Impact of atrial fibrillation on 1-year outcome in patients with implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator: results from the German DEVICE Registry.

Background: Atrial fibrillation (AF) is a cardiac arrhythmia frequently documented in patients requiring implantable cardioverter defibrillators (ICDs) and/or cardiac resynchronization therapy with defibrillator (CRT-D). Patients with diagnosed AF at the point of ICD or CRT-D implantation may have an impaired follow-up outcome. Methods: The German DEVICE I-II registry is a nationwide prospective multicentre database of patients implanted with ICD and CRT-D with clinical follow-up data. We analysed a 1-year follow up of implanted patients with AF and with sinus rhythm (SR). Results: A total of 4,929 ICD/CRT patients are included in the present analysis: 946 (19.2%) were in AF and 3,983 (80.8%) were SR at time of device implantation. AF patients had a significantly more comorbid profile including older age {72 [interquartile range (IQR), 66-77] vs. 66 (IQR, 56-73) years; P<0.001}, and higher rate of patients with left ventricular ejection fraction <30% (68.2% vs. 61.0%; P<0.001), peripheral artery disease (4.5% vs. 2.7%; P=0.002), diabetes (33.6% vs. 25.5%; P<0.001), hypertension (58.4% vs. 51.1%; P<0.001) and renal failure (22.6% vs. 15.3%; P<0.001). The intra-hospital complication rate was 4.3% in the AF and 3.6% in the SR group (P=0.38). In 1-year follow-up AF patients experienced a significantly higher rate of defibrillator shocks (25% vs. 15.3%; P<0.001). One-year estimated mortality was 10.8% in the AF and 5.9% in the SR group (P<0.001), while estimated 1-year major adverse cardiac and cerebrovascular events (MACCE) rate was 11.2% vs. 7.0% (P<0.001). The effects of AF on electrical shocks and mortality persisted after adjusting for age, sex, advanced New York Heart Association (NYHA) class, severely impaired left ventricular ejection fraction (LVEF), coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM), chronic renal failure (CRF), QRS duration, and type of indication for electronic device implantation. Conclusions: Our clinical data on an extended cohort of contemporary patients confirm the significant impact of AF, and its associated comorbidities, upon mortality and major adverse events after implantation of ICD/CRT.

Detection of atrial fibrillation using an implantable loop recorder in patients with previous cryptogenic stroke: the SPIDER-AF registry (Stroke Prevention by Increasing DEtection Rates of Atrial Fibrillation).

BACKGROUND: The use of implantable loop recorder (ILR) to detect atrial fibrillation (AF) in patients with a history of cryptogenic stroke (CS) has seldom been investigated in "real-world" settings. OBJECTIVE: This study aimed to present the results of the Stroke Prevention by Increasing DEtection Rates of Atrial Fibrillation (SPIDER-AF) registry. METHOD: SPIDER is a multicentric, observational registry, including 35 facilities all over Germany. It enrolled outpatients without AF history and with CS before ILR implantation. RESULTS: We included 500 patients (mean age 63.1 ± 12.7 years), 304 (60.8%) were males, with previous stroke (72.6%) and TIA (27.4%). After inclusion, all were followed for at least 12 months. AF was detected in 133 (26.8%), 25.3% of patients with previous stroke and 29.9% with TIA (p = 0.30). AF was detected after a median of 121.5 days (IQR 40.5-223.0). AF was primarily paroxysmal (95.7% after stroke, 100% after TIA). In 19.5% (n = 26) anticoagulation was not administered after AF detection. Mean CHA2DS2-VASc score (OR 1.22; CI 1.01-1.49; p = 0.037) and age > 70 years (OR 0.41; CI 0.19-0.88; p = 0.0020) correlated with AF. Repeat cerebrovascular events at follow-up (28; 5.6%) correlated with AF (OR = 2.17; CI 1.00-4.72; p = 0.049). AF (p = 0.91) and recurrent events (p = 0.43) occurred similarly in females and males. CONCLUSIONS: In the context of cryptogenic strokes ILRs are a valuable tool for early detection of AF. In a real-world scenario, the anticoagulation therapy remains inadequate despite diagnosed AF in a relevant subset of patients requiring optimization of patient management.

Safety, usability, and performance of a wireless left atrial pressure monitoring system in patients with heart failure: the VECTOR-HF trial.

