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.

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.

Changes in platelet function with inflammation in patients undergoing vascular surgery.

The role of platelets in ischaemic events is well established. Aspirin represents the default antiplatelet and blocks the metabolism of arachidonic acid (AA) at the cyclo-oxygenase enzyme (COX). AA is commonly used as a test of response to aspirin, but recent data raise uncertainty about the validity of this approach. Specifically, in some patients AA-induced clotting is not suppressed, but the level of COX-dependent AA metabolite, thromboxane B2 (TXB2) is negligible. Furthermore, AA-induced whole blood clotting varies dynamically in individuals, who are aspirin responsive according to TXB2 levels. The aim of this study was to assess the level of AA-, ADP- and thrombin-mediated platelet reactivity in patients on aspirin before, during, and after major vascular surgery, which represents a model of on/off vascular inflammation. Firstly, we hypothesized, that in association with this inflammatory episode AA-, ADP- and thrombin-induced clotting would change in a dynamic manner. Secondly, that AA-induced clotting will be modified despite complete suppression of platelet TXB2 production by aspirin throughout the periprocedural period, possibly via a lipoxygenase-mediated mechanism. Fourty patients underwent major vascular surgery (open abdominal aortic aneurysm operation, infrainguinal bypass for subcritical limb ischaemia or peripheral aneurysm repair with bypass). They were all on 75 mg of aspirin prior to and throughout the perioperative period and received 5000 units of unfractionated heparin intraoperatively. AA-, ADP-, and thrombin-induced clotting, AA metabolites (TXB2 and 12-Hyroxyeicosatetraenoic acid (12-HETE)) and inflammatory markers (CRP, IL-6, TNF-α and CD40) were measured pre-procedure and at 2, 24, 48 hours, 3 to 5 days and 3 months after surgery. AA-, ADP- and thrombin-induced platelet reactivity was assessed using thrombelastography. TXB2, 12-HETE, IL-6, TNF-α, CD40 were determined using the sequential competitive binding Enzyme-Linked ImmunoAssay technique and CRP was determined using an immune-turbidimetric test on human serum. There was a transient rise in inflammatory markers in the early perioperative period (CRP at 24, 48 hours and 3 to 5 days p < 0.001 and IL-6 at 2, 24, 48 hours and 3 to 5 days p < 0.001 as compared to baseline). Patients had negligible levels of TXB2 throughout, confirming a consistent therapeutic response to aspirin. There was a transient rise in thrombin-mediated clotting (MAThrombin at 48 hours p = 0.001 and 3 to 5 days p < 0.001) and a fall in AA- and ADP-induced clotting in the early post op period (both MAAA and MAADP p = 0.001 at 2 hours). At 3 months, the level of AA- and ADP-induced clotting was significantly higher than at baseline (p = 0.008 for MAAA and p = 0.002 for MAADP), hence demonstrating a rebound effect. These data demonstrate a novel dynamic variation in platelet aggregation with acute vascular inflammation, including AA-induced whole blood clotting which is apparently COX-1 independent.

The influence of advancing age on implantation of drug-eluting stents.

BACKGROUND: The influence of age upon the use of drug-eluting stents (DES) in patients aged ≥ 65 years is uncertain. The aim of this study is to investigate the impact of age increase in patients aged ≥ 65 years in the use of DES in patients undergoing percutaneous coronary intervention (PCI). METHOD: The study cohort comprised 8,598 patients ≥ 65 years of age who underwent stent implantation from April 2003 to March 2014. We defined the first DES era as the period April 2003 to July 2008 and the second DES era as the period July 2008 to March 2014. Multivariable logistic regression was performed for both eras to assess the impact of age increase and analyze independent factors associated with DES implantation. RESULTS: In the first DES era cohort, the two groups of patients differed in their risk factor profile with lower rates of male sex, diabetes, smokers, and hypercholesterolemia in those aged ≥ 75 years. There were more Caucasian and less African-Americans in this age group. Furthermore, patients aged ≥ 75 years had lower left ventricular ejection fraction (LVEF) and baseline haematocrit concentration were more likely to present with an acute myocardial infarction (MI) than stable or unstable angina and had higher rates of a previous history for congestive heart failure (CHF), chronic renal insufficiency (CRI), and peripheral vascular disease (PVD). These differences were broadly similar for patients in the second DES era except for similarities in LVEF, presentation with unstable angina, and PVD, as well as a lower rate for previous PCI. DES use was reduced with increasing age in both the first (OR=0.78; 95% CI=0.69-0.89) and second DES era (OR=0.53; 95% CI=0.47-0.58). In both eras, DES use was less likely in current smokers, patients presenting with acute MI and cardiogenic shock, and those with a previous history of CHF. CONCLUSION: In patients aged ≥ 65 years, the use of DES decreased with increasing age. This observation was apparent in both the first and second DES era. © 2015 Wiley Periodicals, Inc.

