Noninvasive ECG imaging of the intrinsic atrial pacemaker and atrial activation in surgically repaired or palliated congenital heart disease.

INTRODUCTION: Sinus node location, function, and atrial activation are often abnormal in patients with congenital heart disease (CHD), due to anatomical, surgical, and acquired factors. We aimed to perform noninvasive electrocardiographic imaging (ECGI) of the intrinsic atrial pacemaker and atrial activation in patients with surgically repaired or palliated CHD, compared with control patients with structurally normal hearts. METHODS AND RESULTS: Atrial ECGI was performed in eight CHD patients with prespecified diagnoses (Fontan circulation, dextro transposition of the great arteries post Mustard/Senning, tetralogy of Fallot), and three controls. Activation and propagation maps were constructed in presenting rhythm. Wavefront propagation was analyzed to identify (1) intrinsic atrial pacemaker breakout site, (2) morphological right atrial (RA) activation pattern, (3) morphological left atrial (LA) breakout sites (i.e., interatrial connections), (4) LA activation pattern, and (5) putative lines of block. Physiologically appropriate atrial activation and propagation maps were able to be constructed. In the majority of patients, atrial breakouts were in keeping with the sinus node, observed in a crescent-shaped distribution from the anterior superior vena cava to the posterior RA. Ectopic atrial pacemaker sites were demonstrated in the atriopulmonary (AP) Fontan patient (very diffuse posterolateral RA) and Mustard patient (very posterior RA competing with a low RA focus). RA propagation was laminar in controls, but suggested either a line of block or conduction slowing consistent with an atriotomy scar in the tetralogy of Fallot (TOF) patients. Putative lines of block were more complex and RA propagation more abnormal in the atrial switch and AP Fontan patients, compared with the TOF patients. RA activation in the extracardiac Fontan patients was relatively laminar. Earliest LA breakout was most commonly observed in the region of Bachmann's Bundle in both controls and CHD patients, except for posterior LA breakouts in two patients. LA activation was typically more homogeneous than RA activation in CHD patients. CONCLUSION: ECGI can be utilized to create a noninvasive mapping model of atrial activation in postsurgical CHD, demonstrating atrial pacemaker location, putative lines of block and interatrial connections. Once validated invasively, this may have clinical implications in predicting risk of sinus node dysfunction and atrial arrhythmias, or in guiding catheter ablation.

Multi-vessel giant coronary artery aneurysms: An unusual cause of chest pain.

We describe an unusual case of multi-vessel giant coronary artery aneurysms complicated by acute coronary syndrome despite escalation of therapy. A 65-year-old man with hypertension and hypercholesterolemia presented to clinic with atypical chest pain over 4 months. Outpatient computed tomography coronary angiography (CTCA) demonstrated giant coronary aneurysms involving all 3 major coronary arteries. Outpatient coronary angiogram findings were in concordance with the CTCA with no definite obstructive coronary disease. Myocardial perfusion imaging was normal. He was commenced on dual antiplatelet therapy (DAPT). At 6 months, he presented with chest pain and non-ST-elevation myocardial infarction. Repeat coronary angiogram demonstrated occluded first septal LAD branch which previously had aneurysmal dilatation. DAPT was changed to long-term oral anticoagulation. He remains well at 18 months. This case highlights the importance of multi-modality imaging in the diagnosis and workup of coronary artery aneurysms and challenges in management; an individualized approach is required.

Aortic root measurement on CT: linear dimensions, aortic root area and comparison with echocardiography. A retrospective cross sectional study.

