Pathogenic pathways and therapeutic targets of inflammation in heart diseases: A focus on Interleukin-1.

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-1ß, 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.

Integrating platelet reactivity in the age, creatinine and ejection fraction score to predict clinical outcomes following percutaneous coronary intervention in patients with chronic coronary syndrome: the PR-ACEF score.

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.

Comparison of novel ventricular pacing strategies using an electro-mechanical simulation platform.

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.

Electrocardiographic characteristics of right-bundle-branch-block premature ventricular complexes predicting absence of left ventricular scar in athletes with apparently structural normal heart.

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.

Pacing of the specialized His-Purkinje conduction system: 'back to the future'.

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.

Electrocardiogram in arrhytmogenic cardiomyopathy.

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.

The electrocardiogram in non-ischaemic-dilated cardiomyopathy.

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.

Impact of His bundle pacing on right ventricular performance in patients undergoing permanent pacemaker implantation.

BACKGROUND: His-Bundle pacing (HBP) is an emerging technique for physiological pacing. However, its effects on right ventricle (RV) performance are still unknown. METHODS: We enrolled consecutive patients with an indication for pacemaker (PM) implantation to compare HBP versus RV pacing (RVP) effects on RV performance. Patients were evaluated before implantation and after 6 months by a transthoracic echocardiogram. RESULTS: A total of 84 patients (age 75.1±7.9 years, 64% male) were enrolled, 42 patients (50%) underwent successful HBP, and 42 patients (50%) apical RVP. At follow up, we found a significant improvement in RV-FAC (Fractional Area Change)% [baseline: HBP 34 IQR (31-37) vs. RVP 33 IQR (29.7-37.2),p = .602; 6-months: HBP 37 IQR (33-39) vs. RVP 30 IQR (27.7-35), p < .0001] and RV-GLS (Global Longitudinal Strain)% [baseline: HBP -18 IQR (-20.2 to -15) vs. RVP -16 IQR (-18.7 to -14), p = .150; 6-months: HBP -20 IQR(-23 to -17) vs. RVP -13.5 IQR (-16 to -11), p < .0001] with HBP whereas RVP was associated with a significant decline in both parameters. RVP was also associated with a significant worsening of tricuspid annular plane systolic excursion (TAPSE) (p < .0001) and S wave velocity (p < .0001) at follow up. Conversely from RVP, HBP significantly improved pulmonary artery systolic pressure (PASP) [baseline: HBP 38 IQR (32-42) mmHg vs. RVP 34 IQR (31.5-37) mmHg,p = .060; 6-months: HBP 32 IQR (26-38) mmHg vs. RVP 39 IQR (36-41) mmHg, p < .0001] and tricuspid regurgitation (p = .005) irrespectively from lead position above or below the tricuspid valve. CONCLUSIONS: In patients undergoing PM implantation, HBP ensues a beneficial and protective impact on RV performance compared with RVP.

The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: The CANA-HF study.

BACKGROUND: Canagliflozin reduces hospitalizations for heart failure (HF) in type 2 diabetes mellitus (T2DM). Its effect on cardiorespiratory fitness and cardiac function in patients with established HF with reduced ejection fraction (HFrEF) is unknown. METHODS: We conducted a double-blind randomized controlled trial of canagliflozin 100 mg or sitagliptin 100 mg daily for 12 weeks in 88 patients, and measured peak oxygen consumption (VO2 ) and minute ventilation/carbon dioxide production (VE/VCO2 ) slope (co-primary endpoints for repeated measure ANOVA time_x_group interaction), lean peak VO2 , ventilatory anaerobic threshold (VAT), cardiac function and quality of life (ie, Minnesota Living with Heart Failure Questionnaire [MLHFQ]), at baseline and 12-week follow-up. RESULTS: The study was terminated early due to the new guidelines recommending canagliflozin over sitagliptin in HF: 17 patients were assigned to canagliflozin and 19 to sitagliptin, total of 36 patients. There were no significant changes in peak VO2 and VE/VCO2 slope between the two groups (P = .083 and P = .98, respectively). Canagliflozin improved lean peak VO2 (+2.4 mL kgLM-1 min-1 , P = .036), VAT (+1.5 mL kg-1 min-1 , P = .012) and VO2 matched for respiratory exchange ratio (+2.4 mL Kg-1 min-1 , P = .002) compared to sitagliptin. Canagliflozin also reduced MLHFQ score (-12.1, P = .018). CONCLUSIONS: In this small and short-term study of patients with T2DM and HFrEF, interrupted early after only 36 patients, canagliflozin did not improve the primary endpoints of peak VO2 or VE/VCO2 slope compared to sitagliptin, while showing favourable trends observed on several additional surrogate endpoints such as lean peak VO2 , VAT and quality of life.