The role of DNA damage and repair in atherosclerosis: A review.

The global burden of cardiovascular disease is increasing despite therapeutic advances in medication and interventional technologies. Accumulated deoxyribonucleic acid (DNA) damage and subsequent repair pathways are now increasingly recognised as a causal factor in the initiation and progression of atherosclerosis. These molecular alterations have been shown to occur within affected vasculature, plaque microenvironment as well as in circulating cells. The DNA damage response (DDR) pathway is reliant on post-translational modification of sensing proteins which activate a signalling cascade to repair, if possible, DNA damaged sites in response to various environmental and physiological insults. This review summarises the current evidence for DNA damage in atherosclerosis, the key steps involved in the DDR pathway, DNA repair and their subsequent effects on atherosclerotic plaques, as well as the therapeutic options in managing DNA damage-induced atherosclerosis.

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.

A novel, minimally invasive access technique versus standard 18-gauge needle set for femoral access.

OBJECTIVE: To compare access site complications with the Micropuncture 21 gauge (G) needle set to the standard 18G needle in patients undergoing percutaneous coronary intervention (PCI) using the femoral approach. BACKGROUND: Vascular access site complications are the most common problems after PCI. The Micropuncture 21G needle set was recently introduced to minimize such complications. METHODS: A cohort of 3,243 consecutive patients was studied. Patients receiving thrombolytics, IIb/IIIa antagonist, coumadin, or intra-aortic balloon pump were excluded. Micropuncture access was used in 544 patients and standard 18G needle in 2,699. All access sites were managed with a vascular closure device. Primary endpoints included vascular perforation or limb ischemia requiring repair, retroperitoneal bleeding, pseudoaneurysm, arteriovenous fistula, and groin hematoma (>4 cm). RESULTS: Patients undergoing PCI with Micropuncture were at higher risk: they were older (65.9 ± 9 vs. 64.7 ± 11.8, P = 0.03); had lower body surface area (1.9 ± 0.2 vs. 2.0 ± 0.3, P = 0.02); more prevalent peripheral vascular disease [119 (21.9%) vs. 380 (14.1%), P < 0.001] and renal failure [106 (19.6%) vs. 318 (11.8%), P < 0.001]. Overall, there was no significant difference in the access site complications rate using Micropuncture vs. standard needle, 7 (1.3%) vs. 27 (1.0%), respectively, P = 0.54. The Micropuncture group had significantly higher retroperitoneal bleeding, 0.7% vs. 0.18%, P = 0.04. After multivariable adjustment, only age remained significantly associated with vascular complications (OR 1.03, P = 0.04). CONCLUSIONS: Femoral access using the Micropuncture technique did not reduce the incidence of vascular complications and the marginally higher than expected retroperitoneal bleeding is based on very small numbers. The routine use of the Micropuncture set and its technique should be revisited.

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.

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.

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.

Patients with severe asymptomatic carotid artery stenosis do not have a higher risk of stroke and mortality after coronary artery bypass surgery.

BACKGROUND AND PURPOSE: Stroke development is a major concern in patients undergoing coronary artery bypass grafting (CABG). Whether asymptomatic severe carotid artery stenosis (CAS) contributes to the development of stroke and mortality in such patients remains uncertain. METHODS: A retrospective analysis of 878 consecutive patients with documented carotid duplex ultrasound who underwent isolated CABG in our institution from January 2003 to December 2009 was performed. Patients with severe CAS (n=117) were compared with those without severe CAS (n=761) to assess the rates of stroke and mortality during hospitalization for CABG. The 30-day mortality rate was also assessed. RESULTS: Patients with severe CAS were older and had a higher prevalence of peripheral arterial disease and heart failure. Patients with severe CAS had similar rates of in-hospital stroke (3.4% versus 3.6%; P=1.0) and mortality (3.4% versus 4.2%; P=1.0) compared with patients without severe CAS. The 30-day rate of mortality was also similar between the 2 cohorts (3.4% versus 2.9%; P=0.51). CONCLUSIONS: Severe CAS alone is not a risk factor for stroke or mortality in patients undergoing CABG. The decision to perform carotid imaging and subsequent revascularization in association with CABG must be individualized and based on clinical judgment.

