Personalized pulmonary vein isolation with very high-power short-duration lesions guided by left atrial wall thickness: the QDOT-by-LAWT randomized trial.

AIMS: Pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) using very high-power short-duration (vHPSD) radiofrequency (RF) ablation proved to be safe and effective. However, vHPSD applications result in shallower lesions that might not be always transmural. Multidetector computed tomography-derived left atrial wall thickness (LAWT) maps could enable a thickness-guided switching from vHPSD to the standard-power ablation mode. The aim of this randomized trial was to compare the safety, the efficacy, and the efficiency of a LAWT-guided vHPSD PVI approach with those of the CLOSE protocol for PAF ablation (NCT04298177). METHODS AND RESULTS: Consecutive patients referred for first-time PAF ablation were randomized on a 1:1 basis. In the QDOT-by-LAWT arm, for LAWT ≤2.5 mm, vHPSD ablation was performed; for points with LAWT > 2.5 mm, standard-power RF ablation titrating ablation index (AI) according to the local LAWT was performed. In the CLOSE arm, LAWT information was not available to the operator; ablation was performed according to the CLOSE study settings: AI ≥400 at the posterior wall and ≥550 at the anterior wall. A total of 162 patients were included. In the QDOT-by-LAWT group, a significant reduction in procedure time (40 vs. 70 min; P < 0.001) and RF time (6.6 vs. 25.7 min; P < 0.001) was observed. No difference was observed between the groups regarding complication rate (P = 0.99) and first-pass isolation (P = 0.99). At 12-month follow-up, no significant differences occurred in atrial arrhythmia-free survival between groups (P = 0.88). CONCLUSION: LAWT-guided PVI combining vHPSD and standard-power ablation is not inferior to the CLOSE protocol in terms of 1-year atrial arrhythmia-free survival and demonstrated a reduction in procedural and RF times.

Scar architecture affects the electrophysiological characteristics of induced ventricular arrhythmias in hypertrophic cardiomyopathy.

AIMS: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) detects myocardial scarring, a risk factor for ventricular arrhythmias (VAs) in hypertrophic cardiomyopathy (HCM). The LGE-CMR distinguishes core, borderzone (BZ) fibrosis, and BZ channels, crucial components of re-entry circuits. We studied how scar architecture affects inducibility and electrophysiological traits of VA in HCM. METHODS AND RESULTS: We correlated scar composition with programmed ventricular stimulation-inducible VA features using LGE intensity maps. Thirty consecutive patients were enrolled. Thirteen (43%) were non-inducible, 6 (20%) had inducible non-sustained, and 11 (37%) had inducible sustained mono (MMVT)- or polymorphic VT/VF (PVT/VF). Of 17 induced VA, 13 (76%) were MMVT that either ended spontaneously, persisted as sustained monomorphic, or degenerated into PVT/VF. Twenty-seven patients (90%) had LGE. Of these, 17 (57%) had non-sustained or sustained inducible VA. Scar mass significantly increased (P = 0.002) from non-inducible to inducible non-sustained and sustained VA patients in both the BZ and core components. Borderzone channels were found in 23%, 67%, and 91% of non-inducible, inducible non-sustained, and inducible sustained VA patients (P = 0.003). All 13 patients induced with MMVT or monomorphic-initiated PVT/VF had LGE. The origin of 10/13 of these VTs matched scar location, with 8/10 of these LGE regions showing BZ channels. During follow-up (20 months, interquartile range: 7-37), one patient with BZ channels and inducible PVT had an ICD shock for VF. CONCLUSION: Scar architecture determines inducibility and electrophysiological traits of VA in HCM. Larger studies should explore the role of complex LGE patterns in refining risk assessment in HCM patients.

Conduction System Stimulation to Avoid Left Ventricle Dysfunction.

