Journal of the American College of Cardiology, Mar 1, 2017
Background: Diagnosing suspected coronary artery disease (CAD) continues to require substantial h... more Background: Diagnosing suspected coronary artery disease (CAD) continues to require substantial health care resources. Despite improved risk stratification algorithms, the incidence of normal investigations remains high with the use of traditional diagnostic modalities. We therefore tested the diagnostic accuracy to rule out CAD of a new acoustic system CADscor® based on advanced sound analysis from the coronary circulation and myocardium obtained from a simple stethoscope like device. We included 1675 patients with a low to intermediate likelihood of CAD referred for Cardiac CT. If CAD was suspected in any coronary segments, patients were referred to invasive angiography with FFR. CADscore was recorded in all patients. The CADscore algorithm included both acoustic features and clinical risk factors. Low risk is indicated by a CADscore value ≤20. The algorithm was developed using recordings from 711 patients from previous studies and a trainings cohort of 589 patients from the present study. The remaining 1086 patients were used as the validation cohort. Results: CADscore was successfully analyzed in 1464 (87%) patients. Hemodynamic significant CAD was present in 134 (9.3%) patients. There were no differences in the performance of the CADscore algorithm in the training vs. validation cohorts. In the entire cohort, the CADscore differed between coronary artery calcium score (CACS) groups CACS=0 (n=745), CACS 1-400 (n=550) and CACS > 400 (n=142); CADscore: 17 ±11, 24 ±12 and 30 ±12 (p<0.001). CADscore was also significant lower for patients without vs. with hemodynamic significant stenosis 20 ±12 vs 30 ±12 (p<0.001). Diagnostic performance evaluated by receiver operating characteristic curve showed an accuracy of 72% (CI: 67% -77%). Sensitivity, specificity, PPV and NPV were 81% (CI: 74% to 88%), 53% (CI: 50% to 56%), 15% (CI: 13% to 18%), and 97% (CI:95% to 98%). A simple sound based recording device and analysis model enables risk stratification in suspected CAD patients. With a negative predictive value of 97 %, this new acoustic system could be utilized as a first line rule-out test which could reduce demands on more advanced diagnostic modalities.
for the Scandinavian Organization for Randomized Trials With Clinical Outcome IV (SORT OUT IV) In... more for the Scandinavian Organization for Randomized Trials With Clinical Outcome IV (SORT OUT IV) Investigators Background-Among drug-eluting stents released to date, the sirolimus-eluting stent has demonstrated the least amount of late lumen loss, but its efficacy and safety have not been compared head-to-head with the next-generation everolimus-eluting stent. Methods and Results-The Scandinavian Organization for Randomized Trials with Clinical Outcome IV (SORT OUT IV) trial was a randomized multicenter, single-blind, all-comer, 2-arm, noninferiority trial comparing the everolimus-eluting stent with the sirolimus-eluting stent in patients with coronary artery disease. The primary end point was a composite of safety (cardiac death, myocardial infarction, definite stent thrombosis) and efficacy (target vessel revascularization) parameters. The noninferiority criterion was a risk difference of 0.015. Intention-to-treat analyses were done at 9-and 18-month follow-ups. A total of 1390 patients were assigned to receive the everolimus-eluting stent and 1384 patients to the sirolimus-eluting stent. At the 9-month follow-up, 68 patients (4.9%) treated with the everolimus-eluting stent compared with 72 patients (5.2%) treated with the sirolimus-eluting stent experienced the primary end point (hazard ratio, 0.94; 95% confidence interval, 0.67-1.31; P for noninferiorityϭ0.01). At the 18-month follow-up, this differential remained: 99 patients (7.2%) treated with the everolimus-eluting stent versus 105 (7.6%) treated with the sirolimuseluting stent (hazard ratio, 0.94; 95% confidence interval, 0.71-1.23). At the 9-month follow-up, the rate of definite stent thrombosis was higher in the sirolimus-eluting group (2 patients [0.1%] versus 9 patients [0.7%]; hazard ratio, 0.22; 95% confidence interval, 0.05-1.02). At the 18-month follow-up, this difference was sustained (3 patients [0.2%] versus 12 patients [0.9%]; hazard ratio, 0.25; 95% confidence interval, 0.07-0.88). Conclusion-The everolimus-eluting stent was found to be noninferior to the sirolimus-eluting stent.
