Low Sodium Predicts Worse Prognosis in Pulmonary Arterial Hypertension
By Charles Bankhead
PHILADELPHIA, 14 june 2008-- Hyponatremia in patients with pulmonary arterial hypertension portends advanced right heart failure and poor survival, investigators here found.
As compared with patients who had normal sodium levels, those with hyponatremia had more symptomatic heart failure, more peripheral edema, and higher hospitalization rates, Paul R. Forfia, M.D., of the University of Pennsylvania, and colleagues reported in the June 15 issue of the American Journal of Respiratory and Critical Care Medicine.
"Serum sodium has important implications regarding the right heart dysfunction, clinical right heart failure, and patient outcome, and should not be overlooked in the clinical assessment of patients with [pulmonary arterial hypertension]," the authors concluded.
Hyponatremia is a recognized marker of advanced left heart failure and is an independent predictor of poor outcome, but the influence of hyponatremia in pulmonary arterial hypertension and right heart failure is less clear, the authors said.
Given the prevalence and prognostic significance of right heart failure in pulmonary arterial hypertension, Dr. Forfia and colleagues examined the impact of hyponatremia on right-sided failure and prognosis.
They prospectively followed 40 patients with pulmonary arterial hypertension, 13 of whom had hyponatremia, defined as ≤136 mEq/L.
Mean pulmonary artery pressure was 49 mm Hg in patients with hyponatremia and 47 mm Hg in those with normal sodium levels.
Compared with the 27 patients who had normal sodium levels, hyponatremic patients differed significantly with respect to:
Prevalence of World Health Organization class III/IV heart failure, 11 of 13 versus 12 of 27, P=0.02
Prevalence of peripheral edema, 69% versus 26%, P=0.009
Hospitalization rate, 85% versus 41%, P=0.009
Right atrial pressure, 14 versus 9 mm Hg, P<0.001
Stroke volume index, 21 versus 32 ml/m2, P<0.01
Right:Left ventricular area ratio, 1.8 versus 1.3, P<0.001
Tricuspid annular plane systolic excursion, 1.4 versus 2.0 cm, P=0.001
The one- and two-year estimated survival was 93% and 85% in the normonatremic patients versus 38% and 15% in those with hyponatremia (P<0.001).
Hyponatremic patients had an unadjusted mortality hazard ratio of 10.16 versus patients with normal sodium and had a median survival of 8.5 months.
Hyponatremia remained an independent predictor of outcome after adjustment for WHO class, diuretic use, right atrial pressure, and cardiac index.
"Our findings are consistent with prior studies showing that the prognostic significance of [hyponatremia] in patients with [left heart failure] occurs independent of hemodynamics and other measures of ventricular dysfunction," the authors said.
"Taken together, our data suggest that a low serum sodium concentration in [pulmonary arterial hypertension] is an integrative measure that signifies a syndrome of right heart dysfunction and ensuing circulatory maladaptation, analogous to the pathophysiologic paradigm of [left heart failure]."
The authors pointed out several limitations of the study, including the fact that for more than half of the patients, pulmonary hypertension was associated with connective tissue disease. "This population has been shown by our group and others to have worse survival when compared with patients with idiopathic [pulmonary arterial hypertension]," they said.
"Thus, our survival and hazard analyses may be biased by inclusion of a population of patients who were more likely to die, regardless of serum sodium, and thus our findings may be less applicable to other [pulmonary arterial hypertension] populations."
They said that their survival analyses may have also been skewed by lead-time bias because patients with established disease may have been more likely to die in the follow-up period than newly diagnosed patients.
The authors declared no conflicts of interest.
Primary source: American Journal of Respiratory and Critical Care MedicineSource reference:Forfia PR, et al "Hyponatremia predicts right heart failure and poor survival in pulmonary arterial hypertension" Am J Respir Crit Care Med 2008; 177: 1364-1369.
Showing posts with label Pulmonary Arterial Hypertension. Show all posts
Showing posts with label Pulmonary Arterial Hypertension. Show all posts
Saturday, June 14, 2008
Wednesday, June 20, 2007
Guidelines Updated for Treatment of Pulmonary Arterial Hypertension
June 19, 2007 — The American College of Chest Physicians provides an update of the evidence-based treatment recommendations for patients with pulmonary arterial hypertension. The new guidelines are published in the June issue of Chest.