BACKGROUND: Right ventricular apical pacing (RVAP) can produce left ventricle dysfunction. Conduction system pacing (CSP) has been used successfully to reverse left ventricle dysfunction in patients with left bundle branch block. To date, data about CSP prevention of left ventricle dysfunction in patients with preserved left ventricular ejection fraction (LVEF) are scarce and limited mostly to nonrandomized studies. Our aim is to demonstrate that CSP can preserve normal ventricular function compared with RVAP in the setting of a high burden of ventricular pacing. METHODS: Consecutive patients with a high-degree atrioventricular block and preserved or mildly deteriorated LVEF (>40%) were included in this prospective, randomized, parallel, controlled study, comparing conventional RVAP versus CSP. RESULTS: Seventy-five patients were randomized, with no differences between basal characteristics in both groups. The stimulated QRS duration was significantly longer in the RVAP group compared with the CSP group (160.4±18.1 versus 124.2±20.2 ms; p<0.01). Seventy patients were included in the intention-to-treat analyses. LVEF showed a significant decrease in the RVAP group at 6 months compared with the CSP group (mean difference, -5.8% [95% CI, -9.6% to -2%]; P<0.01). Left ventricular end-diastolic diameter showed an increase in the RVAP group compared with the CSP group (mean difference, 3.2 [95% CI, 0.1-6.2] mm; P=0.04). Heart failure-related admissions were higher in the RVAP group (22.6% versus 5.1%; P=0.03). CONCLUSIONS: Conduction system stimulation prevents LVEF deterioration and heart failure-related admissions in patients with normal or mildly deteriorated LVEF requiring a high burden of ventricular pacing. These results are only short term and need to be confirmed by further larger studies. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06026683.

Assessing left atrial intramyocardial fat infiltration from computerized tomography angiography in patients with atrial fibrillation.

AIMS: Epicardial adipose tissue might promote atrial fibrillation (AF) in several ways, including infiltrating the underlying atrial myocardium. However, the role of this potential mechanism has been poorly investigated. The aim of this study is to evaluate the presence of left atrial (LA) infiltrated adipose tissue (inFAT) by analysing multi-detector computer tomography (MDCT)-derived three-dimensional (3D) fat infiltration maps and to compare the extent of LA inFAT between patients without AF history, with paroxysmal, and with persistent AF. METHODS AND RESULTS: Sixty consecutive patients with AF diagnosis (30 persistent and 30 paroxysmal) were enrolled and compared with 20 age-matched control; MDCT-derived images were post-processed to obtain 3D LA inFAT maps for all patients. Volume (mL) and mean signal intensities [(Hounsfield Units (HU)] of inFAT (HU -194; -5), dense inFAT (HU -194; -50), and fat-myocardial admixture (HU -50; -5) were automatically computed by the software. inFAT volume was significantly different across the three groups (P = 0.009), with post-hoc pairwise comparisons showing a significant increase in inFAT volume in persistent AF compared to controls (P = 0.006). Dense inFAT retained a significant difference also after correcting for body mass index (P = 0.028). In addition, more negative inFAT radiodensity values were found in AF patients. Regional distribution analysis showed a significantly higher regional distribution of LA inFAT at left and right superior pulmonary vein antra in AF patients. CONCLUSION: Persistent forms of AF are associated with greater degree of LA intramyocardial adipose infiltration, independently of body mass index. Compared to controls, AF patients present higher LA inFAT volume at left and right superior pulmonary vein antra.

Clinical impact of aging on outcomes of cardioneuroablation for reflex syncope or functional bradycardia: Results from the cardionEuroabLation: patiEnt selection, imaGe integrAtioN and outComEs-The ELEGANCE multicenter study.

