Christiane Haeffele

All Publications

• Transcatheter Valve Replacement in Severe Tricuspid Regurgitation. The New England journal of medicine Hahn, R. T., Makkar, R., Thourani, V. H., Makar, M., Sharma, R. P., Haeffele, C., Davidson, C. J., Narang, A., O'Neill, B., Lee, J., Yadav, P., Zahr, F., Chadderdon, S., Eleid, M., Pislaru, S., Smith, R., Szerlip, M., Whisenant, B., Sekaran, N. K., Garcia, S., Stewart-Dehner, T., Thiele, H., Kipperman, R., Koulogiannis, K., Lim, D. S., Fowler, D., Kapadia, S., Harb, S. C., Grayburn, P. A., Sannino, A., Mack, M. J., Leon, M. B., Lurz, P., Kodali, S. K. 2024

  Abstract

  Severe tricuspid regurgitation is associated with disabling symptoms and an increased risk of death. Data regarding outcomes after percutaneous transcatheter tricuspid-valve replacement are needed.In this international, multicenter trial, we randomly assigned 400 patients with severe symptomatic tricuspid regurgitation in a 2:1 ratio to undergo either transcatheter tricuspid-valve replacement and medical therapy (valve-replacement group) or medical therapy alone (control group). The hierarchical composite primary outcome was death from any cause, implantation of a right ventricular assist device or heart transplantation, postindex tricuspid-valve intervention, hospitalization for heart failure, an improvement of at least 10 points in the score on the Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS), an improvement of at least one New York Heart Association (NYHA) functional class, and an improvement of at least 30 m on the 6-minute walk distance. A win ratio was calculated for the primary outcome by comparing all possible patient pairs, starting with the first event in the hierarchy.A total of 267 patients were assigned to the valve-replacement group and 133 to the control group. At 1 year, the win ratio favoring valve replacement was 2.02 (95% confidence interval [CI], 1.56 to 2.62; P<0.001). In comparisons of patient pairs, those in the valve-replacement group had more wins than the control group with respect to death from any cause (14.8% vs. 12.5%), postindex tricuspid-valve intervention (3.2% vs. 0.6%), and improvement in the KCCQ-OS score (23.1% vs. 6.0%), NYHA class (10.2% vs. 0.8%), and 6-minute walk distance (1.1% vs. 0.9%). The valve-replacement group had fewer wins than the control group with respect to the annualized rate of hospitalization for heart failure (9.7% vs. 10.0%). Severe bleeding occurred in 15.4% of the valve-replacement group and in 5.3% of the control group (P = 0.003); new permanent pacemakers were implanted in 17.4% and 2.3%, respectively (P<0.001).For patients with severe tricuspid regurgitation, transcatheter tricuspid-valve replacement was superior to medical therapy alone for the primary composite outcome, driven primarily by improvements in symptoms and quality of life. (Funded by Edwards Lifesciences; TRISCEND II ClinicalTrials.gov number, NCT04482062.).

  View details for DOI 10.1056/NEJMoa2401918

  View details for PubMedID 39475399

• Quality of Life After Transcatheter Tricuspid Valve Replacement: 1-Year Results From TRISCEND II Pivotal Trial. Journal of the American College of Cardiology Arnold, S. V., Hahn, R. T., Thourani, V. H., Makkar, R., Makar, M., Sharma, R. P., Haeffele, C., Davidson, C. J., Narang, A., O'Neill, B., Lee, J., Yadav, P., Zahr, F., Chadderdon, S., Eleid, M., Pislaru, S., Smith, R., Szerlip, M., Whisenant, B., Sekaran, N., Garcia, S., Stewart-Dehner, T., Grayburn, P. A., Sannino, A., Snyder, C., Zhang, Y., Mack, M. J., Leon, M. B., Lurz, P., Kodali, S., Cohen, D. J. 2024

  Abstract

  Severe tricuspid regurgitation (TR) often causes substantial impairment in patient-reported health status (ie, symptoms, physical and social function, and quality of life), which may improve with transcatheter tricuspid valve replacement (TTVR).We performed an in-depth analysis of health status of patients enrolled in the TRISCEND (Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy using a Novel Device) II pivotal trial to help quantify the benefit of intervention to patients.The TRISCEND II pivotal trial randomized 400 patients with symptomatic and severe or greater TR 2:1 to TTVR with the EVOQUE tricuspid valve replacement system plus optimal medical therapy (OMT) or OMT alone. Health status was assessed with the Kansas City Cardiomyopathy Questionnaire and the 36-Item Short Form Health Survey. Changes in health status over 1 year were compared between treatment groups using mixed-effects repeated-measures models.The analysis cohort included 392 patients, of whom 259 underwent attempted TTVR and 133 received OMT alone (mean age 79.2 ± 7.6 years, 75.5% women, 56.1% with massive or torrential TR). Patients had substantially impaired health status at baseline (mean Kansas City Cardiomyopathy Questionnaire Overall Summary Score [KCCQ-OS] 52.1 ± 22.8; mean 36-Item Short Form Health Survey physical component summary score 35.2 ± 8.4). TTVR+OMT patients reported significantly greater improvement in both disease-specific and generic health status at each follow-up time point. Mean between-group differences in the KCCQ-OS favored TTVR+OMT at each time point: 11.8 points (95% CI: 7.4-16.3 points) at 30 days, 20.8 points (95% CI: 16.1-25.5 points) at 6 months, and 17.8 points (95% CI: 13.0-22.5 points) at 1 year. In subgroup analyses, TTVR+OMT improved health status to a greater extent among patients with torrential or massive TR vs severe TR (treatment effect 23.3 vs 22.6 vs 11.3; interaction P = 0.049). At 1 year, 64.6% of TTVR+OMT patients were alive and well (KCCQ-OS ≥60 points and no decline of ≥10 points from baseline) compared with 31.0% with OMT alone.Compared with OMT alone, treatment of patients with symptomatic and severe or greater TR with TTVR+OMT resulted in substantial improvement in patients' symptoms, function, and quality of life. These benefits were evident 30 days after TTVR, continued to increase through 6 months, and remained durable through 1 year. (TRISCEND II Pivotal Trial [Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy using a Novel Device]; NCT04482062).

