Outcome of adult acute myeloid leukemia patients with extramedullary disease and treatment with venetoclax/hypomethylating agents.

We evaluated response to VEN/HMA in 46 patients with acute myeloid leukemia (AML) characterized by extramedullary disease (EMD). Median age was 65 (range, 19-81) years. Patients had a median of two EMD sites (range, 1-5) and 35 (76%) patients had concurrent bone marrow involvement. Twenty (43%) patients had highrisk genetic features according to the European Leukemia Net 2022 classification. Twenty-nine (63%) were relapsed or refractory after intensive chemotherapy (CTX) including 13 (28%) with prior allogeneic hematopoietic cell transplantation (allo-HCT). Patients received a median of 2 cycles of VEN/HMA (range, 1-31). Twenty (43%) patients achieved complete remission (CR) or CR with incomplete hematological recovery (CRi) after VEN/HMA and five (11%) achieved a partial remission (PR). Six patients were subsequently consolidated with allo-HCT (CR/CRi, n=4; PR, n=2). Median follow-up was 49.1 months (95%-CI, 26.1 months - not reached) and median overall survival (OS) 6.4 months (95%-CI, 5.1-11 months). One-year and 2-years OS rates were 29.3% (95%-CI, 18.6-46.2%) and 12.3% (95%-CI, 5.5-27.6%), respectively. Age with a cut-off of 60 years had no impact on OS (P=0.90). Relapse occurred in 12 of 20 (60%) patients who achieved CR/CRi after VEN/HMA treatment. Of those, all except one succumbed to their disease. Six (30%) patients were in CR/CRi at last follow-up and 2 (10%) died in CR. In our cohort of patients with AML with EMD with high-risk features, treatment with VEN/HMA resulted in an encouraging ORR of 54% with a CR/CRi rate of 43.5%. However, VEN/HMA alone may not be effective in maintaining disease control.

Pre- and post-procedural cardiac imaging (computed tomography and magnetic resonance imaging) in electrophysiology: a clinical consensus statement of the European Heart Rhythm Association and European Association of Cardiovascular Imaging of the European Society of Cardiology.

Imaging using cardiac computed tomography (CT) or magnetic resonance (MR) imaging has become an important option for anatomic and substrate delineation in complex atrial fibrillation (AF) and ventricular tachycardia (VT) ablation procedures. Computed tomography more common than MR has been used to detect procedure-associated complications such as oesophageal, cerebral, and vascular injury. This clinical consensus statement summarizes the current knowledge of CT and MR to facilitate electrophysiological procedures, the current value of real-time integration of imaging-derived anatomy, and substrate information during the procedure and the current role of CT and MR in diagnosing relevant procedure-related complications. Practical advice on potential advantages of one imaging modality over the other is discussed for patients with implanted cardiac rhythm devices as well as for planning, intraprocedural integration, and post-interventional management in AF and VT ablation patients. Establishing a team of electrophysiologists and cardiac imaging specialists working on specific details of imaging for complex ablation procedures is key. Cardiac magnetic resonance (CMR) can safely be performed in most patients with implanted active cardiac devices. Standard procedures for pre- and post-scanning management of the device and potential CMR-associated device malfunctions need to be in place. In VT patients, imaging-specifically MR-may help to determine scar location and mural distribution in patients with ischaemic and non-ischaemic cardiomyopathy beyond evaluating the underlying structural heart disease. Future directions in imaging may include the ability to register multiple imaging modalities and novel high-resolution modalities, but also refinements of imaging-guided ablation strategies are expected.

Luspatercept in combination with recombinant erythropoietin in patients with myelodysplastic syndrome with ring sideroblasts: Stimulating early and late-stage erythropoiesis.

Patients with myelodysplastic syndromes and ring sideroblasts (MDS RS) are clinically characterized by severe anemia and transfusion need. Erythropoiesis-stimulating agents (ESAs), which stimulate hemoglobin production and early maturation of erythroid precursors, are effective only in a portion of patients and for limited time. Luspatercept, an inhibitor of the TGF-beta pathway, is beneficial in unblocking late-stage erythropoiesis and has been approved for MDS RS patients failing or not-candidate to ESAs. ESAs and/or luspatercept failure represents an unmet clinical need and most patients become life-long transfusion dependent. Here, we describe the clinical combination of luspatercept with ESAs (subcutaneous epoetin alpha 40-80 000 IU/week) in seven MDS RS patients. Two patients had ESAs as pre-existing therapy, while five were re-challenged with ESAs as add-on treatment due to luspatercept failure. Three patients achieved hematologic improvement, and one became transfusion independent. No adverse events were noted. This is the first clinical evidence that stimulating both early and late-stage erythropoiesis may offer a further option for this challenging patient population.