OBJECTIVE: We sought to assess the different CT aortic root measurements and determine their relationship to transthoracic echocardiography (TTE). METHODS: TTE and ECG-gated CT images were reviewed from 70 consecutive patients (mean age 54 ± 18 years; 67% male) with tricuspid aortic roots (trileaflet aortic valves) between Nov 2009 and Dec 2013. Three CT planes (coronal, short axis en face and three-chamber) were used for measurement of nine linear dimensions. TTE aortic root dimension was measured as per guidelines from the parasternal long axis view. RESULTS: All CT short axis measurements of the aortic root had excellent reproducibility (intraclass correlation coefficient, ICC 0.96-0.99), while coronal and three-chamber planes had lower reproducibility with ICC 0.90 (95% CI 0.84-0.94) and ICC 0.92 (0.87-0.95) respectively. CT coronal and short axis maximal dimensions were systematically larger than TTE (mean 2 mm larger, p < 0.001), while CT cusp to commissure measurements were systematically smaller (CT RCC-comm mean 2 mm smaller than TTE, p < 0.001). All CT short axis measurements had excellent correlation with aortic root area with CT short axis maximal dimension marginally better than the rest (Pearson's R 0.97). CONCLUSION: Systematic differences exist between CT and TTE dependent on the CT plane of measurement. All CT short axis measurements of the aortic root had excellent reproducibility and correlation with aortic root area with maximal dimension appearing marginally better than the rest. Our findings highlight the importance of specifying the chosen plane of aortic root measurement on CT. ADVANCES IN KNOWLEDGE: Systematic differences in aortic root dimension exist between TTE and the various CT measurement planes. CT coronal and short axis maximal dimensions were systematically larger than TTE, while CT cusp to commissure measurements were smaller. CT readers should indicate the plane of measurement and the specific linear dimension to avoid ambiguity in follow-up and comparison.

SMARTphone-based, early cardiac REHABilitation in patients with acute coronary syndromes: a randomized controlled trial.

BACKGROUND: There are well-documented treatment gaps in secondary prevention of coronary heart disease with a lack of clearly defined strategies to assist early physical activity after acute coronary syndromes (ACS). Smartphone technology may provide an innovative platform to close these gaps. OBJECTIVES: The primary goal of this study was to assess whether a smartphone-based, early cardiac rehabilitation program improved exercise capacity in patients with ACS. METHODS: A total of 206 patients with ACS across six tertiary Australian hospitals were included in this randomized controlled trial. Participants were randomized to usual care (UC; including referral to traditional cardiac rehabilitation), with or without an adjunctive smartphone-based cardiac rehabilitation program (S-CRP) upon hospital discharge. The primary endpoint was change in exercise capacity, measured by the change in 6-minute walk test distance at 8 weeks when compared to baseline, between groups. Secondary endpoints included uptake and adherence to cardiac rehabilitation, changes in cardiac risk factors, psychological well-being and quality of life status. RESULTS: Of the 168 patients with complete follow-up (age 56 ± 10 years; 16% females), 83 were in the S-CRP. At 8-week follow-up, the S-CRP group had a clinically significant improvement in 6-minute walk test distance (Δ117 ± 76 vs. Δ91 ± 110 m; P = 0.02). Patients in the S-CRP were more likely to participate (87% vs. 51%, P < 0.001) and adhere (72% vs. 22%, P < 0.001) to a cardiac rehabilitation program. Compared to UC, patients receiving S-CRP had similar smoking cessation rates, LDL-cholesterol levels, blood pressure reduction, depression, anxiety and quality of life measures (all P = NS). CONCLUSION: In patients with ACS, a S-CRP, as an adjunct to UC improved exercise capacity at 8 weeks in addition to participation and adherence to cardiac rehabilitation (Australian New Zealand Clinical Trials Registry; ACTRN12616000426482).

Epicardial Adipose Tissue Accumulation Confers Atrial Conduction Abnormality.

