Genetic and clinical determinants of abdominal aortic diameter: genome-wide association studies, exome array data and Mendelian randomization study.

Progressive dilation of the infrarenal aortic diameter is a consequence of the ageing process and is considered the main determinant of abdominal aortic aneurysm (AAA). We aimed to investigate the genetic and clinical determinants of abdominal aortic diameter (AAD). We conducted a meta-analysis of genome-wide association studies in 10 cohorts (n = 13 542) imputed to the 1000 Genome Project reference panel including 12 815 subjects in the discovery phase and 727 subjects [Partners Biobank cohort 1 (PBIO)] as replication. Maximum anterior-posterior diameter of the infrarenal aorta was used as AAD. We also included exome array data (n = 14 480) from seven epidemiologic studies. Single-variant and gene-based associations were done using SeqMeta package. A Mendelian randomization analysis was applied to investigate the causal effect of a number of clinical risk factors on AAD. In genome-wide association study (GWAS) on AAD, rs74448815 in the intronic region of LDLRAD4 reached genome-wide significance (beta = -0.02, SE = 0.004, P-value = 2.10 × 10-8). The association replicated in the PBIO1 cohort (P-value = 8.19 × 10-4). In exome-array single-variant analysis (P-value threshold = 9 × 10-7), the lowest P-value was found for rs239259 located in SLC22A20 (beta = 0.007, P-value = 1.2 × 10-5). In the gene-based analysis (P-value threshold = 1.85 × 10-6), PCSK5 showed an association with AAD (P-value = 8.03 × 10-7). Furthermore, in Mendelian randomization analyses, we found evidence for genetic association of pulse pressure (beta = -0.003, P-value = 0.02), triglycerides (beta = -0.16, P-value = 0.008) and height (beta = 0.03, P-value < 0.0001), known risk factors for AAA, consistent with a causal association with AAD. Our findings point to new biology as well as highlighting gene regions in mechanisms that have previously been implicated in the genetics of other vascular diseases.

Myocardial bridging is associated with exercise-induced ventricular arrhythmia and increases in QT dispersion.

BACKGROUND: A myocardial bridge (MB) has been associated with ventricular arrhythmia and sudden death during exercise. QT dispersion (QTd) is a measure of abnormal repolarization and may predict ventricular arrhythmia. We investigated the frequency of ventricular arrhythmias during exercise and the QTd at rest and after exercise, in patients with an MB compared to a normal cohort. METHODS: We studied the rest and stress ECG tracings of patients with an MB suspected by focal septal buckling on exercise echocardiography (EE) (Echo-MB group, N = 510), those with an MB confirmed by another examination (MB group, N = 110), and healthy controls (Control group, N = 198). RESULTS: The frequency of exercise-induced premature ventricular contractions (PVCs) was significantly higher in the Echo-MB and MB groups compared with the Control group (both p < .001). In all, 25 patients (4.9%) in the Echo-MB group, seven patients (6.4%) in the MB group and no patients in the Control group had exercise-induced non-sustained ventricular tachycardia (NSVT). There was no difference in the baseline QTd between the groups. In the Echo-MB and MB groups, QTd postexercise increased significantly when compared with baseline (both p < .001). Patients with NSVT had a higher frequency of male gender and an even greater increase in QTd with exercise compared with the non-NSVT group. DISCUSSION: There is an increased frequency of exercise-induced PVCs and NSVT in patients with MBs. Exercise significantly increases QTd in MB patients, with an even greater increase in QTd in MB patients with NSVT. Exercise in MB patients results in ventricular arrhythmias and abnormalities in repolarization.

Myocardial Bridges on Coronary Computed Tomography Angiography　- Correlation With Intravascular Ultrasound and Fractional Flow Reserve.

