Ablation Index-guided point-by-point ablation versus Grid annotation-guided dragging for pulmonary vein isolation: A randomized controlled trial.

INTRODUCTION: Radiofrequency (RF) atrial fibrillation (AF) ablation using a catheter dragging technique may shorten procedural duration and improve durability of pulmonary vein isolation (PVI) by creating uninterrupted linear ablation lesions. We compared a novel AF ablation approach guided by Grid annotation allowing for "drag lesions" with a standard point-by-point ablation approach in a single-center randomized study. METHODS: Eighty-eight paroxysmal or persistent AF patients were randomized 1:1 to undergo RF-PVI with either a catheter dragging ablation technique guided by Grid annotation or point-by-point ablation guided by Ablation Index (AI) annotation. In the Grid annotation arm, ablation was visualized using 1 mm³ grid points coloring red after meeting predefined stability and contact force criteria. In the AI annotation arm, ablation lesions were created in a point-by-point fashion with AI target values set at 380 and 500 for posterior/inferior and anterior/roof segments, respectively. Patients were followed up for 12 months after PVI using ECGs, 24-h Holter monitoring and a mobile-based one-lead ECG device. RESULTS: Procedure time was not different between the two randomization arms (Grid annotation 71 ± 19 min, AI annotation 72 ± 26 min, p = .765). RF time was significantly longer in the Grid annotation arm compared with the AI annotation arm (49 ± 8 min vs. 37 ± 8 min, respectively, p < .001). Atrial tachyarrhythmia recurrence was documented in 10 patients (23%) in the Grid annotation arm compared with 19 patients (42%) in the AI annotation arm with time to recurrence not reaching statistical significance (p = .074). CONCLUSIONS: This study shows that a Grid annotation-guided dragging approach provides an alternative to point-by-point RF-PVI using AI annotation.

Comparison of the predictive value of ten risk scores for outcomes of atrial fibrillation patients undergoing radiofrequency pulmonary vein isolation.

BACKGROUND: A significant number of patients experience recurrent atrial fibrillation (AF) after ablation. Various risk scores have been described that may predict outcomes after AF ablation. In this study, we aimed to compare ten previously described risk scores with regard to their predictive value for post-ablation AF recurrence and procedural complications. METHODS: A total of 482 AF patients (63% paroxysmal AF, 66% male, mean age 62 ± 9 years) undergoing initial radiofrequency pulmonary vein isolation (PVI) were included in the present analysis. Prior to ablation, all patients underwent both transthoracic echocardiography (TTE) and either cardiac CT imaging or CMR imaging. The following risk scores were calculated for each patient: APPLE, ATLAS, BASE-AF2, CAAP-AF, CHADS2, CHA2DS2-VASc, DR-FLASH, HATCH, LAGO and MB-LATER. RESULTS: Median follow-up was 16 (12-31) months. AF recurrence after a 90-day blanking period was observed in 199 patients (41%), occurring after a median of 183 (124-360) days. AF recurrence was less frequent in paroxysmal AF patients compared to non-paroxysmal AF patients (34% vs. 54%, p < 0.001). Overall periprocedural complication rate was 6%. All scores, except the HATCH score, demonstrated statistically significant but poor predictive value for recurrent AF after ablation (area under curve [AUC] 0.553-0.669). CHA2DS2-VASc and CAAP-AF were the only risk scores with predictive value for procedural complications (AUC 0.616, p = 0.043; AUC 0.615, p = 0.044; respectively). CONCLUSIONS: Currently available risk scores perform poorly in predicting outcomes after AF ablation. These data suggest that the utility of these scores for clinical decision-making is limited.

Impact of local left atrial wall thickness on the incidence of acute pulmonary vein reconnection after Ablation Index-guided atrial fibrillation ablation.

