Hypertension: Mathier MA

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.

This publication has no abstract.

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.

This publication has no abstract.

Benedict N, Seybert A, Mathier MA. · Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. · Clin Ther. · Pubmed #18042471 No free full text.

Abstract: BACKGROUND: Pulmonary arterial hypertension (PAH) is a debilitating chronic disorder of the pulmonary vasculature characterized by elevated mean pulmonary arterial pressure, right-sided heart failure, and early mortality. OBJECTIVES: This paper reviews the available information on PAH, including its pathophysiology, classification of its severity, current treatment options, drug interactions, pharmacokinetics, and cost considerations. The results of clinical trials of the available treatments are summarized, and a suggested treatment algorithm is provided as a guide to the medical management of PAH. METHODS: Pertinent articles were identified by a search of MEDLINE through May 2007 using the terms primary pulmonary hypertension, pulmonary arterial hypertension, prostacyclin, pulmonary vasodilators, endothelin-receptor antagonists, and phosphodiesterase inhibitors. Trials with prospective, randomized designs were given precedence, and prospective studies having nonrandomized, open-label designs or using historical controls were included if they contributed useful knowledge. Retrospective studies were not included. Results: In two 12-week, randomized, open-label trials in patients with moderate to severe PAH (N = 81 and N = 111), exercise capacity, measured on the 6-minute walk test (6-MWT), was significantly improved with intravenous epoprostenol compared with conventional therapy (+31 vs -29 m, respectively, in one study [P = 0.002]; +46 vs -48 m in the other [P < 0.001]). In one of these trials, intravenous epoprostenol also was associated with a significant survival benefit (P < 0.003). In a 12-week, randomized, doubleblind, placebo-controlled trial in 470 patients with moderate to severe PAH, subcutaneous treprostinil plus conventional therapy was associated with a significant improvement on the 6-MWT compared with conventional therapy alone (+10 vs 0 m, respectively; P = 0.006). In a 16-week, randomized, double-blind, placebo-controlled trial in 213 patients with mild to moderate symptoms, the oral endothelin-receptor antagonist bosentan was associated with a significant improvement on the 6-MWT compared with placebo (+36 vs -8 m, respectively; P </= 0.001) and significantly less clinical worsening at 28 weeks (9/144 vs 14/69; P = 0.002). In a 12-week, prospective, randomized, double-blind, placebo-controlled trial in 277 patients with PAH, sildenafil 20, 40, and 80 mg TID were associated with significant improvements on the 6-MWT compared with placebo (all, P < 0.001). In a prospective trial in 76 patients with idiopathic PAH, the inhaled prostacyclin iloprost was associated with overall survival rates of 93%, 79%, 70%, 59%, 59%, and 49% at 3 months and 1, 2, 3, 4, and 5 years, respectively. In an early trial in 64 patients receiving highdose calcium channel blockers, those who had responded to initial drug challenge (defined as a > 20% decrease in pulmonary arterial pressure and pulmonary vascular resistance immediately after challenge) had a survival rate of 94% at 1, 3, and 5 years. CONCLUSIONS: Patients who respond to an acute trial of a vasodilator may be treated with an oral calcium channel blocker, whereas oral therapies such as sildenafil and bosentan have been effective in patients with mild to moderate symptoms. Infusions of the prostacyclin analogues epoprostenol and treprostinil appear to be the treatment of choice for moderate to severe PAH, and agents with alternate routes of delivery such as inhaled iloprost may be advantageous in adjunctive roles. Future trials that focus on the long-term effects of currently available agents, as well as on combination therapy, are needed.

Sakai T, Planinsic RM, Mathier MA, de Vera ME, Venkataramanan R. · Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. · Transpl Int. · Pubmed #19175541 No free full text.

