Cryptic transmission of SARS-CoV-2 and the first COVID-19 wave.

Considerable uncertainty surrounds the timeline of introductions and onsets of local transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally1-7. Although a limited number of SARS-CoV-2 introductions were reported in January and February 2020 (refs.8,9), the narrowness of the initial testing criteria, combined with a slow growth in testing capacity and porous travel screening10, left many countries vulnerable to unmitigated, cryptic transmission. Here we use a global metapopulation epidemic model to provide a mechanistic understanding of the early dispersal of infections and the temporal windows of the introduction of SARS-CoV-2 and onset of local transmission in Europe and the USA. We find that community transmission of SARS-CoV-2 was likely to have been present in several areas of Europe and the USA by January 2020, and estimate that by early March, only 1 to 4 in 100 SARS-CoV-2 infections were detected by surveillance systems. The modelling results highlight international travel as the key driver of the introduction of SARS-CoV-2, with possible introductions and transmission events as early as December 2019 to January 2020. We find a heterogeneous geographic distribution of cumulative infection attack rates by 4 July 2020, ranging from 0.78% to 15.2% across US states and 0.19% to 13.2% in European countries. Our approach complements phylogenetic analyses and other surveillance approaches and provides insights that can be used to design innovative, model-driven surveillance systems that guide enhanced testing and response strategies.

Finger nodules with a papulovesicular hands and feet eruption: a complicated human Orf virus infection.

BACKGROUND: Orf virus (ORFV) is the pathogen responsible for Orf, a zoonotic viral infection that can be spread to humans from sheep and goats. Here, we present a case of human Orf complicated by an immune-related reaction, to raise awareness of this under-recognized disease avoiding unnecessary investigations and overtreatment. CASE REPORT: A 51-year-old woman with no previous medical history presented with a one-week history of three asymptomatic swelling nodules with a grey necrotic center and red outer halo on her index finger. At physical examination there was also a pruritic papulovesicular eruption on her hands and feet. She reported a recent contact with a goat which had a similar nodular lesion in its mouth. A biopsy of the lesions was performed and a diagnosis of Orf complicated by widespread erythema multiforme was made based on the clinical and histopathological features. The lesions spontaneously resolved within the next 2 weeks. CONCLUSIONS: Orf is not very prevalent in our region, so we performed a biopsy of the lesion to guide us toward a diagnosis. However, we should remember that the diagnosis of ecthyma relies on clinical evaluation and epidemiological criteria.

Interdisciplinary approach to solve unusual mortalities in the European common frog (Rana temporaria) in two high-mountain ponds affected by climate change.

The global decline in amphibian populations is a major environmental issue. Chytridiomycosis, Ranaviruses and the red-leg syndrome have been identified in unusual mortality events. However, these infections do not account for all causes of declining amphibian populations. Moreover, several cases of amphibian mortality are difficult to solve without resorting to an interdisciplinary approach. Two cases of unusual mortality in Rana temporaria occurred at two high-mountain ponds (northwest Italy) in April and May 2021. Water and frog samples were analysed to understand the possible causes responsible for the unusual mortalities. Results of the main physicochemical (pH, conductivity, dissolved oxygen, chemical and biochemical oxygen demand) and nutrient (ammonia/ammonium, nitrite, nitrate, total phosphorus) parameters revealed a good condition of the water quality, with the absence of the main cyanotoxins (microcystins/nodularins). However, unseasonably high spring water temperatures were recorded in both ponds (12.73 °C and 14.21 °C for Frog Pond and Selleries Pond, respectively). Frogs (n = 50; snout-vent length: 7.0-9.8 cm; body mass: 85-123 g) collected from Frog Pond mainly presented bumps on the ventral cavity and dermal ulceration associated with the isolation of Carnobacterium maltaromaticum. On the other hand, frogs (n = 5; snout-vent length: 8.0-9.1 cm; body mass: 87-92 g) from Selleries Pond presented petechiae and dermal ulcerations on the rear limbs associated with the isolation of Aeromonas salmonicida and A. sobria. In both mortality events, the interdisciplinary approach revealed an association between frog mortalities and the isolation of bacteria. Isolated bacteria are considered opportunistic pathogens, and the high values of the water temperature has certainly led a stress on the frogs, favouring the spread of bacteria and the death of the frogs. Further studies are needed to assess the pathophysiological effects of the opportunistic bacteria here isolated, clarifying the interactions between emerging pathogens and climate change.

