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Atherosclerosis is the commonest cause of death in Australia. Cardiovascular (CV) risk calculators have an important role in preventative cardiology, although they are are strongly age-dependent and designed to identify individuals at high risk of an imminent event. The imprecision around “intermediate” or “low” risk generates therapeutic uncertainty, and a significant proportion of patients presenting with myocardial infarction come from these groups, often with no warning. This highlights a conundrum: “Low” risk does not mean “no” risk. A fresh approach may be required to address the clinical conundrum around CV preventative approaches in non-high-risk individuals. While probabilistic calculators do not measure atherosclerosis, calculation of Coronary Artery Calcium (CAC) scores by low-dose computed tomography (CT) can provide a snapshot of atherosclerotic burden. In intermediate-risk individuals, CAC is well-established as an aid to CV risk prediction. Although CAC scoring in low-risk asymptomatic people may be considered controversial, CAC has emerged as the single best predictor of CV events in asymptomatic individuals, independent of traditional risk factor calculators. Therefore, apart from the contribution of age and sex, the somewhat arbitrary distinction between “intermediate” and “low” CV risk using probabilistic calculators may need to be reconsidered. A zero CAC score has a very low future event rate and non-zero CAC scores are associated with a progressive, graded increase in risk as the CAC score rises. In this review, we examine the evidence for CAC screening in low-risk individuals, and propose more widespread use of CAC using simple new model intended to enhance established CV risk prediction equations.

Background: Idiopathic VA are traditionally considered benign, although occasional patients develop an ectopy-mediated cardiomyopathy (EMC). It is unclear whether patients with idiopathic VA in the absence of left ventricular (LV) dysfunction harbor a subclinical cardiomyopathy. We aim to assess for cardiomyopathic substrate in patients with idiopathic ventricular arrhythmias (VA) using imaging and electrophysiologic markers of early fibrosis. Methods: Cardiac magnetic resonance (CMR) imaging and ventricular electroanatomic mapping was performed in 3 groups: patients undergoing ablation for idiopathic VA without (Group 1, n = 17) and with LV dysfunction (Group 2 [presumed EMC], n = 12) plus a control group undergoing ablation of supraventricular tachycardia (Group 3, n = 16). Global LV strain, T1 mapping and extended electrogram (EGM) characteristics were compared. Results: Global strain was impaired in patients with presumed EMC (Group 2, p < 0.001). Native T1 times did not differ between groups, however patients in both idiopathic VA groups (Groups 1 and 2) had shorter post-contrast T1 times at 8 min compared to SVT controls (Group 3, p = 0.04). Similarly, the duration of the bipolar EGM was subtly prolonged in both Group 1 and 2 compared to Group 3 (p = 0.002). There were no between group differences in unipolar or bipolar voltage, the no. of bipolar EGM deflections or the maximal unipolar EGM dV/dt. Conclusion: Patients with idiopathic VAs and apparently structurally normal hearts may have subtle CMR and electrophysiologic changes similar in magnitude to that seen in frank presumed EMC, possibly suggestive of an occult cardiomyopathic process.

Objective: Ultra-high-field B0 ≥ 7 tesla (7T) cardiovascular magnetic resonance (CMR) offers increased resolution. However, electrocardiogram (ECG) gating is impacted by the magneto-hydrodynamic effect distorting the ECG trace. We explored the technical feasibility of a 7T magnetic resonance scanner using an ECG trigger learning algorithm to quantitatively assess cardiac volumes and vascular flow. Methods: 7T scans were performed on 10 healthy volunteers on a whole-body research MRI MR scanner (Siemens Healthineers, Erlangen, Germany) with 8 channel Tx/32 channels Rx cardiac coils (MRI Tools GmbH, Berlin, Germany). Vectorcardiogram ECG was performed using a learning phase outside of the magnetic field, with a trigger algorithm overcoming severe ECG signal distortions. Vectorcardiograms were quantitatively analyzed for false negative and false positive events. Cine CMR was performed after 3rd-order B0 shimming using a high-resolution breath-held ECG-retro-gated segmented spoiled gradient echo, and 2D phase contrast flow imaging. Artefacts were assessed using a semi-quantitative scale. Results: 7T CMR scans were acquired in all patients (100%) using the vectorcardiogram learning method. 3,142 R-waves were quantitatively analyzed, yielding sensitivity of 97.6% and specificity of 98.7%. Mean image quality score was 0.9, sufficient to quantitate both cardiac volumes, ejection fraction, and aortic and pulmonary blood flow. Mean left ventricular ejection fraction was 56.4%, right ventricular ejection fraction was 51.4%. Conclusion: Reliable cardiac ECG triggering is feasible in healthy volunteers at 7T utilizing a state-of-the-art three-lead trigger device despite signal distortion from the magnetohydrodynamic effect. This provides sufficient image quality for quantitative analysis. Other ultra-high-field imaging applications such as human brain functional MRI with physiologic noise correction may benefit from this method of ECG triggering.

We present a case of late presentation nontropical endomyocardial fibrosis isolated to the right ventricle and tricuspid valve (TV). In response to deteriorating hemodynamics, surgical debulking and TV removal were performed before initiation of centralized venoarterial extracorporeal membrane oxygenation support. Definitive endomyocardial resection with a TV prosthesis was then successfully completed. (Level of Difficulty: Advanced.), Central Illustration

