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Introduction: Left bundle branch area pacing (LBBAP) comprises pacing at the left ventricular septum (LVSP) or left bundle branch (LBBP). The aim of the present study was to investigate the differences in ventricular electrical heterogeneity between LVSP, LBBP, right ventricular pacing (RVP) and intrinsic conduction with different dyssynchrony measures using the ECG, vectorcardiograpy, ECG belt, and Ultrahigh frequency (UHF-)ECG., Methods: Thirty-seven patients with a pacemaker indication for bradycardia or cardiac resynchronization therapy underwent LBBAP implantation. ECG, vectorcardiogram, ECG belt and UHF-ECG signals were recorded during RVP, LVSP and LBBP, and intrinsic activation. QRS duration (QRSd) was measured from the ECG, QRS area was calculated from the vectorcardiogram, LV activation time (LVAT) and standard deviation of activation time (SDAT) from ECG belt and electrical dyssynchrony (e-DYS16) from UHF-ECG., Results: Both LVSP and LBBP significantly reduced ventricular electrical heterogeneity as compared to underlying LBBB and RV pacing in terms of QRS area (p < .001), SDAT (p < .001), LVAT (p < .001) and e-DYS16 (p < .001). QRSd was only reduced as compared to RV pacing(p < .001). QRS area was similar during LBBP and normal intrinsic conduction, e-DYS16 was similar during LVSP and normal intrinsic conduction, whereas SDAT was similar for LVSP, LBBP and normal intrinsic conduction. For all these variables there was no significant difference between LVSP and LBBP., Conclusion: Both LVSP and LBBP resulted in a more synchronous LV activation than LBBB and RVP. Especially LBBP resulted in levels of LV synchrony comparable to normal intrinsic conduction., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: The clinical impact of Periprocedural myocardial injury (PMI) in patients undergoing permanent pacemaker implantation with Left Bundle Branch Area Pacing (LBBAP) is unknown., Methods: 130 patients undergoing LBBAP from January 2020 to June 2021 and completing 12 months follow up were enrolled to assess the impact of PMI on composite clinical outcome (CCO) defined as any of the following: all-cause death, hospitalization for heart failure (HHF), hospitalization for acute coronary syndrome (ACS) and ventricular arrhythmias (VAs). High sensitivity Troponin T (HsTnT) was measured up to 24-h after intervention to identify the peak HsTnT values. PMI was defined as increased peak HsTnT values at least > 99th percentile of the upper reference limit (URL: 15 pg/ml) in patients with normal baseline values., Results: PMI occurred in 72 of 130 patients (55%). ROC analysis yielded a post-procedural peak HsTnT cutoff of fourfold the URL for predicting the CCO (AUC: 0.692; p = 0.023; sensitivity 73% and specificity 71%). Of the enrolled patients, 20% (n = 26) had peak HsTnT > fourfold the URL. Patients with peak HsTnT > fourfold the URL exhibited a higher incidence of the CCO than patients with peak HsTnT ≤ fourfold the URL (31% vs. 10%; p = 0.005), driven by more frequent hospitalizations for ACS (15% vs. 3%; p = 0.010). Multiple (> 2) lead repositions attempts, the use of septography and stylet-driven leads were independent predictors of higher risk of PMI with peak HsTnT > fourfold the URL., Conclusions: PMI seems common among patients undergoing LBBAP and may be associated with an increased risk of clinical outcomes in case of more pronounced (peak HsTnT > fourfold the URL) myocardial damage occurring during the procedure., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To evaluate if integrating platelet reactivity (PR) evaluation in the original age, creatinine and ejection fraction (ACEF) score could improve the diagnostic accuracy of the model in patients with stable coronary artery disease (CAD). We enrolled patients treated with percutaneous coronary intervention between 2010 and 2011. High PR was included in the model (PR-ACEF). Co-primary end points were a composite of death/myocardial infarction (MI) and major adverse