Association between troponin level and medium-term mortality in 20 000 hospital patients.

INTRODUCTION: Cardiac troponin (cTn) concentrations above the manufacturer recommended upper limit of normal (ULN) are frequently seen in hospital patients without a clinical presentation consistent with type 1 myocardial infarction, and the significance of this is uncertain. The aim of this study was to assess the relationship between medium-term mortality and cTn concentration in a large consecutive hospital population, regardless of whether there was a clinical indication for performing the test. METHOD: This prospective observational study included 20 000 consecutive in-hospital and outpatient patients who had a blood test for any reason at a large teaching hospital, and in whom a hs-cTnI assay was measured, regardless of the original clinical indication. Mortality was obtained via NHS Digital. RESULTS: A total of 20 000 patients were included in the analysis and 18 282 of these (91.4%) did not have a clinical indication for cardiac troponin I (cTnI) testing. Overall, 2825 (14.1%) patients died at a median of 809 days. The mortality was significantly higher if the cTnI concentration was above the ULN (45.3% vs 12.3% p<0.001 log rank). Multivariable Cox analysis demonstrated that the log10 cTnI concentration was independently associated with mortality (HR 1.76 (95% CI 1.65 to 1.88)). Landmark analysis, excluding deaths within 30 days, showed the relationship between cTnI concentration and mortality persisted. CONCLUSION: In a large, unselected hospital population, in 91.4% of whom there was no clinical indication for testing, cTnI concentration was independently associated with medium-term cardiovascular and non-cardiovascular mortality in the statistical model tested.

Global Circumferential and Radial Strain Among Patients With Immune Checkpoint Inhibitor Myocarditis.

BACKGROUND: Global circumferential strain (GCS) and global radial strain (GRS) are reduced with cytotoxic chemotherapy. There are limited data on the effect of immune checkpoint inhibitor (ICI) myocarditis on GCS and GRS. OBJECTIVES: This study aimed to detail the role of GCS and GRS in ICI myocarditis. METHODS: In this retrospective study, GCS and GRS from 75 cases of patients with ICI myocarditis and 50 ICI-treated patients without myocarditis (controls) were compared. Pre-ICI GCS and GRS were available for 12 cases and 50 controls. Measurements were performed in a core laboratory blinded to group and time. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death. RESULTS: Cases and controls were similar in age (66 ± 15 years vs 63 ± 12 years; P = 0.20), sex (male: 73% vs 61%; P = 0.20) and cancer type (P = 0.08). Pre-ICI GCS and GRS were also similar (GCS: 22.6% ± 3.4% vs 23.5% ± 3.8%; P = 0.14; GRS: 45.5% ± 6.2% vs 43.6% ± 8.8%; P = 0.24). Overall, 56% (n = 42) of patients with myocarditis presented with preserved left ventricular ejection fraction (LVEF). GCS and GRS were lower in myocarditis compared with on-ICI controls (GCS: 17.5% ± 4.2% vs 23.6% ± 3.0%; P < 0.001; GRS: 28.6% ± 6.7% vs 47.0% ± 7.4%; P < 0.001). Over a median follow-up of 30 days, 28 cardiovascular events occurred. A GCS (HR: 4.9 [95% CI: 1.6-15.0]; P = 0.005) and GRS (HR: 3.9 [95% CI: 1.4-10.8]; P = 0.008) below the median was associated with an increased event rate. In receiver-operating characteristic (ROC) curves, GCS (AUC: 0.80 [95% CI: 0.70-0.91]) and GRS (AUC: 0.76 [95% CI: 0.64-0.88]) showed better performance than cardiac troponin T (cTnT) (AUC: 0.70 [95% CI: 0.58-0.82]), LVEF (AUC: 0.69 [95% CI: 0.56-0.81]), and age (AUC: 0.54 [95% CI: 0.40-0.68]). Net reclassification index and integrated discrimination improvement demonstrated incremental prognostic utility of GRS over LVEF (P = 0.04) and GCS over cTnT (P = 0.002). CONCLUSIONS: GCS and GRS are lower in ICI myocarditis, and the magnitude of reduction has prognostic significance.

Impact of Adenosine on Wavefront Propagation in Persistent Atrial Fibrillation: Insights From Global Noncontact Charge Density Mapping of the Left Atrium.

