Search

BACKGROUND: Concentric remodeling (cRM) can precede heart failure with preserved ejection fraction (HFpEF), a condition prevalent in women. METHODS: Patients (n=60 593, 54.2% women) visiting outpatient clinics of Cardiology Centers of the Netherlands were analyzed for cRM, HFpEF development, and mortality risk. We studied risk factors for relative wall thickness both sex- stratified and in women and men combined. Biomarker profiling was performed (4534 plasma proteins) in a substudy involving 557 patients (65.4% women) to identify pathways involved in cRM. RESULTS: cRM was present in 23.5% of women and 27.6% of men and associated with developing HFpEF (HR, 2.15 [95% CI, 1.51–2.99]) and mortality risk (HR, 1.09 [95% CI, 1.00–1.19]) in both sexes. Age, heart rate, and hypertension were statistically significantly stronger risk factors for relative wall thickness in women than men. Higher circulating levels of IFNA5 (interferon alpha-5) were associated with higher relative wall thickness in women only. Pathway analysis revealed differential pathway activation by sex and increased expression of inflammatory pathways in women. CONCLUSIONS: cRM is prevalent in approximately 1 in 4 women and men visiting outpatient cardiology clinics and associated with HFpEF development and mortality risk in both sexes. Known risk factors for cRM were more strongly associated in women than men. Proteomic analysis revealed inflammatory pathway activation in women, with a central role for IFNA5. Differential biologic pathway activation by sex in cRM may contribute to the female predominance of HFpEF and holds promise for identification of new therapeutic avenues for prevention and treatment of HFpEF. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the impact of a CT-first strategy on all-cause and cardiovascular mortality in patients presenting with chest pain in outpatient cardiology clinics.Methods: Patients with a first presentation of suspected angina pectoris were identified and their data linked to the registrations of Statistics Netherlands for information on mortality. The linked database consisted of 33 068 patients. CT-first patients were defined as patients with a CT calcium score and coronary CT angiography, within 6 weeks after their initial visit. Propensity score matching (1:5) was used to match patients with and without a CT-first strategy. After matching, 12 545 patients were included of which 2308 CT-first patients and 10 237 patients that underwent usual care.Results: Mean age was 57 years, 56.3% were women and median follow-up was 4.9 years. All-cause mortality was significantly lower in CT-first patients (n=43, 1.9%) compared with patients without CT (n=363, 3.5%) (HR: 0.51, 95% CI 0.37 to 0.70). Furthermore, CT-first patients were more likely to receive cardiovascular preventative and antianginal medication (aspirin: 44.9% vs 27.1%, statins: 48.7% vs 30.3%, beta-blockers: 37.8% vs 25.5%, in CT-first and without CT-first patients, respectively) and to undergo downstream diagnostics and interventions (coronary interventions: 8.5% vs 5.7%, coronary angiography: 16.2% vs 10.6% in CT-first and without CT-first patients, respectively).Conclusions: In a real-world regular care database, a CT-first strategy in patients suspected of angina pectoris was associated with a lowering of all-cause mortality. [ABSTRACT FROM AUTHOR]

