Renin angiotensin system inhibitors and outcome in patients with Takotsubo syndrome: a propensity score analysis of the GEIST registry.

BACKGROUND: Few data are available on long-term drug therapy and its potential prognostic impact after Takotsubo syndrome (TTS). Aim of the study is to evaluate clinical characteristics and long-term outcome of TTS patients on Renin Angiotensin system inhibitors (RASi). METHODS: TTS patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Median follow-up was 31 (Interquartile range 12-56) months. Comparison of RASi treated vs. untreated patients was performed within the overall population and after 1:1 propensity score matching for age, sex, comorbidities, type of trigger and in-hospital complications. REGISTRATION: clinicaltrials.gov, NCT04361994, https://clinicaltrials.gov/study/NCT04361994 RESULTS: Of the 2453 TTS patients discharged alive, 1683 (68%) received RASi therapy. Patients with RASi were older (age 71±11 vs 69±13 years, p=0.01), with higher prevalence of hypertension (74%vs53%, p<0.01) and diabetes (19%vs15%, p=0.01), higher admission left ventricular ejection fraction (LVEF) (41±11% vs 39±12%, p<0.01) and lower rates of in-hospital complications (18.9% vs 29.6%, p<0.01). At multivariable analysis, RASi therapy at discharge was independently associated with lower mortality (HR 0.63, 95%CI 0.45-0.87, p<0.01). Survival analysis showed that at long term, patients treated with RASi had lower mortality rates in the overall cohort (log-rank p=0.001). However, this benefit was not found among patients treated with RASi in the matched cohort (log-rank p=0.168). Potential survival benefit of RASi were present, both in the overall and matched cohort, in two subgroups: patients with admission LVEF ≤40% (HR 0.54 95%CI 0.38-0.78, p=0.001; HR 0.59, 95%CI 0.37-0.95, p=0.030) and diabetes (HR 0.41, 95%CI 0.23-0.73, p= 0.002; HR 0.41, 95%CI 0.21-0.82, p=0.011). CONCLUSIONS: Long-term therapy with RASi after a TTS episode was not associated with lower mortality rates at propensity score analysis. However, potential survival benefit can be found among patients with admission LVEF ≤40% or diabetes.

Early diagnosis, disease stage and prognosis in wild-type transthyretin amyloid cardiomyopathy: The DIAMOND study.

AIMS: Disease staging and prognostic scoring in wild-type transthyretin-related cardiac amyloidosis (ATTRwt-CA) can be captured by two systems (NAC and Columbia scores). However, uncertainty remains as epidemiology of the disease is evolving rapidly. We evaluated features associated with staging systems across ATTRwt-CA patients from different diagnostic pathways, and their association with prognosis. METHODS: We performed an analysis on DIAMOND patients with available data to evaluate NAC and Columbia score. DIAMOND was a retrospective study from 17 Italian referral centres for CA, enrolling 1281 patients diagnosed between 2016 and 2021, and aimed at describing characteristics of pathways leading to ATTRwt-CA diagnosis. Of the original cohort, 811 patients were included in this analysis. Each patient had NAC and Columbia score calculated. Patients were grouped according to NAC and Columbia scoring classes. We described characteristics of patients according to staging classes and diagnostic pathways at diagnosis. Prevalence of early diagnoses, defined as NAC Ia, NYHA class I, no use of diuretics, no history of heart failure (HF) hospitalizations nor of atrial fibrillation prior to diagnosis, was investigated. Finally, prognostic variables were tested alone and grouped as NAC or Columbia scores in Cox univariate and multivariate regression analyses. Prognosis was investigated as all-cause mortality, in the whole population and dividing patients in HF versus other diagnostic pathways. RESULTS: Only 1% of the study population had an early ATTRwt-CA diagnosis. Distribution of prognostic variables and of NAC and Columbia classes was heterogeneous across diagnostic pathways. The prevalence of NAC III and Columbia III was higher in the HF diagnostic pathway, but all NAC and Columbia classes were present in all pathways. Both NAC and Columbia scores were associated with all-cause mortality at univariate Cox regression analysis in the whole population, in patients from the HF diagnostic pathway and in those from other pathways. At multivariate analysis, Columbia score remained significantly associated with the outcome, together with age at diagnosis, left ventricular ejection fraction and maximal wall thickness. CONCLUSIONS: In this contemporary nationwide cohort, an ATTRwt-CA early diagnosis was very rare. Disease staging with NAC and Columbia scoring systems determined classes of patients with heterogeneous features. Both scores were significantly associated with mortality, but other variables also had prognostic significance.

