Is Conduction System Pacing a Valuable Alternative to Biventricular Pacing for Cardiac Resynchronization Therapy?

Cardiac resynchronization therapy (CRT) significantly improves clinical outcomes in patients with ventricular systolic dysfunction and dyssynchrony. Biventricular pacing (BVP) has a class IA recommendation for patients with symptomatic heart failure with reduced ejection fraction (HFrEF) and left bundle branch block (LBBB). However, approximately 30% of patients have a poor therapeutic response and do not achieve real clinical benefit. Pre-implant imaging, together with tailored programming and dedicated device algorithms, have been proposed as possible tools to improve success rate but have shown inconsistent results. Over the last few years, conduction system pacing (CSP) is becoming a real and attractive alternative to standard BVP as it can restore narrow QRS in patients with bundle branch block (BBB) by stimulating and recruiting the cardiac conduction system, thus ensuring true resynchronization. It includes His bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Preliminary data coming from small single-center experiences are very promising and have laid the basis for currently ongoing randomized controlled trials comparing CSP with BVP. The purpose of this review is to delve into the emerging role of CSP as an alternative method of achieving CRT. After framing CSP in a historical perspective, the pathophysiological rationale and available clinical evidence will be examined, and crucial technical aspects will be discussed. Finally, evidence gaps and future perspectives on CSP as a technique of choice to deliver CRT will be summarized.

Transvenous lead extraction of lumenless 3830 pacing lead in conduction system pacing: a single-center experience.

BACKGROUND: The Medtronic SelectSecure Model 3830 lumenless lead (Medtronic, Inc., Minneapolis, MN) is commonly used for conduction system pacing (CSP). However, with this increased use, the potential need for transvenous lead extraction (TLE) also will increase. While extraction of endocardial 3830 leads is rather well described especially in pediatric and adult congenital heart disease population, there is very limited data on extraction of CSP leads. In the present study, we reported our preliminary experience on TLE of CSP leads and provided technical considerations. METHODS: The study population comprised 6 consecutive patients (67% male; mean age 70 ± 22 years) with CSP leads (3830 leads), including left bundle branch pacing (LBBP) lead (n = 3) and His pacing lead (n = 3) undergoing TLE. Overall target leads were 17. The mean implant duration time of CSP leads was 97 ± 90 months [range 8-193). RESULTS: Manual traction was successful in 2 cases and mechanical extraction tools were required in the remaining cases. Sixteen leads (94%) were completely extracted, whereas incomplete removal was observed in one lead (6%) among 1 patient. Of note, in the only lead incompletely removed, we observed retention of < 1-cm remnant of lead material consisting of the screw of 3830 LBBP lead into the interventricular septum. No failure of lead extraction was reported and no major complications occurred. CONCLUSIONS: Our findings demonstrated that at an experienced center the success of TLE of chronically implanted CSP leads is high in the absence of major complications also when mechanical extraction tools are needed.

The Fate of Chlorophylls in Alkali-Treated Green Table Olives: A Review.

This paper reviews the current knowledge regarding modifications to chlorophylls during the processing of green table olives treated with alkali. Particular attention is given to the pheophytinization reactions (substitution of Mg2+ by 2H+ in the chlorophyll chromophore group) that can take place because of pH and/or temperature changes and the possible sequential substitution of the 2H+ with Cu2+ within the chlorophyll porphyrin ring. These reactions may have a direct impact on the commercial value of olive productions as some naturally forming Cu-chlorophylls complexes (i) are identical to strictly forbidden colorants for table olives (E141) and (ii) have been identified as responsible for the unwelcome appearance of the so-called green staining alteration (characterized by bluish-green zones distributed over the olive skin of the drupes).

The weakest point of cardiac resynchronization therapy: new technologies facing old terminology.

Patients with symptomatic heart failure (HF) and left bundle branch block (LBBB) are currently treated with biventricular pacing (BiV) which has a Class IA recommendation. Given the possibility to re-establish the inter and intra-ventricular synchrony, BiV is commonly referred to as cardiac resynchronization therapy (CRT). This wording is widely utilized and over time the terms BiV and CRT have become interchangeable. Conduction system pacing (CSP) is emerging as a valid therapeutic opportunity to obtain CRT restoring the native conduction via the Purkinje network. Therefore the acronym CRT is no longer synonymous with BiV only but could also refer to CSP. A terminology update is needed to include the resource of CSP to ensure better communication among all the stakeholders involved in managing recipients of cardiac devices and should be a fundamental step in advancing the quality of patient care. Making use of the NBG code to describe the implantable cardiac device would ease such terminology update, since only the first three positions of the five letters NBG code are commonly utilized, while the last two are rarely used.

