Effects of age on microvascular function in patients with normal coronary arteries.

BACKGROUND: It has been suggested that coronary microvascular function decreases with age, irrespective of the presence of epicardial atherosclerosis. AIMS: Our aim is to quantitatively investigate the effects of age on microvascular function in patients with normal coronary arteries. METHODS: In 314 patients with angina with no obstructive coronary artery disease (ANOCA), microcirculatory function was tested using the continuous thermodilution method. In 305 patients, the association between age and both resting and hyperaemic myocardial blood flow (Q), microvascular resistance (Rµ), absolute coronary flow reserve (CFR) and microvascular resistance reserve (MRR) was assessed. In addition, patients were divided into 3 groups to test for differences based on age quartiles (≤52 years [24.9%], 53-64 years [49.2%], ≥65 years [25.9%]). RESULTS: The mean age was 59±9 years with a range from 22 to 79 years. The mean resting Q (Qrest) was not different in the 3 age groups (88±34 mL/min, 82±29 mL/min, and 86±38 mL/min, R2=0.001; p=0.62). A trend towards a decreasing mean hyperaemic Q (Qmax) was observed with increasing age (223±79 mL/min, 209±84 mL/min, 200±80 mL/min, R2=0.010; p=0.083). The mean resting Rµ (Rµ,rest) were 1,204±460 Wood units (WU), 1,260±411 WU, and 1,289±455 WU (p=0.23). The mean hyperaemic Rµ (Rµ,hyp) increased significantly with advancing age (429±149 WU, 464±164 WU, 503±162 WU, R2=0.026; p=0.005). Consequently, MRR decreased with age (3.2±1.2, 3.1±1.0, 2.9±0.9; p=0.038). This trend was present in both the patients with (n=121) and without (n=184) coronary microvascular dysfunction (CMD). CONCLUSIONS: There is an age-dependent physiological increase in minimal microvascular resistance and decrease in microvascular function, which is represented by a decreased MRR and is independent of atherosclerosis. The age-dependent decrease in MRR was present in both patients with and without CMD and was most evident in patients with smooth coronary arteries.

ANOCA patients with and without coronary vasomotor dysfunction present with limited electrocardiographic remodeling.

Background: Coronary vasomotor dysfunction (CVDys) comprises coronary vasospasm (CVS) and/or coronary microvascular dysfunction (CMD) and is highly prevalent in patients with angina and non-obstructive coronary artery disease (ANOCA). Invasive coronary function testing (CFT) to diagnose CVDys is becoming more common, enabling pathophysiologic research of CVDys. This study aims to explore the electrophysiological characteristics of ANOCA patients with CVDys. Methods: We collected pre-procedural 12-lead electrocardiograms of ANOCA patients with CVS (n = 35), CMD (n = 24), CVS/CMD (n = 26) and patients without CVDys (CFT-, n = 23) who participated in the NL-CFT registry and underwent CFT. Heart axis and conduction times were compared between patients with CVS, CMD or CVS/CMD and patients without CVDys. Results: Heart axis, heart rate, PQ interval and QRS duration were comparable between the groups. A small prolongation of the QT-interval corrected with Bazett (QTcB) and Fridericia (QTcF) was observed in patients with CVDys compared to patients without CVDys (CVS vs CFT-: QTcB = 422 ± 18 vs 414 ± 18 ms (p = 0.14), QTcF = 410 ± 14 vs 406 ± 12 ms (p = 0.21); CMD vs CFT-: QTcB = 426 ± 17 vs 414 ± 18 ms (p = 0.03), QTcF = 413 ± 11 vs 406 ± 12 ms (p = 0.04); CVS/CMD vs CFT-: QTcB = 424 ± 17 vs 414 ± 18 ms (p = 0.05), QTcF = 414 ± 14 vs 406 ± 12 ms (p = 0.04)). Conclusions: Pre-procedural 12-lead electrocardiograms were comparable between patients with and without CVDys undergoing CFT except for a slightly longer QTc interval in patients with CVDys compared to patients without CVDys, suggesting limited cardiac remodeling in patients with CVDys.