"Pulmonary arterial hypertension (PAH), defined as a mean pulmonary artery pressure (PAPm) ≥ 25 mm Hg with a pulmonary capillary wedge pressure ≤ 15 mm Hg measured by cardiac catheterization, is a disorder that may occur either in the setting of a variety of underlying medical conditions or as a disease that uniquely affects the pulmonary circulation," write David B. Badesch, MD, FCCP, from the University of Colorado Health Sciences Center in Denver, and colleagues. "Irrespective of its etiology, PAH is a serious and often progressive disorder that results in right ventricular dysfunction and impairment in activity tolerance, and may lead to right-heart failure and death. The pathogenesis of PAH is complex and incompletely understood, but includes both genetic and environmental factors that alter vascular structure and function."
Since a consensus panel convened by the American College of Chest Physicians developed guidelines for PAH treatment that were published in 2004, several important clinical trials have been published and new treatments have received regulatory approval. Add-on and combination therapy are being explored as potential new therapeutic options.
These updated guidelines, taking into consideration studies published before September 1, 2006, provide a summary of the original guidelines, a discussion of new studies, and a revised treatment algorithm taking into account recent developments in therapy.
"Due to the complexity of the diagnostic evaluation required and the treatment options available, referral of patients with PAH to a specialized center continues to be strongly recommended," the authors write. "The pace of developments in the treatment for PAH has quickened, with several important clinical trials having been published over the past 2 years that have led to regulatory approval of newer drugs and experience with combinations of existing drugs. These advances are likely to impact on the way physicians should now approach the treatment of PAH."
The treatment algorithm provided summarizes the current approach to therapy for PAH, based on functional class. However, the authors note that functional class is difficult to quantify, may vary among patients and care providers, and may not always correlate with other indexes of disease severity, although it does correlate with outcome (in patients with IPAH [idiopathic PAH]).
When making decisions regarding treatment, one should therefore consider not only functional class but also cardiopulmonary hemodynamics, 6-minute walk distance, signs and symptoms of right-sided heart failure, adverse effect profile, and drug-drug interactions, as well as cost.
Functional class II: The only treatments currently approved for patients with PAH in functional class II are sildenafil and subcutaneous and intravenous treprostinil. Because of the ease of administration and relative efficacy, sildenafil may be the first choice for most of these patients. Clinical trials with sitaxsentan and ambrisentan have included patients with PAH in functional class II, and a trial with bosentan is ongoing. Patients should be encouraged to enroll in clinical trials.
Functional class III: For the treatment of patients with PAH in functional class III, there are now 5 drugs approved by the US Food and Drug Administration, in 3 therapeutic classes, allowing rational therapeutic decisions based on available evidence, knowledge of an individual patient's specific situation, clinical judgment, and patient preferences.
For patients with "early" PAH in functional class III, most experts now consider 1 of the 2 approved oral therapies (bosentan or sildenafil, listed in no specific order). When choosing between these agents, one should take into account relative toxicities (eg, patients with hepatic abnormalities may do better with sildenafil, whereas patients with ocular disease or recurrent epistaxis may do better with bosentan). Sildenafil is generally less expensive.
Patients with more advanced class III disease may need a prostanoid, such as intravenous epoprostenol or treprostinil, inhaled iloprost, or subcutaneous treprostinil. While awaiting additional evidence regarding the use of add-on and combination therapy, one might consider these in the context of enrollment into clinical trials.
Functional class IV: All currently labeled therapies are approved for patients with PAH in functional class IV. However, based on the quality of the evidence and the net risk-benefit profile, the guidelines strongly recommend intravenous epoprostenol as the treatment of choice. Most experts are familiar with how to titrate intravenous epoprostenol in the acute setting, and it has a rapid and predictable onset of action.
As experience with intravenous treprostinil is accumulating, this may be a suitable alternative to intravenous epoprostenol in some cases. Except for patients who refuse intravenous therapy or who are not capable of managing the complex delivery system, oral, subcutaneous, and inhaled agents should generally not be used as first-line therapy for patients with PAH in functional class IV.
"Recommendations regarding therapy obviously need to be applied in light of the individual patient's specific situation," the authors conclude. "The importance of a thorough diagnostic evaluation, looking for underlying causes and contributing factors, cannot be overemphasized. Educational efforts have contributed to improved recognition of PAH, facilitating earlier initiation of therapy [which] should contribute to better clinical outcomes."
