Left atrial mass: relationship between gross anatomy and quantitative echocardiography.

Background: Left atrial (LA) enlargement is associated with increased risk of adverse cardiovascular outcomes. Unlike the left ventricular mass, LA mass has not been described. We sought to define the anatomic mass of the LA using anatomic specimens from autopsy.

Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy.

Arrhythmogenic cardiomyopathy (ACM) is an inherited arrhythmia syndrome characterized by severe structural and electrical cardiac phenotypes, including myocardial fibrofatty replacement and sudden cardiac death. Clinical management of ACM is largely palliative, owing to an absence of therapies that target its underlying pathophysiology, which stems partially from our limited insight into the condition. Following identification of deceased ACM probands possessing ANK2 rare variants and evidence of ankyrin-B loss of function on cardiac tissue analysis, an ANK2 mouse model was found to develop dramatic structural abnormalities reflective of human ACM, including biventricular dilation, reduced ejection fraction, cardiac fibrosis, and premature death.

Refining the World Health Organization Definition: Predicting Autopsy-Defined Sudden Arrhythmic Deaths Among Presumed Sudden Cardiac Deaths in the POST SCD Study.

Background: Conventional definitions of sudden cardiac death (SCD) presume cardiac cause. We studied the World Health Organization-defined SCDs autopsied in the POST SCD study (Postmortem Systematic Investigation of SCD) to determine whether premortem characteristics could identify autopsy-defined sudden arrhythmic death (SAD) among presumed SCDs.

Methods: Between January 2, 2011, and January 4, 2016, we prospectively identified all 615 World Health Organization-defined SCDs (144 witnessed) 18 to 90 years in San Francisco County for medical record review and autopsy via medical examiner surveillance.

Sinus of Valsalva Aneurysm and Infective Endocarditis Involving a Bicuspid Aortic Valve in an Infant With Trisomy 21.

A 19-month-old girl with trisomy 21 and a congenitally bicuspid aortic valve died following a short febrile illness. Autopsy disclosed pericarditis, epimyocardial abscess, infective endocarditis, and a sinus of Valsalva aneurysm. Microscopy demonstrated continuity between the aortic wall and valve leaflet, consistent with an acquired aneurysm.

Oligogenic inheritance of a human heart disease involving a genetic modifier.

Complex genetic mechanisms are thought to underlie many human diseases, yet experimental proof of this model has been elusive. Here, we show that a human cardiac anomaly can be caused by a combination of rare, inherited heterozygous mutations. Whole-exome sequencing of a nuclear family revealed that three offspring with childhood-onset cardiomyopathy had inherited three missense single-nucleotide variants in the , , and genes.

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

 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.

Prospective Countywide Surveillance and Autopsy Characterization of Sudden Cardiac Death: POST SCD Study.

Background: Studies of out-of-hospital cardiac arrest and sudden cardiac death (SCD) use emergency medical services records, death certificates, or definitions that infer cause of death; thus, the true incidence of SCD is unknown. Over 90% of SCDs occur out-of-hospital; nonforensic autopsies are rarely performed, and therefore causes of death are presumed. We conducted a medical examiner-based investigation to determine the precise incidence and autopsy-defined causes of all SCDs in an entire metropolitan area.

A Preliminary Study of Left Ventricular Rotational Mechanics in Children with Noncompaction Cardiomyopathy: Do They Influence Ventricular Function?

Background: Current diagnostic criteria for noncompaction cardiomyopathy (NCC) lack specificity, and the disease lacks prognostic indicators. Reverse apical rotation (RAR) with abnormal rotation of the cardiac apex in the same clockwise direction as the base has been described in adults with NCC. The aim of this study was to test the hypothesis that RAR might differentiate between symptomatic NCC and benign hypertrabeculations and might be associated with ventricular dysfunction.

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.

Sudden Death in Patients With Cardiac Implantable Electronic Devices.

Importance: Interrogations and autopsies of sudden deaths with cardiac implantable electronic devices (CIEDs) are rarely performed. Therefore, causes of sudden deaths with these devices and the incidence of device failure are unknown.

Objective: To determine causes of death in individuals with CIEDs in a prospective autopsy study of all sudden deaths over 35 months as part of the San Francisco, California, Postmortem Systematic Investigation of Sudden Cardiac Death (POST SCD) study.

Plakoglobin immunolocalization as a diagnostic test for arrhythmogenic right ventricular cardiomyopathy.

Background: A recent study using an anti-plakoglobin antibody and immunofluorescence methods in endomyocardial tissue specimens found that a marked reduction in plakoglobin staining was highly sensitive and specific for the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). The purpose of our study was to determine the diagnostic utility of plakoglobin immunolocalization using more standard immunoperoxidase methods suitable for clinical laboratories.

Methods: Between January 2007 and October 2010, all patients at our center with suspected ARVC underwent noninvasive and genetic testing, right ventricular (RV) angiography, electrophysiologic studies, and endomyocardial biopsy from the RV septum.

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.

Sudden death due to nonarrhythmic cause in a patient with L-TGA.

We report a case of sudden death in a clinically stable adult with l-transposition of the great arteries (l-TGA). Sudden death has been reported to be the leading cause of death in l-TGA and is often attributed to arrhythmias in the absence of another identifiable cause. However, the contribution of nonarrhythmic causes to the burden of sudden death in this population is unknown.

Noncompaction in the fetus and neonate: an autopsy study.

