Autopsy in adults with congenital heart disease (ACHD).

The adult congenital heart diseases (ACHD) population is exceeding the pediatric congenital heart diseases (CHD) population and is progressively expanding each year, representing more than 90% of patients with CHD. Of these, about 75% have undergone surgical and/or percutaneous intervention for palliation or correction. Autopsy can be a very challenging procedure in ACHD patients. The approach and protocol to be used may vary depending on whether the pathologists are facing native disease without surgical or percutaneous interventions, but with various degrees of cardiac remodeling, or previously palliated or corrected CHD. Moreover, interventions for the same condition have evolved over the last decades, as has perioperative myocardial preservations and postoperative care, with different long-term sequelae depending on the era in which patients were operated on. Careful clinicopathological correlation is, thus, required to assist the pathologist in performing the autopsy and reaching a diagnosis regarding the cause of death. Due to the heterogeneity of the structural abnormalities, and the wide variety of surgical and interventional procedures, there are no standard methods for dissecting the heart at autopsy. In this paper, we describe the most common types of CHDs that a pathologist could encounter at autopsy, including the various types of surgical and percutaneous procedures and major pathological manifestations. We also propose a practical systematic approach to the autopsy of ACHD patients

Diagnosis of myocardial infarction at autopsy: AECVP reappraisal in the light of the current clinical classification.

Ischemic heart disease is one of the leading causes of morbidity and death worldwide. Consequently, myocardial infarctions are often encountered in clinical and forensic autopsies, and diagnosis can be challenging, especially in the absence of an acute coronary occlusion. Precise histopathological identification and timing of myocardial infarction in humans often remains uncertain while it can be of crucial importance, especially in a forensic setting when third person involvement or medical responsibilities are in question. A proper post-mortem diagnosis requires not only up-to-date knowledge of the ischemic coronary and myocardial pathology, but also a correct interpretation of such findings in relation to the clinical scenario of the deceased. For these reasons, it is important for pathologists to be familiar with the different clinically defined types of myocardial infarction and to discriminate myocardial infarction from other forms of myocardial injury. This article reviews present knowledge and post-mortem diagnostic methods, including post-mortem imaging, to reveal the different types of myocardial injury and the clinical-pathological correlations with currently defined types of myocardial infarction

Cardiac hypertrophy at autopsy.

Since cardiac hypertrophy may be considered a cause of death at autopsy, its assessment requires a uniform approach. Common terminology and methodology to measure the heart weight, size, and thickness as well as a systematic use of cut off values for normality by age, gender, and body weight and height are needed. For these reasons, recommendations have been written on behalf of the Association for European Cardiovascular Pathology. The diagnostic work up implies the search for pressure and volume overload conditions, compensatory hypertrophy, storage and infiltrative disorders, and cardiomyopathies. Although some gross morphologic features can point to a specific diagnosis, systematic histologic analysis, followed by possible immunostaining and transmission electron microscopy, is essential for a final diagnosis. If the autopsy is carried out in a general or forensic pathology service without expertise in cardiovascular pathology, the entire heart (or pictures) together with mapped histologic slides should be sent for a second opinion to a pathologist with such an expertise. Indication for postmortem genetic testing should be integrated into the multidisciplinary management of sudden cardiac death

Measurements on hydrophobic and hydrophilic surfaces using a porous gamma alumina nanoparticle aggregate mounted on Atomic Force Microscopy cantilevers

Atomic Force Microscopy (AFM) measurements are extensively used for a detailed understanding ofmolecular and surface forces. In this study, we present a technique for measuring such forces, using an AFM cantilever attached with a porous gamma alumina nanoparticle aggregate. The modified cantilever was used to measure the forces of interaction of the aggregate with hydrophilic and hydrophobic surfaces. A strong force of attraction was observed between the aggregate and hydrophilic surfaces when the aggregate was kept dry. However, the force of interaction on the aggregate in wet form (water filled in pores) was larger when the adjoining surface had hydrophobic characteristics. The results presented in this study show the versatility of the current technique and indicate its usefulness in directly characterizing hydrophilic/ hydrophobic properties of nano-scale surfaces and patterns

Cardiovascular morbidity and associated risk factors in Spanish patients with chronic inflammatory rheumatic diseases attending rheumatology clinics: Baseline data of the CARMA Project

Objective To establish the cardiovascular (CV) morbidity and associated risk factors for CV disease (CVD) in Spanish patients with chronic inflammatory rheumatic diseases (CIRD) and unexposed individuals attending rheumatology clinics. Methods Analysis of data from the baseline visit of a 10-year prospective study [CARdiovascular in rheuMAtology (CARMA) project] that includes a cohort of patients with CIRD [rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)] and another cohort of matched individuals without CIRD attending outpatient rheumatology clinics from 67 hospitals in Spain. Prevalence of CV morbidity, CV risk factors, and systematic coronary risk evaluation (SCORE) assessment were analyzed. Results A total of 2234 patients (775 RA, 738 AS, and 721 PsA) and 677 unexposed subjects were included. Patients had low disease activity at the time of recruitment. PsA patients had more commonly classic CV risk factors and metabolic syndrome features than did the remaining individuals. The prevalence of CVD was higher in RA (10.5%) than in AS (7.6%), PsA (7.2%), and unexposed individuals (6.4%). A multivariate analysis adjusted for the presence of classic CV risk factors and disease duration revealed a positive trend for CVD in RA (OR = 1.58; 95% CI: 0.90–2.76; p = 0.10) and AS (OR = 1.77; 95% CI: 0.96–3.27; p = 0.07). Disease duration in all CIRD groups and functional capacity (HAQ) in RA were associated with an increased risk of CVD (OR = 2.15; 95% CI: 1.29–3.56; p = 0.003). Most patients had a moderate CV risk according to the SCORE charts. Conclusions Despite recent advances in the management of CIRD, incidence of CVD remains increased in Spanish subjects with CIRD attending outpatient rheumatology clinics