  View details for DOI 10.1016/j.jacc.2024.10.067

  View details for PubMedID 39480380

• Paravalvular Leak Closure After Self-Expanding Transcatheter Aortic Valve Replacement Using a Steerable Sheath. Journal of the Society for Cardiovascular Angiography & Interventions Dawson, L. P., Kim, I., Haeffele, C., Sharma, R. 2024; 3 (8): 102020

  Abstract

  We present the case of an 82-year-old woman with persistent fatigue, exertional dyspnea, and dizziness related to a paravalvular leak following a self-expanding transcatheter aortic valve replacement. Successful closure was performed using a steerable sheath to negotiate a vascular plug closure device through the self-expanding valve structure.

  View details for DOI 10.1016/j.jscai.2024.102020

  View details for PubMedID 39166159

• Mortality and morbidity after combined heart and liver transplantation in the failing Fontan: An updated dual center retrospective study. Clinical transplantation Vaikunth, S. S., Ortega-Legaspi, J. M., Conrad, D. R., Chen, S., Daugherty, T., Haeffele, C. L., Teuteberg, J., Mclean, R., MacArthur, J. W., Woo, Y. J., Maeda, K., Ma, M., Nasirov, T., Hoteit, M., Hilscher, M. B., Wald, J., Mandelbaum, T., Olthoff, K. M., Abt, P. L., Atluri, P., Cevasco, M., Mavroudis, C. D., Fuller, S., Lui, G. K., Kim, Y. Y. 2024; 38 (4): e15302

  Abstract

  As the adult Fontan population with Fontan associated liver disease continues to increase, more patients are being referred for transplantation, including combined heart and liver transplantation.We report updated mortality and morbidity outcomes after combined heart and liver transplant in a retrospective cohort series of 40 patients (age 14 to 49 years) with Fontan circulation across two centers from 2006-2022.The 30-day, 1-year, 5-year and 10-year survival rate was 90%, 80%, 73% and 73% respectively. Sixty percent of patients met a composite comorbidity of needing either post-transplant mechanical circulatory support, renal replacement therapy or tracheostomy. Cardiopulmonary bypass time > 283 min (4.7 h) and meeting the composite comorbidity were associated with mortality by Kaplan Meier analysis.Further study to mitigate early mortality and the above comorbidities as well as the high risk of bleeding and vasoplegia in this patient population is warranted.

  View details for DOI 10.1111/ctr.15302

  View details for PubMedID 38567883

• Hepatocellular carcinoma in survivors after Fontan operation: a case-control study. European heart journal Kim, Y. Y., Lluri, G., Haeffele, C., Daugherty, T., Krasuski, R. A., Serfas, J. D., de Freitas, R. A., Porlier, A., Lubert, A. M., Wu, F. M., Valente, A. M., Krieger, E. V., Buber, J., Rodriguez, F. H., Gaignard, S., Saraf, A., Hindes, M., Earing, M. G., Lewis, M. J., Rosenbaum, M. S., Zaidi, A. N., Hopkins, K., Bradley, E. A., Cedars, A. M., Ko, J. L., Franklin, W. J., Frederickson, A., Ginde, S., Grewal, J., Nyman, A., Min, J., Schluger, C., Rand, E., Rosenthal, B. E., Hilscher, M., Rychik, J., Hoteit, M. A. 2023

  View details for DOI 10.1093/eurheartj/ehad788

  View details for PubMedID 38085593

• Echocardiographic Outcomes With Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients. JACC. Cardiovascular imaging Marcoff, L., Koulogiannis, K., Aldaia, L., Mediratta, A., Chadderdon, S. M., Makar, M. M., Ruf, T. F., Gößler, T., Zaroff, J. G., Leung, G. K., Ku, I. A., Nabauer, M., Grayburn, P. A., Wang, Z., Hawthorne, K. M., Fowler, D. E., Dal-Bianco, J. P., Vannan, M. A., Bevilacqua, C., Meineri, M., Ender, J., Forner, A. F., Puthumana, J. J., Mansoor, A. H., Lloyd, D. J., Voskanian, S. J., Ghobrial, A., Hahn, R. T., Mahmood, F., Haeffele, C., Ong, G., Schneider, L. M., Wang, D. D., Sekaran, N. K., Koss, E., Mehla, P., Harb, S., Miyasaka, R., Ivannikova, M., Stewart-Dehner, T., Mitchel, L., Raissi, S. R., Kalbacher, D., Biswas, S., Ho, E. C., Goldberg, Y., Smith, R. L., Hausleiter, J., Lim, D. S., Gillam, L. D. 2023

  Abstract

  The CLASP IID randomized trial (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial; NCT03706833) demonstrated the safety and effectiveness of the PASCAL system for mitral transcatheter edge-to-edge repair (M-TEER) in patients at prohibitive surgical risk with significant symptomatic degenerative mitral regurgitation (DMR).This study describes the echocardiographic methods and outcomes from the CLASP IID trial and analyzes baseline variables associated with residual mitral regurgitation (MR) ≤1+.An independent echocardiographic core laboratory assessed echocardiographic parameters based on American Society of Echocardiography guidelines focusing on MR mechanism, severity, and feasibility of M-TEER. Factors associated with residual MR ≤1+ were identified using logistic regression.In 180 randomized patients, baseline echocardiographic parameters were well matched between the PASCAL (n = 117) and MitraClip (n = 63) groups, with flail leaflets present in 79.2% of patients. Baseline MR was 4+ in 76.4% and 3+ in 23.6% of patients. All patients achieved MR ≤2+ at discharge. The proportion of patients with MR ≤1+ was similar in both groups at discharge but diverged at 6 months, favoring PASCAL (83.7% vs 71.2%). Overall, patients with a smaller flail gap were significantly more likely to achieve MR ≤1+ at discharge (adjusted OR: 0.70; 95% CI: 0.50-0.99). Patients treated with PASCAL and those with a smaller flail gap were significantly more likely to sustain MR ≤1+ to 6 months (adjusted OR: 2.72 and 0.76; 95% CI: 1.08-6.89 and 0.60-0.98, respectively).The study used DMR-specific echocardiographic methodology for M-TEER reflecting current guidelines and advances in 3-dimensional echocardiography. Treatment with PASCAL and a smaller flail gap were significant factors in sustaining MR ≤1+ to 6 months. Results demonstrate that MR ≤1+ is an achievable benchmark for successful M-TEER. (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial [CLASP IID]; NCT03706833).