Some of the authors have disclosed various financial relationships with pharmaceutical companies and organizations, including the National Institutes of Health, GlaxoSmithKline, United Therapeutics/LungRx, and Actelion. A complete listing of financial relationships is available in the original article.
Chest. 2007;131:1917-1928.
"Pulmonary arterial hypertension (PAH), defined as a mean pulmonary artery pressure (PAPm) ≥ 25 mm Hg with a pulmonary capillary wedge pressure ≤ 15 mm Hg measured by cardiac catheterization, is a disorder that may occur either in the setting of a variety of underlying medical conditions or as a disease that uniquely affects the pulmonary circulation," write David B. Badesch, MD, FCCP, from the University of Colorado Health Sciences Center in Denver, and colleagues. "Irrespective of its etiology, PAH is a serious and often progressive disorder that results in right ventricular dysfunction and impairment in activity tolerance, and may lead to right-heart failure and death. The pathogenesis of PAH is complex and incompletely understood, but includes both genetic and environmental factors that alter vascular structure and function."
Since a consensus panel convened by the American College of Chest Physicians developed guidelines for PAH treatment that were published in 2004, several important clinical trials have been published and new treatments have received regulatory approval. Add-on and combination therapy are being explored as potential new therapeutic options.
These updated guidelines, taking into consideration studies published before September 1, 2006, provide a summary of the original guidelines, a discussion of new studies, and a revised treatment algorithm taking into account recent developments in therapy.
"Due to the complexity of the diagnostic evaluation required and the treatment options available, referral of patients with PAH to a specialized center continues to be strongly recommended," the authors write. "The pace of developments in the treatment for PAH has quickened, with several important clinical trials having been published over the past 2 years that have led to regulatory approval of newer drugs and experience with combinations of existing drugs. These advances are likely to impact on the way physicians should now approach the treatment of PAH."
The treatment algorithm provided summarizes the current approach to therapy for PAH, based on functional class. However, the authors note that functional class is difficult to quantify, may vary among patients and care providers, and may not always correlate with other indexes of disease severity, although it does correlate with outcome (in patients with IPAH [idiopathic PAH]).
When making decisions regarding treatment, one should therefore consider not only functional class but also cardiopulmonary hemodynamics, 6-minute walk distance, signs and symptoms of right-sided heart failure, adverse effect profile, and drug-drug interactions, as well as cost.
Functional class II: The only treatments currently approved for patients with PAH in functional class II are sildenafil and subcutaneous and intravenous treprostinil. Because of the ease of administration and relative efficacy, sildenafil may be the first choice for most of these patients. Clinical trials with sitaxsentan and ambrisentan have included patients with PAH in functional class II, and a trial with bosentan is ongoing. Patients should be encouraged to enroll in clinical trials.
Functional class III: For the treatment of patients with PAH in functional class III, there are now 5 drugs approved by the US Food and Drug Administration, in 3 therapeutic classes, allowing rational therapeutic decisions based on available evidence, knowledge of an individual patient's specific situation, clinical judgment, and patient preferences.
For patients with "early" PAH in functional class III, most experts now consider 1 of the 2 approved oral therapies (bosentan or sildenafil, listed in no specific order). When choosing between these agents, one should take into account relative toxicities (eg, patients with hepatic abnormalities may do better with sildenafil, whereas patients with ocular disease or recurrent epistaxis may do better with bosentan). Sildenafil is generally less expensive.
Patients with more advanced class III disease may need a prostanoid, such as intravenous epoprostenol or treprostinil, inhaled iloprost, or subcutaneous treprostinil. While awaiting additional evidence regarding the use of add-on and combination therapy, one might consider these in the context of enrollment into clinical trials.
Functional class IV: All currently labeled therapies are approved for patients with PAH in functional class IV. However, based on the quality of the evidence and the net risk-benefit profile, the guidelines strongly recommend intravenous epoprostenol as the treatment of choice. Most experts are familiar with how to titrate intravenous epoprostenol in the acute setting, and it has a rapid and predictable onset of action.
As experience with intravenous treprostinil is accumulating, this may be a suitable alternative to intravenous epoprostenol in some cases. Except for patients who refuse intravenous therapy or who are not capable of managing the complex delivery system, oral, subcutaneous, and inhaled agents should generally not be used as first-line therapy for patients with PAH in functional class IV.
