Search

Background: We sought to determine if an association exists between prehospital chest pain severity and markers of myocardial injury., Methods and Results: Patients with confirmed ST elevation myocardial infarction (STEMI) treated by emergency medical services were included in this retrospective cohort analysis of the AVOID study. The primary endpoint was the association of pre-hospital initial chest pain severity, cardiac biomarkers and infarct size based on cardiac magnetic resonance imaging. Groups were categorized based on moderate to severe chest pain (numerical rating scale pain ≥ 5/10) or less than moderate severity to compare procedural and clinical outcomes. 414 patients were included in the analysis. There was a weak correlation between initial pre-hospital chest pain severity and peak creatine kinase (r = 0.16, p = 0.001) and peak cardiac troponin I (r = 0.14, p = 0.005). Both were no longer significant after adjusting for known confounders. There was no association between moderate to severe chest pain on arrival and major adverse cardiac events at 6 months (20% vs. 14%, p=0.12). There was a weak correlation between history of ischemic heart disease (r = 0.16, p = 0.001), percutaneous coronary intervention (r = 0.16, p = 0.001), left anterior descending artery (r = 0.12, p = 0.012) as the culprit vessel and a weak negative correlation between age (r = -0.14, p = 0.039) and chest pain., Conclusion: Only a weak association between pre-hospital chest pain severity and markers of myocardial injury was identified, supporting more judicious use of opioid analgesia with a focus on patient comfort., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier B.V.)

Background: Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) is commonly assumed to represent myocardial fibrosis; however, comparative human histological data are limited, and there is no consensus on the most accurate method for LGE quantitation. We evaluated the relationship between CMR assessment of regional fibrosis and infarct size assessment using serial biomarkers after ST elevation acute myocardial infarction (STEMI)., Methods: Ninety-three patients treated for STEMI (59±10 years, 86% male) underwent CMR 6 months after infarction. Infarct size was quantified by CMR-LGE using manual and range of semi-automated thresholds (range: 2-10 standard deviations [SD]) above reference myocardium and the full width-half maximum (FWHM) technique, and compared with the rise in serum biomarkers. The agreement between CMR and biomarker in the identification of large infarcts based on peak troponin (TnI) levels was also analysed., Results: Quantification methods had a strong influence on the infarct size assessment with CMR-LGE. Significant correlations were observed between LGE and biomarkers across all of the signal intensity thresholds. Whilst there was a wide variation with respect to the estimation of total LGE size (from 6.8±7.7 to 32.1±11.3 grams), the variation in the correlation with peak troponin level was much smaller (r-values ranging from 0.670 to 0.876). There was good agreement between CMR-LGE and biomarker assessment of infarct size; the best agreement between CMR-LGE and large infarction using a threshold of 8SD for peak TnI>50ng/mL (Cohen's kappa (κ)=0.722), and a threshold of 4SD for peak TnI >95ng/mL (κ=0.761)., Conclusions: The correlation between CMR-LGE quantification of infarct size and biomarker release following STEMI at a range of semi-automated thresholds was consistently strong, with good agreement between measures across a range of thresholds., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Galectin-3 is a biomarker of heart disease. However, it remains unknown whether increase in galectin-3 levels is dependent on aetiology or disease-associated conditions and whether diseased heart releases galectin-3 into the circulation. We explored these questions in mouse models of heart disease and in patients with cardiomyopathy. All mouse models (dilated cardiomyopathy, DCM; fibrotic cardiomyopathy, ischemia-reperfusion, I/R; treatment with β-adrenergic agonist isoproterenol) showed multi-fold increases in cardiac galectin-3 expression and preserved renal function. In mice with fibrotic cardiomyopathy, I/R or isoproterenol treatment, plasma galectin-3 levels and density of cardiac inflammatory cells were elevated. These models also exhibited parallel changes in cardiac and plasma galectin-3 levels and presence of trans-cardiac galectin-3 gradient, indicating cardiac release of galectin-3. DCM mice showed no change in circulating galectin-3 levels nor trans-cardiac galectin-3 gradient or myocardial inflammatory infiltration despite a 50-fold increase in cardiac galectin-3 content. In patients with hypertrophic cardiomyopathy or DCM, plasma galectin-3 increased only in those with renal dysfunction and a trans-cardiac galectin-3 gradient was not present. Collectively, this study documents the aetiology-dependency and diverse mechanisms of increment in circulating galectin-3 levels. Our findings highlight cardiac inflammation and enhanced β-adrenoceptor activation in mediating elevated galectin-3 levels via cardiac release in the mechanism.

Background: Regional or diffuse fibrosis is an early feature of hypertrophic cardiomyopathy (HCM) and is related to poor prognosis. Previous studies have documented low-grade inflammation in HCM. The aim of this study was to examine the relationships between circulating inflammatory markers and myocardial fibrosis, systolic and diastolic dysfunction, and the degree of cardiac hypertrophy in HCM patients., Methods and Results: Fifty HCM patients were recruited while 20 healthy subjects served as the control group. Seventeen inflammatory cytokines/chemokines were measured in plasma. Cardiac magnetic resonance imaging and echocardiography were used to assess cardiac phenotypes. Tumour necrosis factor (TNF)-α, interleukin (IL)-6 and serum amyloid P (SAP) were significantly increased in HCM patients compared to controls. IL-6, IL-4, and monocyte chemotactic protein (MCP)-1 were correlated with regional fibrosis while stromal cell-derived factor-1 and MCP-1 were correlated with diffuse fibrosis. Fractalkine and interferon-γ were associated with left ventricular wall thickness. The above associations remained significant in a linear regression model including age, gender, body mass index and family history. TNF-α, IL-6, SAP, MCP-1 and IL-10 were associated with parameters of diastolic dysfunction. White blood cells were also increased in HCM patients and correlated with diffuse fibrosis and diastolic dysfunction. However the associations between parameters of systemic inflammation and diastolic dysfunction were weakened in the linear regression analysis., Conclusions: Systemic inflammation is associated with parameters of the disease severity of HCM patients, particularly regional and diffuse fibrosis. Modifying inflammation may reduce myocardial fibrosis in HCM patients., Competing Interests: None.