Sustained right ventricular dysfunction in severe COVID-19: The role of disseminated intravascular coagulation.

BACKGROUND: Acute right ventricular (RV) failure is common in patients hospitalized with COVID-19. Compared to the conventional echocardiographic parameters, right ventricular longitudinal strain (RVLS) is more sensitive and accurate for the diagnosis of RV systolic dysfunction. OBJECTIVE: Our purpose was to investigate the sustained RV dysfunction echo-quantified by RVLS in patients recovered from severe COVID-19. Furthermore, we aimed to assess whether disseminated intravascular coagulation (DIC) has a key role to predict the impaired RV strain. METHODS: Of 198 consecutive COVID-19 patients hospitalized from March 1, 2020, to April 15, 2020, 45 selected patients who survived from severe COVID-19 were enrolled in the study and referred to our echo-lab for transthoracic echocardiography 6-months after discharge. RVLS was calculated as the mean of the strain values of RV free wall. DIC was defined with a validated scoring system: DIC score equal to or more than 5 is compatible with overt-DIC. Categories of acute respiratory distress syndrome (ARDS) were defined based on PaO2 /FiO2 ratio. RESULTS: A total 26 of 45 patients showed impaired RVLS at 6-months' follow-up. DIC score was significantly higher in patients with worse RVLS than in those with better RVLS (4.8 ± .5 vs. 3.6 ± .6, p =.03). Stages of ARDS did not modulate this relationship. Finally, overt-DIC results the only independent predictor of sustained RV dysfunction (OR 1.233, 95% CI 1.041-1.934, p =.043). CONCLUSIONS: Sustained RV impairment frequently occurs in patients recovered from severe COVID-19. DIC plays a key role, resulting in an independent predictor of sustained RV dysfunction.

Minimal fluoroscopy approach for right-sided supraventricular tachycardia ablation with a novel ablation technology: Insights from the multicenter CHARISMA clinical registry.

BACKGROUND: No data exist on the ability of the novel Rhythmia 3-D mapping system to minimize fluoroscopy exposure during transcatheter ablation of arrhythmias. We report data on the feasibility and safety of a minimal fluoroscopic approach using this system in supraventricular tachycardia (SVT) procedures. METHODS: Consecutive patients were enrolled in the CHARISMA registry at 12 centers. All right-sided procedures performed with the Rhythmia mapping system were analyzed. The acquired electroanatomic information was used to reconstruct 3-D cardiac geometry; fluoroscopic confirmation was used whenever deemed necessary. RESULTS: Three hundred twenty-five patients (mean age = 56 ± 17 years, 57% male) were included: 152 atrioventricular nodal reentrant tachycardia, 116 atrial flutter, 41 and 16 right-sided accessory pathway and atrial tachycardia, respectively. Overall, 27 481 s of fluoroscopy were used (84.6 ± 224 s per procedure, equivalent effective dose = 1.1 ± 3.7 mSv per patient). One hundred ninety-two procedures (59.1%) were completed without the use of fluoroscopy (zero fluoroscopy, ZF). In multivariate analysis, the presence of a fellow in training (OR = 0.15, 95% CI: 0.05-0.46; p = .0008), radiofrequency application (0.99, 0.99-1.00; p = .0002), and mapping times (0.99, 0.99-1.00; p = .042) were all inversely associated with ZF approach. Acute procedural success was achieved in 97.8% of the cases (98.4 vs. 97% in the ZF vs. non-ZF group; p = .4503). During a mean of 290.7 ± 169.6 days follow-up, no major adverse events were reported, and recurrence of the primary arrhythmia was 2.5% (2.1 vs. 3% in the ZF vs. non-ZF group; p = .7206). CONCLUSIONS: The Rhythmia mapping system permits transcatheter ablation of right-sided SVT with minimal fluoroscopy exposure. Even more, in most cases, the system enables a ZF approach, without affecting safety and efficacy.

Renin-angiotensin system inhibitors and mortality in patients with COVID-19.