"Recommendations regarding therapy obviously need to be applied in light of the individual patient's specific situation," the authors conclude. "The importance of a thorough diagnostic evaluation, looking for underlying causes and contributing factors, cannot be overemphasized. Educational efforts have contributed to improved recognition of PAH, facilitating earlier initiation of therapy [which] should contribute to better clinical outcomes."
Some of the authors have disclosed various financial relationships with pharmaceutical companies and organizations, including the National Institutes of Health, GlaxoSmithKline, United Therapeutics/LungRx, and Actelion. A complete listing of financial relationships is available in the original article.
Chest. 2007;131:1917-1928.
Monday, June 18, 2007
FDA Approves Ambrisentan (Letairis) for Pulmonary Arterial Hypertension
ROCKVILLE, Md., June 18 -- The FDA has approved ambrisentan (Letairis), an endothelin receptor antagonist, for pulmonary arterial hypertension (PAH).
The drug, which will be marketed as 5 mg and 10 mg tablets for once daily treatment of PAH, received expedited review as an orphan drug.
John Jenkins, M.D., director of FDA's Office of New Drugs, said ambrisentan is similar to bosentan (Tracleer), which is already approved for PAH but ambrisentan "offers the potential for fewer drug interactions." Patients taking ambrisentan must have monthly blood tests to check for potential liver injury.
The safety and effectiveness of ambrisentan were demonstrated in two randomized, double-blind, 12-week, placebo-controlled phase III clinical trials (ARIES-1 and ARIES-2) that enrolled 393 patients.
In ARIES-1 patients treated with 5 mg of ambrisentan increased six-minute-walk distance by a mean of 31 meters and a median of 27 meters compared with baseline (P =0.008). The 10-mg dose was associated with a mean increase of 51 meters and a median increase of 39 meters (P<0.001).
In ARIES-2, placebo-adjusted mean and median changes from baseline of 59 meters and 45 meters (P<0.001) were observed with the 5-mg dose.
Ambrisentan also significantly delayed time to clinical worsening of PAH, defined as death, lung transplantation, hospitalization for PAH, atrial septostomy, study withdrawal because of the addition of other PAH therapeutic agents, or study withdrawal because of early escape (progressive disease).
The most common side effects from ambrisentan, said the FDA, included swelling of legs and ankles, nasal congestion, sinusitis, and getting red in the face (flushing).
Ambrisentan should not be used by women who are pregnant or may become pregnant because the drug may cause birth defects.
Ambrisentan is manufactured by Gilead Sciences. Primary source: American Society of Clinical Oncology Independent Satellite SymposiumSource reference: "Targeted Therapies and Evolving Treatment Paradigms for Lung Cancer"
The drug, which will be marketed as 5 mg and 10 mg tablets for once daily treatment of PAH, received expedited review as an orphan drug.
John Jenkins, M.D., director of FDA's Office of New Drugs, said ambrisentan is similar to bosentan (Tracleer), which is already approved for PAH but ambrisentan "offers the potential for fewer drug interactions." Patients taking ambrisentan must have monthly blood tests to check for potential liver injury.
The safety and effectiveness of ambrisentan were demonstrated in two randomized, double-blind, 12-week, placebo-controlled phase III clinical trials (ARIES-1 and ARIES-2) that enrolled 393 patients.
In ARIES-1 patients treated with 5 mg of ambrisentan increased six-minute-walk distance by a mean of 31 meters and a median of 27 meters compared with baseline (P =0.008). The 10-mg dose was associated with a mean increase of 51 meters and a median increase of 39 meters (P<0.001).
In ARIES-2, placebo-adjusted mean and median changes from baseline of 59 meters and 45 meters (P<0.001) were observed with the 5-mg dose.
Ambrisentan also significantly delayed time to clinical worsening of PAH, defined as death, lung transplantation, hospitalization for PAH, atrial septostomy, study withdrawal because of the addition of other PAH therapeutic agents, or study withdrawal because of early escape (progressive disease).
The most common side effects from ambrisentan, said the FDA, included swelling of legs and ankles, nasal congestion, sinusitis, and getting red in the face (flushing).
Ambrisentan should not be used by women who are pregnant or may become pregnant because the drug may cause birth defects.
Ambrisentan is manufactured by Gilead Sciences. Primary source: American Society of Clinical Oncology Independent Satellite SymposiumSource reference: "Targeted Therapies and Evolving Treatment Paradigms for Lung Cancer"
Tuesday, April 24, 2007
New Strategies for Pulmonary Arterial Hypertension: Evaluation and Management
The availability of newer drugs for pulmonary arterial hypertension (PAH) has radically changed its management and significantly improved both quality of life and mortality for patients, according to a review published in the April issue of the Southern Medical Journal. This review highlights the presentation of PAH, the diagnostic approach, and treatment options.
