Liver transplantation (LT) has not traditionally been offered to patients with intracardiac shunts (ICSs) or pulmonary hypertension (PH). There is a paucity of data regarding cardiac structural characteristics in LT candidates. We examined echocardiographic characteristics and their role in managing LT candidates diagnosed with ICS and PH. We identified 502 consecutive patients (318 men, mean age 55 ± 11 years) who underwent LT and had preoperative echocardiogram. Demographics, cardiovascular risk factors, and echocardiographic variables were recorded and data were analyzed for end-stage liver disease diagnosis. ICSs were diagnosed with contrast echocardiography and PH was defined as estimated pulmonary artery systolic pressure >40 mm Hg. Primary end points included short-term (30-day) and long-term (mean 41-month) mortalities and the correlation between pre- and perioperative stroke. In our studied population >50% had >2 cardiovascular risk factors and with increasing frequency ICSs were diagnosed in 16%, PH in 25%, and intrapulmonary shunts in 41% of LT candidates. There was no correlation between short- and long-term mortality and ICS (p = 0.71 and 0.76, respectively) or PH (p = 0.79 and 0.71). Importantly, in those with ICS, no strokes occurred. In conclusion, structural differences exist between various end-stage liver disease diagnoses. ICSs diagnosed by echocardiography are not associated with an increased risk of perioperative stroke or increased mortality. A diagnosis of mild or moderate PH on baseline echocardiogram is not associated with worse outcomes and requires further assessment. Based on these findings, patients should not be excluded from consideration for LT based solely on the presence of an ICS or PH.
Patients undergoing liver transplantation (LT) are subject to procoagulant and anticoagulant forces that can contribute to myocardial ischemia and stroke. Intracardiac shunts (ICSs), specifically patent foramen ovale, are prevalent in the general population. Associated factors such as hypercoagulability, hypoxemia, volume shifts, and air entry, which can occur during LT, may place patients with ICSs at a higher risk of poor outcomes. Further, moderate to severe pulmonary hypertension (PH) has been associated with poor outcomes after LT. However, with proper assessment and management LT can be performed safely in patients with PH. At many centers invasive measurement of pulmonary artery pressure is not performed because of concerns for increased complications such as bleeding. In addition, at lower-volume centers, patients may be excluded from consideration as LT candidates owing to the presence of PH diagnosed by estimated pulmonary artery systolic pressure (PASP) on baseline echocardiography, thus precluding serial measurements. This report describes a baseline echocardiographic profile of a cohort of patients with various causes of end-stage liver disease (ESLD) who underwent LT and the association between ICSs and PH and outcomes to make better use of information learned from preoperative echocardiography.
Methods
We identified and included all patients with ESLD who underwent LT at a single institution from 2006 to 2009 and had a preoperative transthoracic echocardiogram in our liver transplant registry. Institutional review board approval was obtained before review of medical records. Demographic characteristics, laboratory results, cardiovascular risk factors, and echocardiographic variables were recorded and data were analyzed for ESLD diagnosis (viral, alcoholic, nonalcoholic steatohepatitis, cryptogenic, and other). Cardiovascular risk factors recorded were advanced age (men ≥55 years old and women ≥65 years old), tobacco use, diabetes mellitus, hypertension, hyperlipidemia, and family history of premature coronary artery disease. Echocardiographic variables recorded were chamber sizes, presence of intracardiac and intrapulmonary shunting, diastolic dysfunction, ejection fraction, and PASP. Chamber quantification and assessment of echocardiographic variables were based on our laboratory’s normal values and American Society of Echocardiography recommendations. Diagnosis and grading of diastolic function were also performed in accordance with American Society of Echocardiography recommendations using 2-dimensional, spectral, and tissue Doppler techniques evaluating mitral inflow and mitral annulus velocities. Left ventricular ejection fraction was determined by visual inspection. PASP was estimated with Doppler echocardiography by measuring the peak systolic pressure gradient between the right ventricle and right atrium using the modified Bernoulli equation added to the estimated right atrial pressure. PH was considered present if PASP was ≥40 mm Hg.
All transthoracic echocardiographic images were obtained with commercially available ultrasound equipment. Echocardiograms included standard 2-dimensional, M-mode, spectral, color, and tissue Doppler and were performed in accordance with American Society of Echocardiography guidelines. Shunting was determined by intravenous injection of agitated saline contrast. Shunts were defined as ICSs if right-to-left shunting occurred within the first 4 cardiac cycles after the appearance of bubbles in the right atrium and intrapulmonary shunts if it occurred in >5 cardiac cycles. Provocative maneuvers (Valsalva and coughing) were performed to accentuate right-to-left shunting if present. Studies were evaluated by board-certified cardiologists trained in echocardiography.