Association of sex with in-hospital management and outcomes of patients with heart failure: Data from the REAL-HF registry.

BACKGROUND: There are sex differences in HF patients. It is not clear whether such differences mainly reflect cultural behaviours and clinical inertia, and the role of sex on clinical outcomes is still controversial. We aimed to investigate the association of sex with in-hospital management and outcomes in patients with HF. METHODS: We analyzed data of 4016 adult patients hospitalized for HF in 2020 to 2021 and enrolled in a multicentre national registry. RESULTS: Women (n = 1,818 [45%]) were older than men (83 vs 77 years, P < .0001), with a higher prevalence of arterial hypertension (73% vs 69%, P = .011) and atrial fibrillation. Women presented more frequently with HF and preserved ejection fraction -HFpEF (55% vs 32%, P < .001). They were more often hospitalized in internal medicine departments (71% vs 51%), and men in highly specialized cardiology units (49% vs 29%). When considering HF pharmacological treatments at discharge in the subgroup with reduced ejection fraction -HFrEF (n=1525), there were no significant differences (49% of women treated with GDMT [guideline-directed medical therapy] vs 52% of men, P = .197). Sex was not associated either with hospital readmissions (30-days OR [95% CI] = 0.89 [0.71-1.11], P = .304; 1-year OR [95% CI] = 1.02[0.88-1.19], P = .777) or with mortality (in-hospital OR [95% CI] = 1.14 [0.73-1.78], P = .558; 1-year OR [95% CI] = 1.08 [0.87-1.33], P = .478). Similar results were obtained when considering different HF categories based on left ventricular ejection fraction. CONCLUSIONS: Women and men exhibited distinct clinical profiles. Although this may have had an impact on hospital pathways (noncardiology/cardiology units) and pharmacological prescriptions, sex per se did not appear as an independent determinant of clinical choices. Moreover, when considering homogeneous groups, women were not undertreated. Finally, female sex was not associated with worse clinical outcomes.

Degenerative Mitral Regurgitation Outcomes in Asian Compared With European-American Institutions.

Background: Clinical outcome and interventional thresholds for degenerative mitral regurgitation (DMR) were developed in studies of patients at European and American institutions (EAIs), but little is known about patients at Asian institutions (AsIs). Objectives: This study sought to contrast DMR presentation/management/outcomes of AsI patients vs EAI patients. Methods: Patients with DMR due to flail leaflet from Hong Kong and Singapore (AsI cohort, n = 737) were compared with EAI patients (n = 682) enrolled in the MIDA (Mitral regurgitation International Database) registry with similar eligibility criteria. Results: AsI patients presented similar DMR lesion/consequences vs EAI patients, but they were younger, with fewer symptoms (74% vs 44% Class I), more sinus rhythm (83% vs 69%), and lower EuroSCORE II (European System for Cardiac Operative Risk Evaluation II) (0.9 ± 0.5 vs 1.4 ± 1.5; all P < 0.0001). Imaging showed smaller absolute left atrial/ventricular dimensions in AsI patients, belying cardiac dilatation with larger body surface area-indexed diameters (all P < 0.01). Surgical/interventional mitral repair was similarly predominant (90% vs 91%; P = 0.47), and early repair was similarly beneficial (for AsI patients, adjusted HR: 0.28; 95% CI: 0.16-0.49; for EAI patients, HR: 0.32; 95% CI: 0.20-0.49; both P < 0.0001). However, AsI patients underwent fewer interventions (55% ± 2% vs 77% ± 2% at 1 year; P < 0.0001) and incurred excess mortality (adjusted HR: 1.60 [95% CI: 1.13-2.27] vs EAI patients; P = 0.008) at long-term postdiagnosis. Propensity score matching (434 patient pairs), which balanced all clinical characteristics, confirmed that there was undertreatment and excess mortality in the long term in AsI patients with DMR (P < 0.0001). Conclusions: Imaging may underestimate volume overload in AsI patients due to smaller cardiac cavities related to smaller body size compared with EAI patients with similar mitral lesions and DMR severity. AsI patients enjoy similar mitral repair predominance and early intervention benefits but undergo fewer mitral interventions than EAI patients and incur subsequent excess mortality, suggesting the need to account for imaging and cultural specificity to improve DMR outcomes worldwide.

