first. Secondary endpoints will be monitored at 30 days, 1, 3, 5, and 10 years. SUMMARY: The Compare-TAVI organization will launch consecutive cohorts wherein patients scheduled for TAVI are randomized to one of two valves. The aim is to ensure that the short- and long-term performance and safety of new valves being introduced is benchmarked against what achieved by best-in-practice contemporary valves.

iNav-based, Automated Coronary Magnetic Resonance Angiography for the Detection of Coronary Artery Stenosis (iNav-AUTO CMRA).

BACKGROUND: Coronary computed tomography angiography (CCTA) is recommended as the first line diagnostic imaging modality in low to intermediate risk individuals suspected of stable coronary artery disease (CAD). However, CCTA exposes patients to ionising radiation and potentially nephrotoxic contrast agents. Invasive coronary angiography (ICA) is the gold-standard investigation to guide coronary revascularisation strategy, however, invasive procedures incur an inherent risk to the patient. Coronary magnetic resonance angiography (Coronary MRA) avoids these issues. Nevertheless, clinical implementation is currently limited due to extended scanning durations, inconsistent image quality, and consequent lack of diagnostic accuracy. Several technical Coronary MRA innovations including advanced respiratory motion correction with 100% scan efficiency (no data rejection), fast image acquisition with motion-corrected undersampled image reconstruction and deep-learning (DL)-based automated planning have been implemented and now await clinical validation in multi-centre trials. METHODS: The objective of the iNav-AUTO CMRA prospective multi-centre study is to evaluate the diagnostic accuracy of a newly developed, state-of-the-art, standardised, and automated Coronary MRA framework compared to CCTA in 230 patients undergoing clinical investigation for CAD. The study protocol mandates the administration of oral beta-blockers to decrease heart rate to below 60bpm and the use of sublingual nitroglycerine spray to induce vasodilation. Additionally, the study incorporates the utilisation of standardised postprocessing with sliding-thin-slab multiplanar reformatting, in combination with evaluation of the source images, to optimize the visualisation of coronary artery stenosis. DISCUSSION: If proven effective, Coronary MRA could provide a non-invasive, needle-free, yet also clinically viable, alternative to CCTA. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov (NCT05473117).

Does targeted positioning of the left ventricular pacing lead towards the latest local electrical activation in cardiac resynchronization therapy reduce the incidence of death or hospitalization for heart failure?

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement. METHODS: The DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1,000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a nonapical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and nonplanned HF hospitalization. Patients are followed for a minimum of 2 years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024. CONCLUSIONS: The DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or nonplanned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT. GOV IDENTIFIER: NCT03280862.

Automated detection of cardiac rest period for trigger delay calculation for image-based navigator coronary magnetic resonance angiography.

BACKGROUND: Coronary magnetic resonance angiography (coronary MRA) is increasingly being considered as a clinically viable method to investigate coronary artery disease (CAD). Accurate determination of the trigger delay to place the acquisition window within the quiescent part of the cardiac cycle is critical for coronary MRA in order to reduce cardiac motion. This is currently reliant on operator-led decision making, which can negatively affect consistency of scan acquisition. Recently developed deep learning (DL) derived software may overcome these issues by automation of cardiac rest period detection. METHODS: Thirty individuals (female, n = 10) were investigated using a 0.9 mm isotropic image-navigator (iNAV)-based motion-corrected coronary MRA sequence. Each individual was scanned three times utilising different strategies for determination of the optimal trigger delay: (1) the DL software, (2) an experienced operator decision, and (3) a previously utilised formula for determining the trigger delay. Methodologies were compared using custom-made analysis software to assess visible coronary vessel length and coronary vessel sharpness for the entire vessel length and the first 4 cm of each vessel. RESULTS: There was no difference in image quality between any of the methodologies for determination of the optimal trigger delay, as assessed by visible coronary vessel length, coronary vessel sharpness for each entire vessel and vessel sharpness for the first 4 cm of the left mainstem, left anterior descending or right coronary arteries. However, vessel length of the left circumflex was slightly greater using the formula method. The time taken to calculate the trigger delay was significantly lower for the DL-method as compared to the operator-led approach (106 ± 38.0 s vs 168 ± 39.2 s, p < 0.01, 95% CI of difference 25.5-98.1 s). CONCLUSIONS: Deep learning-derived automated software can effectively and efficiently determine the optimal trigger delay for acquisition of coronary MRA and thus may simplify workflow and improve reproducibility.