Journal of the American College of Cardiology, 2020
BACKGROUND The prevalence of obstructive coronary artery disease (CAD) in symptomatic patients re... more BACKGROUND The prevalence of obstructive coronary artery disease (CAD) in symptomatic patients referred for diagnostic testing has declined, warranting optimization of individualized diagnostic strategies. OBJECTIVES This study sought to present a simple, clinically applicable tool enabling estimation of the likelihood of obstructive CAD by combining a pre-test probability (PTP) model (Diamond-Forrester approach using sex, age, and symptoms) with clinical risk factors and coronary artery calcium score (CACS). METHODS The new tool was developed in a cohort of symptomatic patients (n = 41,177) referred for diagnostic testing. The risk factor-weighted clinical likelihood (RF-CL) was calculated through PTP and risk factors, while the CACS-weighted clinical likelihood (CACS-CL) added CACS. The 2 calculation models were validated in European and North American cohorts (n = 15,411) and compared with a recently updated PTP table. RESULTS The RF-CL and CACS-CL models predicted the prevalence of obstructive CAD more accurately in the validation cohorts than the PTP model, and markedly increased the area under the receiver-operating characteristic curves of obstructive CAD: for the PTP model, 72 (95% confidence intervals [CI]: 71 to 74); for the RF-CL model, 75 (95% CI: 74 to 76); and for the CACS-CL model, 85 (95% CI: 84 to 86). In total, 38% of the patients in the RF-CL group and 54% in the CACS-CL group were categorized as having a low clinical likelihood of CAD, as compared with 11% with the PTP model. CONCLUSIONS A simple risk factor and CACS-CL tool enables improved prediction and discrimination of patients with suspected obstructive CAD. The tool empowers reclassification of patients to low likelihood of CAD, who need no further testing.
Aims Estimation of pre-test probability (PTP) of disease in patients with suspected coronary art... more Aims Estimation of pre-test probability (PTP) of disease in patients with suspected coronary artery disease (CAD) is a common challenge. Due to decreasing prevalence of obstructive CAD in patients referred for diagnostic testing, the European Society of Cardiology suggested a new PTP (2019-ESC-PTP) model. The aim of this study was to validate that model. Methods and results Symptomatic patients referred for coronary computed tomography angiography (CTA) due to suspected CAD in a geographical uptake area of 3.3 million inhabitants were included. The reference standard was a combined endpoint of CTA and invasive coronary angiography (ICA) with obstructive CAD defined at ICA as a ≥50% diameter stenosis or fractional flow reserve ≤0.80 when performed. The 2019-ESC-PTP, 2013-ESC-PTP, and CAD Consortium basic PTP scores were calculated based on age, sex, and symptoms. Of the 42 328 identified patients, coronary stenosis was detected in 8.8% using the combined endpoint. The 2019-ESC-PTP ...
European Heart Journal - Cardiovascular Imaging, 2019
Aims European and North American guidelines currently recommend pre-test probability (PTP) strati... more Aims European and North American guidelines currently recommend pre-test probability (PTP) stratification based on simple probability models in patients with suspected coronary artery disease (CAD). However, no unequivocal recommendation has yet been established. We aimed to compare the ability of risk factors and different PTP stratification models to predict haemodynamically obstructive CAD with fractional flow reserve (FFR) as reference in low to intermediate probability patients. Methods and results We prospectively included 1675 patients with low to intermediate risk who had been referred to coronary computed tomography angiography (CTA). Patients with coronary stenosis were subsequently investigated by invasive coronary angiography (ICA) with FFR measurement if indicated. Discrimination and calibration were assessed for four models: the updated Diamond–Forrester (UDF), the CAD Consortium Basic, the Clinical, and the Clinical + Coronary artery calcium score (CACS). At coronary ...
Aims Recent technological advances enable diagnosing of obstructive coronary artery disease (CAD)... more Aims Recent technological advances enable diagnosing of obstructive coronary artery disease (CAD) from heart sound analysis with a high negative predictive value. However, the prognostic impact of this approach remains unknown. To investigate the prognostic value of heart sound analysis as two scores, the Acoustic-score and the CAD-score, in patients with suspected CAD which is treated according to standard of care. Methods and results Consecutive patients with angina symptoms referred for coronary computed tomography angiography (CTA) were enrolled. The Acoustic-score was developed from eight acoustic CAD-related features. This score was combined with risk factors to generate the CAD-score. A cut-off score >20 was pre-specified for both scores to indicate disease. If coronary CTA raised suspicion of obstructive CAD, patients were referred to invasive angiography and revascularized when indicated. Of 1675 enrolled patients, 1464 (87.4%) were included in this substudy. The combine...
