Decline of Admission for Acute Coronary Syndromes and Acute Cardiovascular Conditions during COVID-19 Pandemic in Veneto Region.

Background: The present study aimed to examine longitudinal trends in hospitalizations for acute coronary syndrome (ACS) before and during the COVID-19 pandemic, by reviewing the data from 13 hospitals of the Veneto Region, in the north-east of Italy. Methods: We performed a multicenter, retrospective analysis including all the consecutive patients presenting with ACS and other acute cardiovascular (CV) conditions (defined as heart failure, arrhythmias, cardiac arrest and venous thromboembolism) hospitalized in 13 different hospitals of the Veneto Region covering a population of 2,554,818 inhabitants, during the first (between 15 March 2020 and 30 April 2020) and second (between 15 November 2020 and 30 December 2020) COVID-19 pandemic waves (the 2020 cohort). Data were compared with those obtained at the same time-windows of years 2018 and 2019 (the historical cohorts). Results: Compared to the historical cohorts, a significant decrease in the number of ACS cases was observed in 2020 (−27.3%, p = 0.01 and −32%, p < 0.001, comparing 2018 versus 2020 and 2019 and 2020, respectively). The proportion of patients hospitalized for acute CV conditions decreased during the first and second wave COVID-19 pandemic when compared to the historical cohorts (−36.5%, p < 0.001 and −40.6%, p < 0.001, comparing 2018 versus 2020 and 2019 and 2020, respectively). Pearson's correlation evidenced a significant inverse relationship between the number of COVID-19 cases and both ACS hospital admissions (r = −0.881, p = 0.005) and hospitalizations for acute CV conditions (r = −0.738, p = 0.01), respectively. Conclusions: The decrease in hospitalizations for ACS and other acute CV conditions will strongly affect future patients' management since undiagnosed nonfatal CV events represent a source of increased (and unknown) CV morbidity and mortality.

Takotsubo Syndrome during COVID-19 Pandemic in the Veneto Region, Italy.

Background: During the COVID-19 pandemic, the risk of SARS-CoV-2 infection, the public health measures of social distancing, the freedom limitations, quarantine, and the enforced homeworking under the lockdown period, as well as medical causes including COVID-19 infection per se, may have caused major emotional distress, especially in the most vulnerable patients. We aimed to evaluate the variations in the number of admissions due to Takotsubo syndrome (TTS) during the COVID-19 pandemic in the Veneto region. Methods: We retrospectively reviewed and analyzed the number of admissions because of TTS in 13 Divisions of Cardiology located in the Veneto region, the northeastern area of Italy, covering a population of more than 2.5 million inhabitants, during the two major pandemic waves of COVID-19 (the first between 15 March and 30 April 2020 and the second between 15 November and 30 December 2020) that occurred in 2020. Results: In total, 807 acute coronary syndromes were admitted in the 13 enrolling hospitals. Among these, 3.9% had TTS. Compared to the corresponding 2018 and 2019 time periods, we observed a significant increase in the number of TTS cases (+15.6%, p = 0.03 and +12.5%, p = 0.04, comparing 2018 to 2020 and 2019 to 2020, respectively). Geographical distribution of the TTS cases reflected the broad spread of the SARS-CoV-2 infection with a significant direct relationship between TTS incidence and the number of COVID-19 infections according to Pearson's correlation (r = 0.798, p < 0.001). Conclusions: The higher incidence of TTS during the 2020 COVID-19 pandemic waves, especially in the areas that were hit hardest in terms of morbidity and mortality by the SARS-CoV-2 infection, suggest a strong direct and/or indirect role of COVID-19 in the pathogenesis of TTS.