BACKGROUND: Cardioneuroablation (CNA) is a novel treatment for reflex syncope. The effect of aging on CNA efficacy is not fully understood. OBJECTIVE: The purpose of this study was to assess the impact of aging on candidacy and efficacy of CNA for treating vasovagal syncope (VVS), carotid sinus syndrome (CSS), and functional bradyarrhythmia. METHODS: The ELEGANCE (cardionEuroabLation: patiEnt selection, imaGe integrAtioN and outComEs) multicenter study assessed CNA in patients with reflex syncope or severe functional bradyarrhythmia. Patients underwent pre-CNA Holter electrocardiography (ECG), head-up tilt testing (HUT), and electrophysiological study. CNA candidacy and efficacy was assessed in 14 young (18-40 years), 26 middle-aged (41-60 years), and 20 older (>60 years) patients. RESULTS: Sixty patients (37 men; mean age 51 ± 16 years) underwent CNA. The majority (80%) had VVS, 8% had CSS, and 12% had functional bradycardia/atrioventricular block. Pre-CNA Holter ECG, HUT, and electrophysiological findings did not differ across age groups. Acute CNA success was 93%, without differences between age groups (P = .42). Post-CNA HUT response was negative in 53%, vasodepressor in 38%, cardioinhibitory in 7%, and mixed in 2%, without differences across age groups (P = .59). At follow-up (8 months, interquartile range 4-15), 53 patients (88%) were free of symptoms. Kaplan-Meier curves did not show differences in event-free survival between age groups (P = .29). The negative predictive value of a negative HUT was 91.7%. CONCLUSION: CNA is a viable treatment for reflex syncope and functional bradyarrhythmia in all ages, and is highly effective in mixed VVS. HUT is a key step in postablation clinical assessment.

Accuracy of standard bipolar amplitude voltage thresholds to identify late potential channels in ventricular tachycardia ablation.

BACKGROUND: Ventricular tachycardia (VT) is caused by the presence of a slow conduction channel (CC) of border zone (BZ) tissue inside the scar-core tissue. Electroanatomic mapping can depict this tissue by voltage mapping. Areas of slow conduction can be detected as late potentials (LPs) and their abolition is the most accepted ablation endpoint. In the current guidelines, bipolar voltage thresholds for BZ and core scar are 1.5 and 0.5 mV respectively. The performance of these values is controversial. The aim of the study is to analyze the diagnostic yield of current amplitude thresholds in voltage map to define VT substrate in terms of CCs of LPs. Predictors of usefulness of current thresholds will be analyzed. METHODS: All patients with structural heart disease who underwent VT ablation in Hospital Clinic in 2016-2017 were included. Maps with delineation of CCs based on LPs were created with contact force sensor catheter. Thresholds were adjusted for every patient based on CCs. Diagnostic yield and predictors of performance of conventional thresholds were analyzed. RESULTS: During study period, 57 consecutive patients were included (age: 60.4 ± 8.5; 50.2% ischemic cardiomyopathy, LVEF 39.8 ± 13.5%). Cutoff voltages that better identified the scar and BZ according to the LP channels were 0.32 (0.02-2 mV) and 1.84 (0.3-6 mV) respectively. Current voltage thresholds identified correctly core and BZ in 87.7% and 42.1% of the patients respectively. Accuracy was worse in non-ischemic cardiomyopathy (NICM) especially for BZ (28.6% vs 55.2%, p = 0.042). CONCLUSIONS: Accuracy of standard voltage thresholds for scar and BZ is poor in terms of LPs detection. Diagnostic yield is worse in NICM patients specially for border zone.

Late Potential Abolition in Ventricular Tachycardia Ablation.

