We report two patients with severe BPD whose clinical course was complicated by LVDD. Both patients had delayed recognition of LVDD. Although there were subtle findings of LVDD by echocardiogram, cardiac catheterization was required to make the diagnosis in both patients. Both experienced significant hemodynamic and clinical improvement with afterload reduction therapy.
These findings are interesting because they bring to light a potentially treatable cardiac complication of late BPD. Pulmonary edema and PH are known complications of severe BPD attributed to chronic inflammation and impaired pulmonary alveolar and vascular development. Thus, hemodynamic assessment of patients with BPD has focused on evaluation for PH and right sided function. However, left ventricular abnormalities have been associated with death in severe BPD (1
). Persistent late pulmonary edema, despite aggressive diuretic use, or worsening pulmonary edema in response to PH treatment with vasodilators such as iNO or sildenafil () are unexpected responses that may require cardiac catheterization to rule out left sided cardiac dysfunction or anatomic abnormalities, such as pulmonary venous obstruction. LVDD was found in our patients, and treatment with afterload reduction agents (although angiotensin-converting enzyme inhibitors likely have additional mechanisms of action) was associated with improved pulmonary status and subsequent weaning of ventilator support, oxygen, diuretics, and steroids.
LVDD is characterized by increased stiffness and abnormal relaxation of the ventricle, which leads to elevated LV filling pressures and abnormal early diastolic filling (6
). LVDD is difficult to diagnose because it produces signs and symptoms often attributed to the lung disease of BPD, and patients are not routinely screened for this complication. The diagnosis of LVDD in our patients was based on elevated LAP (or its surrogate, PCWP) in the absence of volume overload or evidence of LV systolic dysfunction. Volume overload is an unlikely cause for increased PCWP because both patients were aggressively managed to achieve an even or negative fluid balance around the time of hemodynamic assessment. Thus, although a PCWP of 12 mm Hg measured in patient 2 can be interpreted as being only mildly elevated, it likely represents a significant elevation given the aggressive fluid management. Even though elevated LAP can be due to either LV systolic or diastolic dysfunction or both, measures of systolic function by echocardiogram (percent fractional shortening and LV ejection fraction) appeared normal, suggesting LVDD as the predominant reason for elevated PCWP. A retrospective review of BPD patients undergoing cardiac catheterization at our institution (including the patients reported here) revealed a PCWP ≥ 12 mm Hg in 8 of 33 studies (26%) and ≥ 16 mm Hg in 4 of 33 (12%), suggesting that LVDD may not be uncommon in patients with severe BPD.
Although there are echocardiographic techniques, including Doppler tissue imaging (DTI), that may provide noninvasive assessments of diastolic dysfunction (3
), these techniques have not been well defined in infants and are not generally part of routine echocardiogram studies in patients with BPD. The profile of usual diastolic dysfunction by Doppler echocardiogram is characterized by a higher peak A wave (transmitral flow peak velocity during atrial contraction) than peak E wave (transmitral flow peak velocity of early diastole). Although this profile is considered normal in neonates, with advancing age, the ratio of peak E to peak A wave (E/A) progressively increases, which is interpreted as demonstrating the age-related maturation of myocardial compliance toward an adult pattern. Although pre-term infants may have delayed maturation (3
), prior Doppler studies in both patients had shown this normal progression (data not shown), but at the time of clinical deterioration and cardiac catheterization, the ratio had decreased, consistent with worsening diastolic function. Recently, DTI of the myocardium was used to assess regional myocardial function. The ratio of E to the early diastolic mitral annular tissue Doppler myocardial velocity (Ea), termed E/Ea, correlates with PCWP (7
). Although no specific cutoff values have been described in this population, the measurements performed in Case 1
appear consistent with diastolic dysfunction.
Mechanisms responsible for LVDD and physiological impact on BPD remain unclear, but LVH has been associated with dexamethasone treatment for the prevention of BPD in premature infants (2
). In these patients, LVH completely resolved after steroid discontinuation, but LV chamber size remained low in some infants, suggesting the possibility of persistent subclinical LVDD. Both patients reported here were exposed to systemic steroids, but only the patient in Case 2
was exposed to prolonged and repeated courses.
In summary, these cases suggest that LVDD can be an important complication of severe BPD, especially in patients who fail to respond to traditional therapies. High diagnostic suspicion is required for diagnosis, but treatment of LVDD may improve outcome for selected patients.