Aims The diagnostic performance of non-invasive imaging in patients with prior coronary artery disease (CAD) has not been tested in prospective head-to-head comparative studies. The aim of this study was to compare the diagnostic performance of qualitative single-photon emission computed tomography (SPECT), quantitative positron emission tomography (PET), and qualitative magnetic resonance imaging (MRI) in patients with a prior myocardial infarction (MI) or percutaneous coronary intervention (PCI). Methods and results In this prospective clinical study, all patients with prior MI and/or PCI and new symptoms of ischaemic CAD underwent 99mTc-tetrofosmin SPECT, [15O]H2O PET, and MRI, followed by invasive coronary angiography with fractional flow reserve (FFR) in all coronary arteries. All modalities were interpreted by core laboratories. Haemodynamically significant CAD was defined by at least one coronary artery with an FFR ≤0.80. Among the 189 enrolled patients, 63% had significant CAD. Sensitivity was 67% (95% confidence interval 58–76%) for SPECT, 81% (72–87%) for PET, and 66% (56–75%) for MRI. Specificity was 61% (48–72%) for SPECT, 65% (53–76%) for PET, and 62% (49–74%) for MRI. Sensitivity of PET was higher than SPECT (P  = 0.016) and MRI (P  = 0.014), whereas specificity did not differ among the modalities. Diagnostic accuracy for PET (75%, 68–81%) did not statistically differ from SPECT (65%, 58–72%, P  = 0.03) and MRI (64%, 57–72%, P  = 0.052). Using FFR < 0.75 as a reference, accuracies increased to 69% (SPECT), 79% (PET), and 71% (MRI). Conclusion In this prospective head-to-head comparative study, SPECT, PET, and MRI did not show a significantly different accuracy for diagnosing FFR defined significant CAD in patients with prior PCI and/or MI. Overall diagnostic performances, however, were discouraging and the additive value of non-invasive imaging in this high-risk population is questionable. [ABSTRACT FROM AUTHOR]

Objective: Women with heart failure with reduced ejection fraction (HFrEF) may reach optimal treatment effect at half of the guideline-recommended medication dose. This study investigates prescription practice and its relation with survival of patients with HF in daily care.Methods: Electronic health record data from 13 Dutch outpatient cardiology clinics were extracted for HF receiving at least one guideline-recommended HF medication. Dose changes over consecutive prescriptions were modelled using natural cubic splines. Inverse probability-weighted Cox regression was used to assess the relationship between dose (reference≥50% target dose) and all-cause mortality.Results: The study population comprised 561 women (29% HFrEF (ejection fraction (EF)<40%), 49% heart failure with preserved ejection fraction (EF≥50%); HFpEF and 615 men (47% and 25%, respectively). During a median follow-up of 3.7 years, 252 patients died (48% women; 167 HFrEF, 84 HFpEF). Nine hundred thirty-four patients (46% women) received ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), 795 (48% women) beta blockers and 178 (42% women) mineralocorticoid receptor antagonists (MRAs). In both sexes, the mean target dose across prescriptions was 50% for ACEI/ARBs and beta blockers, and 100% for MRAs. ACEI/ARB dose of <50% was associated with lower mortality in women but not in men with HFrEF. This was not seen in patients with HFpEF. Beta-blocker dose was not associated with all-cause mortality.Conclusion: Patients with HF seen in outpatient cardiology clinics receive half of the guideline-recommended medication dose. Lower ACEI/ARB dose was associated with improved survival in women with HFrEF. These results underscore the importance of (re)defining optimal medical therapy for women with HFrEF. [ABSTRACT FROM AUTHOR]

Introduction: Mobile health (mHealth), an advanced form of eHealth is expected to drastically change the field of traditional healthcare in the near future as wearables and mobile applications are rapidly increasing in number. The majority of patients with congenital heart disease (CHD) now reach adulthood and this relative young patient population seems particularly suited for mHealth, as they require lifelong follow-up, experience high morbidity burden, and were raised in this digital era. In patients with acquired heart disease the potential of eHealth has been demonstrated, yet data are still inconclusive. Areas covered: In this review of the current literature we evaluated the effect of various eHealth interventions in patients with CHD. Our search resulted in a mere 10 studies, which comprised mostly of children or adolescents with severe CHD. Home-monitoring of saturation and weight through mHealth was found to be beneficial in patients after palliation procedures, and video conferencing was found to have a positive effect on anxiety and healthcare utilization. Expert commentary: Due to high morbidity and mortality in patients with CHD and the promising results of eHealth interventions, further research is desperately needed. [ABSTRACT FROM AUTHOR]

