Temporal Changes in Clinical Characteristics and Outcomes of Adults With Congenital Heart Disease.

BACKGROUND: The purpose of this study was to assess differences in the clinical characteristics (defined by congenital heart disease [CHD] anatomic and physiologic classification scheme) of adults with CHD across different eras, and how these differences influence outcomes (heart failure hospitalization and all-cause mortality). METHOD: Patients were divided into depending on year of baseline encounter: cohort #1 (1991-2000, n = 1,984 [27%]), cohort #2 (2001-2010, n = 2,448 [34%]), and cohort #3 (2011-2020, n = 2,847 [39%]). Patients were classified into 3 anatomic groups (simple, moderate, and complex CHD) and 4 physiologic stages (stage A-D). RESULTS: There was a temporal increase in the proportion of patients in physiologic stage C (17% vs 21% vs 24%, P < .001), and stage D (7% vs 8% vs 10%, P = .09), with a corresponding decrease in physiologic stage A (39% vs 35% vs 28%, P < .001). No temporal change in anatomic groups. There was a temporal decrease in the incidence of all-cause mortality (12.7 vs 10.6 vs 9.5 per 1,000 patient-years, P < .001). However, there was a temporal increase in the incidence of heart failure hospitalization (6.8 vs 8.4 vs 11.2 per 1,000 patient-years, P < .001). CHD physiologic stage (but not anatomic groups) was associated with heart failure hospitalization and all-cause mortality. CONCLUSIONS: There is a need for better strategies to identify and treat heart failure, and to modify the risk factors associated with heart failure and all-cause mortality.

Right atrial dysfunction is associated with atrial arrhythmias in adults with repaired tetralogy of fallot.

BACKGROUND: Adults with repaired tetralogy of Fallot (TOF) have right atrial (RA) remodeling and dysfunction, and RA function can be measured using speckle tracking echocardiography. There are limited data about the role of RA strain imaging for risk stratification in this population. We hypothesized that RA reservoir strain can identify TOF patients at risk of developing atrial arrhythmia. To test this hypothesis, we assessed the relationship between RA reservoir strain and atrial arrhythmias in adults with repaired TOF. METHOD: Retrospective cohort study of adults with repaired TOF, and no prior history of atrial arrhythmias. Atrial arrhythmia was defined as atrial fibrillation, atrial flutter/atrial tachycardia, and categorized as new-onset versus recurrent atrial arrhythmias. RESULTS: We identified 426 patients (age 33 ± 12 years; males 208 (49%)) that met the inclusion criteria. The mean RA reservoir strain, conduit strain, and booster strain were 34 ± 11%, 20 ± 9%, and 15 ± 12%, respectively. Of 426 patients, 73 (17%) developed new-onset atrial arrhythmias (atrial flutter/tachycardia n = 42; atrial fibrillation n = 31); annual incidence 1.9%. RA reservoir strain was associated with new-onset atrial arrhythmias (adjusted HR 0.95, 95% CI 0.93-0.97) after multivariable adjustment. Of 73 patients with new-onset atrial arrhythmia, 41 (56%) had recurrent atrial arrhythmia (atrial flutter/tachycardia n = 18; atrial fibrillation n = 23); annual incidence 11.2%. Similarly, RA reservoir strain was associated with recurrent atrial arrhythmias (adjusted HR 0.92, 95% CI 0.88-0.96) after multivariable adjustment. CONCLUSIONS: RA strain indices can identify patients at risk for atrial arrhythmias, and this can in turn, be used to guide the type/intensity of therapy in such patients.

Cardiac Reverse Remodeling and Changes in Heart Failure Indices After Transcatheter Tricuspid Valve Replacement in Adults With Congenital Heart Disease.