AIMS: In heart failure (HF), implantable haemodynamic monitoring devices have been shown to optimize therapy, anticipating clinical decompensation and preventing hospitalization. Direct left-sided haemodynamic sensors offer theoretical benefits beyond pulmonary artery pressure monitoring systems. We evaluated the safety, usability, and performance of a novel left atrial pressure (LAP) monitoring system in HF patients. METHODS AND RESULTS: The VECTOR-HF study (NCT03775161) was a first-in-human, prospective, multicentre, single-arm, clinical trial enrolling 30 patients with HF. The device consisted of an interatrial positioned leadless sensor, able to transmit LAP data wirelessly. After 3 months, a right heart catheterization was performed to correlate mean pulmonary capillary wedge pressure (PCWP) with simultaneous mean LAP obtained from the device. Remote LAP measurements were then used to guide patient management. The miniaturized device was successfully implanted in all 30 patients, without acute major adverse cardiac and neurological events (MACNE). At 3 months, freedom from short-term MACNE was 97%. Agreement between sensor-calculated LAP and PCWP was consistent, with a mean difference of -0.22 ± 4.92 mmHg, the correlation coefficient and the Lin's concordance correlation coefficient values were equal to 0.79 (p < 0.0001) and 0.776 (95% confidence interval 0.582-0.886), respectively. Preliminary experience with V-LAP-based HF management was associated with significant improvements in New York Heart Association (NYHA) functional class (32% of patients reached NYHA class II at 6 months, p < 0.005; 60% of patients at 12 months, p < 0.005) and 6-min walk test distance (from 244.59 ± 119.59 m at baseline to 311.78 ± 129.88 m after 6 months, p < 0.05, and 343.95 ± 146.15 m after 12 months, p < 0.05). CONCLUSION: The V-LAP™ monitoring system proved to be generally safe and provided a good correlation with invasive PCWP. Initial evidence also suggests possible improvement in HF clinical symptoms.

Gut and airway microbiota dysbiosis and their role in COVID-19 and long-COVID.

The gut microbiota plays a crucial role in human health and disease. Gut dysbiosis is known to be associated with increased susceptibility to respiratory diseases and modifications in the immune response and homeostasis of the lungs (the so-called gut-lung axis). Furthermore, recent studies have highlighted the possible role of dysbiosis in neurological disturbances, introducing the notion of the "gut-brain axis." During the last 2 years, several studies have described the presence of gut dysbiosis during coronavirus disease 2019 (COVID-19) and its relationship with disease severity, SARS-CoV-2 gastrointestinal replication, and immune inflammation. Moreover, the possible persistence of gut dysbiosis after disease resolution may be linked to long-COVID syndrome and particularly to its neurological manifestations. We reviewed recent evidence on the association between dysbiosis and COVID-19, investigating the possible epidemiologic confounding factors like age, location, sex, sample size, the severity of disease, comorbidities, therapy, and vaccination status on gut and airway microbial dysbiosis in selected studies on both COVID-19 and long-COVID. Moreover, we analyzed the confounding factors strictly related to microbiota, specifically diet investigation and previous use of antibiotics/probiotics, and the methodology used to study the microbiota (α- and ß-diversity parameters and relative abundance tools). Of note, only a few studies focused on longitudinal analyses, especially for long-term observation in long-COVID. Lastly, there is a lack of knowledge regarding the role of microbiota transplantation and other therapeutic approaches and their possible impact on disease progression and severity. Preliminary data seem to suggest that gut and airway dysbiosis might play a role in COVID-19 and in long-COVID neurological symptoms. Indeed, the development and interpretation of these data could have important implications for future preventive and therapeutic strategies.

Deep learning to detect significant coronary artery disease from plain chest radiographs AI4CAD.