Cardiac Magnetic Resonance derived T1 mapping parameters are a non-invasive method of estimating diffuse myocardial fibrosis. This study aims to to determine the native T1 time, post contrast T1 time and extracellular volume (ECV) derived from T1 mapping and to evaluate the ability of T1 mapping techniques to discriminate healthy myocardium from dilated cardiomyopathy. Seventy-nine participants underwent cardiac magnetic resonance imaging at the Baker Heart and Diabetes Institute, Melbourne, Australia. Fifty-seven healthy volunteers and twenty-two patients with Dilated cardiomyopathy were included in the study. Each participant had T1 mapping sequences performed at 3 T in the mid short axis slice-both SASHA and ShMOLLI T1 mapping were performed. Native T1, post contrast T1 and ECV values were compared in health and dilated cardiomyopathy. Native T1, post contrast T1 and ECV differed significantly between SASHA and ShMOLLI techniques (P < 0.001). All T1 parameters had similar ability to discriminate normal from abnormal myocardium (ROC AUC 0.691 to 0.830). Converting T1 values to Z scores significantly improved the agreement between SASHA and ShMOLLI techniques, particularly for post contrast T1 (ICC 0.19 to 0.895) and ECV (ICC 0.461 to 0.880). T1 mapping values from SASHA and ShMOLLI show strong correlation for post contrast measures, though with a consistent offset for all measures in health and dilated cardiomyopathy. All measures obtained using SASHA and ShMOLLI allow good discrimination between dilated cardiomyopathy and normal myocardium.

Background: We evaluated the ability of transthoracic echocardiography (TTE) to correctly identify abnormal left ventricular (LV) size, function, and mass when compared to cardiac magnetic resonance (CMR). Whilst numerous studies have compared TTE and CMR with respect to correlation between measurements and study reproducibility, few have employed categorical analysis relevant to clinical practice., Methods: Two hundred and fifteen consecutive patients who underwent both TTE and CMR were evaluated for the presence of abnormal LV size, systolic function, and mass. Abnormal LV systolic function was further categorized into grades (mild, moderate, and severe). Quantification of LV morphology and function was performed on TTE and CMR according to published guidelines. The level of agreement between TTE and CMR was compared across binary and categorical variables using Cohen's kappa., Results: Compared to CMR, TTE demonstrated excellent agreement in identification of abnormal versus normal function (κ = 0.87). However, agreement across grades of LV function was less strong (κ = 0.63). Whilst agreement for identification of severe LV dysfunction was good (κ = 0.68), this would still lead to misclassification of severe dysfunction in approximately one in seven cases. Agreement between TTE and CMR was moderate to good for identification of LV dilation (κ = 0.43-0.63), but poor for identification of increased mass (κ = 0.04)., Conclusions: Whilst in clinical practice TTE performs well in identification of normal versus abnormal systolic function, it has substantial limitations across grades of dysfunction and in the assessment of LV size and mass. These limitations have important implications when considering management decisions for patients based on thresholds of LV morphology or function.

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, which generally manifests during adolescence. Adolescents may be diagnosed incidentally, following the investigation of symptoms, or during family screening. Early recognition may prevent sudden cardiac death. First-degree relatives of an adolescent with HCM should be screened for the condition., Objective: The objectives of this article are to review the genetic basis for HCM and discuss clinical presentations of HCM in adolescents, so that general practitioners: develop confidence in requesting investigations in adolescents with suspected or proven HCM consider early referral to a paediatric cardiology department for any adolescent with left ventricular hypertrophy understand family screening guidelines for HCM., Discussion: HCM is a complex cardiac disease with marked heterogeneity. Management strategies should be individually tailored, including avoidance of competitive sports, but encouragement of lower intensity physical activities. Adolescents with HCM should be regularly reviewed in a paediatric cardiology department; however, general practitioners should understand the diagnostic and treatment principles for this condition.

Introduction: Non-sustained ventricular tachycardia (NSVT) is a risk factor for sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We aimed to assess whether diffuse ventricular fibrosis on cardiac magnetic resonance (CMR) imaging could be a surrogate marker for ventricular arrhythmias in patients with HCM., Methods: A total of 100 patients with HCM (mean age 51 ± 13 years, septal wall thickness 20 ± 5 mm) underwent CMR with a 1.5 T scanner to determine the presence of ventricular late gadolinium enhancement (LGE) for focal fibrosis, and post-contrast T1 mapping for diffuse ventricular fibrosis. The presence of NSVT was determined by Holter monitoring and a subset of high risk patients received an implantable cardioverter-defibrillator (ICD)., Results: NSVT was detected in 23 of 100 patients with HCM. Focal ventricular fibrosis (by LGE) was observed in 87%, with no significant difference between patients with (96%) or without NSVT (86%, P = 0.19). However, LGE mass was greater in patients with (16.5 ± 19.1 g) versus without NSVT (7.6 ± 10.2 g, P < 0.01). NSVT was associated with a significant reduction in ventricular T1 relaxation time (422 ± 54 milliseconds) versus patients without NSVT (512 ± 115 milliseconds; P < 0.001). There was significant reduction in ventricular T1 relaxation time in patients with (430 ± 48 milliseconds) versus without aborted SCD (495 ± 113 milliseconds; P = 0.01) over a mean follow-up of 40 ± 10 months. On multivariate analysis post-contrast ventricular T1 relaxation time and septal wall thickness were the only predictors of NSVT., Conclusion: Post-contrast T1 relaxation time on CMR is associated with ventricular arrhythmias in patients with HCM. Diffuse ventricular fibrosis may be an important marker of arrhythmic risk in patients with HCM., (© 2016 Wiley Periodicals, Inc.)