BACKGROUND: There are limited data about changes in cardiac function (cardiac reverse remodeling) and heart failure indices after transcatheter tricuspid valve-in-valve replacement (TT-VIVR). The purpose of this study was to evaluate cardiac reverse remodeling and temporal changes in heart failure indices after TT-VIVR in adults with congenital heart disease. METHODS: Retrospective cohort study of adults with congenital heart disease that underwent TT-VIVR and had >6 months of follow-up (January 1, 2011, to April 30, 2023). Echocardiographic indices of cardiac remodeling and heart failure indices (New York Heart Association class, NT-proBNP (N-terminal pro-brain natriuretic peptide), glomerular filtration rate, and model for end-stage liver disease excluding international normalized ratio score) were assessed preintervention and at 1-, 3-, and 5-year postintervention. RESULTS: Of 39 patients (age 39 [32-46] years), 14 (36%) and 25 (64%) received Melody valve and Sapien valve prosthesis, respectively. At 1-year post-TT-VIVR, there was a temporal improvement in right atrial reservoir strain (17±8% versus 22±8%, P<0.001), right atrial volume (81 [59-108] versus 63 [48-82] mL/m2, P<0.001), right atrial pressure (12±4% versus 6±4%, P<0.001), and right ventricular global longitudinal strain (-15±7% versus -20±7%, P<0.001). Similarly, there was a temporal improvement in NT-proBNP, glomerular filtration rate, model for end-stage liver disease excluding international normalized ratio score, and New York Heart Association class. The temporal improvements in heart failure indices and valve function were maintained at 3- and 5-year post-TT-VIVR. CONCLUSIONS: Considering the significant mortality risk associated with reoperations for tricuspid valve replacement, these data suggest favorable outcomes after TT-VIVR, and support TT-VIVR as a viable alternative to surgical tricuspid valve replacement, especially in high-risk patients.

Differences in Right Heart Function After Pulmonary Valve Replacement in Patients With Pulmonary Valve Stenosis Versus Tetralogy of Fallot.

BACKGROUND: There are limited data about the impact of timing of pulmonary valve replacement (PVR) on right heart reverse remodeling in patients with pulmonary regurgitation following intervention for isolated pulmonary valve stenosis (PS). This study compared differences in postprocedural right heart reverse remodeling after early versus late PVR (defined as PVR before versus after attainment of the conservative consensus criteria proposed by Bokma et al, 2018) in patients with prior intervention for PS, using patients with tetralogy of Fallot as the reference group. METHOD AND RESULTS: Right atrial reservoir strain and right ventricular free wall strain was measured at baseline, 1 and 3 years after PVR. There were 114 patients with PS (early PVR, 87 [76%]; late PVR, 27 [24%]) and 291 patients with tetralogy of Fallot (early PVR, 197 [67%]; late PVR, 96 [33%]). The PS group had greater improvement in right atrial reservoir strain at 1 year (12%±4% versus 8%±4%; P<0.001) and 3 years (15%±6% versus 9%±6%; P<0.001), and a greater improvement in right ventricular free wall strain at 1 year (12%±4% versus 7%±3%, P=0.008) and 3-years (16%±6% versus 12%±5%; P=0.01) after PVR compared with the tetralogy of Fallot group. There was no difference in right heart reverse remodeling between patients who underwent early versus later PVR within the PS group. In contrast, late PVR was associated with less right heart reverse remodeling within the tetralogy of Fallot group. CONCLUSIONS: These data suggest that patients with palliated PS presenting pulmonary regurgitation have a more benign clinical course, and hence delaying PVR in this population may be appropriate.

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.

Coarctation of Aorta With Tricuspid Aortic Valve Is Not Associated With Ascending Aortic Aneurysm.

BACKGROUND: Aortic aneurysm is common in patients with coarctation of aorta (COA), but it is unclear whether the risk of aortic aneurysms is due to COA or related to the presence of other risk factors such as bicuspid aortic valve (BAV) and hypertension. OBJECTIVES: The purpose of this study was to assess the relationship among COA, BAV, and thoracic aortic aneurysms. METHODS: A total of 867 patients with COA (COA group) were matched 1:1:1 to 867 patients with isolated BAV (BAV group) and 867 patients without structural heart disease (SHD) (no-SHD group). The COA group was further subdivided into a COA+BAV subgroup (n = 304 [35%]), and COA with tricuspid aortic valve (TAV) (COA+TAV subgroup [n = 563 (65%)]). Aortic dimensions were assessed at baseline and at 3, 5, and 7 years. RESULTS: Compared with the no-SHD group, the COA+BAV subgroup had larger aortic root diameter (37 mm [Q1-Q3: 30-43 mm] vs 32 mm [Q1-Q3: 27-35 mm]; P < 0.001) and mid ascending aorta dimeter (34 mm [Q1-Q3: 29-40 mm] vs 28 mm [Q1-Q3: 24-31 mm]; P = 0.008). Similarly, the BAV group had larger aortic root diameter (37 mm [Q1-Q3: 30-42 mm] vs 32 mm [Q1-Q3: 27-35 mm]; P < 0.001), and mid ascending aorta dimeter (35 mm [Q1-Q3: 30-40 mm] vs 28 mm [Q1-Q3: 24-31 mm]; P < 0.001). Compared with the COA+TAV subgroup, the COA+BAV subgroup and BAV group were associated with larger aortic root and mid ascending aorta diameter at baseline and follow-up. The risk of acute aortic complications was low in all groups. CONCLUSIONS: These findings suggest that BAV (and not COA) was associated with ascending thoracic aorta dimensions, and that patients with COA+TAV were not at a greater risk of developing ascending aortic aneurysms as compared with patients without SHD.