BACKGROUND: The predictive role of chest radiographs in patients with suspected coronary artery disease (CAD) is underestimated and may benefit from artificial intelligence (AI) applications. OBJECTIVES: To train, test, and validate a deep learning (DL) solution for detecting significant CAD based on chest radiographs. METHODS: Data of patients referred for angina and undergoing chest radiography and coronary angiography were analysed retrospectively. A deep convolutional neural network (DCNN) was designed to detect significant CAD from posteroanterior/anteroposterior chest radiographs. The DCNN was trained for severe CAD binary classification (absence/presence). Coronary angiography reports were the ground truth. Stenosis severity of ≥70% for non-left main vessels and ≥ 50% for left main defined severe CAD. RESULTS: Information of 7728 patients was reviewed. Severe CAD was present in 4091 (53%). Patients were randomly divided for algorithm training (70%; n = 5454) and fine-tuning/model validation (10%; n = 773). Internal clinical validation (model testing) was performed with the remaining patients (20%; n = 1501). At binary logistic regression, DCNN prediction was the strongest severe CAD predictor (p < 0.0001; OR: 1.040; CI: 1.032-1.048). Using a high sensitivity operating cut-point, the DCNN had a sensitivity of 0.90 to detect significant CAD (specificity 0.31; AUC 0.73; 95% CI DeLong, 0.69-0.76). Adding to the AI chest radiograph interpretation angina status improved the prediction (AUC 0.77; 95% CI DeLong, 0.74-0.80). CONCLUSION: AI-read chest radiographs could be used to pre-test significant CAD probability in patients referred for suspected angina. Further studies are required to externally validate our algorithm, develop a clinically applicable tool, and support CAD screening in broader settings.

Every cloud has a silver lining: COVID-19 chest-CT screening prevents unnecessary cardiac surgery.

BACKGROUND: Unenhanced chest CT can identify incidental findings (IFs) leading to management strategy change. We report our institutional experience with routine chest-CT as preoperative screening tool during the COVID-19 pandemic, focusing on the impact of IFs. METHODS: All patients scheduled for cardiac surgery from May 1st to December 31st 2020, underwent preoperative unenhanced chest-CT according to COVID-19 pandemic institutional protocol. We have analyzed IFs incidence, reported consequent operative changes, and identified IFs clinical determinants. RESULTS: Out of 447, 278 patients were included. IFs rate was 7.2% (20/278): a solid mass (11/20, 55%), lymphoproliferative disease (1/20, 5%), SARS-CoV-2 pneumonia (2/20, 10%), pulmonary artery chronic thromboembolism (1/20, 5%), anomalous vessel anatomy (2/20, 10%), voluminous hiatal hernia (1/20, 5%), mitral annulus calcification (1/20, 5%), and porcelain aorta (1/20, 5%) were reported. Based on IFs, 4 patients (20%-4/278, 1.4%) were not operated, 8 (40%-8/278, 2.9%) underwent a procedure different from the one originally planned one, and 8 (40%-8/278, 2.9%) needed additional preoperative investigations before undergoing the planned surgery. At univariate regression, coronary artery disease, atrial fibrillation, and history of cancer were significantly more often present in patients presenting with significant IFs. History of malignancy was identified as the only independent determinant of significant IFs at chest-CT (OR=4.27 IQR: [1.14-14.58], P=0.0227). CONCLUSIONS: Unenhanced chest-CT as a preoperative screening tool in cardiac surgery led to incidental detection of significant clinical findings, which justified even procedures cancellation. Malignancy history is a determinant for CT incidental findings and could support a tailored screening approach for high-risk patients.

Atrioventricular node ablation and pacing for atrial tachyarrhythmias: A meta-analysis of postoperative outcomes.