Background Adenosine shortens action potential duration and refractoriness and provokes atrial fibrillation. This study aimed to evaluate the effect of adenosine on mechanisms of wavefront propagation during atrial fibrillation. Methods and Results The study included 22 patients undergoing catheter ablation for persistent atrial fibrillation. Left atrial mapping was performed using the AcQMap charge density system before and after administration of intravenous adenosine at 1 or more of 3 time points during the procedure (before pulmonary vein isolation, after pulmonary vein isolation, and after nonpulmonary vein isolation ablation). Wave-front propagation patterns were evaluated allowing identification and quantification of localized rotational activation (LRA), localized irregular activation, and focal firing. Additional signal processing was performed to identify phase singularities and calculate global atrial fibrillation cycle length and dominant frequency. A total of 35 paired maps were analyzed. Adenosine shortened mean atrial fibrillation cycle length from 181.7±14.3 to 165.1±16.3, (mean difference 16.6 ms; 95% CI, 11.3-21.9, P<0.0005) and increased dominant frequency from 6.0±0.7 Hz to 6.6±0.8 Hz (95% CI, 0.4-0.9, P<0.0005). This was associated with a 50% increase in the number of LRA occurrences (16.1±7.6-24.2±8.1; mean difference 8.1, 95% CI, 4.1-12, P<0.0005) as well as a 20% increase in the number of phase singularities detected (30.1±7.8-36.6±9.3; mean difference 6.5; 95% CI, 2.6-10.0, P=0.002). The percentage of left atrial surface area with LRA increased with adenosine and 42 of 70 zones (60%) with highest density of LRA coincided with high density LRA zones at baseline with only 28% stable across multiple maps. Conclusions Adenosine accelerates atrial fibrillation and promotes rotational activation patterns with no impact on focal activation. There is little evidence that rotational activation seen with adenosine represents promising targets for ablation aimed at sites of stable arrhythmogenic sources in the left atrium.

Treatment of Non-Culprit Lesions in STEMI: An Incomplete Journey.

Approximately 50% of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) have multivessel coronary artery disease (CAD). A number of randomized studies (Table 1) have all shown that complete revascularization (CR), either at the time of primary percutaneous coronary revascularization (PPCI) or within 45 days of the index admission, is safe and reduces the risk of repeat coronary revascularization and myocardial infarction (MI), particularly in the non-infarct related artery (NIRA). Despite consistently showing clinical benefit for CR, the results from the trials show variations in what drives this effect. Specifically, no study to date has provided a mechanistic insight as to how complete revascularization of chronic bystander disease may lead to the observed clinical benefit. Indeed, the randomized studies, through the variable nature of their results (reduction in MI versus revascularization etc.), have suggested the possibility that there are differing mechanisms for the observed benefit. In this review, we summarize the evidence base, highlight the limitations, and make the case that we need to understand the mechanism(s) underpinning the advantage of revascularization of NIRA in order to establish which patients are most likely to benefit. Without this insight, the current "one size fits all" approach may lead us in the wrong direction.

Relation of High-Sensitivity Troponin to 1 Year Mortality in 20,000 Consecutive Hospital Patients Undergoing a Blood Test for Any Reason.

This was an observational study of the 1-year outcomes of the 20,000 patients included in the original CHARIOT study. The aim of the study was to assess the association between high sensitivity troponin I (hs-cTnI) concentration and 1 year mortality in this cohort. The original CHARIOT study included a consecutive cohort of in- and out-patients undergoing blood tests for any reason. Hs-cTnI concentrations were measured regardless of whether the clinician requested them. These results were nested and not revealed to the team unless requested for clinical reasons. One year mortality data was obtained from NHS Digital as originally planned. Overall, 1782 (8.9%) patients had died at 1 year. Multivariable Cox regression analysis showed that a hs-cTnI concentration above the upper limit of normal was independently associated with the hazard of mortality (HR 2.23; 95% confidence intervals 1.97 to 2.52). Furthermore, the log (10) hs-cTnI concentration was independently associated with the hazard of 1 year mortality (HR 1.77; 95% confidence intervals 1.64 to 1.91). In conclusion, in a large, unselected hospital population of both in- and out-patients, in 18,282 (91.4%) of whom there was no clinical indication for testing, hs-cTnI concentration was associated with 1 year mortality.