Prognostic Role of Tricuspid Annular Plane Systolic Excursion/Right Ventricular Systolic Pressure Ratio in Coarctation of Aorta.

Background: Right ventricular (RV) systolic dysfunction and pulmonary hypertension are associated with mortality in adults with coarctation of aorta (COA). The tricuspid annular plane systolic excursion/RV systolic pressure (TAPSE/RVSP) ratio is a validated noninvasive tool for the assessment of RV-pulmonary arterial (RV-PA) coupling in patients with PA hypertension, but similar data are lacking in adults with COA. The purpose of this study was to assess the relationship between the TAPSE/RVSP ratio and outcomes in this population. Methods: A retrospective cohort study of adults with repaired COA was performed. RV systolic dysfunction was defined as RV free wall strain ≥-24% at baseline, whereas new-onset RV systolic dysfunction was defined RV free wall strain ≥-24% during follow-up. Results: Of 661 patients, TAPSE, RVSP, and TAPSE/pulmonary artery systolic pressure ratio were 22 ± 6 mm, 34 ± 12 mm Hg, and 0.71 (0.48-0.89) mm/mm Hg, respectively. Of 661 patients, 152 (23%) had RV systolic dysfunction at baseline, and TAPSE/RVSP <0.43 mm/mm Hg was the optimal threshold to detect RV systolic dysfunction. TAPSE/RVSP <0.43 mm Hg was associated with RV systolic dysfunction (adjusted odds ratio: 3.11 [1.83-6.19], P = 0.004). Of 509 patients with normal RV systolic function, 42 (8%) and 36 (7%) developed new-onset RV systolic dysfunction and new-onset right heart failure, respectively, during follow-up. TAPSE/RVSP <0.43 mm/mm Hg was associated with new-onset RV systolic dysfunction (adjusted hazard ratio: 1.95 [1.46-2.77], P = 0.008) and new-onset right heart failure (adjusted hazard ratio: 0.81 [0.68-0.92], P = 0.005). Conclusions: The TAPSE/RVSP ratio can potentially be used to identify patients at risk for new-onset RV systolic dysfunction and right heart failure and provide opportunity for proactive interventions to prevent adverse outcomes.