Background Gadolinium-based contrast agents were not approved in the United States for detecting coronary artery disease (CAD) prior to the current studies. Objectives The purpose of this study was to determine the sensitivity and specificity of gadobutrol for detection of CAD by assessing myocardial perfusion and late gadolinium enhancement (LGE) imaging. Methods Two international, single-vendor, phase 3 clinical trials of near identical design, “GadaCAD1” and “GadaCAD2,” were performed. Cardiovascular magnetic resonance (CMR) included gadobutrol-enhanced first-pass vasodilator stress and rest perfusion followed by LGE imaging. CAD was defined by quantitative coronary angiography (QCA) but computed tomography coronary angiography could exclude significant CAD. Results Because the design and results for GadaCAD1 (n = 376) and GadaCAD2 (n = 388) were very similar, results were summarized as a fixed-effect meta-analysis (n = 764). The prevalence of CAD was 27.8% defined by a ≥70% QCA stenosis. For detection of a ≥70% QCA stenosis, the sensitivity of CMR was 78.9%, specificity was 86.8%, and area under the curve was 0.871. The sensitivity and specificity for multivessel CAD was 87.4% and 73.0%. For detection of a 50% QCA stenosis, sensitivity was 64.6% and specificity was 86.6%. The optimal threshold for detecting CAD was a ≥67% QCA stenosis in GadaCAD1 and ≥63% QCA stenosis in GadaCAD2. Conclusions Vasodilator stress and rest myocardial perfusion CMR and LGE imaging had high diagnostic accuracy for CAD in 2 phase 3 clinical trials. These findings supported the U .S. Food and Drug Administration approval of gadobutrol-enhanced CMR (0.1 mmol/kg) to assess myocardial perfusion and LGE in adult patients with known or suspected CAD.

Objectives: The aim of this study was to define normal ventricular electrographic characteristics in T1 mapping–validated normal patients using a contemporary contact force catheter. Background: Reference values for human endocardial ventricular electrographic characteristics have not been defined using contemporary mapping equipment in patients without heart disease or ventricular arrhythmias. Methods: Fourteen patients undergoing SVT ablation underwent mapping of the right ventricle and cardiac magnetic resonance imaging with T1 mapping. Electrograms (EGMs) from sites with >10 g of contact force from the right ventricular free wall (RVFW) and right ventricular septum (RVS) were analyzed. Values 95th percentile were defined as abnormal. Results: The median age was 27 years, 64% of patients were men, and the mean left ventricular ejection fraction was 60%. Native T1 values (mean 979 ms) of the study population were comparable with that of a normal volunteer population. Ninety-five percent of bipolar EGMs had 0.23 mV/ms (RVFW) or >0.24 mV/ms (RVS). Ninety-five percent of unipolar EGMs had a peak-to-peak voltage >3.8 mV (RVFW) or >4.5 mV (RVS). Conclusions: In structurally normal hearts, the threshold for abnormal endocardial unipolar voltage in the RVFW (3.8 mV) is lower than that of the current standard (5.5 mV). The unipolar voltage characteristics of the RVS is distinct from that of the RVFW and left ventricle. This has implications for the detection of intramural or epicardial and especially midseptal scar.

Key Points: 1. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease affecting the right, and/or the left ventricle, and commonly presents as an electrical disorder with ventricular arrhythmias and increased risk of sudden cardiac death. 2. ARVC cannot be diagnosed by a single test, and is a clinical diagnosis supported by electrophysiologic, morpho-functional, genetic, and histological data based on the 2010 Task Force 2 criteria. 3. Familial involvement occurs in more than 50%, and referral to a specialist centre with access to genotyping is appropriate in selected cases. 4. Implantable cardioverter-defibrillator (ICD) therapy carries risk, and appropriate thresholds should apply before offering this, particularly in younger individuals.

Highlights • Left ventricular global longitudinal strain (LV GLS) is a sensitive parameter that correlates with myocardial scar burden and fibrosis with potential value in CRT candidates. • First systematic review evaluating the existing evidence for the prognostic value of LV GLS in patients undergoing CRT implantation. • Despite significantly abnormal baseline GLS at CRT implantation, there is still a significant association between incrementally worse LV GLS at CRT implantation and prognostic outcomes on long-term follow-up., Purpose Cardiac resynchronisation therapy (CRT) has proven mortality benefits for heart failure patients with moderate to severe systolic left ventricular dysfunction and evidence of a left bundle branch block. Determining responders to this therapy can be difficult due to the presence of myocardial fibrosis and scar. Left ventricular global longitudinal strain (LV GLS) is a robust and sensitive measure of myocardial function and fibrosis that has significant prognostic value for a plethora of cardiac pathologies. Our aim was to perform a systematic review of the value of LV GLS for predicting outcomes in patients undergoing CRT. Methods A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocol for reporting on systematic reviews and meta-analyses. An electronic search of all English, adult publications in EMBASE, MEDLINE/PubMed and the Cochrane Database of Systematic reviews was undertaken. Results The search yielded, 9 studies that included 3,981 patients with symptomatic heart failure, undergoing CRT implantation with LV GLS utilised as a predictor of all-cause mortality, cardiovascular death, rehospitalisation, LVAD implantation/ heart transplantation or left ventricular reverse remodelling. Significant heterogeneity was observed in study outcome measures, included populations, LV-GLS cut-offs and follow-up definitions, resulting in the inability to reliably conduct a meta-analyses. Overall, pre-CRT LV GLS was found to be a predictor of outcome post CRT insertion. Conclusions In conclusion, all studies implied that incrementally abnormal baseline LV GLS pre-CRT implantation was associated with a long term poorer outcome.

Background: In early 2020, COVID-19 massively hit Italy, earlier and harder than any other European country. This caused a series of strict containment measures, aimed at blocking the spread of the pandemic. Healthcare delivery was also affected when resources were diverted towards care of COVID-19 patients, including intensive care wards. Aim of the study: The aim is assessing the impact of COVID-19 on cardiac imaging in Italy, compare to the Rest of Europe (RoE) and the World (RoW). Methods: A global survey was conducted in May–June 2020 worldwide, through a questionnaire distributed online. The survey covered three periods: March and April 2020, and March 2019. Data from 52 Italian centres, a subset of the 909 participating centres from 108 countries, were analyzed. Results: In Italy, volumes decreased by 67% in March 2020, compared to March 2019, as opposed to a significantly lower decrease (p < 0.001) in RoE and RoW (41% and 40%, respectively). A further decrease from March 2020 to April 2020 summed up to 76% for the North, 77% for the Centre and 86% for the South. When compared to the RoE and RoW, this further decrease from March 2020 to April 2020 in Italy was significantly less (p = 0.005), most likely reflecting the earlier effects of the containment measures in Italy, taken earlier than anywhere else in the West. Conclusions: The COVID-19 pandemic massively hit Italy and caused a disruption of healthcare services, including cardiac imaging studies. This raises concern about the medium- and long-term consequences for the high number of patients who were denied timely diagnoses and the subsequent lifesaving therapies and procedures.

