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Background: The success of pulmonary vein isolation (PVI) is reduced in persistent AF (PsAF) compared to paroxysmal AF. Adjunctive ablation strategies have failed to show consistent incremental benefit over PVI alone in randomized studies. The left atrial posterior wall is a potential source of non-PV triggers and atrial substrate which may promote the initiation and maintenance of PsAF. Adding posterior wall isolation (PWI) to PVI had shown conflicting outcomes, with earlier studies confounded by methodological limitations., Objectives: To determine whether combining PWI with PVI significantly improves freedom from AF recurrence, compared to PVI alone, in patients with PsAF., Methods: This is a multi-center, prospective, international randomized clinical trial. 338 patients with symptomatic PsAF refractory to anti-arrhythmic therapy (AAD) will be randomized to either PVI alone or PVI with PWI in a 1:1 ratio. PVI involves wide antral circumferential pulmonary vein (PV) isolation, utilizing contact force sensing ablation catheters. PWI involves the creation of a floor line connecting the inferior aspect of the PVs, and a roof line connecting the superior aspect of the PVs. Follow up is for a minimum of 12 months with rhythm monitoring via implantable cardiac device and/or loop monitor, or frequent intermittent monitoring with an ECG device. The primary outcome is freedom from any documented atrial arrhythmia of > 30 seconds off AAD at 12 months, after a single ablation procedure., Conclusions: This randomized study aims to determine the success and safety of adjunctive PWI to PVI in patients with persistent AF., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: This study sought to report P-wave morphology (PWM) from a series of paraseptal (PS) atrial tachycardia (AT), revise then prospectively evaluate a simplified PWM algorithm against a contemporary consecutive cohort with focal AT., Background: The 2006 PWM algorithm was useful in predicting the origin of focal AT. An updated algorithm was developed given advances in multipolar 3-dimensional mapping, potential limitations of PWM in separating PS sites, and a renewed interest in the P-wave in mapping non-pulmonary vein triggers., Methods: The PWM from a consecutive series of 67 patients with PS AT were analyzed. PS sites included were coronary sinus ostium, perinodal, left and right septum, septal tricuspid annulus, superior mitral annulus, and noncoronary cusp. Next the P-wave algorithm was revised and prospectively evaluated by 3 blinded assessors., Results: The P-wave for PS sites was neg/pos (n = 50), iso/pos (n = 10), or isoelectric (n = 4) in lead V 1 (96%). The P-wave algorithm was modified and prospectively applied to 30 consecutive patients with focal AT who underwent successful ablation. Foci (n = 30) originated from the right atrium (33.3%), left atrium (30%), and PS (36.7%). Using the PW algorithm, the correct anatomic location was identified in 93%. Incorrect interpretation of the terminal positive P-wave component (n = 3) and initial negative P-wave deflection (n = 1) in lead V 1 misidentified 4 paraseptal cases., Conclusions: The revised PWM algorithm offers a simplified and accurate method of localizing the responsible site for focal AT. The P-wave remains an important first step in mapping atrial arrhythmias., Competing Interests: Funding Support and Author Disclosures Dr Chieng has been supported by a co-funded National Health and Medical Research Council (NHMRC)/National Heart Foundation postgraduate scholarship. The following industry funding sources regarding activities outside the submitted work have been declared in accordance with ICMJE guidelines. Prof Kistler has received funding from Abbott Medical for consultancy and speaking engagements and fellowship support from Biosense Webster. Prof Kalman has had an NHMRC practitioner fellowship, and research and fellowship support from Medtronic and Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to describe expected changes in a mirror-image prone electrocardiogram (ECG) compared with normal supine, including a range of cardiac conditions., Background: Unwell COVID-19 patients are at risk of cardiac complications. Prone ventilation is recommended but poses practical challenges to acquisition of a 12-lead ECG. The effects of prone positioning on the ECG remain unknown., Methods: 100 patients each underwent 3 ECGs: standard supine front (SF); prone position with precordial leads attached to front (PF); and prone with precordial leads attached to back in a mirror image to front (PB)., Results: Prone positioning was associated with QTc prolongation (PF 437 ± 32 ms vs. SF 432 ± 31 ms; p < 0.01; PB 436 ± 34 ms vs. SF 432 ± 31 ms; p = 0.02). In leads V 1 to V 3 on PB ECG, a qR morphology was present in 90% and changes in T-wave polarity in 84%. In patients with anterior ischemia, ST-segment changes in V 1 to V 3 on