Stage B Heart Failure Is Ubiquitous in Emergency Patients with Asymptomatic Hypertension.

Introduction: Hypertension is the leading risk factor for morbidity and mortality throughout the world and is pervasive in United States emergency departments (ED). This study documents the point prevalence of subclinical heart disease in emergency patients with asymptomatic hypertension. Method: This was a prospective observational study of ED patients with asymptomatic hypertension conducted at two urban academic EDs that belong to an eight-hospital healthcare organization in New York. Adult (≥18 years of age) English- or Spanish-speaking patients who had an initial blood pressure (BP) ≥160/100 millimeters of mercury (mmHg) and second BP ≥140/90 mm Hg, and pending discharge, were invited to participate in the study. We excluded patients with congestive heart failure, renal insufficiency, and atrial fibrillation, or who were pregnant, a prisoner, cognitively unable to provide informed consent, or experiencing symptoms of hypertension. We assessed echocardiographic evidence of subclinical heart disease (left ventricular hypertrophy, and diastolic and systolic dysfunction). Results: A total of 53 patients were included in the study; a majority were young (mean 49.5 years old, [SD 14-52]), self-identified as Black or Other (n = 39; 73.5%), and female (n = 30; 56.6%). Mean initial blood pressure was 172/100 mm Hg, and 24 patients (45.3%) self-reported a history of hypertension. Fifty patients completed an echocardiogram. All (100%) had evidence of subclinical heart disease, with 41 (77.4%) displaying left ventricular hypertrophy and 31 (58.5%) diastolic dysfunction. There was a significant relationship between diastolic dysfunction and female gender [x2 (1, n = 53) = 3.98; P = 0.046]; Black or other race [x2 (3, n = 53) = 9.138; P = 0.03] and Hispanic or other ethnicity [x2 (2, n = 53) = 8.03; P = 0.02]. Less than one third of patients demonstrated systolic dysfunction on echocardiogram, and this was more likely to occur in patients with diabetes mellitus [x2 (1, n = 51) = 4.84; P = 0.02]. Conclusion: There is a high probability that Black, Hispanic, and female patients with asymptomatic hypertension are on the continuum for developing overt heart failure. Emergency clinicians should provide individualized care that considers their unique health needs, cultural backgrounds, and social determinants of health.

The cellular bases of choroid fissure formation and closure.

Defects in choroid fissure (CF) formation and closure lead to coloboma, a major cause of childhood blindness. Despite genetic advances, the cellular defects underlying coloboma remain poorly elucidated due to our limited understanding of normal CF morphogenesis. We address this deficit by conducting high-resolution spatio-temporal analyses of CF formation and closure in the chick, mouse and fish. We show that a small ventral midline invagination initiates CF formation in the medial-proximal optic cup, subsequently extending it dorsally toward the lens, and proximally into the optic stalk. Unlike previously supposed, the optic disc does not form solely as a result of this invagination. Morphogenetic events that alter the shape of the proximal optic cup also direct clusters of outer layer and optic stalk cells to form dorsal optic disc. A cross-species comparison suggests that CF closure can be accomplished by breaking down basement membranes (BM) along the CF margins, and by establishing BM continuity along the dorsal and ventral surfaces of the CF. CF closure is subsequently accomplished via two distinct mechanisms: tissue fusion or the intercalation of various tissues into the inter-CF space. We identify several novel cell behaviors that underlie CF fusion, many of which involve remodeling of the retinal epithelium. In addition to BM disruption, these include NCAD downregulation along the SOX2+ retinal CF margin, and the protrusion or movement of partially polarized retinal cells into the inter-CF space to mediate fusion. Proximally, the inter-CF space does not fuse or narrow and is instead loosely packed with migrating SOX2+/PAX2+/Vimentin+ astrocytes until it is closed by the outgoing optic nerve. Taken together, our results highlight distinct proximal-distal differences in CF morphogenesis and closure and establish detailed cellular models that can be utilized for understanding the genetic bases of coloboma.

Morphogenetic defects underlie Superior Coloboma, a newly identified closure disorder of the dorsal eye.

The eye primordium arises as a lateral outgrowth of the forebrain, with a transient fissure on the inferior side of the optic cup providing an entry point for developing blood vessels. Incomplete closure of the inferior ocular fissure results in coloboma, a disease characterized by gaps in the inferior eye and recognized as a significant cause of pediatric blindness. Here, we identify eight patients with defects in tissues of the superior eye, a congenital disorder that we term superior coloboma. The embryonic origin of superior coloboma could not be explained by conventional models of eye development, leading us to reanalyze morphogenesis of the dorsal eye. Our studies revealed the presence of the superior ocular sulcus (SOS), a transient division of the dorsal eye conserved across fish, chick, and mouse. Exome sequencing of superior coloboma patients identified rare variants in a Bone Morphogenetic Protein (Bmp) receptor (BMPR1A) and T-box transcription factor (TBX2). Consistent with this, we find sulcus closure defects in zebrafish lacking Bmp signaling or Tbx2b. In addition, loss of dorsal ocular Bmp is rescued by concomitant suppression of the ventral-specific Hedgehog pathway, arguing that sulcus closure is dependent on dorsal-ventral eye patterning cues. The superior ocular sulcus acts as a conduit for blood vessels, with altered sulcus closure resulting in inappropriate connections between the hyaloid and superficial vascular systems. Together, our findings explain the existence of superior coloboma, a congenital ocular anomaly resulting from aberrant morphogenesis of a developmental structure.