A 72-year-old woman presented for routine echocardiography 6 months following percutaneous insertion of a left atrial appendage occluder (LAAO) due to atrial fibrillation with contraindications to anticoagulation. The procedure was uncomplicated, and she was clinically well. On echocardiography an abnormality was seen in the posterior pericardial space (Figure 1, arrows). Figure 1 Transthoracic Echocardiogram: left, parasternal long axis. right, parasternal short axis …

Background:Left ventricular non-compaction has been associated with heart failure, arrhythmia, thromboembolism and sudden death. The prevalence of non-compaction in patients with coarctation of the aorta and its clinical significance remains unknown, although obstructive left heart disease is common in patients with non-compaction. We sought to evaluate the prevalence of left ventricular non-compaction in patients with repaired aortic coarctation as well as its effect on left ventricular size and systolic function.Methods and results:In total, 268 patients (Mean age 26 (inter-quartile range 21–37) years, 63% male) undergoing cardiac magnetic resonance imaging for clinical follow-up were included from three tertiary centres for adult congenital heart disease. Clinical data was obtained from medical records and correlated with ventricular volumes and function. Left ventricular non-compaction was defined as a diastolic non-compacted:compacted dimension ratio >2.3 in the worst affected segment on a long-axis view. Left ventricular non-compaction was present in 8.2% of patients with repaired coarctation. Left ventricular end-diastolic volumes and stroke volumes were significantly higher in patients with non-compaction compared to those without. There were no significant differences in ventricular mass or ejection fraction in these two groups.Conclusions:Left ventricular non-compaction is relatively common in patients with repaired coarctation of the aorta and correlates with increased left ventricular end-diastolic volumes.

OBJECTIVES: The INCAPS COVID Oceania study aimed to assess the impact caused by the COVID-19 pandemic on cardiac procedure volume provided in the Oceania region. METHODS: A retrospective survey was performed comparing procedure volumes within March 2019 (pre-COVID-19) with April 2020 (during first wave of COVID-19 pandemic). Sixty-three (63) health care facilities within Oceania that perform cardiac diagnostic procedures were surveyed, including a mixture of metropolitan and regional, hospital and outpatient, public and private sites, and 846 facilities outside of Oceania. The percentage change in procedure volume was measured between March 2019 and April 2020, compared by test type and by facility. RESULTS: In Oceania, the total cardiac diagnostic procedure volume was reduced by 52.2% from March 2019 to April 2020, compared to a reduction of 75.9% seen in the rest of the world (p

Objective: To define the diagnostic yield of cardiac magnetic resonance (CMR) in differentiating the underlying causes of myocardial infarction with nonobstructive coronary arteries (MINOCA) and to determine the long-term prognostic implications of such diagnoses. Methods: Cardiac magnetic resonance evaluation was performed in 227 patients (mean age, 56.4±14.9 years; 120 [53%] female) with a “working diagnosis” of MINOCA as defined by presentation with a troponin-positive acute coronary syndrome (troponin I >0.04 μg/L) and nonobstructed coronary arteries between January 1, 2007, and February 28, 2013. Follow-up was performed to assess the primary composite end point of myocardial infarction, heart failure, and all-cause mortality. Results: Cardiac magnetic resonance identified nonstructural cardiomyopathies in 97 (43%) patients, myocardial infarction in 55 (24%) patients, structural cardiomyopathies in 27 (12%) patients, and pulmonary embolism in 1 patient. No CMR abnormalities were identified in the remaining patients. Kaplan-Meier analysis demonstrated the ability of a CMR diagnosis to predict the risk of the primary composite end point (P=.005) at 5-year follow-up. Worse outcomes were seen among patients with “true” MINOCA and a normal CMR image compared with those with CMR-confirmed myocardial infarction (P=.02). Use of antiplatelets (78% [37/45] vs 95% [52/55]; P=.01), beta blockers (56% [25/45] vs 82% [45/55]; P=.004), and statins (64% [29/45] vs 85% [47/55]; P=.01) was significantly lower in patients with true MINOCA with normal CMR imaging compared with those with CMR-confirmed myocardial infarction. Conclusions: Cardiac magnetic resonance carries a high diagnostic yield in patients with MINOCA and predicts long-term prognosis. Patients with MINOCA with normal CMR imaging had an increased rate of major adverse cardiac events and lower use of guideline-recommended myocardial infarction therapy compared with those with CMR-confirmed myocardial infarction.

Objective:Left ventricular non-compaction is an architectural abnormality of the myocardium, associated with heart failure, systemic thromboembolism, and arrhythmia. We sought to assess the prevalence of left ventricular non-compaction in patients with single ventricle heart disease and its effects on ventricular function.Methods:Cardiac MRI of 93 patients with single ventricle heart disease (mean age 24 ± 8 years; 55% male) from three tertiary congenital centres was retrospectively reviewed; 65 of these had left ventricular morphology and are the subject of this report. The presence of left ventricular non-compaction was defined as having a non-compacted:compacted (NC:C) myocardial thickness ratio >2.3:1. The distribution of left ventricular non-compaction, ventricular volumes, and function was correlated with clinical data.Results:The prevalence of left ventricular non-compaction was 37% (24 of 65 patients) with a mean of 4 ± 2 affected segments. The distribution was apical in 100%, mid-ventricular in 29%, and basal in 17% of patients. Patients with left ventricular non-compaction had significantly higher end-diastolic (128 ± 44 versus 104 ± 46 mL/m2, p = 0.047) and end-systolic left ventricular volumes (74 ± 35 versus 56 ± 35 mL/m2, p = 0.039) with lower left ventricular ejection fraction (44 ± 11 versus 50 ± 9%, p = 0.039) compared to those with normal compaction. The number of segments involved did not correlate with ventricular function (p = 0.71).Conclusions:Left ventricular non-compaction is frequently observed in patients with left ventricle-type univentricular hearts, with predominantly apical and mid-ventricular involvement. The presence of non-compaction is associated with increased indexed end-diastolic volumes and impaired systolic function.

