Arooj R. Khan

Prevalence and outcome of thrombotic and embolic complications in adults after Fontan operation

Background There are limited studies of thrombotic and embolic complications (TEC) in the adult Fontan population. The purpose of the study was to determine the prevalence, risk factors, and outcomes of TECs in this population. Methods Retrospective review of adults with a previous Fontan operation, with follow‐up at Mayo Clinic, 1994‐2014. Systemic TEC was defined as intracardiac thrombus, ischemic stroke, or systemic arterial embolus. Nonsystemic TEC was defined as Fontan conduit/right atrial thrombus or pulmonary embolus. Results We identified 387 patients with a mean (SD) age of 28 (7) years and a mean follow‐up of 8 (2) years. An atriopulmonary connection (APC) was done for 286 patients (74%). Atrial arrhythmias were present in 278 (72%). There were 121 TECs (systemic n = 36, nonsystemic n = 85) in 98 patients (25%). Risk factors for systemic TEC were atrial arrhythmia (hazard ratio 2.28, P = .001) and APC (hazard ratio 1.98, P = .02); nonsystemic TEC also had similar risk factors. All 98 patients received warfarin. Warfarin was discontinued in 10 of 98 because of bleeding, and 8 of these 10 subsequently had a second TEC. Among the 82 patients who had follow‐up imaging, 16 (20%) had resolution of thrombus. In total, 24 of 98 patients had a second TEC, most of whom had inadequate anticoagulation. Conclusions Thrombotic and embolic complication was not uncommon; risk factors for TEC were APC and atrial arrhythmias. Most patients were treated successfully with warfarin alone. A second TEC occurred in most patients whose anticoagulation was discontinued because of bleeding events.

Cardiopulmonary exercise test in adults with prior Fontan operation: The prognostic value of serial testing

BACKGROUND The purpose of the study was to determine the role of cardiopulmonary exercise test (CPET) indices in predicting cardiovascular adverse events (CAEs) in patients with Fontan palliation. CAE was defined as death or cardiac surgery. METHODS Retrospective review of adult Fontan patients who had treadmill CPET at Mayo Clinic, 1994-2013. Patients with loss of follow-up defined as ≥2years without clinical follow-up were excluded. The results of serial CPETs were reviewed, and patients with CPETs meeting the following criteria were selected for analysis: maximum effort on serial CPETs, minimum of 3-year interval between CPETs, and absence of CAE between CPETs. RESULTS A total of 145 patients met inclusion criteria for the study; age at baseline CPET was 24±3years; age at Fontan operation was 11±5years; and 91 (63%) were males. Baseline peak oxygen consumption (VO2) was 22.7±5.4ml/kg/min (63±11% predicted), peak heart rate was 135±31beats per minute, and oxygen saturation at peak exercise was 86±7%. Serial CPETs were performed in 71/145 patients (49%); mean duration between CPETs was 3.8±0.3years. The % predicted peak VO2 decreased by 1.7±0.9 percentage points/year. CAE (deaths n=22; cardiac surgery n=45) occurred in 54/145 patients (37%) within 8±3years. Decline in % predicted peak VO2≥3 percentage points/year was the only predictor of 5-year risk of CAE (HR 1.86, 95% CI 1.11-3.48, P=0.02). CONCLUSIONS Serial CPET is prognostic of CAE in the adult Fontan population, and can be used to risk stratify these patients.

Outcomes in adult Fontan patients with atrial tachyarrhythmias

Background The optimal management strategy for atrial tachyarrhythmia in the Fontan population is unknown. Methods Retrospective review of 264 adult Fontan patients with atrial tachyarrhythmia evaluating 3 clinically adopted scenarios: antiarrhythmic drug (AAD) therapy, catheter ablation (CA), and Fontan conversion (FC). These patients were followed up at Mayo Clinic from 1994 to 2014. The study objective was to compare freedom from atrial tachyarrhythmia recurrence (AR) and occurrence of composite adverse events (stroke, heart failure hospitalization, death, or heart transplant) between treatment groups. Results The age of atrial tachyarrhythmia onset was 25 ± 4 years, time from Fontan operation was 13 ± 6 years, follow‐up was 74 ± 18 months, atriopulmonary Fontan was 215 (81%), and atrial flutter/intra‐atrial reentry tachycardia was 173 (65%). In those managed with AAD (n = 110), freedom from AR was 7% at 60 months. Catheter ablation (n = 31) was associated with an acute procedural success of 94%, and freedom from AR was 41% at 60 months. Fontan conversion (n = 33) resulted in a perioperative mortality of 3%, and freedom from AR was 51% at 60 months. Fontan conversion and CA were similar with regard to AR (P = .14) and significantly better compared with AAD (P < .0001). Adverse events were found to occur more frequently in the patients with AR (P < .0001) and the patients treated with AAD only (P < .0001). Conclusions Catheter ablation and FC operations are associated with less recurrence of atrial tachyarrhythmia compared with AAD. Atrial tachyarrhythmias are more likely to recur in patients with a longer history of the arrhythmia and are associated with more adverse events. Early referral to a specialty center for these interventions should be considered.