Association of renin-angiotensin system inhibitors with risk of death in patients with hypertension (HTN) and coronavirus disease 2019 (COVID-19) is not well characterized. The aim of this study was to evaluate the outcomes of patients with HTN and COVID-19 with respect to different chronic antihypertensive drug intake. We performed a retrospective, observational study from a large cohort of patients with HTN and with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection admitted to the Emergency Rooms (ER) of the Piacenza Hospital network from February 21, 2020 to March 20, 2020. There were 1050 patients admitted to the ERs of the Piacenza Hospital network with COVID-19. HTN was present in 590 patients [median age, 76.2 years (IQR 68.2-82.6)]; 399 (66.1%) patients were male. Of them, 248 patients were chronically treated with ACEi, 181 with ARBs, and 161 with other drugs (O-drugs) including beta blockers, diuretics and calcium-channel inhibitors. With respect to the antihypertensive use, there was no difference between comorbid conditions. During a follow-up of 38 days (IQR 7.0-46.0), 256 patients (43.4%) died, without any difference stratifying for antihypertensive drugs. Of them, 107 (43.1%) were in ACEi group vs 67 (37%) in ARBs group vs 82 (50.7%) in O-drugs group, (log-rank test: p = 0.066). In patients with HTN and COVID-19, neither ACEi nor ARBs were independently associated with mortality. After adjusting for potential confounders in risk prediction, the rate of death was similar. Our data confirm Specialty Societal recommendations, suggesting that treatment with ACEIs or ARBs should not be discontinued because of COVID-19.

Safety, efficacy, and reproducibility of cavotricuspid isthmus ablation guided by the ablation index: acute results of the FLAI study.

AIMS: Ablation index (AI) is a marker of lesion quality during catheter ablation that incorporates contact force, time, and power in a weighted formula. This index was originally developed for pulmonary vein isolation as well as other left atrial procedures. The aim of our study is to evaluate the feasibility and efficacy of the AI for the ablation of the cavotricuspid isthmus (CTI) in patients presenting with typical atrial flutter (AFL). METHODS AND RESULTS: This prospective multicentre non-randomized study enrolled 412 consecutive patients with typical AFL undergoing AI-guided cavotricuspid isthmus ablation. The procedure was performed targeting an AI of 500 and an inter-lesion distance measurement of ≤6 mm. The primary endpoints were CTI 'first-pass' block and persistent block after a 20-min waiting time. Secondary endpoints included procedural and radiofrequency duration and fluoroscopic time. A total of 412 consecutive patients were enrolled in 31 centres (mean age 64.9 ± 9.8; 72.1% males and 27.7% with structural heart disease). The CTI bidirectional 'first-pass' block was reached in 355 patients (88.3%), whereas CTI block at the end of the waiting time was achieved in 405 patients (98.3%). Mean procedural, radiofrequency, and fluoroscopic time were 56.5 ± 28.1, 7.8 ± 4.8, and 1.9 ± 4.8 min, respectively. There were no major procedural complications. There was no significant inter-operator variability in the ability to achieve any of the primary endpoints. CONCLUSION: AI-guided ablation with an inter-lesion distance ≤6 mm represents an effective, safe, and highly reproducible strategy to achieve bidirectional block in the treatment of typical AFL.

A Machine Learning Approach for Mortality Prediction in COVID-19 Pneumonia: Development and Evaluation of the Piacenza Score.