BACKGROUND Right ventricular (RV) failure is the main cause of mortality in pulmonary arterial hypertension (PAH). Exercise testing helps identify early RV maladaptation and systolic dysfunction and facilitates therapy. Myocardial strain has been shown to be more sensitive than ejection fraction (EF) in detecting subclinical ventricular contractile dysfunction. Chronic pressure overload in PAH had been associated with changes in left ventricular (LV) filling. PURPOSE To compare biventricular strains and ventriculo-ventricular interaction in PAH and controls using cardiac magnetic resonance feature tracking (cMRI-FT) and to determine the reproducibility of strain analysis. STUDY TYPE Prospective. POPULATION Nine PAH and nine control subjects. FIELD STRENGTH/SEQUENCE 1.5T MRI balanced steady state free precession. ASSESSMENT RV and LV longitudinal strain (EllRV and EllLV ) were derived using the mid-axial images. Radial (ErrLV ) and circumferential strain (EccLV ) were derived using the mid-ventricular short-axis images. Relationships between strain and volumetric parameters were assessed at rest and during submaximal in-magnet exercise. STATISTICAL TESTS Comparison of rest-to-exercise data between PAH and controls was analyzed using two-way repeated measures analysis of variance. The relationship between volumetric parameters and cMRI-FT were assessed using Pearson's correlation. Reproducibility was assessed by using Bland-Altman plots. RESULTS PAH had significantly lower EllRV at rest (-16.6 ± 2.7 vs. -20.1 ± 3.6, P = 0.03) despite normal RVEF. During exercise, RV systolic contractile reserve measured by EllRV was significantly reduced in PAH (PInteraction = 0.02). In PAH, indexed RV end-systolic volume (ESVi) significantly correlated with EccLV and ErrLV at rest (r = -0.65 and r = -0.70, P < 0.05) and with ErrLV during exercise (r = -0.43, P < 0.05). High observer agreement was demonstrated. DATA CONCLUSION Despite normal resting RVEF, RV systolic function and contractile reserve as measured by EllRV was significantly reduced in PAH. The close relation between RVESVi with EccLV and ErrLV provides evidence of systolic ventriculo-ventricular interaction in PAH. Exercise cMRI-FT may provide a quantitative metric for detection of subclinical RV dysfunction in PAH. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1427-1436.

BACKGROUND The left ventricular (LV) papillary muscles are important components of the mitral valve apparatus. Catheter ablation of ventricular arrhythmias from these sites is challenging. We aim to describe the association between LV papillary muscle ventricular arrhythmias (VAs) and mitral valve prolapse (MVP), and to determine the outcomes of ablation in these patients with a focus on those with MVP and cardiomyopathy. METHODS A total of 152 patients underwent 170 consecutive procedures for ablation of focal VAs. MVP and cardiomyopathy were diagnosed by echocardiography. Outcomes following ablation were assessed in three groups: (1) LV papillary muscle VAs versus other sites, (2) LV papillary muscle VAs by the presence of MVP, and (3) LV papillary muscle VAs in the setting of cardiomyopathy. RESULTS Nine of 23 (39%) patients undergoing ablation of LV papillary muscle VAs had MVP compared to none of 129 (0%) patients at other sites (P

Coronary Artery Calcium Scoring (CAC) is a non-invasive quantitation of coronary artery calcification using computed tomography (CT). It is a marker of atherosclerotic plaque burden and an independent predictor of future myocardial infarction and mortality. Coronary Artery Calcium Scoring provides incremental risk information beyond traditional risk calculators (eg. Framingham Risk Score). Its use for risk stratification is confined to primary prevention of cardiovascular events, and can be considered as "individualised coronary risk scoring" for those not considered to be of high or low risk. Medical practitioners should carefully counsel patients prior to CAC. Coronary Artery Calcium Scoring should only be undertaken if an alteration in therapy including embarking on pharmacotherapy is being considered based on the test result. Patient Groups to Consider Coronary Calcium Scoring: Patient Groups in Whom Coronary Calcium Scoring Should Not be Considered: Coronary Artery Calcium Scoring is not recommended for patients who are: Interpretation of CAC CAC=0 A zero score confers a very low risk of death,1% at 10 years. CAC=1-100 Low risk,10% CAC=101-400 Intermediate risk, 10-20% CAC=101-40075th centile. Moderately high risk, 15-20% CAC400 High risk,20% Management Recommendations Based on CAC Optimal diet and lifestyle measures are encouraged in all risk groups and form the basis of primary prevention strategies. Patients with moderately-high or high risk based on CAC score are recommended to receive preventative medical therapy such as aspirin and statins. The evidence for pharmacotherapy is less robust in patients at intermediate levels of CAC 100-400, with modest benefit for aspirin use; though statins may be reasonable if they are above 75th centile. Aspirin and statins are generally not recommended in patients with CAC100. Repeat CAC Testing In patients with a CAC of 0, a repeat CAC may be considered in 5 years but not sooner. In patients with positive calcium score, routine re-scanning is not currently recommended. However, an annual increase in CAC of15% or annual increase of CAC100 units are predictive of future myocardial infarction and mortality. Cost Effectiveness of CAC Based Primary Prevention Recommendations: There is currently no data in Australia and New Zealand that CAC is cost-effective in informing primary prevention decisions. Given the cost of testing is currently borne entirely by the patient, discussion regarding the implications of CAC results should occur before CAC is recommended and undertaken.

Background The application of left ventricular (LV) global strain by speckle-tracking is becoming more widespread, with the potential for incorporation into routine clinical echocardiography in selected patients. There are no guidelines or recommendations for the training requirements to achieve competency. The aim of this study was to determine the learning curve for global strain analysis and determine the number of studies that are required for independent reporting. Methods Three groups of novice observers (cardiology fellows, cardiac sonographers, medical students) received the same standardized training module prior to undertaking retrospective global strain analysis on 100 patients over a period of 3 months. To assess the effect of learning, quartiles of 25 patients were read successively by each blinded observer, and the results were compared to expert for correlation. Results Global longitudinal strain (GLS) had uniform learning curves and was the easiest to learn, requiring a minimum of 50 patients to achieve expert competency (intraclass correlation coefficient > 0.9) in all three groups over a period of 3 months. Prior background knowledge in echocardiography is an influential factor affecting the learning for interobserver reproducibility and time efficiency. Short-axis strain analysis using global circumferential stain and global radial strain did not yield a comprehensive learning curve, and expert level was not achieved by the end of the study. Conclusions There is a significant learning curve associated with LV strain analysis. We recommend a minimum of 50 studies for training to achieve competency in GLS analysis.