Posterior wall ablation for persistent atrial fibrillation: Very-high-power short-duration versus standard-power radiofrequency ablation.

Background: Posterior wall ablation (PWA) is commonly added to pulmonary vein isolation (PVI) during catheter ablation (CA) of persistent atrial fibrillation (AF). Objective: The purpose of this study was to compare PVI plus PWA using very-high-power short-duration (vHPSD) vs standard-power (SP) ablation index-guided CA among consecutive patients with persistent AF and to determine the voltage correlation between microbipolar and bipolar mapping in AF. Methods: We compared 40 patients undergoing PVI plus PWA using vHPSD to 40 controls receiving PVI plus PWA using SP. The primary efficacy endpoint was recurrence of atrial tachyarrhythmias after a 3-month blanking period. The primary safety outcome was a composite of major complications within 30 days after CA. In the vHPSD group, high-density mapping of the posterior wall was performed using both a multipolar catheter and microelectrodes on the tip of the ablation catheter. Results: PVI was more commonly obtained with vHPSD compared to SP ablation (98%vs 75%; P = .007), despite shorter procedural and fluoroscopy times (P <.001). Survival free from recurrent atrial tachyarrhythmias at 18 months was 68% and 47% in the vHPSD and SP groups, respectively (log-rank P = .071), without major adverse events. The vHPSD approach was significantly associated with reduced risk of recurrent AF at multivariable analysis (hazard ratio 0.39; P = .030). Microbipolar voltage cutoffs of 0.71 and 1.69 mV predicted minimum bipolar values of 0.16 and 0.31 mV in AF, respectively, with accuracies of 0.67 and 0.88. Conclusion: vHPSD PWA plus PVI may be faster and as safe as SP CA among patients with persistent AF, with a trend for superior efficacy. Adapted voltage cutoffs should be used for identifying atrial low-voltage areas with microbipolar mapping.

Survival loss linked to guideline-based indications for degenerative mitral regurgitation surgery.

AIMS: Operating on patients with severe degenerative mitral regurgitation (DMR) is based on ACC/AHA or ESC/EACTS-guidelines. Doubts persist on best surgical indications and their potential association with postoperative survival loss. We sought to investigate whether guideline-based indications lead to late postoperative survival loss in DMR-patients. METHODS AND RESULTS: : We analyzed outcome of 2833 patients from the MIDA-registry undergoing surgical correction of DMR. Patients were stratified by surgical indications: Class-I-trigger (symptoms, left ventricular end-systolic diameter≥40mm, or left ventricular ejection fraction<60%, n=1677), isolated-Class-IIa-trigger (atrial fibrillation [AF], pulmonary hypertension [PH], or left atrial diameter≥55mm, n=568), or no-trigger (n=588). Postoperative survival was compared after matching for clinical differences. Restricted-mean-survival time (RMST) was analyzed. During a median 8.5-year follow-up, 603 deaths occurred. Long-term postoperative survival was lower with Class-I-trigger than in Class-IIa-trigger and no-trigger (71.4±1.9%, 84.3±2.3%, 88.9±1.9% at 10 years, p<0.001). Having at least one Class-I-criterion led to excess mortality (p<0.001), while several Class-I-criteria conferred additional death-risk (HR:1.53, 95%CI:1.42-1.66). Isolated-Class-IIa-triggers conferred an excess mortality risk versus those without (HR:1.46, 95%CI:1.00-2.13, p=0.05). Among these patients, isolated-PH led to decreased postoperative-survival versus those without (83.7%±2.8% vs. 89.3%±1.6%, p=0.011), with the same pattern observed for AF (81.8%±5.0% vs. 88.3%±1.5%, p=0.023). According to RMST-analysis, compare to those operated on without triggers, operating on Class-I-trigger patients led to 9.4-month survival-loss (p<0.001) and operating on isolated-Class-IIa-trigger patients displayed 4.9-month survival loss (p=0.001) after 10-years. CONCLUSIONS: : Waiting for the onset of Class-I or isolated-Class-IIa-triggers before operating on DMR patients is associated with postoperative survival loss. These data encourage an early surgical-strategy.