BACKGROUND: Atrioventricular node ablation (AVNA) and pacemaker (PM) is performed in symptomatic atrial fibrillation (AF) unresponsive to medical treatment and percutaneous ablation. This meta-analysis evaluated results after AVNA and PM. METHODS: Primary and secondary endpoints were early/late overall/cardiac-related mortality and early/late postoperative complications. Meta-regression explored mortality and preoperative characteristics relation. RESULTS: We selected 93 studies with 11,340 patients: 9105 right ventricular (RV)-PM, and 2235 biventricular PM (cardiac resynchronization therapy, CRT). Malignant arrhythmia (2.5%), heart failure (2.4%), and lead dislodgement (2.0%) were most common periprocedural complications. Pooled estimated 30-day mortality was 1.08% (95%CI:0.65-1.77). At 19.9 months median follow-up (IQR: 10.3-34 months), rehospitalization (0.79%/month) and heart failure (0.48%/month) were the most frequent complications. Overall mortality incidence rate (IR) was 0.43%/month (95%CI:0.36-0.51), and cardiac death IR 0.27%/month (95%CI:0.22-0.32). No mortality determinants emerged in the AVNA CRT subgroup. AVNA RV-PM subgroup univariable meta-regression showed inverse relationship between age, ejection fraction (EF), and late cardiac death (Beta = -0.0709 ± 0.0272; p = 0.0092 and Beta = -0.0833 ± 0.0249; p = 0.0008). Coronary artery disease (CAD) was directly associated to follow-up overall/cardiac mortality at univariable (Beta = 0.0550 ± 0.0136, p < 0.0001; Beta = 0.0540 ± 0.0130, p < 0.0001) and multivariable (Beta = 0.0460 ± 0.0189, p = 0.152; Beta = 0.0378 ± 0.0192, p = 0.0491) meta-regression. CONCLUSIONS: Solid long-term evidence supporting AVNA and pace is lacking. Younger patients with reduced LVEF% have increased follow-up cardiac mortality after AVNA RV and may require CRT. Alternative strategies to maintain sinus rhythm and ventricular synchronism should be compared to AVNA to support future treatment strategies.

The V-LAP System for Remote Left Atrial Pressure Monitoring of Patients With Heart Failure: Remote Left Atrial Pressure Monitoring.

OBJECTIVE: Patients with heart failure (HF) are at an increased risk of hospital admissions. The aim of this report is to describe the feasibility, safety and accuracy of a novel wireless left atrial pressure (LAP) monitoring system in patients with HF. METHODS: The V-LAP Left Atrium Monitoring systEm for Patients With Chronic sysTOlic & Diastolic Congestive heart Failure (VECTOR-HF) study is a prospective, multicenter, single-arm, open-label, first-in human clinical trial to assess the safety, performance and usability of the V-LAP system (Vectorious Medical Technologies) in patients with New York Heart Association class III HF. The device was implanted in the interatrial septum via a percutaneous, trans-septal approach guided by fluoroscopy and echocardiography. Primary endpoints included the successful deployment of the implant, the ability to perform initial pressure measurements and safety outcomes. RESULTS: To date, 24 patients have received implants of the LAP-monitoring device. No device-related complications have occurred. LAP was reported accurately, agreeing well with wedge pressure at 3 months (Lin concordance correlation coefficient = 0.850). After 6 months, New York Heart Association class improved in 40% of the patients (95% CI = 16.4%-63.5%), while the 6-minute walk test distance had not changed significantly (313.9 ± 144.9 vs 232.5 ± 129.9 meters; P = 0.076). CONCLUSION: The V-LAP left atrium monitoring system appears to be safe and accurate.

Left atrial appendage closure with the watchman device reduces atrial fibrillation management costs.

AIMS: To report hospitalization costs of patients with non-valvular atrial fibrillation (AF) submitted to percutaneous left atrial appendage closure (LAAC) with the Watchman device. METHODS: Pre- and post-procedural hospitalization AF-related costs were calculated using the DRG system (diagnosis-related groups) and compared. RESULTS: Between 2012 and 2016, 677 non-valvular AF patients underwent LAAC. Median time from first cardiac hospitalization to LAAC was 5.9 years (IQR 1.6-9.1) and median follow-up after LAAC was 4.8 years (IQR 3.6-5.6). LAAC mortality was 1.3% and follow-up mortality 16.9%. Median pre-LAAC hospitalization cost was € 17,867 (IQR € 7512-35,08) and post-LAAC € 8772 (IQR € 1183-25,159) (p < 0.0001). Annualized cost pre-LAAC was 3773 € (IQR € 1644-8,493) and post-LAAC 2,001 € (IQR € 260-6913) (p < 0.0001). Follow-up survivors had significantly lower post-LAAC costs (p < 0.0001) and after a survival cut-off time of 4.6 years LAAC procedural and post-procedural hospitalization costs achieved parity with pre-LACC costs (AUC 0.64; p = 0.02). CHA2DS2-VASc score (B = 0.04; p = 0.02; 95% CI 0.006-0.08), and HAS-BLED score (B = 0.08; p = 0.004; 95% CI 0.02-0.14) were independent determinants for annualized hospitalization costs post-LAAC. At Cox-regression analysis the DRG mean clinical complexity level (CCL) was the only independent determinant for follow-up mortality (OR = 2.2; p < 0.0001; 95% CI 1.6-2.8) with a cut-off value of 2.25 to predict follow-up mortality (AUC 0.72; p < 0.0001; Spec. 70%; Sens. 70%). CONCLUSION: Hospitalization costs pre-LAAC are consistent, and after LAAC, they are significantly reduced. Costs seem related to the patient's risk profile at the time of the procedure. With the increase in post-LAAC survival time, the procedure becomes economically more profitable.