  View details for DOI 10.1016/j.jcmg.2023.09.015

  View details for PubMedID 38099912

• Transfemoral tricuspid valve replacement and one-year outcomes: the TRISCEND study. European heart journal Kodali, S., Hahn, R. T., Makkar, R., Makar, M., Davidson, C. J., Puthumana, J. J., Zahr, F., Chadderdon, S., Fam, N., Ong, G., Yadav, P., Thourani, V., Vannan, M. A., O'Neill, W. W., Wang, D. D., Tchétché, D., Dumonteil, N., Bonfils, L., Lepage, L., Smith, R., Grayburn, P. A., Sharma, R. P., Haeffele, C., Babaliaros, V., Gleason, P. T., Elmariah, S., Inglessis-Azuaje, I., Passeri, J., Herrmann, H. C., Silvestry, F. E., Lim, S., Fowler, D., Webb, J. G., Moss, R., Modine, T., Lafitte, S., Latib, A., Ho, E., Goldberg, Y., Shah, P., Nyman, C., Rodés-Cabau, J., Bédard, E., Brugger, N., Sannino, A., Mack, M. J., Leon, M. B., Windecker, S. 2023

  Abstract

  For patients with symptomatic, severe tricuspid regurgitation (TR), early results of transcatheter tricuspid valve (TV) intervention studies have shown significant improvements in functional status and quality of life associated with right-heart reverse remodelling. Longer-term follow-up is needed to confirm sustained improvements in these outcomes.The prospective, single-arm, multicentre TRISCEND study enrolled 176 patients to evaluate the safety and performance of transcatheter TV replacement in patients with ≥moderate, symptomatic TR despite medical therapy. Major adverse events, reduction in TR grade and haemodynamic outcomes by echocardiography, and clinical, functional, and quality-of-life parameters are reported to one year.Enrolled patients were 71.0% female, mean age 78.7 years, 88.0% ≥ severe TR, and 75.4% New York Heart Association classes III-IV. Tricuspid regurgitation was reduced to ≤mild in 97.6% (P < .001), with increases in stroke volume (10.5 ± 16.8 mL, P < .001) and cardiac output (0.6 ± 1.2 L/min, P < .001). New York Heart Association class I or II was achieved in 93.3% (P < .001), Kansas City Cardiomyopathy Questionnaire score increased by 25.7 points (P < .001), and six-minute walk distance increased by 56.2 m (P < .001). All-cause mortality was 9.1%, and 10.2% of patients were hospitalized for heart failure.In an elderly, highly comorbid population with ≥moderate TR, patients receiving transfemoral EVOQUE transcatheter TV replacement had sustained TR reduction, significant increases in stroke volume and cardiac output, and high survival and low hospitalization rates with improved clinical, functional, and quality-of-life outcomes to one year. Funded by Edwards Lifesciences, TRISCEND ClinicalTrials.gov number, NCT04221490.

  View details for DOI 10.1093/eurheartj/ehad667

  View details for PubMedID 37930776

• Patient-Reported Outcomes in Tricuspid Valve Intervention: Patient Preference Results From the TRISCEND II Trial Brener, M., Barker, C., Davidson, C., Narang, A., Sharma, R., Haeffele, C., Yadav, P., Thourani, V., Kodali, S., Hahn, R., Makkar, R., Makar, M., Hausleiter, J., Nabauer, M., O'Neill, W., Wang, D., Lindman, B., Zahr, F., Chadderdon, S., Eleid, M., Pislaru, S., Mancilla, M., Kemp, L., Mollenkopf, S., Ryan, M., Cohen, D. ELSEVIER SCIENCE INC. 2023: B289-B290

  View details for Web of Science ID 001108754600701

• Emergency Transcatheter Repair for Anterior Leaflet Tear Following Percutaneous Balloon Mitral Valvuloplasty. JACC. Case reports Dowling, C., Haeffele, C., Yeung, A. C., Sharma, R. P. 2023; 23: 101980

  Abstract

  We present the case of a 66-year-old woman who developed severe mitral regurgitation from rupture of the anterior mitral valve leaflet following percutaneous balloon mitral valvuloplasty. Emergency transcatheter mitral valve repair was used to reduce the severity of mitral regurgitation and facilitate definitive surgical treatment. (Level of Difficulty: Advanced.).

  View details for DOI 10.1016/j.jaccas.2023.101980

  View details for PubMedID 37954949

  View details for PubMedCentralID PMC10635879

• CHARACTERISTICS AND OUTCOMES OF HEPATOCELLULAR CARCINOMA IN THE FONTAN SURVIVOR: A MULTICENTER RETROSPECTIVE STUDY EXAMINING LIVER OUTCOMES Rosenthal, B. E., Kim, Y. Y., Nyman, A., Lluri, G., Haeffele, C., De Freitas, R. A., Lubert, A., Krasuski, R., Wu, F., Krieger, E., Saraf, A., Earing, M., Lewis, M. J., Rodriguez, F. H., Zaidi, A., Bradley, E., Cedars, A. M., Franklin, W. J., Ginde, S., Grewal, J., Schluger, C., Min, J., Hilscher, M., Rychik, J., Rand, E., Hoteit, M. A. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1810-S1811

  View details for Web of Science ID 001094865404279

• Fontan Associated Liver Disease: Canary in the Coal Mine or Silent Killer? Journal of the American Heart Association Haeffele, C., McElhinney, D. B. 2023: e031597

  View details for DOI 10.1161/JAHA.123.031597

  View details for PubMedID 37776191

• The Resilient Heart: Exploring Post-Traumatic Stress in Adult Patients With Congenital Heart Disease. The American journal of cardiology Haeffele, C., Sillman, C. 2023

  View details for DOI 10.1016/j.amjcard.2023.07.147

  View details for PubMedID 37612217

• Percutaneous Treatment of an Aorto-Right Ventricular Fistula FollowingBalloon-Expandable Transcatheter Aortic Valve Replacement. JACC. Case reports Dowling, C., Haeffele, C., Pogatchnik, B. P., Sharma, R. P. 2023; 18: 101906

  Abstract

  We present the case of a 71-year-old man who experienced congestive cardiac failure after transcatheter aortic valve replacement with a balloon-expandable transcatheter heart valve. Echocardiography and cardiac computed tomography demonstrated an aorto-right ventricular fistula, and successful percutaneous closure was performed with a vascular plug. (Level of Difficulty: Advanced.).