Stroke prevention and rate or rhythm control are crucial in the management of atrial fibrillation (AF). There is recent evidence for benefit of early rhythm control, yet rate control is the first choice in elderly patients. However, the efficacy and safety of rate and rhythm control in the elderly population remains largely unexplored. Therefore, we analyzed electronic health record data and investigated prescribing patterns and mortality of both strategies in elderly patients with AF. Data from patients with AF who were aged ≥75 years, used a pharmacological rate or rhythm control strategy, and visited Cardiology Centers of the Netherlands between 2007 and 2018 were extracted. Of the 1497 patients (54% female), 316 (21%) were prescribed rhythm control and 1181 (79%) rate control. Patients aged >85 years (OR: 2.28; 95% CI: 1.51-3.44, P< 0.001) and those with permanent AF (OR: 2.71; 95% CI: 1.67-4.41, P< 0.001) were more likely to receive rate control, whereas those with paroxysmal AF were less likely to receive rate control (OR: 0.42; 95% CI: 0.32-0.56, P< 0.001). After correction for relevant confounders, the mortality risk for patients using rhythm control and patients using rate control was similar (HR: 0.89; 95% CI: 0.70-1.12, P = 0.31). A more liberal approach towards prescribing a rhythm control strategy to the elderly patients with AF may be warranted and seems safe. Our data underscore the need for prospective studies to provide definite answers on efficacy and safety of rhythm control in elderly patients with AF. [ABSTRACT FROM AUTHOR]

Background: Right ventricular (RV) dysfunction is associated with increased morbidity and mortality in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo pulmonary endarterectomy (PEA). We studied whether plasma brain natriuretic peptide (BNP) levels can be used to identify RV dysfunction in CTEPH patients. Therefore, plasma BNP levels were studied in relation to cardiac remodeling and function as determined by cardiac magnetic resonance imaging (MRI). Methods: Thirty-eight patients with CTEPH (55 ± 15 years), and ten healthy controls (46 ± 15 years) were studied. The BNP was determined by an immunoradiometric assay. Results: The CTEPH patients had a mean pulmonary artery pressure of 49 ± 13 mm Hg, cardiac index 2.1 ± 0.7 l · min−1 · m−2, and pulmonary vascular resistance of 867 ± 432 dynes · s · cm−5. In CTEPH patients, compared with controls, right ventricular (RV) remodeling was demonstrated. In the patients, BNP was increased and correlated (all p < 0.0001; Spearman rank test) with MRI parameters of RV remodeling and function: end diastolic (r = 0.71) and end systolic (r = 0.74) volumes, RV mass (r = 0.68), leftward ventricular septal bowing (r = −0.80) and ejection fraction (EF; r = −0.81). By receiver operating curve analysis, BNP levels of 11.5 picomole (pmol)/L and 48.5 pmol/L, respectively, detected RV dysfunction as defined by RVEF less than 0.45 and less than 0.30, respectively, with high sensitivity and specificity. Hemodynamically, BNP levels greater than 48.5 pmol/L identified the most severely affected patients. Conclusions: In CTEPH patients, BNP levels correlate with RV remodeling and can be used to identify RV dysfunction. Future studies are warranted on the role of BNP to identify “high risk” CTEPH patients and its relation to postoperative hemodynamic outcome, RV failure, and mortality. [Copyright &y& Elsevier]

Background: In patients with an intra-atrial correction for transposition of the great arteries (TGA) an abnormal response to stress testing is common. However, hemodynamic responses may vary substantially when different stress tests are used. We compared the hemodynamic response to dobutamine stress with the response to physical exercise in patients and controls. Methods: Thirty-nine patients and 25 age/sex-matched control subjects underwent either dobutamine stress (15 µg/kg/min) or submaximal physical exercise cardiovascular magnetic resonance. End-systolic and end-diastolic right ventricular volumes (ESV; EDV) were determined. Five representative patients underwent both stress tests. For these patients, wall thickening reserve was calculated as systolic wall thickening during stress minus systolic wall thickening at rest. Results: In controls, dobutamine stress and physical exercise showed similar responses: stroke volume, cardiac output, and ejection fraction increased significantly, whereas ESV decreased significantly and EDV was unchanged. In patients, stroke volume did not increase with either dobutamine or exercise (- 8.6% vs. 2.9%). Ejection fraction increased significantly with dobutamine (16%, p [ABSTRACT FROM AUTHOR]