[Atrial fibrillation and the limits of oral anticoagulation: for whom are left atrial appendage occluders suitable?] / Vorhofflimmern und Grenzen der oralen Antikoagulation ­ für wen eignen sich Vorhofohrokkluder?

BACKGROUND: Patients with atrial fibrillation are at a significantly increased risk of thromboembolic events, especially ischemic strokes. Oral anticoagulation reduces this risk, but cannot be used in some patients for various reasons and is associated with a relevantly increased risk of bleeding. As an alternative for prophylaxis of thromboembolic events in patients with atrial fibrillation, there are different options of left atrial appendage closure. AIM: This article explains the possibilities of interventional atrial occlusion as well as the suitable patient clientele using an overview of the currently available systems for atrial occlusion, a guideline for patient selection and a summary of the current scientific data. CONCLUSION AND AVAILABLE SCIENTIFIC DATA: In carefully selected patients suffering from atrial fibrillation with relative or absolute contraindications for oral anticoagulation, interventional closure of the atrial appendage is a safe alternative for prophylaxis against thromboembolic events. The currently available scientific evidence from randomized controlled trials is sparse. Nevertheless, extensive amounts of registry study data suggest a benefit, while the results of several large randomized controlled trials are expected in the coming years.

Actual management costs of patients with non-valvular atrial fibrillation treated with percutaneous left atrial appendage closure or oral anticoagulation.

AIMS: Comparing actual management costs in patients with non-valvular atrial fibrillation (AF) treated with percutaneous left atrial appendage closure (LAAC) or OAC only. METHODS AND RESULTS: Patients undergoing percutaneous LAAC and AF patients treated with OAC only were matched for gender, age, and diagnosis related groups (DRG) clinical complexity level (CCL). Costs for cardiovascular outpatient clinic visits and hospitalizations were derived from the actual reimbursement records. Between 1/2012 and 12/2016, 8478 patients were referred: 7801 (92%) managed with OAC and 677 (8%) with percutaneous LAAC. Matching resulted in 558 patients (279 per group) for final analysis. Age was 74.9 ± 7.5 years, 244 were female (43.7%), and DRG CCL was 1.8 ± 1.1. Annualized management cost before percutaneous LAAC was € 3110 (IQR: € 1281-8127). After 4.5 ± 1.4 years follow-up, annualized management cost was € 1297 (IQR: € 607-2735) in OAC patients and € 1013 (IQR: € 0-4770) in patients after percutaneous LAAC (p = 0.003). Percutaneous LAAC was the strongest independent determinant to reduce follow-up costs (B = -0.8; CI: -1.09 ̶̶̶̶̶ -0.6; p < 0.0001). Estimated 3-year survival was 92% in percutaneous LAAC and 90% in OAC patients (p = 0.7). CONCLUSION: Percutaneous LAAC significantly reduces management costs. Management costs are significantly higher for patients treated with only OAC compared to patients after percutaneous LAAC. In spite of their complex comorbid profile, percutaneous LAAC patients show a follow-up survival rate similar to patients solely treated with OAC. Future studies are necessary to investigate the potential net economic and clinical benefit of percutaneous LAAC in patients treated with OAC only.

The Interplay between Gut Microbiota and the Immune System in Liver Transplant Recipients and Its Role in Infections.

