Cardiac troponin T mutation in familial cardiomyopathy with variable remodeling and restrictive physiology.

We identified a unique family with autosomal dominant heart disease variably expressed as restrictive cardiomyopathy (RCM), hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM), and sought to identify the molecular defect that triggered divergent remodeling pathways. Polymorphic DNA markers for nine sarcomeric genes for DCM and/or HCM were tested for segregation with disease. Linkage to eight genes was excluded, but a cardiac troponin T (TNNT2) marker cosegregated with the disease phenotype. Sequencing of TNNT2 identified a heterozygous missense mutation resulting in an I79N substitution, inherited by all nine affected family members but by none of the six unaffected relatives. Mutation carriers were diagnosed with RCM (n = 2), non-obstructive HCM (n = 3), DCM (n = 2), mixed cardiomyopathy (n = 1), and mild concentric left ventricular hypertrophy (n = 1). Endomyocardial biopsy in the proband revealed non-specific fibrosis, myocyte hypertrophy, and no myofibrillar disarray. Restrictive Doppler filling patterns, atrial enlargement, and pulmonary hypertension were observed among family members regardless of cardiomyopathy subtype. Mutation of a sarcomeric protein gene can cause RCM, HCM, and DCM within the same family, underscoring the necessity of comprehensive morphological and physiological cardiac assessment in familial cardiomyopathy screening.

Critical factors determining access to acute stroke care.

OBJECTIVE: Our objective was to assess gender, ethnic, and access-to-care factors critical in delay time (DT) for presentation to the hospital for acute stroke. BACKGROUND: Little information is available on the effect of gender, ethnicity, and access issues on DT. DESIGN: Demographic, access-to-care, and DT information was obtained from emergency department (ED) documentation of stroke patients admitted from July 1995 through June 1997 at Hermann Hospital, Houston, TX. Univariate and multivariate regression analyses were performed. RESULTS: Of the 241 eligible patients, 126 were African American (AA), 82 were non-Hispanic white (NHW), and 33 were Hispanic American (HA). Median DT from symptom onset to presentation to the ED was 222 minutes for AAs, 280 minutes for HAs, and 230 minutes for NHWs. A multivariate regression model estimated DT to ED arrival decreased with ambulance transport (p = 0.003) and increased in patients with a primary care physician (p = 0.145) and in women (p = 0.052). DT to see an ED physician after hospital arrival decreased with ambulance transport (p < 0.001), hemorrhage patients (p = 0.006), and worse stroke severity (p = 0.038), and increased in women (p = 0.041). DT to see a neurologist decreased with hemorrhage (p = 0.002) and ambulance arrival (p = 0.010). Neurologists saw patients within 3 hours of symptom onset in 34% of NHWs, 28% of AAs, and 18% of HAs. CONCLUSION: Gender and access-to-care issues may be important determinants of delay in acute stroke care. Less than 20% of HAs presented to the ED within 3 hours of symptom onset.