Megaselia scalaris and Senotainia tricuspis Infesting Apis mellifera: Detection by Quantitative PCR, Genotyping, and Involvement in the Transmission of Microbial Pathogens.

The Megaselia scalaris and Senotainia tricuspis parasitoid flies of the honeybee Apis mellifera were found to infest apiaries of different European and Mediterranean countries but their prevalence and impact on apiary health are little known. Therefore, in this study, quantitative PCR (qPCR)-based methods were developed for their rapid detection directly in hive matrices. The newly developed qPCR assays were targeted at the mitochondrial cytochrome oxidase subunit I (COI) gene for the M. scalaris and the cytochrome B (cytB) gene for the S. tricuspis. The tests were preliminarily applied to 64 samples of adult honeybees and hive debris collected in the Abruzzo and Molise regions, Central Italy, and the Republic of Kosovo showing that both flies occur in the two countries and more frequently in Italy. The positive apiaries in Italy were re-sampled by capturing viable forager bees and isolating emerging flies to carry out the genotyping and analyses aimed at defining if these flies can transmit honeybee pathogens. Genotyping based on the COI and cytB gene sequencing for M. scalaris and S. tricuspis, respectively, identified one S. tricuspis genotype and diverse genotypes of M. scalaris highly similar to those from distant countries. Some fly isolates harbored the DNA or RNA of honeybee microbial pathogens Paenibacillus larvae, deformed wing viruses A and B (DWVA and B), black queen cell virus (BQCV), chronic paralysis virus (CBPV), and Nosema ceranae. The results indicated that these parasites should be efficiently controlled in apiaries by using rapid detection methods to facilitate the large screening studies and early detection.

Efficacy of early use of Percutaneous Stellate Ganglion Block for electrical storms.

BACKGROUND: Electrical Storm (ES) is a life-threatening condition requiring a rapid management. Percutaneous Stellate Ganglion Block (PSGB) proved to be safe and effective on top of standard therapy, but no data are available about its early use. METHODS: We considered all patients enrolled from 1st July 2017 to 30th April 2024 in the STAR registry (STellate ganglion block for Arrhythmic stoRm), a multicentre, international, observational, prospective registry. We aimed to assess the effectiveness of the first PSGB only. Patients were divided into two groups depending on whether they received PSGB before (Early-PSGB, often due to AAD contraindication) or after (Delayed-PSGB) intravenous antiarrhythmic drugs (AADs other than beta-blockers). RESULTS: We considered 180 PSGB (26 Early-PSGB and 154 AAD-first). In the early-PSGB group we observed a statistically significant reduction of treated arrhythmic events in the hour after PSGB compared to the hour before: 0 (0-0) vs 4.5 (1-10), p<0.001 and the extent of the reduction was similar in the Early-PSGB and delayed-PSGB group [-4.5 (-7 to -2) vs. -2.5 (-3.5 to -1.5), p=ns]. The percentage of patients free from arrhythmias was similar in the two groups up to 12 hours after PSGB (81%vs 84%, p=0.6 after one hour; 77% vs 79%, p=0.8 at three hours and 65% vs 69%, p= 0.7 after 12 hours). CONCLUSIONS: PSGB proved to be effective also when used early in the treatment of ES. Due to its rapidity of action, our results may suggest its early use to reduce the number of defibrillations and possibly to reduce the likelihood of a refractory ES.

Amplitude spectral area of ventricular fibrillation can discriminate survival of patients with out-of-hospital cardiac arrest.

