Faculty Bibliography

BACKGROUND:Previous studies have reported that obesity-related metabolic abnormalities (e.g., diabetes and hypertension) lead to myocardial dysfunction and adverse cardiac remodeling. However, it is unclear whether such cardiac remodeling is from obesity or obesity-related metabolic abnormalities. We hypothesize that overweight and obesity are associated with adverse cardiac remodeling independent of associated metabolic abnormalities. METHODS:We evaluated 6,639 participants from the Framingham Heart Study who underwent echocardiography and had no prevalent cardiovascular disease. Individuals were classified into six obesity sub-phenotypes based on metabolic health (metabolically healthy or metabolically unhealthy) and body mass index (normal weight, overweight, or obese). Obesity subphenotypes were related to echocardiographic measures using multivariable regression analyses. RESULTS:Mean age was 49 years and 55% were women. Overweight and obesity were consistently associated with adverse cardiac remodeling in both metabolic healthy and unhealthy participants. Among metabolically healthy participants, compared to the normal weight group (referent), overweight and obesity were significantly associated with increased left ventricular mass (11.6 and 21.4 gm), left atrium end-systolic dimension (0.27 and 0.48 cm), global longitudinal strain (0.82 and 1.06%), and the ratio of early diastolic trans-mitral flow velocity to early diastolic mitral annulus velocity (0.35 and 0.87) (all p<0.001). Additionally, obesity was significantly associated with mitral annular plane systolic excursion (0.08 cm, p<0.001) and relative wall thickness (0.01, p=0.001) compared to the normal weight referent group. CONCLUSIONS:Increasing body weight was associated with adverse cardiac remodeling regardless of metabolic health status, which suggests that obesity may directly increase the risk of adverse cardiac remodeling.

SARS-CoV-2 vaccines have unquestionably blunted the overall impact of the COVID-19 pandemic, but host factors such as age, sex, obesity, and other co-morbidities can affect vaccine efficacy. We identified individuals in a relatively healthy population of healthcare workers (CORALE study cohort) who had unexpectedly low peak anti-spike receptor binding domain (S-RBD) antibody levels after receiving the BNT162b2 vaccine. Compared to matched controls, "low responders" had fewer spike-specific antibody-producing B cells after the second and third/booster doses. Moreover, their spike-specific T cell receptor (TCR) repertoire had less depth and their CD4⁺ and CD8⁺T cell responses to spike peptide stimulation were less robust. Single cell transcriptomic evaluation of peripheral blood mononuclear cells revealed activation of aging pathways in low responder B and CD4⁺T cells that could underlie their attenuated anti-S-RBD antibody production. Premature lymphocyte aging may therefore contribute to a less effective humoral response and could reduce vaccination efficacy.

WHAT IS KNOWN AND OBJECTIVE/OBJECTIVE:Thyrotoxic periodic paralysis (TPP) with hypokalaemia is a rare acute phenomenon. Reports of the use of high-dose non-selective β-blockers describe symptom resolution, but often administration does not occur promptly enough in the treatment course and patients may experience overcorrection and hyperkalaemia. CASE DESCRIPTION/METHODS:A 37-year-old Hispanic male developed TPP. Patient was successfully treated with low-dose oral propranolol and potassium supplementation with no overcorrection. WHAT IS NEW AND CONCLUSION/CONCLUSIONS:Delay in the administration of non-selective β-blockers may lead to overcorrection of potassium with exogenous supplementation. Low-dose propranolol administered in the Emergency Department was successful in preventing overcorrection of potassium.