Hypertension: McGoon MD

McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J, Anonymous00029, Anonymous00030, Anonymous00031, Anonymous00032, Anonymous00033. · No affiliation provided · J Am Coll Cardiol. · Pubmed #19389575 No free full text.

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McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J, Harrington RA, Anderson JL, Bates ER, Bridges CR, Eisenberg MJ, Ferrari VA, Grines CL, Hlatky MA, Jacobs AK, Kaul S, Lichtenberg RC, Lindner JR, Moliterno DJ, Mukherjee D, Pohost GM, Rosenson RS, Schofield RS, Shubrooks SJ, Stein JH, Tracy CM, Weitz HH, Wesley DJ, Anonymous00037. · No affiliation provided · Circulation. · Pubmed #19332472 No free full text.

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Puri A, McGoon MD, Kushwaha SS. · King George's Medical University, Lucknow, India. · Nat Clin Pract Cardiovasc Med. · Pubmed #17522721 No free full text.

Abstract: The treatment of pulmonary arterial hypertension--once a lethal condition--has evolved considerably over the past few years as the number of therapeutic options available to treat this disease has increased. In this Review we attempt to summarize the current knowledge of the pathogenesis of pulmonary hypertension, in relation to the therapies presently available and those that could become available in the near future. The use of prostacyclin and its analogs, calcium-channel blockers, endothelin-receptor antagonists and phosphodiesterase type 5 inhibitors is reviewed. Newer concepts, such as the use of combination therapy, and the potential for long-term disease amelioration and improvement of outcomes, are also discussed. The role of supportive care and medications not specific to pulmonary hypertension is also examined. In addition, we review the novel emerging therapies, such as imatinib, fasudil, simvastatin, ghrelin and vasoactive intestinal peptide, which hold therapeutic potential for disease modification as well as treatment of symptoms.

Ryu JH, Krowka MJ, Pellikka PA, Swanson KL, McGoon MD. · Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · Mayo Clin Proc. · Pubmed #17352370 links to  free full text

Abstract: Pulmonary hypertension (PH) in patients with interstitial lung diseases (ILDs) is not well recognized and can occur in the absence of advanced pulmonary dysfunction or hypoxemia. To address this topic, we identified relevant studies in the English language by searching the MEDLINE database (1966 to November 2006) and by individually reviewing the references of identified articles. Connective tissue disease-related ILD, sarcoidosis, idiopathic pulmonary fibrosis, and pulmonary Langerhans cell histiocytosis are the ILDs most commonly associated with PH. Pulmonary hypertension is an underrecognized complication in patients with ILDs and can adversely affect symptoms, functional capacity, and survival. Pulmonary hypertension can arise in patients with ILDs through various mechanisms, Including pulmonary vasoconstriction and vascular remodeling, vascular destruction associated with progressive parenchymal fibrosis, vascular inflammation, perivascular fibrosis, and thrombotic angiopathy. Diagnosis of PH in these patients requires a high index of suspicion because the clinical presentation tends to be nonspecific, particularly in the presence of an underlying parenchymal lung disease. Doppler echocardiography is an essential tool in the evaluation of suspected PH and allows ready recognition of cardiac causes. Right heart catheterization is needed to confirm the presence of PH, assess its severity, and guide therapy. Management of PH in patients with ILDs is guided by identification of the underlying mechanism and the clinical context. An increasing number of available pharmacologic agents in the treatment of PH allow possible treatment of PH in some patients with ILDs. Whether specific treatment of PH in these patients favorably alters functional capacity or outcome needs to be determined.

McLaughlin VV, McGoon MD. · University of Michigan Health System, Ann Arbor, MI 48109-0273, USA. · Circulation. · Pubmed #17000921 links to  free full text

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McGoon MD. · Department of Cardiovascular Diseases, Pulmonary Hypertension Clinic, Mayo Clinic, Rochester, Minnesota, USA. · Clin Chest Med. · Pubmed #11590843 No free full text.

Abstract: The goals of evaluating pulmonary hypertension are detection, definition of severity and the nature of the hemodynamic lesion and its consequences, diagnosis of causal or associated conditions, and determination of optimal therapy. These objectives are reliably achieved by a disciplined approach employing multiple diagnostic tools. This chapter outlines the fundamental background and guidelines for assessing pulmonary hypertension, including consideration of several new and less frequently used methods to elucidate the physiologic mechanism. Since early detection and treatment may improve outcome, screening higher risk populations and a diagnostic approach to the milder spectrum of pulmonary hypertension is also addressed.

