Browsing by Author "Morris, Alanna A."

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    Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry
    (American Medical Association, 2023) Jordan, Elizabeth; Kinnamon, Daniel D.; Haas, Garrie J.; Hofmeyer, Mark; Kransdorf, Evan; Ewald, Gregory A.; Morris, Alanna A.; Owens, Anjali; Lowes, Brian; Stoller, Douglas; Tang, W. H. Wilson; Garg, Sonia; Trachtenberg, Barry H.; Shah, Palak; Pamboukian, Salpy V.; Sweitzer, Nancy K.; Wheeler, Matthew T.; Wilcox, Jane E.; Katz, Stuart; Pan, Stephen; Jimenez, Javier; Fishbein, Daniel P.; Smart, Frank; Wang, Jessica; Gottlieb, Stephen S.; Judge, Daniel P.; Moore, Charles K.; Mead, Jonathan O.; Hurst, Natalie; Cao, Jinwen; Huggins, Gordon S.; Cowan, Jason; Ni, Hanyu; Rehm, Heidi L.; Jarvik, Gail P.; Vatta, Matteo; Burke, Wylie; Hershberger, Ray E.; DCM Precision Medicine Study of the DCM Consortium; Medical and Molecular Genetics, School of Medicine
    Importance: Black patients with dilated cardiomyopathy (DCM) have increased familial risk and worse outcomes than White patients, but most DCM genetic data are from White patients. Objective: To compare the rare variant genetic architecture of DCM by genomic ancestry within a diverse population of patients with DCM. Design: Cross-sectional study enrolling patients with DCM who self-identified as non-Hispanic Black, Hispanic, or non-Hispanic White from June 7, 2016, to March 15, 2020, at 25 US advanced heart failure programs. Variants in 36 DCM genes were adjudicated as pathogenic, likely pathogenic, or of uncertain significance. Exposure: Presence of DCM. Main outcomes and measures: Variants in DCM genes classified as pathogenic/likely pathogenic/uncertain significance and clinically actionable (pathogenic/likely pathogenic). Results: A total of 505, 667, and 26 patients with DCM of predominantly African, European, or Native American genomic ancestry, respectively, were included. Compared with patients of European ancestry, a lower percentage of patients of African ancestry had clinically actionable variants (8.2% [95% CI, 5.2%-11.1%] vs 25.5% [95% CI, 21.3%-29.6%]), reflecting the lower odds of a clinically actionable variant for those with any pathogenic variant/likely pathogenic variant/variant of uncertain significance (odds ratio, 0.25 [95% CI, 0.17-0.37]). On average, patients of African ancestry had fewer clinically actionable variants in TTN (difference, -0.09 [95% CI, -0.14 to -0.05]) and other genes with predicted loss of function as a disease-causing mechanism (difference, -0.06 [95% CI, -0.11 to -0.02]). However, the number of pathogenic variants/likely pathogenic variants/variants of uncertain significance was more comparable between ancestry groups (difference, -0.07 [95% CI, -0.22 to 0.09]) due to a larger number of non-TTN non-predicted loss of function variants of uncertain significance, mostly missense, in patients of African ancestry (difference, 0.15 [95% CI, 0.00-0.30]). Published clinical case-based evidence supporting pathogenicity was less available for variants found only in patients of African ancestry (P < .001). Conclusion and relevance: Patients of African ancestry with DCM were less likely to have clinically actionable variants in DCM genes than those of European ancestry due to differences in genetic architecture and a lack of representation of African ancestry in clinical data sets.
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    Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America
    (Elsevier, 2023) Bozkurt, Biykem; Ahmad, Tariq; Alexander, Kevin M.; Baker, William L.; Bosak, Kelly; Breathett, Khadijah; Fonarow, Gregg C.; Heidenreich, Paul; Ho, Jennifer E.; Hsich, Eileen; Ibrahim, Nasrien E.; Jones, Lenette M.; Khan, Sadiya S.; Khazanie, Prateeti; Koelling, Todd; Krumholz, Harlan M.; Khush, Kiran K.; Lee, Christopher; Morris, Alanna A.; Page, Robert L., II; Pandey, Ambarish; Piano, Mariann R.; Stehlik, Josef; Stevenson, Lynne Warner; Teerlink, John R.; Vaduganathan, Muthiah; Ziaeian, Boback; Writing Committee Members; Medicine, School of Medicine
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    Sex Associated Differences in the Clinical Outcomes of Left Ventricular Assist Device Recipients: Insights from INTERMACS
    (American Heart Association, 2023) Shetty, Naman S.; Parcha, Vibhu; Abdelmessih, Peter; Patel, Nirav; Hasnie, Ammar A.; Kalra, Rajat; Pandey, Ambarish; Breathett, Khadijah; Morris, Alanna A.; Arora, Garima; Arora, Pankaj; Medicine, School of Medicine
    Background: Sex-associated differences in clinical outcomes among left ventricular assist device recipients in the United States have been recognized. However, an investigation of the social and clinical determinants of sex-associated differences is lacking. Methods: Left ventricular assist device receiving patients enrolled in Interagency Registry for Mechanically Assisted Circulatory Support between 2005 and 2017 were included. The primary outcome was all-cause mortality. Secondary outcomes included heart transplantation and postimplantation adverse event rates. The cohort was stratified by the social subgroup of race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic), and clinical subgroups of device strategy (destination therapy, bridge to transplant, and bridge to candidacy), and implantation center volume (low [≤20 implants/y], medium [21-30 implants/y], and high [>30 implants/y]). A multivariable-adjusted Cox proportional hazard model was used to assess the risk of death and heart transplantation with prespecified interaction testing. Poisson regression was used to estimate adverse events by sex across the various subgroups. Results: Among 18 525 patients, there were 3968 (21.4%) females. Compared with their male counterparts, Hispanic (adjusted hazard ratio [HRadj], 1.75 [1.23-2.47]) females had the highest risk of death followed by non-Hispanic White females (HRadj, 1.15 [1.07-1.25]; Pinteraction=0.02). Hispanic (HRadj, 0.60 [0.40-0.89]) females had the lowest cumulative incidence of heart transplantation followed by non-Hispanic Black females (HRadj, 0.76 [0.67-0.86]), and non-Hispanic White females (HRadj, 0.88 [0.80-0.96]) compared with their male counterparts (Pinteraction<0.001). Compared with their male counterparts, females on the bridge to candidacy strategy (HRadj, 1.32 [1.18-1.48]) had the highest risk of death (Pinteraction=0.01). The risk of death (Pinteraction=0.44) and cumulative incidence of heart transplantation (Pinteraction=0.40) did not vary by sex in the center volume subgroup. A higher incidence rate of adverse events after left ventricular assist device implantation was also seen in females compared with the males, overall, and across all subgroups. Conclusions: Among left ventricular assist device recipients, the risk of death, the cumulative incidence of heart transplantation, and adverse events differ by sex across the social and clinical subgroups.