Primary outcomes were short- and long-term moralities. Short-term (30-day) mortality was determined from medical record review and data from our institution’s liver transplant registry. Long-term mortality (mean follow-up 41 months) was determined using the Social Security Administration Death Index and medical records. Strokes were diagnosed based on clinical examination during the perioperative period and imaging was performed based on clinical suspicion. The perioperative period constituted the index LT hospitalization from time of admission to discharge.
Results were expressed as mean ± SD unless otherwise specified. Comparisons were made using Fisher’s exact test for nominal variables. Unpaired t tests were used for comparison of continuous variables. Univariate analyses were performed to determine the relation between echocardiographic variables and the specified outcomes. MedCalc 11.0 (MedCalc Software, Mariakerke, Belgium) was used for analysis and a p value <0.05 was considered statistically significant for all analyses.
Results
The total study population consisted of 502 consecutive patients with ESLD (318 men, mean age 55 ± 11 years). Baseline characteristics for the cohort are listed in Table 1 . There was a high prevalence of cardiovascular risk factors in all patients in the study population ( Table 1 ). Baseline echocardiographic measurements are listed in Table 2 . Rates of reported echocardiographic measurements in the total ESLD population included left ventricular end-diastolic and end-systolic dilatations in 7% and 6%, respectively, left atrial enlargement in 57%, left ventricular hypertrophy in 27%, right atrial enlargement in 6%, and right ventricular enlargement in 4%. Of the total study group, agitated saline contrast bubble studies were performed in 400 patients. Of these, ICSs were reported in 16% and intrapulmonary shunts in 41%. Diastolic dysfunction of any grade was present in 9% of subjects and PH in 25%. Severities of PH were mild in 66% (PASP 40 to 49 mm Hg), moderate in 30% (PASP 50 to 59 mm Hg), and severe in 4% (PASP >60 mm Hg). Differences among echocardiographic characteristics among different causes of ESLD were prevalent and are noted in Figure 1 .
Characteristic/Variable | |
---|---|
Age (years), mean ± SD | 55.4 ± 10.9 |
Men | 318 (63%) |
White | 473 (94%) |
Other | 29 (6%) |
History of hypertension | 201 (40%) |
History of hyperlipidemia | 69 (14%) |
Diabetes mellitus | 160 (32%) |
Smoker | 110 (22%) |
Family history of coronary artery disease | 57 (11%) |
Angiographic history of coronary artery disease | 105 (21%) |
Stroke | 15 (3%) |
Cause of end-stage liver disease | |
Viral hepatitis | 153 (31%) |
Alcoholic | 114 (23%) |
Nonalcoholic steatohepatitis | 66 (13%) |
Cryptogenic | 39 (8%) |
Other | 130 (26%) |
Complications of end-stage liver disease | |
Hepatic encephalopathy | 297 (59%) |
Esophageal varices | 307 (61%) |
Spontaneous bacterial peritonitis | 73 (15%) |
Hepatocellular carcinoma | 92 (18%) |
Model for end-stage liver disease, mean ± SD (range) | 22.3 ± 9.1 (6–47) |
Measurement | Mean ± SD (range) | Normal Range ⁎ |
---|---|---|
Left ventricular end-diastolic dimension (cm) | 4.6 ± 0.6 (2.4–6.7) | 3.5–5.5 |
Left ventricular end-systolic dimension (cm) | 3.0 ± 0.6 (1.4–5.1) | 2.5–4.0 |
Septal thickness (cm) | 1.1 ± 0.2 (0.6–2.0) | 0.7–1.2 |
Posterior wall thickness (cm) | 1.1 ± 0.2 (0.6–1.7) | 0.7–1.1 |
Aortic root size (cm) | 3.4 ± 1.1 (2.1–5.3) | 2.0–3.7 |
Left atrial dimension (cm) | 4.0 ± 0.6 (2.5–6.0) | 1.9–3.8 |
Ejection fraction (%) | 57.8 ± 4.2 (35–70) | >55 |
Pulmonary artery systolic pressure (mm Hg) | 35.9 ± 9.3 (17–68) | <40 |
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