Early-onset versus late-onset preeclampsia and risk of coronary atherosclerosis later in life: a clinical follow-up study.

BACKGROUND: Younger women with previous preeclampsia have an increased risk of coronary atherosclerosis. It is unknown if this risk is associated with the time of onset of preeclampsia. OBJECTIVES: The aim of the study was to investigate if women with early-onset preeclampsia have a higher risk of coronary atherosclerosis compared to women with late-onset preeclampsia, independent of other perinatal risk factors. STUDY DESIGN: A total of 911 women with previous preeclampsia aged 35-55 years participated in a clinical follow-up study, including clinical examination, comprehensive questionnaires, and cardiac computed tomography scan 13 years (range 0-28) after index pregnancy. Early-onset preeclampsia versus late-onset preeclampsia was defined as gestational age at delivery < versus ≥ 34+0 gestational weeks, respectively. The primary outcome of the study was the presence of coronary atherosclerosis on the cardiac computed tomography. A logistic regression analysis was performed to investigate the association between time of onset of preeclampsia, perinatal risk factors and the primary outcome. RESULTS: Women with early-onset preeclampsia (N=139) were older (46.2±5.7 vs. 44.4±5.5 years, P<0.001), more likely to have hypertension (51.1% vs. 35.1%, P=<0.001), and had a higher body mass index (27.9±6.3 vs. 26.9±5.5 kg/m2, P=0.051) compared to women with late-onset preeclampsia (N=772) at follow-up. The prevalence of the primary outcome coronary atherosclerosis on the cardiac computed tomography was 28.8% vs. 22.2% (P=0.088) with an adjusted OR=1.74, 95% CI (1.01-3.01), P=0.045 after adjustment for maternal age at index pregnancy, pre-pregnancy body mass index, parity, diabetes in pregnancy, smoking in pregnancy, offspring birth weight and sex, and follow-up length. CONCLUSIONS: Women with early-onset preeclampsia had a slightly higher risk of coronary atherosclerosis compared to women with late-onset preeclampsia. However, based on the current evidence it does not seem indicated to limit screening, diagnostic and preventive measures for cardiovascular disease only to women with early-onset preeclampsia.

Coronary Artery Calcium Score Predicts Major Adverse Cardiovascular Events in Stable Chest Pain.

Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA. Participants were randomly assigned to undergo either ICA or coronary CT. CAC scores from noncontrast CT scans were categorized into low, intermediate, and high groups based on scores of 0, 1-399, and 400 or higher, respectively. The end point of the study was the occurrence of MACE (myocardial infarction, stroke, and cardiovascular death) over a median 3.5-year follow-up, analyzed using Cox proportional hazard regression tests. Results The study involved 1749 participants (mean age, 60 years ± 10 [SD]; 992 female). The prevalence of obstructive coronary artery disease (CAD) at CT angiography rose from 4.1% (95% CI: 2.8, 5.8) in the CAC score 0 group to 76.1% (95% CI: 70.3, 81.2) in the CAC score 400 or higher group. Revascularization rates increased from 1.7% to 46.2% across the same groups (P < .001). The CAC score 0 group had a lower MACE risk (0.5%; HR, 0.08 [95% CI: 0.02, 0.30]; P < .001), as did the 1-399 CAC score group (1.9%; HR, 0.27 [95% CI: 0.13, 0.59]; P = .001), compared with the 400 or higher CAC score group (6.8%). No significant difference in MACE between sexes was observed (P = .68). Conclusion In participants with stable chest pain initially referred for ICA, a CAC score of 0 showed very low risk of MACE, and higher CAC scores showed increasing risk of obstructive CAD, revascularization, and MACE at follow-up. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hanneman and Gulsin in this issue.

The importance of nonobstructive plaque characteristics in symptomatic and asymptomatic coronary artery disease.

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

Normal values of myocardial blood flow measured with dynamic myocardial CT perfusion.

AIMS: Dynamic myocardial CT perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD.We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. METHODS AND RESULTS: A total of 82 healthy individuals (46 women) aged 45-78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 mL/min/g and 3.58 ± 1.14 mL/min/g respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress) and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant inter-segmental differences were found (P < 0.01), which was not related to age, sex or coronary dominance. CONCLUSION: Myocardial blood flow assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex or coronary dominance. Normal values of myocardial blood flow may be helpful in the clinical evaluation of suspected myocardial ischemia using DM-CTP.