Left Ventricular Twist and the "Rigid Body Rotation" Pattern in Patients Treated with Anthracyclines or Anti-HER2.

Background: During the physiological cardiac cycle, the helix orientation of the muscle fibres induces the rotation of the apex relative to the base of the left ventricular (LV). In heart failure, LV torsion is impaired, and rotation at basal and apical levels occurs in the same direction, a phenomenon called rigid body rotation (RBR). We aimed to evaluate whether the RBR pattern and GLS together could improve the diagnosis of cardiotoxicity in patients treated with anthracyclines and/or anti-HER2. Methods: With an observational, retrospective study involving 175 patients (mean age 55 ± 12 years, 94% females), we evaluated the development of cancer therapeutic-related cardiac dysfunction (CTRCD) defined according to ESC guidelines. We characterised LV dysfunction by echocardiographic standard and speckle-tracking (GLS and RBR pattern) measurements. Patients with a previous diagnosis of structural heart disease or atrial fibrillation were excluded. Results: At the time of enrolment, the chemotherapy regimen included trastuzumab (96%), pertuzumab (21%), and anthracyclines (13%). Twenty-two patients (12.5%) developed cardiotoxicity, and thirteen patients developed an RBR within 6 months of follow-up. In all cases, the RBR pattern was associated with cardiotoxicity (p < 0.001), reporting an optimal specificity but poor sensitivity at three and six months. However, the addition of the RBR pattern to the global longitudinal strain (GLS) ≥ -16% increased the odds ratio (OR) from 25.6 to 32.6 at three months and from 32.5 to 49.6 at six months rather than GLS alone. Conclusions: The RBR pattern improves the diagnostic accuracy of GLS for the detection of cardiotoxicity secondary to anthracyclines and anti-HER2-based treatments.

[Cardiac arrest in school: the role of teachers as BLS-D providers]. / Trattamento dell'arresto cardiaco nel contesto scolastico: percezione degli insegnanti come operatori laici di BLS-D.

BACKGROUND: The implementation of BLS-D training courses in the school setting aims to increase the number of future citizens competent in the recognition and treatment of out-of-hospital cardiac arrest to increase overall survival. It is important to make teachers and students aware of their social responsibilities, consolidating collaboration with healthcare professionals. The present study investigates, through a cross-sectional cognitive survey, the perception of the importance of knowledge and diffusion of basic BLS manoeuvres and early defibrillation in the treatment of cardiac arrest. METHODS: An anonymous questionnaire was sent to secondary school teachers, divided into 14 questions: 12 items in closed form according to the Delphi method and the 5-point Likert rating scale, and the last two with different response methods. RESULTS: The total number of teachers who participated in the survey was 120. The majority of respondents believe that it is essential to know and transmit notions related to BLS-D to students, without the need to have an official certification as an instructor. Most of the teachers consider useful to have specific information on the placement and use of the defibrillator, to set reminder systems on life-saving manoeuvres and to share protocols on the management of cardiac arrest. CONCLUSIONS: The introduction of BLS-D training at school determines a constant increase in competent students and therefore the birth of a network of people educated in the management of out-of-hospital cardiac arrest. The teaching skills of teachers also allow them to identify the best strategies to make the learning method clear and valid for students. The autonomy of teachers in fulfilling the role of instructors is still poorly consolidated and shared, thus requiring the support of healthcare professionals.

Human DNA topoisomerase I poisoning causes R loop-mediated genome instability attenuated by transcription factor IIS.