BACKGROUND: Clinical studies have reported that epicardial adipose tissue (EpAT) accumulation associates with the progression of atrial fibrillation (AF) pathology and adversely affects AF management. The role of local cardiac EpAT deposition in disease progression is unclear, and the electrophysiological, cellular, and molecular mechanisms involved remain poorly defined. OBJECTIVES: The purpose of this study was to identify the underlying mechanisms by which EpAT influences the atrial substrate for AF. METHODS: Patients without AF undergoing coronary artery bypass surgery were recruited. Computed tomography and high-density epicardial electrophysiological mapping of the anterior right atrium were utilized to quantify EpAT volumes and to assess association with the electrophysiological substrate in situ. Excised right atrial appendages were analyzed histologically to characterize EpAT infiltration, fibrosis, and gap junction localization. Co-culture experiments were used to evaluate the paracrine effects of EpAT on cardiomyocyte electrophysiology. Proteomic analyses were applied to identify molecular mediators of cellular electrophysiological disturbance. RESULTS: Higher local EpAT volume clinically correlated with slowed conduction, greater electrogram fractionation, increased fibrosis, and lateralization of cardiomyocyte connexin-40. In addition, atrial conduction heterogeneity was increased with more extensive myocardial EpAT infiltration. Cardiomyocyte culture studies using multielectrode arrays showed that cardiac adipose tissue-secreted factors slowed conduction velocity and contained proteins with capacity to disrupt intermyocyte electromechanical integrity. CONCLUSIONS: These findings indicate that atrial pathophysiology is critically dependent on local EpAT accumulation and infiltration. In addition to myocardial architecture disruption, this effect can be attributed to an EpAT-cardiomyocyte paracrine axis. The focal adhesion group proteins are identified as new disease candidates potentially contributing to arrhythmogenic atrial substrate.

A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies.

Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) have transformed the management of many malignancies. Although rare, immune-mediated myocarditis presents unique clinical challenges due to heterogenous presentation, potential life-threatening consequences, and the time-critical need to differentiate it from other causes of cardiac dysfunction. Increasingly, TKI are being combined with ICI to promote immune modulation and improve efficacy. However, these combinations are associated with more toxicities. This series describes six patients with advanced melanoma who developed immune-mediated myocarditis while receiving an anti-PD-1 antibody or an anti-PD-L1 antibody plus a mitogen-activated protein kinase inhibitor. It provides a review of their heterogenous clinical presentations, investigational findings and treatment outcomes. Presentations ranged from asymptomatic cardiac enzyme elevation to death due to heart failure. We highlight the role of cardiac MRI (CMRI), a sensitive and non-invasive tool for the early detection and subsequent monitoring of myocardial inflammation. Five of the six patients exhibited CMRI changes characteristic of myocarditis, including mid-wall myocardial oedema and late gadolinium enhancement in a non-coronary distribution. Critically, two of these patients had normal findings on echocardiogram. Of the five patients who received immunosuppression, four recovered from myocarditis and one died of cardiac failure. The sixth patient improved with cardiac failure management alone. Three of the four patients responding to ICI derived long-term benefit. Clinical vigilance, prompt multimodal diagnosis and multidisciplinary management are paramount for the treatment of immune-mediated myocarditis.

Pacing and implantable cardioverter defibrillator lead perforation as assessed by multiplanar reformatted ECG-gated cardiac computed tomography and clinical correlates.

INTRODUCTION: We aimed to assess the utility of cardiac computed tomography (CT) in the evaluation of right atrial (RA) and right ventricular (RV) pacemaker and implantable cardiac defibrillator lead perforation. METHODS: Images from a 320-slice electrocardiogram-gated cardiac CT scanner were retrospectively independently analyzed by two reviewers for lead position, pericardial effusion, and perforation.Perforation results were correlated with pacing sensing, impedance, and threshold measurements. RESULTS: A total of 52 patients had RV leads and 35 had RA leads. Five of 17 RV apical, one of 35 RV nonapical, and none of the 35 RA leads perforated through the myocardium on CT imaging criteria. Two "clinically" perforated leads (that had protruded 5 mm and 15 mm from the outer edge of the myocardium)had pericardial effusions and changes in pacing parameters, and required RV lead repositioning. In contrast,there were four apparent "radiologic" perforations (that had protruded only an average 1.5±0.5 mm from the outer edge of the myocardium) that did not require repositioning. These had the radiologic appearance of perforation on cardiac CT; however, they were not associated with pericardial effusions or significant changes in RV pacing lead sensing, impedance, and threshold measurements. CONCLUSIONS: Cardiac CT scanning with multiplanar reformatting is useful for documenting lead position and assessing for possible cardiac perforation. The clinical significance and natural history of leads with only the appearance of perforation on cardiac CT is uncertain.

Validation of conventional fluoroscopic and ECG criteria for right ventricular pacemaker lead position using cardiac computed tomography.