Optical coherence tomography: a new imaging modality for plaque characterization and stent implantation.

Optical coherence tomography (OCT) is a novel, catheter-based, invasive imaging system based on near-infrared light with high image resolution (15-20 µm). The system allows for unparalleled imaging of the coronary artery lumen, plaque characterization, assessment of coronary stent strut apposition, neointimal coverage, vascular proliferative response, complications such as focal dissection or thrombus formation, and insight into the time course of stent endothelization. This review will describe the currently available developments in OCT technology and its application in both the clinical and research arenas.

Integrilin in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: The adjunctive use of eptifibatide in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) remains controversial. We therefore set out to determine the safety and efficacy of eptifibatide in this population. METHODS: The study comprised 857 consecutive patients who underwent primary PCI for STEMI at the Washington Hospital Center. Three hundred eighteen patients also received adjunctive therapy with eptifibatide. Patients who had received thrombolysis prior to undergoing cardiac catheterization were excluded. The primary end-point was all-cause mortality and the composite of all-cause mortality or Q-wave MI. The primary safety end-point was the rate of thrombolysis in myocardial infarction (TIMI) major bleeding. RESULTS: The eptifibatide group was younger, had a higher body mass index, and a lower proportion of patients with systemic hypertension, diabetes mellitus, previous history of ischemic heart disease, coronary revascularization, and congestive heart failure. This cohort also used bivalirudin less often (23.3% vs. 72%; P < 0.001). Following multivariable analysis, the eptifibatide group had a significantly lower rate of all-cause mortality (hazard ratio 0.55; 95% confidence interval 0.34-0.89; P = 0.01) and the composite of all-cause mortality or Q-wave MI (hazard ratio 0.59; 95% confidence interval 0.37-0.95; P = 0.03) at 6 months. The rate of TIMI major bleeding was similar in both groups (hazard ratio 0.54; 95% confidence interval 0.25-1.17; P = 0.12). CONCLUSION: The adjunctive use of eptifibatide in patients presenting with STEMI may be associated with improved clinical outcomes. (J Interven Cardiol 2011;24:351-356).

Do patients with drug-eluting stent thrombosis have a similar prognosis to patients presenting with st-Elevation myocardial infarction of de novo lesions?

BACKGROUND: Despite significant advances in stent technology and pharmacotherapy, drug-eluting stent thrombosis (DES-ST) remains a major complication of percutaneous coronary intervention (PCI) and commonly presents as ST-elevation myocardial infarction (STEMI). There are currently little data comparing the in-hospital outcomes of patients presenting with STEMI due to DES-ST with those due to de novo coronary artery disease (CAD). METHODS: Our study comprised 985 consecutive patients who underwent primary PCI for STEMI, 102 of whom were diagnosed as having a definite DES-ST. The primary end-point was the in-hospital composite of death or recurrent myocardial infarction (MI). The secondary end-point was the in-hospital maximum rise in creatine kinase (myocardial band [MB] fraction) and troponin I. RESULTS: The DES-ST group had a higher proportion of patients with diabetes mellitus, hypercholesterolemia, history of ischemic heart disease, coronary revascularization, and chronic renal impairment. The adjusted primary end-point was higher in the DES-ST cohort (12.7% vs. 7.4%; P = 0.05). The 2 cohorts did not differ in the secondary end-point. The independent predictors of the primary end-point were age (hazard ratio [HR]= 1.04; 95% confidence interval [CI]= 1.01 - 1.06; P = 0.005), cardiogenic shock (HR = 11.5; 95% CI = 6.38 - 20.07, P < 0.001), and lesions involving the left anterior descending coronary artery (HR = 1.8; 95% CI = 1.03 - 3.13, P = 0.04). DES-ST was not an independent predictor of the primary end-point (HR = 1.18; 95% CI = 0.53-2.63, P = 0.38). CONCLUSIONS: Patients with STEMI secondary to DES-ST have a poorer in-hospital outcome than do patients in whom STEMI is due to de novo CAD. This difference may be predominantly driven by differences in the baseline characteristics between these cohorts. (J Interven Cardiol 2011;24:320-325).

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.

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.

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.