DNA topoisomerase I can contribute to cancer genome instability. During catalytic activity, topoisomerase I forms a transient intermediate, topoisomerase I-DNA cleavage complex (Top1cc) to allow strand rotation and duplex relaxation, which can lead to elevated levels of DNA-RNA hybrids and micronuclei. To comprehend the underlying mechanisms, we have integrated genomic data of Top1cc-triggered hybrids and DNA double-strand breaks (DSBs) shortly after Top1cc induction, revealing that Top1ccs increase hybrid levels with different mechanisms. DSBs are at highly transcribed genes in early replicating initiation zones and overlap with hybrids downstream of accumulated RNA polymerase II (RNAPII) at gene 5'-ends. A transcription factor IIS mutant impairing transcription elongation further increased RNAPII accumulation likely due to backtracking. Moreover, Top1ccs can trigger micronuclei when occurring during late G1 or early/mid S, but not during late S. As micronuclei and transcription-replication conflicts are attenuated by transcription factor IIS, our results support a role of RNAPII arrest in Top1cc-induced transcription-replication conflicts leading to DSBs and micronuclei.

Speckle-tracking global longitudinal strain predicts death and cardiovascular events in patients with systemic sclerosis.

Aims: Albeit often asymptomatic, heart involvement in systemic sclerosis (SSc) represents a negative prognostic factor, accounting for nearly one-fourth of all deaths. Global longitudinal strain (GLS) is accurate in detecting heart involvement in patients with SSc and no overt cardiac disease and allows early detection and longitudinal monitoring, but its association with clinical endpoints has not been tested so far. The primary outcome was the association between left and right GLS and mortality for all causes. The secondary outcome was the association between left and right GLS and hospitalizations. Methods and results: A prospective longitudinal study enrolling all consecutive patients with SSc without structural heart disease or previous cardiovascular event.A total of 164 patients were enrolled, of whom 19 (11.5%) died during follow-up and 48 (29.3%) were hospitalized. Both left (LV) and right ventricle (RV) GLS at enrolment were independently associated with an increased risk of death for all causes and hospitalizations. Patients with biventricular GLS impairment, respectively, had a 4.2-, 4.9-, and 13.9-fold increased risk of death when compared with patients with only LV, only RV, or no impairment (P < 0.001). The incidence of hospitalization in patients with biventricular GLS impairment was nearly four times higher when compared with patients with only LV or only RV impairment, and nine times higher when compared with normal biventricular GLS (P < 0.001). Conclusion: Biventricular GLS is associated with an increased risk of death and hospitalization in patients with SSc during a median of 3-year follow-up, acting as a reliable and accurate prognostic tool in everyday practice.

Novel Medical Treatments and Devices for the Management of Heart Failure with Reduced Ejection Fraction.

Heart failure (HF) is a growing issue in developed countries; it is often the result of underlying processes such as ischemia, hypertension, infiltrative diseases or even genetic abnormalities. The great majority of the affected patients present a reduced ejection fraction (≤40%), thereby falling under the name of "heart failure with reduced ejection fraction" (HFrEF). This condition represents a major threat for patients: it significantly affects life quality and carries an enormous burden on the whole healthcare system due to its high management costs. In the last decade, new medical treatments and devices have been developed in order to reduce HF hospitalizations and improve prognosis while reducing the overall mortality rate. Pharmacological therapy has significantly changed our perspective of this disease thanks to its ability of restoring ventricular function and reducing symptom severity, even in some dramatic contexts with an extensively diseased myocardium. Notably, medical therapy can sometimes be ineffective, and a tailored integration with device technologies is of pivotal importance. Not by chance, in recent years, cardiac implantable devices witnessed a significant improvement, thereby providing an irreplaceable resource for the management of HF. Some devices have the ability of assessing (CardioMEMS) or treating (ultrafiltration) fluid retention, while others recognize and treat life-threatening arrhythmias, even for a limited time frame (wearable cardioverter defibrillator). The present review article gives a comprehensive overview of the most recent and important findings that need to be considered in patients affected by HFrEF. Both novel medical treatments and devices are presented and discussed.

A Novel Approach to Cardiac Magnetic Resonance Scar Characterization in Patients Affected by Cardiac Amyloidosis: A Pilot Study.