Conduction system pacing in difficult cardiac anatomies: Systematic approach with the 3D electroanatomic mapping guide.

INTRODUCTION: Restoring physiological cardiac electrical activity in patients with conduction disease can be crucial for the survival and quality of life. Conduction system pacing (CSP) is a valuable option, although it is limited by technical challenges in difficult anatomies. 3D electroanatomical mapping (3D-EAM) can support CSP ensuring high electro-anatomical precision and low fluoroscopy. OBJECTIVES: We evaluated the feasibility and effectiveness of a systematic 3D-EAM use to guide CSP in difficult anatomical scenarios (highly dilated atria, congenital cardiomyopathies, failed biventricular implants (BiV) and pacing-induced cardiomyopathy (PICM)). METHODS: Forty-three consecutive patients (27 males, 75 ± 10 years old) with standard pacing indications and difficult anatomical scenarios were included. The right atrium, His cloud, and atrio-ventricular septum were reconstructed by 3D-EAM. The His bundle (HB) was the initial target, while left bundle branch area pacing (LBBAP) was aimed at in case of unsatisfactory parameters, sub-optimally paced QRS, or impossibility of reaching the HB. RESULTS: CSP was successful in 37 (86%) patients (15 HBP; 22 LBBAP). Mean mapping, fluoroscopy, and procedural times were 18 ± 7 min, 7 ± 5 min, 98 ± 47 min, respectively. The mean pacing threshold, R wave sensing, and pacing impedance of CSP lead were 1.2 ± 0.5V@0.5ms, 11.4 ± 6.2 mV, 736 ± 306 Ω, respectively. Baseline and paced QRS were 139 ± 38 ms and 114 ± 23 ms, respectively. No procedural complications were observed. CONCLUSIONS: 3D-EAM allowed the accurate definition of the His cloud and high ventricular septum and effectively guided CSP. It facilitated CSP in complex anatomies, with a procedural success rate of 86%. The results were satisfactory and reproducible, with acceptable fluoroscopy and procedural times.

The Fate of the Chlorophyll Derivatives in Olives Preserved and/or Packaged in Presence of Exogenous Copper.

Chlorophyll pigments are thought to be responsible for the highly appreciated green color of unfermented Castelvetrano-style table olives, but no studies have considered the effects of a controlled addition of copper during storage or packaging at the industrial level. For this purpose, chlorophyll derivatives were analyzed in Nocellara cultivar table olives debittered industrially using the Castelvetrano method, via means of HPLC and MS analyses, following the addition of copper in alkaline brines stored at 4 °C for 3 months in 220 L barrels, and during the subsequent storage in acid brines in commercial 400 g packages at 4 °C for up to 18 months. The presence of copper in storage or in packaging brines both contributed significantly to maintaining the green color of the olives, which was associated with a specific pattern of chlorophyll derivatives, as evidenced by principal component analysis. Notably, re-greening was rapidly achievable also for olives that had yellowed for 18 months at a copper concentration below the limit of EU legislation. Finally, by means of PCA, we also demonstrated that a short-term thermic treatment can work as an accelerated predictive tool in determining the fate of chlorophyll derivatives.

The PhysioVP-AF study, a randomized controlled trial to assess the clinical benefit of physiological ventricular pacing vs. managed ventricular pacing for persistent atrial fibrillation prevention in patients with prolonged atrioventricular conduction: design and rationale.