Unipolar voltage mapping in right ventricular cardiomyopathy: pitfalls, solutions and advantages.

AIMS: Endocardial unipolar and bipolar voltage mapping (UVM/BVM) of the right ventricle (RV) are used for transmural substrate delineation. However, far-field electrograms (EGMs) and EGM changes due to injury current may influence automatically generated UVM. Epicardial BVM is considered less accurate due to the impact of fat thickness (FT). Data on epicardial UVM are sparse. The aim of the study is two-fold: to assess the influence of the manually corrected window-of-interest on UVM and the potential role of epicardial UVM in RV cardiomyopathies. METHODS AND RESULTS: Consecutive patients who underwent endo-epicardial RV mapping with computed-tomography (CT) integration were included. Mapping points were superimposed on short-axis CT slices and correlated with local FT. All points were manually re-analysed and the window-of-interest was adjusted to correct for false high unipolar voltage (UV). For opposite endo-epicardial point-pairs, endo-epicardial bipolar voltage (BV) and UV were correlated for different FT categories. A total of 3791 point-pairs of 33 patients were analysed. In 69% of endocardial points and 63% of epicardial points, the window-of-interest needed to be adjusted due to the inclusion of far-field EGMs, injury current components, or RV-pacing artifacts. The Pearson correlation between corrected endo-epicardial BV and UV was lower for point-pairs with greater FT; however, this correlation was much stronger and less influenced by fat for UV. CONCLUSION: At the majority of mapping sites, the window-of-interest needs to be manually adjusted for correct UVM. Unadjusted UVM underestimates low UV regions. Unipolar voltage seems to be less influenced by epicardial fat, suggesting a promising role for UVM in epicardial substrate delineation.

The transmural activation interval: a new mapping tool to identify ventricular tachycardia substrates in right ventricular cardiomyopathy.

AIMS: In right ventricular cardiomyopathy (RVCM), intramural scar may prevent rapid transmural activation, which may facilitate subepicardial ventricular tachycardia (VT) circuits. A critical transmural activation delay determined during sinus rhythm (SR) may identify VT substrates in RVCM. METHODS AND RESULTS: Consecutive patients with RVCM who underwent detailed endocardial-epicardial mapping and ablation for scar-related VT were enrolled. The transmural activation interval (TAI, first endocardial to first epicardial activation) and maximal activation interval (MAI, first endocardial to last epicardial activation) were determined in endocardial-epicardial point pairs located <10 mm apart. VT-related sites were determined by conventional substrate mapping and limited activation mapping when possible. Nineteen patients (46 ± 16 years, 84% male, 63% arrhythmogenic right ventricular cardiomyopathy, 37% exercise-induced arrhythmogenic remodelling) were inducible for 44 VT [CL 283 (interquartile range, IQR 240-325)ms]. A total of 2569 endocardial-epicardial coupled point pairs were analysed, including 98 (4%) epicardial VT-related sites.The TAI and MAI were significantly longer at VT-related sites compared with other electroanatomical scar sites [TAI median 31 (IQR 11-50) vs. 2 (-7-11)ms, P < 0.001; MAI median 65 (IQR 45-87) vs. 23 (13-39)ms, P < 0.001]. TAI and MAI allowed highly accurate identification of epicardial VT-related sites (optimal cut-off TAI 17 ms and MAI 45 ms, both AUC 0.81). Both TAI and MAI had a better predictive accuracy for VT-related sites than endocardial and epicardial voltage and electrogram (EGM) duration (AUC 0.51-0.73). CONCLUSION: The transmural activation delay in SR can be used to identify VT substrates in patients with RVCM and predominantly hemodynamically non-tolerated VT, and may be an important new mapping tool for substrate-based ablation.

Quality of life and therapeutic management of axial spondyloarthritis patients in Italy: a 12-month prospective observational study.