Ventricular tachycardia (VT) substrate-based ablation has become the gold standard treatment for patients with structural heart disease-related VT. VT is linked to re-entry in relation to myocardial scarring, with areas of conduction block (core scar) and of slow conduction (border zone). Slow conduction areas can be detected in sinus rhythm as late potentials (LPs). LP abolition has been shown to be the best end point to avoid long-term recurrences. Our study aimed to analyze the challenges of LP abolition and the predictors of failure. We analyzed 169 consecutive patients with structural heart disease (61% ischemic cardiomyopathy, left ventricular ejection fraction: 37 ± 13%) who underwent VT ablation between 2013 and 2018. A preprocedural clinical evaluation, including cardiac magnetic resonance, was done in 66% of patients. Electroanatomical mapping with the identification of LPs was performed in all patients. Noninducibility was achieved in 71% (119), and complete LP abolition was achieved in 61% (103) of patients. Incomplete LP abolition was a powerful predictor of VT recurrence (67% vs 33%, hazard ratio 3.19 [2.1 to 4.7]; p <0.001). Lack of use of a high-density mapping catheter (odds ratio 6.2, 1.2 to 38.1; p = 0.028), the septal substrate (odds ratio 9.34, 2.27 to 38.4; p = 0.002), and larger left ventricular mass (190 ± 58 g vs 156 ± 46 g, p = 0.002) were predictors of incomplete LP abolition. The main reasons that contributed to unsuccessful LP abolition were anatomic obstacles (such as the conduction system) and large extension of the LP area. In conclusion, incomplete LP abolition is related to VT recurrence. Lack of use of a high-density mapping catheter, the septal substrate, and larger left ventricular mass are related to incomplete LP abolition.

Cardiac Tomography and Cardiac Magnetic Resonance to Predict the Absence of Intracardiac Thrombus in Anticoagulated Patients Undergoing Atrial Fibrillation Ablation.

Background: Pulmonary veins isolation (PVI) is a standard treatment for recurrent atrial fibrillation (AF). Uninterrupted anticoagulation for a minimum of 3 weeks before ablation and exclusion of left atrial (LA) thrombus with transesophageal echography (TEE) immediately before or during the procedure minimize peri-procedural risk. We aimed to demonstrate the utility of cardiac tomography (CT) and cardiac magnetic resonance (CMR) to rule out LA thrombus prior to PVI. Methods: Patients undergoing PVI for recurrent AF were retrospectively evaluated. Only patients that started anticoagulation at least 3 weeks prior to the CT/CMR and subsequently uninterrupted until the ablation procedure were selected. An intracardiac echo (ICE) catheter was used in all patients to evaluate LA thrombus. The results of CT/CMR were compared to ICE imaging. Results: We included 272 consecutive patients averaging 54.5 years (71% male; 30% persistent AF). Average CHA2DS2VASC score was 0.9 ± 0.83 and mean LA diameter was 42 ± 5.7 mm, 111 (41%) patients were on Acenocumarol and 161 (59%) were on direct oral anticoagulants. Anticoagulation was started 227 ± 392 days before the CT/CMR, and 291 ± 416 days before the ablation procedure. CT/CMR diagnosed intracardiac thrombus in two cases, both in the LA appendage. A new CT/CMR revealed resolution of thrombus after six additional months of uninterrupted anticoagulation. No macroscopic thrombus was observed in any patients with ICE (negative predictive value of 100%; p < 0.01). Conclusions: CT and MRI are excellent surrogates to TEE and ICE to rule out intracardiac thrombus in patients adequately anticoagulated prior AF ablation. This is true even for delayed procedures as long as anticoagulation is uninterrupted.

Cardiac magnetic resonance to predict recurrences after ventricular tachycardia ablation: septal involvement, transmural channels, and left ventricular mass.