Objective: Supplemental oxygen therapy may increase myocardial injury following ST-elevation myocardial infarction (STEMI). In this study, we aimed to evaluate the effect of the dose and duration of oxygen exposure on myocardial injury after STEMI., Methods: Descriptive analysis of data from a multicentre, prospective, randomised, controlled trial of 441 patients with STEMI randomised to supplemental oxygen therapy or room air breathing. The primary endpoint was myocardial infarct size as assessed by cardiac biomarkers, troponin (cTnI) and creatine kinase (CK). Oxygen therapy was commenced by paramedics, and continued for up to 12 h postintervention in hospital. Supplemental oxygen exposure was calculated as the area under the dose×time curve for oxygen administration over the first 12 h, and then assessed for its association with cTnI/CK release using multivariable linear regression., Results: The median supplemental oxygen exposure was 1746 L (IQR: 960-2858). After adjustment for potential confounders, every 100 L increase in oxygen exposure in the first 12 h was associated with a 1.4% (95% CI 0.6% to 2.2%, p<0.001) and 1.2% (95% CI 0.7% to 1.8%, p<0.001) increase in the mean peak cTnI and CK, respectively. Excluding patients who developed cardiogenic shock, recurrent myocardial infarction or desaturations (SpO2<94%) during admission, every 100 L increase in oxygen exposure was associated with a 1.2% (95% CI 0.2% to 2.1%, p=0.01) and 1.0% (95% CI 0.3% to 1.7%, p=0.003) increase in the mean peak cTnI and CK, respectively. The median supplemental oxygen exposure of 1746 L would result in a 21% (95% CI 3% to 37%) increase in infarct size according to the cTnI profile., Conclusions: Supplemental oxygen exposure in the first 12 h after STEMI was associated with a clinically significant increase in cTnI and CK release., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Circulating microRNAs may represent novel markers for cardiovascular diseases. We evaluated whether circulating miRNAs served as potential biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM)., Methods: Cardiac magnetic resonance imaging with postcontrast T1 mapping was performed to non-invasively quantify diffuse myocardial fibrosis in HCM patients who were classified into two groups (T1 < 470 ms or T1 ≥ 470 ms, as likely or unlikely to have diffuse fibrosis, respectively). First, we screened 84 miRNAs using human serum/plasma miRNA array on plasma of 8 HCM patients (4/group based on T1 time) and 4 healthy controls. From the results of this initial array, 16 miRNAs were selected based on their fold changes and relevance to myocardial fibrosis for further validation by Taqman real-time PCR in 55 HCM patients., Results: Among the 16 miRNAs, the expression of miR-96-5p and miR-373-3p was low. The remaining 14 (miR-18a-5p, miR-146a-5p, miR-30d-5p, miR-17-5p, miR-200a-3p, miR-19b-3p, miR-21-5p, miR-193-5p, miR-10b-5p, miR-15a-5p, miR-192-5p, miR-296-5p, miR-29a-3p, and miR-133a-3p) were upregulated in HCM patients with T1 < 470 ms compared with those with T1 ≥ 470 ms, and 11 (except miR-192-5p, miR-296-5p and miR-133a-3p) were significantly inversely correlated with postcontrast T1 values. Individual miRNA had moderate diagnostic value for diffuse myocardial fibrosis (AUC: 0.663-0.742), but the diagnostic value was greatly improved (AUC: 0.87) for a combination of 8 miRNAs. In comparison, circulating markers of collagen turnover did not have predictive values for diffuse myocardial fibrosis., Conclusions: These findings suggest that circulating miRNAs provide attractive candidates as putative biomarkers for diffuse myocardial fibrosis in HCM.

Atrial fibrillation (AF) is the most commonly encountered sustained cardiac rhythm disorder, is an independent risk factor for stroke, heart failure and death, and its development is promoted by a range of common cardiovascular pathologies. The management of AF is directed at these predisposing conditions, at reducing the risk of systemic thromboembolism, and towards rate or rhythm control of the arrhythmia. Guidelines increasingly support the use of catheter ablation (CA) as an early management strategy, with the efficacy of CA crucially dependent on the extent of left atrial (LA) structural remodeling; LA imaging plays a central role in each of identifying comorbidities, risk stratification for stroke, and identification of suitable candidates for CA. An understanding of the strengths and limitations of various echocardiographic modalities, of cardiac computed tomography and of cardiac magnetic resonance imaging is therefore an increasingly important part of the armory of the electrophysiologist. In particular, individualized use of imaging to select patients more likely to benefit from CA of AF is important, and post-procedural imaging to evaluate the extent of reverse LA remodeling after CA is critical to appropriate decisions regarding ongoing anti-arrhythmic therapy and long-term anticoagulation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Oxygen is commonly administered to patients with ST-elevation-myocardial infarction despite previous studies suggesting a possible increase in myocardial injury as a result of coronary vasoconstriction and heightened oxidative stress., Methods and Results: We conducted a multicenter, prospective, randomized, controlled trial comparing oxygen (8 L/min) with no supplemental oxygen in patients with ST-elevation-myocardial infarction diagnosed on paramedic 12-lead ECG. Of 638 patients randomized, 441 patients had confirmed ST-elevation-myocardial infarction and underwent primary end-point analysis. The primary end point was myocardial infarct size as assessed by cardiac enzymes, troponin I, and creatine kinase. Secondary end points included recurrent myocardial infarction, cardiac arrhythmia, and myocardial infarct size assessed by cardiac magnetic resonance imaging at 6 months. Mean peak troponin was similar in the oxygen and no oxygen groups (57.4 versus 48.0 μg/L; ratio, 1.20; 95% confidence interval, 0.92-1.56; P=0.18). There was a significant increase in mean peak creatine kinase in the oxygen group compared with the no oxygen group (1948 versus 1543 U/L; means ratio, 1.27; 95% confidence interval, 1.04-1.52; P=0.01). There was an increase in the rate of recurrent myocardial infarction in the oxygen group compared with the no oxygen group (5.5% versus 0.9%; P=0.006) and an increase in frequency of cardiac arrhythmia (40.4% versus 31.4%; P=0.05). At 6 months, the oxygen group had an increase in myocardial infarct size on cardiac magnetic resonance (n=139; 20.3 versus 13.1 g; P=0.04)., Conclusion: Supplemental oxygen therapy in patients with ST-elevation-myocardial infarction but without hypoxia may increase early myocardial injury and was associated with larger myocardial infarct size assessed at 6 months., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01272713., (© 2015 American Heart Association, Inc.)