Spatial and temporal variability of rotational, focal, and irregular activity: Practical implications for mapping of atrial fibrillation.

BACKGROUND: Charge density mapping of atrial fibrillation (AF) reveals dynamic localized rotational activation (LRA), irregular activation (LIA) and focal firing (FF). Their spatial stability, conduction characteristics and the optimal duration of mapping required to reveal these phenomena and has not been explored. METHODS: Bi-atrial mapping of AF propagation was undertaken using AcQMap (Acutus Medical) and variability of activation patterns quantified up to a duration of 30 s. The frequency of each pattern was quantified at each unique point of the chamber over two separate 30-s recordings before ablation and R2 calculated to quantify spatial stability. Regions with the highest frequency were identified at increasing time durations and compared to the result over 30 s using Cohen's kappa. Properties of regions with the most stable patterns were assessed during sinus rhythm and extrastimulus pacing. RESULTS: In 21 patients, 62 paired LA and RA maps were obtained. LIA was highly spatially stable with R2 between maps of 0.83 (0.71-0.88) compared to 0.39 (0.24-0.57), and 0.64 (0.54-0.73) for LRA and FF, respectively. LIA was most temporally stable with a kappa of >0.8 reached by 12 s. LRA showed greatest variability with kappa >0.8 only after 22 s. Regions of LIA were of normal voltage amplitude (1.09 mv) but showed increased conduction heterogeneity during extrastimulus pacing (p = .0480). CONCLUSION: Irregular activation patterns characterized by changing wavefront direction are temporally and spatially stable in contrast with LRA that is transient with least spatial stability. Focal activation appears of intermediate stability. Regions of LIA show increased heterogeneity following extrastimulus pacing and may represent fixed anatomical substrate.

Electrocardiographic features of immune checkpoint inhibitor associated myocarditis.

BACKGROUND: Myocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis. METHODS: From an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested. RESULTS: Both the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, p<0.001 and p=0.009, respectively). In contrast, the QTc interval at the time of myocarditis (435±39 ms) was not increased compared with pre-myocarditis baseline (422±27 ms, p=0.42). A prolonged QRS duration conferred an increased risk of subsequent MACE (HR 3.28, 95% CI 1.98 to 5.62, p<0.001). After adjustment, each 10 ms increase in the QRS duration conferred a 1.3-fold increase in the odds of MACE (95% CI 1.07 to 1.61, p=0.011). Conversely, there was no association between the QTc interval and MACE among men (HR 1.33, 95% CI 0.70 to 2.53, p=0.38) or women (HR 1.48, 95% CI 0.61 to 3.58, p=0.39). CONCLUSIONS: The QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification.

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis.

BACKGROUND: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited. OBJECTIVES: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis. METHODS: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS: Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE. CONCLUSIONS: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.

Comparison of plaque distribution and wire-free functional assessment in patients with stable angina and non-ST elevation myocardial infarction: an optical coherence tomography and quantitative flow ratio study.

BACKGROUND: Data comparing plaque characteristics and wire-free physiological assessment in the target vessel in patients with stable angina versus acute coronary syndrome are sparse. Therefore, we investigated the difference in plaque distribution between stable angina and non-ST-elevation myocardial infarction (NSTEMI) and explored the relationship between target vessel vulnerability by optical coherence tomography (OCT) and wire-free functional assessment with quantitative flow ratio (QFR). METHODS: Patients with stable angina (n = 25) and NSTEMI (n = 24) were in the final prospective study cohort from the DECODE study (ClinicalTrials.gov, NCT02335086). All 5480 OCT frames in the region of interest were analyzed to study plaque morphology in the target vessel. QFR was analyzed from baseline coronary angiography before percutaneous coronary intervention. Vulnerable vessel score (VVS) was calculated from each plaque, and vessel QFR was then compared. RESULTS: Out of all frames, thin-cap fibroatheroma was common with NSTEMI compared to stable angina (10.9 versus 6.3%, P < 0.01), while fibrous plaque was more commonly seen with stable angina compared to NSTEMI (19.7 versus 14.4%, P < 0.01). Calcified plaque was similar in both clinical settings (approximately 6%). Regression analysis showed that segments with normal vessel walls were located significantly farther from the other plaque types. Longitudinal distances for plaque-type in NSTEMI were numerically greater than those for stable angina; however, the mean difference was less than 10 mm. The VVS had a significant inverse linear correlation with QFR (r = -0.34, P = 0.009). CONCLUSIONS: The plaque distribution by OCT between stable angina and NSTEMI was similar. Target vessel vulnerability was greater in patients with lower QFR value.