McGoon MD, Frost AE, Oudiz RJ, Badesch DB, Galie N, Olschewski H, McLaughlin VV, Gerber MJ, Dufton C, Despain DJ, Rubin LJ. · Mayo Clinic, Rochester, MN 55905, USA. · Chest. · Pubmed #18812445 No free full text.

Abstract: BACKGROUND: Some endothelin receptor antagonists (ERAs) are associated with liver function test (LFT) result abnormalities. However, ambrisentan has an incidence of serum aminotransferase levels more than three times the upper limit of normal (ULN), similar to that observed in PAH patients who are not receiving ERAs. Because ambrisentan may provide benefits in PAH patients who have discontinued ERA therapy due to LFT abnormalities, we evaluated the safety and efficacy of ambrisentan in this patient population. METHODS: Patients who previously discontinued bosentan and/or sitaxsentan due to LFT abnormalities received ambrisentan, 2.5 mg qd, for 4 weeks followed by 5 mg/d for 8 weeks. The primary end point was the incidence of aminotransferase levels more than three times ULN considered by the investigator to be related to ambrisentan and resulting in drug discontinuation. Secondary end points included aminotransferase levels more than five times ULN requiring drug discontinuation and more than three times ULN requiring dose reduction, as well as changes in 6-min walk distance (6MWD), Borg dyspnea index, World Health Organization functional class, and Short Form-36 health survey score. Patients continued treatment beyond the 12-week end point with monthly monitoring of LFTs. RESULTS: Thirty-six patients who previously discontinued bosentan (n = 31), sitaxsentan (n = 2), or both (n = 3) were enrolled. At baseline, 69.4% of patients were receiving prostanoid and/or sildenafil therapy. No patient had an aminotransferase level more than three times ULN that required ambrisentan discontinuation. One patient had a transient aminotransferase level more than three times ULN that resolved following a temporary dose reduction. No additional aminotransferase levels more than three times ULN were observed with long-term treatment (median exposure, 102 weeks), despite dose increases to 10 mg qd in more than half of the patients. Significant improvements in 6MWD and other efficacy assessments were observed. CONCLUSIONS: Ambrisentan treatment may be an option for patients who have discontinued bosentan and/or sitaxsentan therapy due to LFT result abnormalities. Trial registration: Clinicaltrials.gov Identifier NCT00423592.

Frantz RP, Benza RL, Kjellström B, Bourge RC, Barst RJ, Bennett TD, McGoon MD. · Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. · J Heart Lung Transplant. · Pubmed #18582809 No free full text.

Abstract: BACKGROUND: The purpose of this study was to determine whether an implantable hemodynamic monitor (IHM) could be used to judge the response of pulmonary arterial hypertension (PAH) patients to changes in therapy. METHODS: A prospective, non-randomized, multi-center study evaluated physical examination, functional class, echocardiography, brain natriuretic peptide (BNP) levels, exercise capacity assessed by 6-minute walk and cardiopulmonary exercise tests, and quality of life at baseline and at 12 weeks. IHM measurements were continuously available to clinicians between clinic visits. Based on a priori, pre-specified analyses, the relationships between hemodynamic values, PAH treatments and clinical parameters were tracked in an observational fashion. RESULTS: Twenty-four PAH patients underwent IHM implantation prior to a change in PAH therapy. IHM data identified 13 of the 15 patients who improved their 6-minute walk distance by >30 m at 12 weeks (+48 +/- 65 m, p < 0.05), whereas the others walked less (-78 +/- 115 m, not statistically significant). In addition, peak Vo(2), BNP levels and Minnesota Living with Heart Failure Questionnaire scores only improved in the former group. The change in mean pulmonary artery pressure correlated with the change in 6-minute walk distance at 12 weeks (r = -0.71, p < 0.001). Device-related adverse events were comparable to those known to occur with a pacemaker-like device. CONCLUSIONS: Changes in ambulatory continuous hemodynamic measurements predicted changes in 6-minute walk distance after the start or addition of PAH therapy. The IHM also identified patients who had improved exercise tolerance, BNP levels and quality of life. The IHM appeared to be well tolerated and allowed rapid hemodynamic feedback between clinic visits.

Galié N, Badesch D, Oudiz R, Simonneau G, McGoon MD, Keogh AM, Frost AE, Zwicke D, Naeije R, Shapiro S, Olschewski H, Rubin LJ. · University of Bologna, Bologna, Italy. · J Am Coll Cardiol. · Pubmed #16053970 No free full text.