Effect of Body Mass Index on Effectiveness of CT versus Invasive Coronary Angiography in Stable Chest Pain: The DISCHARGE Trial.

Background Recent trials support the role of cardiac CT in the evaluation of symptomatic patients suspected of having coronary artery disease (CAD); however, body mass index (BMI) has been reported to negatively impact CT image quality. Purpose To compare initial use of CT versus invasive coronary angiography (ICA) on clinical outcomes in patients with stable chest pain stratified by BMI category. Materials and Methods This prospective study represents a prespecified BMI subgroup analysis of the multicenter Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial conducted between October 2015 and April 2019. Adult patients with stable chest pain and a CAD pretest probability of 10%-60% were randomly assigned to undergo initial CT or ICA. The primary end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, or stroke. The secondary end point was an expanded MACE composite, including transient ischemic attack, and major procedure-related complications. Competing risk analyses were performed using the Fine and Gray subdistribution Cox proportional hazard model to assess the impact of the relationship between BMI and initial management with CT or ICA on the study outcomes, whereas noncardiovascular death and unknown causes of death were considered competing risk events. Results Among the 3457 participants included, 831 (24.0%), 1358 (39.3%), and 1268 (36.7%) had a BMI of less than 25, between 25 and 30, and greater than 30 kg/m2, respectively. No interaction was found between CT or ICA and BMI for MACE (P = .29), the expanded MACE composite (P = .38), or major procedure-related complications (P = .49). Across all BMI subgroups, expanded MACE composite events (CT, 10 of 409 [2.4%] to 23 of 697 [3.3%]; ICA, 26 of 661 [3.9%] to 21 of 422 [5.1%]) and major procedure-related complications during initial management (CT, one of 638 [0.2%] to five of 697 [0.7%]; ICA, nine of 630 [1.4%] to 12 of 422 [2.9%]) were less frequent in the CT versus ICA group. Participants with a BMI exceeding 30 kg/m² exhibited a higher nondiagnostic CT rate (7.1%, P = .044) compared to participants with lower BMI. Conclusion There was no evidence of a difference in outcomes between CT and ICA across the three BMI subgroups. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article.

Age and Computed Tomography and Invasive Coronary Angiography in Stable Chest Pain: A Prespecified Secondary Analysis of the DISCHARGE Randomized Clinical Trial.

Importance: The effectiveness and safety of computed tomography (CT) and invasive coronary angiography (ICA) in different age groups is unknown. Objective: To determine the association of age with outcomes of CT and ICA in patients with stable chest pain. Design, Setting, and Participants: The assessor-blinded Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial was conducted between October 2015 and April 2019 in 26 European centers. Patients referred for ICA with stable chest pain and an intermediate probability of obstructive coronary artery disease were analyzed in an intention-to-treat analysis. Data were analyzed from July 2022 to January 2023. Interventions: Patients were randomly assigned to a CT-first strategy or a direct-to-ICA strategy. Main Outcomes and Measures: MACE (ie, cardiovascular death, nonfatal myocardial infarction, or stroke) and major procedure-related complications. The primary prespecified outcome of this secondary analysis of age was major adverse cardiovascular events (MACE) at a median follow-up of 3.5 years. Results: Among 3561 patients (mean [SD] age, 60.1 [10.1] years; 2002 female [56.2%]), 2360 (66.3%) were younger than 65 years, 982 (27.6%) were between ages 65 to 75 years, and 219 (6.1%) were older than 75 years. The primary outcome was MACE at a median (IQR) follow-up of 3.5 (2.9-4.2) years for 3523 patients (99%). Modeling age as a continuous variable, age, and randomization group were not associated with MACE (hazard ratio, 1.02; 95% CI, 0.98-1.07; P for interaction = .31). Age and randomization group were associated with major procedure-related complications (odds ratio, 1.15; 95% CI, 1.05-1.27; P for interaction = .005), which were lower in younger patients. Conclusions and Relevance: Age did not modify the effect of randomization group on the primary outcome of MACE but did modify the effect on major procedure-related complications. Results suggest that CT was associated with a lower risk of major procedure-related complications in younger patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02400229.

