Long-term Clinical Outcomes Research Articles

Neonatal heart transplantation in the United States: Trends and outcomes.

Heart transplantation in the neonatal period is associated with excellent survival. However, outcomes data are scant and have been obtained primarily from two single-center reports within the United States. We sought to analyze the outcomes of all neonatal heart transplants performed in the United States using the United Network for Organ Sharing (UNOS) dataset. The UNOS dataset was queried for patients who underwent infant heart transplantation from 1987 to 2021. Patients were divided into two groups based on age - neonates (<=31 days), and older infants (32 days-365 days). Demographic and clinical characteristics were analyzed and compared, along with follow up survival data. Overall, 474 newborns have undergone heart transplantation in the United States since 1987. Freedom from death or re-transplantation for neonates was 63.5%, 58.8% and 51.6% at 5, 10, and 20 years, respectively. Patients in the newborn group had lower unadjusted survival compared to older infants (p < .001), but conditional 1-year survival was higher in neonates (p = .03). On multivariable analysis, there was no significant difference in survival between the two age groups (p = .43). Black race, congenital heart disease diagnosis, earlier surgical era, and preoperative mechanical circulatory support use were associated with lower survival among infant transplants (p < .05). Neonatal heart transplantation is associated with favorable long-term clinical outcomes. Neonates do not have a significant survival advantage over older infants. Widespread applicability is limited by the small number of available donors. Efforts to expand the donor pool to include non-standard donor populations ought to be considered.

Correlation between asymmetrical vein sign of SWI and long-term clinical outcomes in patients with middle cerebral artery ischemic stroke.

To evaluate the association of asymmetrical cortical vein sign (ACVS) and asymmetrical medullary vein sign (AMVS) on susceptibility-weighted imaging (SWI) with 90-day poor outcomes in patients with unilateral middle cerebral artery acute ischemic stroke (AIS) after conservative drug treatment. Clinical data for the participants included age, sex, smoking, alcohol, hypertension, diabetes, hyperlipidemia, coronary heart disease, NHISS-admission, and NHISS-discharge scores. Participants underwent magnetic resonance imaging (MRI) within 12h of hospital admission, including conventional scan sequences and a SWI sequence. Poor prognosis was defined as a modified Rankin scale (mRS) ≥ 3 at 90days. A total of 108 patients were included from January 2021 to March 2022. Twenty-seven (25%) patients had a poor outcome at 90days. Univariate analysis indicated that diabetes, NHISS-admission, NHISS-discharge, DWI-ASPECTS, SWI-ASPECTS, FLAIR-ASPECTS, and AMVS + were associated with 90-day poor outcome. Multivariate regression analysis showed that AMVS + was associated with 90-day poor outcome from the three models (OR = 3.57, P = 0.006; OR = 3.74, P = 0.005; OR = 5.14, P = 0.0057). However, no significant association was found between ACVS + and 90-day poor outcome. AMVS might be a helpful neuroimaging predictor for poor outcome at 90days compared to ACVS in drug-conserving treatment of patients with unilateral middle cerebral artery ischemic stroke.

To cast or not to cast? Postoperative care of ankle fractures: a meta-analysis of randomized controlled trials.

Postoperative care of ankle fractures treated with open reduction and internal fixation (ORIF) is a debated topic. A meta-analysis of Randomized Controlled Trials was conducted with the aim of comparing early mobilization and weightbearing to traditional postoperative protocols. A systematic search of electronic databases was conducted according to the PRISMA guidelines. Only randomized clinical trials were included. Data about clinical outcome, time to return to work and complications were extracted and summarized. Meta-analyses were performed. Twenty studies for a total of 1328 patients were included. Early mobilization was compared to immobilization in 724 patients: the two groups did not significantly differ in terms of short- and long-term clinical outcome (p = 0.08 and p = 0.41, respectively). However, early mobilization resulted to be significantly associated with faster return to work (p = 0.047). Early weightbearing was compared to nonweightbearing in 1088 patients. While the clinical difference between the two groups was not significant at short term (p = 0.08), it was significant at long term (p = 0.002). No other significant differences, in particular regarding complications, were highlighted between different groups. Early motion, early weightbearing and traditional postoperative protocols are all safe strategies after ORIF for unstable ankle fractures. Early mobilization is significantly associated with faster return to work and early weightbearing improves long term clinical outcome.Level of evidence: I.

Impact of early surgical complications on kidney transplant outcomes.

Kidney transplantation (KT) improves clinical outcomes of patients with end stage renal disease. Little has been reported on the impact of early post-operative surgical complications (SC) on long-term clinical outcomes following KT. We sought to determine the impact of vascular complications, urological complications, surgical site complications, and peri-graft collections within 30days of transplantation on patient survival, graft function, and hospital readmissions. We conducted a single-centre, observational cohort study examining adult patients (≥ 18years) who received a kidney transplant from living and deceased donors between January 1st, 2005 and December 31st, 2015 with follow-up until December 31st, 2016 (n = 1,334). Univariable and multivariable analyses were performed with Cox proportional hazards models to analyze the outcomes of SC in the early post-operative period after KT. The cumulative probability of SC within 30days of transplant was 25%, the most common SC being peri-graft collections (66.8%). Multivariable analyses showed significant relationships between Clavien Grade 1 SC and death with graft function (HR 1.78 [95% CI: 1.11, 2.86]), and between Clavien Grades 3 to 4 and hospital readmissions (HR 1.95 [95% CI: 1.37, 2.77]). Early SC following KT are common and have a significant influence on long-term patient outcomes.