Background: Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac condition, with a range of investigation and management options available. Recent research has recommended management within multidisciplinary-dedicated HCM centres., Aim: To assess the clinical impact of attendance at a specialised clinic on the management of HCM., Methods: A retrospective study of patients attending the HCM Clinic @ The Alfred during the first 2 years of operation was performed. Outcome measures comprised improvements in management of HCM as a result of attending the clinic including risk stratification and further investigations, medication changes, referral for implantable cardioverter-defibrillators (ICD) and septal reduction therapy, and screening of first-degree relatives (FDR)., Results: Following specialised clinic attendance, there was an increase in patients investigated with 24-h Holter monitoring by 39%, stress echocardiography by 21% and cardiac magnetic resonance imaging by 70%. Medications were optimised in 47% of patients. Six per cent of patients underwent ICD implantation and 13% underwent septal myectomy. Seventy new FDR were screened identifying 10 new cases of HCM., Conclusions: Attendance at our specialised HCM clinic leads to facilitation of cardiac investigations, optimisation of medical therapy, streamlining of referrals for ICD implantation and septal reduction therapy, and improved family screening. Referral to a specialised clinic offering comprehensive management should be considered for all patients with HCM., (© 2014 Royal Australasian College of Physicians.)

Aim: Myocardial fibrosis is fundamental in the pathogenesis of heart failure. Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) imaging is commonly assumed to represent myocardial fibrosis; however, comparative human histological data are limited, especially in non-ischaemic cardiac disease. Diffuse interstitial myocardial fibrosis is increasingly recognized as central in the pathogenesis of cardiomyopathy and can be quantified using newer CMR techniques such as T1 mapping. We evaluated the relationship of CMR assessment of regional and diffuse fibrosis with human histology., Methods and Results: Eleven patients on the waiting list for heart transplantation (43.5 ± 7.6 years, 64% male) and eight patients undergoing surgical myectomy for obstructive hypertrophic cardiomyopathy (57.1 ± 8.6 years, 63% male) were recruited and underwent CMR prior to cardiac transplantation or myectomy. Quantification of fibrosis in explanted hearts using digitally analysed Masson-trichrome-stained slides was validated against picrosirius red-stained slides analysed using Image J, with an excellent correlation (R = 0.95, P < 0.0001). Significant correlations were observed between LGE and histological fibrosis across a range of signal intensity thresholds in the explanted hearts (range: 2-10 standard deviations above reference myocardium), with maximal accuracy at a threshold of 6 SD (R = 0.91, P < 0.001). Assessment of interstitial myocardial fibrosis with post-contrast T1 times demonstrated a significant correlation on both segmental (R = -0.64, P = 0.002) and per-patient (R = -0.78, P = 0.003) analyses., Conclusion: CMR provides accurate, non-invasive assessment of regional myocardial fibrosis using LGE, while diffuse interstitial myocardial fibrosis is accurately assessed with post-contrast T1 mapping., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aims: In hypertrophic cardiomyopathy (HCM), attempts to associate genotype with phenotype have largely been unsuccessful. More recently, cardiac magnetic resonance (CMR) imaging has enhanced myocardial fibrosis characterization, while next-generation sequencing (NGS) can identify pathogenic HCM mutations. We used CMR and NGS to explore the link between genotype and fibrotic phenotype in HCM., Methods and Results: One hundred and thirty-nine patients with HCM and 25 healthy controls underwent CMR to quantify regional myocardial fibrosis with late gadolinium enhancement (LGE) and diffuse myocardial fibrosis with post-contrast T1 mapping. Collagen content of myectomy specimens from nine HCM patients was determined. Fifty-six HCM patients underwent NGS for 65 cardiomyopathy genes, including 36 HCM-associated genes. Post-contrast myocardial T1 time correlated histologically with myocardial collagen content (r = -0.70, P = 0.03). Compared with controls, HCM patients had more LGE (4.6 ± 6.1 vs. 0%, P < 0.001) and lower post-contrast T1 time (483 ± 83 vs. 545 ± 49 ms, P < 0.001). LGE negatively correlated with left-ventricular (LV) ejection fraction and outflow tract obstruction, whereas lower post-contrast T1 time, suggestive of more diffuse myocardial fibrosis, was associated with LV diastolic impairment and dyspnoea. Patients with identifiable HCM mutations had more LGE (7.9 ± 8.6 vs. 3.1 ± 4.3%, P = 0.03), but higher post-contrast T1 time (498 ± 81 vs. 451 ± 70 ms, P = 0.03) than patients without., Conclusion: In HCM, contrast-enhanced CMR with T1 mapping can non-invasively evaluate regional and diffuse patterns of myocardial fibrosis. These patterns of fibrosis occur independently of each other and exhibit distinct clinical associations. HCM patients with recognized genetic mutations have significantly more regional, but less diffuse myocardial fibrosis than those without., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: There is a complex interplay between the atria and ventricles in atrial fibrillation (AF). Cardiac magnetic resonance (CMR) imaging provides detailed tissue characterization, identifying focal ventricular fibrosis with late gadolinium enhancement (ventricular late gadolinium enhancement) and diffuse fibrosis with postcontrast-enhanced T1 mapping. The aim of the present study was to investigate the relationship between postcontrast ventricular T1 relaxation time on CMR and freedom from AF after pulmonary vein isolation., Methods and Results: One hundred three patients undergoing catheter ablation for symptomatic AF (66% paroxysmal AF; age, 58±10 years; left atrial area, 27±7 cm(2)) underwent preprocedure CMR to determine postcontrast ventricular T1 time. Follow-up included clinical review and 7-day Holter monitors at 6 monthly intervals. All patients underwent successful pulmonary vein isolation. At a mean follow-up of 15±7 months, the single procedure success was 74%. Postcontrast ventricular T1 time was significantly shorter in patients with recurrent AF (366±73 ms) versus patients without AF recurrence (428±90 ms; P=0.002). Univariate predictors of AF recurrence included postcontrast ventricular T1 time, AF type (paroxysmal versus persistent), AF duration, and body mass index. After multivariate analysis, ventricular T1 time (P=0.03) and AF duration (P=0.03) were the only independent predictors. Freedom from AF was present in 84% of patients with a postcontrast ventricular T1 time >380 ms versus 56% in patients with a postcontrast ventricular T1 time <380 ms (P=0.002)., Conclusions: A shorter postcontrast ventricular T1 relaxation time on CMR is associated with reduced freedom from AF after catheter ablation. Diffuse ventricular fibrosis as demonstrated by CMR may, in part, explain recurrent AF after AF ablation., (© 2014 American Heart Association, Inc.)