OBJECTIVES: To evaluate the health-related quality of life (HRQoL), disease activity, treatment adherence, and work ability in the real-world setting in patients with axial spondyloarthritis (axSpA). METHODS: QUASAR was a prospective 12-month, observational study involving 23 rheumatology centres across Italy, including adult patients with axSpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. Patients were followed at baseline, 3, 6, and 12 months for disease activity and health-related QoL (HRQoL), treatment adherence and work ability. Regression analysis was used to assess the association between treatment and outcome variables. RESULTS: 413 (80.7%) out of axSpA 512 patients were diagnosed with ankylosing spondylitis (AS) and 99 (19.3%) with non-radiographic axSpA (nr-axSpA). Nr-axSpA and AS patients had similar baseline disease activity and HRQoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs) were the most frequent medication (n=426, 83.2%). Over the 1-year follow-up, disease activity measures (joint pain and swelling, CRP, global assessment, BASDAI, ASDAS), HRQoL and work ability significantly improved, while few differences emerged between nr-axSpA and AS patients. Treatment satisfaction and adherence questionnaires improved over the 12 months. Patients treated with bDMARDs showed improved outcomes for disease activity measures and HRQoL variables, greater benefit observed in patients with AS. CONCLUSIONS: We found clinical and HRQoL improvement over 1 year in a large, real-world population of nr-axSpA and AS patients treated with bDMARDs or conventional synthetic DMARDs.

Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: a real-life multicentre study.

OBJECTIVES: Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used along biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated the efficacy and safety of baricitinib in real life. METHODS: We prospectively enrolled 446 RA patients treated with baricitinib from 11 Italian centres. Patients were evaluated at baseline and after 3, 6, and 12 months. They were arrayed based on previous treatments as bDMARD-naïve and bDMARD-insufficient responders (IR) after the failure or intolerance to bDMARDs. A sub-analysis differentiated the effects of methotrexate (MTX) and the use of oral glucocorticoids (OGC). RESULTS: Our cohort included 150 (34%) bDMARD-naïve and 296 (66%) bDMARD-IR patients, with 217 (49%) using baricitinib as monotherapy. Considering DAS-28-CRP as the primary outcome, at 3 and 6 months, 114/314 (36%) and 149/289 (51.6%) patients achieved remission, while those in low disease activity (LDA) were 62/314 (20%) and 46/289 (15.9%), respectively; finally at 12 months 81/126 (64%) were in remission and 21/126 (17%) in LDA. At all-timepoints up to 12 months, bDMARDs-naïve patients demonstrated a better clinical response, independently of MTX. A significant reduction in the OGC dose was observed at 3 and 12 months in all groups. The serum positivity for both rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) conferred a lower risk of stopping baricitinib due to inefficacy. Fifty-eight (13%) patients discontinued baricitinib due to adverse events, including thrombotic events and herpes zoster reactivation. CONCLUSIONS: Real-life data confirm the efficacy and safety profiles of baricitinib in patients with RA and provide evidence that drug survival is higher in bDMARDs-naïve and seropositive patients.

CD34-Positive Blast Count and p53 Expression in Bone Marrow Biopsies of Patients with Low-Risk Myelodysplastic Syndromes: Potential Predictive Tools of Response to Erythropoietin Stimulating Agents.

INTRODUCTION: The first-line therapy for patients with low-risk myelodysplastic syndromes (MDSs) commonly consists of erythropoietin stimulating agents (ESAs), with a response rate ranging from 34 to 62%. For nonresponder patients, outside clinical trials, blood transfusions are the most frequent therapeutic option, with detrimental effect on the quality of life and with risks of iron-overload. Since no studies have been yet conducted on this topic, we investigated the potential predictive role of bone marrow (BM) histological evaluation in patients treated with ESAs. MATERIALS AND METHODS: We performed a morphological and immunohistochemical retrospective analysis of BM biopsies of 96 patients with low-risk MDSs subsequently treated with ESAs. RESULTS: In our series, substantial morphological overlap was found between responder and nonresponder patients. On the contrary, patients with a percentage of CD34-positive blasts >3% or with p53 protein expression <1% responded with a significantly higher frequency to ESAs. CONCLUSIONS: Our study reinforces the role of BM biopsy as diagnostic tool in MDSs, being also able to supply information related to response to ESAs and to its loss over time.

Accuracy of electroanatomical mapping-guided cardiac radiotherapy for ventricular tachycardia: pitfalls and solutions.