cardiovascular events (MACE). Overall, 471 patients were enrolled. Compared to the ACEF score, the PR-ACEF showed an improved diagnostic accuracy for death/MI (AUC 0.610 vs 0.670, p < 0.001) and MACE (AUC 0.572 vs 0.634, p < 0.001). These findings were confirmed using internal validation with bootstrap resampling. At 5 years, the PR-ACEF value > 1.75 was independently associated with death/MI [HR 3.51, 95% CI (1.97-6.23)] and MACE [HR 2.77, 95% CI (1.69-4.53)]. The PR-ACEF score was effective in improving the diagnostic performance of the ACEF score at the long-term follow-up., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: An exuberant and dysregulated inflammatory response contributes to the development and progression of cardiovascular diseases (CVDs)., Methods: This narrative review includes original articles and reviews published over the past 20 years and found through PubMed. The following search terms (or combination of terms) were considered: "acute pericarditis," "recurrent pericarditis," "myocarditis," "cardiac sarcoidosis," "atherosclerosis," "acute myocardial infarction," "inflammation," "NLRP3 inflammasome," "Interleukin-1" and "treatment.", Results: Recent evidence supports the role of inflammation across a wide spectrum of CVDs including myocarditis, pericarditis, inflammatory cardiomyopathies (i.e. cardiac sarcoidosis) as well as atherosclerotic CVD and heart failure. Interleukins (ILs) are the signalling mediators of the inflammatory response. The NACHT, leucine-rich repeat and pyrin-domain containing protein 3 (NLRP3) inflammasome play a key role in producing IL-1β, the prototypical pro-inflammatory cytokine involved in CVDs. Other pro-inflammatory cytokines (e.g. tumour necrosis factor) have been implicated in cardiac sarcoidosis. As a proof of this, IL-1 blockade has been proven efficacious in pericarditis and chronic coronary syndrome., Conclusion: Tailored strategies aiming at quenching the inflammatory response have emerged as promising to treat CVDs. In this review article, we summarize recent evidence regarding the role of inflammation across a broad spectrum of CVDs. We also review novel evidence regarding targeted therapeutic strategies., (© 2023 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Electrocardiographic (ECG) findings in arrhythmogenic left ventricular cardiomyopathy (ALVC) are limited to small case series., Objectives: This study aimed to analyze the ECG characteristics of ALVC patients and to correlate ECG with cardiac magnetic resonance and genotype data., Methods: We reviewed data of 54 consecutive ALVC patients (32 men, age 39 ± 15 years) and compared them with 84 healthy controls with normal cardiac magnetic resonance., Results: T-wave inversion was often noted (57.4%), particularly in the inferior and lateral leads. Low QRS voltages in limb leads were observed in 22.2% of patients. The following novel ECG findings were identified: left posterior fascicular block (LPFB) (20.4%), pathological Q waves (33.3%), and a prominent R-wave in V 1 with a R/S ratio ≥0.5 (24.1%). The QRS voltages were lower in ALVC compared with controls, particularly in lead I and II. At receiver-operating characteristic analysis, the sum of the R-wave in I to II ≤8 mm (AUC: 0.909; P < 0.0001) and S-wave in V 1 plus R-wave in V 6  ≤12 mm (AUC: 0.784; P < 0.0001) effectively discriminated ALVC patients from controls. It is noteworthy that 4 of the 8 patients with an apparently normal ECG were recognized by these new signs. Transmural late gadolinium enhancement was associated to LPFB, a R/S ratio ≥0.5 in V 1 , and inferolateral T-wave inversion, and a ringlike pattern correlated to fragmented QRS, SV 1 +RV 6  ≤12 mm, low QRS voltage, and desmoplakin alterations., Conclusions: Pathological Q waves, LPFB, and a prominent R-wave in V 1 were common ECG signs in ALVC. An R-wave sum in I to II ≤8 mm and SV 1 +RV 6  ≤12 mm were specific findings for ALVC phenotypes compared with controls., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. All rights reserved.)