Background: The impact of diffuse atrial fibrosis detected by T1 mapping on the clinical outcome after atrial fibrillation (AF) ablation is unknown., Objective: This study aimed to validate and assess the impact of post-contrast cardiac magnetic resonance (CMR) imaging atrial T1 mapping on the clinical outcome after catheter ablation for AF., Methods: CMR imaging was performed in 3 groups by using a clinical 1.5-T scanner: controls, patients with paroxysmal AF, and patients with persistent AF. A T1 mapping sequence was used to calculate the post-contrast T1 relaxation time (T1 time) at the interatrial septum as an index of diffuse atrial fibrosis. A subset underwent left atrial endocardial bipolar voltage mapping for electrophysiologic correlation. After AF ablation, patients underwent clinical review and 7-day Holter monitoring at 6-month intervals., Results: One hundred thirty-two patients (20 controls, 71 (63%) patients with paroxysmal AF, and 41 (37%) patients with persistent AF) underwent CMR imaging. Post-contrast atrial T1 time was significantly shorter in AF groups (237 ± 42 ms) than in controls (280 ± 37 ms) (P < .001). Post-contrast atrial T1 time correlated with mean septal voltage (R2 = .48; P < .001) and global left atrial voltage (R(2) = .41; P < .001). A diagnosis of AF, AF duration, and left ventricular end-diastolic volume independently predicted shortened post-contrast atrial T1 time. The single procedure success rate was 74% at 12 ± 5 months postablation. Post-contrast atrial T1 time was the only predictor of arrhythmia recurrence in multivariate analysis (P = .015). A post-contrast atrial T1 time of >230 ms was associated with freedom from AF in 85% relative to 62% with a post-contrast atrial T1 time of <230 ms (P = .01)., Conclusion: Post-contrast atrial T1 time as measured using CMR imaging provides an index of atrial fibrosis that correlates with tissue voltage, presence of AF, and clinical outcomes after catheter ablation., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: The optimal management of asymptomatic subjects at intermediate risk of coronary artery disease (CAD) is often uncertain. Re-stratification to a high- or low-risk category may enable optimization of preventative strategies. Coronary computed tomographic angiography (CCTA) enables a minimally invasive assessment of coronary artery plaque quantity and composition. Non-calcified plaque by CCTA is lipid-rich and more vulnerable to rupture and resultant acute coronary syndromes. The purpose of this study was to determine whether novel approaches to CAD risk stratification, such as plasma lipid profiling, may predict non-calcified plaque burden in intermediate risk subjects., Methods and Results: CCTA and several markers of CAD (including plasma lipid profiling, carotid intima-media thickness, aortic pulse wave velocity, and high-sensitivity C-reactive protein) were prospectively performed in 100 asymptomatic patients at intermediate CAD risk according to the Framingham risk score. Segment stenosis scores (SSS) were calculated to evaluate the burden of total, calcified, and non-calcified coronary artery plaque. Non-calcified plaque was observed in 66 subjects and 158 (11%) of 1425 coronary artery segments. Eighteen lipid species demonstrated significant associations with non-calcified plaque burden, but not with total plaque or calcified plaque burden. No other marker of CAD was found to predict coronary artery plaque burden., Conclusions: Plasma lipidomic analysis can predict the burden of non-calcified coronary plaque in asymptomatic subjects at intermediate risk of CAD. Re-stratification of these patients by plasma lipid profiling may enable more appropriate and effective primary prevention management strategies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Hypertrophic cardiomyopathy (HCM) causes significant morbidity and sudden death. First-degree relatives (FDR) of affected patients are at risk due to autosomal dominant inheritance. Guidelines recommend clinical screening, including echocardiography, for all FDR., Aim: We sought to determine adherence to these guidelines, and whether a specialised HCM clinic improves screening rates., Method: This 12-month prospective follow-up study obtained family pedigrees from all patients referred to the HCM Clinic @ The Alfred. The number of living FDR was determined, and whether they had previously been assessed by echocardiography. One year after a coordinated clinic-based family screening approach was instituted, the number of additionally screened FDR was recorded., Results: Three hundred and eight living FDR of 61 HCM patients were identified. Of these, echocardiography had previously been performed in only 80 (26%), yielding 13 (16%) additional cases of HCM. Twelve months after attendance at our clinic, 51 additional FDR were screened (64% improvement) and 8 new cases of HCM were identified., Conclusions: Recommended family screening for HCM is underperformed, resulting in missed opportunities to detect subclinical HCM. A coordinated approach through a specialised HCM clinic improves screening rates, thus referral to such a service should be considered for all patients with HCM and their families., (© 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.)