AIMS: In patients with prolonged atrioventricular (AV) conduction and pacemaker (PM) indication due to sinus node disease (SND) or intermittent AV-block who do not need continuous ventricular pacing (VP), it may be difficult to determine which strategy to adopt. Currently, the standard of care is to minimize unnecessary VP by specific VP avoidance (VPA) algorithms. The superiority of this strategy over standard DDD or DDD rate-responsive (DDD/DDDR) in improving clinical outcomes is controversial, probably owing to the prolongation of the atrialventricular conduction (PR interval) caused by the algorithms. Conduction system pacing (CSP) may offer the most physiological-VP approach, providing appropriate AV conduction and preventing pacing-induced dyssynchrony. METHODS AND RESULTS: PhysioVP-AF is a prospective, controlled, randomized, single-blind trial designed to determine whether atrial-synchronized conduction system pacing (DDD-CSP) is superior to standard DDD-VPA pacing in terms of 3-year reduction of persistent-AF occurrence. Cardiovascular hospitalization, quality-of-life, and safety will be evaluated. Patients with indication for permanent DDD pacing for SND or intermittent AV-block and prolonged AV conduction (PR interval > 180 ms) will be randomized (1:1 ratio) to DDD-VPA (VPA-algorithms ON, septal/apex position) or to DDD-CSP (His bundle or left bundle branch area pacing, AV-delay setting to control PR interval, VPA-algorithms OFF). Approximately 400 patients will be randomized in 24 months in 13 Italian centres. CONCLUSION: The PhysioVP-AF study will provide an essential contribution to patient management with prolonged AV conduction and PM indication for sinus nodal disease or paroxysmal 2nd-degree AV-block by determining whether CSP combined with a controlled PR interval is superior to standard management that minimizes unnecessary VP in terms of reducing clinical outcomes.

Comparative Study of Bioactive Compounds and Biological Activities of Five Rose Hip Species Grown in Sicily.

Nowadays, research on plant extracts has attracted increasing interest. The aim of this study was to compare phenolic profile, vitamin C, and carotenoid content, as well as the biological activities of five different rose species, including Rosa canina, R. corymbifera, R. micrantha, R. rubiginosa, and R. rugosa. These species had different morphological characteristics, with R. rugosa showing higher size of flower petals and higher weight of hips. The highest vitamin C content was found in hip extracts of R. rubiginosa and R. rugosa, which also showed the highest carotenoid amount. R. corymbifera showed the highest phenolic content. No significant antimicrobial activity of extracts containing phenolic compounds against different indicator strains could be detected. Cell monolayer integrity was not affected by treatments with the above-mentioned extracts of R. canina, R. micrantha, and R. rugosa at different concentrations for up to 24 h, while those of R. rubiginosa and R. corymbifera affected intestinal permeability at the highest concentration tested. The partial least squares regression analysis generated a predictive model correlating phenolic compounds with cell monolayer integrity, suggesting a relevant role for catechin, quercitrin, and p-coumaric acid. In conclusion, this study highlights how rose hips belonging to different species can have a diverse phenolic profile, differently influencing intestinal monolayer integrity.

Unraveling the Effects of Carotenoids Accumulation in Human Papillary Thyroid Carcinoma.

Among the thyroid cancers, papillary thyroid cancer (PTC) accounts for 90% of the cases. In addition to the necessity to identify new targets for PTC treatment, early diagnosis and management are highly demanded. Previous data indicated that the multivariate statistical analysis of the Raman spectra allows the discrimination of healthy tissues from PTC ones; this is characterized by bands typical of carotenoids. Here, we dissected the molecular effects of carotenoid accumulation in PTC patients by analyzing whether they were required to provide increased retinoic acid (RA) synthesis and signaling and/or to sustain antioxidant functions. HPLC analysis revealed the lack of a significant difference in the overall content of carotenoids. For this reason, we wondered whether the carotenoid accumulation in PTC patients could be related to vitamin A derivative retinoic acid (RA) biosynthesis and, consequently, the RA-related pathway activation. The transcriptomic analysis performed using a dedicated PCR array revealed a significant downregulation of RA-related pathways in PTCs, suggesting that the carotenoid accumulation in PTC could be related to a lower metabolic conversion into RA compared to that of healthy tissues. In addition, the gene expression profile of 474 PTC cases previously published in the framework of the Cancer Genome Atlas (TGCA) project was examined by hierarchical clustering and heatmap analyses. This metanalysis study indicated that the RA-related pathways resulted in being significantly downregulated in PTCs and being associated with the follicular variant of PTC (FV-PTC). To assess whether the possible fate of the carotenoids accumulated in PTCs is associated with the oxidative stress response, the expression of enzymes involved in ROS scavenging was checked. An increased oxidative stress status and a reduced antioxidant defense response were observed in PTCs compared to matched healthy thyroids; this was possibly associated with the prooxidant effects of high levels of carotenoids. Finally, the DepMap datasets were used to profile the levels of 225 metabolites in 12 thyroid cancer cell lines. The results obtained suggested that the high carotenoid content in PTCs correlates with tryptophan metabolism. This pilot provided novel possible markers and possible therapeutic targets for PTC diagnosis and therapy. For the future, a larger study including a higher number of PTC patients will be necessary to further validate the molecular data reported here.