The findings of this case report suggest that quantitative assessment of plasma neurohormones and magnetic resonance imaging functional parameters in patients with right ventricular pressure overload due to chronic pulmonary embolism might be used as indicators for right ventricular function before and after intervention. Monitoring of changes in these parameters may provide quantitative follow-up of right ventricular function in these patients. [Copyright &y& Elsevier]

Background. Failure of the systemic right ventricle (RV) often complicates adult survival in unoperated or physiologically repaired congenitally corrected transposition of the great arteries (CCTGA). Healthy controls schematically represent an optimal outcome of anatomic repair, which is increasingly performed to treat CCTGA. Magnetic resonance imaging dobutamine stress testing measures cardiac reserve, and sets to compare the left ventricle of controls with the systemic RV of unoperated and physiologically repaired patients with CCTGA.Methods. Baseline and stress magnetic resonance imaging (maximum dobutamine dose, 15 μg/kg/min) assessed systemic RV function in 13 minimally or asymptomatic adult patients with CCTGA (unoperated, n = 7; physiologically repaired, n = 6). The left ventricles of 11 healthy age-matched adults served as controls.Results. Baseline and stress end-diastolic volumes were similar between the systemic RV of unoperated patients and the left ventricle of controls, as well as base line end-systolic volumes. Stress ejection fraction was lower in unoperated and physiologically repaired patients (70 ± 6% and 60 ± 5%, respectively, vs healthy controls (84 ± 8%). However, comparable with healthy controls, both subsets of CCTGA patients responded appropriately to dobutamine stress, as illustrated by similar RV stroke volume, heart rate, mean blood pressure, and cardiac index.Conclusions. Compared with the left ventricles of healthy controls, both patient groups had larger systemic RV volumes, diminished ejection fraction, but an appropriate response to dobutamine stress. Values of unoperated patients are closer to normal than physiologically repaired patients. Magnetic resonance imaging dobutamine may help to define the subgroups of CCTGA patients with favorable anatomy, whereby asymptomatic adult survival could be anticipated without the need for an operation. [Copyright &y& Elsevier]

We explored the effect of dobutamine stress and its possible clinical implications in different groups of asymptomatic patients with chronic right ventricular (RV) pressure overload due to congenital heart disease. Forty-seven asymptomatic and minimally symptomatic patients with chronic RV pressure overload were studied: 24 patients with systemic right ventricles (16 surgically corrected transposition of the great arteries (TGA) (Mustard or Senning), 8 congenitally corrected TGA), 23 patients with chronic pressure overloaded subpulmonic right ventricles, and 11 age- and sex-matched healthy volunteers. Magnetic resonance imaging (MRI) was performed both at baseline and during dobutamine stress to determine RV volumes and ejection fraction. At baseline, RV ejection fraction in patients with surgically corrected TGA was significantly lower than in controls (58 ± 10% vs 70 ± 8%, p = 0.02). During dobutamine stress, RV ejection fraction increased significantly in controls and patient groups except for patients with pressure overloaded subpulmonic right ventricles. RV stroke volume increased in controls (21 ± 21%, p = 0.008); RV stroke volume remained unchanged in patients with congenitally corrected TGA and surgically corrected TGA (2 ± 17%, p = NS; −8 ± 29%, p = NS). A significant RV stroke volume decrease was observed in patients with subpulmonic right ventricles (−15 ± 16%, p = 0.0002). The changes in RV stroke volume were accompanied by a significant decrease in RV end-diastolic volume (−13 ± 14%, p = 0.001) in patients with subpulmonic right ventricles and in patients with surgically corrected TGA (−23 ± 16%, p = 0.0001). In controls and in patients with congenitally corrected TGA there was no change in RV end-diastolic volume (3 ± 15%, p = NS; −5 ± 11%, p = NS). There is a clear heterogeneity in response to MRI dobutamine stress between different groups of patients with chronic RV pressure overload. Our data suggest impaired filling in surgically corrected TGA and decreased contractility in patients with chronic pressure overloaded subpulmonic right ventricles. Dobutamine stress MRI may facilitate follow-up of RV (dys)function in patients with chronic RV pressure overload due to congenital heart disease. [Copyright &y& Elsevier]