  View details for DOI 10.1016/j.jaccas.2023.101906

  View details for PubMedID 37545680

• Morbidity and Mortality in Adult Fontan Patients After Heart or Combined Heart-Liver Transplantation. Journal of the American College of Cardiology Lewis, M. J., Reardon, L. C., Aboulhosn, J., Haeffele, C., Chen, S., Kim, Y., Fuller, S., Forbess, L., Alshawabkeh, L., Urey, M. A., Book, W. M., Rodriguez, F., Menachem, J. N., Clark, D. E., Valente, A. M., Carazo, M., Egbe, A., Connolly, H. M., Krieger, E. V., Angiulo, J., Cedars, A., Ko, J., Jacobsen, R. M., Earing, M. G., Cramer, J. W., Ermis, P., Broda, C., Nugaeva, N., Ross, H., Awerbach, J. D., Krasuski, R. A., Rosenbaum, M. 2023; 81 (22): 2161-2171

  Abstract

  An increasing number of adult Fontan patients require heart transplantation (HT) or combined heart-liver transplant (CHLT); however, data regarding outcomes and optimal referral time remain limited.The purpose of this study was to define survivorship post-HT/CHLT and predictors of post-transplant mortality, including timing of referral, in the adult Fontan population.A retrospective cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers in the United States and Canada was performed. Inclusion criteria included the following: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at the time of referral. Date of "failing" Fontan was defined as the earliest of the following: worsening fluid retention, new ascites, refractory arrhythmia, "failing Fontan" diagnosis by treating cardiologist, or admission for heart failure.A total of 131 patients underwent transplant, including 40 CHLT, from 1995 to 2021 with a median post-transplant follow-up time of 1.6 years (Q1 0.35 years, Q3 4.3 years). Survival was 79% at 1 year and 66% at 5 years. Survival differed by decade of transplantation and was 87% at 1 year and 76% at 5 years after 2010. Time from Fontan failure to evaluation (HR/year: 1.23 [95% CI: 1.11-1.36]; P < 0.001) and markers of failure, including NYHA functional class IV (HR: 2.29 [95% CI: 1.10-5.28]; P = 0.050), lower extremity varicosities (HR: 3.92 [95% CI: 1.68-9.14]; P = 0.002), and venovenous collaterals (HR: 2.70 [95% CI: 1.17-6.20]; P = 0.019), were associated with decreased post-transplant survival at 1 year in a bivariate model that included transplant decade.In our multicenter cohort, post-transplant survival improved over time. Late referral after Fontan failure and markers of failing Fontan physiology, including worse functional status, lower extremity varicosities, and venovenous collaterals, were associated with post-transplant mortality.

  View details for DOI 10.1016/j.jacc.2023.03.422

  View details for PubMedID 37257951

• Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation. Journal of the American College of Cardiology Lewis, M. J., Reardon, L. C., Aboulhosn, J., Haeffele, C., Chen, S., Kim, Y., Fuller, S., Forbess, L., Alshawabkeh, L., Urey, M. A., Book, W. M., Rodriguez, F., Menachem, J. N., Clark, D. E., Valente, A. M., Carazo, M., Egbe, A., Connolly, H. M., Krieger, E. V., Angiulo, J., Cedars, A., Ko, J., Jacobsen, R. M., Earing, M. G., Cramer, J. W., Ermis, P., Broda, C., Nugaeva, N., Ross, H., Awerbach, J. D., Krasuski, R. A., Rosenbaum, M. 2023; 81 (22): 2149-2160

  Abstract

  The impact of Fontan-associated liver disease (FALD) on post-transplant mortality and indications for combined heart-liver transplant (CHLT) in adult Fontan patients remains unknown.The purpose of this study was to assess the impact of FALD on post-transplant outcomes and compare HT vs CHLT in adult Fontan patients.We performed a retrospective-cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers. Inclusion criteria were as follows: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at referral. Pretransplant FALD score was calculated using the following: 1) cirrhosis; 2) varices; 3) splenomegaly; or 4) ≥2 paracenteses.A total of 131 patients (91 HT and 40 CHLT) were included. CHLT recipients were more likely to be older (P = 0.016), have a lower hemoglobin (P = 0.025), require ≥2 diuretic agents pretransplant (P = 0.051), or be transplanted in more recent decades (P = 0.001). Postmatching, CHLT demonstrated a trend toward improved survival at 1 year (93% vs 74%; P = 0.097) and improved survival at 5 years (86% vs 52%; P = 0.041) compared with HT alone. In patients with a FALD score ≥2, CHLT was associated with improved survival (1 year: 85% vs 62%; P = 0.044; 5 years: 77% vs 42%; P = 0.019). In a model with transplant decade and FALD score, CHLT was associated with improved survival (HR: 0.33; P = 0.044) and increasing FALD score was associated with worse survival (FALD score: 2 [HR: 14.6; P = 0.015], 3 [HR: 22.2; P = 0.007], and 4 [HR: 27.8; P = 0.011]).Higher FALD scores were associated with post-transplant mortality. Although prospective confirmation of our findings is necessary, compared with HT alone, CHLT recipients were older with higher FALD scores, but had similar survival overall and superior survival in patients with a FALD score ≥2.