BACKGROUND: Although Ablation Index (AI)-guided ablation facilitates creation of lesions of consistent depth, pulmonary vein (PV) reconnection is still commonly observed after AI-guided pulmonary vein isolation (PVI). The present study aimed to investigate the impact of local left atrial wall thickness on the incidence of acute PV reconnection after AI-guided atrial fibrillation (AF) ablation. METHODS AND RESULTS: Seventy patients (63% paroxysmal AF, 67% male, mean age 63 ± 8 years) who underwent preprocedural CT imaging and AI-guided AF ablation were studied. Occurrence of acute PV reconnection after initial PVI was assessed after a 30-minute waiting period. Ablation procedures were retrospectively analyzed and each ablation circle was subdivided into 8 segments. Minimum AI, force-time integral, contact force, ablation duration, power, impedance drop and maximum interlesion distance were determined for each segment. PV antrum wall thickness was assessed for each segment on reconstructed CT images based on patient-specific thresholds in Hounsfield Units. Acute reconnection occurred in 27/1120 segments (2%, 15 anterior/roof, 12 posterior/inferior) in 19/140 ablation circles (14%). Reconnected segments were characterized by a greater local atrial wall thickness, both in anterior/roof (1.87 ± 0.42 vs. 1.54 ± 0.42 mm; p < 0.01) and posterior/inferior (1.43 ± 0.20 vs. 1.16 ± 0.22 mm; p < 0.01) segments. Minimum AI, force-time integral, contact force, ablation duration, power, impedance drop and maximum interlesion distance were not associated with acute reconnection. CONCLUSIONS: Local atrial wall thickness is associated with acute pulmonary vein reconnection after AI-guided PVI. Individualized AI targets based on local wall thickness may be of use to create transmural ablation lesions and prevent PV reconnection after PVI.

Differences between gap-related persistent conduction and carina-related persistent conduction during radiofrequency pulmonary vein isolation.

BACKGROUND: During pulmonary vein isolation (PVI), nonisolation after initial encircling of the pulmonary veins (PVs) may be due to gaps in the initial ablation line, or alternatively, earliest PV activation may occur on the intervenous carina and ablation within the wide-area circumferential ablation (WACA) circle is needed to eliminate residual conduction. This study investigated prognostic implications and predictors of gap-related persistent conduction (gap-RPC) and carina-related persistent conduction (carina-RPC) during PVI. METHODS AND RESULTS: Two hundred fourteen atrial fibrillation (AF) patients (57% paroxysmal, 61% male, mean age 62 ± 9 years) undergoing first contact force-guided radiofrequency PVI were studied. Preprocedural cardiac computed tomography imaging was used to assess left atrial and PV anatomy. PVI was assessed directly after initial WACA circle creation, after a minimum waiting period of 30 minutes, and after adenosine infusion. Persistent conduction was targeted for additional ablation and classified as gap-RPC or carina-RPC, depending on the earliest activation site. The 1-year AF recurrence rate was higher in patients with gap-RPC (47%) compared to patients without gap-RPC (28%; P = .003). No significant difference in 1-year recurrence rate was found between patients with carina-RPC (37%) and patients without carina-RPC (31%; P = .379). Multivariate analyses identified paroxysmal AF and WACA circumference as independent predictors of gap-RPC, whereas carina width and WACA circumference correlated with carina-RPC. CONCLUSIONS: Gap-RPC is associated with increased AF recurrence risk after PVI, whereas carina-RPC does not predict AF recurrence. Moreover, gap-RPC and carina-RPC have different correlates and may thus have different underlying mechanisms.

Renal function and ear, nose, throat involvement in anti-neutrophil cytoplasmic antibody-associated vasculitis: prospective data from the European Vasculitis Society clinical trials.

OBJECTIVE: We investigated whether ENT involvement is associated with renal biopsy findings and renal function in patients with ANCA-associated vasculitis (AAV). METHODS: Newly diagnosed AAV patients derived from three international, multicentre trials were included. To investigate an association between ENT involvement and estimated glomerular filtration rate (eGFR) at diagnosis and 5-year follow-up, we performed multivariable regression analyses including clinical and histopathological parameters. To investigate whether our findings are specific to ENT involvement, we performed comparable analyses between eGFR and other early disease manifestations (arthralgia/arthritis, cutaneous and lung involvement). RESULTS: One hundred and eighty-five of the 414 patients had ENT involvement. The mean presenting eGFR of patients with and without ENT involvement was 39.16 and 23.88 ml/min/1.73 m(2), respectively (P < 0.001). Mean eGFR increased by 6.76 ml/min/1.73 m(2) with each added ENT symptom (P = 0.007). Patients with ENT involvement had less interstitial fibrosis and tubular atrophy and a prognostically more favourable histopathological class on renal biopsy examination. Multivariable regression analyses correcting for clinical and histopathological parameters showed that ENT involvement is associated with both baseline and 5-year follow-up eGFR. There were no associations between baseline and 5-year follow-up eGFR and arthralgia/arthritis, cutaneous or lung involvement, suggesting that our findings are specific to ENT involvement. CONCLUSION: The presence of ENT involvement in AAV patients is associated with prognostically favourable renal biopsy findings and better renal function. These results indicate that there may be different phenotypes of AAV defined by ENT involvement.

