Free light chain UV quantification compared with immunochemical measurement: How dimers and monomers may influence the results

Serum κ and λ free light chain (FLC) levels are important for the management of plasma cell disorders. Immunochemical measurements on automated platforms with different reagents occasionally return different results that make them not interchangeable. The reasons for this behaviour are not clear and it is not known which result is the most accurate. The aim of the study is to quantify naturally occurring FLCs with a reference method (UV absorbance) in a sample devoid of other sources of UV absorbance. This was possible on a particular urine sample containing only lambda FLC proteins, dialyzed to clear it from low molecular weight UV absorbing compounds. The sample was submitted to Fast Protein Liquid Chromatography separation with a size-exclusion column in order to separate the FLC monomers and dimers. FLCs were also measured with the Freelite and N Latex FLC methods and the results were compared. The results demonstrated that the amount of FLC calculated on the basis of UV absorbance was overestimated by both immunochemical methods, and that the amount measured by the two reagents was affected by the different proportions of dimers or monomers. The present findings may be useful for the comprehension of the immunochemical measurement of FLC

The burden of calcific aortic stenosis. what's behind

In Western countries, calcific aortic valve stenosis (CAS) is widely common, representing the third cause of death among cardiovascular diseases (CVD). The burden of CAS is high, with an increasing prevalence rate related to age. An efficient medical treatment, according to guidelines, lacks to prevent the development and to reduce the progression of CAS. In this context, due to the aging population and the lack of effective medical management, the prevalence is expected to double-triple within the next decades. In our review, we aim to provide an overview of the underlying mechanisms of pathogenesis and the current state of the art regarding pathophysiological insights and novel potential therapeutic targets

Functional Tricuspid Regurgitation: Behind the Scenes of a Long-Time Neglected Disease

Severe tricuspid valve regurgitation has been for a long time a neglected valve disease, which has only recently attracted an increasing interest due to the notable negative impact on the prognosis of patients with cardiovascular disease. It is estimated that around 90% of tricuspid regurgitation is diagnosed as "functional" and mostly secondary to a primary left-sided heart disease and, therefore, has been usually interpreted as a benign condition that did not require a surgical management. Nevertheless, the persistence of severe tricuspid regurgitation after left-sided surgical correction of a valve disease, particularly mitral valve surgery, has been associated to adverse outcomes, worsening of the quality of life, and a significant increase in mortality rate. Similar results have been found when the impact of isolated severe tricuspid regurgitation has been studied. Current knowledge is shifting the "functional" categorization toward a more complex and detailed pathophysiological classification, identifying various phenotypes with completely different etiology, natural history and, potentially, an invasive management. The aim of this review is to offer a comprehensive guide for clinicians and surgeons with a systematic description of "functional" tricuspid regurgitation subtypes, an analysis centered on the effectiveness of existing surgical techniques and a focus on the emergent percutaneous procedures. This latter may be an attractive alternative to a standard surgical approach in patients with high-operative risk or isolated tricuspid regurgitation.Copyright © 2022 Vinciguerra, Sitges, Luis Pomar, Romiti, Domenech-Ximenos, D'Abramo, Wretschko, Miraldi and Greco

Features of Clinical Complexity in European Patients With Atrial Fibrillation: A Report From a European Observational Prospective AF Registry

There is increasing concern regarding impact of clinical complexity in patients with atrial fibrillation (AF). We explored the impact of different clinical complexity features in AF patients. We analyzed patients from a prospective, observational, multicenter Europe-wide AF registry. Features of clinical complexity among patients with CHA2DS2-VASc ≥2 were: (1) history of bleeding; (2) frailty; (3) chronic kidney disease (CKD); (4) ≥2 features. A total of 10,169 patients were analyzed. Of these, 141 (1.4%) had history of bleeding, 954 (9.4%) were frail, 1767 (17.4%) had CKD and 1253 (12.3%) had ≥2 features. All features of clinical complexity were less treated with OAC. History of bleeding (HR 1.94, 95% CI 1.32-2.85), frailty (HR 1.38, 95% CI 1.11-1.71), CKD (HR 1.50, 95% 1.28-1.75) and ≥2 features (HR 2.08, 95% CI 1.73-2.51) were associated with outcomes. Presence of features of clinical complexity is associated with lower use of OAC and higher risk of outcomes