Background: Remote monitoring devices for atrial fibrillation are known to positively contribute to the diagnostic process and therapy compliance. However, automatic algorithms within devices show varying sensitivity and specificity, so manual double-checking of electrocardiographic (ECG) recordings remains necessary., Objective: The purpose of this study was to investigate the validity of the KardiaMobile algorithm within the Dutch telemonitoring program (HartWacht)., Methods: This retrospective study determined the diagnostic accuracy of the algorithm using assessments by a telemonitoring team as reference. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and F1 scores were determined., Results: A total of 2298 patients (59.5% female; median age 57 ± 15 years) recorded 86,816 ECGs between April 2019 and January 2021. The algorithm showed sensitivity of 0.956, specificity 0.985, PPV 0.996, NPV 0.847, and F1 score 0.976 for the detection of sinus rhythm. A total of 29 false-positive outcomes remained uncorrected within the same patients. The algorithm showed sensitivity of 0.989, specificity 0.953, PPV 0.835, NPV 0.997, and F1 score 0.906 for detection of atrial fibrillation. A total of 2 false-negative outcomes remained uncorrected., Conclusion: Our research showed high validity of the algorithm for the detection of both sinus rhythm and, to a lesser extent, atrial fibrillation. This finding suggests that the algorithm could function as a standalone instrument particularly for detection of sinus rhythm., (© 2023 Heart Rhythm Society.)

Background: Concentric remodeling (cRM) can precede heart failure with preserved ejection fraction (HFpEF), a condition prevalent in women., Methods: Patients (n=60 593, 54.2% women) visiting outpatient clinics of Cardiology Centers of the Netherlands were analyzed for cRM, HFpEF development, and mortality risk. We studied risk factors for relative wall thickness both sex-stratified and in women and men combined. Biomarker profiling was performed (4534 plasma proteins) in a substudy involving 557 patients (65.4% women) to identify pathways involved in cRM., Results: cRM was present in 23.5% of women and 27.6% of men and associated with developing HFpEF (HR, 2.15 [95% CI, 1.51-2.99]) and mortality risk (HR, 1.09 [95% CI, 1.00-1.19]) in both sexes. Age, heart rate, and hypertension were statistically significantly stronger risk factors for relative wall thickness in women than men. Higher circulating levels of IFNA5 (interferon alpha-5) were associated with higher relative wall thickness in women only. Pathway analysis revealed differential pathway activation by sex and increased expression of inflammatory pathways in women., Conclusions: cRM is prevalent in approximately 1 in 4 women and men visiting outpatient cardiology clinics and associated with HFpEF development and mortality risk in both sexes. Known risk factors for cRM were more strongly associated in women than men. Proteomic analysis revealed inflammatory pathway activation in women, with a central role for IFNA5. Differential biologic pathway activation by sex in cRM may contribute to the female predominance of HFpEF and holds promise for identification of new therapeutic avenues for prevention and treatment of HFpEF., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT001747., Competing Interests: Disclosures None.

Background: The European Society of Cardiology (ESC) guidelines for the management of adult congenital heart disease (ACHD) recommend screening in patients at risk for arrhythmic events. However, the optimal mode of detection is unknown., Methods: Baseline and follow-up data of symptomatic ACHD patients who received an implantable loop recorder (ILR) or who participated in a smartphone based single-lead electrocardiogram study were collected. The primary endpoint was time to first detected arrhythmia., Results: In total 116 ACHD patients (mean age 42 years, 44% male) were studied. The ILR group ( n = 23) differed from the smartphone based single-lead electrocardiogram group ( n = 93) in having a greater part of males and had more severe CHD and (near) syncope as qualifying diagnosis. In the smartphone based single-lead electrocardiogram group history of arrhythmia and palpitations were more frequent (all p < 0.05). Monitoring was performed for 40 and 79 patient-years for the ILR- and smartphone based single-lead electrocardiogram group, respectively. Arrhythmias occurred in 33 patients with an equal median time for both groups to first arrhythmia of 3 months (HR of 0.7, p = 0.81). Furthermore, atrial fibrillation occurred most often ( n = 16) and common therapy changes included medication changes ( n = 7) and implantation of pacemaker or Implantable Cardioverter Defibrillator (ICD) ( N = 4). Symptoms or mode of detection were not a determinant of the first event., Conclusion: Non-invasive smartphone based single-lead electrocardiogram monitoring could be an acceptable alternative for ILR implantation in detecting arrhythmia in symptomatic ACHD patients in respect to diagnostic yield, safety and management decisions, especially in those without syncope., Competing Interests: IT was shareholder in ventures supplying hardware and software implemented in the methods of this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Koole, Kauw, Kooiman, de Groot, Robbers-Visser, Tulevski, Mulder, Bouma and Schuuring.)

