Improvement in estimated glomerular filtration rate in patients with chronic kidney disease undergoing catheter ablation for atrial fibrillation.

INTRODUCTION: Chronic kidney disease (CKD) and atrial fibrillation (AF) often coexist. We studied the association of CKD with atrial fibrosis and the effect of AF ablation on kidney function. METHODS: AF patients who had a pre- and postablation serum creatinine and who completed a late gadolinium enhancement cardiac magnetic resonance imaging (MRI; LGE-MRI) prior to ablation were included. Estimated glomerular filtration rate (eGFR) was calculated and CKD was staged using the National Kidney Foundation guidelines. Patients with eGFR <30 mL/min/1.73 m(2) were excluded. LGE-MRI was used to quantify atrial fibrosis. Patients were followed for recurrence and change in eGFR. RESULTS: A total of 392 patients were included in the study. A total of 118 (30.2%) had CKD stage 1, 198 (50.4%) CKD stage 2, 56 (14.3%) CKD stage 3A, and 20 (5.1%) CKD stage 3B. Patients with advanced CKD were more likely to be male and to have cardiovascular disease. Atrial fibrosis was not significant different between included CKD stages: 15.8 ± 8.8%, 16.6 ± 12.1%, 17.1 ± 10.4%, and 16.5 ± 8.4% for CKD stage 1, 2, 3A, and 3B, respectively (P = 0.476). At a median of 115 days following ablation, eGFR increased significantly in CKD stage 2 (74 ± 9 to 80 ± 23; P = 0.04), 3A (53 ± 5 to 69 ± 24; P < 0.001), and 3B (40 ± 4 to 71 ± 28; P < 0.01) and decreased in CKD stage 1 (109 ± 18 to 82 ± 28; P < 0.001). Arrhythmia recurrence was associated with atrial fibrosis (hazard ratio [HR] = 1.04, P < 0.01) and persistent AF (HR = 1.5; P = 0.04) but not with CKD stage (HR = 0.98; P = 0.89). CONCLUSIONS: Restoring sinus rhythm with ablation leads to significant improvement of renal function in patients with chronic kidney disease.

Post-contrast myocardial T(1) and ECV disagree in a longitudinal canine study.

Both post-contrast myocardial T1 and extracellular volume (ECV) measurements have been associated with diffuse interstitial fibrosis. The cardiovascular magnetic resonance (CMR) field is migrating towards ECV, because it is largely insensitive to confounders that affect post-contrast myocardial T1 . Despite the theoretical advantages of myocardial ECV over post-contrast myocardial T1 , systematic experimental studies comparing the two measurements are largely lacking. We sought to measure the temporal changes in post-contrast myocardial T1 and ECV in an established canine model with chronic atrial fibrillation. Seventeen mongrel dogs, implanted with a pacemaker to induce chronic atrial fibrillation via rapid atrial pacing, were scanned multiple times for a total of 46 CMR scans at 3T. These dogs with different disease durations (0-22 months) were part of a separate longitudinal study aimed at studying the relationship between AF and pathophysiology. In each animal, we measured native and post-contrast T1 values and hematocrit. Temporal changes in post-contrast myocardial T1 and ECV, as well as other CMR parameters, were modeled with linear mixed effect models to account for repeated measurements over disease duration. In 17 animals, post-contrast myocardial T1 decreased significantly from 872 to 698 ms (p < 0.001), which corresponds to a 24.9% relative reduction. In contrast, ECV increased from 21.0 to 22.0% (p = 0.38), which corresponds to only a 4.5% relative increase. To partially investigate this discrepancy, we quantified collagen volume fraction (CVF) in post-mortem heart tissues of six canines sacrificed at different disease durations (0-22 months). CVF quantified by histology increased from 0.9 to 1.9% (p = 0.56), which agrees better with ECV than with post-contrast myocardial T1 . This study shows that post-contrast myocardial T1 and ECV may disagree in a longitudinal canine study. A more comprehensive study, including histologic, cardiac, and renal functional analyses, is warranted to test rigorously which CMR parameter (ECV or post-contrast myocardial T1 ) agrees better with CVF.

The degree of left atrial structural remodeling impacts left ventricular ejection fraction in patients with atrial fibrillation.