The steady state expression of each gene is the result of a dynamic transcription and degradation of that gene. While regular RNA-seq methods only measure steady state expression levels, RNA-seq of metabolically labeled RNA identifies transcripts that were transcribed during the window of metabolic labeling. Whereas short-read RNA sequencing can identify metabolically labeled RNA at the gene level, long-read sequencing provides much better resolution of isoform-level transcription. Here we combine thiouridine-to-cytosine conversion (TUC) with PacBio long-read sequencing to study the dynamics of mRNA transcription in the GM12878 cell line. We show that using long-TUC-seq, we can detect metabolically labeled mRNA of distinct isoforms more reliably than using short reads. Long-TUC-seq holds the promise of capturing isoform dynamics robustly and without the need for enrichment.

In this review discuss the application of cardiac magnetic resonance (CMR) to the evaluation and quantification of mitral regurgitation and provide a systematic literature review for comparisons with echocardiography. Using the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, we searched Medline and PubMed for original research articles published since 2000 that provided data on the quantification of mitral regurgitation by CMR. We identified 220 articles of which 33 were included. Four main techniques of mitral regurgitation quantification were identified. Reproducibility varied substantially between papers but was high overall for all techniques. However, quantification differed between the techniques studied. When compared with two-dimensional echocardiography, mitral regurgitation fraction and regurgitant volume measured by CMR were comparable but typically lower. CMR has high reproducibility for the quantification of mitral regurgitation in experienced centres, but further technological refinement is needed. An integrated and standardised approach that combines multiple techniques is recommended for optimal reproducibility and precise mitral regurgitation quantification. Definitive outcome studies using CMR as a basis for treatment are lacking but needed.

Background: Many echocardiographic parameters have been proposed to evaluate right ventricular (RV) systolic function. We comprehensively assessed a wide range of quantitative echocardiographic parameters in a single cohort compared with same-day cardiovascular magnetic resonance (CMR). Methods and results: 92 subjects were examined prospectively: Group 1 consisted of 46 healthy controls (21 males, 33.4 ± 11.4 years), Group 2 consisted of 46 patients (20 males, 38.5 ± 18.9 years) undergoing RV functional assessment by CMR (1.5 T). Echocardiography was performed on the same day as CMR; fractional area change (RVFAC), myocardial performance index via spectral Doppler (RVMPI), RVMPI via Doppler tissue imaging (RVMPI-DTI), peak systolic myocardial velocity by DTI (RVSm), tricuspid annular plane systolic excursion (TAPSE), speckle tracking strain, and three dimensional right ventricular ejection fraction (3DE-RV). Linear regression, Bland-Altman and receiver-operator-characteristic (ROC) analyses were performed. At ROC analysis, the most predictive echocardiographic methods were; RVFAC (AUC = 0.892), RVMPI (AUC 0.785), TAPSE (AUC 0.849) and 3DE-RV (AUC 0.909). 3DE-RV appeared the most accurate compared to CMR, although underestimated true RV volumes. Conclusion: As compared to CMR; 3DE-RV, RVFAC, TAPSE and RVMPI were the most reliable predictors of RV function. These parameters can be recommended for clinical use.

Coronary artery disease (CAD) is the leading single cause of death in Australia affecting around 1.4 million people. Coronary computed tomography angiography has an established role in the assessment of patients with low to intermediate pretest probability for CAD who have chest pain and is typically used with the aim to rule out significant coronary artery stenosis. Use was initially limited because of concerns over radiation exposure, a Medicare rebate restricted to specialist referrals and an absence of data supporting its use as an alternative to functional testing in patients with chest pain. Recent advances in scanner technology and image sequencing, along with data from randomised control trials, have addressed these issues and indicate that coronary computed tomography angiography will play a greater role in the assessment of CAD in the coming years.

AIM Transthoracic echocardiography (TTE) is a fundamental investigation for the noninvasive assessment of pulmonary hemodynamics and right heart function. The aim of this study was to assess the correlation and agreement of Doppler calculation of right ventricular systolic pressure (RVSP) and pulmonary vascular resistance (PVR) using "chin" and "beard" measurements of tricuspid regurgitant velocity (TRVmax ), with invasive pulmonary artery systolic pressure (PASP) and PVR. METHODS One hundred patients undergoing right heart catheterisation (RHC) and near simultaneous transthoracic echocardiography were studied. TRVmax was recorded for "chin" measurement (distinct peak TRVmax signal) and where available (63 patients), "beard" measurement (higher indistinct peak TRVmax signal). RESULTS Measurable TRV signal was obtained in 96 patients. Mean RVSPchin 54.7 ± 22.7 mm Hg and RVSPbeard 68.6 = 23 ± 26.3 mm Hg (P