BACKGROUND: Several models have been developed to predict mortality in patients with COVID-19 pneumonia, but only a few have demonstrated enough discriminatory capacity. Machine learning algorithms represent a novel approach for the data-driven prediction of clinical outcomes with advantages over statistical modeling. OBJECTIVE: We aimed to develop a machine learning-based score-the Piacenza score-for 30-day mortality prediction in patients with COVID-19 pneumonia. METHODS: The study comprised 852 patients with COVID-19 pneumonia, admitted to the Guglielmo da Saliceto Hospital in Italy from February to November 2020. Patients' medical history, demographics, and clinical data were collected using an electronic health record. The overall patient data set was randomly split into derivation and test cohorts. The score was obtained through the naïve Bayes classifier and externally validated on 86 patients admitted to Centro Cardiologico Monzino (Italy) in February 2020. Using a forward-search algorithm, 6 features were identified: age, mean corpuscular hemoglobin concentration, PaO2/FiO2 ratio, temperature, previous stroke, and gender. The Brier index was used to evaluate the ability of the machine learning model to stratify and predict the observed outcomes. A user-friendly website was designed and developed to enable fast and easy use of the tool by physicians. Regarding the customization properties of the Piacenza score, we added a tailored version of the algorithm to the website, which enables an optimized computation of the mortality risk score for a patient when some of the variables used by the Piacenza score are not available. In this case, the naïve Bayes classifier is retrained over the same derivation cohort but using a different set of patient characteristics. We also compared the Piacenza score with the 4C score and with a naïve Bayes algorithm with 14 features chosen a priori. RESULTS: The Piacenza score exhibited an area under the receiver operating characteristic curve (AUC) of 0.78 (95% CI 0.74-0.84, Brier score=0.19) in the internal validation cohort and 0.79 (95% CI 0.68-0.89, Brier score=0.16) in the external validation cohort, showing a comparable accuracy with respect to the 4C score and to the naïve Bayes model with a priori chosen features; this achieved an AUC of 0.78 (95% CI 0.73-0.83, Brier score=0.26) and 0.80 (95% CI 0.75-0.86, Brier score=0.17), respectively. CONCLUSIONS: Our findings demonstrated that a customizable machine learning-based score with a purely data-driven selection of features is feasible and effective for the prediction of mortality among patients with COVID-19 pneumonia.

Clinical and epidemiological characteristics of 320 deceased patients with COVID-19 in an Italian Province: A retrospective observational study.

Studies have described clinical features of patients with coronavirus disease (COVID-19). However, limited data concerning the clinical characteristics of the Italian deaths are available. We aim to describe the clinical and epidemiological characteristics of 320 deceased from the Italian experience. We retrospectively collected all consecutive non-survivor patients with laboratory-confirmed COVID-19 infection admitted to the Emergency Rooms (ERs) Piacenza Hospital Network during the first month of COVID-19 pandemic in Italy. Clinical history, comorbidities, laboratory findings and treatment were recorded for each patient. A total of 1050 patients with confirmed COVID-19 pneumonia were admitted to the ERs between 24 February and 22 March 2020. Three hundred and twenty (30.5%) patients died with a median age of 78.0 years, 205 (64%) non-survivors were above 65 years old, 230 (71.9%) were male. Non-survivor patients showed frequently several coexisting medical conditions, with hypertension being the most common comorbidity (235 patients, 73.4%). The in-hospital mortality did not change during the progression of the pandemic. In this retrospective Italian study, most of COVID-19 deceased patients were elderly male aged over than 65 years. Hypertension was the most common coexisting disease. In-hospital mortality was high and showed no variation during the first month of the COVID-19 italian epidemic.

Reproducibility of pulmonary vein isolation guided by the ablation index: 1-year outcome of the AIR registry.

BACKGROUND: Ablation index (AI) is a new lesion quality marker that has been demonstrated to allow a high single-procedure arrhythmia-free survival in single-center studies. This prospective, multi-center study was designed to evaluate the reproducibility of pulmonary vein (PV) isolation guided by the AI. METHODS: A total of 490 consecutive patients with paroxysmal (80.4%) and persistent AF underwent first time PV isolation and were divided in four study groups according to operator's preference in choosing the ablation catheter (a contact force (ST) or contact force surround flow (STSF) catheter) and the AI setting (330-450 or 380-500 at anterior wall or posterior wall, respectively). RESULTS: At 12 months a high rate of freedom from AF recurrences was observed in patients with both paroxysmal and persistent AF (91% vs 83.3%; P = .039). There was no difference in the rate of AF recurrence among the four study groups (4.5% in group ST330-450, 12.2% in group ST 380-500, 14.9% in group STSF330-450, 9.4% in group STSF380-500; P = .083). Recurrence was also similar between patients treated with a ST (8%) or STSF catheter (12.1%; P = .2), and within patients targeting an AI settings of 330 to 450 (10.9%) or 380 to 500 (10.3%; P = .64). In patients with paroxysmal AF, there was no difference (P = .12) in the 1-year freedom from AF recurrence among 14 operators that performed ≥10 ablation procedure. CONCLUSIONS: An ablation protocol respecting strict criteria for contiguity and quality lesion resulted in high rate of 1-year freedom from AF recurrence, irrespective of the ablation catheters, AI settings, and operator.