Liver transplantation (LT) is a life-saving strategy for patients with end-stage liver disease, hepatocellular carcinoma, and acute liver failure. LT success can be hampered by several short-term and long-term complications. Among them, bacterial infections, especially those due to multidrug-resistant germs, are particularly frequent, with a prevalence between 19 and 33% in the first 100 days after transplantation. In the last decades, a number of studies have highlighted how the gut microbiota (GM) is involved in several essential functions to ensure intestinal homeostasis, becoming one of the most important virtual metabolic organs. The GM works through different axes with other organs, and the gut-liver axis is among the most relevant and investigated ones. Any alteration or disruption of the GM is defined as dysbiosis. Peculiar phenotypes of GM dysbiosis have been associated with several liver conditions and complications, such as chronic hepatitis, fatty liver disease, cirrhosis, and hepatocellular carcinoma. Moreover, there is growing evidence of the crucial role of the GM in shaping the immune response, both locally and systemically, against pathogens. This paves the way to the manipulation of the GM as a therapeutic instrument to modulate infectious risk and outcome. In this minireview, we provide an overview of the current understanding of the interplay between the gut microbiota and the immune system in liver transplant recipients and the role of the former in infections.

A multicentre roadmap to restart elective cardiac surgery after COVID-19 peak in an Italian epicenter.

BACKGROUND: During the Italian Phase-2 of the coronavirus pandemic, it was possible to restart elective surgeries. Because hospitals were still burdened with coronavirus disease 2019 (COVID-19) patients, it was focal to design a separate "clean path" for the surgical candidates and determine the possible effects of major surgery on previously infected patients. METHODS: From May to July 2020 (postpandemic peak), 259 consecutive patients were scheduled for elective cardiac surgery in three different centers. Our original roadmap with four screening steps included: a short item questionnaire (STEP-1), nasopharyngeal swab (NP) (STEP-2), computed tomography (CT)-scan using COVID-19 reporting and data system (CO-RADS) scoring (STEP-3), and final NP swab before discharge (STEP-4). RESULTS: Two patients (0.8%) resulted positive at STEP-2: one patient was discharged home for quarantine, the other performed a CT-scan (CO-RADS: <2), and underwent surgery for unstable angina. Chest-CT was positive in 6.3% (15/237) with mean CO-RADS of 2.93 ± 0.8. Mild-moderate lung inflammation (CO-RADS: 2-4) did not delay surgery. Perioperative mortality was 1.15% (3/259), and cumulative incidence of pulmonary complications was 14.6%. At multivariable analysis, only age and cardiopulmonary bypass (CPB) time were independently related to pulmonary complications composite outcome (age >75 years: odds ratio [OR]: 2.6; 95% confidence interval [CI]: 1.25-5.57; p = 0.011; CPB >90 min. OR: 4.3; 95% CI: 1.84-10.16; p = 0.001). At 30 days, no periprocedural contagion and rehospitalization for COVID-19 infections were reported. CONCLUSIONS: Our structured roadmap supports the safe restarting of an elective cardiac surgery list after a peak of a still ongoing COVID-19 pandemic in an epicenter area. Mild to moderate CT residuals of coronavirus pneumonia do not justify elective cardiac surgery procrastination.

Implantation of an Innovative Intracardiac Microcomputer System for Web-Based Real-Time Monitoring of Heart Failure: Usability and Patients' Attitudes.

BACKGROUND: Heart failure (HF) management guided by the measurement of intracardiac and pulmonary pressure values obtained through innovative permanent intracardiac microsensors has been recently proposed as a valid strategy to individualize treatment and anticipate hemodynamic destabilization. These sensors have potential to reduce patient hospitalization rates and optimize quality of life. OBJECTIVE: The aim of this study was to evaluate the usability and patients' attitudes toward a new permanent intracardiac device implanted to remotely monitor left intra-atrial pressures (V-LAP, Vectorious Medical Technologies, Tel Aviv, Israel) in patients with chronic HF. METHODS: The V-LAP system is a miniaturized sensor implanted percutaneously across the interatrial septum. The system communicates wirelessly with a "companion device" (a wearable belt) that is placed on the patient's chest at the time of acquisition/transmission of left heart pressure measurements. At first follow-up after implantation, the patients and health care providers were asked to fill out a questionnaire on the usability of the system, ease in performing the various required tasks (data acquisition and transmission), and overall satisfaction. Replies to the questions were mainly given using a 5-point Likert scale (1: very poor, 2: poor, 3: average, 4: good, 5: excellent). Further patient follow-ups were performed at 3, 6, and 12 months. RESULTS: Use and acceptance of the first 14 patients receiving the V-LAP technology worldwide and related health care providers have been analyzed to date. No periprocedural morbidity/mortality was observed. Before discharge, a tailored educational session was performed after device implantation with the patients and their health care providers. At the first follow-up, the mean score for overall comfort in technology use was 3.7 (SD 1.2) with 93% (13/14) of patients succeeding in applying and operating the system independently. For health care providers, the mean score for overall ease and comfort in use of the technology was 4.2 (SD 0.8). No significant differences were found between the patients' and health care providers' replies to the questionnaires. There was a general trend for higher scores in patients' usability reports at later follow-ups, in which the score related to overall comfort with using the technology increased from 3.0 (SD 1.4) to 4.0 (SD 0.7) (P=.40) and comfort with wearing and adjusting the measuring thoracic belt increased from 2.8 (SD 1.0) to 4.2 (SD 0.4) (P=.02). CONCLUSIONS: Despite the gravity of their HF pathology and the complexity of their comorbid profile, patients are comfortable in using the V-LAP technology and, in the majority of cases, they can correctly and consistently acquire and transmit hemodynamic data. Although the overall patient/care provider satisfaction with the V-LAP system seems to be acceptable, improvements can be achieved after ameliorating the design of the measuring tools. TRIAL REGISTRATION: ClincalTrials.gov NCT03775161; https://clinicaltrials.gov/ct2/show/NCT03775161.