BACKGROUND: Myocardial bridges (MB) are commonly seen on coronary CT angiography (CCTA) in asymptomatic individuals, but in patients with recurrent typical angina symptoms, yet no obstructive coronary artery disease (CAD), evaluation of their potential hemodynamic significance is clinically relevant. The aim of this study was to compare CCTA to invasive coronary angiography (ICA), including intravascular ultrasound (IVUS), to confirm MB morphology and estimate their functional significance in symptomatic patients.Methods and Results:We retrospectively identified 59 patients from our clinical databases between 2009 and 2014 in whom the suspicion for MB was raised by symptoms of recurrent typical angina in the absence of significant obstructive CAD on ICA. All patients underwent CCTA, ICA and IVUS. MB length and depth by CCTA agreed well with length (0.6±23.7 mm) and depth (CT coverage) as seen on IVUS. The product of CT length and depth (CT coverage), (MB muscle index (MMI)), ≥31 predicted an abnormal diastolic fractional flow reserve (dFFR) ≤0.76 with a sensitivity and specificity of 74% and 62% respectively (area under the curve=0.722). CONCLUSIONS: In patients with recurrent symptoms of typical angina yet no obstructive CAD, clinicians should consider dynamic ischemia from an MB in the differential diagnosis. The product of length and depth (i.e., MMI) by CCTA may provide some non-invasive insight into the hemodynamic significance of a myocardial bridge, as compared with invasive assessment with dFFR.

Resequencing and clinical associations of the 9p21.3 region: a comprehensive investigation in the Framingham heart study.

BACKGROUND: 9p21.3 is among the most strongly replicated regions for cardiovascular disease. There are few reports of sequencing the associated 9p21.3 interval. We set out to sequence the 9p21.3 region followed by a comprehensive study of genetic associations with clinical and subclinical cardiovascular disease and its risk factors, as well as with copy number variation and gene expression, in the Framingham Heart Study (FHS). METHODS AND RESULTS: We sequenced 281 individuals (94 with myocardial infarction, 94 with high coronary artery calcium levels, and 93 control subjects free of elevated coronary artery calcium or myocardial infarction), followed by genotyping and association in >7000 additional FHS individuals. We assessed genetic associations with clinical and subclinical cardiovascular disease, risk factor phenotypes, and gene expression levels of the protein-coding genes CDKN2A and CDKN2B and the noncoding gene ANRIL in freshly harvested leukocytes and platelets. Within this large sample, we found strong associations of 9p21.3 variants with increased risk for myocardial infarction, higher coronary artery calcium levels, and larger abdominal aorta diameters and no evidence for association with traditional cardiovascular disease risk factors. No common protein-coding variation, variants in splice donor or acceptor sites, or copy number variation events were observed. By contrast, strong associations were observed between genetic variants and gene expression, particularly for a short isoform of ANRIL and for CDKN2B. CONCLUSIONS: Our thorough genomic characterization of 9p21.3 suggests common variants likely account for observed disease associations and provides further support for the hypothesis that complex regulatory variation affecting ANRIL and CDKN2B gene expression may contribute to increased risk for clinically apparent and subclinical coronary artery disease and aortic disease.

Symptomatic Myocardial Bridging in D-Transposition of the Great Arteries Post-Arterial Switch.

We present Stanford's experience with patients post-arterial switch operation presenting with chest pain found to have hemodynamically significant myocardial bridging. The evaluation of symptomatic patients post-arterial switch should not only include assessment for coronary ostial patency but also for nonobstructive coronary conditions such as myocardial bridging. (Level of Difficulty: Advanced.).

Patient-specific fluid-structure simulations of anomalous aortic origin of right coronary arteries.