OBJECTIVES: The extent of left atrial (LA) wall structural remodeling (fibrosis) detected by late gadolinium enhancement-magnetic resonance imaging (LGE-MRI) is correlated with advanced atrial fibrillation (AF). The concomitant occurrence of AF and left ventricular (LV) dysfunction is not uncommon. We studied the effect of LA fibrosis, a confounder of both AF and LV dysfunction, on LV ejection fraction (EF). STUDY DESIGN: For the analysis, we identified and included 384 patients from our retrospective AF database who underwent LGE-MRI and transthoracic echocardiography prior to AF ablation. Based on the degree of LA fibrosis, patients were categorized into four stages as: Utah 1 (<5% LA fibrosis), Utah 2 (5-20% fibrosis), Utah 3 (20-35% fibrosis), and Utah 4 (>35% fibrosis). RESULTS: The average pre-ablation LVEF was 60.5%±8.5% (n=24) in Utah stage 1 patients, 55.7%±10.3% (n=240) in Utah stage 2 patients, 51.7±11.5% (n=90) in Utah stage 3 patients, and 48.9%±11.6% (n=30) in Utah stage 4 patients (p<0.001, one-way ANOVA). The percentage of LA fibrosis was significantly negatively correlated to LVEF pre-ablation in a univariate analysis (p<0.001). In a multivariate model accounting for age, gender, AF type, and comorbidities such as diabetes and hypertension, Utah stage remained a significant predictor of pre-ablation EF (p<0.001). CONCLUSION: Patients with extensive LA fibrosis appear to have depressed LV function pre-ablation, suggesting that structural remodeling in the LA may also be triggering and promoting remodeling within the ventricular myocardium.

Higher degree of left atrial structural remodeling in patients with atrial fibrillation and left ventricular systolic dysfunction.

BACKGROUND: Catheter ablation significantly improves the left ventricular (LV) function in patients with atrial fibrillation (AF) and LV systolic dysfunction. In this study, we compared the degree of left atrial structural remodeling (LA-SRM) in patients with normal versus reduced LV ejection fraction (LVEF). We also studied the impact of LA-SRM on LVEF improvement in patients undergoing ablation of AF. METHOD AND RESULTS: We categorized 384 patients into 2 groups based on their cardiac function: reduced LVEF group (LVEF ≤50%; n = 105) and normal LVEF group (LVEF > 50%; n = 279). LVEF was determined prior and mean 8 ± 3 months after catheter ablation for AF. Percentage of LA-SRM was quantified using LGE-MRI and patients were classified into 4 groups based on the amount of structural remodeling in their LA wall: minimal ≤ 5%, mild = 5-20%, moderate = 20-35%, and extensive ≥ 35%. The average preablation LA-SRM (21.5 ± 13.2% vs 15.4 ± 10.0%; P < 0.001) was significantly higher in reduced LVEF group than normal LVEF group. Among the 105 patients with reduced LVEF, while there was a modest 11.7 ± 8.4% average increase in LVEF following ablation, the greatest increase was seen in patients with less extensive LA-SRM (minimal = 19.3 ± 5.1%, n = 3, P = 0.02 and mild = 16.6 ± 9.9%, n = 48, P < 0.001). Patients with moderate and extensive fibrosis had an average EF improvement of 8.7 ± 11.1% and 2.8 ± 6.4%, respectively (n = 39, P < 0.001 and n = 15, P = 0.11, respectively). CONCLUSION: Patients with LV systolic dysfunction displayed a comparatively greater LA-SRM than patients with normal LVEF. Patients with lesser LA-SRM experienced a greater improvement in LVEF after catheter ablation for AF.

Relationship between left atrial tissue structural remodelling detected using late gadolinium enhancement MRI and left ventricular hypertrophy in patients with atrial fibrillation.

AIMS: Therapeutic effectiveness of ablation of atrial fibrillation (AF) is related to cardiovascular comorbidities. We studied the relationship between left ventricular hypertrophy (LVH) and left atrial tissue structural remodelling (LA-SRM), in patients presenting for AF ablation. METHODS AND RESULTS: We identified 404 AF patients who received a late gadolinium enhancement magnetic resonance imaging (LGE-MRI) prior to catheter ablation. Left ventricular hypertrophy was defined as LV mass index >116 g/m(2) in men and >104 g/m(2) in women. One hundred and twenty-two patients were classified as the LVH group and 282 as the non-LVH group. We stratified patients into four stages based on their degree of LA-SRM (minimal, <5% fibrosis; mild, >5-20%; moderate, >20-35%; and extensive, >35%). All patients underwent catheter ablation with pulmonary vein isolation and posterior wall and septal debulking. The procedural outcome was monitored over a 1-year follow-up period. The mean LA-SRM was significantly higher in patients with LVH (19.4 ± 13.2%) than in non-LVH patients (15.3 ± 9.8%; P< 0.01). Patients with LVH generally had extensive LA-SRM (moderate and extensive stages; 38.5% of LVH group) as compared with non-LVH patients (23.1% of non-LVH group; P < 0.01). A Cox regression analysis showed that patients with LVH also had significantly higher AF recurrence rates than non-LVH patients (43.2 vs. 28%; P = 0.008) during the 1-year follow-up period post-ablation. CONCLUSION: Patients with LVH tend to have a significantly greater degree of LA-SRM, when compared with patients without LVH. Moreover, LA-SRM is a predictor for procedural success in patients undergoing AF ablation procedure.