Abstract: OBJECTIVES: The purpose of this study was to examine the efficacy and safety of four doses of ambrisentan, an oral endothelin type A receptor-selective antagonist, in patients with pulmonary arterial hypertension (PAH). BACKGROUND: Pulmonary arterial hypertension is a life-threatening and progressive disease with limited treatment options. Endothelin is a vasoconstrictor and smooth muscle cell mitogen that plays a critical role in the pathogenesis and progression of PAH. METHODS: In this double-blind, dose-ranging study, 64 patients with idiopathic PAH or PAH associated with collagen vascular disease, anorexigen use, or human immunodeficiency virus infection were randomized to receive 1, 2.5, 5, or 10 mg of ambrisentan once daily for 12 weeks followed by 12 weeks of open-label ambrisentan. The primary end point was an improvement from baseline in 6-min walk distance (6MWD); secondary end points included Borg dyspnea index, World Health Organization (WHO) functional class, a subject global assessment, and cardiopulmonary hemodynamics. RESULTS: At 12 weeks, ambrisentan increased 6MWD (+36.1 m, p < 0.0001) with similar and statistically significant increases for each dose group (range, +33.9 to +38.1 m). Improvements were also observed in Borg dyspnea index, WHO functional class, subject global assessment, mean pulmonary arterial pressure (-5.2 mm Hg, p < 0.0001), and cardiac index (+0.33 l/min/m2, p < 0.0008). Adverse events were mild and unrelated to dose, including the incidence of elevated serum aminotransferase concentrations >3 times the upper limit of normal (3.1%). CONCLUSIONS: Ambrisentan appears to improve exercise capacity, symptoms, and hemodynamics in patients with PAH. The incidence and severity of liver enzyme abnormalities appear to be low.

McLaughlin VV, Gaine SP, Barst RJ, Oudiz RJ, Bourge RC, Frost A, Robbins IM, Tapson VF, McGoon MD, Badesch DB, Sigman J, Roscigno R, Blackburn SD, Arneson C, Rubin LJ, Rich S, Anonymous00171. · Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA. · J Cardiovasc Pharmacol. · Pubmed #12548091 No free full text.

Abstract: Intravenous epoprostenol is currently FDA approved for management of primary pulmonary hypertension, but it requires intravenous infusion and is associated with adverse effects. The objective of this study was to evaluate the effects of an epoprostenol analog, treprostinil, for management of pulmonary hypertension. Ten tertiary care academic institutions with pulmonary hypertension programs participated in these pilot trials. In the first trial, intravenous epoprostenol and intravenous treprostinil were compared. In the second trial, intravenous treprostinil and subcutaneous treprostinil were compared. In the third trial, subcutaneous treprostinil was compared with placebo infusion during an 8-week period. Intravenous epoprostenol and intravenous treprostinil resulted in a similar reduction in pulmonary vascular resistance acutely (22% and 20%, respectively). Intravenous treprostinil and subcutaneous treprostinil also demonstrated comparable short-term decrease in pulmonary vascular resistance (23% and 28%, respectively). The placebo-controlled 8-week trial demonstrated a mean improvement of 37 +/- 17 m as measured by the 6-minute walk distance in patients receiving treprostinil compared with a 6 +/- 28 m reduction in those receiving placebo. There were trends toward an improvement in cardiac index and pulmonary vascular resistance index in the treprostinil group. Subcutaneous treprostinil has favorable hemodynamic effects when given acutely and in the short term. Treprostinil can be given safely to an ambulatory patient with a novel subcutaneous delivery pump system.

Langleben D, Christman BW, Barst RJ, Dias VC, Galiè N, Higenbottam TW, Kneussl M, Korducki L, Naeije R, Riedel A, Simonneau G, Hirsch AM, Rich S, Robbins IM, Oudiz R, McGoon MD, Badesch DB, Levy RD, Mehta S, Seeger W, Solèr M. · Jewish General Hospital, McGill University, Montreal, Quebec, Canada. · Am Heart J. · Pubmed #12040360 No free full text.

Abstract: BACKGROUND: Circulating mediators, including thromboxane A2, the vasoconstrictor, platelet aggregant, and smooth muscle mitogen, may contribute to the progression of vascular narrowing in primary pulmonary hypertension (PPH). METHODS: To further understand the contribution of thromboxane and to provide novel therapy for PPH, we administered the potent orally active thromboxane synthetase inhibitor and thromboxane receptor antagonist terbogrel for 12 weeks to patients with New York Heart Association functional classification II and III PPH. The study had a multicenter randomized placebo-controlled design. The primary endpoint was a change in the distance walked during 6 minutes. The pharmacologic effects of terbogrel on thromboxane and prostacyclin metabolism also were studied. RESULTS: Although the planned enrollment was 135 patients, the study was halted after only 71 patients had been randomized because of the unforeseen side effect of leg pain, which occurred almost exclusively in patients with terbogrel treatment. Only 52 patients completed the 12-week study, and only 22 patients (31%) were fully compliant with the study medication. The leg pain confounded the primary endpoint of walking distance. On an intention-to-treat analysis, no improvements in 6-minute walk distance or in hemodynamics in patients with terbogrel treatment were seen. However, terbogrel was effective from a pharmacologic standpoint, reducing thromboxane metabolites by as much as 98% (P <.0001), with a modest but statistically insignificant (39%) rise in prostacyclin metabolites. CONCLUSION: Inhibition of thromboxane with an orally active agent is feasible in PPH, but the incidence of severe leg pain with terbogrel precludes its use in this disorder. Similar therapeutic efforts, with other thromboxane inhibitors, should be considered.