Continuous Versus Bolus Thermodilution-Derived Coronary Flow Reserve and Microvascular Resistance Reserve and Their Association With Angina and Quality of Life in Patients With Angina and Nonobstructive Coronaries: A Head-to-Head Comparison.

Background Coronary flow reserve (CFR) and microvascular resistance reserve (MRR) are physiological parameters to assess coronary microvascular dysfunction. CFR and MRR can be assessed using bolus or continuous thermodilution, and the correlation between these methods has not been clarified. Furthermore, their association with angina and quality of life is unknown. Methods and Results In total, 246 consecutive patients with angina and nonobstructive coronary arteries from the multicenter Netherlands Registry of Invasive Coronary Vasomotor Function Testing (NL-CFT) were investigated. The 36-item Short Form Health Survey Quality of Life and Seattle Angina questionnaires were completed by 153 patients before the invasive measurements. CFR and MRR were measured consecutively with bolus and continuous thermodilution. Mean continuous thermodilution-derived coronary flow reserve (CFRabs) was significantly lower than mean bolus thermodilution-derived coronary flow reserve (CFRbolus) (2.6±1.0 versus 3.5±1.8; P<0.001), with a modest correlation (ρ=0.305; P<0.001). Mean continuous thermodilution-derived microvascular resistance reserve (MRRabs) was also significantly lower than mean bolus thermodilution-derived MRR (MRRbolus) (3.1±1.1 versus 4.2±2.5; P<0.001), with a weak correlation (ρ=0.280; P<0.001). CFRbolus and MRRbolus showed no correlation with any of the angina and quality of life domains, whereas CFRabs and MRRabs showed a significant correlation with physical limitation (P=0.005, P=0.009, respectively) and health (P=0.026, P=0.012). In a subanalysis in patients in whom spasm was excluded, the correlation further improved (MRRabs versus physical limitation: ρ=0.363; P=0.041, MRRabs versus physical health: ρ=0.482; P=0.004). No association with angina frequency and stability was found. Conclusions Absolute flow measurements using continuous thermodilution to calculate CFRabs and MRRabs weakly correlate with, and are lower than, the surrogates CFRbolus and MRRbolus. Absolute flow parameters showed a relationship with physical complaints. No relationship with angina frequency and stability was found.

Outcomes with P2Y12 inhibitor monotherapy after PCI according to bleeding risk: A Bayesian meta-analysis.

BACKGROUND: P2Y12 inhibitor monotherapy is a promising novel strategy to reduce bleeding complications compared to dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI). In order to personalise treatment with DAPT based on patients' bleeding risk, we compared outcomes after PCI between P2Y12 inhibitor monotherapy and DAPT according to bleeding risk. METHODS: A search for randomized clinical trials (RCTs) comparing P2Y12 inhibitor monotherapy after a short period of DAPT to standard DAPT after PCI was performed. Outcome differences between treatment groups regarding major bleedings, major adverse cardiac and cerebral events (MACCE) and net adverse clinical events (NACE) were assessed with hazard ratios (HRs) and corresponding credible intervals (CrI) according a Bayesian random effects model in patients with and without high bleeding risk (HBR). RESULTS: Five RCTs including 30,084 patients were selected. P2Y12 inhibitor monotherapy compared to DAPT reduced major bleedings in the total population (HR: 0.65, 95 % CrI: 0.44 to 0.92). The HRs of the HBR and non-HBR subgroups showed a similar reduction of bleedings for monotherapy (HBR: HR 0.66, 95 % CrI: 0.25 to 1.74; non-HBR: HR 0.63, 95 % CrI: 0.36 to 1.09). No notable differences between treatments on MACCE and NACE were observed in either sub-group or in the total population. CONCLUSIONS: Regardless of bleeding risk, P2Y12 inhibitor monotherapy is the favourable choice after PCI regarding major bleedings and does not increase ischemic events compared to DAPT. This suggests that bleeding risk is not decisive when considering P2Y12 inhibitor monotherapy.

Microvascular Resistance Reserve to Assess Microvascular Dysfunction in ANOCA Patients.