"Pulmonary arterial hypertension (PAH), a rare disease involving the pulmonary vascular circuit, is defined as an elevation in pulmonary arterial pressures and is characterized by symptoms of dyspnea, chest pain, and syncope," write Anne V. LaRaia, MD, and Aaron B. Waxman, MD, PhD, from Massachusetts General Hospital, Harvard Medical School, in Boston, Massachusetts. "If left untreated, the disease carries a high mortality rate, with the most common cause of death being decompensated right-sided heart failure. Over the past 5 years, there have been significant advances in this field in regards to understanding the pathogenesis, diagnosis, and classification of PAH."
PAH is a progressive disease causing narrowing and occlusion of pulmonary blood vessels, and has an estimated median survival of approximately 2.8 years. Despite the development of newer medical therapies, therapeutic options remain limited, and treatment is aimed at improving quality of life and survival.
According to the National Institutes of Health Registry on Primary Pulmonary Hypertension, the definition of PAH is a mean pulmonary arterial pressure of 25 mm Hg or greater at rest, with pulmonary capillary wedge pressure of 15 mm Hg or less, and mean pulmonary arterial pressure greater than 30 mm Hg with exercise.
In 2003, the World Health Organization revised the classification of PAH into 5 categories based in part on etiology: pulmonary arterial hypertension, pulmonary venous hypertension, pulmonary hypertension associated with hypoxemia, pulmonary hypertension resulting from chronic thrombotic or embolic disease, and miscellaneous.
Pulmonary arterial hypertension includes idiopathic PAH; familial PAH; disease associated with collagen vascular disease, congenital systemic to pulmonary shunts, portal hypertension, HIV infection, drugs and toxins, or other diseases (glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy); and PAH associated with significant venous or capillary involvement (pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, and persistent pulmonary hypertension).
Pulmonary venous hypertension associated with left-sided heart disease includes left-sided atrial or ventricular heart disease and left-sided valvular heart disease.
Pulmonary hypertension associated with hypoxemia includes chronic obstructive pulmonary disease, interstitial lung disease, sleep-disordered breathing, alveolar hypoventilation disorders, long-term exposure to high altitude, and developmental abnormalities.
Pulmonary hypertension resulting from chronic thrombotic and/or embolic disease includes thromboembolic obstruction of proximal or distal pulmonary arteries, thromboembolic obstruction of distal pulmonary arteries, and pulmonary embolism caused by tumor, parasites, or foreign material.
The miscellaneous group of PAH includes sarcoidosis, histiocytosis X, lymphangiomatosis, and compression of pulmonary vessels by adenopathy, tumor, or fibrosing mediastinitis.
Whatever the cause, the common end result of processes leading to PAH is elevation of pulmonary artery pressures and vascular resistance, with resultant right-sided heart failure. Progressive dyspnea is almost a cardinal feature of PAH, sometimes accompanied by fatigue, syncope, or chest pain.
Diagnostic workup for PAH includes history focusing on the above features and physical examination findings of paradoxical splitting of the second heart sound, the murmur of pulmonic regurgitation and tricuspid regurgitation, right ventricle heave, increased jugular venous pressure with prominent V waves, hepatomegaly with pulsations of the liver, and lower extremity edema associated with right-sided heart failure.
Electrocardiographic changes may include right ventricular hypertrophy, right atrial enlargement, and right axis deviation. Pulmonary function testing, chest radiography including contrast computed tomography and ventilation perfusion scanning, and transthoracic echocardiography also may be helpful. The gold standard is right-sided heart catheterization.
Current wisdom concerning the endothelial dysfunction underlying PAH includes a decrease in nitric oxide and prostacyclin synthesis, and an increase in thromboxane and enthothelin-1 synthesis, resulting in the typical pathology of small vessel smooth muscle hypertrophy, adventitial and intimal proliferation, and plexiform vascular lesions resulting in vascular thrombosis. This physiological basis provides the rationale for many of the new treatment options.
"The availability of newer drugs has resulted in a radical change in the management of this disease with significant improvement in both quality of life and mortality," the authors write. "Ongoing research promises to lead to a more comprehensive understanding of the genetics, etiology, and pathogenesis of pulmonary arterial hypertension, which may ultimately translate into more effective therapeutic options."