Taichman DB, McGoon MD, Harhay MO, Archer-Chicko C, Sager JS, Murugappan M, Chakinali MM, Palevsky HI, Gallop R. · Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, PA 19104, USA. · Mayo Clin Proc. · Pubmed #19567712 No free full text.

Abstract: OBJECTIVE: To assess interrater reliability of the New York Heart Association/World Health Organization functional classification as applied by clinicians (defined as both physicians and nurses in this article) to patients with pulmonary arterial hypertension (PAH). PATIENTS AND METHODS: Between March 16 and August 31, 2007, a survey that described 10 hypothetical patients was completed by physicians and nurses attending a conference on PAH. Results were subsequently validated with physicians and nurses who were contacted online through the Pulmonary Hypertension Association. Respondents were asked to assign each patient's functional class as they would normally in clinical practice. RESULTS: The functional class evaluations were completed by 113 clinicians, 87 (77%) of whom had participated in PAH trials; 106 (94%) reported using functional class when determining therapy. Clinicians reported a broad range of factors they considered when evaluating functional class, and their assessments of functional class varied widely. The intraclass correlation coefficient was 0.58 for the initial patient survey and 0.62 for the online survey. At best, one patient was ranked as either class II (by 60 clinicians [53%]) or class III (by 53 [47%]). Clinicians' rankings spanned at least 3 functional classes for each of the other patients. Equally divergent rankings were observed among nurses and physicians. Cluster analysis identified clinicians' tendencies toward "higher" or "lower" functional class rankings. Of the 113 clinicians, 101 (89%) thought that the patients described resembled those seen in their practices. CONCLUSION: Despite the wide use of the New York Heart Association/World Health Organization functional class in clinical care and as a research tool, interrater agreement may be inadequate. Efforts to promote a uniform approach to evaluating functional class might help to standardize PAH care and research.

McGoon MD, Kane GC. · Pulmonary Hypertension Clinic, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA. · Mayo Clin Proc. · Pubmed #19181654 links to  free full text

Abstract: Pulmonary arterial hypertension is a progressive, symptomatic, and ultimately fatal disorder for which substantial advances in treatment have been made during the past decade. Effective management requires timely recognition and accurate diagnosis of the disorder and appropriate selection among therapeutic alternatives. Despite progress in treatment, obstacles remain that impede the achievement of optimal outcomes. The current article provides an overview of the pathobiologic mechanisms of pulmonary arterial hypertension, including genetic substrates and molecular and cellular mechanisms, and describes the clinical manifestations and classification of pulmonary arterial hypertension. The article also reviews established approaches to evaluation and treatment, with emphasis on the appropriate application of calcium channel blockers, prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors. In addition, the authors discuss unresolved issues that may complicate patient management, such as the clinical importance of mild or exercise-related pulmonary arterial hypertension, and they identify avenues by which treatment may advance in the future through the use of combination treatment, outcomes assessment, and exploration of alternative pharmacologic strategies.

McGoon MD, Krichman A, Farber HW, Barst RJ, Raskob GE, Liou TG, Miller DP, Feldkircher K, Giles S. · Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. · Mayo Clin Proc. · Pubmed #18674477 links to  free full text

Abstract: The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) has been designed to meet the need for current information about patients with pulmonary arterial hypertension (PAH). The main objectives of REVEAL are to better define and understand PAH and to assess the consequences of treatment strategies. REVEAL is collecting clinically relevant data from 3500 consecutively enrolled patients with confirmed PAH diagnoses. Outcomes will be evaluated longitudinally and compared according to the baseline classification of PAH. The primary outcome for group comparisons will be survival. Collected data include World Health Organization functional class, 6-minute walk distance, cardiopulmonary exercise testing, pulmonary function test results, hemodynamic measurements, functional status, hospitalizations, and death. REVEAL will be the richest source of data on patients with World Health Organization group I PAH.