BACKGROUND: Microvascular resistance reserve (MRR) is a new index to assess coronary microvascular (dys)function, which can be easily measured invasively using continuous thermodilution. In contrast to coronary flow reserve (CFR), MRR is independent of epicardial coronary disease and hemodynamic variations. Its measurement is accurate, reproducible, and operator independent. OBJECTIVES: The aim of this study was to establish the range of normal values for MRR and to determine an optimal cutoff point. METHODS: In this exploratory study in 214 patients with angina and no obstructive coronary artery disease, after excluding significant epicardial disease, all physiological parameters, such as fractional flow reserve, index of microvascular resistance, CFR, absolute blood flow, absolute microvascular resistance, and MRR, were measured. On the basis of concordant positive or concordant negative results of index of microvascular resistance and CFR, subgroups of patients were defined with high probability of either normal (n = 122) or abnormal (n = 24) microcirculatory function, and MRR was studied in these groups. RESULTS: Mean MRR in the "normal" group was 3.4 compared with a mean MRR of 1.9 in the "abnormal" group; these values were significantly different between the groups. MRR >2.7 ruled out coronary microvascular dysfunction (CMD) with a certainty of 96%, whereas MRR <2.1 indicated the presence of CMD with a similar high certainty of 96%. CONCLUSIONS: MRR is a suitable index to distinguish the presence or absence of CMD in patients with angina and no obstructive coronary artery disease. The present data indicate that an MRR of 2.7 virtually excludes the presence of CMD, while an MRR value <2.1 confirms its presence.

Contemporary and future invasive coronary vasomotor function testing and treatment in patients with ischaemia with no obstructive coronary arteries.

In the current review, we emphasize the importance of diagnostics and therapy in patients with ischaemia with no obstructive coronary arteries (INOCA). The importance of the diagnostic coronary function test (CFT) procedure is described, including future components including angiography-derived physiology and invasive continuous thermodilution. Furthermore, the main components of treatment are discussed. Future directions include the national registration ensuring a high quality of INOCA care, besides a potential source to improve our understanding of pathophysiology in the various phenotypes of coronary vascular dysfunction, the diagnostic CFT procedure, and treatment.

Efficacy of Diltiazem to Improve Coronary Vasomotor Dysfunction in ANOCA: The EDIT-CMD Randomized Clinical Trial.

BACKGROUND: Diltiazem is recommended and frequently prescribed in patients with angina and nonobstructive coronary artery disease (ANOCA), suspected of coronary vasomotor dysfunction (CVDys). However, studies substantiating its effect is this patient group are lacking. OBJECTIVES: The randomized, placebo-controlled EDIT-CMD (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial) evaluated the effect of diltiazem on CVDys, as assessed by repeated coronary function testing (CFT), angina, and quality of life. METHODS: A total of 126 patients with ANOCA were included and underwent CFT. CVDys, defined as the presence of vasospasm (after intracoronary acetylcholine provocation) and/or microvascular dysfunction (coronary flow reserve: <2.0, index of microvascular resistance: ≥25), was confirmed in 99 patients, of whom 85 were randomized to receive either oral diltiazem or placebo up to 360 mg/d. After 6 weeks, a second CFT was performed. The primary end point was the proportion of patients having a successful treatment, defined as normalization of 1 abnormal parameter of CVDys and no normal parameter becoming abnormal. Secondary end points were changes from baseline to 6-week follow-up in vasospasm, index of microvascular resistance, coronary flow reserve, symptoms (Seattle Angina Questionnaire), or quality of life (Research and Development Questionnaire 36). RESULTS: In total, 73 patients (38 diltiazem vs 35 placebo) underwent the second CFT. Improvement of the CFT did not differ between the groups (diltiazem vs placebo: 21% vs 29%; P = 0.46). However, more patients on diltiazem treatment progressed from epicardial spasm to microvascular or no spasm (47% vs 6%; P = 0.006). No significant differences were observed between the diltiazem and placebo group in microvascular dysfunction, Seattle Angina Questionnaire, or Research and Development Questionnaire 36. CONCLUSIONS: This first performed randomized, placebo-controlled trial in patients with ANOCA showed that 6 weeks of therapy with diltiazem, when compared with placebo, did not substantially improve CVDys, symptoms, or quality of life, but diltiazem therapy did reduce prevalence of epicardial spasm. (Efficacy of Diltiazem to Improve Coronary Microvascular Dysfunction: A Randomized Clinical Trial [EDIT-CMD]; NCT04777045).