Long-term outcomes in a randomized controlled trial of multimodality imaging-guided left ventricular lead placement in cardiac resynchronization therapy.

AIMS: This study aims to investigate the long-term occurrence of the composite endpoint of heart failure (HF) hospitalization or all-cause death (primary endpoint) in patients randomized to cardiac resynchronization therapy (CRT) using individualized multimodality imaging-guided left ventricular (LV) lead placement compared with a routine fluoroscopic approach. Furthermore, this study aims to evaluate whether inter-lead electrical delay (IED) is associated with improved response rate of this endpoint. METHODS AND RESULTS: We reviewed follow-up data until November 2020 for all 182 patients included in the ImagingCRT trial for the occurrence of HF hospitalization and all-cause death. During median (inter-quartile range) time to primary endpoint/censuring of 6.7 (3.3-7.9) years, the rate of the primary endpoint was 60% (n = 53) in the imaging group compared with 52% (n = 48) in the control group [hazard ratio (HR) 1.22, 95% confidence interval (CI) 0.83-1.81, P = 0.31]. Neither the risk of HF hospitalization (HR 1.11, 95% CI 0.62-1.99, P = 0.72) nor of all-cause death differed between treatment groups (HR 1.23, 95% CI 0.82-1.85, P = 0.32). The risk of the primary endpoint was significantly reduced among those with IED ≥100 ms when compared with those with IED <100 ms (HR 0.62, 95% CI 0.39-0.98, P = 0.04). CONCLUSIONS: In this study, an individualized multimodality imaging-guided strategy targeting LV lead placement towards the latest mechanically activated non-scarred myocardial segment during CRT implantation did not reduce HF hospitalization or all-cause death when compared with routine LV lead placement during long-term follow-up. Targeting the latest electrical activation should be studied as an alternative individualized strategy for optimizing LV lead placement in CRT recipients.

Computed Tomography-Derived Fractional Flow Reserve in Patients With Chronic Coronary Syndrome: A Real-World Cohort Study.

OBJECTIVE: This study aimed to investigate the outcome of computed tomography (CT) angiography with optional CT-derived fractional flow reserve (FFRCT) of intermediate-range coronary artery disease in non-emergent patients referred on a suspicion of chronic coronary syndrome. METHODS: Patients were classified as high risk and low-intermediate risk according to the presence of typical angina or either atypical or nonangina chest pain. Outcome was assessed as the cumulative incidence proportion of a composite end point of unstable angina pectoris, unplanned revascularization, nonfatal myocardial infarction, and all-cause mortality. RESULTS: The study included 743 patients. Mean follow-up was 2.2 (range, 0.1-2.5) years. Low-intermediate-risk and high-risk patients who had invasive coronary angiography deferred had comparable proportions of adverse events (1.4% vs 2.6% [P = 0.27]). Adverse events in high-risk patients with FFRCT >0.80 was 3.3% versus 1.4% in patients where no additional testing was performed (P = 0.79). CONCLUSIONS: Computed tomography-derived fractional flow reserve >0.8 conveys an excellent prognosis. Computed tomography angiography with optional FFRCT allows for the safe cancellation of invasive coronary angiography in high-risk patients.

Left Atrial Function Determined by Cardiac Computed Tomography Predicts Device-Detected Atrial High-Rate Episodes in Patients Treated With Cardiac Resynchronization Therapy.