Global modified Delphi consensus on diagnosis, phenotypes, and treatment of SCN8A-related epilepsy and/or neurodevelopmental disorders.

We aimed to develop consensus for diagnosis/management of SCN8A-related disorders. Utilizing a modified Delphi process, a global cohort of experienced clinicians and caregivers provided input on diagnosis, phenotypes, treatment, and management of SCN8A-related disorders. A Core Panel (13 clinicians, one researcher, six caregivers), divided into three subgroups (diagnosis/phenotypes, treatment, comorbidities/prognosis), performed a literature review and developed questions for the modified Delphi process. Twenty-eight expert clinicians, one researcher, and 13 caregivers from 16 countries participated in the subsequent three survey rounds. We defined consensus as follows: strong consensus, ≥80% fully agree; moderate consensus, ≥80% fully/partially agree, <10% disagree; and modest consensus, 67%-79% fully/partially agree, <10% disagree. Early diagnosis is important for long-term clinical outcomes in SCN8A-related disorders. There are five phenotypes: three with early seizure onset (severe developmental and epileptic encephalopathy [DEE], mild/moderate DEE, self-limited (familial) infantile epilepsy [SeL(F)IE]) and two with later/no seizure onset (neurodevelopmental delay with generalized epilepsy [NDDwGE], NDD without epilepsy [NDDwoE]). Caregivers represented six patients with severe DEE, five mild/moderate DEE, one NDDwGE, and one NDDwoE. Phenotypes vary by age at seizures/developmental delay onset, seizure type, electroencephalographic/magnetic resonance imaging findings, and first-line treatment. Gain of function (GOF) versus loss of function (LOF) is valuable for informing treatment. Sodium channel blockers are optimal first-line treatment for GOF, severe DEE, mild/moderate DEE, and SeL(F)IE; levetiracetam is relatively contraindicated in GOF patients. First-line treatment for NDDwGE is valproate, ethosuximide, or lamotrigine; sodium channel blockers are relatively contraindicated in LOF patients. This is the first-ever global consensus for the diagnosis and treatment of SCN8A-related disorders. This consensus will reduce knowledge gaps in disease recognition and inform preferred treatment across this heterogeneous disorder. Consensus of this type allows more clinicians to provide evidence-based care and empowers SCN8A families to advocate for their children.

Incidence and outcome of periinterventional atrial fibrillation in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention

Abstract Background Peri-interventional atrial fibrillation (AF) may be detected in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Data on the thromboembolic risk and long-term clinical outcome in patients with AF limited to the peri-interventional period is scarce. Purpose To assess the incidence and impact on long-term clinical outcome of peri-interventional de-novo AF in STEMI patients. Methods and Results This retrospective single-center cohort study included all patients who underwent PCI between January 2016 and November 2020 (n=491) due to STEMI. Patients were stratified to three cohorts of AF status: Pre-existing AF: n=42 [8.6%], newly diagnosed peri-interventional AF: n=56 [11.4%] and no AF: n=393 [80.0%]. Patients with newly diagnosed peri-interventional AF as well as patients with pre-existing AF had in median a mild-moderately reduced left ventricular ejection fraction (LVEF), patients in sinus rhythm in median a normal LVEF. During the average follow-up time of 4.7 years (min. 2 years, max. 7 years) the rate for readmission for AF or occurrence of AF without hospital admission was increased in patients with peri-interventional de-novo AF or pre-existing AF (n=6 [10.7%], n=10 [23.8%]) compared to those in sinus rhythm n=22 [5.6%] (p&amp;lt;0,001) The occurrence of ischemic stroke was higher in patients with peri-interventional de-novo AF (n=2 [3.6%] or with pre-existing AF (n=2 [4.8%]) compared to those in sinus rhythm (n=6 [1.5%]. (p=0.256) The risk of cardiovascular death was significantly higher in patients with newly diagnosed peri- interventional AF compared to patients with pre-existing or no AF (n=13 [23.2%], n=5 [11.9%], n= 37 [9.4%]) (p=0.009). In the patient group with peri-interventional de-novo AF, only 25.0% (n=13) received long-term oral anticoagulation therapy (OAK). The rate of stroke in patients who received OAK after peri- interventional de-novo AF was 7.7% (n=1) compared to those without OAK 2.6% (n=1). Conclusion Peri-interventional AF is a frequent finding in STEMI patients undergoing primary PCI. Patients with peri-interventional AF had a significantly increased risk for an adverse cardiovascular outcome. Optimal secondary prophylactic measures appear mandatory in this patient population. The significance of long-term OAK therapy is to be determined.

Residual Coronary Risk Factors Associated With Long-Term Clinical Outcomes in Patients With Coronary Artery Disease Treated With High- vs. Low-Dose Statin Therapy - REAL-CAD Substudy.

