nearly three decades have passed since the first successful clinical lung transplant was performed and has become the preferred treatment option for a variety of end - stage pulmonary parenchymal or pulmonary vascular disorders . due to the shortage of available organs as well as the advancement of disease in most transplant candidates ,
a full array of preoperative tests is needed in order to consider these patients appropriate applicants .   as part of the preoperative workup of these patients , investigation of cardiac function with echocardiography and catheterization
has been long considered the norm , yet predictors of outcome from these tests are not well defined . the risk posed by cardiac dysfunction
must be assessed individually based on severity of disease , presence of end - organ damage , and ease of control with standard therapies .
patients with moderate or severe ventricular systolic dysfunction are typically excluded from lung transplantation ; however , there is a paucity of data regarding the prognostic significance of abnormal left ventricular diastolic function or elevated pulmonary pressures .
the study was approved by the university of california , los angeles ( ucla ) institutional review board .
all patients who underwent a bilateral or unilateral lung transplant at ucla medical center from 2002 to 2009 were analyzed ( 394 patients ) by chart review in order to evaluate the prognostic significance of preoperative markers of diastolic function , including invasively measured pulmonary capillary wedge pressure ( pcwp ) and echocardiographic variables of diastolic dysfunction .
diastolic dysfunction was assessed by traditional echocardiographic variables of abnormal diastolic function , including a > e and a > e. criteria for lv diastolic dysfunction were obtained from the 2009 ase guidelines .
exclusion criteria included any patients undergoing re - transplant , patients with lack of presurgical echocardiographic or catheterization data performed at ucla , and patients with systolic left ventricular function less than 40% were excluded .
we identified 111 patients who had pretransplant echocardiographic as well as catheterization data performed at ucla medical center .
echocardiographic information was rereviewed by a blinded cardiologist ( ja ) to ensure the accuracy of the reports .
additionally , pulmonary artery pressures from preoperative catheterizations were analyzed to assess adverse clinical events posttransplant .   for comparing time until each clinical endpoint between groups ,
p values were computed utilizing cox proportional hazards models . for comparing differences between the nondiastolic dysfunction and diastolic dysfunction groups , p values
were calculated using the t - test for quantitative variables or chi - square test for categorical predictors .
if the sample size was too small for the chi - square approximation to be accurate , fisher 's exact test was used instead .
the kruskal - wallis test was used for subgroup analysis of primary lung pathology due to the skewed distribution of these variables .
if a significant effect was observed , follow - up pairwise wilcoxon rank sum tests with dunn - sidak adjusted p values were used to test for specific differences between groups .
all statistical analyses and plots were performed using r ( version 2.13.1 ) and ibm spss ( version 19 ) .
subjects ranged from 22 to 70 years of age ( 62 male and 49 female ) and were transplanted for a variety of disease processes including forty - three cases of idiopathic pulmonary fibrosis , twenty - two of chronic obstructive pulmonary disease , twelve of scleroderma , eight of sarcoidosis , eight of usual interstitial pneumonia , eight of isolated pulmonary hypertension , four of cystic fibrosis , four of various rare etiologies , and two of alpha-1 antitrypsin deficiency cases .   in all , 29 ( 26.1% ) patients met criteria for diastolic dysfunction .  
kaplan - meier curves were constructed , which did not show statistically significant differences of survival between diastolic dysfunction and normal diastolic function groups for all investigated endpoints ( figure 1 ) .
comparative boxplots were constructed which showed no difference in mortality between each subtype of diastolic dysfunction ( figures 2 and 4 ) .  
catheterization data was reviewed and based upon this information , 20 ( 19.8% ) patients were categorized into mildly elevated pcwp ( 1620  mmhg ) and 9 ( 8.9% ) patients with moderate / severely elevated pcwp ( > 20  mmhg ) ( table 2 ) .
mildly and moderately / severely elevated pretransplant pcwps were not associated with adverse clinical events posttransplant ( p = 0.30 ) ( figure 3 ) .
additionally , catheterization profile data between diastolic and nondiastolic dysfunctions did not reveal any statistically significant variables between the two groups , including systolic pulmonary artery pressures ( spap ) ( p = 0.77 ) , diastolic pulmonary artery pressures ( dpap ) ( p = 0.68 ) , mean pulmonary artery pressures ( mpap ) ( p = 0.84 ) , mean pcwp ( p = 0.17 ) , cardiac output ( p = 0.23 ) , cardiac index ( p = 0.21 ) , and left ventricular ejection fraction ( p = 0.99 ) ( table 3 ) .