The effect of fat pad modification during ablation of atrial fibrillation: late gadolinium enhancement MRI analysis.

BACKGROUND: Magnetic resonance imaging (MRI) can visualize locations of both the ablation scar on the left atrium (LA) after atrial fibrillation (AF) ablation and epicardial fat pads (FPs) containing ganglionated plexi (GP). METHODS: We investigated 60 patients who underwent pulmonary vein antrum (PVA) isolation along with LA posterior wall and septal debulking for AF. FPs around the LA surface in well-known GP areas (which were considered as the substitution of GP areas around the LA) were segmented from the dark-blood MRI. Then the FP and the ablation scar image visualized by late gadolinium enhancement (LGE)-MRI on the LA were merged together. Overlapping areas of FP and the ablation scar image were considered as the ablated FP areas containing GP. Patients underwent 24-hour Holter monitoring after ablation for the analysis of heart rate variability. RESULTS: Ablated FP area was significantly wider in patients without AF recurrence than those in patients with recurrence (5.6 ± 3.1 cm(2) vs 4.2 ± 2.7 cm(2) , P = 0.03). The mean values of both percentage of differences greater than 50 ms in the RR intervals (pRR > 50) and standard deviation of RR intervals over the entire analyzed period (SDNN), which were obtained from 24-hour Holter monitoring 1-day post-AF ablation, were significantly lower in patients without recurrence than those in patients with recurrence (5.8 ± 6.0% vs 14.0 ± 10.1%; P = 0.0005, 78.7 ± 32.4 ms vs 109.2 ± 43.5 ms; P = 0.005). There was a significant negative correlation between SDNN and the percentage of ablated FP area (Y = -1.3168X + 118.96, R(2) = 0.1576, P = 0.003). CONCLUSION: Extensively ablating LA covering GP areas along with PVA isolation enhanced the denervation of autonomic nerve system and seemed to improve procedural outcome in patients with AF.

Delayed occurrence of an accelerated idioventricular rhythm with alternating bundle branch block after myocardial infarction as predictor of sudden cardiac arrest: a case report.

BACKGROUND: Accelerated idioventricular rhythm (AIVR) is known as reperfusion arrhythmia in the setting of acute myocardial infarction (AMI). In healthy individuals, it is usually considered to be benign. Alternating bundle branch block (ABBB) often progresses to complete atrioventricular block requiring permanent pacemaker implantation. We report a case of delayed appearance of AIVR following myocardial infarction (MI) in combination with ABBB as precursor of sudden cardiac arrest due to ventricular fibrillation (VF). CASE SUMMARY: A 62-year-old male with pre-existing left bundle branch block (LBBB) was admitted with an acute non-ST segment elevation MI. He underwent successful percutaneous coronary intervention (PCI) of a subtotal proximal left anterior descending artery (LAD) stenosis. Before and after PCI the electrocardiogram (ECG) demonstrated sinus rhythm with LBBB. The patient was discharged 5 days after PCI, left ventricular function at this time was moderately reduced (ejection fraction of 40%). After another 5 days, the patient was admitted for elective cardiac rehabilitation. At this time, the ECG demonstrated an AIVR with right bundle branch block morphology. Due to ABBB, the patient was scheduled for permanent pacemaker implantation. Before pacemaker implantation could take place, the patient developed a sudden cardiac arrest due to VF and was successfully resuscitated. A follow-up coronary angiography revealed no novel lesions. A cardiac resynchronization therapy defibrillator was implanted for secondary prevention of sudden cardiac death. DISCUSSION: Delayed occurrence of AIVR in combination with ABBB following AMI could be a predictor of sudden cardiac death. These patients are probably at high risk for malignant ventricular arrhythmias.