AIMS: Ventricular tachycardia (VT) substrate-based ablation has an increasing role in patients with structural heart disease-related VT. VT is linked to re-entry in relation to myocardial scarring with areas of conduction block (core scar) and areas of slow conduction [border zone (BZ)]. VT substrate can be analysed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Our study aims to analyse the role of LGE-CMR in identifying predictors of VT recurrence after ablation. METHODS AND RESULTS: We analysed 110 consecutive patients who underwent VT ablation from 2013 to 2018. All patients underwent a preprocedural LGE-CMR, and in 94 patients (85.5%), the CMR was used to aid the ablation. All LGE-CMR images were semi-automatically processed using dedicated software to detect scarring and conducting channels. After a median follow-up of 2.7 ± 1.6 years, the overall VT recurrence was 41.8% with an implantable cardioverter-defibrillator shock reduction from 43.6% to 28.2% before and after ablation, respectively. The amount of BZ (26.6 ± 13.9 vs. 19.6 ± 9.7 g, P = 0.012), the total amount of scarring (37.1 ± 18.2 vs. 29 ± 16.3 g, P = 0,033), and left ventricular (LV) mass (168.3 ± 53.3 vs. 152.3 ± 46.4 g, P < 0.001) were associated with VT recurrence. LGE septal distribution [62.5% vs. 37.8%; hazard ratio (HR) 1.67 (1.02-3.93), P = 0.044], channels with transmural path [66.7% vs. 31.4%, HR 3.25 (1.70-6.23), P < 0.001], and midmural channels [54.3% vs. 27.6%, HR 2.49 (1.21-5.13), P = 0.013] were related with VT recurrence. Multivariate analysis showed that the presence of septal LGE [HR 3.67 (1.60-8.38), P = 0.002], transmural channels [HR 2.32 (1.15-4.72), P = 0.019], and LV mass [HR 1.01 (1.005-1.019), P = 0.002] were independent predictors of VT recurrence. CONCLUSION: Pre-procedural LGE-CMR is a helpful and feasible technique to identify patients with high risk of VT recurrence after ablation. LV mass, septal LGE distribution, and transmural channels were predictive factors of post-ablation VT recurrence.

Scar channels in cardiac magnetic resonance to predict appropriate therapies in primary prevention.

BACKGROUND: Scar characteristics analyzed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related with ventricular arrhythmias. Current guidelines are based only on the left ventricular ejection fraction to recommend an implantable cardioverter-defibrillator (ICD) in primary prevention. OBJECTIVES: Our study aims to analyze the role of imaging to stratify arrhythmogenic risk in patients with ICD for primary prevention. METHODS: From 2006 to 2017, we included 200 patients with LGE-CMR before ICD implantation for primary prevention. The scar, border zone, core, and conducting channels (CCs) were automatically measured by a dedicated software. RESULTS: The mean age was 60.9 ± 10.9 years; 81.5% (163) were men; 52% (104) had ischemic cardiomyopathy. The mean left ventricular ejection fraction was 29% ± 10.1%. After a follow-up of 4.6 ± 2 years, 46 patients (22%) reached the primary end point (appropriate ICD therapy). Scar mass (36.2 ± 19 g vs 21.7 ± 10 g; P < .001), border zone mass (26.4 ± 12.5 g vs 16.0 ± 9.5 g; P < .001), core mass (9.9 ± 8.6 g vs 5.5 ± 5.7 g; P < .001), and CC mass (3.0 ± 2.6 g vs 1.6 ± 2.3 g; P < .001) were associated with appropriate therapies. Scar mass > 10 g (25.31% vs 5.26%; hazard ratio 4.74; P = .034) and the presence of CCs (34.75% vs 8.93%; hazard ratio 4.07; P = .003) were also strongly associated with the primary end point. However, patients without channels and with scar mass < 10 g had a very low rate of appropriate therapies (2.8%). CONCLUSION: Scar characteristics analyzed by LGE-CMR are strong predictors of appropriate therapies in patients with ICD in primary prevention. The absence of channels and scar mass < 10 g can identify patients at a very low risk of ventricular arrhythmias in this population.

Cardiac Magnetic Resonance-Guided Ventricular Tachycardia Substrate Ablation.