ISOLPHARM, a new production method of high specific activity beta-emitting radionuclides as radiopharmaceutical precursors / ISOLPHARM, un nuevo método de producción de radionúclidos emisores beta de actividad específica alta como precursores radiofarmacéuticos

Abstract At INFN-LNL (Istituto Nazionale di Fisica Nucleare- Laboratori Nazionali di Legnaro) SPES (Selective Production of Exotic Species), a new facility for the production of radioactive ion beams is being constructed at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro). Radioactive ion beams of neutron-rich nuclei with high purity, in the range of mass between 80 and 160 amu, will be produced by nuclear reactions induced by 40 MeV protons from a cyclotron. The goal of the ISOLPHARM project is to provide a feasibility study for an innovative technology for the production of extremely very high specific activity beta emitting radionuclides as radiopharmaceutical precursors. The ISOL method, adopted in the ISOLPHARM project (a branch of the SPES project), gives the possibility of obtaining pure isobaric beams. In this way, no isotopic contaminations will be present in the beam and afterwards in a proper trapping substrate. The ground-breaking idea of the ISOLPHARM method was granted an International patent (INFN).

Resumen En INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro) SPES (Producción selectiva de especies exóticas), se está construyendo una nueva instalación para la producción de haces de iones radiactivos en INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro). Se producirán haces de iones radiactivos de núcleos ricos en neutrones con alta pureza, en el rango de masa entre 80 y 160 amu, por reacciones nucleares inducidas por protones de 40 MeV de un ciclotrón. El objetivo del proyecto ISOLPHARM es proporcionar un estudio de viabilidad para una tecnología innovadora para la producción de radionúclidos emisores de beta de actividad específica extremadamente alta como precursores radiofarmacéuticos. El método ISOL, adoptado en el proyecto ISOLPHARM (una rama del proyecto SPES), ofrece la posibilidad de obtener haces isobáricos puros. De esta manera, no habrá contaminaciones isotópicas en el haz y luego en un sustrato de atrapamiento adecuado. La idea pionera del método ISOLPHARM recibió una patente internacional (INFN).

G-CSF for Extensive STEMI.

RATIONALE: In the exploratory Phase II STEM-AMI (Stem Cells Mobilization in Acute Myocardial Infarction) trial, we reported that early administration of G-CSF (granulocyte colony-stimulating factor), in patients with anterior ST-segment-elevation myocardial infarction and left ventricular (LV) dysfunction after successful percutaneous coronary intervention, had the potential to significantly attenuate LV adverse remodeling in the long-term. OBJECTIVE: The STEM-AMI OUTCOME CMR (Stem Cells Mobilization in Acute Myocardial Infarction Outcome Cardiac Magnetic Resonance) Substudy was adequately powered to evaluate, in a population showing LV ejection fraction ≤45% after percutaneous coronary intervention for extensive ST-segment-elevation myocardial infarction, the effects of early administration of G-CSF in terms of LV remodeling and function, infarct size assessed by late gadolinium enhancement, and myocardial strain. METHODS AND RESULTS: Within the Italian, multicenter, prospective, randomized, Phase III STEM-AMI OUTCOME trial, 161 ST-segment-elevation myocardial infarction patients were enrolled in the CMR Substudy and assigned to standard of care (SOC) plus G-CSF or SOC alone. In 119 patients (61 G-CSF and 58 SOC, respectively), CMR was available at baseline and 6-month follow-up. Paired imaging data were independently analyzed by 2 blinded experts in a core CMR lab. The 2 groups were similar for clinical characteristics, cardiovascular risk factors, and pharmacological treatment, except for a trend towards a larger infarct size and longer symptom-to-balloon time in G-CSF patients. ANCOVA showed that the improvement of LV ejection fraction from baseline to 6 months was 5.1% higher in G-CSF patients versus SOC (P=0.01); concurrently, there was a significant between-group difference of 6.7 mL/m2 in the change of indexed LV end-systolic volume in favor of G-CSF group (P=0.02). Indexed late gadolinium enhancement significantly decreased in G-CSF group only (P=0.04). Moreover, over time improvement of global longitudinal strain was 2.4% higher in G-CSF patients versus SOC (P=0.04). Global circumferential strain significantly improved in G-CSF group only (P=0.006). CONCLUSIONS: Early administration of G-CSF exerted a beneficial effect on top of SOC in patients with LV dysfunction after extensive ST-segment-elevation myocardial infarction in terms of global systolic function, adverse remodeling, scar size, and myocardial strain. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01969890.