Prevalence and predictors of intracranial aneurysms in patients with bicuspid aortic valve

Objective To determine the prevalence and outcomes of intracranial aneurysm (IA) in patients with bicuspid aortic valve (BAV). Methods Retrospective review of patients with BAV who underwent brain MR angiography at the Mayo Clinic from 1994 to 2013. Results There were 678 patients included in this study—mean age 57±13 years, men 480 (71%), mean follow-up 10±3 years (5913 patient-years). Coarctation of aorta (COA) was present in 154 (23%) patients. There were 59 IAs identified in 52 of 678 patients (7.7%). IA was present in 20/154 patients (12.9%) with COA and 32/524 patients (5.7%) without COA (p<0.001). For the patients without COA, female gender and right–left cusp fusion were risks factors for IA in women after adjustment for all potential variables (HR 1.76, CI 1.31 to 2.68, p=0.03). There was no significant trend in the risk for IA across age tertiles: age ≤40 years versus 41–60 years (HR 1.19, p=0.34), and age 41–60 years versus 61–80 years (HR 1.06, p=0.56). Among the 52 patients with IA, enlargement occurred in three patients (6%), rupture in two patients (4%) and four patients (8%) underwent coil embolisation. For the 626 patients without IA at baseline, no patient developed IA over 7±2 years of imaging follow-up. Conclusions BAV is associated with a higher prevalence of IA compared to the general population, and this risk is higher in patients with COA, right–left cusp fusion and female gender.

Predictors of procedural complications in adult Fontan patients undergoing non-cardiac procedures

Objective Limited data exist regarding the outcomes of non-cardiac procedures (NCPs) in adult patients after Fontan operations (Fontan patients). Methods To compare procedural outcomes after NCPs in Fontan patients with outcomes for two matched control groups: patients with repaired congenital heart disease and biventricular circulation (CHD-BiV) and patients with no heart disease (NHD). We defined cyanosis as oxygen saturation <90% and procedural hypoxia as saturation <80% or a decrease in saturation >10% from baseline. Results There were 538 NCPs in 154 Fontan patients (mean age, 30 years) performed in 1990–2015. Sedation and anaesthesia types were monitored anaesthesia care (256,48%), general anaesthesia (51,9%), minimal sedation (105,20%), local anaesthesia (75,14%) and regional anaesthesia (51,9%). Ninety-three complications occurred in 79 procedures (15%) and included arrhythmia requiring intervention (9), hypotension (14), bradycardia (8), hypoxia (38), heart failure requiring intravenous diuretics (2), acute kidney injury (3), bleeding requiring blood transfusion (1), unplanned procedures for dialysis catheter placement (2), readmission (2), unplanned hospitalisation for hypoxia (8) and unplanned transfer to intensive care unit (1). Baseline cyanosis was the only multivariable risk factor for complications (HR, 1.87 (95% CI 1.14 to 3.67), p=0.04). Procedural complications were more common in the Fontan group (18%) than in the CHD-BiV (5%) and NHD groups (1.4%) (p=0.001). Conclusions Complications after NCPs were more common in Fontan patients, and baseline cyanosis was a risk factor for complications. All-cause mortality was low and may be related to the multidisciplinary care approach used for Fontan patients at our centre.