  View details for DOI 10.1016/j.jacc.2023.03.421

  View details for PubMedID 37257950

• Outcomes After Development of Ventricular Arrhythmias in Single Ventricular Heart Disease Patients With Fontan Palliation. Circulation. Arrhythmia and electrophysiology Giacone, H. M., Chubb, H., Dubin, A. M., Motonaga, K. S., Ceresnak, S. R., Goodyer, W. R., Hanish, D., Trela, A. V., Boramanand, N., Lencioni, E., Boothroyd, D., Graber-Naidich, A., Wright, G., Haeffele, C., Hollander, S. A., McElhinney, D. B., Ma, M., Hanley, F. L., Chen, S. 2023: e011143

  Abstract

  With the advent of more intensive rhythm monitoring strategies, ventricular arrhythmias (VAs) are increasingly detected in Fontan patients. However, the prognostic implications of VA are poorly understood. We assessed the incidence of VA in Fontan patients and the implications on transplant-free survival.Medical records of Fontan patients seen at a single center between 2002 and 2019 were reviewed to identify post-Fontan VA (nonsustained ventricular tachycardia >4 beats or sustained >30 seconds). Patients with preFontan VA were excluded. Hemodynamically unstable VA was defined as malignant VA. The primary outcome was death or heart transplantation. Death with censoring at transplant was a secondary outcome.Of 431 Fontan patients, transplant-free survival was 82% at 15 years post-Fontan with 64 (15%) meeting primary outcome of either death (n=16, 3.7%), at a median 4.6 (0.4-10.2) years post-Fontan, or transplant (n=48, 11%), at a median of 11.1 (5.9-16.2) years post-Fontan. Forty-eight (11%) patients were diagnosed with VA (90% nonsustained ventricular tachycardia, 10% sustained ventricular tachycardia). Malignant VA (n=9, 2.0%) was associated with younger age, worse systolic function, and valvular regurgitation. Risk for VA increased with time from Fontan, 2.4% at 10 years to 19% at 20 years. History of Stage 1 surgery with right ventricular to pulmonary artery conduit and older age at Fontan were significant risk factors for VA. VA was strongly associated with an increased risk of transplant or death (HR, 9.2 [95% CI, 4.5-18.7]; P<0.001), with a transplant-free survival of 48% at 5-year post-VA diagnosis.Ventricular arrhythmias occurred in 11% of Fontan patients and was highly associated with transplant or death, with a transplant-free survival of <50% at 5-year post-VA diagnosis. Risk factors for VA included older age at Fontan and history of right ventricular to pulmonary artery conduit. A diagnosis of VA in Fontan patients should prompt increased clinical surveillance.

  View details for DOI 10.1161/CIRCEP.122.011143

  View details for PubMedID 37254747

• First described mitral clip in an adult extracardiac Fontan patient: a case report. European heart journal. Case reports Haeffele, C. L., Lui, G. K., Peng, L., Chan, F., Sharma, R. P. 2023; 7 (1): ytac479

  Abstract

  The use of transcatheter edge-to-edge repair (TEER) in patients with advanced heart failure has been shown to reduce hospitalizations and increase survival. As patients with Fontan circulations grow older, a significant proportion of them will develop severe atrioventricular (AV) valve regurgitation in the systemic ventricle. Conventional surgical repair and transplant carry high mortality risk for the adult Fontan patient with progressive heart failure.A 51-year-old female extracardiac Fontan patient developed severe AV valve regurgitation and progressive functional decline. Based on her operative risk for conventional surgical intervention or transplant, TEER using the Abbott MitraClip device was performed. The degree of mitral regurgitation was decreased from severe to moderate regurgitation.This is the first known case describing the use of a successful TEER in an adult patient with an extracardiac Fontan. Given the increasing numbers of patients surviving into adulthood with a Fontan circulation, transcatheter interventions may provide an alternative treatment option to conventional surgeries and medical therapies.

  View details for DOI 10.1093/ehjcr/ytac479

  View details for PubMedID 36733686

  View details for PubMedCentralID PMC9887705

• Arrhythmias in Repaired Tetralogy of Fallot: A Scientific Statement From the American Heart Association. Circulation. Arrhythmia and electrophysiology Krieger, E. V., Zeppenfeld, K., DeWitt, E. S., Duarte, V. E., Egbe, A. C., Haeffele, C., Lin, K. Y., Robinson, M. R., Sillman, C., Upadhyay, S. 2022: e000084

  Abstract

  Arrhythmia and sudden cardiac death remain common in repaired tetralogy of Fallot and affect even those with excellent anatomic repairs. Atrial arrhythmia often has mechanisms different from those in acquired heart disease. Ventricular arrhythmia remains a major source of mortality in repaired tetralogy of Fallot. Noninvasive risk stratification is important to identify patients who may benefit from ablation or primary prevention implantable cardioverter defibrillators. Multiple noninvasive risk factors are associated with ventricular arrhythmia, but no universally accepted risk stratification algorithm exists. The mechanism of ventricular arrhythmia is usually attributable to a consistent and discrete set of slowly conducting anatomic isthmuses related to both the native anatomy and the consequences of the surgical repair, which interact with ventricular remodeling to provide arrhythmic substrate. This substrate can be identified during electroanatomic mapping and prophylactically ablated in appropriate patients. This scientific statement discusses the mechanisms and treatment of arrhythmia in repaired tetralogy of Fallot.

  View details for DOI 10.1161/HAE.0000000000000084

  View details for PubMedID 36263773

• Extracorporeal membrane oxygenator as a bridge to heart-liver en bloc transplant in a patient with Fontan circulation. JTCVS techniques Kim, J. L., Vaikunth, S. S., Haeffele, C., MacArthur, J. W. 2022; 12: 171-174

  View details for DOI 10.1016/j.xjtc.2022.01.018

  View details for PubMedID 35403048

• The atrial switch patient with a dilated subpulmonic left ventricle (vol 4,100153, 2021) INTERNATIONAL JOURNAL OF CARDIOLOGY CONGENITAL HEART DISEASE Vaikunth, S. S., Haeffele, C., Mcelhinney, D. B., Lui, G. K., Romfh, A. W. 2021; 5

  View details for DOI 10.1016/j.ijcchd.2021.100223

  View details for Web of Science ID 001109060000011

• A 40-Year-Old Man With Tricuspid Atresia, Status Post-Fontan, With Severe COVID-19 Pneumonia and Pneumothorax. JACC. Case reports Vaikunth, S. S., Bykhovsky, M. R., Romfh, A. W., Haeffele, C. L., Rogers, I. S., Dong, E., Scribner, C., Lui, G. K. 2021

  Abstract

  We report a case of COVID-19 in an adult single-ventricle patient post-Fontan-to our knowledge, the first report in this population documenting the use of the latest management recommendations for this novel disease. Additionally, this patient had significant pre-existing ventricular dysfunction, valvular disease, and comorbidities including HIV. (Level of Difficulty: Advanced.).