supine ECG were no longer visible on PB in 100% and replaced by an R-wave in V 1 . Bundle branch block (BBB) remained detectable in 100% on PB, with left BBB appearing as right BBB on PB in 71% and QRS narrowing with qR in V 1 for right BBB. ST-segment/T-wave changes in limb leads and arrhythmia detection were largely unaffected in PB., Conclusions: As expected, the PB ECG is unreliable for the detection of anterior myocardial injury but remains useful for ST-segment/T-wave abnormalities in limb leads, BBB detection, and rhythm monitoring. The prone ECG is a useful screening tool with diagnostic utility in COVID-19 patients who require prone ventilation., Competing Interests: Funding Support and Author Disclosures Dr. Chieng is supported by a cofunded National Health and Medical Research Council/ National Heart Foundation post-graduate scholarship. Dr. Kalman has received research and fellowship support from Medtronic and Biosense Webster. Prof. Kistler has received funding from Abbott Medical; and fellowship support from Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine the long-term outcomes of restoring sinus rhythm with catheter ablation (CA)., Background: The CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Heart Failure-An MRI-Guided Multicenter Randomized Controlled Trial) study demonstrated that restoration of sinus rhythm with CA significantly improved left ventricular ejection fraction (LVEF) compared with medical rate control (MRC) at 6 months in persistent atrial fibrillation and otherwise unexplained systolic heart failure. However, the long-term outcomes have not been reported., Methods: Patients enrolled in the CAMERA-MRI study were followed for 4 years with echocardiogram and cardiac magnetic resonance. CA involved pulmonary vein isolation and posterior left atrial wall isolation in 94%. Patients crossed over to CA after 6-month study duration. Arrhythmia burden was determined with implanted cardiac monitors or cardiac devices., Results: Sixty-six patients (age 62 ± 10 years, atrial fibrillation duration of 22 ± 16 months, and LVEF 33 ± 9%) were randomized 1:1 to CA versus MRC. Eighteen of 33 patients crossed over from MRC group to CA group. At 4.0 ± 0.9 years, atrial fibrillation recurred in 27 patients (57%) in the CA group with a mean burden of 10.6 ± 21.2% after 1.4 ± 0.6 procedures. There was an absolute increase in LVEF with CA of 16.4 ± 13.3% compared with 8.6 ± 7.6% in MRC (p = 0.001). In the CA group, the absence of ventricular late gadolinium enhancement was associated with a greater improvement in absolute LVEF (19 ± 13% vs. 10 ± 11% in the late gadolinium enhancement-positive group; p = 0.04) and LVEF normalization in 19 patients (58%) versus 4 patients (18%) in the late gadolinium enhancement-positive group (p = 0.008) at 4.0 ± 0.9 years follow-up., Conclusions: CA is superior to MRC in improving LVEF in the long term in patients with atrial fibrillation and systolic heart failure. The greatest recovery in systolic function was demonstrated in the absence of ventricular fibrosis on cardiac magnetic resonance., Competing Interests: Author Disclosures Dr. Sugumar has received support from a co-funded National Health and Medical Research Committee/National Health Foundation post-graduate scholarships and Royal Australian College of Physicians J.J. Billings and Centre of Research Excellence in Cardiovascular Outcomes Improvement scholarships. Prof. Jonathan M. Kalman has received a National Health and Medical Research Committee practitioner fellowship; and research and fellowship support from Medtronic and Biosense Webster, all outside the submitted work. Prof. Kistler has received funding from Abbott Medical for consultancy and speaking engagements, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess the atrial electrophysiological properties and post-ablation outcomes in patients with atrial fibrillation (AF) with and without the rs2200733 single nucleotide variant., Background: The phenotype associated with chromosome 4q25 of the AF-susceptibility locus remains unknown., Methods: In this study, 102 consecutive patients (ages 61 ± 9 years, 64% male) with paroxysmal or persistent AF were prospectively recruited prior to ablation. Patients were genotyped for rs2200733 and high-density left atrial (LA) electroanatomic maps were created using a multipolar catheter during distal coronary sinus (CS) pacing at 600 ms. Voltage, conduction velocity (CV), CV heterogeneity, and fractionated signals of 6 LA segments were determined. Arrhythmia recurrence was assessed by continuous device (51%) and Holter monitoring., Results: Overall, 41 patients (40%) were single nucleotide variant carriers (38 heterozygous, 3 homozygous). A mean of 2,239 ± 852 points per patient were collected. Carriers had relatively increased CV heterogeneity (45.7 ± 7.5% vs. 35.9 ± 2.3%; p < 0.001), complex signals (9.4 ± 2.9% vs 6.0 ± 1.2%; p = 0.008), regional LA slowing, or conduction