It remains unclear which comorbidities, other than lipid parameters, or combination of comorbidities, best predicts cardiovascular events in patients with known coronary artery disease (CAD) treated with statins. Therefore, we aimed to identify the nonlipid-related prognostic factors and risk stratification of patients with stable CAD enrolled in the REAL-CAD study.Methods and Results: Blood pressure, glucose level, and renal function were considered as risk factors in the 11,141 enrolled patients. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unstable angina. The secondary composite endpoint was the primary endpoint and/or coronary revascularization. A significantly worse prognosis at the primary endpoint was observed in the estimated glomerular filtration rate (eGFR) ≤60 group, and the combination of eGFR ≤60 and HbA1c ≥6.0 was the worst (hazard ratio (HR) 1.66; P<0.001). However, even in the eGFR >60 group, systolic blood pressure (SBP) ≥140 mmHg met the secondary endpoint (HR 1.33; P=0.006), and the combination of eGFR ≤60 and HbA1c ≥6.0 was also the worst at the secondary endpoint (HR 1.35; P=0.002). Regarding nonlipid prognostic factors contributing to the incidence of cardiovascular events in statin-treated CAD patients, renal dysfunction was the most significant, followed by poor glucose control and high SBP.

The phenomenon of drug-coating embolism during lower extremity endovascular interventions with paclitaxel-coated balloon.

There is a risk of distal embolization lower extremity endovascular interventions. Possibly a drug-coating embolism caused by coating detachment from intravascular devices. This review focuses on providing updated information on distal embolism in endovascular revascularization of lower extremity arteries, including the use of drug-coated balloons. Drug-coating embolism is a special case of distal embolization during recanalization of the arteries of the lower extremities. Preclinical studies have demonstrated embolization of drug-coated balloons during angioplasty of lower extremity arteries. However, the clinical role of drug-coating embolism is not completely clear. A 2020 meta-analysis found an increased risk of major lower extremity amputation after drug-coated balloon angioplasty in patients with critical limb ischemia. But long-term research is emerging to support the safety of using these devices. Perhaps a more thorough assessment of the quality of life and the degree of compensation of lower limb ischemia with an intraoperative assessment of the frequency of peripheral embolizations using ultrasound emboli detection, as well as microcirculation with transcutaneous oximetry and laser Doppler flowmetry of the operated lower limb will allow a more detailed study of the phenomenon of drug-coating embolism and its impact on long-term clinical outcomes. According to the results of preclinical studies, the use of paclitaxel-coated balloons leads to an increase in the concentration of paclitaxel in distal skeletal muscles. However, paclitaxel concentration in skeletal muscle was significantly higher in first-generation DCBs. The non-target effects of drug-coating balloon are not fully understood and require further study. Understanding the phenomenon of drug-coating embolism can help physicians to better assess the patient risk and to minimize complications.

Feasibility and effectiveness of left bundle branch area pacing after TAVR: the single center experience

Abstract Introduction Transcatheter aortic valve replacement (TAVR) is a safe alternative to open-heart surgery in patients with symptomatic severe aortic stenosis and high surgical risk due to multiple comorbidities, advanced age, and severe left ventricle dysfunction. Due to anatomical considerations of the atrioventricular node, conduction abnormalities requiring the implantation of a pacemaker are common findings after TAVR. High-grade atrioventricular block and new-onset left bundle branch block (LBBB) are the most commonly reported conduction abnormalities after TAVR. Purpose The aim of our study was to assess the feasibility, success rates, and effectiveness of LBBAP in patients requiring pacing after TAVR. Methods A total of 302 patients underwent the TAVR procedure in our institution in the period from January 2022 to November 2023. In this cohort, 38 patients required ventricular pacing in the postoperative period. 16 patients who underwent permanent pacing using LBBAP were included in this observational study. Patients undergoing traditional right ventricular pacing biventricular pacing or leadless pacemaker implantation were excluded from the study. Results LBBAP was successfully performed in 16 patients (89%). 2 patients underwent conventional CRT implantation (1 cardiac resynchronization therapy pacemaker and 1 cardiac resynchronization therapy defibrillator) in order to severe calcification and presence of fibrotic tissue in the target area. The mean age was 60.5±2.74 years, and 10 patients (62.5%) were women. According to the patient’s medical history, 14 patients (84%) had hypertension; coronary artery disease – 2 (12.5%), 2 (12.5%) patients had atrial fibrillation and atrial flutter, and 7 (43.5%) patients had diabetes mellitus. The mean left ventricle ejection fraction (LVEF) was 46.2±14.7%. Interventricular septal thickness 11.8 ± 1.9 mm. Type of conduction diseases: Infranodal AV block and LBBB were present in 9 (56.5%) patients. 5 (31,25%) patients had persistent complete AV block and 2 (12,25%) had Mobitz II AV block. In 2 patients we observed congestive heart failure combined with LBBB. Pre-TAVR QRS morphology was normal in 15 (93%), and RBBB morphology in 1 (7%). The mean QRS duration at baseline was 105±20 ms. Pre-implant QRS duration 135±52 ms. The single-chamber pacemaker was implanted in 1 patient, dual-chamber pacemaker - 13 patients, and cardiac resynchronization therapy defibrillators in 2 patients. Procedural duration and fluoroscopy times were 105. ± 31.9 min and 18 ± 11 min, respectively. Conclusion Complete AV block and new-onset LBBB after TAVR is still an important issue. LBBB correction using conduction system pacing technology is an effective strategy for this type of patient. LBBAP is one of the most exciting developments in pacing therapy over the last few years. Long-term clinical outcomes and safety of physiological pacing data are limited and require further investigations