Long-Term Suppressive cART Is Not Sufficient to Restore Intestinal Permeability and Gut Microbiota Compositional Changes.

Background: We explored the long-term effects of cART on markers of gut damage, microbial translocation, and paired gut/blood microbiota composition, with a focus on the role exerted by different drug classes. Methods: We enrolled 41 cART naïve HIV-infected subjects, undergoing blood and fecal sampling prior to cART (T0) and after 12 (T12) and 24 (T24) months of therapy. Fifteen HIV-uninfected individuals were enrolled as controls. We analyzed: (i) T-cell homeostasis (flow cytometry); (ii) microbial translocation (sCD14, EndoCab, 16S rDNA); (iii) intestinal permeability and damage markers (LAC/MAN, I-FABP, fecal calprotectin); (iv) plasma and fecal microbiota composition (alpha- and beta-diversity, relative abundance); (v) functional metagenome predictions (PICRUSt). Results: Twelve and twenty four-month successful cART resulted in a rise in EndoCAb (p = 0.0001) and I-FABP (p = 0.039) vis-à-vis stable 16S rDNA, sCD14, calprotectin and LAC/MAN, along with reduced immune activation in the periphery. Furthermore, cART did not lead to substantial modifications of microbial composition in both plasma and feces and metabolic metagenome predictions. The stratification according to cART regimens revealed a feeble effect on microbiota composition in patients on NNRTI-based or INSTI-based regimens, but not PI-based regimens. Conclusions: We hereby show that 24 months of viro-immunological effective cART, while containing peripheral hyperactivation, exerts only minor effects on the gastrointestinal tract. Persistent alteration of plasma markers indicative of gut structural and functional impairment seemingly parallels enduring fecal dysbiosis, irrespective of drug classes, with no effect on metabolic metagenome predictions.

Treating Mitral Valve Prolapse in Barlow's Disease by Creation of a Medial MitraClip Bridge and a "New" Lateral Orifice: Rationale for MitraClip NTR Adoption.

Percutaneous mitral valve repair with MitraClip XTR (Abbott Vascular) has been proposed in patients with Barlow's disease, as the extended length of the MitraClip XTR may facilitate "grasping" and limit the number of clips. However, the design of the MitraClip XTR includes arms that 3 mm longer than the NTR device as well as 2 additional frictional elements, and requires a patient selection based mainly on mitral valve tissue quality. We summarize our rationale for using the shorter and smaller MitraClip NTR in patients with Barlow's disease.

The importance of patients' case-mix for the correct interpretation of the hospital fatality rate in COVID-19 disease.

