Sex Differences in Outcomes of Adults With Isolated Coarctation of the Aorta.

Background: Data are limited about the effect (or lack thereof) of sex on clinical outcomes in adults with coarctation of the aorta (COA). The purpose of this study was to compare atherosclerotic cardiovascular disease (ASCVD) risk profile, blood pressure (BP) data, echocardiographic indices, and mortality between men and women with COA. Methods: Retrospective study of adults with COA, and no associated left-sided obstructive lesions, who received care at Mayo Clinic (2003-2022). ASCVD risk profile was assessed as the prevalence of hypertension, hyperlipidemia, type 2 diabetes, obesity, smoking history, and coronary artery disease. A 24-hour BP monitor was used to assess daytime and nighttime BP and calculate nocturnal dipping. Results: Of 621 patients with isolated COA, 375 (60%) were men, and 246 (40%) were women. Women had similar ASCVD risk profile and daytime BP as men. However, women had less nocturnal dipping (7 ± 5 mm Hg vs 16 ± 7 mm Hg, P < 0.001), higher pulmonary artery mean pressure (23 mm Hg [interquartile range: 16-31] vs 20 mm Hg [interquartile range: 15-28], P = 0.04), and higher pulmonary vascular resistance index (3.41 ± 1.14 WU · m2 vs 3.02 ± 0.76 WU · m2, P = 0.006). Female sex was associated with all-cause mortality (adjusted hazard ratio 1.26, 95% confidence interval 1.04-1.94) and cardiovascular mortality (adjusted hazard ratio 1.38, 95% confidence interval 1.09-2.18). Conclusions: Women had a higher risk of both cardiovascular mortality and all-cause mortality compared to the risks in men. This difference may be related to the higher-than-expected ASCVD risk factors, abnormal nocturnal blood pressure, and pulmonary hypertension observed in women in this cohort. Further studies are required to identify optimal measures to address these risk factors.

Contexte: Il existe peu de données sur l'issue clinique en fonction du sexe chez les adultes présentant une coarctation de l'aorte (CoA). Le but de cette étude consistait donc à comparer le profil de risque de maladie cardiovasculaire athéroscléreuse (MCVAS), les données relatives à la pression artérielle (PA), les indices échocardiographiques et le taux de mortalité chez des hommes et des femmes présentant une CoA. Méthodologie: Il s'agissait d'une étude rétrospective réalisée chez des adultes présentant une CoA en l'absence de lésions obstructives gauches, soignés à la clinique Mayo entre 2003 et 2022. Le profil de risque de MCVAS a été évalué en fonction de la prévalence de l'hypertension, de l'hyperlipidémie, du diabète de type 2, de l'obésité, des antécédents tabagiques et de la coronaropathie. Une surveillance sur 24 heures a été utilisée pour évaluer la PA diurne et nocturne, en plus de calculer la chute nocturne de la PA. Résultats: Parmi les 621 patients présentant une CoA isolée, 375 (60 %) étaient des hommes et 246 (40 %) étaient des femmes. Les femmes présentaient une PA diurne et un profil de risque de MCVAS semblables aux hommes. Elles présentaient néanmoins une chute nocturne de la PA moins prononcée (7 ± 5 mmHg vs 16 ± 7 mmHg, p < 0,001), une pression artérielle pulmonaire moyenne plus haute (23 mmHg [max.-min. : 16-31] vs 20 mmHg [max.-min. : 15-28], p = 0,04) et un indice de résistance vasculaire pulmonaire plus élevé (3,41 ± 1,14 UW · m2 vs 3,02 ± 0,76 UW · m2, p = 0,006). Le sexe féminin a été associé à un plus fort taux de mortalité toutes causes confondues (rapport de risques ajusté : 1,26; intervalle de confiance à 95 % : 1,04-1,94) et de mortalité cardiovasculaire (rapport de risques ajusté : 1,38; intervalle de confiance à 95 % : 1,09-2,18). Conclusions: Les femmes sont exposées à un risque de mortalité cardiovasculaire et de mortalité toutes causes confondues plus élevé que les hommes. Cette différence pourrait être attribuable au rôle plus important que prévu joué par les facteurs de risque de MCVAS ainsi qu'à la pression artérielle nocturne anormale et à l'hypertension pulmonaire chez les femmes de cette cohorte. D'autres études sont nécessaires pour savoir quels seraient les paramètres optimaux qui permettraient d'évaluer ces facteurs de risque.

Clinical benefits of angiotensin receptor-Neprilysin inhibitor in adults with congenital heart disease.