lastly , a subgroup analysis of primary lung pathology did reveal did not reveal any mortality difference between groups ( p = 0.176 ) ( table 4 ) ( figure 5 ) . based upon kruskal - wallis test with dunn - sidak adjusted pairwise comparisons ,
pulmonary artery pressures were elevated and statistically significant in the pulmonary artery hypertension group in comparison with other groups . additionally , mean pcwp was statistically lower in the chronic obstruction pulmonary disease group when compared to other groups ( p = 0.05 ) .
over the last twenty years , there has been a steady growth in the number of lung transplant operations performed worldwide with concurrent improvement in both short - and long - term outcomes .
various studies have shown some utility in the preoperative workup of certain variables that may exclude certain candidates from lung transplant .
strong negative predictors of one year survival include use of extracorporeal membrane oxygenation , renal failure , age , total bilirubin > 2.0  mg / dl , cardiac index < 2  l / min , steroid dependence , smoking , and body mass index [ 46 ] .
however , pre - existing coronary artery disease has been shown to have acceptable early and medium - term outcomes .
overall , many guidelines have been developed to help risk - stratify candidacy of potential transplant recipients ; however , there has been a lack of data regarding short- and long - term outcomes of left ventricular diastolic dysfunction as well as elevated pcwp .
given the scarcity of organs as well as the fact that nearly 20% of lung transplant recipients die within the first year of transplantation , we may be failing to identify those at high risk for severe early complications .  
, the mitral inflow velocity profile is used to characterize left ventricular ( lv ) filling dynamics . the e velocity ( e )
represents the early mitral inflow velocity and is influenced by the relative pressures between the left atrium ( la ) and lv , which , in turn , are dependent on multiple variables including la pressure , lv compliance , and the rate of lv relaxation .
the a velocity ( a ) represents the atrial contractile component of mitral filling and is primarily influenced by lv compliance and la contractility . in a less compliant heart , a greater proportion of this blood is pushed into the ventricles during atrial systole . in this scenario ,
the emphasis of ventricular filling during late diastole increases the ( a ) component of the e / a ratio causing a reversal of the ratio , hence an indication of diastolic dysfunction . left atrial volume has also been described as an excellent biomarker of the chronicity of diastolic dysfunction and of cardiovascular disease risk .
parameters of diastolic function such as early diastolic velocities measured as e prime ( e ) , the e to late diastolic filling ( a ) ratio ( e/a ) , and the transmitral to mitral annular early diastolic velocity ratio ( e / e )   have all been shown to predict mortality and cardiovascular events [ 13 , 14 ] .
the early diastolic velocity of the mitral valve annulus ( e ) reflects the rate of myocardial relaxation .
when combined with measurement of the early transmitral flow velocity ( e ) , the resultant ratio ( e / e ) correlates well with mean left ventricular end - diastolic pressure , hence a marker for la pressure .  
left ventricular diastolic dysfunction is a relatively common finding seen on doppler echocardiography ; while multiple studies demonstrate abnormal diastolic function assessment to be associated with increased cardiovascular comorbidity , it can hold varying prognostic significance depending on underlying cardiac ventricular function .
it has been shown that mortality is higher in hospitalized patients with depressed left ventricular ejection fractions of less than 39% .
additionally , diastolic dysfunction has been recognized as a strong predictor of mortality in acute myocardial infarction and congestive heart failure [ 1720 ] . however , isolated diastolic dysfunction has significant clinical implications as well .
there is much heterogeneity regarding the prognosis of patients with diastolic dysfunction , with mortality ranging from 1.3% to 17.5% .
multiple studies have shown prognostic significance of doppler indexes of left ventricular diastolic dysfunction where patterns of abnormal relaxation increase the risk of cardiovascular events [ 2225 ] . in one study among 3,107 patients undergoing cardiac catheterization , the small subgroup ( 1.7% ) with diastolic dysfunction , defined as those with high lv end - diastolic pressure and no systolic dysfunction , coronary heart disease or lv dilation had a high risk of future cardiac morbid events .
this association between echocardiographic markers of abnormal relaxation and decreased survival , even in those with no history of chf , suggests that echocardiography may help identify those who are predisposed to adverse outcomes .
given that many lung transplant candidates are excluded with systolic depression , further evaluation of isolated diastolic dysfunction may help identify those at high risk for complications .
there has been much investigation into doppler echocardiography and comparison with swan - ganz catheterization measurements .
studies have shown that hemodynamic data acquired by echocardiography , including estimation of right atrial , pulmonary artery systolic , and pcwps ; cardiac output ; and pulmonary vascular resistance , correlate to those of invasive catheterization values [ 27 , 28 ] . although correlation is good , estimation of systolic pulmonary artery pressure by echocardiography
is frequently inaccurate in patients with advanced lung disease and leads to considerable over - diagnosis of pulmonary hypertension [ 29 , 30 ] .
in addition , technical limitations of the echocardiogram in this patient population often preclude estimating pulmonary artery systolic pressure .