Coronary CT angiography (CCTA) has high sensitivity, with 3 recent randomized trials favorably comparing CCTA to standard-of-care. Comparison to exercise stress ECG (ExECG), the most available and least expensive standard-of-care worldwide, has not been systematically tested.CT-COMPARE was a randomized, single-center trial of low-intermediate risk chest pain subjects undergoing CCTA or ExECG after the first negative troponin. From March 2010 to April 2011, 562 patients randomized to either dual-source CCTA (n=322) or ExECG (n=240). Primary endpoints were diagnostic performance for ACS, and hospital cost at 30 days. Secondary endpoints were time-to-discharge, admission rates, and downstream resource utilization.ACS occurred in 24 (4%) patients. ExECG had 213 negative studies and 27 (26%) positive studies for ACS with sensitivity of 83% [95% CI: 36, 99.6%], specificity of 91% [CI: 86, 94%], and ROC AUC of 0.87 [CI: 0.70, 1]. CCTA (50% stenosis considered positive) had 288 negative studies and 18/35 (51%) positive studies with a sensitivity of 100% [CI: 81.5, 100], specificity of 94% [CI: 91.2, 96.7%], and ROC of 0.97 [CI: 0.92, 1.0; p=0.2]. Despite CCTA having higher odds of downstream testing (OR 2.0), 30 day per-patient cost was significantly lower for CCTA ($2193 vs $2704, p0.001). Length of stay for CCTA was significantly reduced (13.5h [95% CI: 11.2-15.7], ExECG 19.7h [95% CI: 17.4-22.1], p0.0005), which drove the reduction in cost. No patient had post-discharge cardiovascular events at 30 days.CCTA had improved diagnostic performance compared to ExECG, combined with 35% relative reduction in length-of-stay, and 20% reduction in hospital costs. These data lend further evidence that CCTA is useful as a first line assessment in emergency department chest pain.

Background: Accurate evaluation of the tricuspid regurgitant (TR) spectral Doppler signal is important during transthoracic echocardiographic (TTE) evaluation for pulmonary hypertension (PHT). Contrast enhancement improves Doppler backscatter. However, its incremental benefit with contemporary scanners is less well established. The aim of this study was to assess whether the TR spectral Doppler signal using contemporary scanners was improved using a second generation contrast agent, Definity® (CE), compared to unenhanced TTE (UE). Methods: Analysis of patients who underwent UE then CE TR interrogation was performed. TR signal was evaluated by an experienced reader and graded 1 (clear-high level of confidence of interpretation and complete spectral Doppler envelope), 2 (suboptimal with medium-low level of confidence of interpretation and incomplete envelope), 3 (poor-absent and no measurable spectral Doppler signal). Maximal TR velocity (TRV) was defined as peak velocity that could be clearly identified. An inexperienced sonographer read 30 randomly selected studies. Results: 176 TTE were performed in 173 patients (mean age 57 ± 14.8 years). Wilcoxon signed rank test demonstrated significant improvement (p

This study aims to investigate the measurement of left ventricular flow propagation velocity, V p, using phase contrast magnetic resonance imaging and to assess the discrepancies resulting from inflow jet direction and individual left ventricular size. Three V p measuring techniques, namely non-adaptive (NA), adaptive positions (AP) and adaptive vectors (AV) method, were suggested and compared. We performed the comparison on nine healthy volunteers and nine post-infarct patients at four measurement positions, respectively, at one-third, one-half, two-thirds and the conventional 4 cm distances from the mitral valve leaflet into the left ventricle. We found that the V p measurement was affected by both the inflow jet direction and measurement positions. Both NA and AP methods overestimated V p, especially in dilated left ventricles, while the AV method showed the strongest correlation with the isovolumic relaxation myocardial strain rate (r = 0.53, p

In subjects with aortic regurgitation (AR) or mitral regurgitation (MR), transthoracic echocardiography (TTE) is recommended for surveillance. Few prospective studies have directly compared the ability of TTE and cardiac magnetic resonance (CMR) to predict clinical outcomes in AR and MR. We hypothesized that, given its higher reproducibility, CMR would predict the need for valve surgery or heart failure (HF) hospitalization better than TTE. Quantitative TTE and CMR were performed on the same day for 51 subjects: 29 with chronic AR and 22 with chronic, primary MR for quantification of valve regurgitation. Baseline measurements of valve regurgitation were compared to the combined primary end point of new HF and valve surgery using receiver operating characteristics, simple logistic regression, and Kaplan-Meier survival analyses. The primary end point occurred in 5 AR subjects (all surgery) and 8 MR subjects (7 surgery, 1 HF) after a mean follow-up of 4.4 ± 1.5 years. For AR, CMR-derived regurgitant volume50 ml identified those at high risk with 50% undergoing valve surgery versus 0% for those with regurgitant volume ≤50 ml and was more strongly associated with outcomes than regurgitant volume by TTE (p0.05). For MR, 6.8% of those with regurgitant volume by TTE ≤30 ml developed the primary end point versus 70% in those with regurgitant volume30 ml. Regurgitant volume by CMR showed no significant separation of survival curves for MR. In conclusion, regurgitant volume by CMR was more predictive of outcomes than by TTE in subjects with AR. In MR, the 2 methods performed similarly.

Background Transcatheter pulmonary valve implantation (TPVI) with the Melody® transcatheter pulmonary valve (TPV) has demonstrated good haemodynamic and clinical outcomes in the treatment of right ventricular outflow tract (RVOT) conduit dysfunction in patients with repaired congenital heart disease CHD. We present the first Australian single centre experience of patients treated with Melody TPV. Method A prospective, observational registry was developed to monitor clinical and haemodynamic outcomes in patients with RVOT dysfunction treated with the Melody TPV (Medtronic Inc, Minneapolis, United States). Results Seventeen patients underwent TPVI with Melody TPV at The Prince Charles Hospital between January 2009 and February 2016 with a median (range) age of 34 (R: 15–60). Fifteen (88%) were NYHA Class 2 dyspnoea and 11 (59%) had corrected Tetralogy of Fallot. Indication for TPVI was stenosis in eight (47%), regurgitation in two (12%) and mixed dysfunction in seven (41%). Device implantation was successful in all patients. Peak RVOT gradient was significantly reduced and there was no significant regurgitation post procedure. There was one (6%) major procedural adverse event and two (12%) major adverse events at last recorded follow-up. There were no patient deaths. Follow-up cardiac magnetic resonance imaging revealed a significant reduction in indexed right ventricular end diastolic volume. Conclusion This study confirms the safety and effectiveness of TPVI with Melody TPV for RVOT dysfunction in repaired CHD.