Objectives: The purpose of this study was to use cardiac magnetic resonance (CMR) imaging and invasive left ventricular (LV) pressure-volume (PV) measurements to explore the relationship between diffuse myocardial fibrosis and indexes of diastolic performance in a cohort of cardiac transplant recipients., Background: The precise mechanism of LV diastolic dysfunction in the presence of myocardial fibrosis has not previously been established., Methods: We performed CMR with T1 mapping and obtained invasive LV PV measurements via a conductance catheter in 20 cardiac transplant recipients at the time of clinically-indicated coronary angiography., Results: Both post-contrast myocardial T1 time and extracellular volume fraction correlated with β, the load-independent passive LV stiffness constant (r = -0.71, p = 0.001, and r = 0.58, p = 0.04, respectively). After multivariate analysis, post-contrast myocardial T1 time remained the only independent predictor of β. No significant associations were observed between myocardial T1 time and τ, the active LV relaxation constant, or other load-dependent parameters of diastolic function., Conclusions: Diffuse myocardial fibrosis, assessed by post-contrast myocardial T1 time, correlates with invasively-demonstrated LV stiffness in cardiac transplant recipients. In patients with increased diffuse myocardial fibrosis, abnormal passive ventricular stiffness is therefore likely to be a major contributor to diastolic dysfunction., (Copyright © 2014. Published by Elsevier Inc.)

Background: In hypertrophic cardiomyopathy (HCM), accumulation of myocardial collagen may play a central role in the pathogenesis of diastolic dysfunction and arrhythmia. Previous studies have suggested that peripheral levels of byproducts of collagen synthesis are reflective of myocardial extracellular matrix metabolism, although this has not been validated in detail. Given the potential clinical utility of such biomarkers, we sought to validate the assumed relationship between peripheral markers and myocardial fibrosis in HCM., Methods and Results: Fifty patients with HCM and 25 healthy controls underwent peripheral venous sampling to determine plasma concentrations of key collagen precursors (procollagen I and III N-terminal propeptides [PINP, PIIINP]). Contrast-enhanced cardiac magnetic resonance imaging was performed to quantify regional (by late-gadolinium enhancement) and diffuse (by T1 mapping) myocardial fibrosis. Nineteen subjects also underwent simultaneous arterial and coronary sinus blood sampling (to derive transcardiac concentration gradients of PINP, PIIINP, and C-terminal telopeptide of type I collagen) and right heart catheterization. Despite cardiac magnetic resonance evidence of regional (late-gadolinium enhancement quantity, 6.4±8.0%) and diffuse (T1 time, 478±79 ms) myocardial fibrosis in patients with HCM, peripheral levels of collagen precursors were similar compared with control subjects (PINP, 45.9±22.9 versus 53.4±25.9 μg/L; P=0.21; PIIINP, 4.8±1.7 versus 4.4±1.1 μg/L; P=0.26). No significant net positive transcardiac concentration gradient was detected for either biomarker of collagen synthesis., Conclusions: The cardiac contribution to peripheral levels of byproducts of collagen synthesis in patients with HCM is insignificant. Furthermore, peripheral levels of these biomarkers do not accurately reflect myocardial collagen content in these patients.

Background: Fibrocytes are bone marrow-derived mesenchymal progenitors that have been linked to various fibrotic disorders. This study was undertaken to investigate whether fibrocytes are increased in diffuse myocardial fibrosis in humans., Methods and Results: Thirty-seven patients with hypertrophic cardiomyopathy (HCM) and 20 healthy controls were recruited. Cardiac magnetic resonance imaging with postcontrast T1 mapping was performed to non-invasively quantify diffuse myocardial fibrosis and these patients were classified into 2 groups (T1 < 470 ms or T1 ≥ 470 ms, as likely or unlikely to have diffuse fibrosis, respectively). Circulating fibrocytes (CD45+/CD34+/collagen I+) were measured by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were cultured for 13 days and fibrocytes were quantitated by flow cytometry (CD45+/collagen I+) and real-time PCR (gene expression of matrix proteins). Plasma cytokines/chemokines mediating fibrocyte trafficking and differentiation were measured by multiplex assays. Circulating fibrocytes were decreased in HCM patients compared to controls. The proportion of fibrocytes derived from PBMCs was increased in patients with diffuse fibrosis compared with those without or controls (31.1 ± 4.1% versus 18.9 ± 3.9% and 10.9 ± 2.0%, P < 0.05 and P < 0.001, respectively), and the proportion of fibrocytes was inversely correlated with T1 time (r = -0.37, P = 0.03). Plasma levels of stromal cell-derived factor-1 were elevated in patients with diffuse fibrosis compared with those without or controls (5131 ± 271 pg/mL versus 3893 ± 356 pg/mL and 4172 ± 185 pg/mL, respectively, both P < 0.05)., Conclusions: HCM patients with diffuse fibrosis as assessed by postcontrast T1 mapping have elevated plasma SDF and an enhanced ability of PBMCs to differentiate into fibrocytes, suggesting that fibrocytes may contribute to the pathogenesis of myocardial fibrosis.