The benefit of betrixaban for the extended thromboprophylaxis in acutely ill medical patients.

INTRODUCTION: Patients admitted with acute medical conditions are at prolonged risk for venous thrombosis. The efficacy and safety, and the appropriate duration of thromboprophylaxis have not been clearly determined. In recent years, direct coagulation factor inhibitors have been successfully tested for the prevention and treatment of arterial and venous thromboembolism. Betrixaban is a novel direct inhibitor of factor Xa with a noteworthy pharmacological feature: limited renal clearance. Areas covered: This review focuses on the pharmacological profile of Betrixaban, including its clinical efficacy and safety. It also covers the results of the pivotal APEX trial assessing the safety and efficacy of betrixaban for extended thromboprophylaxis in patients with acute medical conditions. Expert opinion: The role of extended thromboprophylaxis in acutely ill medical patients is subject to debate. The beneficial results in terms of VTE prevention were offset by the relevant increase in major bleeding. Betrixaban is the only direct oral anticoagulant to have shown a favorable risk-benefit profile in this setting especially in patients at higher risk for thrombosis.

Diagnostic value and prognostic implications of early cardiac magnetic resonance in survivors of out-of-hospital cardiac arrest.

BACKGROUND: In patients who survived out-of-hospital cardiac arrest (OHCA), it is crucial to establish the underlying cause and its potential reversibility. OBJECTIVE: The purpose of this study was to assess the incremental diagnostic and prognostic role of early cardiac magnetic resonance (CMR) in survivors of OHCA. METHODS: Among 139 consecutive OHCA patients, the study enrolled 44 patients (median age 43 years; 84% male) who underwent coronary angiography and CMR ≤7 days after admission. The CMR protocol included T2-weighted sequences for myocardial edema and late gadolinium enhancement (LGE) sequences for myocardial fibrosis. RESULTS: Coronary angiography identified obstructive coronary artery disease in 18 of 44 patients in whom CMR confirmed the diagnosis of ischemic heart disease by demonstrating subendocardial or transmural LGE. The presence of myocardial edema allowed differentiation between acute myocardial ischemia (n = 12) and postinfarction myocardial scar (n = 6). Among the remaining 26 patients without obstructive coronary artery disease, CMR in 19 (73%) showed dilated cardiomyopathy in 5, myocarditis in 4, mitral valve prolapse associated with LGE in 3, ischemic scar in 2, idiopathic nonischemic scar in 2, arrhythmogenic cardiomyopathy in 1, hypertrophic cardiomyopathy in 1, and takotsubo cardiomyopathy in 1. In this subgroup of 26 patients, 6 (23%) had myocardial edema. During mean follow-up of 36 ± 17 months, all 18 patients with myocardial edema had an uneventful outcome, whereas 9 of 26 (35%) without myocardial edema experienced sudden arrhythmic death (n = 1), appropriate defibrillator interventions (n = 5), and nonarrhythmic death (n = 3; P = .006). CONCLUSION: In survivors of OHCA, early CMR with a comprehensive tissue characterization protocol provided additional diagnostic and prognostic value. The identification of myocardial edema was associated with a favorable long-term outcome.

Renal Dysfunction: How to Think About That in Acute Coronary Syndromes.

PURPOSE OF REVIEW: Reduction of kidney function and heart disease frequently coexisted in the seam patient. The relation between renal and heart function is quite complex and bring out some unresolved questions about diagnosis (mostly related to the biomarkers levels interpretation), pharmacological therapy (mostly related to drugs kinetics and efficacy), and non-pharmacological therapy. RECENT FINDINGS: Patients with kidney dysfunction (KD) are frequently excluded and underrepresented in the large trials. It is well-known that coronary revascularization reduces mortality also in KD patients presenting with acute coronary syndrome. However, acute kidney injury (AKI), primarily related at contrast medium administration, is worse prognosis. For this reason, prevention, early diagnosis, and effective therapy of ACK are key elements in assistance of these patients. In this context, recently, some new biomarkers of renal function have been proposed. Frequently, patients with acute coronary syndromes and kidney disease are undertreated, worsening their prognosis. Undertreatment and comorbidities associated with renal dysfunction explain the higher mortality of these patients.