AIMS: To analyse and optimize the interobserver agreement for gross target volume (GTV) delineation on cardiac computed tomography (CCT) based on electroanatomical mapping (EAM) data acquired to guide radiotherapy for ventricular tachycardia (VT). METHODS AND RESULTS: Electroanatomical mapping data were exported and merged with the segmented CCT using manual registration by two observers. A GTV was created by both observers for predefined left ventricular (LV) areas based on preselected endocardial EAM points indicating a two-dimensional (2D) surface area of interest. The influence of (interobserver) registration accuracy and availability of EAM data on the final GTV and 2D surface location within each LV area was evaluated. The median distance between the CCT and EAM after registration was 2.7 mm, 95th percentile 6.2 mm for observer #1 and 3.0 mm, 95th percentile 7.6 mm for observer #2 (P = 0.9). Created GTVs were significantly different (8 vs. 19 mL) with lowest GTV overlap (35%) for lateral wall target areas. Similarly, the highest shift between 2D surfaces was observed for the septal LV (6.4 mm). The optimal surface registration accuracy (2.6 mm) and interobserver agreement (Δ interobserver EAM surface registration 1.3 mm) was achieved if at least three cardiac chambers were mapped, including high-quality endocardial LV EAM. CONCLUSION: Detailed EAM of at least three chambers allows for accurate co-registration of EAM data with CCT and high interobserver agreement to guide radiotherapy of VT. However, the substrate location should be taken in consideration when creating a treatment volume margin.

Myocardial calcification is associated with endocardial ablation failure of post-myocardial infarction ventricular tachycardia.

AIMS: In patients with post-myocardial infarction (post-MI) ventricular tachycardia (VT), the presence of myocardial calcification (MC) may prevent heating of a subepicardial VT substrate contributing to endocardial ablation failure. The aims of this study were to assess the prevalence of MC in patients with post-MI VT and evaluate the impact of MC on outcome after endocardial ablation. METHODS AND RESULTS: In 158 patients, the presence of MC was retrospectively assessed on fluoroscopy recordings in seven standard projections obtained during pre-procedural coronary angiograms. Myocardial calcification, defined as a distinct radiopaque area that moved synchronously with the cardiac contraction, was detected in 30 patients (19%). After endocardial ablation, only 6 patients (20%) with MC were rendered non-inducible compared with 56 (44%) without MC (P = 0.033) and of importance, 8 (27%) remained inducible for the clinical VT [compared with 9 (6%) patients without MC; P = 0.003] requiring therapy escalation. After a median follow-up of 31 months, 61 patients (39%) had VT recurrence and 47 (30%) died. Patients with MC had a lower survival free from the composite endpoint of VT recurrence or therapy escalation at 24-month follow-up (26% vs. 59%; P = 0.003). Presence of MC (HR 1.69; P = 0.046), a lower LV ejection fraction (HR 1.03 per 1% decrease; P = 0.017), and non-complete procedural success (HR 2.42; P = 0.002) were independently associated with a higher incidence of VT recurrence or therapy escalation. CONCLUSION: Myocardial calcification was present in 19% of post-MI patients referred for VT ablation and was associated with a high incidence of endocardial ablation failure.

The prognostic value of J-wave pattern for recurrence of ventricular tachycardia after catheter ablation in patients with myocardial infarction.

BACKGROUND: J-waves and fragmented QRS (fQRS) on surface ECGs have been associated with the occurrence of ventricular tachyarrhythmias. Whether these non-invasive parameters can also predict ventricular tachycardia (VT) recurrence after radiofrequency catheter ablation (RFCA) is unknown. Of interest, patients with a wide QRS-complex have been excluded from clinical studies on J-waves, although a J-wave like pattern has been described for wide QRS. METHODS: We retrospectively included 168 patients (67 ± 10 years; 146 men) who underwent RFCA of post-infarct VT. J-wave pattern were defined as J-point elevation ≥ 0.1 mV in at least two leads irrespective of QRS width. fQRS was defined as various RSR` pattern in patients with narrow QRS and more than two R wave in those with wide QRS. The primary endpoint was VT recurrence after RFCA up to 24 months. RESULTS: J-wave pattern and fQRS were present in 27 and 28 patients, respectively. Overlap of J-wave pattern and fQRS was observed in nine. During a median follow-up of 20 (interquartile range 9-24) months, 46 (27%) patients had VT recurrence. Kaplan-Meier curves revealed that both J-wave pattern and fQRS were associated with VT recurrence. Multivariate Cox regression analysis demonstrated that the presence of J-wave pattern (hazard ratio [HR] 2.84; 95% confidence interval [CI] 1.45-5.58; P = .002) and greater number of induced VT (HR 1.29; 95% CI 1.15-1.45; P < .001) were the independent predictors of VT recurrence. CONCLUSIONS: A J-wave pattern-but not fQRS-is independently associated with an increased risk of post-infarct VT recurrence after RFCA irrespective of QRS width. This simple non-invasive parameter may identify patients who require additional treatment.

