Reduction in mortality from implantable cardioverter-defibrillators in non-ischaemic cardiomyopathy patients is dependent on the presence of left ventricular scar.

Aims: In patients with non-ischaemic cardiomyopathy (NICM), the mortality benefit of a primary prevention implantable cardioverter-defibrillator (ICD) has been challenged. Left ventricular (LV) scar identified by cardiac magnetic resonance (CMR) imaging is associated with a high risk of malignant arrhythmia in NICM. We aimed to determine the impact of LV scar on the mortality benefit from a primary prevention ICD in NICM. Methods and results: We recruited 452 consecutive heart failure patients [New York Heart Association (NYHA) Class II/III] with NICM and LV ejection fraction ≤35% from a state-wide CMR service. All patients fulfilled European Society of Cardiology guidelines for primary prevention ICD implantation; however, the decision to implant was at the treating physician's discretion. Baseline clinical and CMR data were recorded prospectively and heart failure mortality risk (MAGGIC score) was calculated. The primary study outcome measurement was all-cause mortality based on presence or absence of ICD, stratified by LV scar. Median follow-up was 37.9 months and there was no difference in MAGGIC score between those who did and did not receive a primary prevention ICD (19.30 ± 5.46 vs. 18.90 ± 5.67, P = 0.50). In patients without LV scar, ICD implantation was not associated with improved mortality [hazard ratio (HR) = 1.22, 95% confidence interval (CI): 0.53-2.78, P = 0.64]. In patients with LV scar, ICD implantation was independently associated with reduced mortality (HR = 0.45, 95% CI: 0.26-0.77, P = 0.003). Conclusions: In patients with NICM, primary prevention ICD implantation is only associated with reduced mortality in patients with LV scar. This may enable more effective selection of NICM patients for ICD implantation compared with current guidelines.

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.

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.

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.

Combined dyssynchrony and scar imaging with cardiac magnetic resonance imaging predicts clinical response and long-term prognosis following cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) is advocated in advanced heart failure; however, patient selection remains challenging. We examined the utility of multi-sequential cardiac magnetic resonance imaging (CMR) in predicting outcome after CRT. METHODS AND RESULTS: We performed multi-sequential CMR on 40 subjects with cardiomyopathy and advanced heart failure, despite optimized medical therapy. All patients had been recommended for CRT according to accepted clinical guidelines. Patients were defined by CMR as likely responders if they had significant mechanical dyssynchrony (> or =65 ms delay between septal and posterolateral wall contraction on cine imaging), and no transmural scarring of the anteroseptal or posterolateral wall on delayed contrast-enhanced imaging. Clinical composite score was recorded at baseline and 6 months post-CRT. Long-term follow-up (transplant-free survival) was 497 +/- 55 days post-CRT. A clinical response was achieved in 19/26 (73%) of the CMR-predicted responders and 2/12 (17%) of the CMR-predicted non-responders (P < 0.01, chi(2)). The sensitivity of CMR for prediction of clinical response to CRT was 90%, with a specificity of 59%. Transplant-free survival post-CRT was achieved in 88% of the CMR-predicted responders and 58% of the CMR-predicted non-responders (P < 0.05, Kaplan-Meier survival analysis). CONCLUSION: Multi-sequential CMR identifies patients with severe cardiomyopathy who will respond to CRT with a favourable long-term prognosis.

Impact of sex, socio-economic status, and remoteness on therapy and survival in heart failure.