Prognostic Impact of New-Onset Atrial Fibrillation After Single or Double Stent Left Main Bifurcation PCI.

OBJECTIVE: Incidence and prognostic value of new-onset atrial fibrillation after single versus double stent strategy in bifurcation left main disease has not been yet investigated. METHODS: We retrospectively analyzed the procedural and medical data of patients referred to our center for complex left main bifurcation disease, treated using crossover provisional stenting, T or T-and-Protrusion, Culotte, and Nano-inverted-T techniques between January 1, 2008, and May 1, 2018. Multivariate Cox-regression analysis was used to assess the role of different stent strategies, adjusted for confounders, on the risk of new-onset atrial fibrillation during the follow-up period. RESULTS: Five hundred two patients (316 males, mean age 70.3 ± 12.8 years, mean Syntax score 31.6 ± 6.3) were evaluated. At a mean follow-up of 37.1 ± 10.8 months (range: 22.1- 39.3 months); Target lesion failure rate was 10.1%. Stent thrombosis and cardiovascular mor- tality were observed in 1.2% and 3.6% in of cases, respectively. New-onset atrial fibrillation occurred in 23 out of 502 patients (4.6%). Patients with new-onset atrial fibrillation resulted more frequently female, older, obese, and diabetic and more frequently experienced target lesion failure and cardiovascular death. New-onset atrial fibrillation-free survival favored single versus double stent technique and among double stent techniques nano-inverted-T tech- niques compared to the others. Single stent strategy had a lower risk of new-onset atrial fibril- lation compared to double stent technique on multivariate analysis (Hazard Ratio (HR): 1.14, 95% CI: 1.10-1.19, P < .001 vs. HR: 1.28, 95% CI: 1.23-1.32, P < .0001). CONCLUSION: New-onset atrial fibrillation in distal left main bifurcation disease treated with per- cutaneous coronary intervention had a low incidence but resulted more frequently after double than after single stenting technique and was associated with worse outcomes.

His Bundle Pacing: My Experience, Tricks, and Tips.

His Bundle Pacing (HBP) is a form of physiologic pacing achieved through implantation of a pacing electrode into the His bundle. HBP began 20 years ago without any dedicated tools. As specific tools became available HBP quickly spread and proved to be a viable alternative to traditional right ventricle pacing. HBP is reliable and effective in preserving the physiologic ventricular synchrony with clinical benefits particularly evident when a high percentage of pacing is required. Unipolar signals from the lead tip guide the implant. 3D electroanatomical mapping could further assist the procedure.

A Review of the Effects of Olive Oil-Cooking on Phenolic Compounds.

The fate of phenolic compounds in oil and food during cooking vary according to the type of cooking. From a nutritional point of view, reviews largely suggest a preference for using extra-virgin olive oil at a low temperature for a short time, except for frying and microwaving, for which there appears to be no significant advantages compared to olive oil. However, due to the poorly pertinent use of terminology, the different protocols adopted in studies aimed at the same objective, the different type and quality of oils used in experiments, and the different quality and quantity of PC present in the used oils and in the studied vegetables, the evidence available is mainly contradictory. This review tries to reanalyse the main experimental reports on the fate, accessibility and bioavailability of phenolic compounds in cooking oils and cooked vegetables, by considering different cooking techniques and types of oil and foods, and distinguishing experimental findings obtained using oil alone from those in combination with vegetables. The re-analysis indicates that incomplete and contradictory observations have been published in the last few years and suggests that further research is necessary to clarify the impact of cooking techniques on the phenolic compounds in oil and vegetables during cooking, especially when considering their nutritional properties.

Covid-19 and diet: an evaluation of information available on internet in Italy.