  View details for DOI 10.1016/j.jaccas.2020.10.032

  View details for PubMedID 33558861

• The atrial switch patient with a dilated subpulmonic left ventricle International Journal of Cardiology Congenital Heart Disease Vaikunth, S. S., Haeffele, C., McElhinney, D. B., Lui, G. K., Romfh, A. 2021; Volume 4 (100153)

  View details for DOI 10.1016/j.ijcchd.2021.100153

• Adult congenital heart disease: left-sided obstructive lesions. Heart (British Cardiac Society) Haeffele, C. 2021

  View details for DOI 10.1136/heartjnl-2019-316364

  View details for PubMedID 34815332

• Clinical Outcomes, Echocardiographic Findings, and Care Quality Metrics for People Living with HIV and Rheumatic Heart Disease in Uganda. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Chang, A. Y., Rwebembera, J., Bendavid, E., Okello, E., Barry, M., Beaton, A. Z., Haeffele, C., Webel, A. R., Kityo, C., Longenecker, C. T. 2021

  Abstract

  Rheumatic Heart Disease (RHD) affects 41 million people worldwide, mostly in low- and middle-income countries, where it is co-endemic with HIV. HIV is also a chronic inflammatory disorder associated with cardiovascular complications, yet the epidemiology of patients affected by both diseases is poorly understood.Utilizing the Uganda National RHD Registry, we described the echocardiographic findings, clinical characteristics, medication prescription rates, and outcomes of all 73 people carrying concurrent diagnoses of HIV and RHD between 2009 and 2018. These individuals were compared to an age- and sex-matched cohort of 365 subjects with RHD only.The median age of the HIV-RHD group was 36 years (IQR 15) and 86% were women. The HIV-RHD cohort had higher rates of prior stroke/transient ischemic attack (12% vs 5%, p=0.02) than the RHD-only group, with this association persisting following multivariable adjustment (OR 3.08, p=0.03). Prevalence of other comorbidities, echocardiographic findings, prophylactic penicillin prescription rates, retention in clinical care, and mortality were similar between the two groups.Patients living with RHD and HIV in Uganda are a relatively young, predominantly female group. Although RHD-HIV comorbid individuals have higher rates of stroke, their similar all-cause mortality and RHD care quality metrics (such as retention in care) compared to those with RHD alone suggest rheumatic heart disease defines their clinical outcome more than HIV does. We believe this study to be one of the first reports of the epidemiologic profile and longitudinal outcomes of patients who carry diagnoses of both conditions.

  View details for DOI 10.1093/cid/ciab681

  View details for PubMedID 34382644

• Comparison of combined heart‒liver vs heart-only transplantation in pediatric and young adult Fontan recipients. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Sganga, D., Hollander, S. A., Vaikunth, S., Haeffele, C., Bensen, R., Navaratnam, M., McDonald, N., Profita, E., Maeda, K., Concepcion, W., Bernstein, D., Chen, S. 2020

  Abstract

  BACKGROUND: Indications for a heart‒liver transplantation (HLT) for Fontan recipients are not well defined. We compared listing characteristics, post-operative complications, and post-transplant outcomes of Fontan recipients who underwent HLT with those of patients who underwent heart-only transplantation (HT). We hypothesized that patients who underwent HLT have increased post-operative complications but superior survival outcomes compared with patients who underwent HT.METHODS: We performed a retrospective review of Fontan recipients who underwent HLT or HT at a single institution. Characteristics at the time of listing, including the extent of liver disease determined by laboratory, imaging, and biopsy data, were compared. Post-operative complications were assessed, and the Kaplan‒Meier survival method was used to compare post-transplant survival. Univariate regression analyses were performed to identify the risk factors for increased mortality and morbidity among patients who underwent HT.RESULTS: A total of 47 patients (9 for HLT, 38 for HT) were included. Patients who underwent HLT were older, were more likely to be on dual inotrope therapy, and had evidence of worse liver disease. Whereas ischemic time was longer for the group who underwent HLT, post-operative complications were similar. Over a median post-transplant follow-up of 17 (interquartile range: 5-52) months, overall mortality for the cohort was 17%; only 1 patient who underwent HLT died (11%) vs 7 patients who underwent HT (18%) (p = 0.64). Among patients who underwent HT, cirrhosis on pre-transplant imaging was associated with worse outcomes.CONCLUSIONS: Despite greater inotrope need and more severe liver disease at the time of listing, Fontan recipients undergoing HLT have post-transplant outcomes comparable with those of patients undergoing HT. HLT may offer a survival benefit for Fontan recipients with liver disease.

  View details for DOI 10.1016/j.healun.2020.12.008

  View details for PubMedID 33485775

• Does liver biopsy accurately measure fibrosis in Fontan associated liver disease? A comparison of liver biopsy pre-combined heart and liver transplant and liver explant post-transplant. Clinical transplantation Vaikunth, S. S., Higgins, J. P., Concepcion, W., Haeffele, C., Wright, G. E., Chen, S., Lui, G. K., Daugherty, T. 2020: e14120

  Abstract

  The accuracy of liver biopsy to stage fibrosis due to Fontan associated liver disease (FALD) remains unclear. We compared results of biopsy pre-combined heart and liver transplantation (CHLT) to results of whole liver explant. Liver biopsy and explants from 15 Fontan patients (ages 16 - 49, median 28 years) were retrospectively reviewed. Staging was as follows: stage 0: no fibrosis, stage 1: pericellular fibrosis, stage 2: bridging fibrosis, stage 3: regenerative nodules. There is no stage 4. Clinical characteristics including Model of End-stage Liver Disease eXcluding INR and Varices, Ascites, Splenomegaly, and Thrombocytopenia (VAST) scores were collected, and descriptive statistics and Mann-Whitney U tests used to analyze data. All patients had biopsies with at least bridging fibrosis, and all had nodularity on explant; transjugular biopsy never overestimated fibrosis. Explant showed higher grade fibrosis (Stage 3) than pre-CHLT biopsy (Stage 2) in 6 of 15 patients and equal grade of fibrosis (Stage 3) in 9 of 15 patients. Though clinical characteristics varied significantly, VAST score was ≥ 2 in all but two patients. Transjugular liver biopsy does not overestimate and can underestimate fibrosis in Fontan patients undergoing CHLT, likely due to the patchy nature of fibrosis in FALD.