Contexte: La dysfonction systolique du ventricule droit (VD) et l'hypertension pulmonaire sont associées à des décès chez les adultes qui présentent une coarctation de l'aorte (CA). Le rapport entre l'excursion systolique du plan de l'anneau tricuspide (TAPSE pour tricuspid annular plane systolic excursion) et la pression systolique du VD (PSVD) est une méthode non invasive pour évaluer le couplage entre le VD et l'artère pulmonaire (VD-AP), qui a été validée chez les patients atteints d'hypertension de l'AP, mais pour laquelle on ne dispose pas de données similaires chez les adultes qui présentent une CA. La présente étude visait à évaluer la relation entre le rapport TAPSE/PSVD et les résultats de santé chez cette population de patients. Méthodologie: Nous avons mené une étude de cohorte rétrospective auprès d'adultes présentant une CA corrigée. La dysfonction systolique du VD était définie comme une déformation (strain) de la paroi libre du VD (DPLVD) ≥ -24 % au début de l'étude, et une dysfonction systolique inaugurale du VD était définie comme une DPLVD ≥ -24 % détectée lors du suivi. Résultats: Pour l'ensemble des 661 patients de l'étude, les valeurs pour la TAPSE, la PSVD et le rapport TAPSE/pression systolique de l'artère pulmonaire étaient respectivement de 22 ± 6 mm, 34 ± 12 mmHg et 0,71 (0,48-0,89) mm/mmHg. Parmi ces 661 patients, 152 (23 %) présentaient initialement une dysfonction systolique du VD, et un rapport TAPSE/PSVD < 0,43 mm/mmHg constituait le seuil optimal pour la détection d'une dysfonction systolique du VD. Un rapport TAPSE/PSVD < 0,43 mm/mmHg était par ailleurs associé à une dysfonction systolique du VD (rapport de cotes ajusté de 3,11 [1,83-6,19], p = 0,004). Au cours du suivi des 509 patients qui présentaient initialement une fonction systolique normale du VD, 42 patients (8 %) ont présenté une dysfonction systolique inaugurale du VD et 36 patients (7 %) ont présenté une insuffisance cardiaque droite inaugurale. Un rapport TAPSE/PSVD < 0,43 mm/mmHg était associé avec la dysfonction systolique inaugurale du VD (rapport des risques instantanés ajusté de 1,95 [1,46-2,77], p = 0,008), et avec l'insuffisance cardiaque droite inaugurale (rapport des risques instantanés ajusté de 0,81 [0,68-0,92], p = 0,005). Conclusions: Le rapport TAPSE/PSVD pourrait permettre de repérer les patients susceptibles de présenter une dysfonction systolique inaugurale du VD ou une insuffisance cardiaque droite inaugurale, ce qui ouvre la voie à des interventions en amont visant à prévenir les résultats défavorables pour ces patients.

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.

Right Ventricular Systolic Dysfunction in Adults With Anatomic Repair of d-Transposition of Great Arteries.

The purpose of this study was to assess the prevalence of right ventricular (RV) systolic dysfunction in adults with anatomic repair of dextro-transposition of great arteries (d-TGAs), and to determine its relation to clinical outcomes across multiple domains (functional status, peak oxygen consumption, N-terminal pro-brain natriuretic peptide, and heart failure hospitalization). Adults with anatomic repair for d-TGA and with echocardiographic images for strain analysis were divided into 2 groups: (1) d-TGA status after an arterial switch operation (d-TGA-ASO group) and (2) d-TGA status after a Rastelli operation (d-TGA-Rastelli group). RV systolic function was assessed using RV global longitudinal strain (RVGLS), and RV systolic dysfunction was defined as RVGLS >-18%. We identified 151 patients (median age 21 years [19 to 28]; d-TGA-ASO group 89 [59%], and d-TGA-Rastelli group 62 [41%]). The mean RVGLS was -22 ± 4%, and 47 patients (31%) had RV systolic dysfunction. The d-TGA-Rastelli group had lower (less negative) RVGLS than that of the d-TGA-ASO group (-19 ± 3% vs -25 ± 3%, p <0.001) and higher prevalence of RV systolic dysfunction (48% vs 19%, p <0.001). RVGLS (absolute value) was associated with peak oxygen consumption (r = 0.58, p <0.001; adjusted R2 = 0.28), log-N-terminal pro-brain natriuretic peptide (r = -0.41, p = 0.004; adjusted R2 = 0.21), New York Heart Association class III/IV (odds ratio 2.29, 1.56 to 3.19, p = 0.01), and heart failure hospitalization (hazard ratio 0.93, 0.88 to 0.98, p = 0.009). RV systolic dysfunction was common in adults with d-TGA and anatomic repair and was associated with clinical outcomes. Longitudinal studies are required to determine the risk factors for progressive RV systolic dysfunction and to identify strategies for preventing RV systolic dysfunction in this population.

Prognostic Value of the Anatomic-Physiologic Classification in Adults With Congenital Heart Disease.