Impact of Different Doses of Omega-3 Fatty Acids on Cardiovascular Outcomes: a Pairwise and Network Meta-analysis.

PURPOSE OF REVIEW: Omega-3 fatty acid (O3FA) supplementation has shown conflicting evidence regarding its benefit in cardiovascular events. We performed a pairwise and network meta-analysis to elucidate the benefit of different doses of O3FA supplementation in cardiovascular prevention. RECENT FINDINGS: Fourteen studies were identified providing data on 125,763 patients. A prespecified cut-off value of < 1 g per day was set for low-dose (LD) O3FA and > 1 g per day for high-dose (HD) O3FA. The efficacy outcomes of interest were total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina, and major vascular events. Safety outcomes of interest were bleeding, gastrointestinal disturbances, and atrial fibrillation events. HD treatment was associated with a lower risk of cardiac death (IRR 0.79, 95% CI [0.65-0.96], p = 0.03 versus control), myocardial infarction (0.71 [0.62-0.82], p < 0.0001 versus control and 0.79 [0.67-0.92], p = 0.003 versus LD), coronary revascularization (0.74 [0.66-0.83], p < 0.0001 versus control and 0.74 [0.66-0.84], p < 0.0001 versus LD), unstable angina (0.73 [0.62-0.86], p = 0.0001 versus control and 0.74 [0.62-0.89], p = 0.002 versus LD), and major vascular events (0.78 [0.71-0.85], p < 0.0001 versus control and 0.79 [0.72-0.88], p < 0.0001 versus LD). HD treatment was associated with increased risk for bleeding events (1.49 [1.2-1.84], p = 0.0002 versus control and 1.63 [1.16-2.3], p = 0.005 versus LD) and increased atrial fibrillation events compared to control (1.35 [1.1-1.66], p = 0.004). HD O3FA treatment was associated with lower cardiovascular events compared to LD and to control, but increased risk for bleeding and atrial fibrillation events.

Phase 1B, Randomized, Double-Blinded, Dose Escalation, Single-Center, Repeat Dose Safety and Pharmacodynamics Study of the Oral NLRP3 Inhibitor Dapansutrile in Subjects With NYHA II-III Systolic Heart Failure.

ABSTRACT: The NLRP3 inflammasome has been implicated in the development and progression of heart failure. The aim of this study was to determine the safety of an oral inhibitor of the NLRP3 inflammasome, dapansutrile (OLT1177), in patients with heart failure and reduced ejection fraction (HFrEF). This was a phase 1B, randomized, double-blind, dose escalation, single-center, repeat dose safety and pharmacodynamics study of dapansutrile in stable patients with HFrEF (New York Heart Association Class II-III). Subjects were randomized to treatment with dapansutrile for up to 14 days at a ratio of 4:1 into 1 of 3 sequential ascending dose cohorts (500, 1000, or 2000 mg) each including 10 patients. Subjects underwent clinical assessment, biomarker determination, transthoracic echocardiogram, and maximal cardiopulmonary exercise testing at baseline, day 14, and day 28 to ascertain changes in clinical status. Placebo cases (N = 2 per cohort) were used as a decoy to reduce bias and not for statistical comparisons. Thirty participants (20 men) were treated for 13 (12-14) days. No serious adverse events during the study were recorded. All clinical or laboratory parameters at day 14 compared with baseline suggested clinical stability without significant within-group differences in the dapansutrile-pooled group or the 3 dapansutrile cohorts. Improvements in left ventricular EF [from 31.5% (27.5-39) to 36.5% (27.5-45), P = 0.039] and in exercise time [from 570 (399.5-627) to 616 (446.5-688) seconds, P = 0.039] were seen in the dapansutrile 2000 mg cohort. Treatment with dapansutrile for 14 days was safe and well tolerated in patients with stable HFrEF.

Takotsubo syndrome: diagnostic work-up and clues into differential diagnosis.

PURPOSE OF REVIEW: Takotsubo syndrome represents an increasingly recognized clinical entity characterized by a reversible acute myocardial dysfunction, often triggered by an emotional or physical stress, and independent of an underlying epicardial coronary artery disease. The diagnosis is often challenging because of the nonspecific clinical presentation and the inconclusive noninvasive diagnostic imaging. RECENT FINDINGS: The present review provides a brief overview of Takotsubo syndrome clinical presentation and guides the clinician through the diagnostic work-up of Takotsubo syndrome, highlighting clues into differential diagnosis. A review of clinical management is also provided. SUMMARY: Despite increasing awareness and recognition, the diagnosis of Takotsubo syndrome remains challenging and Takotsubo syndrome is often underdiagnosed or misdiagnosed. The prompt recognition of Takotsubo syndrome portends relevant prognostic and therapeutic implications.