Aims: Left ventricular scar is an arrhythmic substrate that may be missed by echocardiography and diagnosed only by cardiac magnetic resonance (CMR), which is a time-consuming and expensive imaging modality. Premature ventricular complexes (PVCs) with a right-bundle-branch-block (RBBB) pattern are independent predictors of late gadolinium enhancement (LGE) but their positive predictive value is low. We studied which electrocardiographic features of PVCs with an RBBB pattern are associated with a higher probability of the absence of an underlying LGE., Methods: The study included 121 athletes (36 ± 16 years; 48.8% men) with monomorphic PVCs with an RBBB configuration and normal standard clinical investigations who underwent CMR. LGE was identified in 35 patients (29%), predominantly in those with PVCs with a superior/intermediate axis (SA-IntA) compared to inferior axis (IA) (38% vs. 10%, P = 0.002). Among patients with SA-IntA morphology, the contemporary presence of qR pattern in lead aVR and V1 was exclusively found in patients without LGE at CMR (51.0% vs. 0%, P < 0.0001). Among patients with IA, the absence of LGE correlated to a narrow ectopic QRS (145 ± 16 vs. 184 ± 27 msec, P < 0.001)., Conclusions: Among athletes with apparently idiopathic PVCs with a RBBB configuration, the presence of a concealed LGE at CMR was documented in 29% of cases, mostly in those with a SA-IntA. In our experience, the contemporary presence of qR pattern in lead aVR and V1 in PVCs with RBBB/SA-IntA morphology or, on the other hand, a relatively narrow QRS in PVCs with an IA, predicted absence of LGE., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Focus of pacemaker therapy is shifting from right ventricular (RV) apex pacing (RVAP) and biventricular pacing (BiVP) to conduction system pacing. Direct comparison between the different pacing modalities and their consequences to cardiac pump function is difficult, due to the practical implications and confounding variables. Computational modelling and simulation provide the opportunity to compare electrical, mechanical, and haemodynamic consequences in the same virtual heart., Methods and Results: Using the same single cardiac geometry, electrical activation maps following the different pacing strategies were calculated using an Eikonal model on a three-dimensional geometry, which were then used as input for a lumped mechanical and haemodynamic model (CircAdapt). We then compared simulated strain, regional myocardial work, and haemodynamic function for each pacing strategy. Selective His-bundle pacing (HBP) best replicated physiological electrical activation and led to the most homogeneous mechanical behaviour. Selective left bundle branch (LBB) pacing led to good left ventricular (LV) function but significantly increased RV load. RV activation times were reduced in non-selective LBB pacing (nsLBBP), reducing RV load but increasing heterogeneity in LV contraction. LV septal pacing led to a slower LV and more heterogeneous LV activation than nsLBBP, while RV activation was similar. BiVP led to a synchronous LV-RV, but resulted in a heterogeneous contraction. RVAP led to the slowest and most heterogeneous contraction. Haemodynamic differences were small compared to differences in local wall behaviour., Conclusion: Using a computational modelling framework, we investigated the mechanical and haemodynamic outcome of the prevailing pacing strategies in hearts with normal electrical and mechanical function. For this class of patients, nsLBBP was the best compromise between LV and RV function if HBP is not possible., Competing Interests: Conflict of interest: J.L. has received research grants from Medtronic. F.W.P. has received research grants from Medtronic, Abbott, Microport CRM, and Biotronik. K.V. has received research grants from Medtronic, Abbott and has a consultancy agreement with Medtronic and Abbott. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Studies investigating clinical outcomes of patients with or without endothelial disfunction (ED) treated with percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) using second generation drug eluting stents (DES) are lacking., Methods: We prospectively collected data from 109 patients undergoing PCI with second generation DES due to stable CAD between December 2014 and September 2016. ED was evaluated evaluating the flow mediated dilation (FMD) at the brachial artery level and defined by an FMD < 7 %. Primary outcome were major adverse cardiovascular events (MACE), secondary outcomes were target vessel failure (TVR), myocardial infarction (MI) and all-cause death., Results: Five-year follow-up was available in all patients. Median FMD didn't significantly differ between patients who experienced the outcome and those who didn't [no TVR vs. TVR: p = 0.358; no MI vs. MI: p = 0.157; no death vs. death: p = 0.355; no MACE vs. MACE: p = 0.805]. No association between ED and an increased risk for the primary outcome as well as for the secondary ones was evident [MACE: 17.0 % vs. 14.3 %, HR 0.87 (0.33-2.26), log rank p = 0.780; TVR: 9.4 % vs. 5.4 %, HR 0.53 (0.12-2.24), log rank p = 0.384; MI: 3.7 % vs. 8.9 %, HR 2.46 (0.47-12.76), log rank p = 0.265; death: 7.5 % vs. 3.6 %, HR 0.53 (0.09-2.90), log rank p = 0.458]. These findings were confirmed using a lower threshold of FMD to define ED and at one-year landmark analysis., Conclusions: ED is not associated with an increased risk of adverse events at long-term follow-up in a contemporary cohort of patients undergoing PCI with second generation DES., Competing Interests: Declaration of competing interest Authors report the absence of any conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Criteria for diagnosis of arrhythmogenic cardiomyopathy (ACM) were first proposed in 1994 and subsequently revised in 2010 and in 2020 by an international task force. According to the last