Journal of the American College of Cardiology, Oct 1, 2012
Background: Recent data suggests that atrial fibrillation (AF) is associated with worse outcomes ... more Background: Recent data suggests that atrial fibrillation (AF) is associated with worse outcomes after PCI for STEMI. We investigated the incidence and impact of baseline and new onset AF in pts undergoing primary PCI from the large, prospective, randomized HORIZONS-AMI trial. Methods: HORIZONS-AMI was a large-scale, multicenter, international, randomized trial comparing different antithrombotic regimens and stents during primary PCI in STEMI. The primary endpoint was net adverse cardiac events (NACE; the composite of death, reinfarction, ischemia-driven TVR, stroke, or non-CABG-related major bleeding. Pts with and without AF at baseline and with and without new onset AF post-PCI were compared at 3 years. Results: Baseline AF was present in 69/3,599 patients (1.9%), and AF developed after PCI in an additional 172/3,358 patients (5.1%). Three-year NACE rates were not significantly different between pts who did and did not have AF at baseline (34.2% vs. 26.4%, pϭ0.12). Nor were the 3-year rates of mortality different in pts with and without baseline AF (10.4% vs 6.7%, pϭ0.22). In contrast, compared to pts who remained in sinus rhythm, pts with new onset AF after PCI had higher 3-year rates of NACE (45.7% vs. 25.4%), mortality (14.9% vs. 6.3%), reinfarction (14.3% vs. 6.9%), stroke (7.4% vs. 1.6%) and major bleeding (21.0% vs. 8.0%) (all pϽ0.0001). By multivariable analysis, new onset AF was one of the strongest independent predictors of NACE (HR [95%CI]ϭ 1.80 [1.37, 2.37], pϽ0.0001) and death (1.88 [1.23, 2.88], pϽ0.003) at 3 years. Conclusions: In the large, multicenter HORIZONS-AMI trial, the presence of AF at baseline was not associated with inferior outcomes in pts with STEMI undergoing primary PCI. However, the development of AF post-PCI was associated with markedly higher rates of adverse events and mortality. New approaches to prevent or treat post-PCI AF may further improve outcomes after primary PCI.
Purpose: Remote ischemic conditioning (RIC) increases myocardial salvage, whereas extended system... more Purpose: Remote ischemic conditioning (RIC) increases myocardial salvage, whereas extended system delay reduces myocardial salvage and increases infarct size in patients with ST-elevation myocardial infarction (STEMI). We investigated the influence of RIC on the effect of system delay in STEMI patients undergoing primary percutaneous coronary intervention (pPCI). Methods: In a prospective, single-blinded randomized controlled trial (n=251), we studied STEMI patients randomized to treatment with either pPCI alone or pPCI+RIC. RIC was performed during transport to hospital as 4 cycles of 5 min upper arm ischemia followed by 5 min of reperfusion. Area-at-risk, myocardial salvage index and final infarct size were assessed by single photon emission computerized tomography (SPECT). System delay was defined as time from emergency medical service call to pPCI-wire. Data were obtained from emergency medical service registries and files. Results: Data for final infarct size and system delay were available for 202 patients, and data for myocardial salvage index and system delay were available for 129 patients. Patients were equally distributed among treatment with pPCI alone or pPCI+RIC. Area-at-risk and system delay did not differ between patients treated with pPCI alone or pPCI+RIC (p=0.974 and p=0.909, respectively). While system delay in patients treated with pPCI alone was associated with significantly reduced myocardial salvage index (p=0.008) and increased final infarct size (p=0.043), these associations were attenuated in patients treated with pPCI+RIC (p=0.737 and p=0.628, respectively) with significantly different slopes (p=0.022) as shown for myocardial salvage index (figure). Conclusion: RIC attenuates the effect of extended system delay on myocardial salvage index and final infarct size in STEMI patients treated with pPCI, suggesting that the cardioprotective effect of RIC increases with extended duration of ischemia.