Background: Evidence of the association between AMplitude Spectral Area (AMSA) of ventricular fibrillation and outcome after out-of-hospital cardiac arrest (OHCA) is limited to short-term follow-up. In this study, we assess whether AMSA can stratify the risk of death or poor neurological outcome at 30 days and 1 year after OHCA in patients with an initial shockable rhythm or with an initial non-shockable rhythm converted to a shockable one. Methods: This is a multicentre retrospective study of prospectively collected data in two European Utstein-based OHCA registries. We included all cases of OHCAs with at least one manual defibrillation. AMSA values were calculated after data extraction from the monitors/defibrillators used in the field by using a 2-s pre-shock electrocardiogram interval. The first detected AMSA value, the maximum value, the average value, and the minimum value were computed, and their outcome prediction accuracy was compared. Multivariable Cox regression models were run for both 30-day and 1-year deaths or poor neurological outcomes. Neurological cerebral performance category 1-2 was considered a good neurological outcome. Results: Out of the 578 patients included, 494 (85%) died and 10 (2%) had a poor neurological outcome at 30 days. All the AMSA values considered (first value, maximum, average, and minimum) were significantly higher in survivors with good neurological outcome at 30 days. The average AMSA showed the highest area under the receiver operating characteristic curve (0.778, 95% CI: 0.7-0.8, p < 0.001). After correction for confounders, the highest tertiles of average AMSA (T3 and T2) were significantly associated with a lower risk of death or poor neurological outcome compared with T1 both at 30 days (T2: HR 0.6, 95% CI: 0.4-0.9, p = 0.01; T3: HR 0.6, 95% CI: 0.4-0.9, p = 0.02) and at 1 year (T2: HR 0.6, 95% CI: 0.4-0.9, p = 0.01; T3: HR 0.6, 95% CI: 0.4-0.9, p = 0.01). Among survivors at 30 days, a higher AMSA was associated with a lower risk of mortality or poor neurological outcome at 1 year (T3: HR 0.03, 95% CI: 0-0.3, p = 0.02). Discussion: Lower AMSA values were significantly and independently associated with the risk of death or poor neurological outcome at 30 days and at 1 year in OHCA patients with either an initial shockable rhythm or a conversion rhythm from non-shockable to shockable. The average AMSA value had the strongest association with prognosis.

Validation of Utstein-Based score to predict return of spontaneous circulation (UB-ROSC) in patients with out-of-hospital cardiac arrest.

BACKGROUND AND AIMS: The Utstein Based-ROSC (UB-ROSC) score has been developed to predict ROSC in OHCA victims. Aim of the study was to validate the UB-ROSC score using two Utstein-based OHCA registries: the SWiss REgistry of Cardiac Arrest (SWISSRECA) and the Lombardia Cardiac Arrest Registry (Lombardia CARe), northern Italy. METHODS: Consecutive patients with OHCA of any etiology occurring between January 1st, 2019 and December 31st 2021 were included in this retrospective validation study. UB-ROSC score was computed for each patient and categorized in one of three subgroups: low, medium or high likelihood of ROSC according to the UB-ROSC cut-offs (≤-19; -18 to 12; ≥13). To assess the performance of the UB-ROSC score in this new cohort, we assessed both discrimination and calibration. The score was plotted against the survival to hospital admission. RESULTS: A total of 12.577 patients were included in the study. A sustained ROSC was obtained in 2.719 patients (22%). The UB-ROSC model resulted well calibrated and showed a good discrimination (AUC 0.71, 95% CI 0.70-0.72). In the low likelihood subgroup of UB-ROSC, only 10% of patients achieved ROSC, whereas the proportion raised to 36% for a score between -18 and 12 (OR 5.0, 95% CI 2.9-8.6, p < 0.001) and to 85% for a score ≥13 (OR 49.4, 95% CI 14.3-170.6, p < 0.001). CONCLUSIONS: UB-ROSC score represents a reliable tool to predict ROSC probability in OHCA patients. Its application may help the medical decision-making process, providing a realistic stratification of the probability for ROSC.

Electrical storm treatment by percutaneous stellate ganglion block: the STAR study.

BACKGROUND AND AIMS: An electrical storm (ES) is a clinical emergency with a paucity of established treatment options. Despite initial encouraging reports about the safety and effectiveness of percutaneous stellate ganglion block (PSGB), many questions remained unsettled and evidence from a prospective multicentre study was still lacking. For these purposes, the STAR study was designed. METHODS: This is a multicentre observational study enrolling patients suffering from an ES refractory to standard treatment from 1 July 2017 to 30 June 2023. The primary outcome was the reduction of treated arrhythmic events by at least 50% comparing the 12 h following PSGB with the 12 h before the procedure. STAR operators were specifically trained to both the anterior anatomical and the lateral ultrasound-guided approach. RESULTS: A total of 131 patients from 19 centres were enrolled and underwent 184 PSGBs. Patients were mainly male (83.2%) with a median age of 68 (63.8-69.2) years and a depressed left ventricular ejection fraction (25.0 ± 12.3%). The primary outcome was reached in 92% of patients, and the median reduction of arrhythmic episodes between 12 h before and after PSGB was 100% (interquartile range -100% to -92.3%). Arrhythmic episodes requiring treatment were significantly reduced comparing 12 h before the first PSGB with 12 h after the last procedure [six (3-15.8) vs. 0 (0-1), P < .0001] and comparing 1 h before with 1 h after each procedure [2 (0-6) vs. 0 (0-0), P < .001]. One major complication occurred (0.5%). CONCLUSIONS: The findings of this large, prospective, multicentre study provide evidence in favour of the effectiveness and safety of PSGB for the treatment of refractory ES.