block (31.7 ± 8.2% vs. 17.9 ± 1.9%; p = 0.013) particularly in the posterior and lateral walls. There were no differences in CV, voltage, atrial refractoriness, or sinus node function. At follow-up (median: 27 months; range 19 to 31 months), carriers had lower arrhythmia-free survival (51% vs. 80%; p = 0.003). On multivariable analysis, carrier status was independently associated with CV heterogeneity (p = 0.001), complex signals (p = 0.002), and arrhythmia recurrence (p = 0.019)., Conclusions: These data provide the first evidence that the rs2200733-tagged haplotype alters LA electrical remodeling and is a determinant of long-term outcome following AF ablation. The molecular mechanisms underpinning these changes warrant further investigation., Competing Interests: Author Relationship With Industry Dr. Wong has received support from co-funded National Health and Medical Research Council (NHMRC)/Heart Foundation post-graduate scholarships. Dr. Fatkin has received support from the NHMRC, Victor Chang Cardiac Research Institute, Estate of the Late RT Hall, and Simon Lee Foundation. Prof. Kalman has received support from an NHMRC practitioner fellowship; and has received research and fellowship support from Biosense Webster, Boston Scientific, St. Jude Medical, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020. Published by Elsevier Inc.)

Background: Female gender is associated with an increased recurrence of atrial fibrillation (AF) after catheter ablation (CA). Although AF is more common in men, women constitute a significant proportion with persistent atrial fibrillation (PsAF)., Objective: The purpose of this study was to determine whether multiple ablation procedures improves arrhythmia outcomes in females with PsAF compared to men., Methods: We performed a multicenter observational study to determine long-term arrhythmia outcomes in patients undergoing >1 CA for PsAF. CA involved pulmonary vein (PV) isolation with additional ablation including linear, posterior wall isolation, electrogram-guided, or a combination of these., Results: A total of 281 patients had >1 ablation procedure for PsAF and were included in this analysis (mean age 58.7 ± 9.3 years; 86 [30.6%] female; left atrial [LA] area 27.0 ± 5.3 cm 2 ; PsAF duration 1.7 ± 1.7 years). At mean follow-up of 45.5 ± 31.8 months, freedom from recurrent AF was present in 148 patients(52.7%) after 2.2 ± 0.5 procedures. After multivariate analysis, female gender (hazard ratio [HR] 2.10; P <.001) and enduring PV isolation (HR 1.64; P = .01) were independently associated with AF recurrence. Enduring PV isolation was significantly higher in women than in men (33.7% vs 19.5%; P = .01)., Conclusion: Female gender was independently and strongly associated with arrhythmia recurrence in patients undergoing multiple procedures for PsAF. PV reconnection was less likely, and fewer reconnected PVs occurred in women. Further studies are required to better understand the mechanisms responsible for AF in females to assist in closing the gender gap in the success of CA., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine the impact of rate and direction on left atrial (LA) substrate., Background: The extent to which substrate mapped in sinus rhythm varies according to cycle length and direction of wave front propagation is unknown., Methods: A total of 73 consecutive patients with atrial fibrillation (AF) underwent electroanatomic LA mapping before pulmonary vein isolation using multipolar catheter during distal coronary sinus (CS) pacing at 600 ms and 300 ms. Additional maps were created during left superior pulmonary vein pacing at 300 ms. Bipolar voltage, conduction velocity (CV), and complex signals were determined., Results: Mean age was 61 ± 9 years, 67% were men, and 53% had persistent AF. Global mean voltage was lower with CS pacing at 300 ms compared with 600 ms (1.56 ± 0.47 mV vs. 1.74 ± 0.48 mV; p < 0.001). This was seen in all LA segments. Global CV was reduced (30.4 ± 13.0 cm/s vs. 38.6 ± 14.0 cm/s; p < 0.001) with greater complex signals at 300 ms (8.9% vs. 5.3%; p < 0.005). Compared with CS pacing, left superior pulmonary vein pacing demonstrated highly regional changes with decreased voltage (1.04 ± 0.43 mV vs. 1.47 ± 0.53 mV; p = 0.01) and CV (24.4 ± 13.0 cm/s vs. 39.9 ± 16.6 cm/s; p = 0.008), and greater complex signals posteriorly. Longer AF duration in paroxysmal AF (p = 0.02) and shorter duration in persistent AF (p = 0.015) and left ventricular ejection fraction (p = 0.016) were independent predictors of voltage change., Conclusions: In patients with AF, variation in cycle length and direction of wave front activation produce both generalized and regional changes in voltage, CV, and complex fractionation, resulting in significant changes in substrate maps. This study highlights the potential limitations of static low-voltage maps to identify the AF ablation target zone., (Copyright © 2019. Published by Elsevier Inc.)