Genes causing inherited forms of cardiomyopathies. A current compendium.

Cardiomyopathies (diseases of the heart muscle) are a relevant but heterogeneous group of cardiac diseases. The underlying structural myocardial alterations, detectable with contemporary cardiac imaging modalities and also on twelve-lead surface ECG, embody both linkage and differentiation of the respective clinical forms. Most of these are defined to the heart, however, cardiac involvement is also known in the presence of specific metabolic or muscular systemic diseases. In many of the known cardiomyopathies, a genetic background has been elucidated thus indicating a potential familial disease. This, in turn, also harbors the risk that more family members may be affected besides the index patient.

Cardiac computed tomography in patients with symptomatic new-onset atrial fibrillation, rule-out acute coronary syndrome, but with intermediate pretest probability for coronary artery disease admitted to a chest pain unit.

BACKGROUND: Atrial fibrillation (AF) and coronary artery disease (CAD) may be encountered coincidently in a large portion of patients. However, data on coronary artery calcium burden in such patients are lacking. Thus, we sought to determine the value of cardiac computed tomography (CCT) in patients presenting with new-onset AF associated with an intermediate pretest probability for CAD admitted to a chest pain unit (CPU). METHODS: Calcium scores (CS) of 73 new-onset, symptomatic AF subjects without typical clinical, electrocardiographic, or laboratory signs of acute coronary syndrome (ACS) admitted to our CPU were analyzed. In addition, results from computed tomography angiography (CTA) were related to coronary angiography findings whenever available. RESULTS: Calcium scores of zero were found in 25%. Median Agatston score was 77 (interquartile range: 1-270) with gender- and territory-specific dispersal. CS scores above average were present in about 50%, high (> 400)-to-very high (> 1000) CS scores were found in 22%. Overall percentile ranking showed a relative accordance to the reference percentile distribution. Additional CTA was performed in 47%, revealing stenoses in 12%. Coronary angiography was performed in 22% and resulted in coronary intervention or surgical revascularization in 7%. On univariate analysis, CS > 50th percentile failed to serve as an independent determinant of significant stenosis during catheterization. CONCLUSIONS: Within a CPU setting, relevant CAD was excluded or confirmed in almost 50%, the latter with a high proportion of coronary angiographies and subsequent coronary interventions, underlining the diagnostic value of CCT in symptomatic, non-ACS, new-onset AF patients when admitted to a CPU.

Coronary Artery Calcium as an Independent Surrogate Marker in the Risk Assessment of Patients With Atrial Fibrillation and an Intermediate Pretest Likelihood for Coronary Artery Disease Admitted to a German Chest Pain Unit.

BACKGROUND: About 10% of patients admitted to a chest pain unit (CPU) exhibit atrial fibrillation (AF). HYPOTHESIS: To determine whether calcium scores (CS) are superior over common risk scores for coronary artery disease (CAD) in patients presenting with atypical chest pain, newly diagnosed AF, and intermediate pretest probability for CAD within the CPU. METHODS: In 73 subjects, CS was related to the following risk scores: Global Registry of Acute Coronary Events (GRACE) score, including a new model of a frequency-normalized approach; Thrombolysis In Myocardial Infarction score; European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE); Framingham risk score; and Prospective Cardiovascular Münster Study score. Revascularization rates during index stay were assessed. RESULTS: Median CS was 77 (interquartile range, 1-270), with higher values in men and the left anterior descending artery. Only the modified GRACE (ρ = 0.27; P = 0.02) and the SCORE (ρ = 0.39; P < 0.005) were significantly correlated with CS, whereas the GRACE (τ = 0.21; P = 0.04) and modified GRACE (τ = 0.23; P = 0.02) scores were significantly correlated with percentile groups. Only the CS significantly discriminated between those with and without stenosis (P < 0.01). CONCLUSIONS: Apart from modified GRACE score, overall correlations between risk scores and calcium burden, as well as revascularization rates during index stay, were low. By contrast, the determination of CS may be used as an additional surrogate marker in risk stratification in AF patients with intermediate pretest likelihood for CAD admitted to a CPU.

Renal sympathetic denervation using MR-guided high-intensity focused ultrasound in a porcine model.