Background Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) has been recommended to distinguish Tako-tsubo cardiomyopathy (TTC) from either acute myocardial infarction or myocarditis. Method 44 consecutive patients with confirmed Mayo Clinic criteria for TTC underwent CMR imaging at 1.5 Tesla during the acute phase. 10 patients who had CMRI to exclude scar related ventricular tachycardia, and had negative studies, were used as negative controls. LGE was quantitated at two signal intensity thresholds (CircleCVi software) at > 2 and > 5 standard-deviations (SD) above reference myocardium, and compared to biomarkers. Findings Mean door-to-CMR time was 57 hours. 18 patients (41%) had LGE > 2 SD localized to the area of abnormal wall motion, representing 28.9 ± 11.2% LV mass. In 16 of these 18 patients (89%) LGE signal intensity was > 5 SD above normal myocardium, representing 12.1 ± 10% LV mass. LGE signal intensity was significantly greater in TTC than in matched controls (p 5 SD above normal myocardium. Presence of LGE was associated with worse myocardial injury in the acute setting, with no difference in recovery of function.

In well-compensated PAH, early RV maladaptation is best captured by changes in SV/ESV at exercise by cardiac MRI http://ow.ly/MyEi302UUeL

Coronary CT angiography and coronary calcium scoring offer a new approach to the diagnosis of coronary artery disease (CAD). They hold significant promise in improving patient outcomes, through identification of atherosclerosis and improved risk assessment. Coronary calcium scoring has proven predictive value concerning the occurrence of future cardiovascular events and outperforms current risk evaluation methods such as the Framingham Risk Score. Coronary CT angiography allows visualisation of the coronary artery lumen, detection of stenoses as well as visualisation of both calcified and non-calcified plaque. The accuracy of coronary CT angiography to detect obstructive coronary artery disease has been established by numerous trials. In particular the negative predictive value of the test approaches 100% in low and intermediate risk groups. Outcomes data demonstrate significant prognostic ability of coronary CT angiography. Modern techniques allow substantial reduction of dose values and radiation exposure of coronary CT angiography has significantly fallen. Coronary CT angiography can be reliably performed with doses similar to the level of annual background radiation, and less than one-third of a Tc Sestamibi scan. Coronary CT angiography has been approved for Medicare reimbursement for specific indications when performed by accredited providers. High quality examinations, experience and careful patient selection and preparation are required to ensure optimal results of coronary CT angiography, and to guide clinical decisions.

Exclusion of ischemia is important in patients with newly diagnosed systolic heart failure (HF). We prospectively compared standard-of-care invasive catheter angiography (iCA) and echocardiography to a novel non-invasive strategy of both Coronary Computed Tomographic Angiography (CCTA) and Cardiovascular MRI (CMR) to determine the etiology of myocardial dysfunction Prospective data were collected from consecutive patients referred for iCA to investigate echocardiographically-confirmed new onset HF. CMR (1.5T GE) and dual source CCTA were performed within 2-7 days of iCA. Results were blinded and separately analyzed by expert readers. 426 coronary segments from 28 prospectively enrolled patients were analyzed by CCTA and quantitative iCA. The per-patient sensitivity and specificity of CCTA was 100% and 90%, respectively, negative predictive value (NPV) 100%, positive predictive value (PPV) 78%. Mean ejection fraction by CMR was 24%. Presence of ischemic-type LGE on CMR conferred a 67% sensitivity, 100% specificity, 90% NPV and 100% PPV. Combining CCTA with CMR conferred 100% specificity, 100% sensitivity, 100% PPV and 100% NPV for detection or exclusion of coronary disease. In patients with negative CCTA all invasive angiograms could have been avoided. In addition, two patients with no ischemic LGE by CMR had severe coronary disease on both CCTA and iCA, indicating global hibernation. This is a noteworthy finding in contrast to previous reports which suggested that absence of LGE rules out significant CAD. CCTA with CMR in newly-diagnosed HF enables non-invasive assessment of coronary artery disease, the severity and etiology of myocardial dysfunction and defines suitability for revascularization. Absence of ischemic-type LGE at CMR does not exclude CAD as a cause of LV dysfunction. A first-line strategy of functional and anatomic imaging with CMR and CCTA appears appropriate in newly diagnosed HF.

RV Scar by Electroanatomical Mapping and CMR. Introduction: Assessment of late gadolinium enhancement (LGE) at cardiac magnetic resonance is often used to detect scar in patients with arrhythmias of right ventricular (RV) origin. Recently, electroanatomic mapping (EAM) has been shown to reliably detect scars corresponding to different cardiomyopathic substrates. We compared LGE with EAM for the detection of scar in patients with arrhythmias of RV origin.

Background In ST-elevation myocardial infarction (STEMI) patients, the main stimuli involved in endothelial progenitor cells (EPCs) mobilization are not fully understood. We aimed to assess by cardiac magnetic resonance (CMR) whether the extent of ischemic myocardium (area at risk (AAR)) or of necrotic myocardium (infarct size (IS)) can be correlated to levels of circulating EPCs. Methods Peripheral EPCs were measured in fifteen STEMI patients at 24h after successful primary percutaneous coronary intervention (pPCI). Between two and four days after pPCI all patients underwent CMR assessment of myocardial AAR, IS, myocardial salvage (MS) and microvascular obstruction at late gadolinium enhancement CMR (LG-MVO). Results CD34+/KDR+, CD34+/KDR+/CD45dim, CD34+/KDR+/CD45−, EPCs were related to extent of AAR (rho=0.51, p =0.05; rho=0.55, p =0.03; rho=0.72, p =0.002, respectively), while no relationships were detected with IS, MS or LG-MVO. Conclusions Our data show that EPCs were strongly correlated to extent of myocardial AAR, thus suggesting that progenitor cells mobilization in STEMI develops in response to myocardial ischemia and not to myocardial necrosis.