Objectives: Uncertainty about the benefit of (high-intensity) statins for women remains due to under-representation of women in primary prevention trials and scarcity of sex-stratified data. This study evaluates the sex-specific relation between statin treatment and survival and the additional benefit of high-intensity statins., Methods: Electronic health record data from 47 801 patients (17 008 statin users and 30 793 non-users) without prior cardiovascular disease were extracted from thirteen Dutch outpatient cardiology clinics. Patients prescribed statins at baseline were propensity-score matched to those eligible for statin therapy (low-density lipoprotein >2.5 mmol/L) without a statin prescription. Statins were divided into low-intensity and high-intensity according to Dutch guidelines. Mortality data were obtained via linkage to the national mortality registry. Cox regression was used to evaluate the relationship between statin prescription and intensity and all-cause and cardiovascular mortality., Results: Propensity score matching created a cohort of 8631 statin users and 8631 non-users. 35% of women and 28% of men received a low-intensity statin. The beneficial effect of statins on both all-cause and cardiovascular mortality was stronger in women (HR 0.66, 95% CI 0.58 to 0.74 and HR 0.55, 95% CI 0.39 to 0.71, respectively) than in men (HR 0.89, 95% CI 0.81 to 0.95 and HR 0.93, 95% CI 0.77 to 1.08, respectively). High-intensity statins conferred modest protection against all-cause mortality (HR 0.94, 95% CI 0.88 to 1.00) and cardiovascular mortality (HR 0.86, 95% CI 0.74 to 0.98) in both sexes., Conclusions: The protective effect of primary prevention statins was stronger in women than men for both all-cause and cardiovascular mortality. High-intensity statins conferred a modest additional benefit in both sexes. Statins seem to be effective regardless of treatment intensity, especially in women., Competing Interests: Competing interests: LH, IIT and GAS are employed by Cardiology Centers of the Netherlands. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: There is limited quantitative evidence on the effect of symptom-driven telemonitoring for cardiac arrhythmias on patient-reported outcomes. We evaluated the effect of a symptom-driven remote arrhythmia monitoring programme on the patient-reported health-related quality of life (HRQoL), sense of safety, physical limitations, and self-management., Methods and Results: This was an observational retrospective longitudinal study of the symptom-driven HartWacht-telemonitoring programme using a remote single-lead electrocardiogram monitoring system. Real-world patient data from participants who were enrolled in the telemonitoring programme for (suspected) symptomatic atrial fibrillation (AF) between July 2017 and September 2019 were evaluated. Primary outcomes were the patient-reported generic HRQoL, disease-specific HRQoL, sense of safety, physical limitations, and self-management at date of enrolment, 3 months and 6 months of follow-up. Outcomes were compared to a historical control group consisting of AF patients receiving standard care. A total of 109 participants in the HartWacht programme [59 men (54%); mean age 61 ± 11 years; 72% diagnosed AF] were included in complete case analysis. There was no significant change in HRQoL and sense of safety during follow-up. A significant improvement in the perceived physical limitations was observed. The level of self-management declined significantly during follow-up. Comparisons to the historic control group ( n  = 83) showed no difference between the patient-reported disease-specific HRQoL, sense of safety and physical limitations at 6 months of follow-up., Conclusion: Symptom-driven remote arrhythmia monitoring for AF does not seem to affect HRQoL and sense of safety, whereas the perceived physical limitations tend to improve. Patient-reported self-management declined during the first 6 months of participation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To assess the diagnostic value of non-acute chest pain characteristics for coronary