BACKGROUND: Initial catheter-based renal sympathetic denervation (RSD) studies demonstrated promising results in showing a significant reduction of blood pressure, while recent data were less successful. As an alternative approach, the objective of this study was to evaluate the feasibility of using magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) to perform RSD in a porcine model. METHODS: An intravascular fiber optic temperature probe was used to confirm energy delivery during MRgHIFU. This technique was evaluated both in a vascular phantom and in a normotensive pig model. Five animals underwent unilateral RSD using MRgHIFU, and both safety and efficacy were assessed. MRI was used to evaluate the acoustic window, target sonications, monitor the near-field treatment region using MR thermometry imaging, and assess the status of tissues post-procedure. An intravascular fiber optic temperature probe verified energy delivery. Animals were sacrificed 6 to 9 days post-treatment, and pathological analysis was performed. The norepinephrine present in the kidney medulla was assessed post-mortem. RESULTS: All animals tolerated the procedure well with no observed complications. The fiber optic temperature probe placed in the target renal artery confirmed energy delivery during MRgHIFU, measuring larger temperature rises when the MRgHIFU beam location was focused closer to the tip of the probe. Following ablation, a significant reduction (p = 0.04) of cross-sectional area of nerve bundles between the treated and untreated renal arteries was observed in all of the animals with treated nerves presenting increased cellular infiltrate and fibrosis. A reduction of norepinephrine (p = 0.14) in the kidney medulla tissue was also observed. There was no indication of tissue damage in arterial walls. CONCLUSIONS: Performing renal denervation non-invasively with MRgHIFU was shown to be both safe and effective as determined by norepinephrine levels in a porcine model. This approach may be a promising alternative to catheter-based strategies.

Identification of novel mutations in LMNA associated with familial forms of dilated cardiomyopathy.

The lamin A/C proteins are major structural and functional components of the nuclear lamina. Mutations identified in LMNA encoding lamin A/C belong to the most frequently described causes for inherited forms of dilated cardiomyopathy (DCM). To elucidate the clinical characteristics of LMNA mutation carriers we performed genetic analysis of LMNA in 20 unrelated patients with DCM and cardiac conduction disease. In six small nuclear families heterozygous mutations in LMNA were identified. Two missense mutations led to the substitution of highly conserved amino acid residues within the rod domain of lamin A/C and four not-yet-described nonsense mutations cause the formation of predicted truncated lamin A/C missing parts of the tail domain. DCM was the most prominent clinical characteristic of the affected family members with a high degree of involvement of conduction system defects and less often accompanied by muscular dystrophy. The cardiac phenotype of the affected family members was severe and progressive with age, indicating the necessity for a genetic testing for LMNA mutations in patients with familial DCM and early onset of conduction disorders.

A new mechanism preventing proarrhythmia in chronic heart failure: rapid phase-III repolarization explains the low proarrhythmic potential of amiodarone in contrast to sotalol in a model of pacing-induced heart failure.

AIMS: Life-threatening arrhythmias are a major problem in chronic heart failure (CHF). The aim of the present study was to investigate the mechanism underlying the low proarrhythmic potential of amiodarone in a model of pacing-induced heart failure. METHODS AND RESULTS: Heart failure was induced in 35 female rabbits by rapid ventricular pacing, resulting in a significant decrease of ejection fraction. Thirty-four rabbits were sham-operated. In 17 of 35 CHF-rabbits and 20 of 34 'sham'-rabbits, amiodarone (50 mg/kg/day) was fed for 6 weeks. Eight monophasic action potentials and a simultaneously recorded 12-lead electrocardiogram showed prolongation of QT-interval and action potential duration (APD(90)) in all failing hearts (P< 0.05). Amiodarone pre-treatment led to a prolongation of APD(90) (+19 ms) as compared with sham-controlled hearts but showed only a marginal effect on APD(90) in failing hearts. Infusion of sotalol (50-100 µM) led to a significant prolongation of APD(90) in sham and a further prolongation of APD(90) in failing hearts [+55 ms (50 µM); +70 ms (100 µM); P< 0.01 as compared with sham hearts]. Sotalol led to a triangular action potential configuration in sham and failing hearts, whereas amiodarone did not cause triangularization but caused a rapid phase-III repolarization. Moreover, amiodarone did not increase dispersion of repolarization either in sham or in failing hearts. Infusion of sotalol led to a significant increase in dispersion of repolarization in sham (+29 ms) and a further increase in failing hearts (+67 ms; P< 0.05). CONCLUSION: Chronic amiodarone results in a rapid phase-III-repolarization and does not increase dispersion of repolarization. These electrophysiological findings are present in healthy hearts and are preserved in heart failure. This contributes to the low proarrhythmic potential of amiodarone in heart failure.