Galiè N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, Badesch DB, McGoon MD, McLaughlin VV, Roecker EB, Gerber MJ, Dufton C, Wiens BL, Rubin LJ, Anonymous00214. · Institute of Cardiology, University of Bologna, Via Massarenti, 9, 40138-Bologna, Italy. · Circulation. · Pubmed #18506008 links to  free full text

Abstract: BACKGROUND: Ambrisentan is a propanoic acid-based, A-selective endothelin receptor antagonist for the once-daily treatment of pulmonary arterial hypertension. METHODS AND RESULTS: Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Study 1 and 2 (ARIES-1 and ARIES-2) were concurrent, double-blind, placebo-controlled studies that randomized 202 and 192 patients with pulmonary arterial hypertension, respectively, to placebo or ambrisentan (ARIES-1, 5 or 10 mg; ARIES-2, 2.5 or 5 mg) orally once daily for 12 weeks. The primary end point for each study was change in 6-minute walk distance from baseline to week 12. Clinical worsening, World Health Organization functional class, Short Form-36 Health Survey score, Borg dyspnea score, and B-type natriuretic peptide plasma concentrations also were assessed. In addition, a long-term extension study was performed. The 6-minute walk distance increased in all ambrisentan groups; mean placebo-corrected treatment effects were 31 m (P=0.008) and 51 m (P<0.001) in ARIES-1 for 5 and 10 mg ambrisentan, respectively, and 32 m (P=0.022) and 59 m (P<0.001) in ARIES-2 for 2.5 and 5 mg ambrisentan, respectively. Improvements in time to clinical worsening (ARIES-2), World Health Organization functional class (ARIES-1), Short Form-36 score (ARIES-2), Borg dyspnea score (both studies), and B-type natriuretic peptide (both studies) were observed. No patient treated with ambrisentan developed aminotransferase concentrations >3 times the upper limit of normal. In 280 patients completing 48 weeks of treatment with ambrisentan monotherapy, the improvement from baseline in 6-minute walk at 48 weeks was 39 m. CONCLUSIONS: Ambrisentan improves exercise capacity in patients with pulmonary arterial hypertension. Improvements were observed for several secondary end points in each of the studies, although statistical significance was more variable. Ambrisentan is well tolerated and is associated with a low risk of aminotransferase abnormalities.

Shapiro BP, McGoon MD, Redfield MM. · Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA. · Chest. · Pubmed #17218561 links to  free full text

Abstract: BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) preferentially affects young women. However, a subset of patients with IPAH is elderly. Our objective was to compare elderly (age >/= 65 years) vs younger persons with unexplained pulmonary hypertension (PH) and a presumptive diagnosis of IPAH. METHODS: Clinical, echocardiographic, hemodynamic, and survival data were collected on consecutive patients with suspected IPAH after evaluation in a large tertiary center PH clinic. RESULTS: Of 197 patients (mean age +/- SD, 52 +/- 16 years; 80% female), 48 patients (24%) were elderly. Elderly and younger patients had similar symptom severity, systolic pulmonary artery (PA) pressure (82.7 +/- 20.3 mm Hg vs 86.9 +/- 18.8 mm Hg, respectively; p = 0.21), and severity of right ventricular enlargement and dysfunction. Elderly patients had higher pulmonary capillary wedge pressure (PCWP) [15.3 +/- 7.3 mm Hg vs 11.1 +/- 5.3 mm Hg; p < 0.0001] and more frequently failed (56%) to meet hemodynamic criteria for IPAH (PH with PCWP < 15 mm Hg) than did younger patients (19%). Elderly patients also had higher systemic systolic (p < 0.0001) and pulse (p < 0.0001) pressures and more cardiovascular disease. Among those patients with normal PCWP, elderly patients had worse survival than young patients (p = 0.007). Among those patients with elevated PCWP, elderly patients had lower PA pressures (p = 0.04) and better survival (p = 0.02). CONCLUSIONS: Elderly patients with clinically suspected IPAH often fail to meet hemodynamic criteria for IPAH due to elevated PCWP. Studies to define the proper diagnostic strategy and the safety and efficacy of pulmonary vasodilators in elderly patients with unexplained PH are needed.

Krowka MJ, Swanson KL, Frantz RP, McGoon MD, Wiesner RH. · Divisions of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · Hepatology. · Pubmed #17133488 No free full text.