consensus of 2020, ACM is defined as a heart muscle disease affecting right ventricle, left ventricle or both, whose principal pathologic feature is fibrofatty myocardial replacement that impairs systolic ventricular function and predisposes to lethal ventricular arrhythmias. ECG findings not only could help to early recognize affected patients but also could identify the ones with maximum risk of ventricular arrhythmias and sudden cardiac death., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The conduction system of the human heart is composed of specialized cardiomyocytes that initiate and propagate the electric impulse with consequent rhythmic and synchronized contraction of the atria and ventricles, resulting in the normal cardiac cycle. Although the His-Purkinje system (HPS) was already described more than a century ago, there has been a recent resurgence of conduction system pacing (CSP), where pacing leads are positioned in the His bundle region and left bundle branch area to provide physiological cardiac activation as alternatives to the unnatural myocardial stimulation obtained with conventional right ventricular and biventricular pacing. In this review, we describe the fundamental anatomical and pathophysiological aspects of the specialized HPS along with the CSP technique's nuts and bolts to highlight its potential benefits in everyday clinical practice., Competing Interests: Conflict of interest: All authors have reported that they have no relationships relevant to the contents of this review to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This article summarizes the main electrocardiogram (ECG) findings in dilated cardiomyopathy (DCM) patients. Recent reports are described in the great 'pot' of DCM peculiar ECG patterns that are typical of specific forms of DCM. Patients with late gadolinium enhancement on CMR, who are at greatest arrhythmic risk, have also distinctive ECG features. Future studies in large DCM populations should evaluate the diagnostic and prognostic value of the ECG., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Advances in cardiac implantable electronic devices (CIEDs) have prolonged life expectancy in various medical settings. However, the issue of hypersensitivity to components of CIEDs is still a concern. Since 1970, allergic reactions to metallic and nonmetallic components of CIEDs have been reported. Hypersensitivity reactions to medical devices are rare and not fully understood. In some cases, diagnosis and treatment are difficult. Cardiologists should always keep in mind pacemaker allergy when a patient appears with wound complications and no signs of infection. Patch testing should be tailored toward the specific biomaterials used in a device, in addition to testing with standard screening allergens in select cases., Competing Interests: No financial support was received and none of the authors has any conflict of interest., (© 2023 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Background: Left bundle branch area pacing (LBBAP) is an emerging technique to achieve cardiac resynchronization therapy (CRT), but its feasibility and safety in elderly patients with heart failure with reduced ejection fraction and left bundle branch block is hardly investigated., Methods: We enrolled consecutive patients with an indication for CRT comparing pacing parameters and complication rates of LBBAP-CRT in elderly patients (≥ 75 years) versus younger patients (< 75 years) over a 6-month follow-up., Results: LBBAP was successful in 55/60 enrolled patients (92%), among which 25(45%) were elderly. In both groups, LBBAP significantly reduced the QRS duration (elderly group: 168 ± 15 ms to 136 ± 12 ms, p < 0.0001; younger group: 166 ± 14 ms to 134 ± 11 ms, p < 0.0001) and improved LVEF (elderly group: 28 ± 5% to 40 ± 7%, p < 0.0001; younger group: 29 ± 5% to 41 ± 8%, p < 0.0001). The pacing threshold was 0.9 ± 0.8 V in the elderly group vs. 0.7 ± 0.5 V in the younger group (p = 0.350). The R wave was 9.5 ± 3.9 mV in elderly patients vs. 10.7 ± 2.7 mV in younger patients (p = 0.341). The fluoroscopic (elderly: 13 ± 7 min vs. younger: 11 ± 7 min, p = 0.153) and procedural time (elderly: 80 ± 20 min vs. younger: 78 ± 16 min, p = 0.749) were comparable between groups. Lead dislodgement occurred in 2(4%) patients, 1 in each group (p = 1.000). Intraprocedural septal perforation occurred in three patients (5%), 2(8%) in the elderly group (p = 0.585). One patient (2%) in the elderly group had a pocket infection., Conclusions: LBBAP is a feasible and safe technique for delivering physiological pacing in elderly patients who are candidates for CRT with suitable pacing parameters and low complication rates., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Biventricular pacing (BVP) is the established treatment to perform cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and left bundle branch block (LBBB). However, BVP is an unnatural pacing modality still conditioned by the high percentage of non-responders and coronary sinus anatomy. Conduction system pacing (CSP)-His bundle pacing (HBP) and Left bundle branch area pacing (LBBAP)- upcomes as the physiological alternative to BVP in the quest for the optimal CRT. CSP showed promising results in terms of better electro-mechanical ventricular synchronization compared to BVP. However, only a few randomized control trials are currently available, and technical challenges, along with the lack of information on long-term clinical outcomes, limit the establishment of a primary role for CSP over conventional BVP in CRT candidates. This review provides a comprehensive literature revision of potential applications of CSP for CRT in diverse clinical scenarios, underlining the current controversies and prospects of this technique., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bressi, Grieco, Luermans, Burri and Vernooy.)

