Christiane Haeffele, MD

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

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) age16 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

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) age16 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), require2 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 score2, 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 score2.

View details for DOI 10.1016/j.jacc.2023.03.421

View details for PubMedID 37257950

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

View details for DOI 10.1016/j.xjtc.2022.01.018

View details for PubMedID 35403048

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

View details for DOI 10.1016/j.ijcchd.2021.100153

View details for DOI 10.1136/heartjnl-2019-316364

View details for PubMedID 34815332

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

Abstract

BACKGROUND: Indications for a heartliver 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 KaplanMeier 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

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

View details for Web of Science ID 000522979100541

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

View details for DOI 10.1016/j.ijcchd.2020.100057

View details for DOI 10.1016/j.jaccas.2020.05.081

View details for PubMedID 32835286

View details for PubMedCentralID PMC7294284

View details for DOI 10.1016/j.jaccas.2019.05.031

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

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

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 12.6years, 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

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

View details for Web of Science ID 000375188701794

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

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