Genetic screening for hereditary transthyretin amyloidosis with polyneuropathy in western Sicily: Two years of experience in a neurological clinic.

BACKGROUND AND PURPOSE: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils. METHODS: A prospective systematic genetic screening for ATTRv-PN was proposed in patients presenting with a sensory-motor idiopathic polyneuropathy and two or more "red flags" among the following: family history of polyneuropathy or cardiopathy, bilateral carpal tunnel syndrome, cardiac insufficiency, renal amyloidosis, lumbar tract stenosis, autonomic dysfunction, idiopathic gastrointestinal disease, amyloid deposits on biopsy, and vitreous opacities. The detection rate was calculated, and nonparametric analyses were carried out to underline differences among screened positive versus negative patients. RESULTS: In the first step, 145 suspected patients underwent genetic testing, revealing a diagnosis of ATTRv-PN in 14 patients (10%). Then, cascade screening allowed early recognition of 33 additional individuals (seven symptomatic ATTRv-PN patients and 26 presymptomatic carriers) among 84 first-degree relatives. Patients with a positive genetic test presented a higher frequency of unexplained weight loss, gastrointestinal symptoms, and family history of cardiopathy. CONCLUSIONS: A systematic screening for ATTRv-PN yielded an increased recognition of the disease in our neurological clinic. Unexplained weight loss associated with axonal polyneuropathy had the highest predictive value in the guidance of clinical suspicion. A focused approach for the screening of ATTRv-PN could lead to an earlier diagnosis and identification of asymptomatic carriers, who will be promptly treated after a strict follow-up at the clinical onset.

Mitral valve transcatheter edge-to-edge repair with PASCAL Vs MitraClip: A aystematic teview and meta-analysis.

BACKGROUND: Transcatheter edge-to-edge repair (TEER) using the MitraClip (Abbott Vascular) system has emerged as a standard treatment for patients with symptomatic severe secondary or inoperable primary mitral regurgitation (MR). The relatively recent approval of the PASCAL Transcatheter Valve Repair System (Edwards Lifesciences) has expanded the options of TEER devices. However, evidence comparing PASCAL with MitraClip systems is still limited. METHODS: We conducted a systematic literature research and meta-analysis in PubMed, Medline, and EMBASE databases for studies comparing PASCAL and MitraClip systems. RESULTS: Four observational studies and 1 randomized controlled trial, involving 1315 patients total, were eligible for inclusion. All patients exhibited symptomatic (NYHA II-IV) MR grades 3+ or 4+. Baseline characteristics were comparable across all included studies. The clinical outcomes were assessed according to the Mitral Valve Academic Research Consortium consensus. The procedural success rates for the 2 devices were comparable in terms of achieving post-procedural MR grades of less than or equal to 2+ and less than or equal to 1+. Furthermore, most patients improved their clinical status, with no significant differences between patients treated with PASCAL and those treated with MitraClip. In terms of safety, both procedures exhibited low overall mortality rates and occurrence of major adverse events (MAE), without significant difference between the 2 devices. These findings remained consistent in both short- and long-term follow-up assessments. CONCLUSIONS: Our study revealed similar effectiveness and safety profiles between the PASCAL and MitraClip devices in patients experiencing significant symptomatic MR.

Amplitude spectral area of ventricular fibrillation and defibrillation success at low energy in out-of-hospital cardiac arrest.