Clonal hematopoiesis of indeterminate potential in persons with HIV.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with older age, inflammation and with risk of coronary artery disease (CAD). We aimed to characterize the burden of CHIP, and to explore the association between CHIP, inflammatory markers, and CAD in older persons with HIV (PWH). METHODS: From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included 190 individuals older than 55 years of age. We defined CHIP as variant allele fraction at least 2%. CAD was categorized according to the most severe coronary artery lesion on coronary computed tomography (CT) angiography as no coronary atherosclerosis; any atherosclerosis defined as at least 1% stenosis and obstructive CAD defined as at least 50% stenosis. RESULTS: In the entire population (median age 66 years, 87% men), we identified a total of 62 mutations distributed among 49 (26%) participants. The three most mutated genes were DNMT3A , TET2 , and ASXL1 , accounting for 49, 25, and 16% of mutations, respectively. Age and sex were the only variables associated with CHIP. IL-1ß, IL-1Ra, IL-2, IL-6, IL-10, soluble CD14, soluble CD163 and TNF-α were not associated with CHIP, and CHIP was not associated with any atherosclerosis or with obstructive CAD in adjusted analyses. CONCLUSION: In older, well treated, Scandinavian PWH, more than one in four had at least one CHIP mutation. We did not find evidence of an association between CHIP and inflammatory markers or between CHIP and CAD. CHIP is an unlikely underlying mechanism to explain the association between inflammation and CAD in treated HIV disease.

Plasma activin A rises with declining kidney function and is independently associated with mortality in patients with chronic kidney disease.

Background: Plasma (p-)activin A is elevated in chronic kidney disease-mineral and bone disorder (CKD-MBD). Activin A inhibition ameliorates CKD-MBD complications (vascular calcification and bone disease) in rodent CKD models. We examined whether p-activin A was associated with major adverse cardiovascular events (MACE), all-cause mortality and CKD-MBD complications in CKD patients. Methods: The study included 916 participants (741 patients and 175 controls) from the prospective Copenhagen CKD cohort. Comparisons of p-activin A with estimated glomerular filtration rate (eGFR), coronary and thoracic aorta Agatston scores, and bone mineral density (BMD) were evaluated by univariable linear regression using Spearman's rank correlation, analysis of covariance and ordinal logistic regression with adjustments. Association of p-activin A with rates of MACE and all-cause mortality was evaluated by the Aalen-Johansen or Kaplan-Meier estimator, with subsequent multiple Cox regression analyses. Results: P-activin A was increased by CKD stage 3 (124-225 pg/mL, P < .001) and correlated inversely with eGFR (r = -0.53, P < 0.01). P-activin A was associated with all-cause mortality [97 events, hazard ratio 1.55 (95% confidence interval 1.04; 2.32), P < 0.05] after adjusting for age, sex, diabetes mellitus (DM) and eGFR. Median follow-up was 4.36 (interquartile range 3.64-4.75) years. The association with MACE was not significant after eGFR adjustment. Agatston scores and BMD were not associated with p-activin A. Conclusion: P-activin A increased with declining kidney function and was associated with all-cause mortality independently of age, sex, DM and eGFR. No association with MACE, vascular calcification or BMD was demonstrated.

Impact of smoking in patients with suspected coronary artery disease in the randomised DISCHARGE trial.

OBJECTIVES: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status. MATERIALS AND METHODS: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications). RESULTS: Of 3445 randomised patients with smoking data (mean age 59.1 years + / - 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy. CONCLUSION: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers. CLINICAL RELEVANCE STATEMENT: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400229. KEY POINTS: • No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. • A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. • A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers.

Computed Tomography Versus Invasive Coronary Angiography in Patients With Diabetes and Suspected Coronary Artery Disease.