Objectives: Anomalous aortic origin of the right coronary artery (AAORCA) may cause ischemia and sudden death. However, the specific anatomic indications for surgery are unclear, so dobutamine-stress instantaneous wave-free ratio (iFR) is increasingly used. Meanwhile, advances in fluid-structure interaction (FSI) modeling can simulate the pulsatile hemodynamics and tissue deformation. We sought to evaluate the feasibility of simulating the resting and dobutamine-stress iFR in AAORCA using patient-specific FSI models and to visualize the mechanism of ischemia within the intramural geometry and associated lumen narrowing. Methods: We developed 6 patient-specific FSI models of AAORCA using SimVascular software. Three-dimensional geometries were segmented from coronary computed tomography angiography. Vascular outlets were coupled to lumped-parameter networks that included dynamic compression of the coronary microvasculature and were tuned to each patient's vitals and cardiac output. Results: All cases were interarterial, and 5 of 6 had an intramural course. Measured iFRs ranged from 0.95 to 0.98 at rest and 0.80 to 0.95 under dobutamine stress. After we tuned the distal coronary resistances to achieve a stress flow rate triple that at rest, the simulations adequately matched the measured iFRs (r = 0.85, root-mean-square error = 0.04). The intramural lumen remained narrowed with simulated stress and resulted in lower iFRs without needing external compression from the pulmonary root. Conclusions: Patient-specific FSI modeling of AAORCA is a promising, noninvasive method to assess the iFR reduction caused by intramural geometries and inform surgical intervention. However, the models' sensitivity to distal coronary resistance suggests that quantitative stress-perfusion imaging may augment virtual and invasive iFR studies.

Colocalization of Coronary Plaque with Wall Shear Stress in Myocardial Bridge Patients.

PURPOSE: Patients with myocardial bridges (MBs) have a higher prevalence of atherosclerosis. Wall shear stress (WSS) has previously been correlated with plaque in coronary artery disease patients, but such correlations have not been investigated in symptomatic MB patients. The aim of this paper was to use a multi-scale computational fluid dynamics (CFD) framework to simulate hemodynamics in MB patient, and investigate the co-localization of WSS and plaque. METHODS: We identified N = 10 patients from a previously reported cohort of 50 symptomatic MB patients, all of whom had plaque in the proximal vessel. Dynamic 3D models were reconstructed from coronary computed tomography angiography (CCTA), intravascular ultrasound (IVUS) and catheter angiograms. CFD simulations were performed to compute WSS proximal to, within and distal to the MB. Plaque was quantified from IVUS images in 2 mm segments and registered to CFD model. Plaque area was compared to absolute and patient-normalized WSS. RESULTS: WSS was lower in the proximal segment compared to the bridge segment (6.1 ± 2.9 vs. 16.0 ± 7.1 dynes/cm2, p value < 0.01). Plaque area and plaque burden measured from IVUS peaked at 1-3 cm proximal to the MB entrance, coinciding with the first diagonal branch. Normalized WSS showed a statistically significant moderate correlation with plaque area (r = 0.41, p < 0.01). CONCLUSION: WSS may be obtained non-invasively in MB patients and provides a surrogate marker of plaque area. Using CFD, it may be possible to non-invasively assess the extent of plaque area, and identify patients who could benefit from frequent monitoring or medical management.

Imaging of coronary inflammation with FDG-PET: feasibility and clinical hurdles.

Conventional algorithms and noninvasive imaging tests for the identification of stable, hemodynamically significant coronary artery disease offer little insight into the detection of potentially vulnerable and inflamed coronary plaques, those most likely to rupture and cause acute coronary syndromes. Positron emission tomography (PET) with fluorodeoxyglucose (FDG) serves as a potential novel modality for the identification of plaque inflammation, as initial studies in animal and human studies have demonstrated that FDG uptake correlates with macrophage accumulation and inflammation. Therapy with anti-inflammatory agents has also been demonstrated in the arterial vasculature to reduce plaque FDG uptake. Although imaging of coronary inflammation with FDG-PET holds tremendous promise, several hurdles remain to be surmounted prior to widespread clinical application.

A 40-Year-Old Man With Tricuspid Atresia, Status Post-Fontan, With Severe COVID-19 Pneumonia and Pneumothorax.

We report a case of COVID-19 in an adult single-ventricle patient post-Fontan-to our knowledge, the first report in this population documenting the use of the latest management recommendations for this novel disease. Additionally, this patient had significant pre-existing ventricular dysfunction, valvular disease, and comorbidities including HIV. (Level of Difficulty: Advanced.).

Impact of Diastolic Vessel Restriction on Quality of Life in Symptomatic Myocardial Bridging Patients Treated With Surgical Unroofing: Preoperative Assessments With Intravascular Ultrasound and Coronary Computed Tomography Angiography.

[Figure: see text].

Abnormal shear stress and residence time are associated with proximal coronary atheroma in the presence of myocardial bridging.