Objectives: This study sought to determine the long-term right atrial (RA) electrical and structural changes in a subgroup from the CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction-Magnetic Resonance Imaging) study., Background: Catheter ablation (CA) is successful in restoring ventricular function in patients with atrial fibrillation (AF) and otherwise unexplained cardiomyopathy, as demonstrated in the randomized study of CA versus rate control (CAMERA-MRI). It is unknown if this is associated with atrial remodeling., Methods: Detailed electroanatomical (EA) mapping of the RA using CARTO3 and a force sensing catheter was performed at initial CA and electively at least 12 months after CA in patients with >90% reduction in AF burden following ablation. Bipolar voltage, fractionation, and conduction velocity were collected in 4 segments together with echo and cardiac magnetic resonance imaging., Results: Fifteen patients (mean age 59.1 ± 6.8 years) underwent repeat RA EA mapping. At a mean follow-up of 23.4 ± 11.9 months, left ventricular (LV) ejection fraction improved from 33.6 ± 3.2% to 54.1 ± 3.2% (p = 0.001), RA area decreased from 28.4 ± 2.0 cm 2 to 20.8 ± 1.2 cm 2 (p < 0.001), and left atrial area decreased from 32.9 ± 2.3 cm 2 to 26.8 ± 1.4 cm 2 (p = 0.007). On EA mapping, RA bipolar voltage increased from 1.6 ± 0.1 mV to 1.9 ± 0.1 mV (p = 0.04). Tissue voltage increased across all regions, which achieved statistical significance at the posterior (p = 0.002) and septal (p = 0.01) segments. There was a significant decrease in complex fractionated electrograms from 21.7 ± 3.5% to 8.3 ± 1.8% (p = 0.002); however, no significant change occurred in global or regional conduction velocities (p = 0.5)., Conclusions: Recovery of atrial electrical and structural changes was observed following restoration of sinus rhythm and recovery of LV function in patients who underwent CA for persistent AF and LV systolic dysfunction. The randomized CAMERA MRI study demonstrated significant improvement in LV systolic function with AF ablation compared with rate control. The present study demonstrated reverse electrical and structural atrial recovery in concert with recovery of LV systolic function at 2 years post-AF ablation. This may partially explain the long-term success of CA in patients with AF and otherwise unexplained cardiomyopathy., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation and heart failure (HF) frequently coexist and are associated with a significant increase in morbidity and mortality. Despite the shared common risk factors atrial fibrillation and HF subtypes exacerbate each other. This review provides an overview of the pathophysiologic relationship between atrial fibrillation and the two most common types of heart failure syndromes: HF with reduced ejection fraction and HF with preserved ejection fraction., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Regular alcohol intake is an important modifiable risk factor associated with atrial fibrillation (AF) and left atrial (LA) dilation., Objective: The purpose of this study was to determine the impact of different degrees of alcohol consumption on atrial remodeling using high-density electroanatomic mapping., Methods: We enrolled 75 patients before AF ablation to undergo high-density LA mapping (CARTO, Biosense Webster) using a multipolar catheter. The Confidense algorithm was used to create maps during distal coronary sinus pacing at 600 ms. Bipolar voltage and complex atrial activity were assessed, and isochronal activation maps were created to determine global conduction velocity (CV). Patients were classified as lifelong nondrinkers, mild drinkers (2-7 drinks/week), or moderate drinkers (8-21 drinks/week)., Results: High-density electroanatomic mapping (mean 1016 ± 445 points per patient) was performed on 25 lifelong nondrinkers, 25 mild drinkers (4.4 ± 2.3 drinks/week), and 25 moderate drinkers (14.0 ± 4.2 drinks/week). Moderate drinkers had significantly lower mean global bipolar voltages (1.53 ± 0.62 mV vs 1.89 ± 0.45 mV; P = .02), slower CV (33.5 ± 14.4 cm/s vs 41.7 ± 12.1 cm/s; P = .04), and a higher proportion of complex atrial potentials (7.8% ± 4.7% vs 4.5% ± 2.7%; P = .004) compared to nondrinkers. Global voltage and CV did not