Leadless pacemaker technology: clinical evidence of new paradigm of pacing

Despite continuous technological developments, transvenous pacemakers (PM) are still associated with significant immediate and long-term complications, mostly lead or pocket-related. Recent technological advances brought to the introduction in clinical practice of leadless PM for selected cohort of patients. These miniaturize devices are implanted through the femoral vein and advanced to the right ventricle, without leaving leads in place. Lack of upper extremity vascular access and/or high infective risk in patients requiring VVI pacing are the most common indications to leadless PM. The recently introduced MICRA AV leadless PM also allows ventricular synchronization through mechanical sensing of atrial contraction waves, thus solving the problem of AV synchronization. This review will discuss and summarize available clinical evidence on leadless PM, their performance compared to transvenous devices, current applications and future perspectives

Successful ventricular tachycardia radioablation in a patient with previous chemical pleurodesis: A case report

IntroductionStereotactic arrhythmia radioablation (STAR) is a novel technique for the ablation of ventricular tachycardia in patients with contraindications to standard procedures, i.e., radiofrequency ablation.Case presentationWe report the case of a 73-year-old man with non-ischemic dilated cardiomyopathy and recurrent VT episodes. Electroanatomic mapping showed VT prevalently of epicardial origin, but direct epicardial access through subxyphoid puncture could not be performed due to pleuropericardial adhesions from a past history of chemical pleurodesis. STAR was performed, with no VT recurrence at 6 months follow-up.ConclusionsPrevious experiences with STAR have demonstrated its importance in the management of patients with refractory VT in whom other ablation strategies were not successful. Our case report highlights the use of STAR as a second choice in a patient with an unfavorable VT anatomical location and technical limitations to an optimal radiofrequency ablation. Moreover, it confirms STAR's effectiveness in the ablation of complex transmural lesions, which are more often associated with non-ischemic structural heart disease

ORal anticoagulants In fraGile patients with percutAneous endoscopic gastrostoMy and atrIal fibrillation: the (ORIGAMI) study

BACKGROUND: Randomized trials support the safety and efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with nonvalvular atrial fibrillation, leading to increased use of these compounds. Crushed forms of DOACs have been shown to be reliable, but evidence supporting percutaneous endoscopic gastrostomy (PEG) delivery is lacking. PEG is a long-term option for enteral food and drug delivery in patients unable to maintain oral intake, bypassing the risks and disadvantages of parenteral nutrition.AIMS: The ORal anticoagulants In fraGile patients with percutAneous endoscopic gastrostoMy and atrIal fibrillation (ORIGAMI) study investigates the safety and efficacy of Edoxaban administered via PEG in patients with atrial fibrillation and a clinical indication for a long-term anticoagulation.DESIGN: In this prospective, single-centre observational study, 12 PEG-treated patients with indication to anticoagulation will receive edoxaban via PEG and will be followed up to 6 months. Plasma antifactor Xa activity and edoxaban concentrations will be assessed. Thromboembolic (ischaemic stroke, systemic embolism, venous thromboembolism) and bleeding events (Bleeding Academic Research Consortium and Thrombolysis in Myocardial Infarction) will be recorded at 1 and 6 months.PRELIMINARY CASES: A retrospective analysis of five atrial fibrillation cases undergoing PEG implantation at our Institution who received edoxaban via PEG showed plasma anti-FXa levels at a steady state of 146 ± 15 ng/ml, without major adverse event at a mean follow-up of 6 months.CONCLUSION: ORIGAMI prospectively investigates PEG-administration of edoxaban in PEG-treated patients requiring long-term anticoagulation. Our preliminary retrospective data support this route of DOAC administration. CLINICALTRIALS.GOV IDENTIFIER: NCT04271293

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner

Heart failure with preserved ejection fraction diagnosis and treatment: An updated review of the evidence

Over the last several decades, clinicians and clinical scientists have had growing interest in heart failure (HF) diagnosis and treatment. While HF with reduced ejection fraction (EF) is a well-known clinical entity with several therapeutic strategies proven to be successful, HF with preserved ejection fraction is a more heterogenous syndrome with a prevalence that has increased in the last two decades, without effective therapeutic strategies. Great strides have been made in the detection of predisposing risk factors and pathological mechanisms; however, pharmacological therapies have shown to be ineffective in reducing cardiovascular mortality in the HF with preserved EF (HFpEF) population, opening the way to the necessity of developing new precision medicine based approaches. On the other hand, novel therapies and device interventions still require refinements with the ultimate goal of offering new clinically treatments for the HFpEF population. The aim of the present review is to provide insights into the HFpEF pathophysiology, diagnostic pathways and the latest updates on treatment strategies and their potential future application in routine clinical practice

Short-Term Atrioventricular Dysfunction Recovery after Post-TAVI Pacemaker Implantation

Permanent pacemaker implantation (PPI) represents a frequent complication after transcatheter aortic valve implantation (TAVI) due to atrio-ventricular (AV) node injury. Predictors of early AV function recovery were investigated. We analyzed 50 consecutive patients (82 +/- 6 years, 58% males, EuroSCORE: 7.8 +/- 3.3%, STS mortality score: 5 +/- 2.8%). Pacemaker interrogations within 4-6 weeks from PPI were performed to collect data on AV conduction. The most common indication of PPI was persistent third-degree (44%)/high-degree (20%) AV block/atrial fibrillation (AF) with slow ventricular conduction (16%) after TAVI. At follow-up, 13 patients (26%) recovered AV conduction (i.e., sinus rhythm with stable 1:1 AV conduction/AF with a mean ventricular response >50 bpm, associated with a long-term ventricular pacing percentage < 5%). At multivariate analysis, complete atrio-ventricular block independently predicted pacemaker dependency at follow-up (p = 0.019). Patients with persistent AV dysfunction showed a significant AV conduction time prolongation after TAVI (PR interval from 207 +/- 50 to 230 +/- 51, p = 0.02; QRS interval from 124 +/- 23 to 147 +/- 16, p < 0.01) compared to patients with recovery, in whom AV conduction parameters remained unchanged. Several patients receiving PPI after TAVI have recovery of AV conduction within a few weeks. Longer observation periods prior to PPI might be justified, and algorithms to minimize ventricular pacing should be utilized whenever possible

