In patients who have lung diseases with respiratory failure—most notably patients with chronic obstructive pulmonary disease (COPD)—pulmonary hypertension and right ventricular dysfunction can develop. Such development has been attributed to increased right ventricular afterload because of pulmonary hypertension.
34,35 However, patients who have COPD and respiratory failure may also have LV diastolic dysfunction.
36 For example, a right ventricular pressure overload may cause a leftward displacement of the interventricular septum, which in turn may cause LV diastolic dysfunction.
37 However, in a dog model with pulmonary emphysema and hypoxia, LV diastolic dysfunction was present without septum bowing.
38 This finding suggests that intrinsic mechanisms in the LV myocardium participate in LV diastolic dysfunction.
38
There are many other causes of alveolar hypoxia that are responsible for right ventricular failure and LV diastolic dysfunction, such as obstructive sleep apnea (OSA) with or without obesity hypoventilation. Many obese patients with OSA also have essential hypertension and diabetes, placing them at increased risk for DHF. Currently, the pathophysiologic mechanisms linking OSA with diastolic dysfunction and DHF are not clearly understood. One explanation is that elevations in nocturnal blood pressure and sympathetic nervous system activity in patients who have OSA create ventricular pressure overload.
39,40 It is speculated that, as DHF occurs in patients who have other diseases, such as chronic hypertension and aortic stenosis, increased pressure overload at the cellular level results in decreased levels of SERCA and increased levels of phospholamban.
41 As stated earlier, increased pressure slows the removal of calcium from the cytosol, leading to impaired ventricular relaxation. In an experimental study,
42 ventricular pressure overload impaired myocardial relaxation. Concurrently, pressure overload causes activation of multiple cellular signals that create myocardial tissue hypertrophy and interstitial fibrosis, both of which increase passive stiffness.
43 In addition, impaired coronary flow reserve, which causes silent ischemia, worsens ventricular active relaxation when LV diastolic pressure begins to rise.
Another possible mechanism to explain the presence of diastolic dysfunction in patients who have pulmonary diseases relates to futile inspiratory efforts. Such efforts result in elevated negative intrathoracic pressure, leading to an increase in LV transmural pressure and enhanced ventricular afterload without an increase in systemic arterial pressure.
44 All of the aforementioned effects of enhanced negative intrathoracic pressure have been demonstrated to affect LV filling.
44,45 Abnormalities in diastolic function, substantially related to repetitive OSA events during sleep, are very common in patients with OSA. These alterations could be reversed, at least in part, with continuous positive airway pressure therapy.
46
Patients with a variety of diseases and DHF have different pressure-volume mechanisms involved in their pathology. At one end of the spectrum are patients who have heart failure on the basis of diastolic dysfunction, and at the other end are patients with arterial hypertension. In the latter group, hearts appear to be very mildly dilated, with little or no detectable abnormality of systolic or diastolic pressure-volume relationships, and subtle changes in total body volume may induce DHF.
47 Another scenario involves ischemic heart disease with or without minor myocardial infarction where mild systolic dysfunction is not evident by measurement of ejection fraction but is sufficient to induce a neurohormonal response that can lead to salt and water retention.
22,47