Journal of the American Heart Association, Feb 4, 2020
Background Polygenic risk scores ( PRS s) based on risk variants from genome‐wide association stu... more Background Polygenic risk scores ( PRS s) based on risk variants from genome‐wide association studies predict coronary artery disease ( CAD ) risk. However, it is unknown whether the PRS is associated with specific CAD characteristics. Methods and Results We consecutively included 1645 patients with suspected stable CAD undergoing coronary computed tomography angiography. A multilocus PRS was calculated as the weighted sum of CAD risk variants. Plaques were evaluated using an 18‐segment model and characterized by stenosis severity and composition (soft [0%‐19% calcified], mixed‐soft [20%‐49% calcified], mixed‐calcified [50%‐79% calcified], or calcified [≥80% calcified]). Coronary artery calcium score and segment stenosis score were used to characterize plaque burden. For each standard deviation increase in the PRS , coronary artery calcium score increased by 78% ( P =4.1e‐26) and segment stenosis score increased by 16% ( P =2.4e‐29) in the fully adjusted model. The PRS was associated with a higher prevalence of obstructive plaques (odds ratio [ OR ] : 1.78, P =5.6e‐16), calcified ( OR : 1.69, P =6.5e‐17), mixed‐calcified ( OR : 1.67, P =7.3e‐9), mixed‐soft ( OR : 1.45, P =1.6e‐6), and soft plaques ( OR : 1.49, P =2.5e‐6), and a higher prevalence of plaque in each coronary vessel (all P &lt;1.0e‐4). However, when analyzing data on a plaque level (3007 segments with plaque in 849 patients) the PRS was not associated with stenosis severity, plaque composition, or localization (all P &gt;0.05). Conclusions Our results suggest that polygenic risk based on large genome‐wide association studies increases CAD risk through an increased burden of coronary atherosclerosis rather than promoting specific plaque features. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 02264717.
Background: Polygenic risk scores (PRSs) are associated with coronary artery disease (CAD), but t... more Background: Polygenic risk scores (PRSs) are associated with coronary artery disease (CAD), but the clinical potential of using PRSs at the single-patient level for risk stratification has yet to be established. We investigated whether adding a PRS to clinical risk factors (CRFs) improves risk stratification in patients referred to coronary computed tomography angiography on a suspicion of obstructive CAD. Methods: In this prespecified diagnostic substudy of the Dan-NICAD trial (Danish study of Non-Invasive testing in Coronary Artery Disease), we included 1617 consecutive patients with stable chest symptoms and no history of CAD referred for coronary computed tomography angiography. CRFs used for risk stratification were age, sex, symptoms, prior or active smoking, antihypertensive treatment, lipid-lowering treatment, and diabetes. In addition, patients were genotyped, and their PRSs were calculated. All patients underwent coronary computed tomography angiography. Patients with a su...
In patients with ST-segment elevation myocardial infarction (STEMI), ischemic postconditioning (i... more In patients with ST-segment elevation myocardial infarction (STEMI), ischemic postconditioning (iPOST) have shown ambiguous results in minimizing reperfusion injury. Previous findings show beneficial effects of iPOST in patients with STEMI treated without thrombectomy. However, it remains unknown whether the cardioprotective effect of iPOST in these patients persist on long term. In the current study, all patients were identified through the DANAMI-3-iPOST database. Patients were randomized to conventional primary percutaneous coronary intervention (PCI) or iPOST in addition to PCI. Cumulative incidence rates were calculated, and multivariable analyses stratified according to thrombectomy use were performed. The primary end point was a combination of cardiovascular mortality and hospitalization for heart failure. From 2011 to 2014, 1,234 patients with STEMI were included with a median follow-up of 4.8 years. In patients treated without thrombectomy (n = 520), the primary end point occurred in 15% (48/326) in the iPOST group and in 22% (42/194) in the conventional group (unadjusted hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.41 to 0.94, p = 0.023). In adjusted Cox analysis, iPOST remained associated with reduced long-term risk of cardiovascular mortality (HR 0.53, 95% CI 0.29 to 0.97, p = 0.039). In patients treated with thrombectomy (n = 714), there was no significant difference between iPOST (17%, 49/291) and conventional treatment (17%, 72/423) on the primary end point (unadjusted HR 1.01, 95% CI 0.70 to 1.45, p = 0.95). During a follow-up of nearly 5 years, iPOST reduced long-term occurrence of cardiovascular mortality and hospitalization for heart failure in patients with STEMI treated with PCI but without thrombectomy.
Introduction: The recent guidelines from The European Society of Cardiology recommend angiography... more Introduction: The recent guidelines from The European Society of Cardiology recommend angiography within 24 hours in high-risk patients with acute coronary syndrome without persisting ST-elevations...