BACKGROUND: Atheromatous plaques tend to form in the coronary segments proximal to a myocardial bridge (MB), but the mechanism of this occurrence remains unclear. This study evaluates the relationship between blood flow perturbations and plaque formation in patients with an MB. METHODS AND RESULTS: A total of 92 patients with an MB in the mid left anterior descending artery (LAD) and 20 patients without an MB were included. Coronary angiography, intravascular ultrasound, and coronary physiology measurements were performed. A moving-boundary computational fluid dynamics algorithm was used to derive wall shear stress (WSS) and peak residence time (PRT). Patients with an MB had lower WSS (0.46 ± 0.21 vs. 0.96 ± 0.33 Pa, p < 0.001) and higher maximal plaque burden (33.6 ± 15.0 vs. 14.2 ± 5.8%, p < 0.001) within the proximal LAD compared to those without. Plaque burden in the proximal LAD correlated significantly with proximal WSS (r = -0.51, p < 0.001) and PRT (r = 0.60, p < 0.001). In patients with an MB, the site of maximal plaque burden occurred 23.4 ± 13.3 mm proximal to the entrance of the MB, corresponding to the site of PRT. CONCLUSIONS: Regions of low WSS and high PRT occur in arterial segments proximal to an MB, and this is associated with the degree and location of coronary atheroma formation.

Invasive assessment of myocardial bridging in patients with angina and no obstructive coronary artery disease.

AIMS: Angina and no obstructive coronary artery disease (ANOCA) is common. A potential cause of angina in this patient population is a myocardial bridge (MB). We aimed to study the anatomical and haemodynamic characteristics of an MB in patients with ANOCA. METHODS AND RESULTS: Using intravascular ultrasound (IVUS), we identified 184 MBs in 154 patients. We evaluated MB length, arterial compression, and halo thickness. MB muscle index (MMI) was defined as MB length×halo thickness. Haemodynamic testing of the MB was performed using an intracoronary pressure/Doppler flow wire at rest and during dobutamine stress. We defined an abnormal diastolic fractional flow reserve (dFFR) as ≤0.76 during stress. The median MB length was 22.9 mm, arterial compression 30.9%, and halo thickness 0.5 mm. The median MMI was 12.1. Endothelial and microvascular dysfunction were present in 85.4% and 22.1%, respectively. At peak dobutamine stress, 94.2% of patients had a dFFR ≤0.76 within and/or distal to the MB. MMI was associated with an abnormal dFFR. CONCLUSIONS: In select patients with ANOCA who have an MB by IVUS, the majority have evidence of a haemodynamically significant dFFR during dobutamine stress, suggesting the MB as being a cause of their angina. A comprehensive invasive assessment of such patients during coronary angiography provides important diagnostic information that can guide management.

Off-Pump Minithoracotomy Versus Sternotomy for Left Anterior Descending Myocardial Bridge Unroofing.

BACKGROUND: Myocardial bridge (MB) of the left anterior descending (LAD) coronary artery occurs in approximately 25% of the population. When medical therapy fails in patients with a symptomatic, hemodynamically significant MB, MB unroofing represents the optimal surgical management. Here, we evaluated minimally invasive MB unroofing in selected patients compared with sternotomy. METHODS: MB unroofing was performed in 141 adult patients by sternotomy on-pump (ST-on, n = 40), sternotomy off-pump (ST-off, n = 62), or minithoracotomy off-pump (MT, n = 39). Angina symptoms were assessed preoperatively and 6 months postoperatively using the Seattle Angina Questionnaire. Matching included all MT patients and 31 ST-off patients with similar MB characteristics, no previous cardiac operations or coronary interventions, and no concomitant procedures. RESULTS: MT patients tended to have a shorter MB length than ST-on and ST-off patients (2.57 vs 2.93 vs 3.09 cm, P = .166). ST-on patients had a longer hospital stay than ST-off and MT patients (5.0 vs 4.0 vs 3.0 days, P < .001), and more blood transfusions (15.2% vs 0.0% vs 2.6%, P = .002). After matching, MT patients had a shorter hospital stay than ST-off patients (3.0 vs 4.0 days, P = .005). No deaths or major complications occurred in any group. In all groups, MB unroofing yielded significant symptomatic improvement regarding physical limitation, angina stability, angina frequency, treatment satisfaction, and quality of life. CONCLUSIONS: We report our single-center experience of off-pump minimally invasive MB unroofing, which may be safely performed in carefully selected patients, yielding dramatic improvements in angina symptoms at 6 months after the operation.