Background: Atrial fibrillation (AF) and systolic heart failure (HF) frequently coexist. Restoration of sinus rhythm by catheter ablation may result in a variable improvement in left ventricular (LV) function. Late-gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging identifies irreversible structural change and may predict incomplete recovery of LV function., Objective: To prospectively select patients with AF and symptomatic HF but without LV LGE and report the impact of AF ablation on LV function., Methods: Patients with AF and symptomatic HF (LV ejection fraction <50%) resistant to at least 1 antiarrhythmic drug and prior electrical cardioversion underwent contrast-enhanced CMR. LGE-negative patients underwent pulmonary vein isolation and left atrial roof line with continued antiarrhythmic medications until follow-up CMR 6 months postablation. Sixteen patients (aged 52 ± 11 years; mean AF duration 37 ± 39 months; left atrial size 44 ± 13 mL/m(2)) underwent AF ablation., Results: At 6 months, 15 of the 16 patients maintained sinus rhythm and underwent CMR. LV ejection fraction increased from 40% ± 10% at baseline to 60% ± 6% (P < .001) and LV end-systolic volume index decreased from 52 ± 12 to 36 ± 9 mL/m(2) (P < .001). Left atrial size decreased from 44 ± 13 to 36 ± 11 mL/m(2) (P < .01)., Conclusions: In patients with AF and LV dysfunction in the absence of LGE on CMR, ventricular function normalizes following the restoration of sinus rhythm. CMR may assist in the selection of patients with combined AF and systolic HF most likely to benefit from catheter ablation., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Successful arrhythmia ablation normalizes ejection fraction (EF) in tachycardia-mediated cardiomyopathy, but recurrent heart failure and late sudden death have been reported. The aim of this study was to characterize the left ventricle (LV) of tachycardia-mediated cardiomyopathy patients long after definitive arrhythmia cure., Methods and Results: Thirty-three patients with a history of successfully ablated incessant focal atrial tachycardia 64±36 months prior, and 20 healthy controls were recruited. At ablation, 18 patients had EF<50% (AT-low EF) that recovered within 3 months from 37±12 to 56±4% (P<0.001), whereas 15 patients had EF>55% (AT-normal EF). No subjects had EF of 50% to 55%. Subjects underwent echocardiography with speckle tracking and contrast-enhanced cardiac MRI with ventricular T1 mapping as an index of diffuse fibrosis. Contrast-enhanced cardiac MRI was performed using a clinical 1.5-T scanner and 0.2 mmol/kg gadolinium-diethylene triamine penta-acetic acid for contrast. Subject characteristics were similar across the 3 groups. Compared with AT-normal EF patients and controls, AT-low EF patients had lower EF (60±6 versus 64±4 and 65±4%; P<0.05), greater indexed LV end-diastolic volume (102±34 versus 84±14 and 85±16 mL/m(2); P<0.05), and greater indexed LV end-systolic volume (41±11 versus 31±7 and 30±8 mL/m(2); P<0.01) on contrast-enhanced cardiac MRI. Compared with controls, AT-low EF patients had reduced global LV corrected T1 time (442±53 versus 529±61; P<0.05) consistent with diffuse fibrosis., Conclusions: Tachycardia-mediated cardiomyopathy patients exhibit differences in LV structure and function including diffuse fibrosis long after arrhythmia cure, indicating that recovery is incomplete.

After the advent of ECG gated cardiac CT angiography (CCTA) there has been significant improvement in image quality of the ascending aorta. As a result the sinuses of valsalva are readily assessable. Sinuses of valsalva aneurysm can cause significant dysfunction of the aortic root and annulus and can be congenital or acquired. The aneurysm most commonly originates from the right coronary sinus. Complications related to sinuses of valsalva aneurysm can cause chest pain and can be life threatening. The cardiac imager should actively assess the sinuses of valsalva in every CCTA study., (© 2012 The Authors. Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists.)

Cardiac resynchronisation therapy (CRT) can reduce symptoms, hospitalisations, and mortality in patients with severe left ventricular (LV) systolic dysfunction and electro-mechanical dyssynchrony. Unfortunately, approximately 30 % of eligible patients fail to respond to CRT. This study prospectively compared electrocardiography (ECG), echocardiography, and cardiac magnetic resonance (CMR) imaging for the prediction of response to CRT. We performed ECG, echocardiography and CMR on 46 patients prior to planned CRT implantation. Patients were divided into predicted responder and non-responder groups using previously described criteria for each modality. Changes in indicators of CRT response were recorded 6 months post-implantation, and later for transplant-free survival. Less dyspnoea, lower levels of N-terminal pro-brain natriuretic peptide, more LV reverse remodelling, and longer transplant-free survival were observed in predicted responders compared to predicted non-responders using each of the three modalities (p < 0.05 for each comparison). Additionally, for patients with QRS duration <150 ms and/or non-left bundle branch block (non-LBBB) QRS morphology, CMR predicted both clinical response and improved longer term transplant-free survival (80 % transplant-free survival in predicted responders vs. 20 % in predicted non-responders, p = 0.04). ECG and cardiac imaging techniques predict improvements in markers of response following CRT with similar accuracy. However, for CRT candidates with shorter, non-LBBB QRS complexes, a subgroup known to derive less benefit from CRT, CMR may predict those who are more likely to gain both symptomatic and survival benefits.

Objectives: The purpose of this study was to evaluate diffuse myocardial fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF)., Background: Diffuse myocardial fibrosis is a hallmark of cardiomyopathy. Unlike replacement fibrosis, it is not visualized on delayed-enhancement cardiac magnetic resonance (CMR) imaging, but may be quantified with contrast-enhanced T(1) mapping methods. In atrial fibrillation (AF), it may be induced by arrhythmia or reflect pre-existing cardiomyopathy., Methods: Ninety subjects underwent CMR using a clinical 1.5-T scanner: 23 controls, 40 paroxysmal AF patients, and 27 persistent AF patients. Cardiac morphology and function was evaluated from CMR cine imaging. A histologically validated T(1) mapping sequence was used to calculate post-contrast T(1) relaxation time (T(1) time) of the LV myocardium as an index of diffuse myocardial fibrosis., Results: Age was similar across controls, paroxysmal AF patients, and persistent AF patients (54 ± 12 years, 58 ± 9 years, and 56 ± 10 years, p = NS). Persistent AF patients had larger indexed left atrium volume (55 ± 18 ml vs. 41 ± 12 ml and 47 ± 14 ml) and lower ejection fraction (54 ± 10% vs. 65 ± 6% and 61 ± 8%) than controls and paroxysmal AF patients (p < 0.05). Post-contrast ventricular T(1) time differed across all groups (controls, 535 ± 86 ms; paroxysmal AF, 427 ± 95 ms; persistent AF, 360 ± 84 ms; p < 0.001). Univariate predictors of post-contrast ventricular T(1) time included age, sex, AF category, ejection fraction, LV mass, congestive heart failure, and body mass index. After multivariate analysis, age, AF category, and ejection fraction remained independent predictors., Conclusions: Post-contrast ventricular T(1) mapping identifies diffuse LV fibrosis in patients with AF and provides new insights into the association between AF and adverse ventricular remodeling., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The presence of myocardial fibrosis is associated with worse clinical outcomes in hypertrophic cardiomyopathy (HCM). Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) sequences can detect regional, but not diffuse myocardial fibrosis. Post-contrast T(1) mapping is an emerging CMR technique that may enable the non-invasive evaluation of diffuse myocardial fibrosis in HCM. The purpose of this study was to non-invasively detect and quantify diffuse myocardial fibrosis in HCM with CMR and examine its relationship to diastolic performance., Methods: We performed CMR on 76 patients - 51 with asymmetric septal hypertrophy due to HCM and 25 healthy controls. Left ventricular (LV) morphology, function and distribution of regional myocardial fibrosis were evaluated with cine imaging and LGE. A CMR T(1) mapping sequence determined the post-contrast myocardial T(1) time as an index of diffuse myocardial fibrosis. Diastolic function was assessed by transthoracic echocardiography., Results: Regional myocardial fibrosis was observed in 84% of the HCM group. Post-contrast myocardial T(1) time was significantly shorter in patients with HCM compared to controls, consistent with diffuse myocardial fibrosis (498 ± 80 ms vs. 561 ± 47 ms, p < 0.001). In HCM patients, post-contrast myocardial T(1) time correlated with mean E/e' (r = -0.48, p < 0.001)., Conclusions: Patients with HCM have shorter post-contrast myocardial T(1) times, consistent with diffuse myocardial fibrosis, which correlate with estimated LV filling pressure, suggesting a mechanistic link between diffuse myocardial fibrosis and abnormal diastolic function in HCM.