artery disease in women and men referred to outpatient cardiology clinics., Design and Setting: This is an observational study performed at outpatient cardiology centres of the Netherlands., Participants: The study population consisted of 1028 patients with non-acute chest pain (505 women)., Analysis and Results: Twenty-four women (5%) and 75 men (15%) were diagnosed with coronary artery disease by invasive coronary angiography or CT angiography during regular care follow-up. Elastic net regression was performed to assess which chest pain characteristics and risk factors were of diagnostic value. The overall model selected age, provocation by temperature or stress, relief at rest and functional class as determinants and was accurate in both sexes (area under the curve (AUC) of 0.76 (95% CI 0.68 to 0.85) in women and 0.83 (95% CI 0.78 to 0.88) in men). Both sex-specific models selected age, pressuring nature, radiation, duration, frequency, progress, provocation and relief at rest as determinants. The female model additionally selected dyspnoea, body mass index, hypertension and smoking while the male model additionally selected functional class and diabetes. The sex-specific models performed better than the overall model, but more so in women (AUC: 0.89, 95% CI 0.81 to 0.96) than in men (AUC: 0.84, 95% CI 0.73 to 0.90)., Conclusions: In both sexes, the diagnostic value of non-acute chest pain characteristics and risk factors for coronary artery disease was high. Provocation, relief at rest and functional class of chest pain were the most powerful diagnostic predictors in both women and men. When stratified by sex the performance of the model improved, mostly in women., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Unlabelled: Hybrid imaging using PET in conjunction with CT-based coronary angiography (PET/CTCA) enables near-simultaneous quantification of myocardial blood flow (MBF) and anatomical evaluation of coronary arteries. CTCA is an excellent imaging modality to rule out obstructive coronary artery disease (CAD), but functional assessment is warranted in the presence of a CTCA-observed stenosis because the specificity of CTCA is relatively low. Quantitative H(2)(15)O PET/CTCA may yield complementary information and enhance diagnostic accuracy. The purpose of this study was to evaluate the diagnostic accuracy of quantitative H(2)(15)O PET/CTCA in a clinical cohort of patients with suspected CAD who underwent both cardiac H(2)(15)O PET/CTCA and invasive coronary angiography (ICA). In addition, this study aimed to evaluate and compare the accuracy of hyperemic MBF versus coronary flow reserve (CFR)., Methods: Patients (n = 120; mean age ± SD, 61 ± 10 y; 77 men and 43 women) with a predominantly intermediate pretest likelihood for CAD underwent both quantitative H(2)(15)O PET/CTCA and ICA. A ≥50% stenosis at ICA or a fractional flow reserve ≤ 0.80 was considered significant., Results: Obstructive CAD was diagnosed in 49 of 120 patients (41%). The diagnostic accuracy of hyperemic MBF was significantly higher than CFR (80% vs. 68%, respectively, P = 0.02), with optimal cutoff values of 1.86 mL/min/g and 2.30, respectively. On a per-patient basis, the sensitivity, specificity, negative predictive value, and positive predictive value of CTCA were 100%, 34%, 100%, and 51%, respectively, as compared with 76%, 83%, 83%, and 76%, respectively, for quantitative hyperemic MBF PET. Quantitative H(2)(15)O PET/CTCA reduced the number of false-positive CTCA studies from 47 to 6, although 12 of 49 true-positive CTCAs were incorrectly reclassified as false-negative hybrid scans on the basis of (presumably) sufficient hyperemic MBF. Compared with CTCA (61%) or H(2)(15)O PET (80%) alone (both P < 0.05), the hybrid approach significantly improved diagnostic accuracy (85%)., Conclusion: The diagnostic accuracy of quantitative H(2)(15)O PET/CTCA is superior to either H(2)(15)O PET or CTCA alone for the detection of clinically significant CAD. Hyperemic MBF was more accurate than CFR, implying that a single measurement of MBF in diagnostic protocols may suffice.