OBJECTIVE: We aimed to document data on the epidemiology and factors associated with clinical course leading to death of patients hospitalised with COVID-19. METHODS: Prospective observational cohort study on patients hospitalised with COVID-19 disease in February-24th/May-17th 2020 in Milan, Italy. Uni-multivariable Cox regression analyses were performed. Death's percentage by two-weeks' intervals according to age and disease severity was analysed. RESULTS: A total of 174/539 (32.3%) patients died in hospital over 8228 person-day follow-up; the 14-day Kaplan-Meier probability of death was 29.5% (95%CI: 25.5-34.0). Older age, burden of comorbidities, COVID-19 disease severity, inflammatory markers at admission were independent predictors of increased risk, while several drug-combinations were predictors of reduced risk of in-hospital death. The highest fatality rate, 36.5%, occurred during the 2nd-3rd week of March, when 55.4% of patients presented with severe disease, while a second peak, by the end of April, was related to the admission of older patients (55% ≥80 years) with less severe disease, 30% coming from long-term care facilities. CONCLUSIONS: The unusual fatality rate in our setting is likely to be related to age and the clinical conditions of our patients. These findings may be useful to better allocate resources of the national healthcare system, in case of re-intensification of COVID-19 epidemics.

A Comparison of Tenofovir Predose Concentrations in Generic Pre-exposure Prophylaxis Formulations: A Short Communication.

BACKGROUND: There is extensive evidence to show that pre-exposure prophylaxis (PrEP) using tenofovir disoproxil fumarate (TDF)-based formulations dramatically reduces the risk of HIV acquisition among individuals without HIV infection. Here, the authors aim to compare tenofovir plasma predose concentrations in subjects taking PrEP daily versus on demand and using different TDF-based generic formulations. METHODS: Subjects providing informed signed consent for the measurement of tenofovir plasma levels were included in the study. Predose drug concentrations were stratified according to PrEP administration and the type of TDF-based formulation. The control group consisted of patients with HIV infection who were matched for renal function and were administered branded TDF that was not combined with boosted-antiretroviral drugs. RESULTS: The study consisted of 100 subjects (mean age, 39 ± 10 years; body weight, 77 ± 11 kg). A wide distribution in tenofovir predose concentrations was observed, with values ranging from 17 to 297 ng/mL (coefficient of variation 77%). No significant differences were noted in tenofovir predose concentrations between subjects who were administered PrEP daily (n = 75) or on demand (n = 25) [94 (35-255) versus 104 (37-287) ng/mL; P = 0.476]. Comparable tenofovir predose concentrations were found between patients with HIV infection (n = 220) who were administered branded TDF and those without HIV infection who were treated with 5 different generic TDF-based formulations with generics-to-branded ratios. These were always within the range of 80%-125% and were used to define bioequivalence. CONCLUSIONS: The marketed generic formulations of TDF delivered tenofovir plasma predose concentrations comparable with those delivered by branded formulations.

Patients with chronic autoimmune thyroiditis are not at higher risk for developing clinically overt thyroid cancer: a 10-year follow-up study.

OBJECTIVE: The association between chronic autoimmune thyroiditis (CAT) and differentiated thyroid cancer (DTC) remains controversial. The incidence of DTC increases when screening procedures are implemented, as typically occurs in CAT patients being routinely submitted to thyroid ultrasound (US). The aim of this study was to longitudinally evaluate the long-term development of DTC in patients with CAT. DESIGN AND METHODS: A retrospective longitudinal cohort study was designed. For the study, 510 patients with chronic autoimmune thyroiditis (CAT) with a 10-year follow-up were enrolled. Patients were divided in two groups according to the presence (CAT+ NOD+; n = 115) or absence (CAT+ NOD-; n = 395) of co-existent nodules at diagnosis. The main outcome measures were appearance of new thyroid-nodules and development of DTC during follow-up. RESULTS: During a 10-year median follow-up period, new thyroid-nodules were detected in 34/115 (29.5%) patients in the CAT+ NOD+ group and in 41/395 (10.3%) in the CAT+ NOD- group (P < 0.001). Logistic regression analysis showed that thyroid-volume at diagnosis and belonging to the CAT+ NOD+ group significantly predicted the appearance of a new thyroid nodule during follow-up, independently of baseline age and sex. Among the 75 patients experiencing the appearance of a new nodule, 27 (39%) met the criteria for fine-needle-aspiration-cytology (FNAC). A benign cytological diagnosis was rendered in all cases. CONCLUSIONS: In our series of CAT patients, the appearance of new thyroid-nodules was frequent, but none of them were found to be malignant. The presence of CAT appears to be associated with a negligible risk of developing clinically overt DTC.