Journal of the American College of Cardiology, Mar 1, 2017
Background: Diagnosing suspected coronary artery disease (CAD) continues to require substantial h... more Background: Diagnosing suspected coronary artery disease (CAD) continues to require substantial health care resources. Despite improved risk stratification algorithms, the incidence of normal investigations remains high with the use of traditional diagnostic modalities. We therefore tested the diagnostic accuracy to rule out CAD of a new acoustic system CADscor® based on advanced sound analysis from the coronary circulation and myocardium obtained from a simple stethoscope like device. We included 1675 patients with a low to intermediate likelihood of CAD referred for Cardiac CT. If CAD was suspected in any coronary segments, patients were referred to invasive angiography with FFR. CADscore was recorded in all patients. The CADscore algorithm included both acoustic features and clinical risk factors. Low risk is indicated by a CADscore value ≤20. The algorithm was developed using recordings from 711 patients from previous studies and a trainings cohort of 589 patients from the present study. The remaining 1086 patients were used as the validation cohort. Results: CADscore was successfully analyzed in 1464 (87%) patients. Hemodynamic significant CAD was present in 134 (9.3%) patients. There were no differences in the performance of the CADscore algorithm in the training vs. validation cohorts. In the entire cohort, the CADscore differed between coronary artery calcium score (CACS) groups CACS=0 (n=745), CACS 1-400 (n=550) and CACS > 400 (n=142); CADscore: 17 ±11, 24 ±12 and 30 ±12 (p<0.001). CADscore was also significant lower for patients without vs. with hemodynamic significant stenosis 20 ±12 vs 30 ±12 (p<0.001). Diagnostic performance evaluated by receiver operating characteristic curve showed an accuracy of 72% (CI: 67% -77%). Sensitivity, specificity, PPV and NPV were 81% (CI: 74% to 88%), 53% (CI: 50% to 56%), 15% (CI: 13% to 18%), and 97% (CI:95% to 98%). A simple sound based recording device and analysis model enables risk stratification in suspected CAD patients. With a negative predictive value of 97 %, this new acoustic system could be utilized as a first line rule-out test which could reduce demands on more advanced diagnostic modalities.
for the Scandinavian Organization for Randomized Trials With Clinical Outcome IV (SORT OUT IV) In... more for the Scandinavian Organization for Randomized Trials With Clinical Outcome IV (SORT OUT IV) Investigators Background-Among drug-eluting stents released to date, the sirolimus-eluting stent has demonstrated the least amount of late lumen loss, but its efficacy and safety have not been compared head-to-head with the next-generation everolimus-eluting stent. Methods and Results-The Scandinavian Organization for Randomized Trials with Clinical Outcome IV (SORT OUT IV) trial was a randomized multicenter, single-blind, all-comer, 2-arm, noninferiority trial comparing the everolimus-eluting stent with the sirolimus-eluting stent in patients with coronary artery disease. The primary end point was a composite of safety (cardiac death, myocardial infarction, definite stent thrombosis) and efficacy (target vessel revascularization) parameters. The noninferiority criterion was a risk difference of 0.015. Intention-to-treat analyses were done at 9-and 18-month follow-ups. A total of 1390 patients were assigned to receive the everolimus-eluting stent and 1384 patients to the sirolimus-eluting stent. At the 9-month follow-up, 68 patients (4.9%) treated with the everolimus-eluting stent compared with 72 patients (5.2%) treated with the sirolimus-eluting stent experienced the primary end point (hazard ratio, 0.94; 95% confidence interval, 0.67-1.31; P for noninferiorityϭ0.01). At the 18-month follow-up, this differential remained: 99 patients (7.2%) treated with the everolimus-eluting stent versus 105 (7.6%) treated with the sirolimuseluting stent (hazard ratio, 0.94; 95% confidence interval, 0.71-1.23). At the 9-month follow-up, the rate of definite stent thrombosis was higher in the sirolimus-eluting group (2 patients [0.1%] versus 9 patients [0.7%]; hazard ratio, 0.22; 95% confidence interval, 0.05-1.02). At the 18-month follow-up, this difference was sustained (3 patients [0.2%] versus 12 patients [0.9%]; hazard ratio, 0.25; 95% confidence interval, 0.07-0.88). Conclusion-The everolimus-eluting stent was found to be noninferior to the sirolimus-eluting stent.