Background: His bundle pacing (HBP) may be a challenging procedure, often involving a long fluoroscopic time (FT) and a long procedural time (PT). We sought to evaluate whether the use of a new nonfluroscopic mapping (NFM) system, the KODEX-EPD, is able to reduce FT and PT when mapping is performed by the pacing catheter rather than an electrophysiological mapping catheter., Methods and Results: We included 46 consecutive patients (77 ± 8 years; 63% male) who underwent HBP; in 22 a NFM-guided procedure with the KODEX-EPD system was performed (group 1), whereas in 24 a conventional fluoroscopy-guided approach was used (group 2). Pacing indications were sick sinus syndrome in 13, atrioventricular block in 21, and cardiac resynchronization therapy in 12 cases. Both a lumen-less fixed helix lead and a stylet-driven extendable helix lead were used, respectively, in 24% and 76% of patients. HBP was successful in 22 patients (100%) in group 1 and 23 patients (96%) in group 2. The FT was significantly reduced in group 1 (183 ± 117 s vs 464.1 ± 352 s in group 2, p  = .012). There were no significant differences between groups in PT and other procedural outcomes., Conclusions: The KODEX-EPD system may be safely used in HBP procedures. It is effective in reducing ionizing radiation exposure, as evidenced by the significant drop in FT, without increasing PT., Competing Interests: Authors declare no conflict of interests for this article., (© 2022 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Background: Takotsubo syndrome is associated with life threatening arrhythmias, and the apical ballooning pattern is characterized by a peculiar QT prolongation and particularly high-risk of arrhythmias., Objectives: The aim of the study was to determine the association of QT interval on electrocardiogram for ventricular arrhythmic complications in patients with apical ballooning Takotsubo syndrome in a diverse population at a large urban hospital in the U.S., Methods: We reviewed 105 cases of apical ballooning Takotsubo syndrome in patients admitted between 2011 and 2017. Two cardiologists reviewed the electrocardiograms to measure QT interval, adjusted for rate using the Fridericia formula (QT C F), and ventricular arrhythmic complications during the hospitalization. Data are reported as median and interquartile range or number and percentage., Results: Of the 105 patients, 86 (82%) were female, and 34 (32%) were self-reported Black or African American. The mean age was 65 years (range: 58-72 years). Left ventricular ejection fraction was 25% (range: 25%-35%). Heart rate was 101 beats/min (range: 83-121 beats/min). Ten (11%) patients experienced a ventricular arrhythmic complication and had significantly longer QT C F (470 [range: 422-543] milliseconds) than did those without complications (417 [range: 383-456] milliseconds, P = 0.031). The area under the curve for QT C F was 0.708 (95% CI: 0.536-0.880; P = 0.031). Twenty-eight (27%) patients had a QT C F ≥460 milliseconds and significantly more arrhythmic complications (21% vs 5%, odds ratio 4.997 [95% CI: 1.288-19.237], P = 0.021). QT C F was an independent predictor of ventricular arrhythmias: odds ratio 1.090 for each 10-millisecond increase in QT C F (95% CI: 1.004-1.183; P = 0.040, corrected for sex)., Conclusions: In a diverse population of patients with apical ballooning Takotsubo syndrome admitted to a large urban hospital in the United States, QT C F at admission ≥460 milliseconds identifies patients at high risk for in-hospital arrhythmic complications. Further studies are needed to determine strategies aimed at shortening QT interval to potentially prevent life-threatening arrhythmic events., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Historically, regular exercise contributed to reduce the arrhythmic burden and improve cardiovascular outcomes in the general population. However, a heightened risk of atrial fibrillation (AF) seems to occur mainly amongst endurance athletes. The exact mechanisms are not fully elucidated, but dynamic interactions between electro-anatomical changes induced by exercise, the autonomic system, variable triggers, along individual genetic predisposition are the main contributors to AF development in athletes. The type and training load of sports are also crucial in determining the arrhythmogenic milieu predisposing to AF insurgence and perpetuation. Moreover, a sex difference seems to influence an increased risk of AF only in men undergoing strenuous exercise, whereas women appear protected even during more vigorous training. In the absence of solid evidence, the advent of modern technologies could help to monitor and deep investigate the peculiar aspects of AF in these athletes. This review aims to describe the pathophysiology, diagnosis, and management of AF in athletes, shedding light on possible future strategies to face AF in this population.