OBJECTIVE: The objective of this study was to examine whether left atrial (LA) volumes and function were associated with atrial high-rate episodes (AHREs) in patients with cardiac resynchronization therapy (CRT). METHODS: Ninety-two consecutive patients without prior atrial fibrillation underwent clinical evaluation, echocardiograms, and cardiac computed tomography (CT) before CRT implantation and after 6 months. Left atrial volumes and LA emptying fraction (LAEF) were derived by CT images reconstructed at 5% phase increments of the cardiac cycle. Cox regression was used to assess associations between AHRE and LA anatomical and functional variables. RESULTS: Twenty-two patients (24%) developed AHRE during 1.9 years (SD, 1 year) At baseline, higher LAEF was associated with a lower risk of AHRE (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.91-0.98; P = 0.003), and large LA minimal (LAmin) volume was related to higher risk of AHRE (HR, 1.03; 95% CI, 1.00-1.06; P = 0.04). When combining LAEF and LAmin volume, only LAEF remained associated with occurrence of AHRE. Higher passive LAEF was associated with lower risk of AHRE (HR, 0.95; 95% CI, 0.91-0.98; P = 0.003). CONCLUSIONS: In patients with CRT, low preimplant LAEF measured by cardiac CT was independently associated with device-detected AHRE.

Electrically vs. imaging-guided left ventricular lead placement in cardiac resynchronization therapy: a randomized controlled trial.

AIMS: To test in a double-blinded, randomized trial whether the combination of electrically guided left ventricular (LV) lead placement and post-implant interventricular pacing delay (VVd) optimization results in superior increase in LV ejection fraction (LVEF) in cardiac resynchronization therapy (CRT) recipients. METHODS AND RESULTS: Stratified according to presence of ischaemic heart disease, 122 patients were randomized 1:1 to LV lead placement targeted towards the latest electrically activated segment identified by systematic mapping of the coronary sinus tributaries during CRT implantation combined with post-implant VVd optimization (intervention group) or imaging-guided LV lead implantation by cardiac computed tomography venography, 82Rubidium myocardial perfusion imaging and speckle tracking echocardiography targeting the LV lead towards the latest mechanically activated non-scarred myocardial segment (control group). Follow-up was 6 months. Primary endpoint was absolute increase in LVEF. Additional outcome measures were changes in New York Heart Association class, 6-minute walk test, and quality of life, LV reverse remodelling, and device related complications. Analysis was intention-to-treat. A larger increase in LVEF was observed in the intervention group (11 ± 10 vs. 7 ± 11%; 95% confidence interval 0.4-7.9%, P = 0.03); when adjusting for pre-specified baseline covariates this difference did not maintain statistical significance (P = 0.09). Clinical response, LV reverse remodelling, and complication rates did not differ between treatment groups. CONCLUSION: Electrically guided CRT implantation appeared non-inferior to an imaging-guided strategy considering the outcomes of change in LVEF, LV reverse remodelling and clinical response. Larger long-term studies are warranted to investigate the effect of an electrically guided CRT strategy.

Integrated prediction of lesion-specific ischaemia from quantitative coronary CT angiography using machine learning: a multicentre study.

OBJECTIVES: We aimed to investigate if lesion-specific ischaemia by invasive fractional flow reserve (FFR) can be predicted by an integrated machine learning (ML) ischaemia risk score from quantitative plaque measures from coronary computed tomography angiography (CTA). METHODS: In a multicentre trial of 254 patients, CTA and invasive coronary angiography were performed, with FFR in 484 vessels. CTA data sets were analysed by semi-automated software to quantify stenosis and non-calcified (NCP), low-density NCP (LD-NCP, < 30 HU), calcified and total plaque volumes, contrast density difference (CDD, maximum difference in luminal attenuation per unit area) and plaque length. ML integration included automated feature selection and model building from quantitative CTA with a boosted ensemble algorithm, and tenfold stratified cross-validation. RESULTS: Eighty patients had ischaemia by FFR (FFR ≤ 0.80) in 100 vessels. Information gain for predicting ischaemia was highest for CDD (0.172), followed by LD-NCP (0.125), NCP (0.097), and total plaque volumes (0.092). ML exhibited higher area-under-the-curve (0.84) than individual CTA measures, including stenosis (0.76), LD-NCP volume (0.77), total plaque volume (0.74) and pre-test likelihood of coronary artery disease (CAD) (0.63); p < 0.006. CONCLUSIONS: Integrated ML ischaemia risk score improved the prediction of lesion-specific ischaemia by invasive FFR, over stenosis, plaque measures and pre-test likelihood of CAD. KEY POINTS: • Integrated ischaemia risk score improved prediction of ischaemia over quantitative plaque measures • Integrated ischaemia risk score showed higher prediction of ischaemia than standard approach • Contrast density difference had the highest information gain to identify lesion-specific ischaemia.