Mortality after transvenous lead extraction: A risk prediction model for sustainable care delivery

Background and aims: Transvenous lead extraction (TLE) has become a pivotal part of a comprehensive lead management strategy, dealing with a continuously increasing demand. Nonetheless, the literature about the long-term impact of TLE on survivals is still lacking. Given these knowledge gaps, the aim of our study was to analyse very long-term mortality in patients undergoing TLE in public health perspective. Methods: This prospective, single-centre, observational study enrolled consecutive patients with cardiac implantable electronic device (CIED) who underwent TLE, from January 2005 to January 2021. The main goal was to establish the independent predictors of very long-term mortality after TLE. We also aimed at assessing procedural and hospitalization-related costs. Results: We enrolled 435 patients (mean age 70 ± 12 years, with mean lead dwelling time 6.8 ± 16.7 years), with prevalent infective indication to TLE (92%). Initial success of TLE was achieved in 98% of population. After a median follow-up of 4.5 years (range: 1 month-15.5 years), 150 of the 435 enrolled patients (34%) died. At multivariate analysis, death was predicted by: age (≥77 years, OR: 2.55, CI: 1.8-3.6, p < 0.001), chronic kidney disease (CKD) defined as severe reduction of estimated glomerular filtration rate (eGFR <30 mL/min/1.73 m2 , OR: 1.75, CI: 1.24-2.4, p = 0.001) and systolic dysfunction assessed before TLE defined as left ventricular ejection fraction (LVEF) <40%, OR: 1.78, CI 1.26-2.5, p = 0.001. Mean extraction cost was €5011 per patient without reimplantation and €6336 per patient with reimplantation respectively. Conclusions: Our study identified three predictors of long-term mortality in a high-risk cohort of patients with a cardiac device infection, undergoing successful TLE. The future development of a mortality risk score before might impact on public health strategy

Atrioventricular conduction in PM recipients after transcatheter aortic valve implantation: Implications using Wenckebach point measurement

BackgroundAtrioventricular (AV) conduction disturbances requiring permanent pacemaker implantation (PPI) are a common complication after transcatheter aortic valve implantation (TAVI). However, a significant proportion of patients might recover AV conduction at follow-up. ObjectivesThe aim of our study was to evaluate the recovery of AV conduction by determination through Wenckebach point in patients with PPI and therefore identify patients who could benefit from device reprogramming to avoid unnecessary RV pacing. MethodsWe enrolled 43 patients that underwent PM implantation after TAVI at our Department from January 2018 to January 2021. PM interrogation was performed at follow-up and patients with native spontaneous rhythm were further assessed for AV conduction through WP determination. ResultsA total of 43 patients requiring a PM represented the final study population, divided in patients with severely impaired AV conduction (no spontaneous valid rhythm or WP < 100; 26) and patients with valid AV conduction (WP >= 100; 17). In the first group patients had a significantly higher number of intraprocedural atrioventricular block (AVB) (20 vs. 1, p < 0.005), showed a significant higher implantation depth in LVOT (7.7 +/- 2.2 vs. 4.4 +/- 1.1, p < 0.05) and lower Delta MSID (-0.28 +/- 3 vs. -3.94 +/- 2, p < 0.05). ConclusionAV conduction may recover in a significant proportion of patients. In our study, valve implantation depth in the LVOT and intraprocedural AV block are associated with severely impaired AV conduction. Regular PM interrogation and reprogramming are required to avoid unnecessary permanent right ventricular stimulation in patients with AV conduction recovery

Oral anticoagulants in fragile patients with percutaneous endoscopic gastrostomy and atrial fibrillation: the ORIGAMI pilot investigation

Abstract Background: Extensive data support the superior safety without any trade-off in efficacy of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation, deep venous thrombosis or pulmonary embolism. Whether DOACs may be successfully used to treat complex and fragile patients with percutaneous endoscopic gastrostomy (PEG) remains to be proven. The purpose of this pilot study was to evaluate the feasibility, anticoagulant effect, and preliminary safety/efficacy profile of edoxaban administered via PEG in patients with an indication for long-term oral anticoagulation. Methods: In this prospective, single-arm, pilot study, 12 patients with PEG and guideline-recommended indication for anticoagulation for nonvalvular atrial fibrillation were prospectively enrolled. Crushed edoxaban at approved doses was administered via PEG. Quantitative measures of edoxaban's anti-factor Xa activity were performed at steady state. Thromboembolic and bleeding events were assessed at one-month follow-up. Results: Steady state edoxaban plasma levels were at therapeutic range in all patients; mean plasma concentration was 208.5 (±78.6) ng/ml. At one month follow-up, none had suffered a thromboembolic event; one developed minor bleeding, and one died from non-cardiovascular death, owing to sudden worsening of a pre-existing underlying severe condition. Conclusions: In this pilot investigation, we report for the first time that crushed edoxaban, administered at approved doses through PEG in fragile and complex patients, is feasible, results in therapeutic edoxaban concentrations, and is apparently effective and safe