Noncompaction refers to an uncommon structural abnormality of the heart's ventricular myocardium characterized by an abnormally thick layer of left ventricular trabeculations, as well as hypoplastic papillary muscles. The condition is associated with a variable clinical phenotype including heart failure, thromboembolism, and sudden death. In this retrospective study of fetal and neonatal autopsy hearts with noncompaction, clinical profiles were correlated with gross and histologic findings and compared with a set of age-matched controls.

Monoamniotic monochorionic twins discordant for noncompaction cardiomyopathy.

Occasionally "identical twins" are phenotypically different, raising the question of zygosity and the issue of genetic versus environmental influences during development. We recently noted monochorionic-monoamniotic twins, one of which had an isolated cardiac abnormality, noncompaction cardiomyopathy, a condition characterized by cardiac ventricular hypertrabeculation. We examined the prenatal course and subsequent pathologic correlation since ventricular morphogenesis may depend on early muscular contraction and blood flow.

Characteristics of sudden arrhythmic death in a diverse, urban community.

Background: Sudden cardiac death (SCD) remains a major public health problem; however, its true burden remains unknown with widely variable estimates of its incidence. We aimed to examine the contemporary epidemiology and autopsy characteristics of SCD in an ethnically diverse community.

Methods: Three physicians reviewed all deaths of individuals aged ≥20 years reported to the San Francisco medical examiner in 2007 for presentations fitting World Health Organization (WHO) SCD criteria-within 1 hour of symptom onset (witnessed) or within 24 hours of being observed alive and symptom free (unwitnessed).

Evaluation of the acute effects of distal coronary microembolization using multidetector computed tomography and magnetic resonance imaging.

The purpose of this study was to test the potential of clinical imaging modalities, 64-slice multidetector computed tomography (MDCT) and 1.5T magnetic resonance imaging (MRI) for qualitative and quantitative evaluation of acute microinfarcts and to determine the effects of <120 μm microemboli on left ventricular function, perfusion, cardiac injury biomarkers, arrhythmia, and cellular and vascular structures. Under X-ray fluoroscopy, 40-120 μm (16 mm(3) ) microemboli were delivered to embolize the left anterior descending (LAD) coronary artery of nine pigs.

Furthering the link between the sarcomere and primary cardiomyopathies: restrictive cardiomyopathy associated with multiple mutations in genes previously associated with hypertrophic or dilated cardiomyopathy.

Mutations in genes that encode components of the sarcomere are well established as the cause of hypertrophic and dilated cardiomyopathies. Sarcomere genes, however, are increasingly being associated with other cardiomyopathies. One phenotype more recently recognized as a disease of the sarcomere is restrictive cardiomyopathy (RCM).

Sterile radial artery granuloma after transradial cardiac catheterization.

Transradial cardiac catheterization has lower rates of arterial access site complications than transfemoral procedures. However, there are complications that are unique to the transradial route. We present the case of a sterile granuloma occurring at the site of radial arterial access as a reaction to the hydrophilic coating on the sheath.

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

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.

Genetic modifier of mitochondrial superoxide dismutase-deficient mice delays heart failure and prolongs survival.

Mn superoxide dismutase (MnSOD)-deficient mice (Sod2-/-) suffer from mitochondrial damage and have various survival times and phenotypic presentations that are dependent on the genetic background of the mutant mice. The mitochondrial NADPH transhydrogenase (NNT) was identified as a putative genetic modifier based on a genome-wide quantitative trait association study on the molecular defect of the protein in more severely affected Sod2-/- mice and on the biological function of NNT. Hence, Sod2-/- mice on the C57BL/6J (B6J) background have the shortest survival time, and the mice are homozygous for the truncated Nnt allele (Nnt ( T )).

Anomalous mitral arcade in twin-twin transfusion syndrome.

Background: Echocardiography has documented acquired pulmonary stenosis and cardiomyopathy in recipient fetuses in twin-twin transfusion syndrome. At autopsy, we also have identified anomalous mitral arcade, a rare valve deformity associated with mitral regurgitation.

Methods And Results: To identify a profile for anomalous mitral arcade, we compared clinicopathological data from 11 sets of autopsied twin-twin transfusion syndrome fetuses, including 4 twin pairs in whom the recipient had anomalous mitral arcade (affected) and 7 pairs in whom both had structurally normal mitral valves (unaffected).

Left ventricular rupture due to HIV-associated T-cell lymphoma.

Patients with lymphoma can develop cardiac involvement that includes malignant pericardial effusions and myocardial infiltration, but extensive myocardial invasion by tumor with resultant rupture has been reported only rarely. We report a case of a patient with human immunodeficiency virus and T-cell lymphoma who presented with signs and symptoms that were suggestive of a non-ST-elevation myocardial infarction. Plans were made for cardiac catheterization, but the patient developed thrombocytopenia after the initiation of heparin and eptifibatide.

QTc prolongation and family history of sudden death in a patient with desmin cardiomyopathy.

This case report describes a pregnant female patient who presented with new-onset congestive heart failure symptoms and prolonged QTc, with strong family history of sudden death. Endomyocardial biopsy and genetic testing revealed myocardial desmin accumulation and a previously described mutation in the DES (desmin) gene, as well as variants in two LQT genes, SCN5A and KCNH2. The case highlights the phenotypic variability for a particular desmin genotype, and the possible interaction of desminopathy with LQT variants not independently associated with large differences in current properties or QT prolongation from wild type.