Background and Objectives: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. Materials and Methods: This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. Results: A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary (p = 0.003) and the secondary outcome of pacemaker implantation (p = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance (p = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. Conclusions: CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study.

Conduction system disease management in patients candidate and/or treated for the aortic valve disease: an Italian Survey promoted by Italian Association of Arrhythmology and Cardiac Pacing (AIAC).

BACKGROUND: Conduction system disorders represent a frequent complication in patients undergoing surgical (surgical aortic valve replacement, SAVR) or percutaneous (transcatheter aortic valve implantation, TAVI) aortic valve replacement. The purpose of this survey was to evaluate experienced operators approach in this clinical condition. METHODS: This survey was independently conducted by the Italian Association of Arrhythmology and Cardiac Pacing (AIAC) and it consisted of 24 questions regarding the respondents' profile, the characteristics of participating centres, and conduction disease management in different scenarios. RESULTS: Fifty-five physicians from 55 Italian arrhythmia centres took part in the survey. Prophylactic pacemaker implantation is rare. In case of persistent complete atrioventricular block (AVB), 49% and 73% respondents wait less than one week before implanting a definitive pacemaker after SAVR and TAVI, respectively. In case of second degree AVB, the respondents wait some days more for definitive implantation. Respondents consider bundle branch blocks, in particular pre-existing left bundle branch block (LBBB), the worst prognostic factors for pacemaker implantation after TAVI. The implanted valve type is considered a relevant element to evaluate. In patients with new-onset LBBB and severe/moderate left ventricular systolic dysfunction, respondents would implant a biventricular pacemaker in 100/55% of cases, respectively. CONCLUSIONS: Waiting time before a definitive pacemaker implantation after aortic valve replacement has reduced compared to the past, and it is anticipated in TAVI vs. SAVR. Bundle branch blocks are considered the worse prognostic factor for pacemaker implantation after TAVI. The type of pacemaker implanted in new-onset LBBB patients without severe left ventricular systolic dysfunction is heterogeneous.

Complications of left bundle branch area pacing compared with biventricular pacing in candidates for resynchronization therapy: Results of a propensity score-matched analysis from a multicenter registry.

BACKGROUND: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well-established therapy in patients with reduced left ventricular ejection fraction, heart failure, and left bundle branch block. Left bundle branch area pacing (LBBAP) has recently been shown to be a feasible and effective alternative to BVP. Comparative data on the risk of complications between LBBAP and BVP among patients undergoing CRT are lacking. OBJECTIVE: The aim of this study was to compare the long-term risk of procedure-related complications between LBBAP and BVP in a cohort of patients undergoing CRT. METHODS: This prospective, multicenter, observational study enrolled 668 consecutive patients (mean age 71.2 ± 10.0 years; 52.2% male; 59.4% with New York Heart Association class III-IV heart failure symptoms) with left ventricular ejection fraction 33.4% ± 4.3% who underwent BVP (n = 561) or LBBAP (n = 107) for a class I or II indication for CRT. Propensity score matching for baseline characteristics yielded 93 matched pairs. The rate and nature of intraprocedural and long-term post-procedural complications occurring during follow-up were prospectively collected and compared between the 2 groups. RESULTS: During a mean follow-up of 18 months, procedure-related complications were observed in 16 patients: 12 in BVP (12.9%) and 4 in LBBAP (4.3%) (P = .036). Compared with patients who underwent LBBAP, those who underwent BVP showed a lower complication-free survival (P = .032). In multivariate analysis, BVP resulted an independent predictive factor associated with a higher risk of complications (hazard ratio 3.234; P = .042). Complications related to the coronary sinus lead were most frequently observed in patients who underwent BVP (50.0% of all complications). CONCLUSION: LBBAP was associated with a lower long-term risk of device-related complications compared with BVP in patients with an indication for CRT.

Giant aneurysm of the left atrial appendage: a case report.