Abstract: Portopulmonary hypertension (POPH) is the elevation of pulmonary artery pressure due to increased resistance to pulmonary blood flow in the setting of portal hypertension. Increased mortality has occurred with attempted liver transplantation in such patients and thus, screening for POPH is advised. We examined the relationship between screening echocardiography and right heart catheterization determinations of pressure, flow, volume, and resistance. A prospective, echocardiography-catheterization algorithm was followed from 1996 to 2005. Consecutive transplantation candidates underwent Doppler echocardiography to determine right ventricular systolic pressure (RVSP). Of 1,235 patients, 101 with RVSP >50 mm Hg underwent catheterization to measure mean pulmonary artery pressure (MPAP), flow via cardiac output (CO), central volume via pulmonary artery occlusion pressure (PAOP), and resistance via calculated pulmonary vascular resistance (PVR). Bland-Altman analysis suggested marked discordance between echocardiography-derived RVSP and catheterization results. All-cause pulmonary hypertension (MPAP >25 mm Hg) was documented in 90/101 (90%) patients. Using current pressure and resistance diagnostic guidelines (MPAP >25 mm Hg, PVR > or =240 dynes/s/cm(-5)), POPH was documented in 66/101 (65%) patients. Elevated MPAP was due to increased CO and/or PAOP in 35/101 (35%) patients with normal resistance (PVR <240 dynes/s/cm(-5)). The transpulmonary gradient (MPAP-PAOP) further characterized POPH in the presence of increased volume. Model for end stage liver disease (MELD) scores correlated poorly with MPAP and PVR. In conclusion, right heart catheterization is necessary to confirm POPH and frequently identifies other reasons for pulmonary hypertension (e.g., high flow and increased central volume) in liver transplantation candidates. Severity of POPH correlates poorly with MELD scores.

Mahapatra S, Nishimura RA, Oh JK, McGoon MD. · Division of Cardiology, Mayo Clinic, Rochester, Minnesota 55902, USA. · J Am Soc Echocardiogr. · Pubmed #16880101 No free full text.

Abstract: OBJECTIVES: We sought to determine if a novel measurement of pulmonary vascular (PV) capacitance (PVCAP) by Doppler echocardiography predicts all-cause mortality in patients with primary pulmonary arterial (PA) hypertension (PPAH). BACKGROUND: The prognosis of patients with PPAH is variable and has been difficult to predict using clinical or hemodynamic parameters. PVCAP is a measure of the workload on the right ventricle (RV) and we recently have shown that PVCAP determined by cardiac catheterization is a strong predictor of survival. This same hemodynamic information to calculate PVCAP can be derived from Doppler echocardiography. Therefore, the purpose of this study was to determine if PVCAP from noninvasive Doppler echocardiography would be a useful measure of survival in patients with PPAH. METHODS: We analyzed clinical and hemodynamic variables on all patients with PPAH who had a right heart catheterization and echocardiogram from January to December 1999. Because capacitance is directly proportional to stroke volume and inversely proportional to PA pulse pressure, PVCAP was defined as stroke volume/pulse pressure. PVCAP was derived noninvasively from a comprehensive 2-dimensional and Doppler echocardiogram. Using the peak systolic tricuspid regurgitation velocity and the end-diastolic pulmonary regurgitation velocity, the modified Bernoulli equation was used to calculate the PA systolic and diastolic pressures, respectively. Stroke volume was obtained using the volumetric flow through the left ventricular outflow tract. PVCAP was then analyzed as a predictor of mortality, adjusting for other known modifiers of risk. RESULTS: In all, 54 patients (13 men) were studied with a mean age of 44 +/- 11 years, ejection fraction of 62 +/- 11%, and RV systolic pressure of 90 +/- 21 mm Hg. In all, 24% were in World Health Organization (WHO) class II, 52% in class III, and 24% in class IV. During follow-up of 1498 +/- 108 days, 12 patients died. The strongest noninvasive predictor of mortality was PVCAP (risk ratio 3.0/mL/mm Hg decrease in PVCAP, 95% confidence interval 1.2-8.0, P = .0212). WHO class, RV index of myocardial performance, RV systolic pressure, and RV ejection time were weaker predictors. PVCAP was also a stronger predictor of mortality than invasively determined PV resistance, right atrial pressure, and mean PA pressure. In multivariate analysis, PVCAP was the only noninvasive predictor of mortality. In quartile analysis the lowest PVCAP quartile had a 4-year mortality of 39% whereas the highest PVCAP had a mortality of 7%. CONCLUSION: The novel measure of PVCAP, as determined by Doppler echocardiography, is a strong noninvasive predictor of mortality in patients with PPAH and adds prognostic value to conventional risk markers.