Abstract: Treprostinil is a prostacyclin analog and has been used on idiopathic pulmonary arterial hypertension (PAH). There is only limited clinical experience using treprostinil to manage PAH in patients with end-stage liver disease (ESLD). We report three ESLD patients with PAH, who were treated with continuous intravenous treprostinil. A 59-year-old woman with ESLD secondary to alcoholic hepatitis had portopulmonary hypertension with mean pulmonary arterial pressure (mPAP) of 44 mmHg and transpulmonary gradient (TPG) of 23 mmHg. Treprostinil at 45 ng/kg/min for 6 months decreased mPAP to 23 (TPG to 8). A 53-year-old man had ESLD secondary to alcoholic hepatitis with PAH caused by multiple pulmonary embolisms (mPAP of 32 and TPG of 23). Treprostinil at 36 ng/kg/min for 3 months decreased mPAP to 23 and TPG to 14. Both patients underwent uneventful liver transplantation. A 48-year-old man had ESLD secondary to hepatitis C and portopulmonary hypertension with mPAP of 60 and TPG of 44. Two years after intravenous treprostinil at 106 ng/kg/min, his mPAP decreased to 44 and TPG to 30. These results demonstrate that for a selected group of ESLD patients with PAH, a continuous intravenous infusion of treprostinil appears to be safe and effective.

Rajagopalan N, Simon MA, Suffoletto MS, Shah H, Edelman K, Mathier MA, López-Candales A. · Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. · Echocardiography. · Pubmed #19054039 No free full text.

Abstract: BACKGROUND: Determination of pulmonary vascular resistance (PVR) in patients with suspected or known pulmonary hypertension (PH) requires right heart catheterization. Our purpose was to use Doppler echocardiography to estimate PVR in patients with PH. METHODS: Patient population consisted of 52 patients (53 +/- 12 years; 35 females) who underwent Doppler echocardiography and right heart catheterization within 24 hours of each other. The ratio of peak tricuspid regurgitation velocity (TRV) and right ventricular outflow time-velocity integral (VTI(RVOT)) was measured via transthoracic echocardiography and correlated to invasively determined PVR. A linear regression equation was generated to determine PVR by echocardiography based upon the TRV/VTI(RVOT) ratio. PVR by echocardiography was compared to invasive PVR using Bland-Altman analysis. RESULTS: Significant correlation was demonstrated between TRV/VTI(RVOT) and PVR by catheterization (r = 0.73; P < 0.001). However, Bland-Altman analysis showed that agreement between PVR determined by echocardiography and invasive PVR was poor (bias = 0; standard deviation = 4.3 Wood units). In a subset of patients with invasive PVR < 8 Wood units (26 patients), correlation between TRV/VTI(RVOT) and invasive PVR was strong (r = 0.94; P < 0.001). In these patients, agreement between PVR by echocardiography and invasive PVR was satisfactory (bias = 0; standard deviation = 0.5 Wood units). There was no correlation between TRV/VTI(RVOT) and invasive PVR in patients with PVR > 8 Wood units (n = 26; r = 0.17). CONCLUSION: While TRV/VTI(RVOT) correlates significantly with PVR, using it to estimate PVR in a PH patient population cannot be recommended.

Rajagopalan N, Simon MA, Shah H, Mathier MA, López-Candales A. · Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15513-2582, USA. · Echocardiography. · Pubmed #18445057 No free full text.

Abstract: OBJECTIVES: The objective of this study was to correlate tissue Doppler imaging of the right ventricle (RV) with pulmonary hemodynamics in patients referred for right heart catheterization. METHODS: Seventy subjects (mean age 54 +/- 13; 35 males) prospectively underwent tissue Doppler imaging of the RV and right heart catheterization within 1 day of each other. Peak systolic velocity and strain were measured at the RV free wall and correlated with pulmonary hemodynamics. RESULTS: RV myocardial velocity demonstrated no correlation with any hemodynamic variable. While RV strain demonstrated significant correlation with cardiac index (r =-0.61; P < 0.001), correlations with transpulmonary gradient (r = 0.26; P < 0.05) and pulmonary vascular resistance (r = 0.30; P < 0.05) were weaker. Subgroup analysis revealed that in patients with left ventricular systolic dysfunction (n = 31), RV strain showed no correlation with any hemodynamic variable. In patients with normal left ventricular systolic function (n = 39), correlations were significant between RV strain and mean pulmonary artery pressure (r = 0.59; P < 0.001), pulmonary vascular resistance (r = 0.60; P < 0.001), and cardiac index (r =-0.67; P < 0.001). CONCLUSIONS: RV myocardial strain correlates significantly with pulmonary hemodynamics in patients with pulmonary hypertension and normal left ventricular function. However, there is no correlation with RV performance in patients with left ventricular dysfunction.