Arrhythmic mitral valve prolapse with versus without prior mitral valve repair: clinical profiles, electrophysiological substrates, and long-term clinical outcomes

Abstract Background Arrhythmic mitral valve prolapse (AMVP) is characterized by an arrhythmogenic left ventricular substrate, with high prevalence of myocardial scar. Whether patients with prior mitral valve repair for mitral valve prolapse (MVP) and new-onset complex ventricular arrhythmias (VAs) after cardiac surgery have different electroanatomical substrate and arrhythmic outcomes compared with AMVP patients without prior mitral valve surgery is currently unknown. Purpose We sought to compare the electroanatomical substrate and long-term clinical outcomes of patients with new-onset complex VAs after mitral valve surgery to AMVP patients without prior surgery. Methods We conducted a multicenter, prospective, observational study, enrolling MVP patients with prior mitral valve repair and new-onset complex VAs (&amp;gt;1000 premature ventricular contractions [PVCs]/day, nonsustained ventricular tachycardia [NSVT], and sustained VT) after cardiac surgery (group A,n=9), and patients with MVP, complex VAs and no prior surgery (group B,n=20). Each patient underwent a comprehensive diagnostic workup, including left ventricular electroanatomical mapping. Clinical-imaging data, as well as the location and segmental extension of both low-voltage areas and late potentials were assessed and compared between the two groups. The primary outcome was the occurrence of sustained VT or ventricular fibrillation(VF) during follow-up. Results In group A, complex VAs were first diagnosed after a median of 30(8-56) months following mitral valve repair. The characteristics of patients from the two study groups are presented in the Table. Patients from group A were older, sustained VT was nonsignificantly more common at baseline, the PVC count nonsignificantly higher, and LVEF nonsignificantly lower. Mitral annular disjunction was never observed in group A, while it was found in 7 patients from group B (p=0.066). At LV electroanatomical voltage mapping, bipolar and unipolar low-voltage areas (LVAs) were equally common in the two groups overall, and typically involved basal perimitral regions. However, patients from group B had concomitant bipolar and unipolar LVAs 50% of times, with larger unipolar LVAs, while patients from group A mostly showed isolated bipolar LVAs. Over a median follow-up of 15 (12-41) months, patients from group A (n=3, 33%) had slightly higher incidence of sustained VT or VF (HR: 1.91; 95% CI, 1.06-42.65; log-rank p=0.02, Figure) than patients from group B (n=2, 10%). Conclusion Compared to patients with AMVP and no prior cardiac surgery, patients with new-onset complex VAs after mitral valve repair for MVP have a slightly different clinical profile and electroanatomical substrate, characterized by predominant bipolar LVAs in the perimitral region. The long-term risk of major ventricular arrhythmias appears slightly higher in MVP patients with prior mitral valve surgery, mandating at least an equally careful risk assessment in both groups.

Comparison of pulsed field ablation and thermal ablation for repeat procedures after failed prior thermal ablation for atrial fibrillation

Abstract Background Procedural efficiency and long-term clinical outcome after a first pulmonary vein isolation (PVI) for atrial fibrillation (AF) with pulsed-field ablation (PFA) has recently been reported to be non-inferior compared to radiofrequency ablation (RFA) and cryoballoon ablation (CBA). Studies comparing PFA and RFA for a first redo procedure in patients with failed prior thermal PVI are lacking. Purpose We sought to compare procedural efficiency and 1-year success rate (i.e maintenance of sinus rhythm) between PFA and RFA in patients undergoing a first redo procedure due to recurrence of atrial tachyarrhythmias after a prior thermal PVI. Methods Patients with recurrences after a 90-day blanking period following an index PVI with either RFA or CBA referred for a first redo ablation were enrolled. All redo procedures were done using a 3D electro-anatomical mapping to identify PV reconnections and guide repeat PVI by either PFA or RFA. In cases of incomplete or ostial isolation, the PFA group was treated using the standard 8-applications per vein while the CLOSE protocol was used for segmental PVI completion in the RFA group. Extra-PV lesion sets were added at the discretion of the treating physician. Patients were followed with 7d-Holter ECGs 3, 6, and 12 months after reablation. Recurring arrhythmias were categorized as persistent AF, paroxysmal AF, or atrial flutter. Secondary endpoints were periprocedural complications, total ablation time, radiation time and exposure. Results A total of 220 patients (median age 67 [IQR 58-74] years, 64% male, 64% persistent AF) were enrolled and equally treated with PFA or RFA (110 in both groups). There were no statistically significant differences in the clinical characteristics at baseline. Procedure time was shorter in the PFA group (95 vs. 122 minutes, p=0.001) whereas radiation time and dose were higher in the PFA group (17.0 vs. 6.4 minutes, p=&amp;lt;0.001 and 4.9 vs. 2.2 Gycm2, p=&amp;lt;0.001). Additional posterior wall ablation (PFA) or roof line (RFA) was performed predominantly in the PFA group (61 patients, 55.5 %) and in 5 patients (4.5 %) in the RFA group (p=0.001). Major complications occurred in 3 patients in the PFA group and in 1 patient in the RFA group (see Picture 2). Freedom from arrhythmia in Kaplan-Meier analysis 12 months after the reablation was 61% (CI 50-74%) in the PFA group and 59% (CI 49-71%; log-rank test p=0.81). No differences in outcomes were observed in the pooled group between paroxysmal AF (60%, CI: 50-72%) and persistent AF (61%, CI: 51-73%, p=0.64). Recurrence of organized atrial tachycardia was more common in the PFA group (p=0.018) Conclusion In patients undergoing a first redo procedure after a first round of thermal PVI and with recurrence of atrial tachyarrhythmia, PFA for reablation resulted in shorter procedure times compared to RFA despite more frequent posterior wall ablation. Long-term arrhythmia-free survival after the redo procedure was similar in both groups.Kaplan-Meier analysis of redo proceduresProcedure and outcome data

Staged Versus Same-Day Surgery in Circumferential Minimally Invasive Deformity Correction.