Incremental value of adenosine-induced stress myocardial perfusion imaging with dual-source CT at cardiac CT angiography.

PURPOSE: First, to assess the feasibility of a protocol involving stress-induced perfusion evaluated at computed tomography (CT) combined with cardiac CT angiography in a single examination and second, to assess the incremental value of perfusion imaging over cardiac CT angiography in a dual-source technique for the detection of obstructive coronary artery disease (CAD) in a high-risk population. MATERIALS AND METHODS: Institutional review board approval and informed patient consent were obtained before patient enrollment in the study. The study was HIPAA compliant. Thirty-five patients at high risk for CAD were prospectively enrolled for evaluation of the feasibility of CT perfusion imaging. All patients underwent retrospectively electrocardiographically gated (helical) adenosine stress CT perfusion imaging followed by prospectively electrocardiographically gated (axial) rest myocardial CT perfusion imaging. Analysis was performed in three steps: (a)Coronary arterial stenoses were scored for severity and reader confidence at cardiac CT angiography, (b)myocardial perfusion defects were identified and scored for severity and reversibility at CT perfusion imaging, and (c)coronary stenosis severity was reclassified according to perfusion findings at combined cardiac CT angiography and CT perfusion imaging. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of cardiac CT angiography before and after CT perfusion analysis were calculated. RESULTS: With use of a reference standard of greater than 50% stenosis at invasive angiography, all parameters of diagnostic accuracy increased after CT perfusion analysis: Sensitivity increased from 83% to 91%; specificity, from 71% to 91%; PPV, from 66% to 86%; and NPV, from 87% to 93%. The area under the receiver operating characteristic curve increased significantly, from 0.77 to 0.90 (P < .005). CONCLUSION: A combination protocol involving adenosine perfusion CT imaging and cardiac CT angiography in a dual-source technique is feasible, and CT perfusion adds incremental value to cardiac CT angiography in the detection of significant CAD.

Direct comparison of rest and adenosine stress myocardial perfusion CT with rest and stress SPECT.

INTRODUCTION: We have recently described a technique for assessing myocardial perfusion using adenosine-mediated stress imaging (CTP) with dual source computed tomography. SPECT myocardial perfusion imaging (SPECT-MPI) is a widely utilized and extensively validated method for assessing myocardial perfusion. The aim of this study was to determine the level of agreement between CTP and SPECT-MPI at rest and under stress on a per-segment, per-vessel, and per-patient basis. METHODS: Forty-seven consecutive patients underwent CTP and SPECT-MPI. Perfusion images were interpreted using the 17 segment AHA model and were scored on a 0 (normal) to 3 (abnormal) scale. Summed rest and stress scores were calculated for each vascular territory and patient by adding corresponding segmental scores. RESULTS: On a per-segment basis (n = 799), CTP and SPECT-MPI demonstrated excellent correlation: Goodman-Kruskall gamma = .59 (P < .0001) for stress and .75 (P < .0001) for rest. On a per-vessel basis (n = 141), CTP and SPECT-MPI summed scores demonstrated good correlation: Pearson r = .56 (P < .0001) for stress and .66 (P < .0001) for rest. On a per-patient basis (n = 47), CTP and SPECT-MPI demonstrated good correlation: Pearson r = .60 (P < .0001) for stress and .76 (P < .0001) for rest. CONCLUSIONS: CTP compares favorably with SPECT-MPI for detection, extent, and severity of myocardial perfusion defects at rest and stress.

Accuracy of a novel stress echocardiography pattern for myocardial bridging in patients with angina and no obstructive coronary artery disease - A retrospective and prospective cohort study.

