Coronary microembolization causes long-term detrimental effects on regional left ventricular function.

Abstract Objectives. To investigate whether coronary microemboli have long-term effects on left ventricular (LV) function in an experimental model. Furthermore, to determine if first-pass perfusion and late gadolinium enhancement (LGE) patterns differs between small- and large-sized microemboli. Design. Six pigs underwent left anterior descending (LAD)-coronary microembolization with small-sized (40-120 μm, n∼250 000) microemboli using a combined x-ray and MRI-system. MR-images before, one hour after and 7-8 weeks after microembolization were obtained. Results were compared to MRI obtained by large-sized (100-300 μm, n∼7200) microemboli. Results. Cine MRI showed an acute drop in ejection fraction (from 49.5 ± 2.6% to 32.5 ± 2.8) that substantially recovered at 7-8 weeks (47.5 ± 3.2%). Regional LV-function assessed as circumferential, longitudinal and radial strain declined in both microinfarcts and remote regions followed by partial recovery at 7-8 weeks. The decline in LV function and the severe perfusion deficit from the small microemboli was similar to the large microemboli at one hour. There was a significant recovery in perfusion at 7-8 weeks in the microinfarcts. LGE demonstrated the microinfarcts at 7-8 weeks but not at one hour and the microinfarcts were confirmed by histopathology. Conclusion. Microembolization causes long-term, regional LV dysfunction and this study confirmed the need of a comprehensive MRI-protocol for the detection of microinfarcts. These findings suggest that even small microemboli (40-120 μm in diameter), which may escape the distal protective devices influence cardiac function

Sudden neurologic death masquerading as out-of-hospital sudden cardiac death

OBJECTIVE: To characterize the frequency of and risk factors for out-of-hospital sudden neurologic deaths. METHODS: During the initial 25 months (February 1, 2011–March 1, 2013) of the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death Study, we captured incident WHO criteria sudden cardiac deaths (SCDs) through active surveillance of consecutive out-of-hospital deaths, which must be reported to the medical examiner by law. All cases were referred for full autopsy with detailed examination of the heart and cranial vault, toxicology, and histology. A multidisciplinary committee adjudicated a final cause of death. RESULTS: Of 352 incident SCDs, 335 (95%) underwent systematic evaluation including full autopsy. Of these 335 cases, 18 (5.4%) were sudden neurologic deaths (mean age 60.6 years [SD 17.6, range 27–87]; 67.7% female), which accounted for 14.9% of the 121 noncardiac sudden deaths. The risk of sudden neurologic death compared to non-neurologic SCD was lower in male and white participants (p < 0.01). Neurologic causes included intracranial hemorrhage (8), sudden unexpected death in epilepsy (6, including 2 with juvenile myoclonic epilepsy), aneurysmal subarachnoid hemorrhage (2), acute ischemic stroke (1), and aspiration from Huntington disease (1). Most deaths were unwitnessed (16; 89%) with asystole at presentation (17; 94%). Prior stroke/TIA was not associated with risk of stroke (odds ratio [OR] 1.4 [95% confidence interval (CI) 0.18–11.8], p = 0.73), but antithrombotic medication use was (OR 3.9 [95% 1.01–15.5], p = 0.05). CONCLUSIONS: Sudden neurologic death is an important cause of out-of-hospital apparent SCDs. Low prevailing autopsy rates may result in systematic misclassification of apparent SCDs and underestimation of the incidence of sudden neurologic death

How does Fetal Autopsy after Pregnancy Loss or Termination for Anomalies and other Complications Change Recurrence Risk?

Abstract Objective Historically, fetal autopsy was common after terminations for anomalies. Previous studies report that fetal autopsy confirms ultrasound findings in the majority of cases. This study aims to examine correlation between prenatal and autopsy diagnoses at University of California, San Francisco (UCSF) and evaluate whether autopsy adds diagnostic information, specifically information that changes risk of recurrence for future pregnancies. Study Design We conducted a retrospective chart review of all fetal autopsies performed at UCSF between 1994 and 2009. Prenatal diagnosis was compared with autopsy diagnosis; for cases where there was a change in diagnosis, an MFM (maternal-fetal medicine specialist) reviewed the case to assign risk of recurrence before and after autopsy. Results Overall, there was concordance between prenatal diagnosis and autopsy diagnosis in greater than 91.7% of cases. Autopsy added information that resulted in a change in recurrence risk in 2.3% of cases (n = 9). Conclusion For the vast majority of cases, there is agreement between prenatal and autopsy diagnosis after pregnancy loss or termination for fetal anomalies. Only a small percentage of autopsies change recurrence risk. This may be useful when counseling women about method of termination and when counseling couples about whether to have an autopsy

Novel interstitial 2.6 Mb deletion on 9q21 associated with multiple congenital anomalies.

Array comparative genomic hybridization (aCGH) is now commonly used to identify copy number changes in individuals with developmental delay, intellectual disabilities, autism spectrum disorders, and/or multiple congenital anomalies. We report on an infant with multiple congenital anomalies and a novel 2.6 Mb interstitial deletion within 9q21.32q21.33 detected by aCGH. Her clinical presentation included dysmorphic craniofacial features, cleft palate, atrial septal defect, bicornuate uterus, bilateral hip dislocation, hypotonia, and recurrent pneumonia. Parental aCGH studies were negative for copy loss in this region. To our knowledge, no similar deletions have been reported in available databases or published literature. This deletion encompasses 12 genes, and prediction algorithms as well as experimental data suggest that a subset is likely to be haploinsufficient. Included are a neurotrophin receptor (NKG2D), a gene implicated in cilia function (KIF27), an adaptor protein important for ubiquitin-dependent protein quality control (UBQLN1), a gene important for transcription and signaling (HNRNPK), and a gene involved in maintaining genomic stability (RMI1). Identifying additional patients with similar copy losses and further study of these genes will contribute to a better understanding of the pathophysiology of multiple congenital anomalies