  View details for DOI 10.1111/ctr.14120

  View details for PubMedID 33053213

• Outcomes of Heart and Combined Heart-Liver Transplant in Pediatric Fontan Patients Chen, S., Bensen, R., Profita, E., McDonald, N., Lui, G., Haeffele, C., Rosenthal, D. N., Bernstein, D., Maeda, K., Concepcion, W., Hollander, S. ELSEVIER SCIENCE INC. 2020: S453–S454

  View details for Web of Science ID 000522637203137

• MORBIDITY AND MORTALITY IN ADULT FONTAN PATIENTS REFERRED FOR TRANSPLANT: A REPORT FROM THE FOSTER STUDY Lewis, M. J., Haeffele, C., Chen, S., Reardon, L., Aboulhosn, J. A., Nugaeva, N., Ross, H., Kim, Y., Krasuski, R. A., Valente, A., Carazo, M., Krieger, E., Angiulo, J., Book, W., Rodriguez, F., Egbe, A., Jacobson, R., Earing, M., Cramer, J. W., Cedars, A. M., Ko, J., Broda, C., Ermis, P., Rosenbaum, M. ELSEVIER SCIENCE INC. 2020: 546

  View details for Web of Science ID 000522979100534

• CLINICAL CHARACTERISTICS OF "FAILING" ADULT FONTAN PATIENTS ACROSS 14 CENTERS: A REPORT FROM THE FOSTER STUDY Lewis, M. J., Haeffele, C., Chen, S., Reardon, L., Aboulhosn, J. A., Nugaeva, N., Ross, H., Kim, Y., Krasuski, R. A., Valente, A., Carazo, M., Krieger, E., Angiulo, J., Book, W., Rodriguez, F., Egbe, A., Jacobson, R., Earing, M., Cramer, J. W., Cedars, A. M., Ko, J., Broda, C., Ermis, P., Rosenbaum, M. ELSEVIER SCIENCE INC. 2020: 553

  View details for Web of Science ID 000522979100541

• MORBIDITY AND MORTALITY IN ADULT FONTAN PATIENTS AFTER HEART OR COMBINED HEART LIVER TRANSPLANT: A REPORT FROM THE FOSTER STUDY Lewis, M. J., Reardon, L., Aboulhosn, J. A., Haeffele, C., Chen, S., Kim, Y., Book, W., Rodriguez, F., Valente, A., Carazo, M., Krieger, E., Angiulo, J., Egbe, A., Cedars, A. M., Ko, J., Jacobson, R., Earing, M., Ermis, P., Broda, C., Cramer, J. W., Nugaeva, N., Ross, H., Krasuski, R. A., Rosenbaum, M. ELSEVIER SCIENCE INC. 2020: 653

  View details for Web of Science ID 000522979100641

• Heart failure in the adult Ebstein patient. Heart failure reviews Schultz, K. n., Haeffele, C. L. 2020

  Abstract

  Ebstein anomaly comprises approximately 1% of all congenital heart diseases. It occurs when the tricuspid valve fails to properly delaminate from the right ventricle, resulting in a clinical spectrum of abnormal tricuspid valve morphology and right ventricular dysfunction. Due to the anatomy of the tricuspid valve and right ventricle, as well as associated right- and left-sided pathology, patients are at risk for both right and left ventricular failure and the associated symptoms of each. Ebstein patients are also at risk for atrial arrhythmias, due to the atrial enlargement intrinsic to the anatomy, as well as the presence of potential accessory pathways. Arrhythmias are generally poorly tolerated, particularly in the setting of ventricular dysfunction. Cyanosis may also be present in Ebstein patients, due to the common occurrence of atrial communications, which can exacerbate other symptoms of heart failure. Treatment of heart failure can be through pharmacologic and procedural interventions, depending on the underlying cause of heart failure. While early heart failure symptoms may be treated with medical management, most Ebstein patients will require surgery. Various surgical and catheter-based interventions targeting the tricuspid valve and the atrialized right ventricular tissue have been developed to help treat the underlying cause of the heart failure. The optimal timing of transcatheter and surgical intervention in the Ebstein patient to prevent or treat heart failure needs further study.

  View details for DOI 10.1007/s10741-020-09930-2

  View details for PubMedID 32472521

• Predicting 10-year mortality in adults with congenital heart disease International Journal of Cardiology Congenital Heart Disease Fernandes, S. M., Lui, G. K., Long, J., Lin, A., Rogers, I. S., Sillman, C., Romfh, A., Dade, T., Dong, E., Haeffele, C., Scribner, C., Major, M., McElhinney, D. 2020

  View details for DOI 10.1016/j.ijcchd.2020.100057

• The Hidden Victims of the COVID-19 Pandemic: Congenital Heart Disease Patients. JACC. Case reports El-Saiedi, S. A., Haeffele, C. n., Hanna, B. M., Lui, G. K. 2020; 2 (9): 1411–13

  View details for DOI 10.1016/j.jaccas.2020.05.081

  View details for PubMedID 32835286

  View details for PubMedCentralID PMC7294284

• Fontan Liver Lesions: Not Always HCC JACC: Case Reports Haeffele, C., Aggarwal, A., Lutchman, G., Veldtman, G. R., Lui, G. K. 2020; 1 (12)

  View details for DOI 10.1016/j.jaccas.2019.05.031

• Percutaneous Pulmonary Vein Stenting to Treat Severe Pulmonary Vein Stenosis After Surgical Reconstruction. Innovations (Philadelphia, Pa.) Dalal, A. R., Markham, R. n., Haeffele, C. n., Sharma, R. n., Watkins, A. C. 2020: 1556984520933962

  Abstract

  A 36-year-old female underwent left lower lobectomy with left atrial and left upper pulmonary vein (LUPV) reconstruction with a bovine pericardial patch for an intrathoracic pheochromocytoma. Postoperatively, she developed shortness of breath and transesophageal echocardiography demonstrated LUPV stenosis with increased velocities. Computed tomography angiogram of the chest revealed LUPV stenosis at the left atrium ostium with an area of 39 mm2. Under angiographic and echocardiographic guidance, a 10 × 19 mm Omnilink Elite uncovered stent was deployed in the LUPV ostia. While reported following left atrial ablation, pulmonary vein stenting can be successful in a pulmonary vein surgically reconstructed with bovine pericardium.