The optimal energy for defibrillation has not yet been identified and very often the maximum energy is delivered. We sought to assess whether amplitude spectral area (AMSA) of ventricular fibrillation (VF) could predict low energy level defibrillation success in out-of-hospital cardiac arrest (OHCA) patients. This is a multicentre international study based on retrospective analysis of prospectively collected data. We included all OHCAs with at least one manual defibrillation. AMSA values were calculated by analyzing the data collected by the monitors/defibrillators used in the field (Corpuls 3 and Lifepak 12/15) and using a 2-s-pre-shock electrocardiogram interval. We run two different analyses dividing the shocks into three tertiles (T1, T2, T3) based on AMSA values. 629 OHCAs were included and 2095 shocks delivered (energy ranging from 100 to 360 J; median 200 J). Both in the "extremes analysis" and in the "by site analysis", the AMSA values of the effective shocks at low energy were significantly higher than those at high energy (p = 0.01). The likelihood of shock success increased significantly from the lowest to the highest tertile. After correction for age, call to shock time, use of mechanical CPR, presence of bystander CPR, sex and energy level, high AMSA value was directly associated with the probability of shock success [T2 vs T1 OR 3.8 (95% CI 2.5-6) p < 0.001; T3 vs T1 OR 12.7 (95% CI 8.2-19.2), p < 0.001]. AMSA values are associated with the probability of low-energy shock success so that they could guide energy optimization in shockable cardiac arrest patients.

Use of Mechanical Chest Compression for Resuscitation in Out-Of-Hospital Cardiac Arrest-Device Matters: A Propensity-Score-Based Match Analysis.

BACKGROUND: Devices for mechanical cardiopulmonary resuscitation (CPR) are recommended when high quality CPR cannot be provided. Different devices are available, but the literature is poor in direct comparison studies. Our aim was to assess whether the type of mechanical chest compressor could affect the probability of return of spontaneous circulation (ROSC) and 30-day survival in Out-of-Hospital Cardiac Arrest (OHCA) patients as compared to manual standard CPR. METHODS: We considered all OHCAs that occurred from 1 January 2015 to 31 December 2022 in seven provinces of the Lombardy region equipped with three different types of mechanical compressor: Autopulse®(ZOLL Medical, MA), LUCAS® (Stryker, MI), and Easy Pulse® (Schiller, Switzerland). RESULTS: Two groups, 2146 patients each (manual and mechanical CPR), were identified by propensity-score-based random matching. The rates of ROSC (15% vs. 23%, p < 0.001) and 30-day survival (6% vs. 14%, p < 0.001) were lower in the mechanical CPR group. After correction for confounders, Autopulse® [OR 2.1, 95%CI (1.6-2.8), p < 0.001] and LUCAS® [OR 2.5, 95%CI (1.7-3.6), p < 0.001] significantly increased the probability of ROSC, and Autopulse® significantly increased the probability of 30-day survival compared to manual CPR [HR 0.9, 95%CI (0.8-0.9), p = 0.005]. CONCLUSION: Mechanical chest compressors could increase the rate of ROSC, especially in case of prolonged resuscitation. The devices were dissimilar, and their different performances could significantly influence patient outcomes. The load-distributing-band device was the only mechanical chest able to favorably affect 30-day survival.

aMplitude spectral area of ventricular fibrillation and amiOdarone Study in patients with out-of-hospital cArdIaC arrest. The MOSAIC study.

Objective: Antiarrhythmic drugs are recommended for out of hospital cardiac arrest (OHCA) with shock-refractory ventricular fibrillation (VF). Amplitude Spectral Area (AMSA) of VF is a quantitative waveform measure that describes the amplitude-weighted mean frequency of VF, it correlates with intramyocardial adenosine triphosphate (ATP) concentration, it is a predictor of shock efficacy and an emerging indicator to guide defibrillation and resuscitation efforts. How AMSA might be influenced by amiodarone administration is unknown. Methods: In this international multicentre observational study, all OHCAs receiving at least one shock were included. AMSA values were calculated by retrospectively analysing the pre-shock ECG interval of 2 s. Multivariable models were run and a propensity score based on the probability of receiving amiodarone was created to compare two randomly matched samples. Results: 2,077 shocks were included: 1,407 in the amiodarone group and 670 in the non-amiodarone group. AMSA values were lower in the amiodarone group [8.8 (6-12.7) mV·Hz vs. 9.8 (6-14) mV·Hz, p = 0.035]. In two randomly matched propensity score-based groups of 261 shocks, AMSA was lower in the amiodarone group [8.2 (5.8-13.5) mV·Hz vs. 9.6 (5.6-11.6), p = 0.042]. AMSA was a predictor of shock success in both groups but the predictive power was lower in the amiodarone group [Area Under the Curve (AUC) non-amiodarone group 0.812, 95%CI: 0.78-0.841 vs. AUC amiodarone group 0.706, 95%CI: 0.68-0.73; p < 0.001]. Conclusions: Amiodarone administration was independently associated with the probability of recording lower values of AMSA. In patients who have received amiodarone during cardiac arrest the predictive value of AMSA for shock success is significantly lower, but still statistically significant.