Distribution of contemporary sensitivity troponin in the emergency department and relationship to 30-day mortality: The CHARIOT-ED substudy.

BACKGROUND: Contemporary sensitivity troponin (cs-cTn) concentrations above the upper limit of normal (ULN) are seen in a wide range of clinical conditions and evidence is growing that suggests cs-cTn may be a biomarker of future morbidity and mortality. OBJECTIVES: Our aim was to test the hypothesis that cs-cTn, measured in the emergency department, may be a biomarker for 30-day mortality, irrespective of the patient's presentation. METHOD: In all 5,708 consecutive cases, contemporary sensitivity troponin I (cs-cTnI) was measured either as requested by the clinical team or as part of the study, in which case both the clinical team and the patient were unaware of the result. Basic demographics were available from the original study and 30-day mortality was derived from NHS Digital data. RESULTS: In patients whose cs-cTnI test was requested solely as part of the study, 30-day mortality increased with increasing cs-cTnI concentrations (0% with undetectable concentrations to 14.7% with concentrations above the ULN). Multivariable Cox regression analysis showed that log(10)cs-cTnI concentration was independently associated with 30-day mortality. CONCLUSION: Increasing cs-cTnI concentrations are associated with higher short-term mortality as well as length of stay. As such, cs-cTnI measurements may provide useful prognostic information.

Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis.

AIMS: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented. METHODS AND RESULTS: From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE. CONCLUSION: These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.

Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis.

BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis. OBJECTIVES: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis. METHODS: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death. RESULTS: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8). CONCLUSIONS: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF.

Fractional Flow Reserve Derived from Computed Tomography Coronary Angiography in the Assessment and Management of Stable Chest Pain: Rationale and Design of the FORECAST Trial.

BACKGROUND: Fractional flow reserve measurement based on computed tomography (FFRCT) is a novel, well validated, non-invasive method for determining the presence and extent of coronary artery disease (CAD) combined with a physiological assessment of vessel-specific ischemia in patients with chest pain. Previous studies indicate that FFRCT reduces the uptake of invasive angiography that shows no significant CAD, without compromising patient safety. The clinical effectiveness and economic impact of using FFRCT instead of other tests in the initial evaluation of patients with stable chest pain has not been tested in a randomized trial. METHODS: The FORECAST trial will randomise 1400 patients with stable chest pain to receive either FFRCT or routine clinical assessment as directed by the National Institute for Health and Care Excellence (NICE) CG95 guideline for Chest Pain of Recent Onset. The primary endpoint will be resource utilisation over the subsequent nine months, including non-invasive cardiac investigations, invasive coronary angiography, coronary revascularization, hospitalization for cardiac events, and the use of cardiac medications. Key pre-specified secondary endpoints will be major adverse cardiac events, angina severity, quality of life, patient satisfaction, time to definitive management plan, time to completion of initial evaluation, number of hospital attendances, and working days lost in patients who are in employment. CONCLUSION: The FORECAST randomized trial will assess the clinical and economic outcomes of using FFRCT as the primary test to evaluate patients presenting with stable chest pain.

Early Oxidative Stress Response in Patients with Severe Aortic Stenosis Undergoing Transcatheter and Surgical Aortic Valve Replacement: A Transatlantic Study.