Longer inter-lead electrical delay is associated with response to cardiac resynchronization therapy in patients with presumed optimal left ventricular lead position.

Aims: In a randomized trial of cardiac resynchronization therapy (CRT), a presumed optimal left ventricular (LV) lead position close to the latest mechanically activated non-scarred myocardium was achieved in 98% of patients by standard implantation. We evaluated whether inter-lead electrical delay (IED) was associated with response to CRT in these patients. Methods and results: We prospectively included 160 consecutive patients undergoing CRT. Pre-implant speckle-tracking echocardiography radial strain and 99mTc myocardial perfusion imaging determined the latest mechanically activated non-scarred myocardial segment. We measured procedural IED as the time interval between sensed signals in right ventricular and LV lead electrograms. All patients had LV pacing site concordant or adjacent to the latest mechanically activated non-scarred segment verified by cardiac computed tomography. Response to CRT was defined as ≥15% reduction in LV end-systolic volume at 6 months follow-up. Selecting a practical IED cut-off value of 100 ms, more patients with long IED than patients with short IED responded to CRT (87 vs. 68%; P = 0.004). In multivariate logistic regression analysis, IED ≥100 ms remained associated with CRT response after adjusting for baseline characteristics, including QRS duration and scar burden [odds ratio 3.19 (1.24-8.17); P = 0.01]. Categorizing IED by tertiles, CRT response improved with longer IED (P = 0.03). Comparable response rates were observed in patients with a concordant and adjacent LV lead position. Conclusion: A longer IED was associated with more pronounced LV reverse remodelling response in CRT recipients with a presumed optimal LV lead position concordant or adjacent to the latest mechanically activated non-scarred segment.

High burden of coronary atherosclerosis in patients with cirrhosis.

BACKGROUND: Population studies report increased cardiovascular mortality in patients with cirrhosis. Coronary artery disease may be a trait of end-stage liver disease, but whether it is frequent or extensive in cirrhosis in general is unknown. Thus, we aimed to assess the prevalence and extent of coronary artery disease in unselected cirrhosis patients. MATERIALS AND METHODS: Using coronary computed tomography angiography, we investigated 52 patients from all Child-Pugh classes and aetiologies of cirrhosis without known cardiac disease for presence and severity of coronary artery disease in a cross-sectional design. Persons referred with new-onset chest pain served as controls. RESULTS: The prevalence of coronary artery disease was not significantly different between cirrhosis patients and controls (77% vs. 65%, P=0·19). However, cirrhosis patients had a markedly higher coronary artery calcification (Agatston) score than controls (120 [interquartile range, 0-345] vs. 5 [interquartile range, 0-86] HU, P=0·001). Likewise, patients with cirrhosis had a higher prevalence of extensive (≥5 coronary segments involved; 45% vs. 18%, P=0·01) and multivessel coronary disease (≥2 vessels involved; 75% vs. 53%, P=0·02). Furthermore, the total plaque volume whether noncalcified or calcified was higher in cirrhosis (117 [interquartile range, 0-310] vs. 36 [interquartile range, 0-148] mm3 , P=0·02). CONCLUSION: Coronary artery disease is equally prevalent in patients with cirrhosis and subjects with new-onset chest pain, but cirrhosis patients have more extensive and severe disease including several coronary high-risk features associated with myocardial ischaemia and a poor clinical outcome. The potential of preventive measures for coronary artery disease in cirrhosis needs attention.

Coronary CT Angiography Derived Fractional Flow Reserve: The Game Changer in Noninvasive Testing.