The harm of delayed diagnosis of arrhythmogenic cardiac sarcoidosis: a case series.

AIMS: Cardiac sarcoidosis (CS) is a known cause of ventricular tachycardia (VT). However, an arrhythmogenic presentation may not prompt immediate comprehensive evaluation. We aimed to assess the diagnostic and disease course of patients with arrhythmogenic cardiac sarcoidosis (ACS). METHODS AND RESULTS: From the Leiden VT-ablation-registry, consecutive patients with CS as underlying aetiology were retrospectively included. Data on clinical presentation, time-to-diagnosis, cardiac function, and clinical outcomes were collected. Patients were divided in early (<6 months from first cardiac presentation) and late diagnosis. After exclusion of patients with known causes of non-ischaemic cardiomyopathy (NICM), 15 (12%) out of 129 patients with idiopathic NICM were ultimately diagnosed with CS and included. Five patients were diagnosed early; all had early presentation with VTs. Ten patients had a late diagnosis with a median delay of 24 (IQR 15-44) months, despite presentation with VT (n = 5) and atrioventricular block (n = 4). In 6 of 10 patients, reason for suspicion of ACS was the electroanatomical scar pattern. In patients with early diagnosis, immunosuppressive therapy was immediately initiated with stable cardiac function during follow-up. Adversely, in 7 of 10 patients with late diagnosis, cardiac function deteriorated before diagnosis, and in only one cardiac function recovered with immunosuppressive therapy. Six (40%) patients died (five of six with late diagnosis). CONCLUSION: Arrhythmogenic cardiac sarcoidosis is an important differential diagnosis in NICM patients referred for VT ablation. Importantly, the diagnosis is frequently delayed, which leads to a severe disease course, including irreversible cardiac dysfunction and death. Early recognition, which can be facilitated by electroanatomical mapping, is crucial.

Arrhythmia exacerbation after post-infarction ventricular tachycardia ablation: prevalence and prognostic significance.

AIMS: Catheter ablation is an effective treatment for post-infarction ventricular tachycardia (VT). However, some patients may experience a worsened arrhythmia phenotype after ablation. We aimed to determine the prevalence and prognostic impact of arrhythmia exacerbation (AE) after post-infarction VT ablation. METHODS AND RESULTS: A total of 1187 consecutive patients (93% men, median age 68 years, median ejection fraction 30%) who underwent post-infarction VT ablation at six centres were included. Arrhythmia exacerbation was defined as post-ablation VT storm or incessant VT in patients without prior similar events. During follow-up (median 717 days), 426 (36%) patients experienced VT recurrence. Events qualifying as AE occurred in 67 patients (6%). Median times to VT recurrence with and without AE were 238 [interquartile range (IQR) 35-640] days and 135 (IQR 22-521) days, respectively (P = 0.25). Almost half of the patients (46%) who experienced AE experienced it within 6 months of the index procedure. Patients with AE had had longer ablation times during the ablation procedures compared to the rest of the patients (median 42 vs. 34 min, P = 0.02). Among patients with VT recurrence, the risk of death or heart transplantation was significantly higher in patients with than without AE (hazard ratio 1.99, 95% CI 1.28-3.10; P = 0.002) after adjusting for age, gender, ejection fraction, cardiac resynchronization therapy, post-ablation non-inducibility, and post-ablation amiodarone use. CONCLUSION: Arrhythmia exacerbation after ablation of infarct-related VT is infrequent but is independently associated with an adverse long-term outcome among patients who experience a VT recurrence. The mechanisms and mitigation strategies of AE after catheter ablation require further investigation.

Optimizing ablation duration using dormant conduction to reveal incomplete isolation with the second generation cryoballoon: A randomized controlled trial.