Background: Sarcopenia impairs cardiorespiratory fitness (CRF) in patients with heart failure with reduced ejection fraction (HFrEF). Obesity has also been shown to impair CRF; however, the effects of sarcopenia on CRF in patients with obesity and HFrEF are unknown. The aim of this analysis was to examine differences in CRF between patients with sarcopenic obesity (SO) and non-SO (NSO) with HFrEF. We also assessed associations between skeletal muscle mass index (SMMI) and CRF., Methods: Forty patients with HFrEF and obesity underwent cardiopulmonary exercise testing to collect measures of CRF including peak oxygen consumption (VO 2 ), circulatory power, oxygen uptake efficiency slope, O 2 pulse, and exercise time. Body composition was performed in all patients using bioelectrical impedance analysis to quantify fat mass index and divide patients into SO and NSO based on SMMI cutoffs. Results are presented as mean (SD) or median [interquartile range] as appropriate., Results: Nearly half (43% [n=17]) of patients had SO. Patients with SO had a lower SMMI than those with NSO, and no differences in fat mass index were observed between groups. Those with SO achieved a lower absolute peak VO 2 (NSO, 1.62±0.53 L·min -1 versus SO, 1.27±0.44 L·min -1 , P =0.035), oxygen uptake efficiency slope (NSO, 1.92±0.59 versus SO, 1.54±0.48, P =0.036), and exercise time (NSO, 549±198 seconds versus SO, 413±140 seconds, P =0.021) compared to those with NSO. On multivariate analysis, SMMI remained a significant predictor of absolute peak VO 2 when adjusted for age, sex, adiposity, and HF severity., Conclusions: In patients with HFrEF and obesity, sarcopenia, defined as low SMMI, is associated with a clinically significant reduction in CRF, independent of adiposity.

His bundle pacing (HBP) has emerged as a feasible alternative to right (RVP) and biventricular pacing (BVP) for Cardiac Resynchronization Therapy (CRT). This study sought to assess, in ex-vivo experimental models, the optimal setup for HBP in terms of electrode placement and pacing protocol to achieve superior electrical synchrony in the case of complete His-Purkinje block and left bundle branch block (LBBB). We developed a 3D model of His bundle and bundle branches, embedded in a patient-specific biventricular heart model reconstructed from CT images. A monodomain reaction-diffusion model was adopted to describe the propagation of cardiac action potential, and a custom procedure was developed to compute pseudo-ECGs. Experimental measurements of tip electrode potential waveforms have been performed on ex-vivo swine myocardium to determine the appropriate boundary condition for delivering the electrical stimulus in the numerical model. An extended parametric analysis, investigating the effect of the electrode orientation and helix length, pacing protocol, and atrioventricular delay, allowed us to determine the optimal setup for HBP therapy. Both selective (S-HBP) and non-selective (NS-HBP) His bundle pacing were tested, as the variable anatomical location of the His bundle can result in the activation of the surrounding myocardium. Our study indicates a perpendicular placement of the electrode as the most advantageous for restoring the physiological function of the His-Purkinje system. We found that higher-energy protocols can compensate for the effects of an angled placement though concurring to potential tip fibrosis. Promisingly, we also revealed that an increased electrode helix length can provide optimal resynchronization even with low-energy pacing protocols. Our results provide informative guidance for implant procedure and therapy optimization, which will hopefully have clinical implications further improving the procedural success rates and patients' quality of life, due to reduced incidence of lead revision and onset of complications., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Aims: To investigate the levels of platelet reactivity and the impact of high platelet reactivity (HPR) on long-term clinical outcomes of complex higher-risk and indicated patients (CHIP) with stable coronary artery disease (CAD) treated with elective percutaneous coronary intervention (PCI)., Methods: We enrolled 500 patients undergoing elective PCI for stable CAD and treated with aspirin and clopidogrel. Patients were divided into four groups based on the presence of CHIP features and HPR. Primary endpoint was the occurrence of major adverse clinical events (MACE) at 5 years., Results: The prevalence of HPR was significantly greater in the CHIP population rather than non-CHIP patients (39.9% vs 29.8%, P = 0.021). Patients with both CHIP features and HPR showed the highest estimates of MACE (22.1%, log-rank P = 0.047). At Cox proportional hazard analysis, the combination of CHIP features and HPR was an independent predictor of MACE (hazard ratio 2.57, 95% confidence interval 1.30-5.05, P = 0.006)., Conclusion: Among patients with stable