Electrocardiographic features of 431 consecutive, critically ill COVID-19 patients: an insight into the mechanisms of cardiac involvement.

AIMS: Our aim was to describe the electrocardiographic features of critical COVID-19 patients. METHODS AND RESULTS: We carried out a multicentric, cross-sectional, retrospective analysis of 431 consecutive COVID-19 patients hospitalized between 10 March and 14 April 2020 who died or were treated with invasive mechanical ventilation. This project is registered on ClinicalTrials.gov (identifier: NCT04367129). Standard ECG was recorded at hospital admission. ECG was abnormal in 93% of the patients. Atrial fibrillation/flutter was detected in 22% of the patients. ECG signs suggesting acute right ventricular pressure overload (RVPO) were detected in 30% of the patients. In particular, 43 (10%) patients had the S1Q3T3 pattern, 38 (9%) had incomplete right bundle branch block (RBBB), and 49 (11%) had complete RBBB. ECG signs of acute RVPO were not statistically different between patients with (n = 104) or without (n=327) invasive mechanical ventilation during ECG recording (36% vs. 28%, P = 0.10). Non-specific repolarization abnormalities and low QRS voltage in peripheral leads were present in 176 (41%) and 23 (5%), respectively. In four patients showing ST-segment elevation, acute myocardial infarction was confirmed with coronary angiography. No ST-T abnormalities suggestive of acute myocarditis were detected. In the subgroup of 110 patients where high-sensitivity troponin I was available, ECG features were not statistically different when stratified for above or below the 5 times upper reference limit value. CONCLUSIONS: The ECG is abnormal in almost all critically ill COVID-19 patients and shows a large spectrum of abnormalities, with signs of acute RVPO in 30% of the patients. Rapid and simple identification of these cases with ECG at hospital admission can facilitate classification of the patients and provide pathophysiological insights.

Propagation of Epidemics Along Lines with Fast Diffusion.

It has long been known that epidemics can travel along communication lines, such as roads. In the current COVID-19 epidemic, it has been observed that major roads have enhanced its propagation in Italy. We propose a new simple model of propagation of epidemics which exhibits this effect and allows for a quantitative analysis. The model consists of a classical SIR model with diffusion, to which an additional compartment is added, formed by the infected individuals travelling on a line of fast diffusion. The line and the domain interact by constant exchanges of populations. A classical transformation allows us to reduce the proposed model to a system analogous to one we had previously introduced Berestycki et al. (J Math Biol 66:743-766, 2013) to describe the enhancement of biological invasions by lines of fast diffusion. We establish the existence of a minimal spreading speed, and we show that it may be quite large, even when the basic reproduction number [Formula: see text] is close to 1. We also prove here further qualitative features of the final state, showing the influence of the line.

Influence of a road on a population in an ecological niche facing climate change.

We introduce a model designed to account for the influence of a line with fast diffusion-such as a road or another transport network-on the dynamics of a population in an ecological niche.This model consists of a system of coupled reaction-diffusion equations set on domains with different dimensions (line / plane). We first show that, in a stationary climate, the presence of the line is always deleterious and can even lead the population to extinction. Next, we consider the case where the niche is subject to a displacement, representing the effect of a climate change. We find that in such case the line with fast diffusion can help the population to persist. We also study several qualitative properties of this system. The analysis is based on a notion of generalized principal eigenvalue developed and studied by the authors (2019).

Spread of Zika virus in the Americas.

We use a data-driven global stochastic epidemic model to analyze the spread of the Zika virus (ZIKV) in the Americas. The model has high spatial and temporal resolution and integrates real-world demographic, human mobility, socioeconomic, temperature, and vector density data. We estimate that the first introduction of ZIKV to Brazil likely occurred between August 2013 and April 2014 (90% credible interval). We provide simulated epidemic profiles of incident ZIKV infections for several countries in the Americas through February 2017. The ZIKV epidemic is characterized by slow growth and high spatial and seasonal heterogeneity, attributable to the dynamics of the mosquito vector and to the characteristics and mobility of the human populations. We project the expected timing and number of pregnancies infected with ZIKV during the first trimester and provide estimates of microcephaly cases assuming different levels of risk as reported in empirical retrospective studies. Our approach represents a modeling effort aimed at understanding the potential magnitude and timing of the ZIKV epidemic and it can be potentially used as a template for the analysis of future mosquito-borne epidemics.