Case report: epipericardial fat necrosis-a rare cause of chest pain.

BACKGROUND: Epipericardial fat necrosis (EFN) is a rare cause of chest pain, which is often unrecognized. CASE SUMMARY: A 58-year-old man previously known with a transient ischaemic attack presented with a sharp, substernal chest pain. Pulmonary embolism was ruled out by computed tomography (CT) angiography. However, CT angiography revealed an inhomogeneous epipericardial mass. On cardiovascular magnetic resonance imaging, the mass had an inhomogeneous signal intensity without infiltration of surrounding tissue. Late gadolinium enhancement imaging showed subtle hyperenhancement. Tissue characterization by means of parametric mapping revealed very low native T1 relaxation times and increased T2 relaxation times. In conclusion, the epipericardial mass showed fibrofatty inflammatory markers, suggestive of EFN. The chest pain resolved spontaneously. Follow-up CT 3 months later showed a marked regression of the mass which confirmed the diagnosis EFN. DISCUSSION: Epipericardial fat necrosis is a benign and self-limiting inflammatory cause of chest pain, which can be diagnosed with multi-modality imaging and must not be overlooked in the differential diagnosis of patients with acute pleuritic chest pain.

Features of atherosclerosis in patients with angina and no obstructive coronary artery disease.

BACKGROUND: An association between atherosclerosis and coronary vasospasm has previously been suggested. However, to date, no conclusive data on the whole spectrum of these disorders have been published. AIMS: This study aimed to define specific morphological features of atherosclerosis in patients with angina and no obstructive coronary artery disease (ANOCA) due to coronary vasospasm. METHODS: From February 2019 to January 2020, we enrolled 75 patients referred to our laboratory for a coronary function test (CFT) due to ANOCA and suspected coronary vasomotor dysfunction. The CFT consisted of an acetylcholine test and a physiology assessment with hyperaemic indexes using adenosine. Patients were divided into two groups according to the presence or absence of coronary vasospasm triggered by acetylcholine (ACH+ and ACH-, respectively). In addition, optical coherence tomography (OCT) was performed to assess the lipid index (LI), a surrogate for lipid area, and the prevalence of markers of plaque vulnerability. RESULTS: ACH+ patients had a higher LI than ACH- patients (LI: 819.85 [460.95-2489.03] vs 269.95 [243.50-878.05], respectively, p=0.03), and a higher prevalence of vulnerable plaques (66% vs 38%, p=0.04). Moreover, ACH+ patients showed a higher prevalence of neovascularisation compared to ACH- subjects (37% vs 6%, p=0.02) and a trend towards a higher prevalence of all individual markers, in particular thin-cap fibroatheroma (20% vs 0%, p=0.06). No differences were detected between patterns of coronary vasospasm. CONCLUSIONS: The presence of coronary vasospasm, regardless of its phenotype, is associated with higher lipid burden, plaque vulnerability and neovascularisation.

Relation Between Coronary Tortuosity and Vasomotor Dysfunction in Patients Without Obstructed Coronaries?

Background: A large proportion of patients with angina and no obstructive coronary artery disease (ANOCA) has underlying coronary vasomotor dysfunction (CVDys), which can be diagnosed by a coronary function test (CFT). Coronary tortuosity is a common angiographic finding during the CFT. Yet, no data exist on the association between vasomotor dysfunction and coronary tortuosity. Aim: To investigate the association between CVDys and coronary tortuosity in patients with ANOCA Methods: All consecutive ANOCA patients who underwent clinically indicated CFT between February 2019 and November 2020 were included. CFT included acetylcholine spasm testing to diagnose epicardial or microvascular spasm, and adenosine testing to diagnose microvascular dysfunction (MVD). MVD was defined as an index of microvascular resistance (IMR) ≥ 25 and/or coronary flow reserve (CFR) <2.0. Coronary tortuosity, was scored (no, mild, moderate or severe) based on the angles of the curvatures in the left anterior descending (LAD) artery on angiography. Results: In total, 228 patients were included (86% female, mean age 56 ± 9 years). We found coronary artery spasm in 81% of patients and MVD in 45% of patients (15%: abnormal CFR, 30%: abnormal IMR). There were 73 patients with no tortuosity, 114 with mild tortuosity, 41 with moderate tortuosity, and no patients with severe tortuosity. No differences were found in cardiovascular risk factors or medical history, and the prevalence of CVDys did not differ between the no tortuosity, mild tortuosity and moderate tortuosity group (82, 82, and 85%, respectively). Conclusion: In this study, CVDys was not associated with coronary tortuosity. Future experimental and clinical studies on the complex interplay between coronary tortuosity, wall shear stress, endothelial dysfunction and coronary flow are warranted.