A systematic review and meta-analysis on oncological radiotherapy in patients with a cardiac implantable electronic device: Prevalence and predictors of device malfunction in 3121 patients

Background: The number of patients with cardiac implantable electronic devices (CIEDs) undergoing radiotherapy (RT) for cancer treatment is growing. At present, prevalence and predictors of RT-induced CIEDs malfunctions are not defined. Methods: Systematic review and meta-analysis conducted following the PRISMA recommendations. PubMed, Scopus and Google Scholar were searched from inception to 31/01/2022 for studies reporting RT-induced malfunctions in CIEDs patients. Aim was to assess the prevalence of RT-induced CIEDs malfunctions and identify potential predictors. Results: Thirty-two out of 3962 records matched the inclusion criteria and were included in the meta-analysis. A total of 135 CIEDs malfunctions were detected among 3121 patients (6.6%, 95% confidence interval [CI]: 5.1%–8.4%). The pooled prevalence increased moving from pacemaker (PM) to implantable cardioverter defibrillator (ICD), and cardiac resynchronization therapy and defibrillator (CRT-D) groups (4.1%, 95% CI: 2.9–5.8; 8.2% 95% CI: 5.9–11.3; and 19.8%, 95% CI: 11.4–32.2 respectively). A higher risk ratio (RR) of malfunctions was found when neutron-producing energies were used as compared to non-neutron-producing energies (RR 9.98, 95% CI: 5.09–19.60) and in patients with ICD/CRT-D as compared to patients with PM/CRT-P (RR 2.07, 95% CI: 1.40–3.06). On the contrary, no association was found between maximal radiation dose at CIED >2 Gy and CIEDs malfunctions (RR 0.93; 95% CI: 0.31–2.76). Conclusions: Radiotherapy related CIEDs malfunction had a prevalence ranging from 4% to 20%. The use of neutron-producing energies and more complex devices (ICD/CRT-D) were associated with higher risk of device malfunction, while the radiation dose at CIED did not significantly impact on the risk unless higher doses (>10 Gy) were used

Co-infection of SARS-CoV-2 with Chlamydia or Mycoplasma pneumoniae: a case series and review of the literature

Introduction: The novel coronavirus SARS-CoV-2 has spread all over the world causing a global pandemic and representing a great medical challenge. Nowadays, there is limited knowledge on the rate of co-infections with other respiratory pathogens, with viral co-infection being the most representative agents. Co-infection with Mycoplasma pneumoniae has been described both in adults and pediatrics whereas only two cases of Chlamydia pneumoniae have been reported in a large US study so far. Methods: In the present report, we describe a series of seven patients where co-infection with C. pneumoniae (n = 5) or M. pneumoniae (n = 2) and SARS-CoV-2 was detected in a large teaching hospital in Rome. Results and conclusion: An extensive review of the updated literature regarding the co-infection between SARS-CoV-2 and these atypical pathogens is also performed

Different techniques of surgical left atrial appendage closure and their efficacy. a systematic review