Elliott CG, Glissmeyer EW, Havlena GT, Carlquist J, McKinney JT, Rich S, McGoon MD, Scholand MB, Kim M, Jensen RL, Schmidt JW, Ward K. · LDS Hospital, University of Utah School of Medicine, Salt Lake City, Utah, USA. · Circulation. · Pubmed #16717148 links to  free full text

Abstract: BACKGROUND: Vasoreactivity tests are fundamental in evaluating pulmonary arterial hypertension (PAH). Mutations of the transforming growth factor-beta type II receptor gene, BMPR2, predispose to the development of pulmonary hypertension and may alter the response to vasodilators. Previous investigations have not examined the relationship of BMPR2 mutations to vasoreactivity. METHODS AND RESULTS: We identified 133 consecutive unrelated patients with either idiopathic or familial PAH. Sixty-six patients were excluded because we lacked either DNA samples (n=18) or complete data from a vasoreactivity test (n=48). The remaining 67 patients were screened for BMPR2 DNA sequence variations, and specific variations were confirmed by gene sequencing. The vasoreactivity of patients with nonsynonymous BMPR2 variations was compared with that of patients without nonsynonymous BMPR2 variations. We found nonsynonymous BMPR2 variations in 27 of 67 patients with idiopathic (n=16 of 52) or familial (n=11 of 15) PAH. Vasoreactivity was identified in 3.7% of 27 patients with nonsynonymous BMPR2 variations and in 35% of 40 patients without nonsynonymous BMPR2 variations (P=0.003). Five of the 27 nonsynonymous variations occur commonly in healthy individuals. None of the remaining 22 patients with BMPR2 variations demonstrated vasoreactivity, and the analysis remained unchanged when we assumed that nonsynonymous BMPR2 variations were present in all 15 patients with familial PAH. CONCLUSIONS: Patients with familial or idiopathic PAH and nonsynonymous BMPR2 variations are unlikely to demonstrate vasoreactivity. Further trials are required to determine whether long-term therapy can be directed by tests for BMPR2 variations.

Mahapatra S, Nishimura RA, Sorajja P, Cha S, McGoon MD. · Division of Cardiology, Mayo Clinic, Rochester, Minnesota, USA. · J Am Coll Cardiol. · Pubmed #16487848 No free full text.

Abstract: OBJECTIVES: The purpose of this study was to determine if pulmonary vascular capacitance predicts survival in patients with idiopathic pulmonary arterial hypertension (IPAH). BACKGROUND: The prognosis of patients with IPAH is difficult to predict, despite knowledge of clinical and hemodynamic parameters previously identified as predictors. METHODS: We proposed a capacitance index of stroke volume divided by pulmonary pulse pressure (SV/PP) and prospectively gathered data on IPAH patients who underwent a right heart catheterization. SV/PP was analyzed as a predictor of mortality after adjusting for other modifiers of risk. RESULTS: During 4-year follow-up of 104 patients, 21 patients died. When compared with conventional markers, SV/PP was the strongest univariate predictor of mortality (hazard ratio 17.0 per ml.mm Hg(-1) decrease, 95% confidence interval 13.0 to 22.0; p < 0.0001). In successive bivariate analysis, SV/PP was the only predictor of mortality. In quartile analysis, the lowest SV/PP quartile had a 4-year mortality of 61%; the highest SV/PP had no deaths. CONCLUSIONS: The capacitance index (SV/PP) is a strong independent predictor of mortality in patients with IPAH.

Ramakrishna G, Sprung J, Ravi BS, Chandrasekaran K, McGoon MD. · Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. · J Am Coll Cardiol. · Pubmed #15893189 No free full text.

Abstract: OBJECTIVES: We sought to determine the predictors of short-term morbidity and mortality (< 30 days) after noncardiac surgery in patients with pulmonary hypertension (PH). BACKGROUND: Pulmonary hypertension is considered to be a significant preoperative risk factor. METHODS: The PH and surgical data bases were matched from 1991 to 2003. Patients were excluded if PH was secondary to left heart disease, not present before surgery, or the procedure involved cardiopulmonary bypass. Univariate and multivariate logistic regression analyses were used to identify variables associated with short-term morbidity and mortality. RESULTS: Of 1,276 patients in the PH database, 145 patients (73% female) met all study criteria. The mean age (+/-SD) was 60.1 +/- 16.0 years. Right ventricular systolic pressure (RVSP) (mean +/- SD) on the two-dimensional echocardiogram was 68 +/- 21 mm Hg. There were 60 patients (42%) who experienced one or more short-term morbid event(s) (1.8 events/patient experiencing any event). A history of pulmonary embolism (p = 0.01), New York Heart Association functional class > or = II (p = 0.02), intermediate- to high-risk surgery (p = 0.04), and duration of anesthesia > 3 h (p = 0.04) were independent predictors of short-term morbidity. There were 10 early deaths (7%). A history of pulmonary embolism (p = 0.04), right-axis deviation (p = 0.02), right ventricular (RV) hypertrophy (p = 0.04), RV index of myocardial performance > or = 0.75 (p = 0.03), RVSP/systolic blood pressure > or = 0.66 (p = 0.01), intraoperative use of vasopressors (p < 0.01), and anesthesia when nitrous oxide was not used (p < 0.01) were each associated with postoperative mortality. CONCLUSIONS: In patients with PH undergoing noncardiac surgery with general anesthesia, specific clinical, diagnostic, and intraoperative factors may predict worse outcomes.