Background: Left atrial appendage aneurysm (LAAA) is a rare condition mostly due to congenital malformations or secondary causes (i.e. mitral regurgitation). Case summary: We present a case of a 47-year-old male with a history of atrial fibrillation treated with propafenone presented to our emergency department for palpitation and epigastric pain. The electrocardiogram showed atrial fibrillation at high ventricular rate and a new-onset left bundle branch block. Urgent coronary angiogram excluded coronary artery disease. Echocardiography and cardiac magnetic resonance revealed a giant LAAA. The electrocardiogram alterations were deemed secondary to aberrancy and treatment with class IC antiarrhythmic. The patient was discussed in the heart team, and considering his will to avoid surgery, he was managed conservatively with closed follow-up, anticoagulant and antiarrhythmic therapy, and internal loop recorder. At 1-year follow-up, he showed asymptomatic and without arrhythmias. Discussion: Few cases are described in the literature; therefore, there is uncertainty in treatment and prognosis. Diagnosis is achieved with multimodality imaging. Treatment can be surgical with aneurysmectomy or conservative with regular follow-up by imaging examinations and pharmacological therapy aimed to prevent complications such as thrombosis and arrhythmias. Since high-quality scientific data are lacking, shared decision-making is essential for the management of patients affected by LAAA. In our clinical case, our patient's will to not undergo surgery was considered, and therefore, a conservative management with strict follow-up and medications was chosen.

Age-Related Differences in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

BACKGROUND: The role of age in the short- and long-term prognosis of takotsubo syndrome (TTS) is controversial. The aim of the present study was to evaluate age-related differences and prognostic implications among patients with TTS. METHODS AND RESULTS: In total, 2492 consecutive patients with TTS enrolled in an international registry were stratified into 4 groups (<45, 45-64, 65-74, and ≥75 years). The median long-term follow-up was 480 days (interquartile range, 83-1510 days). The primary outcome was all-cause mortality (in-hospital and out-of-hospital mortality). The secondary end point was TTS-related in-hospital complications. Among the 2479 patients, 58 (2.3%) were aged <45 years, 625 (25.1%) were aged 45 to 64 years, 733 (29.4%) were aged 65 to 74 years, and 1063 (42.6%) were aged ≥75 years. Young patients (<45 years) had a higher prevalence of men (from youngest to oldest, 24.1% versus 12.6% versus 9.7% versus 11.4%; P<0.01), physical triggers (46.6% versus 27.5%, 33.9%, and 38.4%; P<0.01), and non-apical forms of TTS (25.9% versus 23.7%, 12.7%, and 9%; P<0.01) than those aged 45 to 64, 65 to 74, and ≥75 years. During hospitalization, young patients experienced a higher rate of in-hospital complications (32.8% versus 23.4%, 27.4%, and 31.9%; P=0.01), but in-hospital mortality was higher in the older group (0%, 1.6%, 2.9%, and 5%; P=0.001). Long-term all-cause mortality was significantly higher in the older cohort (5.6%, 6.4%, 11.3%, and 22.3%; log-rank P<0.001), as was long-term cardiovascular mortality (0%, 0.9%, 1.9%, and 3.2%; log-rank P=0.01). CONCLUSIONS: Young patients with TTS have a typical phenotype characterized by a higher prevalence of male sex, non-apical ballooning patterns, and in-hospital complications. However, in-hospital and long-term mortality are significantly lower in young patients with TTS. REGISTRATION: URL: https://classic.clinicaltrials.gov/ct2/show/NCT04361994. Unique identifier: NCT04361994.

Neurological Disorders in Takotsubo Syndrome: Clinical Phenotypes and Outcomes.

BACKGROUND: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS-associated neurological phenotypes and outcome. METHODS AND RESULTS: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short- and long-term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in-hospital stay (8 [interquartile range, 5-12] versus 6 [interquartile range, 5-9] days; P<0.01) and more often experienced in-hospital complications (27% versus 16%; P=0.01) mainly driven by cardiogenic shock and in-hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P<0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long-term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P<0.01). Neurological disorder was an independent predictor of both the 60-day and long-term mortality rate (odds ratio, 1.78 [95% CI, 1.07-2.97]; P=0.02; hazard ratio, 1.72 [95% CI, 1.33-2.22]; both P<0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long-term mortality rates, 29.2% and 9.7%, respectively). CONCLUSIONS: Neurological disorders identify a high-risk TTS subgroup for enhanced short- and long-term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed.