Objectives: This prospective study aimed to assess regional and temporal patterns of extracellular matrix (ECM) changes post-myocardial infarction (MI)., Background: A fundamental process in the development of ischemic left ventricular (LV) dysfunction is LV remodeling, characterized by structural and functional abnormalities throughout the myocardium including the noninfarcted (remote) myocardium and interstitium., Methods: Contrast-enhanced cardiac magnetic resonance (CMR) was performed on MI patients acutely (mean: 5 days post-MI, n = 25) and repeated subacutely (mean: 139 days post-MI, n = 21), and was also performed in a separate group of 15 patients with chronic MI (mean: 2,580 days post-MI, n = 15). Twenty volunteers without a history of MI acted as controls. CMR was used to evaluate LV morphology and function, with post-contrast T1 mapping to semiquantitatively assess changes in the ECM. Putative mediators of myocardial inflammation and fibrosis, including macrophage migration inhibitory factor (MIF), were also measured., Results: Age, sex, and diabetic and hypertensive status did not differ between MI groups and controls. Compared with controls, patients early post-acute MI demonstrated reduced LV ejection fraction (50.25 ± 7.29% vs. 66.7 ± 6.2% [controls], p < 0.0001). Myocardium remote to the infarction early post-acute MI, compared with controls, demonstrated reduced systolic thickening (60 ± 5.0% vs. 106 ± 7.6%, p ≤ 0.0002), and lower post-contrast myocardial T1 times suggestive of ECM expansion (437 ± 113 ms vs. 549 ± 119 ms, p = 0.01). In a subgroup analysis between early post-acute MI and controls of similar age and sex, the remote sector post-contrast myocardial T1 times remained significantly shorter post-acute MI compared with controls (420 ± 121 ms vs. 529 ± 113 ms, p = 0.03). Serum levels of MIF inversely correlated with global myocardial T1 time in patients early post-acute MI (r = -0.6, p = 0.01), suggesting a coupling of regional healing with acute LV remodeling., Conclusions: Within a week of acute MI, the remote myocardium exhibits systolic dysfunction and expansion of the ECM, which is coupled with physiological infarct healing. Further prospective studies with larger sample sizes are needed to verify these important findings., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Experimental studies suggest that deferoxamine (DFO) limits the generation of reactive oxygen species by chelating redox-active iron and thereby may reduce ischemia-reperfusion injury and myocardial infarct (MI) size. We investigated whether DFO administered before reperfusion by primary percutaneous coronary intervention (PPCI) would ameliorate oxidative stress and MI size., Methods and Results: We randomly assigned 60 patients with ST-elevation-MI to receive an intravenous bolus of DFO (500 mg) immediately before PPCI followed by a 12-hour infusion (50 mg/kg of body weight) (n=28) or normal saline bolus and infusion (placebo group, n=32). MI size was measured by contrast-enhanced cardiac MRI (CMRI; day 3±1), creatine kinase and troponin I area-under-the-curve, and severity of wall motion abnormality on echocardiography. Clinical follow-up including repeat CMRI and echocardiography were performed at 3 months (100±17 days). Oxidative stress was assessed by plasma F(2)-isoprostane levels. DFO and placebo groups were well balanced with respect to baseline characteristics, symptom- and door-to-balloon times, pre-PPCI coronary patency, and infarct-related artery location. Serum iron levels were decreased with DFO treatment after PPCI compared with placebo (3.0±2.5 versus 12.6±5.5 μmol/L, P<0.0001), which persisted until the end of the infusion. In DFO-treated patients, there was a significant reduction in plasma F(2)-isoprostane levels immediately after PPCI (2878±1461 versus 2213±579 pmol/L, P=0.04). However, there was no difference in CMRI-determined infarct size (DFO, 17.4±10.8%, versus placebo, 18.6±10.2%; P=0.73), myocardial salvage index at 3 days or at 3 months, or the area-under-the-curve for creatine kinase or troponin I., Conclusions: Adjunctive DFO treatment after the onset of ischemia and continued periprocedurally ameliorates oxidative stress without limiting infarct size., Clinical Trial Registration: URL: http://www.anzctr.org.au/. Unique identifier: ACTRN12608000308392.

Cardiac magnetic resonance imaging (CMR) has matured into a robust, accurate and highly reproducible imaging modality for the assessment of cardiac function and ischaemic heart disease. The unique physical properties of CMR permit depiction of pathology-specific tissue contrast based on differences in tissue composition, such as myocardial oedema, necrosis and fibrosis. This can be imaged at high spatial resolution allowing characterisation of the acuity of an ischaemic event, the presence and extent of myocardial ischaemia, necrosis and viability. Prognostically important information obtained from CMR evaluation of ischaemic heart disease, such as left ventricular ejection fraction, infarct size and transmurality, infarct location and the presence of intraventricular mechanical dyssynchrony may be used to guide coronary revascularisation, device and medical therapies., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)