Journal of the American College of Cardiology, 2020
BACKGROUND The prevalence of obstructive coronary artery disease (CAD) in symptomatic patients re... more BACKGROUND The prevalence of obstructive coronary artery disease (CAD) in symptomatic patients referred for diagnostic testing has declined, warranting optimization of individualized diagnostic strategies. OBJECTIVES This study sought to present a simple, clinically applicable tool enabling estimation of the likelihood of obstructive CAD by combining a pre-test probability (PTP) model (Diamond-Forrester approach using sex, age, and symptoms) with clinical risk factors and coronary artery calcium score (CACS). METHODS The new tool was developed in a cohort of symptomatic patients (n = 41,177) referred for diagnostic testing. The risk factor-weighted clinical likelihood (RF-CL) was calculated through PTP and risk factors, while the CACS-weighted clinical likelihood (CACS-CL) added CACS. The 2 calculation models were validated in European and North American cohorts (n = 15,411) and compared with a recently updated PTP table. RESULTS The RF-CL and CACS-CL models predicted the prevalence of obstructive CAD more accurately in the validation cohorts than the PTP model, and markedly increased the area under the receiver-operating characteristic curves of obstructive CAD: for the PTP model, 72 (95% confidence intervals [CI]: 71 to 74); for the RF-CL model, 75 (95% CI: 74 to 76); and for the CACS-CL model, 85 (95% CI: 84 to 86). In total, 38% of the patients in the RF-CL group and 54% in the CACS-CL group were categorized as having a low clinical likelihood of CAD, as compared with 11% with the PTP model. CONCLUSIONS A simple risk factor and CACS-CL tool enables improved prediction and discrimination of patients with suspected obstructive CAD. The tool empowers reclassification of patients to low likelihood of CAD, who need no further testing.
Aims Estimation of pre-test probability (PTP) of disease in patients with suspected coronary art... more Aims Estimation of pre-test probability (PTP) of disease in patients with suspected coronary artery disease (CAD) is a common challenge. Due to decreasing prevalence of obstructive CAD in patients referred for diagnostic testing, the European Society of Cardiology suggested a new PTP (2019-ESC-PTP) model. The aim of this study was to validate that model. Methods and results Symptomatic patients referred for coronary computed tomography angiography (CTA) due to suspected CAD in a geographical uptake area of 3.3 million inhabitants were included. The reference standard was a combined endpoint of CTA and invasive coronary angiography (ICA) with obstructive CAD defined at ICA as a ≥50% diameter stenosis or fractional flow reserve ≤0.80 when performed. The 2019-ESC-PTP, 2013-ESC-PTP, and CAD Consortium basic PTP scores were calculated based on age, sex, and symptoms. Of the 42 328 identified patients, coronary stenosis was detected in 8.8% using the combined endpoint. The 2019-ESC-PTP ...
European Heart Journal - Cardiovascular Imaging, 2019
Aims European and North American guidelines currently recommend pre-test probability (PTP) strati... more Aims European and North American guidelines currently recommend pre-test probability (PTP) stratification based on simple probability models in patients with suspected coronary artery disease (CAD). However, no unequivocal recommendation has yet been established. We aimed to compare the ability of risk factors and different PTP stratification models to predict haemodynamically obstructive CAD with fractional flow reserve (FFR) as reference in low to intermediate probability patients. Methods and results We prospectively included 1675 patients with low to intermediate risk who had been referred to coronary computed tomography angiography (CTA). Patients with coronary stenosis were subsequently investigated by invasive coronary angiography (ICA) with FFR measurement if indicated. Discrimination and calibration were assessed for four models: the updated Diamond–Forrester (UDF), the CAD Consortium Basic, the Clinical, and the Clinical + Coronary artery calcium score (CACS). At coronary ...
Aims Recent technological advances enable diagnosing of obstructive coronary artery disease (CAD)... more Aims Recent technological advances enable diagnosing of obstructive coronary artery disease (CAD) from heart sound analysis with a high negative predictive value. However, the prognostic impact of this approach remains unknown. To investigate the prognostic value of heart sound analysis as two scores, the Acoustic-score and the CAD-score, in patients with suspected CAD which is treated according to standard of care. Methods and results Consecutive patients with angina symptoms referred for coronary computed tomography angiography (CTA) were enrolled. The Acoustic-score was developed from eight acoustic CAD-related features. This score was combined with risk factors to generate the CAD-score. A cut-off score >20 was pre-specified for both scores to indicate disease. If coronary CTA raised suspicion of obstructive CAD, patients were referred to invasive angiography and revascularized when indicated. Of 1675 enrolled patients, 1464 (87.4%) were included in this substudy. The combine...