CAD undergoing elective PCI and treated with aspirin and clopidogrel, the combination of CHIP features and HPR identifies a cohort of patients with the highest risk of MACE at 5 years, who might benefit from more potent antiplatelet strategies., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Previous studies suggested that N-terminal pro-brain natriuretic peptide (NT-proBNP) level is a powerful independent predictor of death or heart failure (HF) when measured at admission in patients with chest pain or acute coronary syndrome. Little is known about the role of NT-proBNP level measured during a hospitalization for ST segment elevation myocardial infarction (STEMI) in predicting clinical outcomes. We evaluated the optimal NT-proBNP timing (admission, 72 hours, or delta [Δ] NT-proBNP [72 hours minus admission]) to predict 1-year new-onset HF in STEMI patients., Methods: We measured NT-proBNP levels at admission and 72 hours in 72 patients with STEMI. HF events were adjudicated and defined as hospitalization for HF or need for new initiation of a loop diuretic at 1-year follow-up. Values are presented as medians and interquartile range or frequencies (%) as appropriate. Cox regression analysis was used to determine predictors of adverse events. A receiver-operative-curve was constructed to identify the discriminative value and optimal cut-off points for NT-proBNP., Results: Patients (age 56 [49-64] years, males 59 [82%]) were followed for a median duration of 365 [180-365] days. HF events were recorded in 9 (12.5%) patients. NT-proBNP values at admission, 72 hours, and ΔNT-proBNP were 89 (26-268) pg/mL, 452 (223-1064) pg/mL, and 283 (68-686) pg/mL, respectively. NT-proBNP at 72 hours and ΔNT-proBNP, but not admission NT-proBNP predicted new-onset HF events at follow-up (P=0.03, P=0.002 and P=0.89, respectively). The optimal area under the curve of 0.771 (95%, CI [0.630-0.912], P= 0.009) and cut-off value of 830 pg/mL (sensitivity 79%; specificity 76%) were found for NT-proBNP at 72 hours. The Kaplan-Meier survival curves for NT-proBNP at 72 hours dichotomized above and below this cut-off value, confirmed NT-proBNP at 72 hours >830 pg/mL as predictive of HF events (log-rank statistic = 8.688, P=0.003)., Conclusions: NT-proBNP level at 72 hours and ΔNT-proBNP (72 hours minus admission), but not at time of admission, predicted HF events in patients following STEMI.

We investigated the interaction between chronic kidney disease (CKD) and high platelet reactivity (HPR) in determining long-term clinical outcomes following elective PCI for stable coronary artery disease (CAD). A total of 500 patients treated with aspirin and clopidogrel were divided based on the presence of CKD (defined as glomerular filtration rate of < 60 ml/min/1.73 m 2 ) and HPR (defined as a P2Y12 reaction unit value ≥ 240 at VerifyNow assay). Primary endpoint was the occurrence of major adverse clinical events (MACE) at 5 years. Patients with both CKD and HPR showed the highest estimates of MACE (25.6%, p = 0.005), all-cause death (17.9%, p = 0.004), and cardiac death (7.7%, p = 0.004). The combination of CKD and HPR was an independent predictor of MACE (HR 3.12, 95% CI 1.46-6.68, p = 0.003). In conclusion, the combination of CKD and HPR identifies a cohort of patients with the highest risk of MACE at 5 years., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To date, only a few comparisons between subcutaneous implantable cardioverter-defibrillator (S-ICD) patients undergoing and those not undergoing defibrillation testing (DT) at implantation (DT+ vs DT-) have been reported., Objective: The purpose of this study was to compare long-term clinical outcomes of 2 propensity-matched cohorts of DT+ and DT- patients., Methods: Among consecutive S-ICD patients implanted across 17 centers from January 2015 to October 2020, DT- patients were 1:1 propensity-matched for baseline characteristics with DT+ patients. The primary outcome was a composite of ineffective shocks and cardiovascular mortality. Appropriate and inappropriate shock rates were deemed secondary outcomes., Results: Among 1290 patients, a total of 566 propensity-matched patients (283 DT+; 283 DT-) served as study population. Over median follow-up of 25.3 months, no significant differences in primary outcome event rates were found (10 DT+ vs 14 DT-; P = .404) as well as for ineffective shocks (5 DT- vs 3 DT+; P = .725). At multivariable Cox regression analysis, DT performance was associated with a reduction of neither the primary combined outcome nor ineffective shocks at follow-up. A high PRAETORIAN score was positively associated with both the primary outcome (hazard ratio 3.976; confidence interval 1.339-11.802; P = .013) and ineffective shocks alone at follow-up (hazard ratio 19.030; confidence interval 4.752-76.203; P = .003)., Conclusion: In 2 cohorts of strictly propensity-matched patients, DT performance was not associated with