Comparison of Magnetic Resonance Analysis of Myocardial Scarring With Biomarker Release Following S-T Elevation Myocardial Infarction.

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.

Hypertrophic cardiomyopathy in the adolescent.

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.

Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction.

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.

Diffuse Ventricular Fibrosis on Cardiac Magnetic Resonance Imaging Associates With Ventricular Tachycardia in Patients With Hypertrophic Cardiomyopathy.

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.

Circulating microRNAs as biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy.

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.

Diffuse myocardial fibrosis in hypertrophic cardiomyopathy can be identified by cardiovascular magnetic resonance, and is associated with left ventricular diastolic dysfunction.

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.

Association between pre-hospital chest pain severity and myocardial injury in ST elevation myocardial infarction: A post-hoc analysis of the AVOID study.

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.

Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure.

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 ß-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 ß-adrenoceptor activation in mediating elevated galectin-3 levels via cardiac release in the mechanism.

Systemic inflammation is associated with myocardial fibrosis, diastolic dysfunction, and cardiac hypertrophy in patients with hypertrophic cardiomyopathy.

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.

Assessment of the accuracy of common clinical thresholds for cardiac morphology and function by transthoracic echocardiography.

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.

SASHA versus ShMOLLI: a comparison of T1 mapping methods in health and dilated cardiomyopathy at 3 T.

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.

Effect of supplemental oxygen exposure on myocardial injury in ST-elevation myocardial infarction.

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.

The role of left atrial imaging in the management of atrial fibrillation.

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.

Histological validation of cardiac magnetic resonance analysis of regional and diffuse interstitial myocardial fibrosis.

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.

Plasma lipidomic analysis predicts non-calcified coronary artery plaque in asymptomatic patients at intermediate risk of coronary artery disease.

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.

Diffuse myocardial fibrosis evaluated by post-contrast t1 mapping correlates with left ventricular stiffness.

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 ß, 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 ß. 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.

Evaluating the utility of circulating biomarkers of collagen synthesis in hypertrophic cardiomyopathy.

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.

Diffuse ventricular fibrosis measured by T1 mapping on cardiac MRI predicts success of catheter ablation for atrial fibrillation.

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.