Outcomes of Hospitalization in Adults with Fontan Palliation: The Mayo Clinic Experience

Background The outcomes of hospitalization in the Fontan population have not been specifically studied. The purpose of this study was to describe outcomes of hospitalization (frequency and indications for hospitalization, and in‐hospital mortality) in this population and to determine how these outcomes differ from those of other adults with congenital heart disease (CHD). Methods This was a retrospective study of adult Fontan patients hospitalized at Mayo Clinic Rochester in 1990‐2015. We selected age‐ and gender‐matched control group of patients with repaired CHD and biventricular circulation hospitalized within the study period. Results A total of 367 Fontan patients (age 31 ± 7 years and 259 [71%] with atriopulmonary Fontan) had 853 hospital admissions in 4 years (58 hospitalizations per 100 patient‐years). The most common indications were arrhythmia (n = 188, 22%), heart failure (n = 169, 20%), and cardiac surgery (n = 133, 16%). Overall in‐hospital mortality was 4% (n = 38), and the highest in‐hospital mortality occurred in patients hospitalized for cardiac surgery (n = 15, 11%) and heart failure (n = 13, 8%). In comparison to the repaired CHD and biventricular circulation group, the Fontan group had more frequent hospitalizations (22 vs 58 per 100 patient‐years, P < .001) and higher overall in‐hospital mortality (1% vs 5%, P < .001), mortality after cardiac surgery (2% vs 11%, P = .01), and mortality for heart failure–related hospitalizations (2% vs 8%, P = .04). Conclusions Adults with Fontan palliation had more frequent hospitalization and in‐hospital mortality compared to the rest of the CHD population. Arrhythmia and heart failure were the most common indications for hospitalization. Perhaps optimal management of heart failure and arrhythmia may improve outcomes in this population.

Outcomes of cardiac pacing in adult patients after a Fontan operation

Background Cardiac pacing can be challenging after a Fontan operation, and limited data exist regarding pacing in adult Fontan patients. The objectives of our study were to determine risk factors for pacing and occurrence of device‐related complications (DRCs) and pacemaker reinterventions. Methods We performed a retrospective review of Fontan patients from 1994 through 2014. We defined DRCs as lead failure, lead recall, cardiac perforation, lead thrombus/vegetation, or device‐related infection, and cardiovascular adverse events (CAEs) as venous thrombosis, stroke, death, or heart transplant. Pacemaker reintervention was defined as lead failure or recall. Results Of 439 patients, 166 (38%) had pacemakers implanted (79 during childhood; 87, adulthood); 114 patients (69%) received epicardial leads initially, and 52 (31%), endocardial leads. Pacing was initially atrial in 52 patients (31%); ventricular, 30 (18%); or dual chamber, 84 (51%). There were 37 reinterventions (1.9% per year) and 48 DRCs (2.4% per year). Pacemaker implantation during childhood was a risk factor for DRCs (hazard ratio, 2.01 [CI, 1.22–5.63]; P = .03). There were 70 CAEs (venous thrombosis, 5; stroke, 11; transplant, 8; and death, 46), yielding a rate of 3.5% per year. DRCs, CAEs, and reintervention rates were comparable for patients with epicardial or endocardial leads. Conclusions More than one‐third of adult Fontan patients referred to Mayo Clinic had pacemaker implantation. Epicardial leads were associated with high rate of pacemaker reinterventions but similar DRC rates in comparison to endocardial leads.

Venous congestion and pulmonary vascular function in Fontan circulation: Implications for prognosis and treatment

BACKGROUND Elevation in central venous pressure (CVP) plays a fundamental pathophysiologic role in Fontan circulation. Because there is no sub-pulmonary ventricle in this system, CVP also provides the driving force for pulmonary blood flow. We hypothesized that this would make Fontan patients more susceptible to even low-level elevation in pulmonary vascular resistance index (PVRI), resulting in greater systemic venous congestion and adverse outcomes. METHODS Adult Fontan patients and controls without congenital heart disease undergoing clinical evaluation that included cardiac catheterization and echocardiography were examined retrospectively. Outcomes including all-cause mortality and the development of Fontan associated diseases (FAD, defined as protein losing enteropathy, cirrhosis, heart failure hospitalization, arrhythmia, or thromboembolism) were assessed from longitudinal assessment. RESULTS As compared to controls (n = 82), Fontan patients (n = 164) were younger (36 vs 45 years, p < 0.001), more likely to be on anticoagulation or antiplatelet therapy, and more likely to have atrial arrhythmia or cirrhosis. There was a strong correlation between CVP and PVRI in the Fontan group (r = 0.79, p < 0.001), but there was no such relationship in controls. Elevated PVRI identified patients at increased risk for FAD (HR 1.92, 95% CI 1.39-2.41, p = 0.01), and composite endpoint of FAD and/or death (HR 1.89, 95% CI 1.32-2.53, p = 0.01) per 1 WU∗m2 increment. CONCLUSIONS Systemic venous congestion, which is the primary factor in the pathogenesis of FAD and death, is related to even low-level abnormalities in pulmonary vascular function. Multicenter studies are needed to determine whether interventions targeting pulmonary vascular structure and function can improve outcomes in the Fontan population.