INTRODUCTION: Efficacy of cryoballoon ablation depends on balloon-tissue contact and ablation duration. Prolonged duration may increase extracardiac complications. The aim of this study is to determine the optimal additional ablation duration after acute pulmonary vein isolation (PVI). METHODS: Consecutive patients with paroxysmal AF were randomized to three groups according to additional ablation duration (90, 120, or 150 seconds) after acute PVI (time-to-isolation). Primary outcome was reconnection/dormant conduction (DC) after a 30 minutes waiting period. If present, additional 240 seconds ablations were performed. Ablations without time-to-isolation <90 seconds, esophageal temperature <18°C or decreased phrenic nerve capture were aborted. Patients were followed with 24-hour Holter monitoring at 3, 6, and 12 months. RESULTS: Seventy-five study patients (60 ± 11 years, 48 male) were included. Reconnection/DC per vein significantly decreased (22%, 6% and 4%) while aborted ablations remained stable (respectively 4, 5, and 7%) among the 90, 120, and 150 seconds groups. A shorter cryo-application time, longer time-to-isolation, higher balloon temperature and unsuccessful ablations predicted reconnection/DC. Freedom of atrial fibrillation was, respectively, 52, 56, and 72% in 90, 120, and 150 seconds groups ( P = 0.27), while repeated procedures significantly decreased from 36% to 4% ( P = 0.041) in the longer duration group compared to shorter duration group (150 seconds vs 90 seconds group). In multivariate Cox-regression only reconnection/DC predicted recurrence. CONCLUSION: Prolonging ablation duration after time-to-isolation significantly decreased reconnection/DC and repeated procedures, while recurrences and complications rates were similar. In a time-to-isolation approach, an additional ablation of 150 seconds ablation is the most appropriate.

Real-world experience with decitabine as a first-line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy.

Despite widespread use of decitabine to treat acute myeloid leukaemia (AML), data on its effectiveness and safety in the real-world setting are scanty. Thus, to analyze the performance of decitabine in clinical practice, we pooled together patient-level data of three multicentric observational studies conducted since 2013 throughout Italy, including 306 elderly AML patients (median age 75 years), unfit for intensive chemotherapy, treated with first-line decitabine therapy at the registered schedule of 20 mg/m2 /iv daily for 5 days every 4 weeks. Overall response rate (ORR), overall survival (OS) curves, and multivariate hazard ratios (HRs) of all-cause mortality were computed. Overall, 1940 cycles of therapy were administered (median, 5 cycles/patient). A total of 148 subjects were responders and, therefore, ORR was 48.4%. Seventy-one patients (23.2%) had complete remission, 32 (10.5%) had partial remission, and 45 (14.7%) had haematologic improvement. Median OS was 11.6 months for patients with favourable-intermediate cytogenetic risk and 7.9 months for those with adverse cytogenetic risk. Median relapse-free survival after CR was 10.9 months (95% confidence interval [CI]: 8.7-16.0). In multivariate analysis, mortality was higher in patients with adverse cytogenetic risk (HR=1.58; 95% CI: 1.13-2.21) and increased continuously with white blood cell (WBC) count (HR=1.12; 95% CI: 1.06-1.18). A total of 183 infectious adverse events occurred in 136 patients mainly (>90%) within the first five cycles of therapy. This pooled analysis of clinical care studies confirmed, outside of clinical trials, the effectiveness of decitabine as first-line therapy for AML in elderly patients unfit for intensive chemotherapy. An adverse cytogenetic profile and a higher WBC count at diagnosis were, in this real life setting, unfavourable predictors of survival.

Observational study on the QUality of life of Italian Axial SpondyloARthritis patients (QUASAR): baseline data.