Journal of the American College of Cardiology, Oct 1, 2012
Background: Recent data suggests that atrial fibrillation (AF) is associated with worse outcomes ... more Background: Recent data suggests that atrial fibrillation (AF) is associated with worse outcomes after PCI for STEMI. We investigated the incidence and impact of baseline and new onset AF in pts undergoing primary PCI from the large, prospective, randomized HORIZONS-AMI trial. Methods: HORIZONS-AMI was a large-scale, multicenter, international, randomized trial comparing different antithrombotic regimens and stents during primary PCI in STEMI. The primary endpoint was net adverse cardiac events (NACE; the composite of death, reinfarction, ischemia-driven TVR, stroke, or non-CABG-related major bleeding. Pts with and without AF at baseline and with and without new onset AF post-PCI were compared at 3 years. Results: Baseline AF was present in 69/3,599 patients (1.9%), and AF developed after PCI in an additional 172/3,358 patients (5.1%). Three-year NACE rates were not significantly different between pts who did and did not have AF at baseline (34.2% vs. 26.4%, pϭ0.12). Nor were the 3-year rates of mortality different in pts with and without baseline AF (10.4% vs 6.7%, pϭ0.22). In contrast, compared to pts who remained in sinus rhythm, pts with new onset AF after PCI had higher 3-year rates of NACE (45.7% vs. 25.4%), mortality (14.9% vs. 6.3%), reinfarction (14.3% vs. 6.9%), stroke (7.4% vs. 1.6%) and major bleeding (21.0% vs. 8.0%) (all pϽ0.0001). By multivariable analysis, new onset AF was one of the strongest independent predictors of NACE (HR [95%CI]ϭ 1.80 [1.37, 2.37], pϽ0.0001) and death (1.88 [1.23, 2.88], pϽ0.003) at 3 years. Conclusions: In the large, multicenter HORIZONS-AMI trial, the presence of AF at baseline was not associated with inferior outcomes in pts with STEMI undergoing primary PCI. However, the development of AF post-PCI was associated with markedly higher rates of adverse events and mortality. New approaches to prevent or treat post-PCI AF may further improve outcomes after primary PCI.
Purpose: Remote ischemic conditioning (RIC) increases myocardial salvage, whereas extended system... more Purpose: Remote ischemic conditioning (RIC) increases myocardial salvage, whereas extended system delay reduces myocardial salvage and increases infarct size in patients with ST-elevation myocardial infarction (STEMI). We investigated the influence of RIC on the effect of system delay in STEMI patients undergoing primary percutaneous coronary intervention (pPCI). Methods: In a prospective, single-blinded randomized controlled trial (n=251), we studied STEMI patients randomized to treatment with either pPCI alone or pPCI+RIC. RIC was performed during transport to hospital as 4 cycles of 5 min upper arm ischemia followed by 5 min of reperfusion. Area-at-risk, myocardial salvage index and final infarct size were assessed by single photon emission computerized tomography (SPECT). System delay was defined as time from emergency medical service call to pPCI-wire. Data were obtained from emergency medical service registries and files. Results: Data for final infarct size and system delay were available for 202 patients, and data for myocardial salvage index and system delay were available for 129 patients. Patients were equally distributed among treatment with pPCI alone or pPCI+RIC. Area-at-risk and system delay did not differ between patients treated with pPCI alone or pPCI+RIC (p=0.974 and p=0.909, respectively). While system delay in patients treated with pPCI alone was associated with significantly reduced myocardial salvage index (p=0.008) and increased final infarct size (p=0.043), these associations were attenuated in patients treated with pPCI+RIC (p=0.737 and p=0.628, respectively) with significantly different slopes (p=0.022) as shown for myocardial salvage index (figure). Conclusion: RIC attenuates the effect of extended system delay on myocardial salvage index and final infarct size in STEMI patients treated with pPCI, suggesting that the cardioprotective effect of RIC increases with extended duration of ischemia.