Role of Doppler Echocardiography for Cardiac Output Assessment in Fontan Patients

Background To determine (1) correlation between Doppler stroke volume index (SVI) and cardiac magnetic resonance imaging (CMRI) SVI and (2) association between Doppler SVI and Fontan‐associated diseases (FAD) and Fontan failure. Methods Review of Fontan patients who underwent same‐day CMRI and transthoracic echocardiography (TTE), 2005 to 2015. We defined FAD as cardiac thrombus, protein‐losing enteropathy, arrhythmia, and hospitalization for heart failure. Fontan failure was defined as Fontan conversion or revision, heart transplantation or listing, or death. Results Fifty‐three patients with systemic left ventricle (LV) underwent 86 sets of TTE/CMRI. Mean (SD) age 31 (6) years. SVI (45 [16] vs 42 [13] mL/m2), CI (3.0 [1.1] vs 2.8 [0.8] L min−1 m−2), and ejection fraction (53 [4]% vs 51 [5]%) were similar for both modalities (P > .05 for all). Doppler SVI correlated with CMRI (r = 0.68; P < .001). Sixteen patients had cirrhosis, and these patients had a higher CI (3.9 [0.9] vs 2.8 [1.0] L min−1 m−2; P < .01). Among the 37 patients without cirrhosis, Doppler SVI <39 mL/m2 was associated with FAD (odds ratio [OR], 2.11; 95% confidence limit, 1.26–3.14; P = .02); Fontan failure was more common in patients with CI was <2.5 L min−1 m−2 (3/9 [33%] vs 0/28 [0%], P = .01). Another 11 patients with systemic right ventricle (RV) underwent 17 sets of TTE/CMRI, mean (SD) age 17 (3) years, and CMRI SVI also correlated with Doppler SVI (r = 0.75; P < .001). Conclusion Doppler SVI correlated with CMRI SVI in patients with systemic LV and systemic RV. The association between output measures (SVI and CI) and FAD were seen only in single LV patients (single RV patients not assessed for this outcome due to small numbers). An association between low Doppler CI and Fontan failure was suggested in a small number of single LV patients.

Mechanism for temporal changes in exercise capacity after Fontan palliation: Role of Doppler echocardiography

Background The objective was to better understand Doppler hemodynamics and exercise capacity in patients with Fontan palliation by delineating the hemodynamic mechanism for temporal changes in their peak oxygen consumption (&OV0312;o2). Methods We performed a retrospective review of adult Fontan patients with systemic left ventricle (LV) who underwent serial transthoracic echocardiograms (TTE) and cardiopulmonary exercise tests (CPET) at Mayo Clinic in 2000‐2015. TTE and CPET data were used (1) to determine agreement between &OV0312;o2 and Doppler‐derived LV function indices (eg, stroke volume index [SVI] and cardiac index [CI]) and (2) to determine agreement between temporal changes in peak &OV0312;o2 and LV function indices. Results Seventy‐five patients (44 men; 59%) underwent 191 pairs of TTE and CPET. At baseline, mean age was 24 ± 3 years, peak &OV0312;o2 was 22.9 ± 4.1 mL/kg/min (63 ± 11 percent predicted), SVI was 43 ± 15 mL/m2, and CI was 2.9 ± 0.9 L/min/m2. Peak &OV0312;o2 correlated with SVI (r = 0.30, P < .001) and with CI (r = 0.45, P < .001) in the 153 pairs of TTE and CPET in patients without cirrhosis. Temporal changes in percent predicted peak &OV0312;o2 correlated with changes in SVI (r = 0.48, P = .005) and CI (r = 0.49, P = .004) among the 33 patients without interventions during the study. In the 19 patients with Fontan conversion, percent predicted peak &OV0312;o2 and chronotropic index improved. Conclusions Overall, there was a temporal decline in peak &OV0312;o2 that correlated with decline in Doppler SVI. In the patients who had Fontan conversion operation, there was a temporal improvement in peak &OV0312;o2 that correlated with improvement in chronotropic index.