although echocardiography can help estimate preoperative variables for lung transplant candidates , it should be used in conjunction with invasive catheterization rather than replacing it as the sole cardiac assessment modality .
ben - dor and associates have shown that the prevalence of significant coronary artery disease ( cad ) among lung transplant candidates may be low but can not be accurately predicted by risk factors .
the presence of preoperative mild or moderate cad has been shown not to result in increased perioperative morbidity or mortality or significantly affect the short - term or long - term survival in comparison with recipients without cad .  
transplantation remains the only therapeutic option for selected patients with advanced pulmonary arterial hypertension ( pah ) who continue to deteriorate despite optimal medical therapy .
given the current shortage of donor organ availability worldwide , there is a need for inclusion of more discriminatory markers of pah prognosis in donor - lung allocation scores to identify patients at risk and optimize survival to transplantation .
have demonstrated that increased preoperative pah is an independent risk factor for the development of grade 3 primary graft dysfunction within the first 48 hours after transplant .
additional studies have also shown this correlation between elevated pah and primary graft dysfunction [ 3639 ] . the relatively high early ( 30 days and 3 months )
mortality in pah lung transplant recipients in part reflects primary graft dysfunction , a syndrome characterized by noncardiogenic pulmonary edema , hypoxemia , and diffuse alveolar damage within the first 72 hours following lung transplant [ 37 , 4042 ] . because most pah patients are receiving chronic warfarin
further , following single lung transplant , allograft blood flow is increased in patients with a preoperative diagnosis of pah compared with emphysema [ 34 , 43 ] .
hence , estimation of pah variables is a critical component in the lung transplant workup . despite these previous studies ,
our data reveals no end - point difference between patients with normal , mildly elevated , and moderate - severely elevated pah .
although no statistically significant difference is found , there is indeed a unfavorable trend with regard to mortality in pulmonary hypertension patients .
given the small power in this subgroup analysis , further analysis of this patient population is necessary to access its clinical impact .
the objectives of therapy for left ventricular diastolic dysfunction include improvement of preload and afterload hemodynamics .
ace inhibitors and angiotensin inhibitors may provide some additional benefit given their reduction in both pre- and afterload as well as interstitial fibrosis .
additionally , heart rate control is also imperative given its prolongation of left ventricular filling to counterbalance the resistance of inflow due to the stiffened ventricle .  
this is a retrospective single - center review and has inherent limitations associated with all retrospective studies .
the lung transplant patients are also highly selected in accordance with our selection protocol . as a result , there may have been a selection bias as the study does not include recipients and experience from other centers .   in summary , there are many different factors that need to be accounted for when deciding to evaluate and list patients for lung transplantation .
a team approach incorporating the surgeon , pulmonologist , and cardiologist is necessary to ensure optimum outcomes in this difficult and challenging group of patients .
pretransplant recipient variables significantly influence early and late survival following lung transplantation , suggesting that some patients face a higher than average risk of mortality during the first year after transplant , as well as severely diminished longer - term survival , that challenges the goals of equitable organs allocation .
further investigation regarding transplant variables are needed to help develop better guidelines , which will ultimately help with optimal utilization of these scarce organs .
the present study demonstrates that prelung transplant invasive and echocardiographic findings of elevated pulmonary pressures , and abnormal left ventricular diastolic function are not predictive of adverse posttransplant clinical events .
 
 background . orthotopic lung transplantation 
 is now widely performed in patients with advanced lung disease . 
 patients with moderate or severe ventricular systolic dysfunction are typically excluded from lung transplantation ; however , there is a paucity of data regarding the prognostic significance of abnormal left ventricular diastolic function and elevated pretransplant pulmonary pressures . methods . 
 we reviewed the characteristics of 111 patients who underwent bilateral and unilateral lung transplants from 200 to 2009 in order to evaluate the prognostic significance of preoperative markers of diastolic function , including invasively measured pulmonary capillary wedge pressure ( pcwp ) and echocardiographic variables of diastolic dysfunction including mitral a > e and a > e. results . 
 out of 111 patients , 62 were male ( 56% ) and average age was 54.0  10.5 years . 
 traditional echocardiographic doppler variables of abnormal diastolic function , including a > e and 
 a > e , did not predict adverse events ( p = 0.49 ) . 
 mildly elevated pretransplant pcwp ( 1620  mmhg ) and moderately / severely elevated pcwp ( > 20  mmhg ) were not associated with adverse clinical events after transplant ( p = 0.30 ) . 
 additionally , all clinical endpoints did not show any statistical significance between the two groups 
 . conclusions . 
 pre - lung transplant invasive and echocardiographic findings of elevated pulmonary pressures and abnormal left ventricular diastolic function are not predictive of adverse posttransplant clinical events . 