Myocardial ischemia/reperfusion-related oxidative stress as a result of cardiopulmonary bypass is thought to contribute to the adverse clinical outcomes following surgical aortic valve replacement (SAVR). Although the acute response following this procedure has been well characterized, much less is known about the nature and extent of oxidative stress induced by the transcatheter aortic valve replacement (TAVR) procedure. We therefore sought to examine and directly compare the oxidative stress response in patients undergoing TAVR and SAVR. A total of 60 patients were prospectively enrolled in this exploratory study, 38 patients undergoing TAVR and 22 patients SAVR. Reduced and oxidized glutathione (GSH, GSSG) in red blood cells as well as the ferric-reducing ability of plasma (FRAP) and plasma concentrations of 8-isoprostanes were measured at baseline (S1), during early reperfusion (S2), and 6-8 hours (S3) following aortic valve replacement (AVR). TAVR and SAVR were successful in all patients. Patients undergoing TAVR were older (79.3 ± 9.5 vs. 74.2 ± 4.1 years; P < 0.01) and had a higher mean STS risk score (6.6 ± 4.8 vs. 3.2 ± 3.0; P < 0.001) than patients undergoing SAVR. At baseline, FRAP and 8-isoprostane plasma concentrations were similar between the two groups, but erythrocytic GSH concentrations were significantly lower in the TAVR group. After AVR, FRAP was markedly higher in the TAVR group, whereas 8-isoprostane concentrations were significantly elevated in the SAVR group. In conclusion, TAVR appears not to cause acute oxidative stress and may even improve the antioxidant capacity in the extracellular compartment.

Deoxyribonucleic Acid Repair Activity Is Associated with Healed Coronary Plaque Rupture by Optical Coherence Tomography.

Deoxyribonucleic acid (DNA) damage and repair signaling cascades are related to the development of atherosclerosis. Pathological studies have demonstrated that healed coronary plaque rupture (HCPR) contributes to plaque progression and predisposes to sudden ischemic cardiac death. The objective of this study is to investigate the relationship between HCPR detected by optical coherence tomography (OCT) and DNA ligase. Forty-two patients with both OCT and DNA ligase were prospectively enrolled. The population included patients with stable angina pectoris (SA) and non-ST-elevation myocardial infarction (NSTEMI). It was found that the prevalence of HCPR was greater in subjects with higher DNA ligase activity (correlation coefficient 0.36, p = 0.019). The presence of HCPR in patients with NSTEMI was greater than in patients with SA per OCT analysis; however, there was no statistical difference in this limited population (22.53% versus 12.83%, respectively, p = 0.116). DNA repair activity by DNA ligase was associated with HCPR in advanced coronary artery plaque by OCT.

DNA Damage and Repair in Patients With Coronary Artery Disease: Correlation With Plaque Morphology Using Optical Coherence Tomography (DECODE Study).

OBJECTIVE: The aim of this study was to examine DNA ligase activity and expression of DNA damage response pathway (DDR) genes in patients with stable angina (SA) and non-ST elevation myocardial infarction (NSTEMI) and determine whether they correlate with plaque morphology. BACKGROUND: Patients with coronary artery disease (CAD) have evidence of deoxyribonucleic acid (DNA) damage in peripheral blood mononuclear cells (PBMCs). It is unclear whether this represents excess damage or defective DNA repair activity. METHODS: DNA ligase activity and the expression of 22 DDR genes were measured in PBMCs of patients (both SA (n = 47) and NSTEMI (n = 42)) and in age and gender-matched controls (n = 35). Target lesion anatomical assessment was undertaken with frequency domain optical coherent tomography. RESULTS: DNA ligase activity was different across the three groups of patients (control = 119 ±â€¯53, NSTEMI = 115.6 ±â€¯85.1, SA = 81 ±â€¯55.7 units/g of nuclear protein; ANOVA p = 0.023). Pair wise comparison demonstrated that this significance is due to differences between the control and SA patients (p = 0.046). Genes involved in double strand break repair and nucleotide excision repair pathways were differentially expressed in patients with SA and NSTEMI. In SA patients, fibrocalcific plaques were strongly associated with GTSE1, DDB1, MLH3 and ERCC1 expression. By contrast, in NSTEMI patients the strongest association was observed between fibrous plaques and ATM and XPA expression. CONCLUSION: PBMCs from patients with CAD exhibit differences in DNA ligase activity and expression of DDR genes. Expression levels of certain DDR genes are strongly associated with plaque morphology and may play a role in plaque development and progression. Trial Registration Number URL: www.Clinicaltrials.gov; NCT02335086.