Coronary atherosclerosis scoring with semiquantitative CCTA risk scores for prediction of major adverse cardiac events: Propensity score-based analysis of diabetic and non-diabetic patients.

AIMS: We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders. METHODS: Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability. RESULTS: A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265). CONCLUSION: Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone.

Superior Risk Stratification With Coronary Computed Tomography Angiography Using a Comprehensive Atherosclerotic Risk Score.

OBJECTIVES: This study was designed to assess the prognostic value of a new comprehensive coronary computed tomography angiography (CTA) score compared with the stenosis severity component of the Coronary Artery Disease-Reporting and Data System (CAD-RADS). BACKGROUND: Current risk assessment with coronary CTA is mainly focused on maximal stenosis severity. Integration of plaque extent, location, and composition in a comprehensive model may improve risk stratification. METHODS: A total of 2,134 patients with suspected but without known CAD were included. The predictive value of the comprehensive CTA score (ranging from 0 to 42 and divided into 3 groups: 0 to 5, 6 to 20, and >20) was compared with the CAD-RADS combined into 3 groups (0% to 30%, 30% to 70% and ≥70% stenosis). Its predictive performance was internally and externally validated (using the 5-year follow-up dataset of the CONFIRM [Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry], n = 1,971). RESULTS: The mean age of patients was 55 ± 13 years, mean follow-up 3.6 ± 2.8 years, and 130 events (myocardial infarction or death) occurred. The new, comprehensive CTA score showed strong and independent predictive value using the Cox proportional hazard analysis. A model including clinical variables plus comprehensive CTA score showed better discrimination of events compared with a model consisting of clinical variables plus CAD-RADS (0.768 vs. 0.742, p = 0.001). Also, the comprehensive CTA score correctly reclassified a significant proportion of patients compared with the CAD-RADS (net reclassification improvement 12.4%, p < 0.001). Good predictive accuracy was reproduced in the external validation cohort. CONCLUSIONS: The new comprehensive CTA score provides better discrimination and reclassification of events compared with the CAD-RADS score based on stenosis severity only. The score retained similar prognostic accuracy when externally validated. Anatomic risk scores can be improved with the addition of extent, location, and compositional measures of atherosclerotic plaque. (Comprehensive CTA risk score calculator is available at: http://18.224.14.19/calcApp/).

Gender-Specific Differences in All-Cause Mortality Between Incomplete and Complete Revascularization in Patients With ST-Elevation Myocardial Infarction and Multi-Vessel Coronary Artery Disease.

The best revascularization strategy (complete vs incomplete revascularization) in patients with ST-elevation myocardial infarction (STEMI) is still debated. The interaction between gender and revascularization strategy in patients with STEMI on all-cause mortality is uncertain. The aim of the present study was to evaluate gender-specific difference in all-cause mortality between incomplete and complete revascularization in patients with STEMI and multi-vessel coronary artery disease. The study population consisted of 375 men and 115 women with a first STEMI and multi-vessel coronary artery disease without cardiogenic shock at admission or left main stenosis. The 30-day and 5-year all-cause mortality was examined in patients categorized according to gender and revascularization strategy (incomplete and complete revascularization). Within the first 30 days, men and women with incomplete revascularization were associated with higher mortality rates compared with men with complete revascularization. However, the gender-strategy interaction variable was not independently associated with 30-day mortality after STEMI when corrected for baseline characteristics and angiographic features. Within the survivors of the first 30 days, men with incomplete revascularization (compared with men with complete revascularization) were independently associated with all-cause mortality during 5 years of follow-up (hazard ratios 3.07, 95% confidence interval 1.24;7.61, p = 0.016). In contrast, women with incomplete revascularization were not independently associated with 5-year all-cause mortality (hazard ratios 0.60, 95% confidence interval 0.14;2.51, p = 0.48). In conclusion, no gender-strategy differences occurred in all-cause mortality within 30 days after STEMI. However, in the survivors of the first 30 days, incomplete revascularization in men was independently associated with all-cause mortality during 5-year follow-up, but this was not the case in women.