INTRODUCTION: It is hypothesized that pacing the right ventricular (RV) septum is associated with less deleterious outcomes than RV apical pacing. Our aim was to validate fluoroscopic and electrocardiography (ECG) criteria for describing pacemaker and implantable cardioverter defibrillator RV "septal" lead position against the proposed gold standard: cardiac computed tomography (CT). METHODS: Using the conventional fluoroscopic criteria, we intended to place RV nonapical leads on the interventricular septum. Lead positions were later retrospectively analyzed with CT and correlated with ECGs and fluoroscopic projections: posterior-anterior, 40° left anterior oblique (LAO), 40° right anterior oblique (RAO), and left lateral. RESULTS: Only 21% (nine of 35) of presumed "septal" RV nonapical leads using the conventional fluoroscopic criteria were on the true septum. A schema developed to define septal position in the RAO fluoroscopic view had high agreement with CT images. ECG criteria had only fair to moderate agreement with CT. The paced QRS duration was significantly longer (P < 0.001) with RV apical pacing (176 ± 10.7 ms), compared to RV nonapical pacing (144.5 ± 14.3 ms). CONCLUSION: Using the conventional fluoroscopic criteria, only a minority of RV leads were implanted on the true RV septum. Instead, aiming for the middle of the cardiac silhouette in the RAO fluoroscopic view, confirming rightward orientation in the LAO view, and having a paced QRS duration <140 ms may allow the implanting cardiologist a simple, more accurate method to achieve true RV septal lead positioning.

Proximity of pacemaker and implantable cardioverter-defibrillator leads to coronary arteries as assessed by cardiac computed tomography.

INTRODUCTION: There have been rare case reports of damage to adjacent coronary arteries by screw-in pacemaker and implantable cardioverter-defibrillator (ICD) leads. Our aim was to assess the proximity of pacemaker and ICD leads to the major coronary anatomy using cardiac computed tomography (CT). METHODS: Cardiac CT images were retrospectively analyzed to assess the spatial relationship of device lead tips to the major coronary anatomy. RESULTS: Fifty-two right ventricular (RV) leads (17 apical, 35 nonapical) and 35 right atrial (RA) leads were assessed. Leads on the RV antero-septal junction (20 of 52) were close (median 4.7 mm) to, and orientated toward, the left anterior descending (LAD) coronary artery. RA leads in the anterior (26 of 35) and lateral (seven of 35) walls of the RA appendage were not close to (16.9 ± 7.7 mm and 18.9 ± 12.4 mm, respectively) and directed away from the right coronary artery. However, an RA lead adjacent to the superior border of the tricuspid valve was 4.3 mm from the right coronary artery and an RA lead on the medial wall of the RA appendage was 1.6 mm away from the aorta. An RV pacemaker lead in the lateral wall of the RV inlet was 3.4 mm from the right coronary artery. CONCLUSIONS: In our cohort, a majority of RV leads were on the antero-septal junction and close to the overlying LAD coronary artery. RA leads adjacent to the tricuspid valve or on the medial RA appendage were in close proximity to the right coronary artery and aorta, respectively.

Assessment of right ventricular volumes and function using cardiovascular magnetic resonance cine imaging after atrial redirection surgery for complete transposition of the great arteries.

Cardiovascular magnetic resonance (CMR) imaging is the reference standard for measurement of right ventricular (RV) volumes and function. To date, no study has compared methods of data acquisition and analysis by CMR for adults with a systemic RV. Our objective was to evaluate RV size and function using axial and short axis views in adults post atrial switch (Mustard) surgery. A total of 34 adults (20 male, mean age at CMR 32 ± 6 years) were identified at our centre. Volumes, RV end-diastolic (EDV) and end-systolic (ESV) were measured in short axis and axial orientations by two independent experienced readers, blinded to clinical and CMR data. Intra and interobserver measurements in each view were compared using Bland-Altman plots and intraclass correlation coefficients (ICC). Although mean volumes were larger in the axial as compared with the short axis view [RVEDV 247 ± 67 vs. 233 ± 54 ml (p = 0.002) and RVESV 148 ± 54 vs. 136 ± 50 ml (p = 0.001)], mean RV ejection fractions (EF) were similar [41 ± 9 % vs. 43 ± 12 % (p = 0.13)]. Bland-Altman plots demonstrated better agreement for axial measures of RVEDV and right ventricular ejection fraction (RVEF) within and between observers. Similarly, ICC values were stronger for axial as compared with short axis volumes and function-intraobserver RVEDV 0.99 (0.98-0.99) versus 0.96 (0.92-0.98) and RVEF 0.96 (0.93-0.98) versus 0.90 (0.82-0.95); interobserver RVEDV 0.97 (0.94-0.98) versus 0.90 (0.73-0.95) and RVEF 0.85 (0.53-0.94) versus 0.82 (0.67-0.90). Axially derived measurements of RV volumes and function have better agreement and reproducibility as compared with short axis values; whereas axial volumes tend to be larger, RVEF is not significantly different between the two methods.