BACKGROUND: Myocardial bridge (MB) may cause angina in patients with no obstructive coronary artery disease (CAD). We previously reported a novel stress echocardiography (SE) pattern of focal septal buckling with apical sparing in the end-systolic to early-diastolic phase that is associated with the presence of an MB. We evaluated the diagnostic accuracy of this pattern, and prospectively validated our results. METHODS: The retrospective cohort included 158 patients with angina who underwent both SE and coronary CT angiography (CCTA). The validation cohort included 37 patients who underwent CCTA in the emergency department for angina, and prospectively underwent SE. CCTA was used as a reference standard for the presence/absence of an MB, and also confirmed no obstructive CAD. RESULTS: In the retrospective cohort, an MB was present in 107 (67.7%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 91.6%, 70.6%, 86.7% and 80%, respectively. On logistic regression, focal septal buckling and Duke treadmill score were associated with an MB. In the validation cohort, an MB was present in 31 (84%). The sensitivity, specificity PPV and NPV were 90.3%, 83.3%, 96.5% and 62.5%, respectively. On logistic regression, focal septal buckling was associated with an MB. CONCLUSION: Presence of focal septal buckling with apical sparing on SE is an accurate predictor of an MB in patients with angina and no obstructive CAD. This pattern can reliably be used to screen patients who may benefit from advanced non-invasive/invasive testing for an MB as a cause of their angina.

Thrombolysis in Myocardial Infarction (TIMI) Risk Index predicts long-term mortality and heart failure in patients with ST-elevation myocardial infarction in the TIMI 2 clinical trial.

BACKGROUND: TIMI (Thrombolysis in Myocardial Infarction) Risk Index (TRI) is a simple bedside score that predicts 30-day mortality in patients with ST-elevation myocardial infarction (MI). We sought to evaluate whether TRI was predictive of long-term mortality and clinical events. METHODS: In the TIMI 2 trial, 3,153 patients (mean age 57 +/- 10 years, 82% men) were randomized to invasive (n = 1,583) versus conservative (n = 1,570) strategy postfibrinolysis with median follow-up of 3 years. TIMI Risk Index was divided into 5 groups. The primary end point was all-cause mortality. Secondary analyses included recurrent MI, congestive heart failure (CHF), and combined end points. RESULTS: When compared with group 1, mortality in group 5 was more than 5-fold higher (hazard ratio [HR] 5.83, P < .0001) and was also increased in group 4 (HR 2.80, P < .0001) and group 3 (HR 1.96, P = .002) (c statistic 0.69). No difference was seen between groups 1 and 2 (P = .74). A similar increasing gradient effect was seen across TRI strata with group 5 having the highest risk for CHF (HR 4.13, P < .0001) and the highest risk for composite death/CHF (HR 4.35, P < .0001) over group 1. There was no difference in recurrent MI between the groups (P = .22). After controlling for other risk indicators, the relationship between TRI and mortality remained significant: group 5, HR 4.11, P < .0001; group 4, HR 2.14, P = .0009; group 3, HR 1.69, P = .02. When stratified by TRI groups, no differences in mortality or composite death/MI were found between treatment strategies. CONCLUSIONS: The simple TRI can predict increased long-term mortality, CHF, and composite death/CHF.

Association of aortic valve calcification to the presence, extent, and composition of coronary artery plaque burden: from the Rule Out Myocardial Infarction using Computer Assisted Tomography (ROMICAT) trial.