Long-term prognostic value of single-photon emission computed tomography myocardial perfusion imaging after primary PCI for STEMI.

Aims: The aim of this study was to determine the long-term prognostic value of infarct size and myocardial ischaemia on single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Methods and results: In total, 1092 STEMI patients who underwent primary PCI and SPECT MPI within 1-6 months were included (median follow-up time of 6.9 years). In the entire cohort, SPECT infarct size was independently associated with the composite of cardiac death or reinfarction [hazard ratio (HR) per 10% increase in summed rest score 1.33; 95% confidence interval (95% CI) 1.12-1.58; P = 0.001], whereas myocardial ischaemia was not (HR per 5% increase in summed difference score 1.18; 95% CI 0.94-1.48; P = 0.16). Addition of SPECT infarct size to a model including the clinical variables provided significant incremental prognostic value for the prediction of cardiac death or reinfarction (global χ2 13.8 vs. 24.2; P = 0.002), whereas addition of SPECT ischaemia did not add significantly (global χ2 24.2 vs. 25.6; P = 0.24). In the subgroup of patients with left ventricular ejection fraction (LVEF) ≤ 45%, SPECT infarct size was independently associated with cardiac death or reinfarction (HR 1.59; 95% CI 1.15-2.22; P = 0.006), whereas in patients with LVEF > 45%, only SPECT ischaemia was independently associated with cardiac death or reinfarction (HR 1.28; 95% CI 1.00-1.63; P = 0.050). Conclusion: In patients with first STEMI and primary PCI, SPECT infarct size was independently associated with cardiac death and/or reinfarction, whereas myocardial ischaemia was not. In patients with LVEF ≤ 45%, SPECT infarct size was independently associated with cardiac death or reinfarction, whereas myocardial ischaemia was not. Conversely, in patients with LVEF > 45%, only SPECT ischaemia was independently associated with cardiac death or reinfarction.

Different manifestation of irradiation induced coronary artery disease detected with coronary computed tomography compared with matched non-irradiated controls.

BACKGROUND AND PURPOSE: Patients who received chest irradiation for treatment of a malignancy are at increased risk for the development of coronary artery atherosclerosis. Little is known about the anatomical coronary artery plaque characteristics of irradiation induced coronary artery disease (CAD). This study aimed to evaluate potential differences in the presence, extent, severity, composition and location of CAD in patients treated with mediastinal irradiation compared with non-irradiated controls matched on age, gender and cardiovascular risk factors. MATERIAL AND METHODS: Seventy-nine asymptomatic Hodgkin and non-Hodgkin lymphoma survivors, all treated with mediastinal irradiation with or without chemotherapy, who underwent coronary computed tomography angiography (CTA) to exclude or detect CAD were included. Patients were 1:3 matched with non-irradiated controls (n=237) for age, gender, diabetes, hypertension, hypercholesterolemia, family history of CAD and currently smoking. Mean age at cancer diagnosis was 26±9years and age at the time of coronary CTA was 45±11years. RESULTS: More patients had an abnormal CTA (defined as any coronary artery atherosclerosis): 59% vs. 36% (P<0.001) and significantly more patients had two vessel CAD: 10% vs. 6% and three vessel/left main CAD: 24% vs. 9% compared with controls (overall P<0.001). The maximum stenosis severity among patients was less often <30% (53% vs. 68%) and more often >70% (7% vs. 0%) (overall P=0.001). Patients had more coronary artery plaques in proximal coronary artery segments: left main (17% vs. 6%, P=0.004), proximal left anterior descending artery (30% vs. 16%, P=0.004), proximal right coronary artery (25% vs 10%, P<0.001) and proximal left circumflex artery (14% vs 6%, P=0.022), whereas the number of plaques in non-proximal segments did not differ between groups. CONCLUSIONS: Hodgkin and non-Hodgkin lymphoma survivors treated with mediastinal irradiation with or without chemotherapy showed a higher presence, greater severity, larger extent and more proximally located CAD compared with age, gender and risk factor matched non-irradiated controls. These findings represent features of higher risk CAD and may explain the worse cardiovascular outcome after chest irradiation.