BACKGROUND: The prognostic role of the congenital heart disease (CHD) anatomic/physiologic classification has not been systematically studied. The purpose of this study was to determine whether CHD physiologic stage provided improvement in prognostic power (to predict all-cause mortality) beyond conventional clinical risk models. METHODS: Retrospective study of adults with CHD at the Mayo Clinic (2003-2019). The CHD physiologic stage was assessed at baseline and 36 (24-48) months, and patients were classified into stages A to D at these time points. Clinical stability (remaining in the same stage), clinical improvement (moving to less advanced stage), and clinical deterioration (moving to more advanced stage) were determined at 36 months. We defined conventional clinical risk indices as age/sex, functional class, comorbidities, cardiac procedures, hepatorenal dysfunction, and ventricular/valvular dysfunction. RESULTS: Of 5321 patients, 1649 (31%), 1968 (37%), 1224 (23%), and 480 (9%) were in stages A, B, C, and D at baseline. Of 5321 patients, 4588 (86%) also had assessments at 36 months, and of these patients, 3347 (73%), 386 (8%), and 855 (19%) had clinical stability, deterioration, and improvement, respectively. Patients with clinical improvement were more likely to have undergone cardiac procedures between both assessments. Both baseline CHD physiologic stage (hazard ratio, 1.13 [95% CI, 1.09-1.17]; P<0.001, per unit increase in stage) and change in CHD physiologic stage (hazard ratio, 1.46 [95% CI, 1.32-1.61]; P=0.007, per unit increase in stage) were associated with mortality after adjustments for conventional risk indices and provided incremental improvement in prognostic power beyond conventional clinical risk models as evidence by an increase in C statistic from 0.702 (0.681-0.724) to 0.769 (0.754-0.787). CONCLUSIONS: The CHD physiologic stage can potentially be used for risk stratification, as well as to monitor disease progression and response to therapy.

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.

Outcomes after implantation of right-sided mechanical valve prostheses in congenital heart disease.

BACKGROUND: Bioprosthetic valves are often used for pulmonary valve replacement (PVR) and tricuspid valve replacement (TVR) because of concerns about mechanical valve thrombosis in the right heart. The purpose of this study was to assess prosthetic valve function and outcomes (prosthetic valve dysfunction, reoperations and major bleeding events) after mechanical PVR and TVR and to compare these to bioprostheses implanted in the same positions. METHOD: Case-control study of adults with congenital heart disease that underwent mechanical TVR or PVR (2003-2021) at Mayo Clinic Rochester, Minnesota. For each mechanical prosthesis, we identified two patients that received bioprosthesis in the same position (1:2 matching). RESULTS: We identified 48 consecutive patients that underwent mechanical PVR (n=39, age 32 (26-38) years, men 22 (56%)) and/or mechanical TVR (n=17, age 36 (31-42) years, men 9 (53%)), as control group of 78 patients (age 30 (24-36) years, men 44 (56%)) and 34 patients (age 34 (29-39) years, men 18 (53%)) that underwent bioprosthetic PVR and TVR, respectively. The most common diagnoses in patients that received mechanical prosthesis were: tetralogy of Fallot (n=14, 19%), aortic stenosis status post Ross operation (n=11, 23%), truncus arteriosus (n=5, 11%), atrioventricular canal defect (n=4, 8%), Ebstein anomaly (n=3, 6%), double outlet right ventricle (n=2, 4%), valvular pulmonic stenosis (n=2, 4%). Compared with the bioprosthesis group, the mechanical prosthesis group had lower temporal increase in Doppler systolic mean gradient after PVR (∆ -1±2 vs 3±2 mm Hg, p<0.001) and Doppler diastolic mean gradient after TVR (∆ 0±1 vs 2±1 mm Hg, p=0.005). The mechanical prosthesis group also had lower risk of prosthetic valve dysfunction after PVR (1.0% vs 2.8% /year, p=0.02) and after TVR (2.6% vs 4.3% /year, p=0.008), but higher risk of major bleeding events (2.2% vs 0.1% /year, p<0.001). CONCLUSIONS: Patients that received right-sided mechanical valve prostheses had lower temporal increase in valve gradient, lower risk of prosthetic valve dysfunction, but higher risk of bleeding complications compared with those that underwent right-sided bioprosthetic valve implantation.

Left ventricular adaptation to aortic regurgitation in adults with repaired coarctation of aorta.