Toxoplasma gondii seroprevalence in beef cattle raised in Italy: a multicenter study.

Toxoplasmosis represents an important public health issue, with the consumption of raw or undercooked meat being a major way of human infection. The role of beef in the transmission of the parasite to humans is questioned due to lower quantity of tissue cysts compared with other meat-producing species. However, the habit of consuming raw beef is regionally diffused, and the risk posed by Toxoplasma gondii infection in cattle should not be overlooked. Therefore, to update information on T. gondii in cattle reared in Italy, a multicentric seroepidemiological survey was designed and implemented in four Northern regions (Liguria, Lombardy, Piedmont, and Trentino Alto Adige) and Sardinia. Overall, a convenience sampling was performed, collecting 1444 serum samples from 57 beef cattle herds. Thirteen beef breeds were sampled, besides cross-breed; bovines age varied from 3 months to over 12 years. Sera were tested with a commercial ELISA for the detection of anti-T. gondii antibodies. Individual and herd data were analyzed by binary logistic regression analysis. A T. gondii seroprevalence of 10.2% was recorded, with differences among regions and values ranging from 5.3% in Liguria to 18.6% in the Piedmont region (p value = 0.0001). Both young and adult animals and males and females tested positive, without any significant difference (age and gender: p value > 0.05). Lower seroprevalence values were recorded in cattle born in Italy (8.7%) if compared with animals imported from abroad (13.4%) (p value = 0.046). The spread of T. gondii in beef cattle destined to Italian consumers is confirmed, suggesting the need of continuous monitoring of the infection.

Phosphoinositide 3-Kinase Gamma Inhibition Protects From Anthracycline Cardiotoxicity and Reduces Tumor Growth.

BACKGROUND: Anthracyclines, such as doxorubicin (DOX), are potent anticancer agents for the treatment of solid tumors and hematologic malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of phosphoinositide 3-kinase γ (PI3Kγ) in DOX-induced cardiotoxicity and the potential cardioprotective and anticancer effects of PI3Kγ inhibition. METHODS: Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ-selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography, and DOX-mediated signaling was assessed in whole hearts or isolated cardiomyocytes. The dual cardioprotective and antitumor action of PI3Kγ inhibition was assessed in mouse mammary tumor models. RESULTS: PI3Kγ kinase-dead mice showed preserved cardiac function after chronic low-dose DOX treatment and were protected against DOX-induced cardiotoxicity. The beneficial effects of PI3Kγ inhibition were causally linked to enhanced autophagic disposal of DOX-damaged mitochondria. Consistently, either pharmacological or genetic blockade of autophagy in vivo abrogated the resistance of PI3Kγ kinase-dead mice to DOX cardiotoxicity. Mechanistically, PI3Kγ was triggered in DOX-treated hearts, downstream of Toll-like receptor 9, by the mitochondrial DNA released by injured organelles and contained in autolysosomes. This autolysosomal PI3Kγ/Akt/mTOR/Ulk1 signaling provided maladaptive feedback inhibition of autophagy. PI3Kγ blockade in models of mammary gland tumors prevented DOX-induced cardiac dysfunction and concomitantly synergized with the antitumor action of DOX by unleashing anticancer immunity. CONCLUSIONS: Blockade of PI3Kγ may provide a dual therapeutic advantage in cancer therapy by simultaneously preventing anthracyclines cardiotoxicity and reducing tumor growth.

Sarcoptic Mange of Fox Origin in Multiple Farm Animals and Scabies in Humans, Switzerland, 2018.

Fox-derived Sarcoptes scabiei mites caused an outbreak of mange on a farm in Switzerland in 2018. Pruritic skin lesions suggestive of S. scabiei mite infestation developed in 4 humans who had direct contact with affected farm animals but not foxes. Sarcoptic mange is continuously spreading; such outbreaks affecting humans could start occurring more frequently.

Mortality and morbidity reduction after frequent premature ventricular complexes ablation in patients with left ventricular systolic dysfunction.