OBJECTIVE: To compare cardiac computed tomography (CT) with invasive coronary angiography (ICA) as the initial strategy in patients with diabetes and stable chest pain. RESEARCH DESIGN AND METHODS: This prespecified analysis of the multicenter DISCHARGE trial in 16 European countries was performed in patients with stable chest pain and intermediate pretest probability of coronary artery disease. The primary end point was a major adverse cardiac event (MACE) (cardiovascular death, nonfatal myocardial infarction, or stroke), and the secondary end point was expanded MACE (including transient ischemic attacks and major procedure-related complications). RESULTS: Follow-up at a median of 3.5 years was available in 3,541 patients of whom 557 (CT group n = 263 vs. ICA group n = 294) had diabetes and 2,984 (CT group n = 1,536 vs. ICA group n = 1,448) did not. No statistically significant diabetes interaction was found for MACE (P = 0.45), expanded MACE (P = 0.35), or major procedure-related complications (P = 0.49). In both patients with and without diabetes, the rate of MACE did not differ between CT and ICA groups. In patients with diabetes, the expanded MACE end point occurred less frequently in the CT group than in the ICA group (3.8% [10 of 263] vs. 8.2% [24 of 294], hazard ratio [HR] 0.45 [95% CI 0.22-0.95]), as did the major procedure-related complication rate (0.4% [1 of 263] vs. 2.7% [8 of 294], HR 0.30 [95% CI 0.13 - 0.63]). CONCLUSIONS: In patients with diabetes referred for ICA for the investigation of stable chest pain, a CT-first strategy compared with an ICA-first strategy showed no difference in MACE and may potentially be associated with a lower rate of expanded MACE and major procedure-related complications.

Coronary artery disease grading by cardiac CT for predicting outcome in patients with stable angina.

BACKGROUND: The coronary atheroma burden drives major adverse cardiovascular events (MACE) in patients with suspected coronary heart disease (CHD). However, a consensus on how to grade disease burden for effective risk stratification is lacking. The purpose of this study was to compare the effectiveness of common CHD grading tools to risk stratify symptomatic patients. METHODS: We analyzed the 5-year outcome of 381 prospectively enrolled patients in the CORE320 international, multicenter study using baseline clinical and cardiac computer-tomography (CT) imaging characteristics, including coronary artery calcium score (CACS), percent atheroma volume, "high-risk" plaque, disease severity grading using the CAD-RADS, and two simplified CAD staging systems. We applied Cox proportional hazard models and area under the curve (AUC) analysis to predict MACE or hard MACE, defined as death, myocardial infarction, or stroke. Analyses were stratified by a history of CHD. Additional forward selection analysis was performed to evaluate incremental value of metrics. RESULTS: Clinical characteristics were the strongest predictors of MACE in the overall cohort. In patients without history of CHD, CACS remained the only independent predictor of MACE yielding an AUC of 73 (CI 67-79) vs. 64 (CI 57-70) for clinical characteristics. Noncalcified plaque volume did not add prognostic value. Simple CHD grading schemes yielded similar risk stratification as the CAD-RADS classification. Forward selection analysis confirmed prominent role of CACS and revealed usefulness of functional testing in subgroup with known CHD. CONCLUSION: In patients referred for invasive angiography, a history of CHD was the strongest predictor of MACE. In patients without history of CHD, a coronary calcium score yielded at least equal risk stratification vs. more complex CHD grading.

Coronary Artery Disease in Persons With Human Immunodeficiency Virus Without Detectable Viral Replication.

Background: We aimed to determine the prevalence of coronary artery disease (CAD) in persons with human immunodeficiency virus (HIV; PWH) and investigate whether inflammatory markers, including interleukin 6, IL-1ß, and high-sensitivity C-reactive protein (hsCRP), were associated with CAD. Methods: From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included virologically suppressed PWH who underwent coronary computed tomographic (CT) angiography. Any atherosclerosis was defined as >0% stenosis, and obstructive CAD as ≥50% stenosis. Results: Among 669 participants (mean age [standard deviation], 51 [11] years; 89% male), 300 (45%) had atherosclerosis, and 119 (18%) had obstructive CAD. The following risk factors were associated with any atherosclerosis and with obstructive CAD: age, male sex, hypertension, diabetes, smoking, dyslipidemia, time with HIV, and current protease inhibitor use. Interleukin 6 (IL-6) and hsCRP levels >2 mg/L were associated with any atherosclerosis and with obstructive CAD in univariable analyses but not after adjustment for traditional risk factors. IL-1ß was not associated with CAD. Conclusions: In a large population of PWH without viral replication, almost half had angiographically verified atherosclerosis. High concentrations of IL-6 and hsCRP were associated with CAD in univariable analyses, but adjustment for cardiovascular risk factors attenuated the association, suggesting that inflammation may mediate the association between traditional risk factors and CAD.