Mathier MA, Zhang J, Ramanathan RC. · Department of Cardiology, University of Pittsburgh, Pittsburgh, PA 15213, USA. · Chest. · Pubmed #18321907 links to  free full text

Abstract: Pulmonary arterial hypertension (PAH) and morbid obesity both dramatically impair functional capacity. New therapies have emerged for both conditions, including pharmaceutical agents for the former and bariatric surgery for the latter. The presence of both conditions simultaneously, however, may limit the applicability and effectiveness of these therapies. We report a case of a morbidly obese patient with severe PAH and functional impairment. A three-drug combination regimen consisting of oral bosentan and sildenafil, and inhaled iloprost produced sufficient hemodynamic improvement to allow for the performance of bariatric surgery. Over the subsequent 7 months, body weight, oxygen requirement, functional class, and 6-min walk distance all improved dramatically despite the persistence of PAH. While such surgery is typically denied to patients with PAH, we suggest that aggressive medical therapy for patients with PAH may allow for its safe performance, and that the clinical improvement resulting from the subsequent weight loss may be quite dramatic.

Rajagopalan N, Simon MA, Mathier MA, López-Candales A. · Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA. · Int J Cardiol. · Pubmed #17714807 No free full text.

Abstract: BACKGROUND: Standard echocardiographic assessment of right ventricular (RV) function is problematic due to the complex RV geometry. We used tissue Doppler imaging to identify RV dysfunction in patients with pulmonary hypertension (PH). METHODS: Study population consisted of 44 patients (mean age 52+/-11; 30 females) with PH who underwent color tissue Doppler imaging of the RV and right heart catheterization within 2 days of each other. Peak systolic velocity and strain were measured at the RV free wall and correlated with invasive measures of PH and RV function. Myocardial velocity and strain was also measured in 20 healthy volunteers who served as normal controls (mean age 47+/-13; 13 females). RESULTS: PH patients had significantly reduced RV free wall velocity (6.4+/-2.1 cm/s vs. 8.2+/-2.1 cm/s; p<0.05) and RV strain (-18+/-7% vs. -28+/-6%; p<0.001) versus controls. RV peak strain demonstrated excellent correlation with transpulmonary gradient (r=0.72; p<0.001), pulmonary vascular resistance (r=0.73; p<0.001), and significant inverse correlation with cardiac index (r=-0.69; p<0.001). RV velocity had a significant, but weaker, correlation with cardiac index (r=0.33; p<0.05) and no association with transpulmonary gradient or pulmonary vascular resistance. In a multivariate model, RV strain but not RV velocity was independently associated with cardiac index. CONCLUSIONS: RV myocardial strain demonstrated excellent correlation with hemodynamic variables indicative of RV performance in PH patients.

Rajagopalan N, Saxena N, Simon MA, Edelman K, Mathier MA, López-Candales A. · Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA. · Congest Heart Fail. · Pubmed #17673871 No free full text.

Abstract: The authors performed tissue Doppler imaging of the tricuspid annulus in patients with pulmonary hypertension to assess its correlation with invasive indices of right ventricular function. The study population consisted of 32 patients with suspected pulmonary hypertension who underwent pulsed tissue Doppler imaging of the tricuspid annulus and right heart catheterization. Peak systolic (Sa), early diastolic (Ea), and late diastolic (Aa) velocities of the lateral tricuspid annulus were measured and correlated with hemodynamic variables. Peak Sa demonstrated excellent correlation with hemodynamic variables, including cardiac index (r=0.78; P<.001), pulmonary vascular resistance (r=-0.79; P<.001), and transpulmonary gradient (r=-0.72; P<.001). Peak Sa <10 cm/s predicted cardiac index <2.0 L/min/m2 with 89% sensitivity and 87% specificity. In conclusion, tissue Doppler imaging of the tricuspid annulus is a complementary method to assess right ventricular function in pulmonary hypertensive patients.