AIMS: Ablation of frequent premature ventricular complexes (PVCs) improves left ventricular ejection fraction in patients with left ventricular (LV) systolic dysfunction. This study aims to evaluate the long-term hard outcomes and potential prognostic variables in this population. METHODS AND RESULTS: Prospective multicentre study including 101 consecutive patients [56 ± 12 years old, 62 (61%) men] with LV systolic dysfunction and frequent PVCs who underwent PVC ablation before November 2015. The last evaluation performed was considered the long-term follow-up (LTFUP) evaluation. Mean follow-up was 34 ± 16 months (range 24-84 months). Ablation was successful in 95 (94%) patients. There was a significant reduction in the PVC burden from 21 ± 12% at baseline to 3.8 ± 6% at LTFUP, P < 0.001. Left ventricular ejection fraction improved from 32 ± 8% at baseline to 39 ± 12% at LTFUP (P < 0.001) and New York Heart Association class from 2.2 ± 0.6% to 1.3 ± 0.6% (P < 0.001). Brain natriuretic peptide levels decreased from 136 (78-321) to 68 (32-144) pg/mL (P = 0.007). Most of this improvement occurs during the first 6 months after ablation. Persistent abolition of at least 18 points of the baseline PVC burden was independently and inversely associated with the composite endpoint of cardiac mortality, cardiac transplantation, or hospitalization for heart failure during follow-up [hazard ratio 0.18 (0.05-0.66), P = 0.01]. CONCLUSION: In patients with LV systolic dysfunction, ablation of frequent PVCs induces a significant improvement in functional, structural, and neurohormonal status, which persists at LTFUP. A sustained reduction in the baseline PVC burden is associated with a lower risk of cardiac mortality, cardiac transplantation, or hospitalization for heart failure during follow-up.

Reproducibility of acute pulmonary vein isolation guided by the ablation index.

BACKGROUND: Atrial fibrillation (AF) ablation outcome is still operator dependent. Ablation Index (AI) is a new lesion quality marker that has been demonstrated to allow acute durable pulmonary vein (PV) isolation followed by a high single-procedure arrhythmia-free survival. This prospective, multicenter study was designed to evaluate the reproducibility of acute PV isolation guided by the AI. METHODS: A total of 490 consecutive patients with paroxysmal (80.4%) and persistent AF underwent first time PV encircling and were divided in four study groups according to operator preference in choosing the ablation catheter (a contact force [ST] or contact force surround flow [STSF] catheter) and the AI setting (330 at posterior and 450 at anterior wall or 380 at posterior and 500 at anterior wall). Radiofrequency was delivered targeting interlesion distance ≤6 mm. RESULTS: The rate of first-pass PV isolation (ST330 90 ± 16%, ST380 87 ± 19%, STSF330 90 ± 17%, STSF380 91 ± 15%, P = .585) was similar among the four study groups, whereas procedure (ST330 129 ± 44 minutes, ST380 144 ± 44 minutes, STSF330 120 ± 72 minutes, STSF380 125 ± 73 minutes, P < .001) and fluoroscopy time (ST330 542 ± 285 seconds, ST380 540 ± 416 seconds, STSF330 257 ± 356 seconds, STSF380 379 ± 454 seconds, P < 0.001) significantly differed. The difference in the rate of first-pass isolation was not statistical different (P = .06) among the 12 operators that performed at least 15 procedures. CONCLUSIONS: An ablation protocol respecting strict criteria for contiguity and quality lesion results in high and comparable rate of acute PV isolation among operator performing ablation with different catheters, AI settings, procedure, and fluoroscopy times.

Can a Quantum Walk Tell Which Is Which?A Study of Quantum Walk-Based Graph Similarity.

We consider the problem of measuring the similarity between two graphs using continuous-time quantum walks and comparing their time-evolution by means of the quantum Jensen-Shannon divergence. Contrary to previous works that focused solely on undirected graphs, here we consider the case of both directed and undirected graphs. We also consider the use of alternative Hamiltonians as well as the possibility of integrating additional node-level topological information into the proposed framework. We set up a graph classification task and we provide empirical evidence that: (1) our similarity measure can effectively incorporate the edge directionality information, leading to a significant improvement in classification accuracy; (2) the choice of the quantum walk Hamiltonian does not have a significant effect on the classification accuracy; (3) the addition of node-level topological information improves the classification accuracy in some but not all cases. We also theoretically prove that under certain constraints, the proposed similarity measure is positive definite and thus a valid kernel measure. Finally, we describe a fully quantum procedure to compute the kernel.