BACKGROUND: Aortic regurgitation (AR) can develop in adults with repaired coarctation of aorta (COA), but there are limited data about left ventricular (LV) remodeling and clinical outcomes in this population. The purpose of the study was to compare LV remodeling (LV mass index [LVMI], LV ejection fraction [LVEF], and septal E/e') and onset of symptoms before aortic valve replacement, and LV reverse remodeling (%-change in LVMI, LVEF and E/e') after aortic valve replacement in patients with versus without repaired COA presenting with AR. METHODS: Asymptomatic adults with repaired COA presenting with moderate/severe AR (AR-COA group) were matched 1:2 to asymptomatic adults without COA and similar severity of AR (control group). RESULTS: Although both groups (AR-COA n = 52, and control n = 104) had similar age, sex, body mass index, aortic valve gradient, and AR severity, the AR-COA group had higher LVMI (124 ± 28 versus 102 ± 25 g/m2, p < 0.001) and E/e' (12.3 ± 2.3 versus 9.5 ± 2.1, p = 0.02) but similar LVEF (63 ± 9% versus 67 ± 10%, p = 0.4). COA diagnosis (adjusted HR 1.95, 95%CI 1.49-2.37, p < 0.001), older age, E/e', and LV hypertrophy were associated with onset of symptoms. Of 89 patients (AR-COA n = 41, and control n = 48) with echocardiographic data at 1-year post- aortic valve replacement, the AR-COA group had less regression of LVMI (-8% [95%CI -5 to -11] versus -17% [95%CI -15 to -21], p < 0.001) and E/e' (-5% [95% CI -3 to -7] versus -16% [95% CI -13 to -19], p < 0.001). CONCLUSIONS: Patients with COA and AR had a more aggressive clinical course, and perhaps may require a different threshold for surgical intervention.

Prognostic Performance of Right Ventricular Global Longitudinal Strain Measurements in Patients With Ebstein Anomaly.

BACKGROUND: There are limited data on the prognostic role of right ventricular global longitudinal strain (RVGLS) in patients with Ebstein anomaly. OBJECTIVES: This study sought to assess the relationship between RVGLS and mortality and to compare prognostic performance of RVGLS with conventional echocardiographic indices of right ventricular (RV) systolic function. METHODS: This study identified adults with Ebstein anomaly with echocardiographic assessment of RV systolic function (RVGLS, RV fractional area change [RVFAC], RV tissue Doppler systolic velocity [RV s'], and tricuspid annular plane systolic excursion [TAPSE]) from 2003 to 2020. For ease of presentation, RVGLS was modeled as absolute values (ie, without the negative sign). RESULTS: Of 620 patients (median age 37 years; men 261 [42%]), the mean absolute RVGLS, RVFAC, RV s', and TAPSE were 18% ± 5%, 32% ± 9%, 14 ± 6 cm/s, and 22 ± 8 mm, respectively. There were correlations between absolute RVGLS and RVFAC (r = 0.71; P < 0.001), between absolute RVGLS and RV s' (r = 0.41; P = 0.03), and between absolute RVGLS and TAPSE (r = 0.44; P = 0.002). Of 620 patients, 47 (8%) died during follow-up, and 34 of these deaths were cardiovascular. Absolute RVGLS was independently associated with all-cause mortality (adjusted HR: 0.94; 95% CI: 0.92-0.96 per unit increase) and cardiovascular mortality (adjusted HR: 0.92; 95% CI: 0.90-0.94 per unit increase). Absolute RVGLS had superior prognostic power (ie, ability to predict mortality) as compared with RVFAC, RV s', or TAPSE. CONCLUSIONS: These data support the use of RVGLS for risk stratification in Ebstein anomaly, and further studies are required to assess how interventions may affect different patients according to risk stratification.

Risk of pulmonary artery dissection in adults with congenital heart disease.

BACKGROUND: There are limited data about the risk of pulmonary artery (PA) dissection in adults with congenital heart disease (CHD), and the purpose of this study was to estimate the incidence of PA dissection in this population. METHODS: Retrospective cohort study of adults with CHD that underwent cross-sectional imaging (2003-2020). PA aneurysm was defined as main or branch PA diameter > 40 mm or > 30 mm respectively, and severe PA aneurysm was defined as main or branch PA diameter > 50 mm. RESULTS: Of 1, 673 patients (41 ± 10 years; male 58%), 493 (24%), 286 (19%), and 306 (20%) had aneurysms of the main, right, and left PA respectively, while 66 (4%) had severe PA aneurysm. During a median follow-up of 8.2 (interquartile range 3.7-10.3) years, there was one PA dissection in a patient with Eisenmenger syndrome, thus the incidence of PA dissection was 14 per 100,000 patient-years. Of 779 females, 163 had one or more pregnancies during follow-up, and 41 (25%) of these patients had known PA aneurysm at the time of conception. There was no PA dissection during pregnancy. Of the 163 patients, 91 (56%) had cross-sectional imaging before and after pregnancy, there was no significant difference in PA dimension before versus after pregnancy (main PA 35 ± 5 versus 36 ± 4 mm, p = 0.6; right PA 21 ± 3 versus 33 ± 4 mm, p = 0.1; and left PA 23 ± 4 versus 22 ± 4 mm, p = 0.4). CONCLUSIONS: The risk of PA dissection was extremely low even in patients with severe PA aneurysm, or in patients with PA aneurysm that became pregnant. Collectively, these data suggest a benign natural history for patients without severe pulmonary hypertension and encourage and a conservative approach in managing patients with PA aneurysm.