Impact of computed tomography myocardial perfusion following computed tomography coronary angiography on downstream referral for invasive coronary angiography, revascularization and, outcome at 12 months.

AIMS: The aim of this study was to assess the impact of adding stress computed tomography (CT) myocardial perfusion (CTP) to coronary CT angiography (CTA) on downstream referral for invasive coronary angiography (ICA), revascularization, and outcome in patients presenting with new-onset chest pain. METHODS AND RESULTS: Three hundred and eighty-four patients were referred for cardiac CT. Patients with lesions ≥50% stenosis underwent subsequently stress CTP. Perfusion scans were considered abnormal if a defect was observed in ≥ 1 segment. Downstream performance of ICA, revascularization, and the occurrence of major cardiovascular events (death, non-fatal myocardial infarction, and unstable angina requiring urgent revascularization) were assessed within 12 months. In total, 119 patients showed ≥50% stenosis on coronary CTA; stress CTP was normal in 61 patients, abnormal in 38 patients and was not performed in 20 patients. After normal stress CTP, 19 (31%) patients underwent ICA and 9 (15%) underwent revascularization. After abnormal stress CTP, 36 (95%) patients underwent ICA and 29 (76%) revascularizations were performed. Multivariable analyses showed a five-fold reduction in likelihood of proceeding to ICA when a normal stress CTP was added to a coronary CTA showing obstructive CAD. Major cardiovascular event rates at 12 months for patients with obstructive CAD and normal stress CTP (N = 61) were low: 1 myocardial infarction, 1 urgent revascularization, and 1 non-cardiac death. CONCLUSION: The performance of stress CTP in patients with obstructive CAD at coronary CTA in the same setting is feasible and reduces the referral rate for ICA and revascularization. Secondly, the occurrence of major cardiovascular events at 12 months follow-up in patients with normal stress CTP is low.

Long-Term Prognosis of Patients With Intramural Course of Coronary Arteries Assessed With CT Angiography.

OBJECTIVES: The aim of the present study was to evaluate, in low-to-intermediate pre-test probability patients who were referred for coronary computed tomography angiography (CTA) and did not show obstructive coronary artery disease (CAD), whether an intramural course of a coronary artery is associated with worse outcome compared with patients without an intramural course of the coronary arteries. BACKGROUND: The prognostic value of an intramural course of the coronary arteries on coronary CTA in patients without obstructive CAD is not well-known. METHODS: The study population consisted of 947 patients with a low-to-intermediate pre-test probability who were referred for coronary CTA and who did not have obstructive CAD. During follow-up, the occurrence of unstable angina pectoris that required hospitalization, nonfatal myocardial infarction, and all-cause mortality was evaluated. RESULTS: On coronary CTA, 210 patients (22%) had an intramural course of a coronary artery. The median depth of the intramural course was 1.9 mm (interquartile range: 1.4 to 2.6 mm). In 84 patients (40%), the depth of the intramural course was considered deep (>2 mm surrounded by myocardium). During a median follow-up of 4.9 years (interquartile range: 3.2 to 6.9 years), a total of 43 events occurred: hospitalization due to unstable angina pectoris in 13 patients (1.4%); 7 patients (0.7%) had a nonfatal myocardial infarction; and 23 patients died (2.4%). The 6-year cumulative event rate of unstable angina pectoris requiring hospitalization (0.0% vs. 1.1%), nonfatal myocardial infarction (0.5% vs. 0.4%), all-cause mortality (1.9% vs. 2.2%) as well as the combined endpoint of all 3 events (2.4% vs. 3.7%) was similar in patients with and without an intramural course of a coronary artery. CONCLUSIONS: In patients without obstructive CAD on coronary CTA, the presence of an intramural course of a coronary artery was not associated with worse outcome.