Background: Atrial fibrillation has been identified as an independent risk factor for thromboembolic events. Since 1948 different surgical techniques have described the feasibility and the rationale of left atrial surgical appendage closure. The aim of this systematic review is to evaluate the reported patency rates of different surgical techniques. Methods: This systematic review was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Two independent investigators searched the PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and OVID & REG; (Wolters Kluwer, Alphen aan den Rijn, Netherlands) to identify relevant studies. Consecutively, a PICO (Population, Intervention, Comparison and Outcomes) strategy assessment of literature was performed to search eventual other relevant studies that may have been ignored. Results: A total of 42 studies were included in our analysis. The total number of patients who underwent surgical left atrial appendage closure was 5671, and in 61.2% an imaging follow up was performed, mostly with transesophageal echocardiographic evaluation. Success rate for the different techniques was: Clip deployment 98%; Lariat procedure 88%; Surgical amputation 91%; Endocardial suture 74.3%, Epicardial suture 65%; Left atrial appendage closure (LAAC) ligation 60.9%; Stapler technique with excision of left atrial appendage (LAA) 100%; Stapler without excision 70%. Conclusions: To date, data on surgical left atrial appendage closure are poor and not standardized, even if reported rates are acceptable and comparable to transcatheter procedures. If validated on large-scale non-retrospective and multicentric studies, these promising developments may offer a valuable alternative for patients with atrial fibrillation (AF) and ineligible for oral anticoagulation therapy

Epidemiology of subclinical atrial fibrillation in patients with cardiac implantable electronic devices: A systematic review and meta-regression

Background: In recent years, attention to subclinical atrial fibrillation (SCAF), defined as the presence of atrial high-rate episodes (AHREs), in patients with cardiac implantable electronic devices (CIEDs), has gained much interest as a determinant of clinical AF and stroke risk. We aim to perform a systematic review and meta-regression of the available scientific evidence regarding the epidemiology of SCAF in patients receiving CIEDs. Methods: PubMed and EMBASE were searched for all studies documenting the prevalence of AHREs in patients (n=100 or more, <50% with history of AF) with CIEDs from inception to 20th August 2021, screened by two independent blind reviewers. This study was registered in PROSPERO: CRD42019106994. Results: Among the 2614 results initially retrieved, 54 studies were included, with a total of 72,784 patients. Meta-analysis of included studies showed a pooled prevalence of SCAF of 28.1% (95%CI: 24.3-32.1%), with high heterogeneity between studies (I2=98%). A multivariable meta-regression was able to explain significant proportion of heterogeneity (R2=61.9%, p<0.001), with age and follow-up time non-linearly, directly and independently associated with occurrence of SCAF. Older age, higher CHA2DS2-VASc score, history of AF, hypertension, CHF, and stroke/TIA were all associated with SCAF occurrence. Conclusions: In this systematic review and meta-regression analysis, SCAF was frequent among CIED recipients and was non-linearly associated with age and follow-up time. Older age, higher thromboembolic risk, and several cardiovascular comorbidities were associated with presence of SCAF

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

BACKGROUND: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The 'Atrial fibrillation Better Care' (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. METHODS: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. RESULTS: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58-0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52-0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58-0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56-0.98) and composite outcome (aHR: 0.76, 95%CI 0.60-0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. CONCLUSIONS: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Yield of diagnosis and risk of stroke with screening strategies for atrial fibrillation: a comprehensive review of current evidence

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. The presence of AF is associated with increased risk of systemic thromboembolism, but with the uptake of oral anticoagulant (OAC) and implementation of a holistic and integrated care management, this risk is substantially reduced. The diagnosis of AF requires a 30-s-long electrocardiographic (ECG) trace, irrespective of the presence of symptoms, which may represent the main indication for an ECG tracing. However, almost half patients are asymptomatic at the time of incidental AF diagnosis, with similar risk of stroke of those with clinical AF. This has led to a crucial role of screening for AF, to increase the diagnosis of population at risk of clinical events. The aim of this review is to give a comprehensive overview about the epidemiology of asymptomatic AF, the different screening technologies, the yield of diagnosis in asymptomatic population, and the benefit derived from screening in terms of reduction of clinical adverse events, such as stroke, cardiovascular, and all-cause death. We aim to underline the importance of implementing AF screening programmes and reporting about the debate between scientific societies’ clinical guidelines recommendations and the concerns expressed by the regulatory authorities, which still do not recommend population-wide screening. This review summarizes data on the ongoing trials specifically designed to investigate the benefit of screening in terms of risk of adverse events which will further elucidate the importance of screening in reducing risk of outcomes and influence and inform clinical practice in the next future