L. Ling

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

AIMSnIn 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.nnnMETHODS AND RESULTSnOne 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.nnnCONCLUSIONnIn 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.

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

BACKGROUNDnAtrial 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.nnnOBJECTIVEnTo prospectively select patients with AF and symptomatic HF but without LV LGE and report the impact of AF ablation on LV function.nnnMETHODSnPatients 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.nnnRESULTSnAt 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).nnnCONCLUSIONSnIn 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.

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

BACKGROUNDnThe impact of diffuse atrial fibrosis detected by T1 mapping on the clinical outcome after atrial fibrillation (AF) ablation is unknown.nnnOBJECTIVEnThis 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.nnnMETHODSnCMR 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.nnnRESULTSnOne 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).nnnCONCLUSIONnPost-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.

Associations Between Fibrocytes and Postcontrast Myocardial T1 Times in Hypertrophic Cardiomyopathy

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.

Determining the Optimal Dose of Adenosine for Unmasking Dormant Pulmonary Vein Conduction Following Atrial Fibrillation Ablation: Electrophysiological and Hemodynamic Assessment. DORMANT-AF Study

The significance of adenosine induced dormant pulmonary vein (PV) conduction in atrial fibrillation (AF) ablation remains controversial. The optimal dose of adenosine to determine dormant PV conduction is yet to be systematically explored.

A multicentre study of AF ablation outcomes in patients with concurrent left ventricular dysfunction - aetiology of cardiomyopathy determines outcome

A. McLellan1,2,3, L. Ling1,2,3, S. Azzopardi 1,2, G. Lee1,2, G. Lee1,2,3, S. Kumar1,2,3, M. Wong1,2,3, T. Walters 1,2,3, J. Lee 3, K. Halloran3, M. Stiles 7, N. Lever 8, S. Fynn9, P. Heck9, P. Sanders 6, J. Morton3,4, J. Kalman3,4, P. Kistler 1,2,3,4,5,∗ 1 Alfred Heart Centre, Alfred Hospital, Melbourne, Victoria, Australia 2 Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia 3Department of Cardiology, Royal Melbourne Hospital, and Department of Medicine, University of Melbourne, Parkville, Victoria, Australia 4 Melbourne Private Hospital, Parkville, Victoria, Australia 5 Avenue Private Hospital, Windsor, Victoria, Australia 6 Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, South Australia, Australia 7 Waikato Hospital, New Zealand 8 Auckland City Hospital, Auckland, New Zealand 9 Papworth Hospital, Cambridge, United Kingdom