differ significantly in mild drinkers, but there was a significant increase in global complex potentials (6.6% ± 4.6%; P = .04) and regional low-voltage zones (<0.5 mV) in the septum and lateral wall (P <.05) compared with nondrinkers., Conclusion: Regular moderate alcohol consumption, but not mild consumption, is an important modifiable risk factor for AF associated with lower atrial voltage and conduction slowing. These electrical and structural changes may explain the propensity to AF in regular drinkers., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine the impact of regular alcohol consumption on left atrial (LA) mechanical and reservoir function., Background: Earlier studies suggest that regular alcohol intake is associated with increased atrial fibrillation (AF) and LA dilatation., Methods: This study prospectively enrolled 160 patients with paroxysmal or persistent AF to undergo 3-T cardiac magnetic resonance (CMR) imaging in sinus rhythm. Patients self-reported alcohol consumption in standard drinks (∼12 g alcohol) per week over the preceding 12 months and were categorized into 4 groups: 1) lifelong nondrinkers; 2) mild drinkers (3 to 10 standard drinks/week); 3) moderate drinkers (11 to 20 standard drinks/week); 4) heavy drinkers (>20 standard drinks/week). Permanent AF and cardiomyopathy were excluded. On CMR, maximum LA volume (LA max ) and minimum LA volume (LA min ), global LA emptying fraction (LAEF) as (LA max  - LA min ) / LA max , and LA reservoir function as (LA max  - LA min ) / LA min were calculated., Results: Regular alcohol consumption (mean 15.8 ± 6.9 standard drinks/week, n = 120) was associated with larger LA size (LA volume index 50 ± 13 ml/m 2 vs. 43 ± 12 ml/m 2 ; p = 0.005), reduction in LAEF (40 ± 14% vs. 52 ± 15%; p < 0.001), and reduction in reservoir function (77 ± 48% vs. 119 ± 63%; p < 0.001) compared with lifelong nondrinkers (n = 40). There were progressive dose-related impairments in LAEF (mild 45.4 ± 13.5% vs. moderate 39.1 ± 14.7% vs. heavy drinkers 35.6 ± 12.6%; p < 0.01) and reservoir function (mild 95.8 ± 55.6% vs. moderate 74.8 ± 47.1% vs. heavy drinkers 61.7 ± 34.4%; p < 0.01). Predictors of atrial mechanical dysfunction included weekly alcohol intake (p = 0.001), older age (p = 0.018), and persistent AF (p = 0.016), but not binge drinking or beverage type., Conclusions: In patients with AF, habitual alcohol consumption is associated with significantly increased LA size and atrial mechanical dysfunction compared with nondrinkers., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) can improve left ventricular (LV) function and HF symptoms. We aimed to investigate whether long-term maintenance of sinus rhythm impacts on hard outcomes such as stroke and death., Methods and Results: An international multicentre registry was compiled from seven centres for consecutive patients undergoing catheter ablation of AF. Long-term freedom from AF was examined in patients with and without HF. The impact of maintaining sinus rhythm on rates of stroke and death was also examined. A total of 1273 patients were included: 171 with HF and 1102 without. Median follow-up was 3.1 years (IQR 2.0-4.3). The final procedure success rate was no different for paroxysmal AF (PAF) (78.7 vs. 85.7%, P = 0.186), but significantly different for persistent AF (57.3 vs. 75.8%, P < 0.001). Multivariate analysis showed that HF independently predicted recurrent arrhythmia [hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.2-2.4, P = 0.002]. New York Heart Association class decreased from 2.3 ± 0.7 at baseline to 1.5 ± 0.8 at follow-up (P < 0.001). Left ventricular ejection fraction (LVEF) increased from 34.3 ± 9.0 to 45.8 ± 12.8% (P < 0.001). Recurrent AF was strongly predictive of stroke or death in HF patients (HR 8.33, 95% CI 1.86-37.7, P = 0.001)., Conclusion: Long-term success rates for persistent (but not paroxysmal) AF ablation are significantly lower in HF patients. Left ventricular function and HF symptoms were improved following ablation. In HF patients, recurrent arrhythmia strongly predicted stroke and death during follow-up., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. 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: 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.