We sought to compare long-term clinical and radiographic outcomes in patients who underwent staged vs same-day circumferential minimally invasive surgery (cMIS) for adult spinal deformity (ASD). We reviewed staged and same-day cMIS ASD cases in a prospective multi-institution database to compare preoperative and 2-year clinical and radiographic parameters between cohorts. A total of 85 patients with a 2-year follow-up were identified (27 staged, 58 same-day). Staged patients had more extensive surgeries and greater hospital length of stay (all P < .001). There were no significant differences in preoperative or 2-year postoperative clinical metrics between cohorts. Patients in the staged cohort also had greater preoperative coronal deformity and thus experienced greater reduction in coronal deformity at 2 years (all P < .01). Patients undergoing staged or same-day cMIS correction had similar outcomes at 2 years postoperatively. Staged cMIS ASD correction may be more appropriate in patients with greater deformity, higher frailty, and who require longer, more extensive surgeries.

Cardioneuroablation for vasovagal syncope. Results from an EHRA Survey

Abstract Background Cardioneuroablation (CNA) is a recently introduced catheter-based therapy for vasovagal syncope (VVS), involving the modulation of the cardiac autonomic nervous system. Over the past decade, the body of evidence supporting CNA has consistently grown, sparking increased interest, and leading to broader adoption of this novel therapy for VVS treatment. However, several knowledge gaps persist, particularly concerning clinical indications, methodology, and long-term outcomes. Purpose The aim of this survey is to provide a comprehensive overview of the daily utilization of CNA in Europe. Methods and Results Among 204 participants, half reported that they are already performing CNA in their centres. The survey indicated CNA as an emerging therapy, with most centres initiating this treatment within the last two years. A significant majority of those who responded (71%) adopted a systematic approach by targeting ganglionated plexuses (GPs) in both the right atrium (RA) and left atrium (LA) as their first-line approach. The second most common approach (16%) involved performing ablation LA GPs only in the cases where there is no response following RA ablation. Figure 1 shows the GPs usually targeted for ablation. The most frequent procedural endpoint was the increase in the heart rate. Ninety percent of respondents relied on an anatomical approach for GP localization, while 59% also guided the procedure using electrogram analysis. Less frequently used approaches included pre-procedural imaging (20%), high-frequency stimulation (17%), and spectral analysis (10%). Only 11% of physicians discharged patients who underwent CNA without anticoagulation or antiplatelet therapy. In most cases (58%), respondents discharged their patients with anticoagulation, while 28% on single antiplatelet therapy. Overall, CNA is considered an effective procedure (80% of responders rating its effectiveness at or above 70%) and a safe procedure (with an estimated 1% rate of procedure-related complications, with symptomatic sinus tachycardia being the most frequently reported). Conclusions This survey confirmed high expectations for the future of this therapy, as most responders anticipate that CNA will be indicated as a first-line therapy for patients with recurrent cardioinhibitory VVS. Future efforts are necessary to standardize the procedural flow and peri-procedural patient management.

Slow pathway ablation in pediatric patients: long-term outcomes in a high-volume center according to baseline electrophysiologic characteristics

Abstract Background Slow pathway ablation (SPA) in pediatric patients with documented paroxysmal supraventricular tachycardia (PSVT) has been proven safe and effective. Arrhythmia induction is often difficult in the pediatric population. Accordingly, empirical SPA is frequently adopted in this population. Real-world data about long-term outcomes of slow pathway ablation (SPA) in relation to tachycardia inducibility and electrophysiologic characteristics in pediatric patients with PSVT in a high-volume center are lacking. Purpose To compare long-term clinical outcomes of SPA in pediatric patients with and without intraprocedural documentation of DAVP and AV nodal reentrant tachycardia induction. Methods In this retrospective sigle-center study, all SPA procedures performed on pediatric patients (under 18 years) at our Institution since 2016 were considered. All patients had documented PSVT with short RP interval, no evidet ventricular pre-excitatio on surface ECG and normal echocardiography. Baseline EPS was performed to exclude the presence of concealed accessory pathway and isoproterenol infusion was used to exclude focal atrial tachycardias. According to intraprocedural EP characteristics, three group of patients were identified: Group 1 with AVNRT induction; Group 2 with dual atrioventricular nodal physiology (DAVP) and no tachycardia induction; Group 3 without DAVP. According to previous documentation of a short RP PSVT and after discussion with patients’ families, SPA was performed in all patients. The endpoint of the ablation was to eliminate slow pathway conduction and AV node re-entrant beat. Follow up visits were scheduled three and twelve months after ablation for all patients. Results 1734 patients underwent SPA since 2016 at our Institution. 1092 patients (73.4%) showed AVNRT induction during EPS (Group 1). 433 patients (14.2%) showed DAVP without tachycardia induction (Group 2). 209 patients (12.4%) didn’t show DAVP at EPS (Group 3). Age and gender were similar among the three groups. SPA was performed with acute procedural success in all patients. After 36-month median follow-up, freedom from palpitations was 98.5% in Group 1, 97.1% in Group 2 and 92.3% in Group 3. A survival analysis showed the best outcomes in group 1 and no significant difference in recurrence rate among the groups 2 and 3 (Figure 1). No permanent heart blocks, neither other major complication was observed. Conclusions When performed by experienced operators and in high-volume centers, SPA is a safe and effective procedure in pediatric patients with documented short RP PSVT. Success rate is highest with AVNRT induction and good without AVNRT induction, regardless of AV node dual conduction at baseline EPS. Such high success rate depends on careful exclusion of others arrhythmia mechanisms (i.e., focal atrial tachycardias, AV re-entrant tachycardias) that, although infrequent in children, are the main determinants of arrhythmia recurrences.