Estimation of Left Ventricular Filling Pressure Using Left Atrial Strain in Coarctation of Aorta.

BACKGROUND: Left atrial (LA) reservoir strain <18% and booster strain <8% have been proposed as the optimal threshold to detect increased left ventricular (LV) filling pressure in patients with acquired heart disease. The purpose of this study was to determine whether these LA strain cut-off points can detect increased LV filling pressure in adults with coarctation of aorta (COA). METHODS: This retrospective study included adults with COA (n = 126; age, 36 ± 16 years) who underwent non-simultaneous cardiac catheterization and echocardiography. Increased LV filling pressure was defined as pulmonary artery wedge pressure (PAWP) >12 mm Hg or LV end-diastolic pressure (LVEDP) >16 mm Hg. RESULTS: The median PAWP was 13 mm Hg (interquartile range [IQR], 11-18) and PAWP had a good correlation with LA reservoir strain (r = -0.69; P<.001) and LA booster strain (r = -0.61; P<.001). LA reservoir strain <18% had superior diagnostic power to detect PAWP >12 mm Hg as compared with LA volume index >34 mL/m², septal E/e' >15, lateral E/e' >13, and tricuspid regurgitation velocity >2.8 m/s (P<.05 for all). The median LVEDP was 17 mm Hg (IQR, 14-20) and LVEDP had a modest correlation with LA reservoir strain (r = -0.39; P<.001) and LA booster strain (r = -0.33; P<.01). LA reservoir strain <18% had superior diagnostic power to detect LVEDP >16 mm Hg as compared with LA volume index >34 mL/m², septal E/e' >15, lateral E/e' >13, and tricuspid regurgitation velocity >2.8 m/s (P<.05 for all). CONCLUSIONS: These data suggest that LA strain could potentially be used to identify patients with increased LV filling pressure, thereby improving patient selection for cardiac catheterization and interventions.

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.

Prognostic Value of the H2FPEF Score in Adults With Repaired Coarctation of Aorta.

Background: Risk stratification is challenging in adults with repaired coarctation of aorta (COA) because of the complex interaction of multiple hemodynamic factors and differences in left ventricular adaptation to these factors. The H2FPEF score was originally developed for differentiating between heart failure with preserved ejection fraction and noncardiac dyspnea, but it has been shown to be useful for prognostication in other cardiovascular pathologies. Objectives: The purpose of this study was to assess the prognostic role of the H2FPEF score in adults with repaired COA. Methods: This is a retrospective cohort study of adults with repaired COA at the Mayo Clinic (2003-2019). The H2FPEF score was calculated at baseline and at 5-year follow-up. Cardiovascular events (heart failure hospitalization, transplant, or cardiovascular death) were ascertained from medical records. Results: We identified 712 patients (age 33 years [range 21-45 years]; 419 [59%] males). The baseline H2FPEF score was 2.2 ± 1.4. There was a temporal increase in the H2FPEF score at 5 years (ΔH2FPEF score 0.34 ± 0.11) due to the increase in the prevalence of hypertension, obesity, and high filling pressures. The H2FPEF score correlated with left atrial volume (r = 0.73, P < 0.001), right atrial volume (r = 0.41, P < 0.001), right ventricular fractional area change (r = -0.46, P < 0.001), and left ventricular e' (r = -0.52, P < 0.001). Both the baseline H2FPEF score and ΔH2FPEF score were independently associated with cardiovascular events. Conclusions: These results suggest that the H2FPEF score can be used for prognostication in patients with COA. The temporal increase in the H2FPEF score was due to factors such as hypertension, obesity, and high filling pressures, and hence, it provides potential therapeutic targets to improve outcomes in this population.