Chances of renal recovery for dialysis-dependent ANCA-associated glomerulonephritis.

In patients who have anti-neutrophil cytoplasm autoantibody (ANCA)-associated glomerulonephritis and are on dialysis at time of diagnosis, renal function is sometimes insufficiently restored by immunosuppressive treatment, which often coincides with potentially lethal adverse effects. This study investigated the clinical and histologic variables that determine the chances of dialysis independence, dialysis dependence, or death after 12 mo in these patients. Sixty-nine patients who had ANCA-associated glomerulonephritis and were dialysis dependent at diagnosis received uniform, standard immunosuppressive therapy plus either intravenous methylprednisolone or plasma exchange. Eleven clinical and histologic variables were assessed. Univariate and binary logistic regression analyses were performed. Predictive parameters were entered into a two-step binary logistic regression analysis to differentiate among the outcomes of dialysis independence, dialysis dependence, or death. The point at which the chance of therapy-related death exceeded the chance of dialysis independence was determined. The chance of recovery exceeded the chance of dying in most cases. Intravenous methylprednisolone as adjunctive therapy plus <18% normal glomeruli and severe tubular atrophy increased the chance of therapy-related death over the chance of dialysis independence. Plasma exchange treatment plus severe tubular atrophy and <2% normal glomeruli increased the chance of therapy-related death over that of dialysis independence. Even with ominous histologic findings, the chance of renal recovery exceeds the chance of therapy-related death when these patients are treated with plasma exchange as adjunctive therapy.

Clinical and histologic determinants of renal outcome in ANCA-associated vasculitis: A prospective analysis of 100 patients with severe renal involvement.

This study aimed to identify clinical and histologic prognostic indicators of renal outcome in patients with ANCA-associated vasculitis and severe renal involvement (serum creatinine >500 micromol/L). One hundred patients who were enrolled in an international, randomized, clinical trial to compare plasma exchange with intravenous methylprednisolone as an additional initial treatment were analyzed prospectively. Diagnostic renal biopsies were performed upon entry into the study. Thirty-nine histologic and nine clinical parameters were determined as candidate predictors of renal outcome. The end points were renal function at the time of diagnosis (GFR0) and 12 mo after diagnosis (GFR12), dialysis at entry and 12 mo after diagnosis, and death. Multivariate analyses were performed. Predictive of GFR0 were age (r = -0.40, P = 0.04), arteriosclerosis (r = -0.53, P = 0.01), segmental crescents (r = 0.35, P = 0.07), and eosinophilic infiltrate (r = -0.41, P = 0.04). Prognostic indicators for GFR12 were age (r = -0.32, P = 0.01), normal glomeruli (r = 0.24, P = 0.04), tubular atrophy (r = -0.28, P = 0.02), intraepithelial infiltrate (r = -0.26, P = 0.03), and GFR0 (r = 0.29, P = 0.01). Fibrous crescents (r = 0.22, P = 0.03) were predictive of dialysis at entry. Normal glomeruli (r = -0.30, P = 0.01) and treatment arm (r = -0.28, P = 0.02) were predictive of dialysis after 12 mo. No parameter predicted death. Both chronic and acute tubulointerstitial lesions predicted GFR12 in severe ANCA-associated glomerulonephritis, whereas plasma exchange was a positive predictor of dialysis independence after 12 mo for the entire patient group. Plasma exchange remained a positive predictor when patients who were dialysis dependent at presentation were analyzed separately (r = -0.36, P = 0.01). Normal glomeruli were a positive predictor of dialysis independence and improved renal function after 12 mo, indicating that the unaffected part of the kidney is vital in determining renal outcome.

An index for renal outcome in ANCA-associated glomerulonephritis.