OBJECTIVES: This study assessed the feasibility and potential benefit of performing ventricular tachycardia (VT) substrate ablation procedures guided by cardiac magnetic resonance (CMR)-derived pixel signal intensity (PSI) maps. BACKGROUND: CMR-aided VT ablation using PSI maps from late gadolinium enhancement-CMR (LGE-CMR), together with electroanatomical map (EAM) information, has been shown to improve outcomes of VT substrate ablation. METHODS: Eighty-four patients with scar-dependent monomorphic VT who underwent substrate ablation were included in the study. In the last 28 (33%) consecutive patients, the procedure was guided by CMR. Procedural data, as well as acute and follow-up outcomes, were compared between patients who underwent guided CMR and 2 control groups: 1) patients who had PSI maps were available but the EAM was acquired and used to select the ablation targets (CMR aided); and 2) patients with no CMR-derived PSI maps available (no CMR). RESULTS: Mean procedure duration was lower in CMR-guided substrate ablation compared with CMR-aided and no CMR (107 ± 59 min vs. 203 ± 68 min and 227 ± 52 min; p < 0.001 for both comparisons). CMR-guided ablation required less fluoroscopy time than CMR-aided ablation and no CMR (10 ± 4 min vs. 23 ± 11 min and 20 ± 9 min, respectively; p < 0.001 for both comparisons) and less radiofrequency time (15 ± 8 min vs. 20 ± 15 min and 26 ± 10 min; p = 0.16 and p < 0.001, respectively). After substrate ablation, VT inducibility was lower in CMR-guided ablation compared with CMR-aided ablation and no CMR (18% vs. 32% and 46%; p = 0.35 and p = 0.04, respectively), without significant differences in complications. After 12 months, VT recurrence was lower in those who underwent CMR-guided ablation compared with no CMR (log-rank: 0.019), with no differences with CMR-aided ablation. CONCLUSIONS: CMR-guided VT ablation is feasible and safe, significantly reduces the procedural, fluoroscopy, and radiofrequency times, and is associated with a higher noninducibility rate and lower VT recurrence after substrate ablation.

Ventricular scar channel entrances identified by new wideband cardiac magnetic resonance sequence to guide ventricular tachycardia ablation in patients with cardiac defibrillators.

AIMS: Ventricular tachycardia (VT) substrate-based ablation has become a standard procedure. Electroanatomical mapping (EAM) detects scar tissue heterogeneity and define conduction channels (CCs) that are the ablation target. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is able to depict CCs and increase ablation success. Most patients undergoing VT ablation have an implantable cardioverter-defibrillator (ICD) that can cause image artefacts in LGE-CMR. Recently wideband (WB) LGE-CMR sequence has demonstrated to decrease these artefacts. The aim of this study is to analyse accuracy of WB-LGE-CMR in identifying the CC entrances. METHODS AND RESULTS: Thirteen consecutive ICD-patients who underwent VT ablation after WB-LGE-CMR were included. Number and location of CC entrances in three-dimensional EAM and in WB-LGE-CMR reconstruction were compared. Concordance was compared with a historical cohort matched by cardiomyopathy, scar location, and age (26 patients) with LGE-CMR prior to ICD and VT ablation. In WB-CMR group, 101 and 93 CC entrances were identified in EAM and WB-LGE-CMR, respectively. In historical cohort, 179 CC entrances were identified in both EAM and LGE-CMR. The EAM/CMR concordance was 85.1% and 92.2% in the WB and historical group, respectively (P = 0.66). There were no differences in false-positive rate (CC entrances detected in CMR and absent in EAM: 7.5% vs 7.8% in WB vs. conventional CMR, P = 0.92) nor in false-negative rate (CC entrances present in EAM not detected in CMR: 14.9% vs.7.8% in WB vs. conventional CMR, P = 0.23). Epicardial CCs was predictor of poor CMR/EAM concordance (OR 2.15, P = 0.031). CONCLUSION: Use of WB-LGE-CMR sequence in ICD-patients allows adequate VT substrate characterization to guide VT ablation with similar accuracy than conventional LGE-CMR in patients without an ICD.

Follow-Up After Myocardial Infarction to Explore the Stability of Arrhythmogenic Substrate: The Footprint Study.