Aims In 30–40% of patients with acute ischaemic stroke, the cause remains undefined (cryptogenic stroke). Contrast transoesophageal echocardiography (TEE) is considered the gold standard for patent foramen ovale (PFO) detection. Recently, however, cardiac magnetic resonance (CMR) has also been applied to detect PFO. In this study, we compared the diagnostic value of CMR and TEE in detecting PFO in a group of patients with apparently cryptogenic stroke. Methods and results Twenty-five patients (age 50 ± 13 years, 16 males) with apparently cryptogenic ischaemic stroke underwent contrast-enhanced TEE and contrast CMR for detection of possible PFO. Both imaging studies were performed during Valsalva manoeuvre. PFO grading results were assessed visually both for TEE and for CMR, according to the entity of contrast passage in the left atrium (grade 0 = no PFO; grades 1, 2, and 3 = mild, medium, and wide PFO, respectively). TEE detected PFO in 16 patients (64%). Contrast-enhanced CMR identified a PFO in 7 (44%) of these patients. TEE showed a grade 1 PFO in five patients, a grade 2 PFO in eight patients, and a grade 3 PFO in three patients. Of these patients, CMR failed to identify PFO in all five patients with a grade 1 PFO, in one patient with a grade 2 PFO, and one patient with grade 3 PFO according to TEE. None of the nine patients without PFO at TEE was shown to have a PFO at CMR. When compared with TEE, the present methodology of CMR had a sensitivity of 50%, specificity of 100%, negative predictive value of 31%, and a positive predictive value of 100%. Conclusion Our data suggest that TEE is the cornerstone imaging diagnostic test to detect and characterize PFO in patients with ischaemic stroke, and is shown to be better compared with the current CMR sequences.

Background Gated Blood Pool Imaging (GBPI) has low inter-test variability compared to echocardiography, and is often used when accurate repeated measurements of left ventricular ejection fraction are required such as in the surveillance of post-transplant patients. The aim of this study was to determine if cardiac MRI (CMR) could replace Gated Blood Pool Imaging for annual assessment of left ventricular (LV) function in the surveillance of patients post-cardiac transplantation. Methods Forty-nine patients at various stages of post-cardiac transplantation presenting for annual review underwent LV functional assessment with GBPI and CMR. LV ejection fractions (EF) obtained from the two methods were compared and limits of agreement determined. Results The mean EF (plus and minus two standard deviations) was 58.3 ± 18% for GBPI and 57.6 ± 18% for CMR. The two methods were found to provide clinically equivalent results. Conclusions Assessment of LVEF with CMR offers comparable values to GBPI in post-heart transplant patients. However, CMR also allows quantitative volumetric analysis of ventricular volumes and assessment of wall motion and valvular function. As is now accepted in native heart assessment, CMR should be considered the “gold standard” for post-transplant volumetric and functional evaluation. CMR offers information over-and-above traditional imaging modalities.

Chronic total occlusion (CTO) intervention constitutes approximately 10–20% of all angioplasty procedures at selected centers. Benefits of CTO revascularization, in addition to relief of angina, include improvement of left ventricular function, reduced risk of major adverse cardiac events and potentially increased survival. Although several techniques, devices and guidewires have been developed for use in CTO, leading to an increased success rate, limitations of angiography in visualizing occluded arteries makes CTO interventions technically challenging. This article focuses on the principle intracoronary imaging techniques, such as intravascular ultrasound and optical coherence tomography, that may provide guidance during CTO revascularization, improving procedure timing, safety and efficacy.

Idiopathic ventricular arrhythmias (VAs) occur in pts without apparent structural heart disease (SHD), although some develop left ventricular (LV) dysfunction over time. It is not clear whether a subclinical myopathic process occurs in pts with idiopathic VAs and preserved LVEF. We prospectively

Pulmonary hypertension (PH) is a progressively fatal disease having a significant impact on right ventricular (RV) function, a major determinant of long-term outcome in PH patients. In our clinic we frequently noticed the combination of PH and reduced RV function, but with discordant Tricuspid Annular Plane Systolic Excursion (TAPSE) values. The present study focuses on whether RV free wall strain measured using 2-dimensional speckle-tracking echocardiography is able to predict mortality in this subgroup of PH patients. 57 patients with PH and RV dysfunction (visual echocardiographic assessment of ≥2) and pseudo-normalized TAPSE values (defined as ≥16 mm) were retrospectively evaluated. Patients were divided by RV free −20 % as cut-off value. Follow-up data on all-cause mortality were registered after a median follow-up time of 27.9 ± 1.7 months. RV free of ≥−20 % was predictive of all-cause mortality after a median follow-up time of 27.9 ± 1.7 months (HR 3.76, 95 % CI 1.02–13.92, p = 0.05). RV free ≥−20 % remained a significant predictor of all-cause mortality (HR 4.30, 95 % CI 1.11–16.61, p = 0.04) after adjusting for PH-specific treatment. On the contrary, TAPSE was not a significant predictor of all-cause mortality. RV free wall strain provides prognostic information in patients with PH and RV dysfunction, but with normal TAPSE values. Future studies with larger cohorts, longer follow-up periods and inclusion of more echocardiographic parameters measuring LV and RV function could confirm the strength of RV free ≥−20 % as a predictor of mortality for this subgroup of patients with PH.

Cardiac magnetic resonance (CMR) has the potential to provide early detection of cardiac involvement in Fabry disease. We aimed to gain further insight into this by assessing a cohort of Fabry patients using CMR.Fifty genotype-positive Fabry subjects (age 45±2 years; 50% male) referred for CMR and 39 matched controls (age 40±2 years; 59% male) were recruited. Patients had a mean Mainz severity score index of 15±2 (range 0-46), reflecting an overall mild degree of disease severity. Compared with controls, Fabry subjects had a 34% greater left ventricular mass (LVM) index (82±5 vs 61±2 g/m(2), p=0.001) and had a significantly greater papillary muscle contribution to total LVM (13±1 vs 6±0.5%, p0.001), even in the absence of left ventricular hypertrophy (LVH). Late gadolinium enhancement (LGE) was present in 15 Fabry subjects (9/21 males and 6/23 females). The most common site for LGE was the basal inferolateral wall (93%, 14/15). There was a positive association between LVM index and LGE. Despite this, there were two males and three females with no LVH that displayed LGE. Of Fabry subjects who were not on enzyme replacement therapy at enrolment (n=28), six were reclassified as having cardiac involvement (four LVH-negative/LGE-positive, one LVH-positive/LGE-positive and one LVH-positive/LGE-negative).CMR was able to detect cardiac involvement in 48% of this Fabry cohort, despite the overall mild disease phenotype of the cohort. Of those not on ERT, 21% were reclassified as having cardiac involvement allowing improved risk stratification and targeting of therapy.