"Pulmonary arterial hypertension (PAH), a rare disease involving the pulmonary vascular circuit, is defined as an elevation in pulmonary arterial pressures and is characterized by symptoms of dyspnea, chest pain, and syncope," write Anne V. LaRaia, MD, and Aaron B. Waxman, MD, PhD, from Massachusetts General Hospital, Harvard Medical School, in Boston, Massachusetts. "If left untreated, the disease carries a high mortality rate, with the most common cause of death being decompensated right-sided heart failure. Over the past 5 years, there have been significant advances in this field in regards to understanding the pathogenesis, diagnosis, and classification of PAH."
PAH is a progressive disease causing narrowing and occlusion of pulmonary blood vessels, and has an estimated median survival of approximately 2.8 years. Despite the development of newer medical therapies, therapeutic options remain limited, and treatment is aimed at improving quality of life and survival.
According to the National Institutes of Health Registry on Primary Pulmonary Hypertension, the definition of PAH is a mean pulmonary arterial pressure of 25 mm Hg or greater at rest, with pulmonary capillary wedge pressure of 15 mm Hg or less, and mean pulmonary arterial pressure greater than 30 mm Hg with exercise.
In 2003, the World Health Organization revised the classification of PAH into 5 categories based in part on etiology: pulmonary arterial hypertension, pulmonary venous hypertension, pulmonary hypertension associated with hypoxemia, pulmonary hypertension resulting from chronic thrombotic or embolic disease, and miscellaneous.
Pulmonary arterial hypertension includes idiopathic PAH; familial PAH; disease associated with collagen vascular disease, congenital systemic to pulmonary shunts, portal hypertension, HIV infection, drugs and toxins, or other diseases (glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy); and PAH associated with significant venous or capillary involvement (pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, and persistent pulmonary hypertension).
Pulmonary venous hypertension associated with left-sided heart disease includes left-sided atrial or ventricular heart disease and left-sided valvular heart disease.
Pulmonary hypertension associated with hypoxemia includes chronic obstructive pulmonary disease, interstitial lung disease, sleep-disordered breathing, alveolar hypoventilation disorders, long-term exposure to high altitude, and developmental abnormalities.
Pulmonary hypertension resulting from chronic thrombotic and/or embolic disease includes thromboembolic obstruction of proximal or distal pulmonary arteries, thromboembolic obstruction of distal pulmonary arteries, and pulmonary embolism caused by tumor, parasites, or foreign material.
The miscellaneous group of PAH includes sarcoidosis, histiocytosis X, lymphangiomatosis, and compression of pulmonary vessels by adenopathy, tumor, or fibrosing mediastinitis.
Whatever the cause, the common end result of processes leading to PAH is elevation of pulmonary artery pressures and vascular resistance, with resultant right-sided heart failure. Progressive dyspnea is almost a cardinal feature of PAH, sometimes accompanied by fatigue, syncope, or chest pain.
Diagnostic workup for PAH includes history focusing on the above features and physical examination findings of paradoxical splitting of the second heart sound, the murmur of pulmonic regurgitation and tricuspid regurgitation, right ventricle heave, increased jugular venous pressure with prominent V waves, hepatomegaly with pulsations of the liver, and lower extremity edema associated with right-sided heart failure.
Electrocardiographic changes may include right ventricular hypertrophy, right atrial enlargement, and right axis deviation. Pulmonary function testing, chest radiography including contrast computed tomography and ventilation perfusion scanning, and transthoracic echocardiography also may be helpful. The gold standard is right-sided heart catheterization.
Current wisdom concerning the endothelial dysfunction underlying PAH includes a decrease in nitric oxide and prostacyclin synthesis, and an increase in thromboxane and enthothelin-1 synthesis, resulting in the typical pathology of small vessel smooth muscle hypertrophy, adventitial and intimal proliferation, and plexiform vascular lesions resulting in vascular thrombosis. This physiological basis provides the rationale for many of the new treatment options.
"The availability of newer drugs has resulted in a radical change in the management of this disease with significant improvement in both quality of life and mortality," the authors write. "Ongoing research promises to lead to a more comprehensive understanding of the genetics, etiology, and pathogenesis of pulmonary arterial hypertension, which may ultimately translate into more effective therapeutic options."
Subscribe to:
Posts (Atom)