Left atrial appendage clipping during hybrid atrial fibrillation ablation: a very long-term, single-center experience

Abstract Background/introduction Epicardial left atrial appendage (LAA) clipping is an effective strategy for stroke prophylaxis in high thromboembolic (TE) and bleeding risk patients with atrial fibrillation (AF). In addition to LAA exclusion from systemic circulation, clipping promotes concomitant appendage isolation, which might have positive impacts on arrhythmia control. Purpose The aim of this study was to report safety, success rate, and the long-term clinical outcomes of LAA clipping in a large cohort of AF patients undergoing concomitant hybrid ablation. Methods Consecutive patients undergoing hybrid AF ablation between 2013 and 2023 were enrolled. Hybrid ablation was performed in a one-step procedure consisting of thoracoscopic epicardial radiofrequency (RF) ablation followed by endocardial mapping and ablation, if needed. Ablation lesion set included pulmonary vein (PV) and posterior wall (PW) isolation, as well as RF applications to the LAA/posterolateral ridge. LAA clipping was performed via Atriclip exclusion system (Atricure, Inc., The Nederlands) after epicardial ablation. Additional endocardial lesions were performed in case of incomplete epicardial ablation or at physician’s discretion. Results A total of 130 patients were included (mean age: 65±9.4; 72.3% males); among them, 19.2% and 55.4% had persistent or long-standing persistent AF, respectively. Mean CHA2DS2-VASC and HAS-BLED were 3.1±1.1 and 2.3+-0.5. Five patients (3.8 %) had absolute contraindication to long-term oral anticoagulation, 3 (2.3%) had previous life-threatening bleeding events, 17 (13.1%) had a previous TE event. The final clip size was 35mm in 90.7% cases. Acute success was achieved in 97.7%; failure was due to LAA size (n=1), proximity to phrenic nerve (n=1), or bypass graft (n=1). One patient had incomplete occlusion due to a large secondary lobe, which required a second clip. No periprocedural complications related to clipping were documented. At a mean follow-up of 51±35 months, one (0.8%) patient had a stroke and 3 (2.3%) a transient ischemic attack (4 events per 552 patient/years; 0.7%). One patient had a microreentrant tachycardia mapped from the area near the LAA clipping. Conclusion In a large cohort undergoing hybrid AF ablation, epicardial LAA clipping was safe and highly successful. Acute failure was rare and due to LAA morphology or proximity to phrenic nerve and bypass graft. Thromboembolic event rate was very low.

#606 Impact of real-world off-label dose of apixaban on long-term clinical outcomes in patients with atrial fibrillation and chronic kidney disease

Abstract Background and Aims Apixaban represent one of the cornerstone treatments to prevent cardioembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the choices of Apixaban dose guided by the decision-making process of the physician, which considers specific according to kidney functions are inconsistent in the real-world practice. The objective of the present study is to evaluate the effects of real-world Off-label dose of Apixaban on long-term clinical outcomes in NVAF patients with chronic kidney disease (CKD). Method Our database of AF patients diagnosed with CKD from 2018 to 2023 was used to obtain laboratory, echocardiography, electrocardiogram (ECG), and clinical outcomes data. Inclusion criteria were all AF patients with CKD using Apixaban. And we compared bleeding, systemic thrombotic events including stroke/systemic embolism and death according to off-label real -world dose of Apixaban. Results Among 635 patients with AF and CKD (76.9 ± 10.4 years), 335 (52.8%) patients took off-label underdosed Apixaban. Difference in the baseline characteristics was not observed among patients including CHA2DS2 VASc score and HASBLED score. During the median 18-month follow-up, a lower incidence of bleeding events (P = 0.001) was observed in the off-label underdosed Apixaban group compared to those with standard dose or off-label overdosed Apixaban. However, there was no significant difference of systemic thrombotic events including stroke/systemic embolism and death according to off-label real-world dose of Apixaban (off-label underdose vs. standard dose, P = 1.000; off-label overdose vs. standard dose, P = 1.000; off-label underdose vs. off-label overdose, P = 0.609). In multivariate analysis, HASBLED score was independent risk factors for bleeding events (OR 9.650; CI 1.998-46.622; P = 0.005). Conclusion Compared with standard or off-label overdose of Apixaban, off-label underdose of Apixaban was associated with a lower risk of bleeding in patients with AF and CKD, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing tailored to specific clinical features and drug pharmacokinetics of the Asian patients.