PURPOSE OF REVIEW: To summarize the scientific basis of CT derived fractional flow reserve (FFRCT) and present an updated review on the evidence from clinical trials and real-world observational data RECENT FINDINGS: In prospective multicenter studies of patients with stable coronary artery disease (CAD), FFRCT showed high diagnostic performance. More recently, FFRCT has advanced to the realm of clinical utility and real-world clinical practice with emerging data showing that FFRCT when compared to standard care is efficient in safely reducing downstream utilization of invasive coronary angiography (ICA), and costs, as well as improving the diagnostic yield of ICA. Moreover, FFRCT may broaden applicability of frontline coronary CTA testing to patients with high pre-test risk of CAD. Introducing FFRCT into clinical practice has the potential to significantly improve the management of patients with stable CAD. The optimal FFRCT testing interpretation strategy, as well as the relative cost-efficiency of FFRCT against standard noninvasive functional testing, need further investigation.

Coronary plaque quantification and fractional flow reserve by coronary computed tomography angiography identify ischaemia-causing lesions.

AIMS: Coronary plaque characteristics are associated with ischaemia. Differences in plaque volumes and composition may explain the discordance between coronary stenosis severity and ischaemia. We evaluated the association between coronary stenosis severity, plaque characteristics, coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT), and lesion-specific ischaemia identified by FFR in a substudy of the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). METHODS AND RESULTS: Coronary CTA stenosis, plaque volumes, FFRCT, and FFR were assessed in 484 vessels from 254 patients. Stenosis >50% was considered obstructive. Plaque volumes (non-calcified plaque [NCP], low-density NCP [LD-NCP], and calcified plaque [CP]) were quantified using semi-automated software. Optimal thresholds of quantitative plaque variables were defined by area under the receiver-operating characteristics curve (AUC) analysis. Ischaemia was defined by FFR or FFRCT ≤0.80. Plaque volumes were inversely related to FFR irrespective of stenosis severity. Relative risk (95% confidence interval) for prediction of ischaemia for stenosis >50%, NCP ≥185 mm(3), LD-NCP ≥30 mm(3), CP ≥9 mm(3), and FFRCT ≤0.80 were 5.0 (3.0-8.3), 3.7 (2.4-5.6), 4.6 (2.9-7.4), 1.4 (1.0-2.0), and 13.6 (8.4-21.9), respectively. Low-density NCP predicted ischaemia independent of other plaque characteristics. Low-density NCP and FFRCT yielded diagnostic improvement over stenosis assessment with AUCs increasing from 0.71 by stenosis >50% to 0.79 and 0.90 when adding LD-NCP ≥30 mm(3) and LD-NCP ≥30 mm(3) + FFRCT ≤0.80, respectively. CONCLUSION: Stenosis severity, plaque characteristics, and FFRCT predict lesion-specific ischaemia. Plaque assessment and FFRCT provide improved discrimination of ischaemia compared with stenosis assessment alone.

White Matter Lesions, Carotid and Coronary Atherosclerosis in Late-Onset Depression and Healthy Controls.

BACKGROUND: Cerebral white matter lesions (WMLs) are more common in individuals with late-onset or late-life depression. It has been proposed that carotid atherosclerosis may predispose to WMLs by inducing cerebral hypoperfusion. This hemodynamic effect of carotid atherosclerosis could be important for the formation of WMLs in depression. METHODS: The case-control study included 29 patients with late-onset major depressive disorder and 27 controls matched for sex, age, and tobacco use. WML volume, carotid intima-media thickness, and coronary plaque volume were assessed using magnetic resonance imaging, ultrasound scan, and coronary computed tomography (CT) angiography, respectively. RESULTS: The mean age for the total sample was 59.7 ± 4.7 years. There was no difference in carotid intima-media thickness between patients and controls (p = 0.164), whereas a higher WML volume in the patients was found (p = 0.051). In both patients and controls, WML volume was associated with carotid but not with coronary atherosclerosis. In adjusted multiple linear regression, a 0.1mm increase in averaged carotid intima-media thickness was associated with a 52% (95% CI: 8.4-112, p = 0.032) increase in WML volume. The association between carotid intima-media thickness and WML volume was, however, similar in patients and controls. CONCLUSIONS: In older persons aged between 50 and 70 years, WMLs do not seem to be a part of generalized atherosclerotic disease, but seem to be dependent on atherosclerosis in the carotid arteries. Carotid atherosclerosis, however, could not explain the higher WML load observed in the depressed patients, and thus, studies are needed to establish the mechanisms linking depression and WMLs.