Impact of platelet reactivity on 5-year clinical outcomes following percutaneous coronary intervention: a landmark analysis.

We investigated the impact of suboptimal platelet reactivity on clinical outcomes after percutaneous coronary intervention (PCI). We enrolled 500 patients with stable coronary artery disease undergoing elective PCI. Platelet reactivity was measured before PCI using the VerifyNow P2Y12 assay. Primary endpoint was the incidence of ischemic or bleeding events at 1 month and 5 years. Patients with high platelet reactivity (HPR) showed significantly higher rates of ischemic events both during the 1st month after PCI (HR 2.06, 95% CI 1.02-4.06), and beyond 1 month compared with patients without HPR (HR 1.73, 95% CI 1.02-2.95). Conversely, compared with patients without low platelet reactivity (LPR), patients with LPR presented significantly higher rates of bleeding only during the 1st month (HR 3.67, 95% CI 1.68-8.02). In conclusion, pre-procedural HPR is associated with ischemic events even beyond the 1st month after PCI. The association of LPR with bleeding events seems to be confined to the periprocedural period.

Efficacy and safety of oral anticoagulant therapy in frail patients with atrial fibrillation.

Antithrombotic treatment of frail patients with AF presents various challenges. The fear of bleeding often leds to a large underuse of anticoagulant agents in these patients, although more recent data indicate that oral anticoagulation  (especially with the newer, direct anticoagulants) is increasingly used. While there is a need for more real world data, available evidence suggests that non-vitamin K antagonist oral anticoagulants (NOACs) are an effective alternative to warfarin in frail patients with AF for preventing thromboembolic events, with a better safety profile. Logical considerations and evidence-base data related to the reduced bleeding risk (also including major bleeding and intracranial bleeding) of NOACs make these drugs the anticoagulant agents of choice in frail patients; however, in this setting an individualised approach should be taken, taking into consideration the risk of thromboembolic and bleeding events, other comorbidities and patient-related factors, rather than a generalised "one drug fits all" approach.

Interleukin-1ß blockade improves left ventricular systolic/diastolic function and restores contractility reserve in severe ischemic cardiomyopathy in the mouse.

BACKGROUND: Interleukin-1ß (IL-1ß) modulates the inflammatory response during acute myocardial infarction (AMI) and progression to ischemic cardiomyopathy. We investigated whether blockade of IL-1ß after the onset of the cardiac dysfunction prevented left ventricular (LV) adverse remodeling in a mouse model of anterior nonreperfused AMI. METHODS: Infarct size and LV systolic function were assessed by echocardiography 7 days after coronary artery ligation. Mice with large infarct size and LV ejection fraction (LVEF) <40% were randomly assigned to treatment with a monoclonal antibody directed toward IL-1ß antibody (10 mg/kg IL-1ß-AB) or with a cyclosporine directed antibody (10 mg/kg control-AB). Echocardiogram was repeated after 10 weeks, followed by assessment of contractile reserve using isoproterenol challenge and LV catheterization. RESULTS: After 10 weeks, control-AB-treated mice showed significantly increased LV end-diastolic diameter (+15%, P < 0.001) and decreased LVEF (-18%, P = 0.050). IL-1ß-AB had no significant effect on LV end-diastolic diameter (+10%, P = 0.25 vs. control-AB) but significantly prevented LVEF reduction (+7%, P = 0.031 vs. control-AB), enlargement of the right ventricle (P = 0.024), impairment in myocardial performance index (P = 0.028) and contractile reserve (P = 0.008), and increased LV end-diastolic pressure (P = 0.030). CONCLUSIONS: IL-1ß blockade using a monoclonal antibody in mice with severe LV dysfunction after AMI prevents further deterioration in LV systolic and diastolic function and restores contractile reserve.

Clinical impact and predictors of periprocedural myocardial injury among patients undergoing left bundle branch area pacing.

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.

Conduction system pacing for cardiac resynchronization therapy: State of the art, current controversies, and future perspectives.

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.

Feasibility and safety of left bundle branch area pacing-cardiac resynchronization therapy in elderly patients.

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.

Low fluoroscopy permanent His bundle pacing using a new electroanatomic mapping system (KODEX EPD). A multicenter experience.

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.

Impact of Endothelial Dysfunction on Long-Term Clinical Outcomes in Patients With Chronic Coronary Syndromes Treated With Second Generation Drug-Eluting Stent Implantation.

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.