First results on Ge resonant laser photoionization in hollow cathode lamp.

In the framework of the research and development activities of the SPES project regarding the optimization of the radioactive beam production, a dedicated experimental study has been recently started in order to investigate the possibility of in-source ionization of germanium using a set of tunable dye lasers. Germanium is one of the beams to be accelerated by the SPES ISOL facility, which is under construction at Legnaro INFN Laboratories. The three-step, two color ionization schemes have been tested using a Ge hollow cathode lamp. The slow and the fast optogalvanic signals were detected and averaged by an oscilloscope as a proof of the laser ionization inside the lamp. As a result, several wavelength scans across the resonances of ionization schemes were collected with the fast optogalvanic signal. Some comparisons of ionization efficiency for different ionization schemes were made. Furthermore, saturation curves of the first excitation transitions have been obtained. This investigation method and the setup built in the laser laboratory of the SPES project can be applied for the photo-ionization scheme studies also for the other possible radioactive elements.

Therapeutic hypothermia in Italian Intensive Care Units after 2010 resuscitation guidelines: still a lot to do.

BACKGROUND: Therapeutic hypothermia (TH) is one of three interventions that have demonstrated to improve patients' neurological outcome after cardiac arrest. The aim of this study was to investigate the effect of the 2010 resuscitation guidelines on TH implementation in various Italian Intensive Care Units (ICU). METHODS: A structured questionnaire was submitted to Italian ICU. The questionnaire was addressed to determine the procedures of TH in each ICU or, on the contrary, the reason for not employing the therapy. RESULTS: We obtained complete information from 770 of 847 Italian ICU (91%). Out of 405 Units included in the analysis only 223 (55.1%) reported to use TH in comatose patients after return of spontaneous circulation. The trend of TH implementation shows a stable increase, particularly after 2006 but there is no evident acceleration after the strong indication of the 2010 guidelines. There was a rise of about 3.4 times in the number of Italian ICU using TH as compared to the 2007 survey (an increase of 68% per year). One hundred and eighty-two (44.9%) units did not use TH mainly because of lack of equipment, economic issues or the conviction of the difficulty of execution. CONCLUSIONS: TH is still under-used in Italy (55.1%) even though the therapy is strongly recommended in the 2010 guidelines. However, the increase in the adoption of hypothermia has been significant in the past 5 years (68%/years) and the awareness of the efficacy is almost consolidated among intensivists, being logistic problems the leading cause for non-adoption.

Laser system generating 250-mJ bunches of 5-GHz repetition rate, 12-ps pulses.

We report on a high-energy solid-state laser based on a master-oscillator power-amplifier system seeded by a 5-GHz repetition-rate mode-locked oscillator, aimed at the excitation of the dynamic Casimir effect by optically modulating a microwave resonator. Solid-state amplifiers provide up to 250 mJ at 1064 nm in a 500-ns (macro-)pulse envelope containing 12-ps (micro-)pulses, with a macro/micropulse format and energy resembling that of near-infrared free-electron lasers. Efficient second-harmonic conversion allowed synchronous pumping of an optical parametric oscillator, obtaining up to 40 mJ in the range 750-850 nm.

High-gain diode-pumped amplifier for generation of microjoule-level picosecond pulses.

A diode-pumped single-pass amplifier system relying on two grazing-incidence Nd:YVO(4) slabs was developed to increase the energy of low-repetition-rate pulses from a decimated low-power cw mode-locked oscillator. Single-pass unsaturated gain up to 1.3x10(5) was achieved, and amplified pulses of 10-muJ energy and 8.0-ps duration were obtained. Efficient second harmonic generation (SHG) at 532 nm was achieved, as well as traveling-wave parametric conversion in the range 770-1020 nm (signal) and 1110-1720 nm (idler).