Genetic risk of fatty liver disease and mortality in the general population: A Mendelian randomization study.

BACKGROUND & AIMS: Fatty liver disease has been associated with higher all-cause as well as liver-related, ischemic heart disease (IHD)-related and extrahepatic cancer-related mortality in observational epidemiological studies. We tested the hypothesis that fatty liver disease is a causal risk factor for higher mortality. METHODS: We genotyped seven genetic variants known to be associated with fatty liver disease (in PNPLA3, TM6SF2, HSD17B13, MTARC1, MBOAT7, GCKR, and GPAM) in 110 913 individuals from the Danish general population. Hepatic steatosis was measured by hepatic computed tomography in n = 6965. Using a Mendelian randomization framework, we tested whether genetically proxied hepatic steatosis and/or elevated plasma alanine transaminase (ALT) was associated with liver-related mortality. RESULTS: During a median follow-up of 9.5 years, 16 119 individuals died. In observational analyses, baseline elevated plasma ALT was associated with higher all-cause (1.26-fold), liver-related (9-fold), and extrahepatic cancer-related (1.25-fold) mortality. In genetic analyses, the risk alleles in PNPLA3, TM6SF2, and HSD17B13 were individually associated with higher liver-related mortality. The largest effects were seen for the PNPLA3 and TM6SF2 risk alleles, for which homozygous carriers had 3-fold and 6-fold, respectively, higher liver-related mortality than non-carriers. None of the risk alleles, individually or combined into risk scores, were robustly associated with all-cause, IHD-related, or extrahepatic cancer-related mortality. In instrumental variable analyses, genetically proxied hepatic steatosis and higher plasma ALT were associated with liver-related mortality. CONCLUSIONS: Human genetic data support that fatty liver disease is a causal driver of liver-related mortality.

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.

Quantification of myocardial blood flow using dynamic myocardial CT perfusion compared with 82Rb PET.

PURPOSE: Absolute measures of myocardial blood flow (MBF) obtained with dynamic myocardial CT perfusion (DM-CTP) are underestimated when compared with reference standards. This is to some extent explained by incomplete extraction of iodinated contrast agent (iCA) to the myocardial tissue. We aimed to establish an extraction function for iCA, use the function to calculate MBFCT and to compare this with MBF measured with 82Rb positron emission tomography (PET). MATERIALS AND METHODS: Healthy individuals without coronary artery disease (CAD) were examined with 82Rb PET and DM-CTP. The factors a and ß of the generalized Renkin-Crone model were estimated using a non-linear least squares model. The factors providing the best fit for the data were subsequently used to calculate MBFCT. RESULTS: Of consecutive 91 individuals examined, 79 were eligible for analysis. The factors a and ß providing the best fit of the nonlinear least-squares model to the data were a â€‹= â€‹0.614 and ߠ​= â€‹0.218 (R-squared â€‹= â€‹0.81). Conversion of the CT inflow parameter (K1) values using the derived extraction function resulted in a significant correlation between MBF measured during stress using CT and PET (P â€‹= â€‹0.039). CONCLUSION: In healthy individuals, flow estimates obtained with dynamic myocardial CT perfusion during stress were, after conversion to MBF using the extraction of iodinated CT contrast agent, correlated with absolute MBF quantified with 82Rb PET.

Coronary and extra-coronary artery calcium scores as predictors of cardiovascular events and mortality in chronic kidney disease stages 1-5: a prospective cohort study.