Journal of the American Heart Association, Feb 4, 2020
Background Polygenic risk scores ( PRS s) based on risk variants from genome‐wide association stu... more Background Polygenic risk scores ( PRS s) based on risk variants from genome‐wide association studies predict coronary artery disease ( CAD ) risk. However, it is unknown whether the PRS is associated with specific CAD characteristics. Methods and Results We consecutively included 1645 patients with suspected stable CAD undergoing coronary computed tomography angiography. A multilocus PRS was calculated as the weighted sum of CAD risk variants. Plaques were evaluated using an 18‐segment model and characterized by stenosis severity and composition (soft [0%‐19% calcified], mixed‐soft [20%‐49% calcified], mixed‐calcified [50%‐79% calcified], or calcified [≥80% calcified]). Coronary artery calcium score and segment stenosis score were used to characterize plaque burden. For each standard deviation increase in the PRS , coronary artery calcium score increased by 78% ( P =4.1e‐26) and segment stenosis score increased by 16% ( P =2.4e‐29) in the fully adjusted model. The PRS was associated with a higher prevalence of obstructive plaques (odds ratio [ OR ] : 1.78, P =5.6e‐16), calcified ( OR : 1.69, P =6.5e‐17), mixed‐calcified ( OR : 1.67, P =7.3e‐9), mixed‐soft ( OR : 1.45, P =1.6e‐6), and soft plaques ( OR : 1.49, P =2.5e‐6), and a higher prevalence of plaque in each coronary vessel (all P &lt;1.0e‐4). However, when analyzing data on a plaque level (3007 segments with plaque in 849 patients) the PRS was not associated with stenosis severity, plaque composition, or localization (all P &gt;0.05). Conclusions Our results suggest that polygenic risk based on large genome‐wide association studies increases CAD risk through an increased burden of coronary atherosclerosis rather than promoting specific plaque features. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 02264717.
Background: Polygenic risk scores (PRSs) are associated with coronary artery disease (CAD), but t... more Background: Polygenic risk scores (PRSs) are associated with coronary artery disease (CAD), but the clinical potential of using PRSs at the single-patient level for risk stratification has yet to be established. We investigated whether adding a PRS to clinical risk factors (CRFs) improves risk stratification in patients referred to coronary computed tomography angiography on a suspicion of obstructive CAD. Methods: In this prespecified diagnostic substudy of the Dan-NICAD trial (Danish study of Non-Invasive testing in Coronary Artery Disease), we included 1617 consecutive patients with stable chest symptoms and no history of CAD referred for coronary computed tomography angiography. CRFs used for risk stratification were age, sex, symptoms, prior or active smoking, antihypertensive treatment, lipid-lowering treatment, and diabetes. In addition, patients were genotyped, and their PRSs were calculated. All patients underwent coronary computed tomography angiography. Patients with a su...
In patients with ST-segment elevation myocardial infarction (STEMI), ischemic postconditioning (i... more In patients with ST-segment elevation myocardial infarction (STEMI), ischemic postconditioning (iPOST) have shown ambiguous results in minimizing reperfusion injury. Previous findings show beneficial effects of iPOST in patients with STEMI treated without thrombectomy. However, it remains unknown whether the cardioprotective effect of iPOST in these patients persist on long term. In the current study, all patients were identified through the DANAMI-3-iPOST database. Patients were randomized to conventional primary percutaneous coronary intervention (PCI) or iPOST in addition to PCI. Cumulative incidence rates were calculated, and multivariable analyses stratified according to thrombectomy use were performed. The primary end point was a combination of cardiovascular mortality and hospitalization for heart failure. From 2011 to 2014, 1,234 patients with STEMI were included with a median follow-up of 4.8 years. In patients treated without thrombectomy (n = 520), the primary end point occurred in 15% (48/326) in the iPOST group and in 22% (42/194) in the conventional group (unadjusted hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.41 to 0.94, p = 0.023). In adjusted Cox analysis, iPOST remained associated with reduced long-term risk of cardiovascular mortality (HR 0.53, 95% CI 0.29 to 0.97, p = 0.039). In patients treated with thrombectomy (n = 714), there was no significant difference between iPOST (17%, 49/291) and conventional treatment (17%, 72/423) on the primary end point (unadjusted HR 1.01, 95% CI 0.70 to 1.45, p = 0.95). During a follow-up of nearly 5 years, iPOST reduced long-term occurrence of cardiovascular mortality and hospitalization for heart failure in patients with STEMI treated with PCI but without thrombectomy.
Introduction: The recent guidelines from The European Society of Cardiology recommend angiography... more Introduction: The recent guidelines from The European Society of Cardiology recommend angiography within 24 hours in high-risk patients with acute coronary syndrome without persisting ST-elevations...
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Papers by Hans Bøtker