BACKGROUND: There are limited data about the clinical benefits of angiotensin receptor-neprilysin inhibitor (ARNI) in adults with congenital heart disease (CHD). The purpose of the study was to assess the clinical benefits (chamber function and heart failure indices) of ARNI in adults with CHD. METHOD: In this retrospective cohort study, we compared the temporal change in chamber function and heart failure indices between 35 patients that received ARNI for >6 months, and a propensity matched control group (n = 70) of patients that received angiotensin converting enzyme inhibitor or angiotensin-II receptor blocker (ACEI/ARB) within the same period. RESULTS: Of the 35 patients in the ARNI group, 21 (60%) had systemic left ventricle (LV) while 14 (40%) had systemic right ventricle (RV). Compared to the ACEI/ARB group, the ARNI group had greater relative improvement in LV global longitudinal strain (GLS) (28% versus 11% increase from baseline, p < 0.001) and RV-GLS (11% versus 4% increase from baseline, p < 0.001), and greater relative improvement in New York Heart Association functional class (-14 versus -2% change from baseline, p = 0.006) and N-terminal pro-brain natriuretic peptide levels (-29% versus -13% change from baseline, p < 0.001). These results were consistent across different systemic ventricular morphologies. CONCLUSIONS: ARNI was associated with improvement in biventricular systolic function, functional status, and neurohormonal activation, suggesting prognostic benefit. These results provide a foundation for a randomized clinical trial to empirically test the prognostic benefits of ARNI in adults with CHD, as the next step towards evidence-based recommendations for heart failure management in this population.

Relationship between left atrial myopathy and atrial fibrillation in adults with coarctation of aorta.

Background: Although patients with coarctation of aorta (COA) have clinical risk factors for atrial fibrillation (AF), there are limited data about AF prevalence, and role of left atrial (LA) indices for risk stratification in this population. We hypothesized that LA indices (LA reservoir strain and LA volume index) were associated with AF, and would identify patients at risk for AF progression. Methods: We analyzed electrocardiograms/Holters, and echocardiograms of adult COA patients at Mayo Clinic (2000-2018). Results: Of 776 patients, 726(94 %), 46(5.9 %) and 4(0.5 %) had no history of AF, paroxysmal AF, and persistent AF respectively; yielding AF prevalence of 6.4 %. LA reservoir strain (AUC 0.782 [0.751-0.808]) had more robust association with AF as compared to LA volume index (AUC difference -0.115, p < 0.001).Among 726 patients without prior AF, 25(3.4 %) had new-onset AF during follow-up. LA reservoir strain <25 % and LA volume index >34 ml/m2 were independent predictors of new-onset AF (HR 1.81 [1.15-3.85], and HR 1.41 [1.03-4.78], respectively). Of 46 patients with paroxysmal AF, 22(48 %) had recurrent AF, and LA reservoir strain <25 % was an independent predictor of recurrent AF (HR 1.94 [1.41-4.17]). LV pressure overload and stiffness indices were associated with progressive LA dysfunction and new-onset AF. Conclusions: Collectively, these data suggest that LA strain can potentially be used for AF risk stratification. Further studies are required to determine whether LA strain can proactively identify patients that will respond favorably to different antiarrhythmic therapies, and whether interventions to reduce LV pressure overload will improve LA function and reduce AF progression.

Bone marrow derived long-lived plasma cell phenotypes are heterogeneous and can change in culture.

Bone marrow-derived long-lived plasma cells (LLPCs) are thought to be a major source of alloantibody in sensitized transplant patients. However, studies of LLPCs have been hampered not only by the fact that they are rare and difficult to isolate and culture but also due to the lack of consensus regarding a definitive cell-surface phenotype. The goal of the current study was to determine if LLPCs have a specific, stable cell-surface phenotype. PCs were isolated from high-volume (120cc) bone marrow aspirates that were enriched first by negative selection then positive selection using anti-CD38 antibody-coated beads and purified by cell sorting. A typical isolation resulted in >100,000 PCs that were sorted into 4 populations with variable numbers of PCs: CD19+/CD138+/CD38Hi (64.1% of the PCs), CD19-/CD138+/CD38Hi (20.9%), CD19+/CD138-/CD38Hi (10.7%), and CD19-/CD138-/CD38Hi (4.3%). The purity of each subset was 96-99%. Each subset contained PCs secreting IgG and IgA. Measles- and tetanus-specific PCs (i.e. putative IgG secreting, antigen-specific LLPCs). LLPCs were identified in both the CD19+/CD138+/CD38Hi and CD19-/CD138+/CD38Hi subsets and in the smaller CD138- subsets (when pooled). Thus, all CD38Hi subsets contained LLPCs. Cultured PCs maintained viability (>50%) and function and could be retrieved for analyses. During 7 days of culture, cell surface expression changed from baseline in many PCs. For example, approximately 20% of CD19 + CD138+/CD38Hi cells (the largest PC subset) became CD19-. CFSE assays showed no division and only a small percentage of LLPCs were Ki-67 positive suggesting that the cells did not divide in culture and that the antibody detected was not from plasmablasts. We conclude that human bone marrow LLPCs have a heterogeneous expression of CD19 and CD138, which can change during cell culture. The fact that LLPCs were found in all four subsets raises the possibility that a large percentage of PCs in the bone marrow may be LLPCs.