BACKGROUND: The aim of this study is to analyze the predictive value of clinical, serological, and histological parameters for renal outcome in antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis by multivariate analysis and create an index valid for clinical use. METHODS: Data from 160 patients with Wegener's granulomatosis, microscopic polyangiitis, and idiopathic rapidly progressive glomerulonephritis without immune deposits (renal-limited vasculitis) were collected. The Cockcroft formula was used to assess renal function expressed by glomerular filtration rate (GFR) at the time of renal biopsy (t = 0) and 1 year later (t = 1). Other clinical parameters were age, sex, and diagnosis. ANCA test results were scored as cytoplasmic ANCA/antiproteinase 3 (anti-PR3) or perinuclear ANCA/antimyeloperoxidase (anti-MPO) positive or negative. Histological data included normal glomeruli, fibrinoid necrosis, extracapillary proliferation, granulomas, interstitial edema, focal and diffuse infiltrates, fibrosis, tubular cylinders/casts, tubular atrophy, tubular necrosis, sclerosis, mesangial proliferation, mesangial matrix expansion, arteriosclerosis, and infiltrates in arterioles. In a separate analysis, we explored whether there were histological differences between patients with anti-PR3 and anti-MPO ANCA test results. RESULTS: Forty percent of the variation in renal function at the time of biopsy can be explained by the presence or absence of tubular atrophy, normal glomeruli, fibrinoid necrosis, extracapillary proliferation, and age. Renal function at the time of biopsy is the best predictor for renal function at t = 1 in patients with ANCA-associated glomerulonephritis. Together with normal glomeruli, fibrinoid necrosis, and age, it explains more than 60% of the variation in GFR at t = 1. ANCA subtype has no independent contribution in predicting patient prognosis. Results translated into a clinically relevant index: GFR at t = 1 = 36.96 + 0.65* (GFR at t = 0) + 10.52 (if normal glomeruli present) + 7.72 (if fibrinoid necrosis present) - 0.42* (age). CONCLUSION: The index created with results from this study provides an indication of renal outcome in patients diagnosed with ANCA-associated glomerulonephritis.

Glomerulonephritis in the vasculitides: advances in immunopathology.

Systemic vasculitis refers to a condition of blood vessel inflammation, of which the causes are various. In a substantial number of cases, autoantibodies against neutrophil cytoplasm constituents (ANCAs) are present. The authors then refer to the systemic vasculitis as ANCA-associated systemic vasculitis. Renal disease is an unfavorable component, leading to dialysis dependency in a considerable number of patients. This review aims to summarize in brief what was reported about ANCA-associated vasculitis in the recent past. What the exact pathogenic role of ANCAs in the development of systemic vasculitis is remains uncertain, and it is still not clear how their presence leads to the histopathologic lesions called vasculitis.

Determinants of outcome in ANCA-associated glomerulonephritis: a prospective clinico-histopathological analysis of 96 patients.

BACKGROUND: The predictive value of clinical and renal histological features for renal outcome in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis was investigated in a prospective analysis of 96 patients with ANCA-associated vasculitis, and moderate renal involvement (creatinine <500 micromol/L). METHODS: The extent of 39 histological features in 96 biopsies (performed at entry in a clinical trial) was scored by two independent observers, according to a standardized protocol. Age, gender, diagnosis, glomerular filtration rate at entry (GFR0), ANCA-specificity, proteinuria, and treatment of these 96 patients were also taken into account. Treatment was standardized and started after the biopsy was performed. End-points included renal function at 18 months (GFR18), GFR18 corrected for GFR0 (CORGFR18), and the occurrence of relapse or death. RESULTS: Parameters that most strongly correlated with GFR18 were GFR0 (r = 0.67), interstitial fibrosis (r = -0.45), glomerulosclerosis (r = -0.37), and tubular atrophy (r = -0.36). Parameters that most strongly correlated with CORGFR18 were segmental (r = 0.45) and cellular (r = 0.30) crescents, and fibrinoid necrosis (r = 0.46). None of the clinical and histological features predicted the occurrence of relapse or death. By applying a stepwise linear multiple regression analysis, we designed a formula for the estimation of renal function at 18 months: GFR18 (mL/min) = 17 + 0.71 x GFR0 (mL/min) + 0.34 x fibrinoid necrosis (%) + 0.33 x segmental crescents (%), (r2 = 0.60; standard deviation = 19 mL/min). Our results were independent of diagnosis, ANCA-specificity, and treatment limb. CONCLUSIONS: These data suggest that in ANCA-associated glomerulonephritis, GFR0 and predominantly chronic renal lesions are potent predictors of GFR18. Active lesions are associated with renal function recovery and may be reversible. The formula for the estimation of GFR18 shows that a combination of GFR0 and renal histology is a better predictor for GFR18 than GFR0 only.