Rationale and design of the Prospective LongitudinAl Trial of FFRCT: Outcome and Resource IMpacts study.

BACKGROUND: Fractional flow reserve (FFR) measured by coronary computed tomography angiography (FFRCT) has been validated against invasive FFR. However, there are no data on how the use of FFRCT affects patient care and outcomes. The aim of this study is to compare standard practice guided by usual care testing to FFRCT-guided management in symptomatic subjects with suspected coronary artery disease (CAD). METHODS: In this prospective nonrandomized trial, symptomatic patients with suspected CAD will be enrolled in 2 consecutive cohorts: a usual care-guided pathway (cohort 1) and an FFRCT-guided pathway (cohort 2). Each cohort is divided into 2 groups according to whether noninvasive or invasive diagnostic testing was planned before enrollment. In all subjects, the patient's clinical team will review all diagnostic test results and determine a treatment strategy. A total sample size of 580 subjects will be enrolled and followed up for 12 months. RESULTS: The primary end point is the comparison of the percentage of patients with planned invasive testing who have a catheterization (invasive coronary angiography) within 90 days from initial assessment, which does not show a significant stenosis (defined as coronary artery stenosis >50% or invasive FFR ≤0.80). Secondary end points include the rate of invasive coronary angiography without obstructive CAD in those with planned noninvasive testing and, in all groups, noninferiority of resource use, quality of life, medical radiation exposure, and major adverse cardiac events up to 365 days of follow-up. CONCLUSIONS: The study compares clinical and economic outcomes based on diagnostic evaluation using FFRCT with that based on standard diagnostic strategies.

The paced electrocardiogram cannot be used to identify left and right ventricular pacing sites in cardiac resynchronization therapy: validation by cardiac computed tomography.

AIMS: Paced electrocardiogram characteristics to confirm left ventricular (LV) and right ventricular (RV) pacing sites in cardiac resynchronization therapy (CRT) have not been validated with accurate knowledge of pacing lead positions. We aimed to evaluate the ability of the paced QRS morphology to differentiate between various LV and RV lead positions using cardiac computed tomography (CT) as the reference for LV and RV pacing site. METHODS AND RESULTS: Ninety-seven CRT patients were included. The QRS morphology was evaluated during forced LV-only and RV-only pacing. Pacing lead positions were assessed in a standard LV 16-segment model and a simplistic RV 6-segment model using cardiac CT. Ten patients with LV lead displacement or a LV pacing site outside the non-apical free wall were excluded from the analysis of the LV paced QRS complex. Pacing within the LV free wall was associated with a superior and a right-axis deviation (P = 0.02 and 0.04, respectively). Pacing from basal LV segments mainly produced a late (V5 or later) precordial QRS transition as compared with mid-LV pacing (P = 0.001). No significant associations were found between RV pacing site and QRS axis or precordial transition. Different QRS morphologies were observed during single-chamber pacing from identical LV or RV myocardial segments. CONCLUSION: Weak associations exist between LV and RV pacing sites and the paced QRS axis. None of the paced QRS characteristics can be used to reliably confirm specific LV and RV pacing sites in CRT patients.

Left and right ventricular lead positions are imprecisely determined by fluoroscopy in cardiac resynchronization therapy: a comparison with cardiac computed tomography.

AIMS: Fluoroscopy is the routine method for localizing left ventricular (LV) and right ventricular (RV) lead positions in cardiac resynchronization therapy (CRT). However, the ability of fluoroscopy to determine lead positions in a standard ventricular segmentation is unknown. We aimed to evaluate the accuracy and reproducibility of fluoroscopy to determine LV and RV lead positions in CRT when compared with cardiac computed tomography (CT). METHODS AND RESULTS: Fifty-nine patients undergoing CRT were included. Bi-plane fluoroscopy and cardiac CT were evaluated in all patients. Pacing lead positions were assessed in a standard LV 16-segment model and in a simplistic RV 8-segment model. Four patients with LV lead displacement were excluded from the agreement analysis of LV lead position. Agreement of LV lead position between fluoroscopy and cardiac CT was observed in 19 (35%) patients with fluoroscopy demonstrating a 1-segment and ≥2-segment error in 30 (55%) and 6 (11%) patients, respectively. Agreement of RV lead position was found in 13 (22%) patients with fluoroscopy showing a 1-segment and ≥ 2-segment error in 28 (47%) and 18 (31%) patients, respectively. The interobserver agreement on LV and RV lead positions was poor for fluoroscopy (kappa 0.20 and 0.23, respectively) and excellent for cardiac CT (kappa 0.87 and 0.85, respectively). CONCLUSION: Fluoroscopy is inaccurate and modestly reproducible when assessing LV and RV lead positions in a standard ventricular segmentation when compared with cardiac CT. Cardiac CT should be applied to determine the exact pacing site in future research evaluating the optimal pacing lead position in CRT.