Potential clinical impact of cardiovascular magnetic resonance assessment of ejection fraction on eligibility for cardioverter defibrillator implantation.

BACKGROUND: For the primary prevention of sudden cardiac death, guidelines provide left ventricular ejection fraction (EF) criteria for implantable cardioverter defibrillator (ICD) placement without specifying the technique by which it should be measured. We sought to investigate the potential impact of performing cardiovascular magnetic resonance (CMR) for EF on ICD eligibility. METHODS: The study population consisted of patients being considered for ICD implantation who were referred for EF assessment by CMR. Patients who underwent CMR within 30 days of echocardiography were included. Echocardiographic EF was determined by Simpson's biplane method and CMR EF was measured by Simpson's summation of discs method. RESULTS: Fifty-two patients (age 62±15 years, 81% male) had a mean EF of 38 ± 14% by echocardiography and 35 ± 14% by CMR. CMR had greater reproducibility than echocardiography for both intra-observer (ICC, 0.98 vs 0.94) and inter-observer comparisons (ICC 0.99 vs 0.93). The limits of agreement comparing CMR and echocardiographic EF were - 16 to +10 percentage points. CMR resulted in 11 of 52 (21%) and 5 of 52 (10%) of patients being reclassified regarding ICD eligibility at the EF thresholds of 35 and 30% respectively. Among patients with an echocardiographic EF of between 25 and 40%, 9 of 22 (41%) were reclassified by CMR at either the 35 or 30% threshold. Echocardiography identified only 1 of the 6 patients with left ventricular thrombus noted incidentally on CMR. CONCLUSIONS: CMR resulted in 21% of patients being reclassified regarding ICD eligibility when strict EF criteria were used. In addition, CMR detected unexpected left ventricular thrombus in almost 10% of patients. Our findings suggest that the use of CMR for EF assessment may have a substantial impact on management in patients being considered for ICD implantation.

A computed tomography-based coronary lesion score to predict acute coronary syndrome among patients with acute chest pain and significant coronary stenosis on coronary computed tomographic angiogram.

We tested the hypothesis that morphologic lesion assessment helps detect acute coronary syndrome (ACS) during index hospitalization in patients with acute chest pain and significant stenosis on coronary computed tomographic angiogram (CTA). Patients who presented to an emergency department with chest pain but no objective signs of myocardial ischemia (nondiagnostic electrocardiogram and negative initial biomarkers) underwent CT angiography. CTA was analyzed for degree and length of stenosis, plaque area and volume, remodeling index, CT attenuation of plaque, and spotty calcium in all patients with significant stenosis (>50% in diameter) on CTA. ACS during index hospitalization was determined by a panel of 2 physicians blinded to results of CT angiography. For lesion characteristics associated with ACS, we determined cutpoints optimized for diagnostic accuracy and created lesion scores. For each score, we determined the odds ratio (OR) and discriminatory capacity for the prediction of ACS. Of the overall population of 368 patients, 34 had significant stenosis and 21 of those had ACS. Scores A (remodeling index plus spotty calcium: OR 3.5, 95% confidence interval [CI] 1.2 to 10.1, area under curve [AUC] 0.734), B (remodeling index plus spotty calcium plus stenosis length: OR 4.6, 95% CI 1.6 to 13.7, AUC 0.824), and C (remodeling index plus spotty calcium plus stenosis length plus plaque volume <90 HU: OR 3.4, 95% CI 1.5 to 7.9, AUC 0.833) were significantly associated with ACS. In conclusion, in patients presenting with acute chest pain and stenosis on coronary CTA, a CT-based score incorporating morphologic characteristics of coronary lesions had a good discriminatory value for detection of ACS during index hospitalization.