#2374 Long-term clinical outcomes in pediatric patients with primary nephrogenic insipidus

Abstract Background and Aims Nephrogenic diabetes insipidus (NDI) is a rare inherited disorder, and there is a paucity of studies assessing long-term clinical outcomes in affected individuals. This study aims to evaluate the long-term clinical outcomes, encompassing growth and kidney function, in pediatric patients with NDI. Method This multicenter retrospective study included forty-nine children diagnosed with NDI. The medical records of these patients were retrospectively reviewed, and a linear mixed model was employed to analyze variations in growth and kidney function with increasing age. Results Mutations in the AVPR2 and AQP2 genes were identified in 40 (81.6%) and 4 (8.2%) patients, retrospectively, while pathogenic variants were either not found or not tested in 5 (10.2%) patients. The median ages at diagnosis and the last follow-up were 0.41 (interquartile ranges (IQR) 0.12−0.64) years and 9.97 (IQR 2.42−18.66) years, respectively. Thiazide treatment was administered to all patients, with 43 (87.8%) and 14 (28.6%) patients also receiving amiloride and indomethacin, respectively, in conjunction with thiazide. Our analysis using linear mixed models revealed significant changes in growth including height, weight, and body mass index (BMI) with increasing age. The estimated marginal means (EMM) for height Z score decreased from −0.114 (95% confidence interval (CI) −0.507 to 0.279) at diagnosis to −1.464 (95% CI −1.880 to −1.048) at 2 years of age, subsequently increasing to −0.706 (95% CI −1.186 to −0.225) at 14 years of age (P &amp;lt; 0.001). The height Z score at 19 year of age is −0.899 (95% CI −1.434 to −0.365), significantly lower than those at diagnosis (P = 0.038). The EMM for weight Z score increased from −1.580 (95% CI −2.009 to −1.149) at one year of age to 0.760 (95% CI 0.170 to 1.350) at 19 years of age, exhibiting a steady increase (P &amp;lt; 0.001). The EMM for BMI Z score demonstrated a consistent increase after age of 2 years (P &amp;lt; 0.001), which were −0.326 (95% CI −0.835 to 0.182) at 2 years of age and 1.210 (95% CI 0.602 to 1.817) at 19 years of age. The proportion of obesity increased from 3.2% at 3 years of age to 33.3% at 19 years of age. The EMM for estimated glomerular filtration rate (eGFR) consistently increased from 82.8 (95% CI 75.2 to 90.3) mL/min/m2 to 100.8 (95% CI 88.9 to 112.7) mL/min/m2. Although eGFR less than 60 mL/min/m2 is not present, the eGFR less than 90 mL/min/m2 is 47.5% at last follow up. Conclusion At the end of growth, the height Z score is low, and the proportion of obesity is high. To improve the growth pattern, clinicians need to monitor nutritional status and establish nutritional support during follow-up in patients with NDI. Since mild decreased kidney function developed in half, patients with NDI need long-term follow-up evaluation for kidney function.

The critical role of neuroimaging in hemicrania continua: Asystematic review and case series.

Hemicrania continua is a primary unilateral headache characterized by ipsilateral parasympathetic and sympathetic autonomic features. A key diagnostic criterion is its dramatic response to indomethacin treatment; however, various vascular or structural abnormalities have been reported to cause secondary hemicrania continua, presenting with clinical features similar to those of the primary headache presentation. We reviewed the literature to compile secondary hemicrania continua cases, highlighting the importance of imaging during the evaluation. Additionally, we also contributed our three cases to the existing studies. We conducted a review of articles from the PubMed and EMBASE databases that described reported cases of secondary hemicrania continua, covering the period from 1993 to 2021. Our review included detailed patient information, signs, and symptoms of hemicrania continua, as well as information on indomethacin usage and headache resolution (if pertinent). Secondary hemicrania continua can result from a remarkably diverse range of structural and vascular lesions, yet clinical reports on long-term follow-up are lacking. Notably, cases may exhibit a classical response to indomethacin, emphasizing the importance of neuroimaging in excluding secondary cases. Our search yielded 41 cases meeting our criteria. We excluded six cases that were not treated with indomethacin or were unresponsive to it. Additionally, we present three cases that highlight the necessity of neuroimaging in evaluating hemicrania continua, along with short- and long-term clinical outcomes following indomethacin and lesion-directed treatments. Case 1 presented with daily right-sided headaches and cranial autonomic symptoms. Her pain completely resolved with indomethacin use. Neuroimaging of the brain revealed a laterally directed saccular aneurysm of the right internal carotid artery. Case 2 presented with continuous left-sided unilateral headaches with superimposed exacerbations. She complained of left-sided photophobia with a dull sensation in the left ear. Her symptoms decreased after 2 weeks of indomethacin use. Neuroimaging of the head indicated a benign tumor with mass effect into the left lateral medulla and inferior cerebellar peduncle. Case 3 presented with a right side-locked headache with daily, severe superimposed exacerbations. She had photophobia in the right eye and a right-sided Horner's syndrome, along with tearing during her exacerbations. Neuroimaging of the brain revealed a pituitary tumor and her pain completely resolved with indomethacin. Hemicrania continua is a rare headache disorder that can be either primary or secondary. Importantly, response to indomethacin can still occur in secondary hemicrania continua. Thus, neuroimaging should be considered to rule out underlying structural etiology in all cases, regardless of their clinical responsiveness to indomethacin therapy.