A randomized trial of long-term remote monitoring of pacemaker recipients (The COMPAS trial)

International audienceAIMS: Professional practice guidelines recommend that pacemaker recipients be followed regularly. However, the majority of scheduled ambulatory visits is unproductive and imposes a heavy burden on the health-care system. METHODS AND RESULTS: The COMPAS randomized, multicentre, non-inferiority trial examined the safety of long-term remote monitoring of pacemakers. Between December 2005 and January 2008, 538 patients were randomly assigned to remote monitoring follow-up (active group) vs. standard care (control group). The primary objective was to confirm that the proportion of patients who experienced at least one major adverse event (MAE), including all-cause death and hospitalizations for device-related or cardiovascular adverse events, was not >7% higher in the active than in the control group. MAE-free survivals and quality of life were compared in both groups. The characteristics of the study groups were similar. Over a follow-up of 18.3 months, 17.3% of patients in the active and 19.1% in the control group experienced at least one MAE (P < 0.01 for non-inferiority). Hospitalizations for atrial arrhythmias (6 vs. 18) and strokes (2 vs. 8) were fewer (P < 0.05), and the number of interim ambulatory visits was 56% lower (P < 0.001) in the active than the control group. Changes in pacemaker programming or drug regimens were made in 62% of visits in the active vs. 29% in the control group (P < 0.001). Quality of life remained unchanged in both groups. CONCLUSION: Remote monitoring was a safe alternative to conventional care and significantly lowered the number of ambulatory visits during long-term follow-up of permanently paced patients. ClinicalTrials.gov identifier: NCT00989326

Dabigatran in patients with atrial fibrillation: perioperative and periinterventional management

In any type of invasive surgery, the patient’s individual risk of thromboembolism has to be weighed against the risk of bleeding. Based on various everyday situations in clinical routine, the purpose of the present expert recommendations is to provide appropriate perioperative and periinterventional management for patients with atrial fibrillation undergoing long-term treatment with the thrombin inhibitor dabigatran. As we currently have no routine laboratory test to measure therapeutic levels of the substance or the risk of bleeding, general measures such as a standardized documentation of the patient’s history, a sufficient time interval between the last preoperative dose and the procedure, and careful control of local hemostasis should be given special attention

Genetically determined cardiomyopathies at autopsy: the pivotal role of the pathologist in establishing the diagnosis and guiding family screening.

Cardiomyopathies (CMP) comprise a heterogenous group of diseases affecting primarily the myocardium, either genetic and/or acquired in origin. While many classification systems have been proposed in the clinical setting, there is no internationally agreed pathological consensus concerning the diagnostic approach to inherited CMP at autopsy. A document on autopsy diagnosis of CMP is needed because the complexity of the pathologic backgrounds requires proper insight and expertise. In cases presenting with cardiac hypertrophy and/or dilatation/scarring with normal coronary arteries, a suspicion of inherited CMP must be considered, and a histological examination is essential. Establishing the actual cause of the disease may require a number of tissue-based and/or fluid-based investigations, be it histological, ultrastructural, or molecular. A history of illicit drug use must be looked for. Sudden death is frequently the first manifestation of disease in case of CMP, especially in the young. Also, during routine clinical or forensic autopsies, a suspicion of CMP may arise based on clinical data or pathological findings at autopsy. It is thus a challenge to make a diagnosis of a CMP at autopsy. The pathology report should provide the relevant data and a cardiac diagnosis which can help the family in furthering investigations, including genetic testing in case of genetic forms of CMP. With the explosion in molecular testing and the concept of the molecular autopsy, the pathologist should use strict criteria in the diagnosis of CMP, and helpful for clinical geneticists and cardiologists who advise the family as to the possibility of a genetic disease

A common missense variant of <i>LILRB₅</i> is associated with statin intolerance and myalgia

Aims A genetic variant in LILRB5 (leukocyte immunoglobulin-like receptor subfamily-B) (rs12975366: T > C: Asp247Gly) has been reported to be associated with lower creatine phosphokinase (CK) and lactate dehydrogenase (LDH) levels. Both biomarkers are released from injured muscle tissue, making this variant a potential candidate for susceptibility to muscle-related symptoms. We examined the association of this variant with statin intolerance ascertained from electronic medical records in the GoDARTS study. Methods and results In the GoDARTS cohort, the LILRB5 Asp247 variant was associated with statin intolerance (SI) phenotypes; one defined as having raised CK and being non-adherent to therapy [odds ratio (OR) 1.81; 95% confidence interval (CI): 1.34–2.45] and the other as being intolerant to the lowest approved dose of a statin before being switched to two or more other statins (OR 1.36; 95% CI: 1.07–1.73). Those homozygous for Asp247 had increased odds of developing both definitions of intolerance. Importantly the second definition did not rely on CK elevations. These results were replicated in adjudicated cases of statin-induced myopathy in the PREDICTION-ADR consortium (OR1.48; 95% CI: 1.05–2.10) and for the development of myalgia in the JUPITER randomized clinical trial of rosuvastatin (OR1.35, 95% CI: 1.10–1.68). A meta-analysis across the studies showed a consistent association between Asp247Gly and outcomes associated with SI (OR1.34; 95% CI: 1.16–1.54). Conclusion This study presents a novel immunogenetic factor associated with statin intolerance, an important risk factor for cardiovascular outcomes. The results suggest that true statin-induced myalgia and non-specific myalgia are distinct, with a potential role for the immune system in their development. We identify a genetic group that is more likely to be intolerant to their statins