OBJECTIVES: This study aimed to characterize the long-term scar remodeling process after an acute myocardial infarction (AMI) and the underlying scar-related arrhythmogenic substrate using serial late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). BACKGROUND: Little is known about the time course needed for completion of the scar healing process after an AMI, which can be assessed by noninvasive cardiac imaging techniques such as LGE-CMR. METHODS: Fifty-six patients with revascularized ST-segment elevation AMI (STEMI) were consecutively included. LGE-CMR (3-T) was obtained at 7 days, 6 months, and 4 years after STEMI. The myocardium was segmented into 10 layers from the endocardium to epicardium, characterizing the core, border zone (BZ), and BZ channels (BZCs) using a dedicated post-processing software. RESULTS: Mean age of the patients was 57 ± 11 years; 77% were men. Left ventricular ejection fraction improved at 6 months from 47% to 51% (p < 0.001) and remained stable at 4 years (53%; p = 0.21). Total scar mass decreased from 20.3 ± 14.6 g to 15.3 ± 13.3 g (6 months) and to 12.7 ± 11.7 g (4 years) (p < 0.001). Thirty of 56 (53%) patients showed a mean of 1.5 ± 1.3 BZCs/patient at 7 days, decreasing to 1.2 ± 1.3 (6 months) and 0.8 ± 1.0 (4 years) (p < 0.01). Only 42% of the initial BZCs remained present after 4 years. There were no arrhythmic events after a mean follow-up of 62.5 ± 7.4 months. CONCLUSIONS: CMR data post-processing permitted a dynamic assessment of quantitative and qualitative post-AMI scar characteristics. Scar size and number of BZCs steadily decreased 4 years after AMI. BZC distribution was significantly modified during this time. These dynamic parameters could be reliably assessed with CMR; their evaluation might be of prognostic value.

Prognosis after pacemaker implantation in extreme elderly.

AIMS: Significant comorbidities may limit the potential benefit of pacemaker (PM) implantation in extreme elderly. A short-term mortality risk prediction score, able to identify high-risk patients, may be a useful tool in this population. METHODS AND RESULTS: We retrospectively analyzed 538 patients aged >80 years at the time of implant who underwent PM implantation. Kaplan-Meier survival and multivariable Cox regression analyses were performed to identify patient, procedural or complication variables predictive of death. The ACP (Aging in Cardiac Pacing) Score was constructed by assigning weighted values to the variables identified by hazard ratios, combined into an additive mortality risk score equation. One, two and three-year overall mortality rate was 11%, 21% and 32% respectively. Renal failure (HR 1.63; CI 1.15-2.31; p = .006), active neoplasia (HR 1.78; CI 1.27-2.51; p = .008), connective tissue disorder (3.07; CI 1.34-7.08; p = .048), cerebrovascular disease (HR 1.75; CI 1.25-2.46; p = .001) and the use of a single lead device (HR 2.27; CI 1.6-3.24; p < .001) were independently associated with worse survival. The ACP Score showed discrete predictive ability (AUC 0,6792 CI 0,63-0,73). Kaplan-Meier survival curves comparing low vs high ACP Scores demonstrated that low ACP scores were associated with reduced mortality rates (p < .001). CONCLUSIONS: Significant comorbidities were associated with worse survival after PM implantation in extreme elderly. The ACP Score is a novel tool that may help to identify patients with high mortality risk after device implantation.

[Latest news and perspectives in cardiogenetics]. / Attualità e nuove prospettive in tema di cardiogenetica.

In recent years, cardiogenetics is emerging as a major discipline for the study of many pathologies, with immediate clinical effects for patients who were previously managed by the cardiologist alone. Recent acquisitions have allowed significant improvements in terms of diagnostic characterization, prognostic stratification and guidance for treatment for both patients with genetic disease and their family members. At present, cardiogenetics has an important role for the clinical management of patients with cardiomyopathies and channelopathies. We present an updated review of the literature and a proposal of organizational model.