OBJECTIVES: To describe the baseline characteristics of the patients enrolled in the QUality of life in patients with Axial SpondyloARthritis (QUASAR) study in terms of quality of life (QoL), disease activity, therapy adherence, and work ability in a real-world setting. METHODS: QUASAR is an Italian multicentre, prospective 12-month observational study, including consecutive adult patients classified as axial spondyloarthritis (axSpA) according to the Assessment of SpondyloArthritis international Society criteria for axSpA. RESULTS: Of 512 patients enrolled in 23 rheumatology centres, 80.7% had ankylosing spondylitis (AS) and 19.3% had non-radiographic axSpA (nr-axSpA). Mean ages were 34.1±13.3 years at axSpA symptoms onset and 39.5±13.0 years at diagnosis. Of the patients, 51.4% presented with ≥1 extra articular manifestation (EAM); the most common were psoriasis (17.8%) and uveitis (16.4%). Patients with nr-axSpA and AS had similar EAM rates, disease activity, and QoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs; 83.2%) were the most commonly received medication, followed by conventional synthetic DMARDs (22.9%) and non-steroidal anti-inflammatory drugs (NSAIDs; 16.6%). At baseline, higher treatment satisfaction was reported with bDMARDs which, together with NSAIDs, were associated with the best overall scores for disease activity, function, and QoL in the overall population and AS subgroup. CONCLUSIONS: QUASAR is the first Italian prospective study that comprehensively evaluated a large axSpA patient sample in a real-world setting. This interim analysis at baseline confirmed that i) patients with AS and nr-axSpA have similar QoL and disease burden, ii) nearly all axSpA patients receive treatment, and iii) bDMARDs and NSAIDs, overall, yield better disease activity and QoL.

Impact of left atrial box surface ratio on the recurrence after ablation for persistent atrial fibrillation.

BACKGROUND: The posterior wall of the left atrium (LA) is a well-known substrate for atrial fibrillation (AF) maintenance. Isolation of the posterior wall between the pulmonary veins (box lesion) may improve ablation success. Box lesion surface area size varies depending on the individual anatomy. This retrospective study evaluates the influence of box lesion surface area as a ratio of total LA surface area (box surface ratio) on arrhythmia recurrence. METHODS: Seventy consecutive patients with persistent AF (63 ± 11 years, 53 men) undergoing computed tomography (CT) imaging and ablation procedure consisting of a first box lesion were included in this study. Box lesion surface area was measured on electroanatomical maps and total LA surface area was derived from CT. Patients were followed with 24-h electrocardiography and exercise tests at 3, 6, and 12 months after AF ablation. Arrhythmia recurrence was defined as any AF/atrial tachycardia (AT) beyond 3 months without antiarrhythmic drugs. RESULTS: During a median follow-up of 13 (interquartile range = 10-17) months, 42 (60%) patients had AF/AT recurrence. Multivariate Cox proportional regression analysis showed that a larger box surface ratio protected against recurrence (hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.690-0.955; P = 0.012). Left atrial volume index (HR = 1.01 [0.990-1.024, P = 0.427] and a history of mitral valve surgery (HR = 2.90; 95% CI = 0.970-8.693; P = 0.057) were not associated with AF recurrence in multivariate analysis. CONCLUSION: A larger box lesion surface area as a ratio of total LA surface area is protective for AF/AT recurrence after ablation for persistent AF.

Whole human heart histology to validate electroanatomical voltage mapping in patients with non-ischaemic cardiomyopathy and ventricular tachycardia.

Aims: Electroanatomical voltage mapping (EAVM) is an important diagnostic tool for fibrosis identification and risk stratification in non-ischaemic cardiomyopathy (NICM); currently, distinct cut-offs are applied. We aimed to evaluate the performance of EAVM to detect fibrosis by integration with whole heart histology and to identify the fibrosis pattern in NICM patients with ventricular tachycardias (VTs). Methods and results: Eight patients with NICM and VT underwent EAVM prior to death or heart transplantation. EAVM data was projected onto slices of the entire heart. Pattern, architecture, and amount of fibrosis were assessed in transmural biopsies corresponding to EAVM sites. Fibrosis pattern in NICM biopsies (n = 507) was highly variable and not limited to mid-wall/sub-epicardium. Fibrosis architecture was rarely compact, but typically patchy and/or diffuse. In NICM, biopsies without abnormal fibrosis unipolar voltage (UV) and bipolar voltage (BV) showed a linear association with wall thickness (WT). The amount of viable myocardium showed a linear association with both UV and BV. Accordingly, any cut-off to delineate fibrosis performed poorly. An equation was generated calculating the amount of fibrosis at any location, given WT and UV or BV. Conclusion: Considering the linear relationships between WT, amount of fibrosis and both UV and BV, the search for any distinct voltage cut-off to identify fibrosis in NICM is futile. The amount of fibrosis can be calculated, if WT and voltages are known. Fibrosis pattern and architecture are different from ischaemic cardiomyopathy and findings on ischaemic substrates may not be applicable to NICM.