Association Between Postresuscitation 12-Lead ECG Features and Early Mortality After Out-of-Hospital Cardiac Arrest: A Post Hoc Subanalysis of the PEACE Study.

Background Once the return of spontaneous circulation after out-of-hospital cardiac arrest is achieved, a 12-lead ECG is strongly recommended to identify candidates for urgent coronary angiography. ECG has no apparent role in mortality risk stratification. We aimed to assess whether ECG features could be associated with 30-day survival in patients with out-of-hospital cardiac arrest. Methods and Results All the post-return of spontaneous circulation ECGs from January 2015 to December 2018 in 3 European centers (Pavia, Lugano, and Vienna) were collected. Prehospital data were collected according to the Utstein style. A total of 370 ECGs were collected: 287 men (77.6%) with a median age of 62 years (interquartile range, 53-70 years). After correction for the return of spontaneous circulation-to-ECG time, age >62 years (hazard ratio [HR], 1.78 [95% CI, 1.21-2.61]; P=0.003), female sex (HR, 1.5 [95% CI, 1.05-2.13]; P=0.025), QRS wider than 120 ms (HR, 1.64 [95% CI, 1.43-1.87]; P<0.001), the presence of a Brugada pattern (HR, 1.49 [95% CI, 1.39-1.59]; P<0.001), and the presence of ST-segment elevation in >1 segment (HR, 1.75 [95% CI, 1.59-1.93]; P<0.001) were independently associated with 30-day mortality. A score ranging from 0 to 26 was created, and by dividing the population into 3 tertiles, 3 classes of risk were found with significantly different survival rate at 30 days (score 0-4, 73%; score 5-7, 66%; score 8-26, 45%). Conclusions The post-return of spontaneous circulation ECG can identify patients who are at high risk of mortality after out-of-hospital cardiac arrest earlier than other forms of prognostication. This provides important risk stratification possibilities in postcardiac arrest care that could help to direct treatments and improve outcomes in patients with out-of-hospital cardiac arrest.

Impact of sex and role of coronary artery disease in out-of-hospital cardiac arrest presenting with refractory ventricular arrhythmias.

Introduction: There are limited data on sex-related differences in out-of hospital cardiac arrests (OHCAs) with refractory ventricular arrhythmias (VA) and, in particular, about their relationship with cardiovascular risk profile and severity of coronary artery disease (CAD). Purpose: Aim of this study was to characterize sex-related differences in clinical presentation, cardiovascular risk profile, CAD prevalence, and outcome in OHCA victims presenting with refractory VA. Methods: All OHCAs with shockable rhythm that occurred between 2015 and 2019 in the province of Pavia (Italy) and in the Canton Ticino (Switzerland) were included. Results: Out of 680 OHCAs with first shockable rhythm, 216 (33%) had a refractory VA. OHCA patients with refractory VA were younger and more often male. Males with refractory VA had more often a history of CAD (37% vs. 21%, p 0.03). In females, refractory VA were less frequent (M : F ratio 5 : 1) and no significant differences in cardiovascular risk factor prevalence or clinical presentation were observed. Male patients with refractory VA had a significantly lower survival at hospital admission and at 30 days as compared to males without refractory VA (45% vs. 64%, p < 0.001 and 24% vs. 49%, p < 0.001, respectively). Whereas in females, no significant survival difference was observed. Conclusions: In OHCA patients presenting with refractory VA the prognosis was significantly poorer for male patients. The refractoriness of arrhythmic events in the male population was probably due to a more complex cardiovascular profile and in particular due to a pre-existing CAD. In females, OHCA with refractory VA were less frequent and no correlation with a specific cardiovascular risk profile was observed.

