Pulmonary Arterial Hypertension in Women.

Pulmonary arterial hypertension (PAH) is characterized by pathological hemodynamic elevation in pulmonary artery pressure. Development of international registries over the last decade has raised awareness about the disease, leading to the development of new and improved therapies. Paradigm shifts such as these warrant review of existing literature regarding PAH, especially in females, as the disease continues to affect women more than males. The aim of this review is to provide an update on the classification, pathophysiology, diagnosis, and treatment of PAH while focusing specifically on its impact on women.

Update on the clinical utility of sildenafil in the treatment of pulmonary arterial hypertension.

Sildenafil is an orally administered phosphodiesterase type 5 inhibitor that is approved for the treatment of pulmonary arterial hypertension (PAH). The hemodynamic effects of sildenafil are mitigated primarily via potentiating the effects of endogenous nitric oxide, leading to smooth muscle cell relaxation and reductions in pulmonary arterial pressures and pulmonary vascular resistance. When added to standard background therapy in patients with idiopathic or associated PAH from congenital heart disease, anorexigen use, or connective tissue disease, sildenafil treatment results in improved exercise capacity as measured by 6 minute walk distance, improved hemodynamics, and favorable changes in quality of life. Sildenafil use is contraindicated with concomitant nitrate administration, and caution should be exercised when used in combination with antihypertensive agents due to risks of precipitating hypotension. Side effects are generally mild, and include flushing, headaches, and epistaxis. The combination of sildenafil with intravenous epoprostenol is safe and well tolerated, and further improves exercise capacity. Sildenafil is approved only for treatment of PAH, and although emerging data suggest a potential role in treating other types of pulmonary hypertension, larger trials are required to confirm these findings.

Noninvasive assessment of right ventricular function: will there be resurgence in radionuclide imaging techniques?

Right ventricular (RV) function is increasingly being recognized as an important prognostic marker in multiple cardiopulmonary disease states, including congestive heart failure, pulmonary arterial hypertension, and chronic obstructive pulmonary disease. Accurate and reproducible measures of RV function, although technically challenging, are highly relevant in the clinical setting. Radionuclide techniques (eg, first-pass radionuclide angiography for quantifying RV systolic function) were developed nearly 40 years ago. More recently, MRI and transthoracic echocardiography have become the diagnostic imaging techniques of choice for the noninvasive evaluation of RV function. However, developments in single photon emission computed tomography (SPECT), positron emission tomography (PET), and hybrid SPECT/CT and PET/CT systems have greatly improved the image quality and contrast resolution of radionuclide imaging of the heart, allowing for coregistered physiologic and anatomical information of the right ventricle in three dimensions. These improvements in cardiac imaging provide new opportunities for assessing RV myocardial perfusion, function, and anatomy in the same setting. Such imaging approaches may in the future provide assistance with proactive disease management, including early diagnosis of impending RV dysfunction in high-risk patients and for guiding decisions to initiate and/or modify treatments.

Sildenafil and assessment of pulmonary arterial reactivity in heart failure.

Pulmonary hypertension is a daunting accompaniment of advanced heart failure. Efforts to safely and consistently lower pulmonary vascular resistance are necessary but fraught with challenges. In this report the authors explore the novel use of sildenafil, an inhibitor of phosphodiesterase-5, in tackling pulmonary hypertension in heart failure. The salutary effects of this agent deserve further study.

Ethnic disparity in clinical outcome after heart transplantation is abrogated using tacrolimus and mycophenolate mofetil-based immunosuppression.

BACKGROUND: Black American heart transplant recipients receiving cyclosporine-based primary immunoprophylaxis suffer higher rates of allograft rejection with hemodynamic compromise, infections, and posttransplant coronary artery disease. We examined the hypothesis that a combination of tacrolimus and mycophenolate mofetil "resurrects" clinical outcome of black Americans to those seen in white heart transplant recipients. METHODS: Sixty-three adult primary heart transplant recipients were included in this study. Twenty black American and 21 white patients who received tacrolimus-based primary immunoprophylaxis were enrolled in this prospective, observational parallel cohort investigation. A separate group of 22 black American patients were randomly allocated to receive cyclosporine-microemulsion-based primary prophylaxis and served as the control population for assessing outcomes in the black American group. Adjunctive immunosuppression included mycophenolate mofetil and corticosteroids. The primary end-point was the freedom from allograft rejection requiring treatment at 1 year. Secondary end-points included rejection with hemodynamic compromise, and patient or graft survival. Adverse events evaluated included development of infections requiring hospitalization and nonimmunological outcomes including hyperlipidemia, hypertension, and diabetes mellitus (new onset or worsened). RESULTS: Tacrolimus-treated black American patients had greater freedom from allograft rejection requiring treatment at 1 year than those treated with cyclosporine (64% vs. 37%, P=0.01). No differences were noted between tacrolimus-treated black Americans and whites in the primary end point (64% and 67% respectively, P=nonsignificant [NS]). Tacrolimus-based immunosuppression was associated with better 1-year survival in black Americans compared with cyclosporine (95% vs. 73%, P=0.04), and this end point was similar to that achieved in tacrolimus-treated white heart transplant recipients (95%). No differences in infection rates were noted among either group. Cyclosporine-treated black Americans suffered more hyperlipidemia and worse hypertension than tacrolimus-treated patients. CONCLUSIONS: Compared with cyclosporine, an immunosuppressive strategy using tacrolimus in black Americans achieves superior efficacy with regard to allograft rejection, higher allograft survival, and similar safety. Furthermore, tacrolimus-based immunosuppression is similar in immunological efficacy and safety in black Americans and in white heart transplant recipients.