BACKGROUND AND AIM: During Coronavirus disease 2019 (Covid-19) Italy experienced deep lockdown with closure of almost all activities, with the exception for food shops and few others. During this quarantine, alteration of dietary habits occurred, due to the changes in food availability and mandatory meal house-consumption. The change in dietary habits could somehow be directed by freely accessible information available on internet.  Thus, s we evaluated the type and the scientific quality of the information provided to the Italian population by the most visible web sites found on google, relating diet in Covid-19 time. METHODS: we systematically perform a reliability and content analysis of Italian language websites using google as search engine and a combinations of diet/nutrition/Covid-19 as search terms Results: 88 webpages were included in the study, the great part representing newspaper webpages. Institutional webpages, despite having high scientific quality, did not have high visibility. Generally, all the other webpages reported information of medium-quality scientific level. CONCLUSION: finding appropriate solutions to redirect the population's attention to more reliable and accessible information is mandatory.

The Role of Bioactive Phenolic Compounds on the Impact of Beer on Health.

This review reports recent knowledge on the role of ingredients (barley, hop and yeasts), including genetic factors, on the final yield of phenolic compounds in beer, and how these molecules generally affect resulting beer attributes, focusing mainly on new attempts at the enrichment of beer phenols, with fruits or cereals other than barley. An entire section is dedicated to health-related effects, analyzing the degree up to which studies, investigating phenols-related health effects of beer, have appropriately considered the contribution of alcohol (pure or spirits) intake. For such purpose, we searched Scopus.com for any kind of experimental model (in vitro, animal, human observational or intervention) using beer and considering phenols. Overall, data reported so far support the existence of the somehow additive or synergistic effects of phenols and ethanol present in beer. However, findings are inconclusive and thus deserve further animal and human studies.

Occurrence of persistent atrial fibrillation during pacing for sinus node disease: The influence of His bundle pacing versus managed ventricular pacing.

INTRODUCTION: In patients with sinus node disease (SND), the dual-chamber pacemaker (PM) is programmed in DDDR mode with an algorithm to avoid unnecessary right ventricular (RV) pacing. This pacing mode may prolong PR interval with consequently atrioventricular (AV) asynchrony which is associated with a higher risk of atrial fibrillation (AF). We evaluate whether preserving AV synchrony by setting a fixed AV delay during physiological RV pacing, that is, His bundle pacing (HBP), could reduce the risk of AF occurrence in comparison with a standard pacing mode with an algorithm to avoid unnecessary RV pacing (DDD-VPA). METHODS AND RESULTS: We collected retrospective data from 313 consecutive patients who had undergone PM for SND. The first occurrence of persistent AF (>7 consecutive days) as a function of the pacing mode was evaluated. HBP and DDD-VPA were implemented in 82 and 231 patients, respectively. Persistent AF occurred in 128 (40.9%) patients over a median follow-up of 70 months (67-105). The DDD-VPA pacing mode was significantly correlated with the occurrence of persistent AF only when the basal PR was long (>180 ms). The risk of persistent AF was significantly lower in patients on HBP than in those on DDD-VPA, adjusted HR = .57 (95% CI, .36- .89, p=.014). Other independent predictors of persistent AF occurrence were: A history of AF (HR = 3.91; 95% CI, 2.48-6.19, p = .001), age, and long PR interval (HR = 2.98; 95% CI, 2.00-4.43, p=.001). CONCLUSION: In SND patients and long basal PR interval, the HBP may reduce the risk of persistent AF in comparison with the DDD-VPA.

Estimulación por marcapasos del haz de His: el mito se hace realidad / His bundle pacing: the myth is approaching standard medical care

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Implantation technique of His bundle pacing.

His bundle pacing (HBP) preserves physiological ventricular synchrony, with clinical benefits particularly evident when a high percentage of ventricular pacing is required. First experiences with standard leads and manually shaped stylets produced the impression that HBP is highly complex and time-consuming. However, with dedicated leads and sheaths, reliable HBP can be achieved in routine clinical practice. Implantation success in more than 90% of patients can be reached with current technology and has been shown to be reliable and effective, both at implantation and during long-term follow-up. At the same time, fluoroscopy and total procedural time can be reduced. New customized technologies will continue to improve the implant success rate and system performance. Large randomized trials will prove the long-term clinical benefits of HBP definitively and may render HBP the first choice in patients requiring ventricular pacing.