BACKGROUND: Aortic valve calcification (AVC) is associated with cardiovascular risk factors and coronary artery calcification. We sought to determine whether AVC is associated with the presence and extent of overall plaque burden, as well as to plaque composition (calcified, mixed, and noncalcified). METHODS: We examined 357 subjects (mean age 53 +/- 12 years, 61% male) who underwent contrast-enhanced electrocardiogram-gated 64-slice multidetector computed tomography from the ROMICAT trial for the assessment of presence and extent of coronary plaque burden according to the 17-coronary segment model and presence of AVC. RESULTS: Patients with AVC (n = 37, 10%) were more likely than those without AVC (n = 320, 90%) to have coexisting presence of any coronary plaque (89% vs 46%, P < .001) and had a greater extent of coronary plaque burden (6.4 vs 1.8 segments, P < .001). Those with AVC had >3-fold increase odds of having any plaque (adjusted odds ratio [OR] 3.6, P = .047) and an increase of 2.5 segments of plaque (P < .001) as compared to those without AVC. When stratified by plaque composition, AVC was associated most with calcified plaque (OR 5.2, P = .004), then mixed plaque (OR 3.2, P = .02), but not with noncalcified plaque (P = .96). CONCLUSION: Aortic valve calcification is associated with the presence and greater extent of coronary artery plaque burden and may be part of the later stages of the atherosclerosis process, as its relation is strongest with calcified plaque, less with mixed plaque, and nonsignificant with noncalcified plaque. If AVC is present, consideration for aggressive medical therapy may be warranted.

Extended cardiac ambulatory rhythm monitoring in adults with congenital heart disease: Arrhythmia detection and impact of extended monitoring.

BACKGROUND: Arrhythmias are a leading cause of death in adults with congenital heart disease (ACHD). While 24-48-hour monitors are often used to assess arrhythmia burden, extended continuous ambulatory rhythm monitors (ECAM) can record 2 weeks of data. The utility of this device and the arrhythmia burden identified beyond 48-hour monitoring have not been evaluated in the ACHD population. Additionally, the impact of ECAM has not been studied to determine management recommendations. OBJECTIVE: To address the preliminary question, we hypothesized that clinically significant arrhythmias would be detected on ECAM beyond 48 hours and this would lead to clinical management changes. METHODS: A single center retrospective cohort study of ACHD patients undergoing ECAM from June 2013 to May 2016 was performed. The number and type of arrhythmias detected within and beyond the first 48 hours of monitoring were compared using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Three hundred fourteen patients had monitors performed [median age 31 (IQR 25-41) years, 61% female). Significant arrhythmias were identified in 156 patients (50%), of which 46% were noted within 48 hours. A management change based on an arrhythmia was made in 49 patients (16%). CONCLUSIONS: ECAM detects more clinically significant arrhythmias than standard 48-hour monitoring in ACHD patients. Management changes, including medication changes, further testing or imaging, and procedures, were made based on results of ECAM. Recommendations and guidelines have been made based on arrhythmias on 48-hour monitoring; the predictive ability and clinical consequence of arrhythmias found on ECAM are not yet known.

Accuracy of non-invasive stress testing in women and men with angina in the absence of obstructive coronary artery disease.

OBJECTIVE: While >20% of patients presenting to the cardiac catheterization laboratory with angina have no obstructive coronary artery disease (CAD), a majority (77%) have an occult coronary abnormality (endothelial dysfunction, microvascular dysfunction (MVD), and/or a myocardial bridge (MB)). There are little data regarding the ability of noninvasive stress testing to identify these occult abnormalities in patients with angina in the absence of obstructive CAD. METHODS: We retrospectively evaluated 155 patients (76.7% women) with angina and no obstructive CAD who underwent stress echocardiography and/or electrocardiography before angiography. We evaluated Duke treadmill score, heart rate recovery (HRR), metabolic equivalents, and blood pressure response. During angiography, patients underwent invasive testing for endothelial dysfunction (decrease in epicardial coronary artery diameter >20% after intracoronary acetylcholine), MVD (index of microcirculatory resistance ≥25), and intravascular ultrasound for the presence of an MB. RESULTS: Stress echocardiography and electrocardiography were positive in 58 (43.6%) and 57 (36.7%) patients, respectively. Endothelial dysfunction was present in 96 (64%), MVD in 32 (20.6%), and an MB in 83 (53.9%). On multivariable logistic regression, stress echo was not associated with any abnormality, while stress ECG was associated with endothelial dysfunction. An abnormal HRR was associated with endothelial dysfunction and MVD, but not an MB. CONCLUSION: Conventional stress testing is insufficient for identifying occult coronary abnormalities that are frequently present in patients with angina in the absence of obstructive CAD. A normal stress test does not rule out a non-obstructive coronary etiology of angina, nor does it negate the need for comprehensive invasive testing.