significant differences in cardiovascular mortality and ineffective shocks. The PRAETORIAN score is capable of correctly identifying a large percentage of patients at risk for ineffective shock conversion in both cohorts., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Takotsubo syndrome (TS) is an acute, reversible form of heart failure, often mimicking an acute coronary syndrome (ACS). Data regarding racial differences in TS are inconsistent. The aim is to assess clinical features associated with unfavorable in-hospital outcomes between African American (AA) and Caucasian (CAU) patients., Methods: A retrospective electronic health record query identified 44 AA patients and 110 CAU patients with a diagnosis of TS. Our primary outcome was a composite of death, stroke, and cardiogenic shock during hospitalization. Variables associated with an increased risk of the primary composite outcomes were included in a logistic regression model., Results: Compared to CAU patients, AA patients were a more comorbid population, and presented a higher prevalence of history of illicit drug use (27.3% vs. 13.6% P=0.044). There were no significant differences regarding in-hospital complication rates between AA and CAU patients. In the logistic regression model, infection was associated with greater risk of developing the primary outcome in AA patients (OR=7.26 [95% CI 1.22-43.17], P=0.029), whereas angina was a protective factor (OR=0.11 [95% CI 0.02-0.65], P=0.015). In CAU patients, severely depressed ejection fraction and worse peak creatinine during hospitalization increased risk of developing the primary outcome (OR=5.88 95% CI [2.01-17.17], P<0.001 and OR=1.64 [95% CI 1.15-2.58], P=0.031, respectively). Meanwhile, emotional stressors were protective (OR=0.16 [95% CI 0.03-0.88], P=0.004)., Conclusions: Despite experiencing the same rate of in-hospital complications, the clinical profiles of AA patients are distinct from CAU patients admitted for TS, and clinical variables correlated with worse in-hospital outcomes also differ by race.

We evaluated the predictive power of age, creatinine, and ejection fraction (ACEF) score on mortality at 5-year follow-up in a population of 471 patients with chronic coronary syndrome (CCS) treated with percutaneous coronary intervention (PCI). Patients in the ACEF-High tertile showed the highest incidence of death at 5 years (15.7% vs. 2.6% in ACEF-Low and 4.3% in ACEF-Mid; log rank p<0.001). The ACEF score could significantly discriminate between patients who died and those who were still alive at 5 years (AUC 0.741, 95% CI 0.654-0.828), and an ACEF score >1.32 was identified as the optimal cutoff point to predict 5-year mortality (sensitivity 74%, specificity 68%). An ACEF score >1.32 was an independent predictor of 5-year mortality (HR 5.77, 95% CI 2.70-12.31; p<0.001). Our study shows that the ACEF score can predict mortality at 5-year follow-up in patients with CCS treated with PCI., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Hematopoietic cell transplantation (HCT) is an established and potentially curative therapeutic option for hematologic cancers. HCT survivors are at risk of developing long-term complications impacting on morbidity and mortality. Orthostatic hypotension (OH) and postural tachycardia syndrome (POTS) have been anecdotally described after HCT. However, the incidence and clinical characteristics of patients with OH and POTS after HCT has not been well defined., Methods: This retrospective study included 132 patients who had HCT between March 2011 and July 2018 and were referred to Cardio-oncology clinic. Patients were screened for OH and POTS. Using logistic regression analysis we evaluated the association between clinical factors and the incidence of OH and POTS., Results: Median age was 58 (47-63) years, 87 (66%) patients were male, 95 (72%) were Caucasian. OH was diagnosed in 30 (23%) subjects and POTS in 12 (9%) after the HCT. No significant differences in demographic characteristics were found when comparing patients with and without OH or POTS. The two groups did not differ for cardiovascular diseases prevalence nor for the prior use of antihypertensive drugs. Previous radiotherapy and treatment with specific chemotherapy drugs were found to be associated with the incidence of OH or POTS, but none of the factors maintained the significance in the multivariate model. Pharmacological therapy was required in 38 (91%) cases, including a b-adrenergic blocker (n = 24, 57%), midodrine (n = 24, 57%) and fludrocortisone (n = 7, 18%)., Conclusion: Orthostatic intolerance syndromes are commonly diagnosed in patients referred to the cardiologist after HCT, involving approximately 1/3 of patients and requiring pharmacological therapy to cope with symptoms in the majority of cases. Risk factors specific to this population are identified but cannot fully explain the incidence of POTS and OH after HCT., (© 2021. The Author(s).)