AIMS: This study aims to determine if traditional markers of disadvantage [female sex, low socio-economic status (SES), and remoteness] are associated with lower prescription of evidence-based therapy and higher mortality among patients with moderate-severe heart failure with reduced ejection fraction. METHODS AND RESULTS: We recruited 452 consecutive class II-III heart failure with reduced ejection fraction patients. Baseline clinical data were recorded prospectively. The primary outcome was the association of female sex on overall survival. Secondary outcomes included association between evidence-based therapy delivery and sex and association of SES and remoteness on heart failure therapy and survival. The Australian Bureau of Statistics generated all indices. Median follow-up was 37.9 months. One hundred and nine patients (24.3%) were women. There was no difference in overall survival based on sex (hazard ratio = 1.19, 95% confidence interval: 0.74-1.92, 0.48). There was no difference in prescription of beta-blockers [χ2 (1) = 0.91, 0.66], angiotensin-converting enzyme inhibitors [χ2 (1) = 0.001, 0.97], nor aldosterone antagonists [χ2 (1) = 2.71, 0.10]. There was no difference in rates of primary prevention implantable cardioverter-defibrillator implantation in men compared with women [χ2 (1) = 0.35, 0.56]. Neither higher SES nor inner city residence conferred an overall survival benefit. CONCLUSIONS: In this Australian cohort of heart failure patients, delivery of care and likelihood of death are comparable between the sexes, SES groups, and rural vs. city residents.

Regression of Diffuse Ventricular Fibrosis Following Restoration of Sinus Rhythm With Catheter Ablation in Patients With Atrial Fibrillation and Systolic Dysfunction: A Substudy of the CAMERA MRI Trial.

OBJECTIVES: This study sought to determine if diffuse ventricular fibrosis improves in patients with atrial fibrillation (AF)-mediated cardiomyopathy following the restoration of sinus rhythm. BACKGROUND: AF coexists in 30% of heart failure (HF) patients and may be an underrecognized reversible cause of left ventricular systolic dysfunction. Myocardial fibrosis is the hallmark of adverse cardiac remodeling in HF, yet its reversibility is unclear. METHODS: Patients with persistent AF and an idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%) were randomized to catheter ablation (CA) or ongoing medical rate control as a pre-specified substudy of the CAMERA-MRI (Catheter Ablation versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction-an MRI-Guided Multi-centre Randomised Controlled Trial) trial. All patients had cardiac magnetic resonance imaging scans (including myocardial T1 time), serum B-type natriuretic peptide, 6-min walk tests, and Short Form-36 questionnaires performed at baseline and 6 months. Sixteen patients with no history of AF or left ventricular systolic dysfunction were enrolled as normal controls for T1 time. RESULTS: Thirty-six patients (18 in each treatment arm) were included in this substudy. Demographics, comorbidities, and myocardial T1 times were well matched at baseline. At 6 months, patients in the CA group had a significant reduction in myocardial T1 time from baseline compared with the medical rate control group (-124 ms; 95% confidence interval [CI]: -23 to -225 ms; p = 0.0176), although it remained higher than that of normal controls at 6 months (p = 0.0017). Improvements in myocardial T1 time with CA were associated with significant improvements in absolute LVEF (+12.5%; 95% CI: 5.9% to 19.0%; p = 0.0004), left ventricular end-systolic volume (p = 0.0019), and serum B-type natriuretic peptide (-216 ng/l; 95% CI: -23 to -225 ng/l; p = 0.0125). CONCLUSIONS: The improvement in LVEF and reverse ventricular remodeling following successful CA of AF-mediated cardiomyopathy is accompanied by a regression of diffuse fibrosis. This suggests timely treatment of arrhythmia-mediated cardiomyopathy may minimize irreversible ventricular remodeling.

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.

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.

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.

Magnetic resonance post-contrast T1 mapping in the human atrium: validation and impact on clinical outcome after catheter ablation for atrial fibrillation.

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.

A comprehensive evaluation of myocardial fibrosis in hypertrophic cardiomyopathy with cardiac magnetic resonance imaging: linking genotype with fibrotic phenotype.

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.

Diffuse ventricular fibrosis is a late outcome of tachycardia-mediated cardiomyopathy after successful ablation.

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.

Sinus rhythm restores ventricular function in patients with cardiomyopathy and no late gadolinium enhancement on cardiac magnetic resonance imaging who undergo catheter ablation for atrial fibrillation.

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.

Diffuse ventricular fibrosis in atrial fibrillation: noninvasive evaluation and relationships with aging and systolic dysfunction.

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.