Long-term clinical outcomes of patients with drug-induced type 1 Brugada electrocardiographic pattern: A nationwide cohort registry study.

BACKGROUND: There are limited real-world data on the extended prognosis of patients with drug-induced type 1 Brugada electrocardiogram (ECG). OBJECTIVE: We assessed the clinical outcomes and predictors of life-threatening arrhythmias in patients with drug-induced type 1 Brugada ECG. METHODS: This multicenter retrospective study, conducted at 21 Italian and Swiss hospitals from July 1997 to May 2021, included consecutive patients with drug-induced type 1 ECG. The primary outcome, a composite of appropriate ICD therapies and sudden cardiac death, was assessed along with the clinical predictors of these events. RESULTS: A total of 606 patients (mean age 49.7 ± 14.7 years; 423 [69.8%] men) were followed for a median of 60.3 months (interquartile range 23.0-122.4 months). Nineteen patients (3.1%) experienced life-threatening arrhythmias, with a median annual event rate of 0.5% over 5 years and 0.25% over 10 years. The SCN5A mutation was the only predictor of the primary outcome (hazard ratio 4.54; P = .002), whereas a trend was observed for unexplained syncope (hazard ratio 3.85; P = .05). In patients who were asymptomatic at presentation, the median annual rate of life-threatening arrhythmias is 0.24% over 5 years and increases to 1.2% if they have inducible ventricular fibrillation during programmed ventricular stimulation. CONCLUSION: In patients with drug-induced type 1 Brugada ECG, the annual risk of life-threatening arrhythmias is low, with the SCN5A mutation as the only independent predictor. Unexplained syncope correlated with worse clinical outcomes. Ventricular fibrillation inducibility at programmed ventricular stimulation significantly increases the median annual rate of life-threatening arrhythmias from 0.24% to 1.2% over 5 years.

High-power short-duration catheter ablation of atrial fibrillation: is it really a new era? Comparison between new and old radiofrequency contact force-sensing catheters.

BACKGROUND: The clinical performance of high-power, short-duration (HPSD) pulmonary vein isolation (PVI) with the novel flexible tip TactiFlex™ (TFSE) catheter, as compared to standard-power, long-duration (SPLD) PVI using the TactiCath™ (TCSE) catheter among patients undergoing catheter ablation (CA) of atrial fibrillation (AF) is currently unknown. METHODS: We conducted a prospective, observational, single-centre study including 40 consecutive patients undergoing PVI for paroxysmal/persistent AF, using HPSD ablation with the novel TFSE catheter (HPSD/TFSE group). Based on propensity score-matching, forty patients undergoing SPLD PVI with the TCSE catheter were identified (SPLD/TCSE group). In the HPSD/TFSE group, RF lesions were performed by delivering 40-50 W for 10-20 s, while in the SPLD/TCSE group, RF power was 30-35 W, targeting a lesion size index (LSI) of 4.0-5.5. The co-primary study outcomes were time required to complete PVI and first pass isolation (FPI). RESULTS: PVI was achieved in 100% of patients in both groups, and no major adverse events were observed. Remarkably, PVI time was shorter in the HPSD/TFSE, compared to the SPLD/TCSE group(9 [7-9] min vs. 50 [37-54] min; p < 0.001), while FPI rate was non-significantly higher in the former group(91% [146/160] vs 83% [134/160]; p = 0.063). Shorter procedural (108 [91-120] min vs. 173 [139-187] min, p < 0.001), total RF (9 [7-11] min vs. 43 [32-53] min, p < 0.001), fluoroscopy times(15 [10-19] min vs. 18 [13-26] min, p = 0.014), and lower DAP (1461 [860-2181] vs. 7200 [3400-20,800], p < 0.001) were recorded in the HPSD/TFSE group. A higher average impedance drop was obtained with HPSD/TFSE CA(17[17-18]Ω vs. 16 [15-17] Ω, p < 0.001). CONCLUSIONS: In our initial clinical experience, HPSD PVI with the TFSE catheter proved faster than SPLD PVI with the TCSE catheter, at least equally effective in terms of FPI, and it was associated with greater impedance drop.