Secondary pulmonary hypertension

Primary pulmonary hypertension is a disease of unclear etiology that is characterized by abnormally high mean pulmonary arterial pressures, in the absence of a demonstrable cause. A wide variety of pulmonary and cardiac diseases can lead to secondary pulmonary hypertension. 

Vascular changes include thickening of pulmonary vessels that may lead to endothelial dysfunction of the pulmonary arteries. Later, structural changes increase pulmonary pressures, especially during exercise. In severe COPD, secondary pulmonary hypertension leads to right-sided heart failure (cor pulmonale). 

Inhalation of aerosolized iloprost is being tested in patients with severe primary or secondary pulmonary hypertension refractory to conventional therapy. The aim is to produce predominantly pulmonary vasodilatation without significant systemic effects. In an uncontrolled series of 19 patients, the most common adverse effects of inhaled iloprost were coughing, nausea, edema, and thoracic pain (4). In most patients, these effects were transient and rarely required a change in therapy. 

Prostacyclin lowers peripheral, pulmonary, and coronary resistance. It has been used to treat both primary pulmonary hypertension and secondary pulmonary hypertension, which sometimes occurs after mitral valve surgery. A commercial preparation of prostacyclin (epoprostenol) is approved for treatment of primary pulmonary hypertension, in which it appears to improve symptoms and prolong survival. However, because of its extremely short plasma half-life, the drug must be administered as a continuous intravenous infusion through a central line. Several prostacyclin analogs with longer half-lives have been developed and treprostinil was recently approved for use in pulmonary hypertension (Horn, 2002). This drug is administered by continuous subcutaneous infusion. 

Secondary Pulmonary Hypertension. Secondary pulmonary hypertension is seen in some heart transplant candidates, and documenting the potential for reversibility when the primary defect is corrected is important in selecting appropriate heart transplant candidates and liver transplant patients as well. Aerosolized prostacyclin has been shown at least as effective as inhaled NO 40 ppm for this purpose in heart transplant candidates [170], while aerosolized epoprostenol has been shown similarly useful in liver transplant candidates. Delivery of iloprost was faster with an ultrasonic nebulizer but equally efficacious as compared to a jet nebulizer [171]. The role of aerosolized prostacyclin and related medications for pulmonary hypertension and for diagnostic evaluation of transplant candidates remains to be proven. Certainly, a successful aerosol treatment for pulmonary hypertension would be well received because of the inconvenience of the current method of constant infusion via an indwelling catheter. From an economic viewpoint, the market is small, so the chance of recovery of investment in new treatment would be limited. 

The consequences of long-standing COPD and chronic hypoxemia include the development of secondary pulmonary hypertension that progresses slowly if appropriate treatment of COPD is not initiated. Pulmonary hypertension is the most common cardiovascular complication of COPD and can result in cor pulmonale, or right-sided heart failure. ... 

The clinical consequences of significant mitral regurgitation are numerous and include impaired quality of life (particularly with dyspnea and fatigue on exertion), left ventricular enlargement and dysfunction, arrhythmias such as atrial fibrillation, secondary pulmonary hypertension and sudden cardiac death. Concomitant mitral regurgitation can be particularly deleterious in patients with either congestive heart failure or ischemic heart disease (15,16). 

Treatment strategies for progressive pulmonary venous hypertension should focus on treatment of the underlying disease. For patients with advanced decompensated systolic heart failure and secondary pulmonary hypertension, it is essential to reduce the pulmonary vascular resistance prior to heart transplantation to prevent acute RV failure of the donor heart. The use of continuous milrinone, occasionally nesirit-ide, and earlier intervention with mechanical circulatory device support (19) as a bridge to cardiac transplantation is considered a standard approach for this group of patients. Earlier intervention with valve repair or replacement for patients with mitral valve disease and aortic valve disease with associated pulmonary hypertension is recommended. 

Lewis GD, Shah R, Shahzad K, et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation 2007 116 1555-62. 

McLaughlin VV,GenthnerDE,Panella MM, etal. Compassionate use of continuous prostacyclin in the management of secondary pulmonary hypertension a case series. Ann Intern Med 1999 130(9) 740-3. 

Other animal models have been employed to more closely mimic IPF that can follow an acute lung injury. In this syndrome, the pulmonary fibrosis occurs as a result of a severe lung injury (acute lung injury/ARDS), resulting in severe complications, with secondary pulmonary hypertension and... 

Sexton P, Wilsher ML. Secondary pulmonary hypertension. Respir Med CME 2010 3 1-9. 

Idiopathic pulmonary fibrosis Alpha-l-antitrypsin deficiency Primary pulmonary hypertension Re-transplantation Secondary pulmonary hypertension Lymphangioleiomyomatosis Langerhans cell histiocytosis Sarcoidosis... 

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