Mutation Load of Multiple Ion Channel Gene Mutations in Brugada Syndrome.

Brugada syndrome is a primary arrhythmic syndrome that accounts for 20% of all sudden cardiac death cases in individuals with a structurally normal heart. Pathogenic variants associated with Brugada syndrome have been identified in over 19 genes, with SCN5A as a pivotal gene accounting for nearly 30% of cases. In contrast to other arrhythmogenic channelopathies (such as long QT syndrome), digenic inheritance has never been reported in Brugada syndrome. Exploring 66 cardiac genes using a new custom next-generation sequencing panel, we identified a double heterozygosity for pathogenic mutations in SCN5A and TRPM4 in a Brugada syndrome patient. The parents were heterozygous for each variation. This novel finding highlights the role of mutation load in Brugada syndrome and strongly suggests the adoption of a gene panel to obtain an accurate genetic diagnosis, which is mandatory for risk stratification, prevention, and therapy.

Amino terminal pro brain natriuretic peptide predicts all-cause mortality in patients with chronic obstructive pulmonary disease: Systematic review and meta-analysis.

Natriuretic peptides (NPs) are a family of prognostic biomarkers in patients with heart failure (HF). HF is one of the most frequent comorbidities in patients with chronic obstructive pulmonary disease (COPD). However, the prognostic role of NP in COPD patients remains unclear. The aim of this meta-analysis was to evaluate the relation between NP and all-cause mortality in COPD patients. We performed a systematic review and meta-analysis of observational studies assessing prognostic implications of elevated NP levels on all-cause mortality in COPD patients. Nine studies were considered for qualitative analysis for a total of 2788 patients. Only two studies focused on Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and brain natriuretic peptide (BNP), respectively, but seven studies focused on pro-BNP (NT-proBNP) and were included in the quantitative analysis. Elevated NT-proBNP values were related to increased risk of all-cause mortality in COPD patients both with and without exacerbation (hazard ratio (HR): 2.87, p < 0.0001 and HR: 3.34, p = 0.04, respectively). The results were confirmed also after meta-regression analysis for confounding factors (previous cardiovascular history, hypertension, HF, forced expiratory volume at 1 second and mean age). NT-proBNP may be considered a reliable predictive biomarker of poor prognosis in patients with COPD.

The frailty in elderly patients receiving cardiac interventional procedures (FRASER) program: rational and design of a multicenter prospective study.

BACKGROUND: Frailty has become a high-priority issue in cardiovascular medicine because of the aging of cardiovascular patients. Simple and reproducible tools to assess frailty in elderly patients are clearly on demand. Their application may help physicians in the selection of invasive and medical treatments and in the timing and modality of the follow-up. The frailty in elderly patients receiving cardiac interventional procedures (FRASER) program is designed with the aim to validate the use of the short physical performance battery (SPPB) as prognostic tools in patients admitted to hospital for acute coronary syndrome (ACS). METHODS: The FRASER program is a multicenter prospective study involving 4 Italian cardiology units. The FRASER program enrolls only patients aged ≥70 years. The core of the FRASER program includes patients admitted to hospital for ACS. The aims are (1) to describe SPPB distribution before hospital discharge and (2) to investigate the prognostic role of SPPB score. The primary outcome is a composite of 1-year all-cause mortality and hospital readmission for any cause. Ancillary analyses will be focused on different study populations (patients hospitalized for arrhythmias or acute heart failure or symptomatic severe aortic stenosis) and on different tools to assess frailty (multidimensional prognostic index, clinical frailty score, grip strength). DISCUSSION: The FRASER program will fill critical gaps in the knowledge regarding the link between frailty, cardiovascular disease, interventional procedures and outcome and will help physicians in the generation of a more personalized risk assessment and in the identification of potential targets for interventions.