Bhatia S, Frantz RP, Severson CJ, Durst LA, McGoon MD. · Department of Internal Medicine, Mayo Clinic, Rochester, Minn 55905, USA. · Mayo Clin Proc. · Pubmed #14531479 links to  free full text

Abstract: OBJECTIVE: To determine the immediate and long-term effects of adding sildenafil, a phosphodiesterase-5 inhibitor, to the medical regimen of patients with pulmonary arterial hypertension (PAH). PATIENTS AND METHODS: Thirteen patients with PAH received empirical adjunctive sildenafil treatment at the Mayo Clinic in Rochester, Minn, between November 1, 2000, and August 31, 2001. All received a 25-mg dose of sildenafil, increased by 25 mg at 8-hour intervals, if tolerated, up to 100 mg during hemodynamic monitoring for 24 to 48 hours. Long-term effects on right heart hemodynamics were assessed by noninvasive right ventricular systolic pressure, right ventricular index of myocardial performance, and a 6-minute walk test. RESULTS: Sildenafil significantly increased cardiac output (CO) (P = .04) and decreased pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and mean arterial pressure (P < or = .01) at peak measurements (obtained 1-2 hours after highest dose). At trough measurements (obtained 8 hours after highest dose), sildenafil significantly decreased pulmonary artery systolic pressure, mean pulmonary artery pressure, and mean arterial pressure (P = .01). Ten patients discharged from the hospital were taking the highest-tolerated dose of sildenafil every 8 hours. The right ventricular systolic pressure and right index of myocardial performance showed no significant improvement at follow-up (117 +/- 70 days), although concomitant treatment with epoprostenol could be tapered in 2 patients. Changes in New York Heart Association classes were inconsistent, and improvements in the 6-minute walk test were not significant. CONCLUSION: Sildenafil has an immediate pulmonary vasodilator effect in patients already receiving vasodilators for PAH. Its long-term effects on right heart function and functional status are equivocal. A large, prospective, well-designed study is needed to determine the effects of sildenafil on PAH, both in untreated and concurrently treated patients.

Bhatia S, Morrison JF, Bower TC, McGoon MD. · Department of Internal Medicine, Mayo Clinic, Rochester, Minn 55905, USA. · Mayo Clin Proc. · Pubmed #12839088 links to  free full text

Abstract: We describe 2 patients who presented with symptoms and clinical evidence of pulmonary hypertension. The first patient, who had severe pulmonary hypertension, underwent correction of an acquired arteriovenous (AV) fistula, which led to improvement according to clinical and noninvasive hemodynamic criteria. The second patient had severely symptomatic pulmonary hypertension associated with a large, previously unrecognized, superior mesenteric AV fistula after intra-abdominal surgery. Surgical correction of the fistula resulted in normalization of pulmonary hemodynamics assessed by right heart catheterization. Truly reversible substrates of pulmonary hypertension are rare. Acquired systemic AV fistulas are a less recognized cause of secondary pulmonary hypertension. It is unknown whether high blood flow peripheral AV shunts ultimately lead to endothelial proliferation, vascular smooth muscle hypertrophy, plexiform lesions, and other histopathologic changes that are seen in patients with left-to-right shunts due to atrial septal defects, ventricular septal defects, and patent ductus arteriosus.

Voelkel NF, Quaife RA, Leinwand LA, Barst RJ, McGoon MD, Meldrum DR, Dupuis J, Long CS, Rubin LJ, Smart FW, Suzuki YJ, Gladwin M, Denholm EM, Gail DB, Anonymous00323. · Pulmonary Hypertension Center, University of Colorado at Denver and Health Sciences Center, 4200 E Ninth Ave, MC: C272, Denver, CO 80262, USA. · Circulation. · Pubmed #17060398 links to  free full text

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Newman JH, Fanburg BL, Archer SL, Badesch DB, Barst RJ, Garcia JG, Kao PN, Knowles JA, Loyd JE, McGoon MD, Morse JH, Nichols WC, Rabinovitch M, Rodman DM, Stevens T, Tuder RM, Voelkel NF, Gail DB, Anonymous00383. · Departments of Medicine, Nashville VA Medical Center (GRECC), and Vanderbilt University, Nashville, Tenn, USA. · Circulation. · Pubmed #15210611 links to  free full text

This publication has no abstract.