#2284 Clinical characteristics and renal survival of patients with monoclonal gammopathy of renal significance (MGRS)

Abstract Background and Aims Monoclonal gammopathy of renal significance (MGRS) comprises a diverse group of renal disorders related to a nephrotoxic monoclonal immunoglobulin. Due to the rarity of the disease and the recent definition of MGRS-associated kidney lesions, data about long-term clinical outcomes remain limited. Method A single-center, retrospective cohort study was conducted including data of all patients with biopsy-proven MGRS who were followed at our center between 2005 and 2023. We examined the clinicopathologic characteristics and renal survival of the patients. Disease progression was defined as an eGFR decline &amp;gt;30% or end-stage kidney disease (ESKD). Univariate Cox regression analysis was used to assess the relationship between clinical features and disease progression. Results A total of 23 adults (males 43.5%) with a median age of 65 years (IQR 55-70) were included in our study. At presentation, median eGFR was 51 ml/min/1.73 m2 (IQR 40-80) and proteinuria 3.94 g/24 h (IQR 2.00-6.26). Serum or urine monoclonal protein was not detected in 4 patients (18.2%). MGRS-associated renal lesions included Ig-related amyloidosis (n = 8), monoclonal immunoglobulin deposition disease (n = 7), cryoglobulinemic glomerulonephritis (n = 2), C3 glomerulopathy (n = 2), proliferative glomerulonephritis with monoclonal IgG deposits (n = 1), immunotactoid glomerulopathy (n = 1) and miscellaneous (n = 2). Most patients were treated with a plasma cell-directed regimen (77.3%) and the rest with B-cell-directed (13.6%) or conservative therapy (9.1%). Median follow-up for the cohort was 45 months (IQR 27-67). Thirteen patients responded to treatment (52.1%), achieving a reduction in proteinuria (0.44 vs 3.94 g/24 h, p:001) and maintenance of eGFR (60 vs 56 ml/min, p:0.363) at the last follow-up visit. All responders had received clone-directed therapy. Disease progression occurred in 8 patients (34.8%), three of whom reached ESKD (13.0%). Renal survival, defined as survival without ESKD, was 84.6% at 48 months (CI 73.3-101.7). Factors that were associated with disease progression were Ig-related amyloidosis (HR: 6.94, CI: 1.30-36.84, p:0.023) and eGFR &amp;lt; 45 ml/min at diagnosis (HR: 14.73, CI: 1.62-132.95, p:0.017). Conclusion MGRS is a heterogeneous clinical entity manifesting with varying degrees of proteinuria and kidney injury. Impaired kidney function at diagnosis and Ig-related amyloidosis correlated with worse renal prognosis in our cohort. Early identification and clone-directed treatment of MGRS may improve long-term renal survival.

#1207 Post transplant diabetes mellitus in kidney transplanted patients: factors related and impact on long-term outcome

Abstract Background Alterations in glucose metabolism are one of the most important complications of renal transplant recipients. The aim of this study was to analyze their prevalence and determinants and assess their influence on the main long-term clinical outcomes in a cohort of kidney transplant recipients. Methods we retrospectively analyzed the data of 832 kidney transplant recipients between 2004 and 2020 in our center. Patients were studied at 1 (T1), 6 (T6), and 12 (T12) months after transplantation and followed clinically for a follow-up time of 103 ± 60 months. At T6, an oral glucose tolerance test (OGTT) was performed in 484 patients. Results The mean age of the cohort studied was 49 ± 13 years, with a mean dialysis vintage of 54 ± 52 months. Hemodialysis was the therapy before KTx in 70.6% of patients, whereas 20.9% had been treated with peritoneal dialysis. The 8.5% of patients received a pre-emptive KTx. Fifty-seven percent of the patients were male and 83.5% had a KTx from a deceased donor. Both at T1 and T12, immunosuppressive therapy was mainly composed of steroids (average cumulative dose at T12: 2914 ± 962 mg), calcineurin inhibitors and mycophenolate. In our cohort at T12, diabetic patients were 237 (28.6%), of which 51 (6.2%) were already affected by diabetes before KTx. Of note, we diagnosed diabetes by OGTT in 23 KTxps, while in 90 KTxps, OGTT showed prediabetic alterations. Patients with glucose metabolism abnormalities were significantly older, had an altered lipid profile associated with higher BMI values and a significantly higher inflammatory index. Interestingly, our data showed that graft loss was not affected by any type of alteration of glucose metabolism. On the contrary, we found that mortality was significantly higher in patients with pre-transplant diabetes and in those with alterations in glucose metabolism detected with OGTT (both including diabetes and considering only IGT and IFG). Conclusions Our data showed that age at transplantation, lipid profile, and the inflammatory state were the variables that most influenced the development of PTDM. Interestingly, mortality was significantly associated with pre-transplant diabetes and alteration in glucose metabolism. This allowed us to highlight the impact of prediabetes status and the importance of OGTT as a screening test in post-transplant and potentially pre-transplant. Future randomized controlled trials will be able to resume the topic, including the analysis of the effects of new antidiabetic drugs.