  View details for DOI 10.1177/1556984520933962

  View details for PubMedID 32639846

• Fontan Liver Lesions: Not Always HCC. JACC. Case reports Haeffele, C., Aggarwal, A., Lutchman, G., Veldtman, G. R., Wu, F. M., Lui, G. K. 2019; 1 (2): 175-178

  Abstract

  A 24-year-old Fontan procedure patient underwent surveillance liver cardiac magnetic resonance imaging. Findings were suggestive of hepatocellular carcinoma (HCC). Currently, HCC is diagnosed based on imaging alone. Given her otherwise reassuring clinical profile, she underwent liver biopsy. Pathology demonstrated focal nodular hyperplasia. This raises concern for overdiagnosis of HCC in Fontan patients without tissue confirmation. (Level of Difficulty: Advanced.).

  View details for DOI 10.1016/j.jaccas.2019.05.031

  View details for PubMedID 34316779

  View details for PubMedCentralID PMC8301494

• Risk Estimates for Atherosclerotic Cardiovascular Disease in Adults With Congenital Heart Disease AMERICAN JOURNAL OF CARDIOLOGY Lui, G. K., Rogers, I. S., Ding, V. Y., Hedlin, H. K., MacMillen, K., Maron, D. J., Sillman, C., Romfh, A., Dade, T. C., Haeffele, C., Grady, S. R., McElhinney, D. B., Murphy, D. J., Fernandes, S. M. 2017; 119 (1): 112-118

  Abstract

  The adult with congenital heart disease (CHD) is at risk of developing atherosclerotic cardiovascular disease (ASCVD). We performed a cross-sectional study to describe established ASCVD risk factors and estimate 10-year and lifetime risk of ASCVD in adults over age 18 with CHD of moderate or great complexity using 3 validated risk assessment tools-the Framingham Study Cardiovascular Disease Risk Assessment, the Reynolds Risk Score, and the ASCVD Risk Estimator. We obtained extensive clinical and survey data on 178 enrolled patients, with average age 37.1 ± 12.6 years, 51% men. At least 1 modifiable ASCVD risk factor was present in 70%; the 2 most common were overweight/obesity (53%) and systemic hypertension (24%). Laboratory data were available in 103 of the 178 patients. Abnormal levels of glycated hemoglobin, high-sensitivity C-reactive protein, and high-density lipoprotein were each found in around 30% of patients. The 10-year ASCVD predicted risk using all 3 tools was relatively low (i.e., at least 90% of patients <10% risk), yet the median estimated lifetime risk was 36%. In conclusion, ASCVD risk factors are prevalent in adults with CHD. The risk estimation tools suggest that this population is particularly vulnerable to ASCVD with aging and should undergo guideline-based screening and management of modifiable risk factors.

  View details for DOI 10.1016/j.amjcard.2016.09.023

  View details for PubMedID 28247847

• UTILIZATION OF SPECIALTY CARE CENTERS IN CALIFORNIA FOR LABOR AND DELIVERY IN WOMEN WITH CONGENITAL HEART DISEASE Haeffele, C., Lui, G., Saynina, O., Grady, S., Chamberlain, L., Fernandes, S. ELSEVIER SCIENCE INC. 2016: 950

  View details for DOI 10.1016/S0735-1097(16)30951-2

  View details for Web of Science ID 000375188701794

• Dextro-Transposition of the Great Arteries Long-term Sequelae of Atrial and Arterial Switch CARDIOLOGY CLINICS Haeffele, C., Lui, G. K. 2015; 33 (4): 543-?

  Abstract

  Over the last 50 years, improved surgical techniques and progressive medical management have allowed patients with complete or dextro-transposition of the great arteries (D-TGA) to survive into adulthood. Older adult patients underwent an atrial switch procedure (Mustard or Senning operation), whereas the younger cohort of patients with TGA has undergone the arterial switch operation (ASO). The Mustard/Senning maintains the right ventricle as the systemic ventricle, whereas the more recently adopted ASO attempts to restore normal physiologic and anatomic relationships. Neither operation is without consequence. Neither is without consequence and require long term follow up.

  View details for DOI 10.1016/j.ccl.2015.07.012

  View details for Web of Science ID 000364729200006

  View details for PubMedID 26471819

• Receptor-selective coactivators as tools to define the biology of specific receptor-coactivator pairs MOLECULAR CELL Gaillard, S., Grasfeder, L. L., Haeffele, C. L., Lobenhofer, E. K., Chu, T., Wolfinger, R., Kazmin, D., Koves, T. R., Muoio, D. M., Chang, C., McDonnell, D. P. 2006; 24 (5): 797-803

  Abstract

  In the absence of specific high-affinity agonists and antagonists, it has been difficult to define the target genes and biological responses attributable to many of the orphan nuclear receptors (ONRs). Indeed, it appears that many members of this receptor superfamily are not regulated by classical small molecules but rather their activity is controlled by interacting cofactors. Motivated by this finding, we have developed an approach to genetically isolate specific receptor-cofactor pairs in cells, allowing us to define the biological responses attributable to each complex. This is accomplished by using combinatorial peptide phage display to engineer the receptor interacting domain of each cofactor such that it interacts selectively with one nuclear receptor. In this study, we describe the customization of PGC-1alpha and its use to study the biology of the estrogen-related receptor alpha (ERRalpha) in cultured liver cells.

  View details for DOI 10.1016/j.molcel.2006.10.012

  View details for Web of Science ID 000242812000015

  View details for PubMedID 17157261