Long-term renal injury in ANCA-associated vasculitis: an analysis of 31 patients with follow-up biopsies.

BACKGROUND: We reported previously that in renal disease in relation to antineutrophil cytoplasm auto-antibodies (ANCA)-associated vasculitis, renal outcome correlates better with the percentage of normal glomeruli than with separate active lesions. This may imply that glomeruli, once affected by necrotizing and crescentic lesions, are irreversibly damaged. We quantified and evaluated the course of renal lesions in the present study. METHODS: We retrospectively analysed 31 patients with renal disease in relation to ANCA-associated vasculitis, all treated with immunosuppressive drugs. In all patients, a renal biopsy was performed at diagnosis. A follow-up biopsy was performed in all patients on the indication of a suspected renal relapse, after a mean interval of 31 months. RESULTS: The mean percentage of normal glomeruli in the renal biopsy did not change over time (29% in the initial and 30% in the follow-up biopsy). The mean percentage of glomeruli with crescents, however, significantly decreased from 57 to 30% (P<0.001). The percentage of glomerulosclerosis significantly increased from 12 to 39% (P<0.001). The data were independent of diagnosis, gender, age, time interval between the biopsies, and treatment. CONCLUSIONS: This is the first study to quantify glomerular changes between two time points in patients with renal vasculitis. Our results suggest that, on average, no new glomeruli are recruited into the active disease process. The sum of the percentage of crescentic and sclerotic glomeruli in the initial biopsies is larger than the percentage of sclerotic glomeruli in the follow-up biopsies. Thus, therapy seems not only to prevent normal glomeruli from being recruited into the active disease process for a certain time, but seems also to allow part of the active lesions to revert into a normal phenotype, although another part of the active lesions will be transformed to a chronic phenotype.

Renal histology in ANCA-associated vasculitis: differences between diagnostic and serologic subgroups.

BACKGROUND: Differences in renal histopathology between microscopic polyangiitis (MPA) and Wegener's granulomatosis (WG), and between anti-neutrophil cytoplasm autoantibody (ANCA) test results in patients with ANCA-associated vasculitis may provide insight into the differences in pathogenesis and raise the opportunity of classifying the vasculitides more accurately. The possible differences in histopathology are investigated in this study. METHODS: We report an analysis of 173 patients with renal disease in microscopic polyangiitis or Wegener's granulomatosis. A total of 173 renal biopsies, performed at diagnosis, were scored by two observers separately, using a previously standardized protocol. Consensus on each biopsy was achieved during a central review. RESULTS: Normal glomeruli were more common in WG than in MPA (P < 0.001). Glomerulosclerosis was more prominent in MPA than in WG (P=0.003). Interstitial fibrosis (P < 0.001), tubular atrophy (P < 0.001), and tubular casts (P=0.005) were more frequently present and more severe in MPA than in WG. Presence of glomerulosclerosis was more extensive in patients with myeloperoxidase (MPO)-ANCA than with proteinase 3 (PR3)-ANCA (P=0.022). Interstitial fibrosis (P=0.008), tubular necrosis (P=0.030), tubular atrophy (P=0.013), and intra-epithelial infiltrates (P=0.006) were more frequently present and more severe in MPO-ANCA than in PR3-ANCA. CONCLUSIONS: Glomerulonephritis in relation to MPA has more characteristics of chronic injury at the time of presentation than glomerulonephritis in relation to WG. This difference may be due to a delayed establishment of diagnosis in patients with MPA compared to patients with WG. Both active and chronic lesions are more abundantly present in MPO-ANCA-positive patients than in patients with PR3-ANCA-positivity, which suggests that the pathogenesis of renal disease in these ANCA subsets could be different. Our results also suggest that ANCA test results may be useful in classifying ANCA-associated vasculitides.