Hypertrophic Cardiomyopathy and Atrial Fibrillation: A Systematic Review and Meta-analysis of Anticoagulation Strategy.

BACKGROUND: Atrial fibrillation (AF) frequently complicates hypertrophic cardiomyopathy (HCM), and anticoagulation significantly decreases the risk of stroke in this population. To date, no randomized controlled trials (RCTs) have compared direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs). The present study aimed to systematically compare the two anticoagulation strategies in terms of effectiveness and safety. METHOD: We performed a systematic literature search and meta-analysis in the PubMed, MEDLINE, and EMBASE databases for studies reporting all-cause mortality, major bleeding, or thromboembolic events (TEs). Since no RCTs were available, we included observational studies only. The overall hazard ratio (HR) and 95% confidence interval (CI) for each analyzed parameter were pooled using a random-effects model. RESULTS: Five observational studies including 6919 patients were eligible for inclusion. Compared with VKAs, DOACs were associated with statistically significant lower rates of all-cause mortality (HR 0.64, 95% CI 0.35-0.54; p < 0.00001), comparable major bleeding events (HR 0.64, 95% CI 0.40-1.03; p = 0.07), and TEs (HR 0.94, 95% CI 0.73-1.22; p = 0.65). CONCLUSIONS: Compared with VKAs, a DOAC-based strategy might represent an effective and safe strategy regarding all-cause mortality, major/life-threatening bleeding complications, and TEs in HCM patients with concomitant AF. However, further prospective studies are necessary to reinforce a DOAC-based anticoagulation strategy in this population.

Influence of Nanoaggregation Routes on the Structure and Thermal Behavior of Multiple-Stimuli-Responsive Micelles from Block Copolymers of Oligo(ethylene glycol) Methacrylate and the Weak Acid [2-(Hydroxyimino)aldehyde]butyl Methacrylate.

In this work, we compare nanoaggregation driven by pH-induced micellization (PIM) and by the standard solvent displacement (SD) method on a series of pH-, light-, and thermosensitive amphiphilic block copolymers. Specifically, we investigate poly(HIABMA)-b-poly(OEGMA) and poly(HIABMA)-b-poly(DEGMA-r-OEGMA), where HIABMA = [(hydroxyimino)aldehyde]butyl methacrylate, OEGMA = oligo(ethylene glycol)methyl ether methacrylate, and DEGMA = di(ethylene glycol)methyl ether methacrylate. The weakly acidic HIA group (pKa ≈ 8) imparts stability to micelles at neutral pH, unlike most of the pH-responsive copolymers investigated in the literature. With SD, only some of our copolymers yield polymeric micelles (34-59 nm), and their thermoresponsivity is either poor or altogether absent. In contrast, PIM affords thermoresponsive, smaller micelles (down to 24 nm), regardless of the polymer composition. In some cases, cloud points are remarkably well defined and exhibit limited hysteresis. By combining turbidimetric, dyamic light scattering, and small-angle X-ray scattering measurements, we show that SD yields loose micelles with POEGMA segments partly involved in the formation of the hydrophobic core, whereas PIM yields more compact core-shell micelles with a well-defined PHIABMA core. We conclude that pH-based nanoaggregation provides advantages over block-selective solvation to obtain compact micelles exhibiting well-defined responses to external stimuli.

Complete Revascularization and One-Year Survival with Good Neurological Outcome in Patients Resuscitated from an Out-of-Hospital Cardiac Arrest.