BACKGROUND: Vascular calcification is a known risk factor for cardiovascular events and mortality in patients with chronic kidney disease (CKD). However, since there is a lack of studies examining several arterial regions at a time, we aimed to evaluate the risk of major adverse cardiovascular events (MACE) and all-cause mortality according to calcium scores in five major arterial sites. METHODS: This was a prospective study of 580 patients from the Copenhagen CKD Cohort. Multidetector computed tomography of the coronary and carotid arteries, the thoracic aorta, the abdominal aorta and the iliac arteries was used to determine vascular calcification at baseline. Calcium scores were divided into categories: 0, 1-100, 101-400 and >400. RESULTS: During the follow-up period of 4.1 years a total of 59 cardiovascular events and 64 all-cause deaths occurred. In Cox proportional hazards models adjusted for age, sex, estimated glomerular filtration rate, hypertension, diabetes mellitus, hypercholesterolemia and smoking, only the coronary and carotid arteries, and the thoracic aorta were independent predictors of the designated endpoints. When examining the potential of calcification in the five arterial sites for predicting MACE, the difference in C-statistic was also most pronounced in these three sites, at 0.21 [95% confidence interval (CI) 0.16%-0.26%, P < .001], 0.26 (95% CI 0.22%-0.3%, P < .001) and 0.20 (95% CI 0.16%-0.24%, P < .001), respectively. This trend also applied to all-cause mortality. CONCLUSIONS: The overall results, including data on specificity, suggest that calcium scores of the coronary and carotid arteries have the most potential for identifying patients with CKD at high cardiovascular risk and for evaluating new therapies.

Technical Considerations for Dynamic Myocardial Computed Tomography Perfusion as Part of a Comprehensive Evaluation of Coronary Artery Disease Using Computed Tomography.

Dynamic myocardial computed tomography perfusion (DM-CTP) has good diagnostic accuracy for identifying myocardial ischemia as compared with both invasive and noninvasive reference standards. However, DM-CTP has not yet been implemented in the routine clinical examination of patients with suspected or known coronary artery disease. An important hurdle in the clinical dissemination of the method is the development of the DM-CTP acquisition protocol and image analysis. Therefore, the aim of this article is to provide a review of critical parameters in the design and execution of DM-CTP to optimize each step of the examination and avoid common mistakes. We aim to support potential users in the successful implementation and performance of DM-CTP in daily practice. When performed appropriately, DM-CTP may support clinical decision making. In addition, when combined with coronary computed tomography angiography, it has the potential to shorten the time to diagnosis by providing immediate visualization of both coronary atherosclerosis and its functional relevance using one single modality.

Coronary CT and timing of invasive coronary angiography in patients ≥75 years old with non-ST segment elevation acute coronary syndromes.

BACKGROUND: The ability of coronary CT angiography (cCTA) to rule out significant coronary artery disease (CAD) in older patients with non-ST segment elevation acute coronary syndromes (NSTEACS) is unclear since valid cCTA analysis may be limited by extensive coronary artery calcification. In addition, the effect of very early invasive coronary angiography (ICA) with possible revascularisation is debated. METHODS: This is a posthoc analysis of patients ≥75 years included in the Very Early vs Standard Care Invasive Examination and Treatment of Patients with Non-ST-Segment Elevation Acute Coronary Syndrome Trial. cCTA was performed prior to the ICA. The diagnostic accuracy of cCTA was investigated. Presence of a coronary artery stenosis ≥50% by subsequent ICA was used as reference. Patients were randomised to a very early (within 12 hours of diagnosis) or a standard ICA (within 48-72 hours of diagnosis). The primary composite endpoint was 5-year all-cause mortality, non-fatal recurrent myocardial infarction or hospital admission for refractory myocardial ischaemia or heart failure. RESULTS: Of 452 (21%) patients ≥75 years, 161 (35.6%) underwent cCTA. 19% of cCTAs excluded significant CAD. The negative predictive value (NPV) of cCTA was 94% (95% CI 79 to 99) and the sensitivity 98% (95% CI 94 to 100). No significant differences in the frequency of primary endpoints were seen in patients randomised to very early ICA (at 5-year follow-up, n=100 (46.9%) vs 122 (51.0%), log-rank p=0.357). CONCLUSION: In patients ≥75 years with NSTEACS, cCTA before ICA showed a high NPV. A very early ICA <12 hours of diagnosis did not significantly improve long-term clinical outcomes.