Coronary plaque volume and composition assessed by computed tomography angiography in patients with late-onset major depression.

BACKGROUND: Depression is a stronger predictor for the onset of or death from clinical coronary artery disease than traditional cardiovascular risk factors. The association between depression and coronary artery disease has previously been investigated in non-contrast enhanced computed tomography studies with conflicting results. The aim of this study was to further elucidate the depression-coronary artery disease relation by use of coronary computed tomography angiography. METHODS: The calcified and noncalcified coronary plaque volumes were determined by semiautomatic volumetric quantification in 28 patients with late-onset major depression and 27 controls. The calcified plaque proportion, i.e., the calcified plaque volume divided by the total plaque volume, was used to assess the plaque composition. RESULTS: There was no statistically significant difference in the total (p = 0.48), calcified (p = 0.15), and noncalcified (p = 0.62) plaque volume between patients and controls, and the total plaque volume did not predict depression, odds ratio = 1.001 [95% confidence interval: 0.999-1.003; p = 0.23]. However, the calcified plaque proportion was twice as high in patients compared with controls (14% vs. 7%, p = 0.044). Correspondingly, having depression was associated with an increased calcified plaque proportion of 11.3 [95% confidence interval: 2.63-20.1; p = 0.012] percentage points after adjustment for demographics and cardiovascular risk factors. CONCLUSION: The proportion of the total coronary plaque volume that was calcified was significantly higher in patients with late-onset major depression than in controls, indicating a difference in plaque composition.

Long-term cardiac computed tomography follow-up after left atrial appendage occlusion.

BACKGROUND: Left atrial appendage occlusion (LAAO) is performed increasingly, but long-term follow-up imaging data are lacking. AIMS: The aim of this study was to evaluate the safety and durability of the Amplatzer Amulet device >4 years after LAAO. METHODS: This was a prospective observational cohort study including 52 patients implanted with the Amplatzer Amulet device at Aarhus University Hospital, Denmark. A >4-year follow-up cardiac computed tomography (CT) scan after LAAO was performed and compared with the results from the 2-month and 12-month scans. The primary outcome was left atrial appendage (LAA) sealing based on distal LAA contrast patency and peridevice leakage (PDL), stratified into complete occlusion (grade 0 [G0]) and grade 1-3 leakage (G1-3), respectively. Secondary outcomes were low- and high-grade hypoattenuated thickening (HAT), device-related thrombosis (DRT) and device durability. RESULTS: The median (interquartile range [IQR]) follow-up time from LAAO to the latest CT scan was 5.8 years (4.5; 6.3). At 2-month (n=52), 12-month (n=27) and >4-year CT follow-ups (n=52), rates of both complete occlusion (33%, 37%, 35%) and G2 leaks (52%, 52%, 48%) remained stable. Rates of G1 leaks varied (14%, 4%, 6%) and G3 leaks rose (2%, 7%, 12%) from earliest to latest follow-up. The median left atrial (LA) volume increased from 127 mL (96; 176) to 144 mL (108; 182) and 147 mL (107; 193). No DRT was found. The structural device integrity was preserved. CONCLUSIONS: This study indicates a stable LAA sealing status throughout the follow-up period, emphasising the importance of the procedural result in avoiding PDL. Few patients displayed PDL progression, which might partly be related to LA remodelling with increasing volume. The long-term device durability appears excellent. Larger studies are warranted to confirm these findings.