Background. The survival benefit of complete versus infarct-related artery (IRA)-only revascularization during the index hospitalization in patients resuscitated from an out-of-hospital cardiac arrest (OHCA) with multivessel disease is unknown. Methods. We considered all the OHCA patients prospectively enrolled in the Lombardia Cardiac Arrest Registry (Lombardia CARe) from 1 January 2015 to 1 May 2021 who underwent coronary angiography (CAG) at the Fondazione IRCCS Policlinico San Matteo (Pavia). Patients' prehospital, angiographical and survival data were reviewed. Results. Out of 239 patients, 119 had a multivessel coronary disease: 69% received IRA-only revascularization, and 31% received a complete revascularization: 8 during the first procedure and 29 in a staged-procedure after a median time of 5 days [IQR 2.5−10.3]. The complete revascularization group showed significantly higher one-year survival with good neurological outcome than the IRA-only group (83.3% vs. 30.4%, p < 0.001). After correcting for cardiac arrest duration, shockable presenting rhythm, peak of Troponin-I, creatinine on admission and the need for circulatory support, complete revascularization was independently associated with the probability of death and poor neurological outcome [HR 0.3 (95%CI 0.1−0.8), p = 0.02]. Conclusions. This observation study shows that complete myocardial revascularization during the index hospitalization improves one-year survival with good neurological outcome in patients resuscitated from an OHCA with multivessel coronary disease.

Direct oral anticoagulants or vitamin K antagonists after TAVR: A systematic review and meta-analysis.

BACKGROUND: Several patients undergoing transcatheter aortic valve replacement (TAVR) also require oral anticoagulation (OAC) for atrial fibrillation (AF) or deep vein thromboembolism. However, the optimal type of OAC strategy (direct oral anticoagulants, DOACs, or vitamin K antagonists, VKA) is still unclear in this setting. METHOD: We performed systematic literature research and meta-analysis in PubMed, Medline, and EMBASE databases for studies reporting either all-cause mortality, major/life-threatening bleeding or stroke events. RESULTS: Ten observational studies and two randomized controlled trials (RCTs) including a total of 29,485 patients were eligible for inclusion. Compared to VKA, DOACs use after TAVR was associated with a modest but significantly lower rates of all-cause mortality (RR 0.90; 95% CI: 0.81-0.99, p-value 0.04) with results mainly driven by observational studies. Cardiovascular mortality (RR 1.03; 95% CI: 0.81-1.30; p-value 0.84), total stroke events (RR 0.97; 95% CI: 0.76-1.23, p-value 0.79), major/life-threatening bleeding (RR 0.93; 95% CI: 0.72-1.21, p-value 0.61) and minor bleeding (RR 0.96; 95% CI: 0.74-1.23; p-value 0.72) were similar between VKA and DOACs. CONCLUSION: Considering the totality of available evidence, in patients who underwent TAVR with a concomitant indication for OAC, DOACs-based strategy is an effective and safe anticoagulation strategy compared to VKA.

Genotype-Driven Pathogenesis of Atrial Fibrillation in Hypertrophic Cardiomyopathy: The Case of Different TNNT2 Mutations.

Atrial dilation and atrial fibrillation (AF) are common in Hypertrophic CardioMyopathy (HCM) patients and associated with a worsening of prognosis. The pathogenesis of atrial myopathy in HCM remains poorly investigated and no specific association with genotype has been identified. By re-analysis of our cohort of thin-filament HCM patients (Coppini et al. 2014) AF was identified in 10% of patients with sporadic mutations in the cardiac Troponin T gene (TNNT2), while AF occurrence was much higher (25-75%) in patients carrying specific "hot-spot" TNNT2 mutations. To determine the molecular basis of arrhythmia occurrence, two HCM mouse models expressing human TNNT2 variants (a "hot-spot" one, R92Q, and a "sporadic" one, E163R) were selected according to the different pathophysiological pathways previously demonstrated in ventricular tissue. Echocardiography studies showed a significant left atrial dilation in both models, but more pronounced in the R92Q. In E163R atrial trabeculae, in line with what previously observed in ventricular preparations, the energy cost of tension generation was markedly increased. However, no changes of twitch amplitude and kinetics were observed, and there was no atrial arrhythmic propensity. R92Q atrial trabeculae, instead, displayed normal ATP consumption but markedly increased myofilament calcium sensitivity, as previously observed in ventricular preparations. This was associated with reduced inotropic reserve and slower kinetics of twitch contractions and, importantly, with an increased occurrence of spontaneous beats and triggered contractions that represent an intrinsic arrhythmogenic mechanism promoting AF. The association of specific TNNT2 mutations with AF occurrence depends on the mutation-driven pathomechanism (i.e., increased atrial myofilament calcium sensitivity rather than increased myofilament tension cost) and may influence the individual response to treatment.