Thrombus aspiration during primary percutaneous coronary intervention is associated with reduced myocardial edema, hemorrhage, microvascular obstruction and left ventricular remodeling.

BACKGROUND: Thrombus aspiration (TA) has been shown to improve microvascular perfusion during primary percutaneous coronary intervention (PCI) for patients with ST-segment elevation myocardial infarction (STEMI). The objective of our study was to assess the relationship between TA and myocardial edema, myocardial hemorrhage, microvascular obstruction (MVO) and left ventricular remodeling in STEMI patients using cardiovascular magnetic resonance (CMR). METHODS: Sixty patients were enrolled post primary PCI and underwent CMR on a 1.5 T scanner at 48 hours and 6 months. Patients were retrospectively stratified into 2 groups: those that received TA (35 patients) versus that did not receive thrombus aspiration (NTA) (25 patients). Myocardial edema and myocardial hemorrhage were assessed by T2 and T2* quantification respectively. MVO was assessed via a contrast-enhanced T1-weighted inversion recovery gradient-echo sequence. RESULTS: At 48 hours, infarct segment T2 (NTA 57.9 ms vs. TA 52.1 ms, p = 0.022) was lower in the TA group. Also, infarct segment T2* was higher in the TA group (NTA 29.3 ms vs. TA 37.8 ms, p = 0.007). MVO incidence was lower in the TA group (NTA 88% vs. TA 54%, p = 0.013).At 6 months, left ventricular end-diastolic volume index (NTA 91.9 ml/m2 vs. TA 68.3 ml/m2, p = 0.013) and left ventricular end systolic volume index (NTA 52.1 ml/m2 vs. TA 32.4 ml/m2, p = 0.008) were lower and infarct segment systolic wall thickening was higher in the TA group (NTA 3.5% vs. TA 74.8%, p = 0.003). CONCLUSION: TA during primary PCI is associated with reduced myocardial edema, myocardial hemorrhage, left ventricular remodeling and incidence of MVO after STEMI.

Association of pericardial fat and coronary high-risk lesions as determined by cardiac CT.

OBJECTIVE: Pericardial adipose tissue (PAT) is a pathogenic fat depot associated with coronary atherosclerosis and cardiovascular events. We hypothesized that higher PAT is associated with coronary high-risk lesions as determined by cardiac CT. METHODS: We included 358 patients (38% female; median age 51 years) who were admitted to the ED with acute chest pain and underwent 64-slice CT angiography. The cardiac CT data sets were assessed for presence and morphology of CAD and PAT. Coronary high-risk lesions were defined as >50% luminal narrowing and at least two of the following characteristics: positive remodeling, low-density plaque, and spotty calcification. PAT was defined as any pixel with CT attenuation of -190 to -30 HU within the pericardial sac. RESULTS: Based on cardiac CT, 50% of the patients (n=180) had no CAD, 46% (n=165) had CAD without high-risk lesions, and 13 patients had CAD with high-risk lesions. The median PAT in patients with high-risk lesions was significantly higher compared to patients without high-risk lesions and without any CAD (151.9 [109.0-179.4]cm(3) vs. 110.0 [81.5-137.4]cm(3), vs. 74.8 [58.2-111.7]cm(3), respectively p=0.04 and p<0.0001). These differences remained significant after adjusting for traditional risk factors including BMI (all p<0.05). The area under the ROC curve for the identification of high-risk lesions was 0.756 in a logistic regression model with PAT as a continuous predictor. CONCLUSION: PAT volume is nearly twice as high in patients with high-risk coronary lesions as compared to those without CAD. PAT volume is significantly associated with high risk coronary lesion morphology independent of clinical characteristics and general obesity.