Echocardiographic Ratio Shows Pre- and Post-Capillary Pulmonary Hypertension - The Cardiology Advisor
Echocardiographic Ratio Shows Pre- and Post-Capillary Pulmonary Hypertension - The Cardiology Advisor |
| Posted: 25 Jun 2019 01:00 AM PDT  In patients with pulmonary hypertension (PH), echocardiographic pulmonary to left atrial global strain ratio accurately discriminated between pre-capillary and post-capillary PH, according to a study published in the International Journal of Cardiology. Researchers evaluated the ability of echocardiographic pulmonary to left atrial global strain ratio to differentiate pre-capillary and post-capillary PH to see whether echocardiographic pulmonary to left atrial ratio or echocardiographic pulmonary to left atrial global strain ratio had a superior diagnostic capacity. Patients with unexplained dyspnea or heart failure who were referred for right heart catheterization were included in this study. Transthoracic echocardiography measured left ventricular ejection fraction, wave Doppler measured max tricuspid regurgitation peak velocity, and speckle tracking echocardiography measured left atrial global strain. These measurements were used to calculate echocardiographic pulmonary to left atrial global strain ratio. Right heart catheterization was used to measure mean right atrial pressure and pulmonary artery pressure. Of the 130 patients included in this study, 64 demonstrated pre-capillary PH, 66 demonstrated post-capillary PH, with 39 classified as isolated post-capillary PH, and 27 demonstrated combined post- and pre-capillary PH. When analyzing the baseline characteristics, echocardiographic pulmonary to left atrial global strain ratio was lower in pre-capillary PH than post-capillary PH (0.19 vs 0.45; P =.02), and echocardiographic pulmonary to left atrial ratio was higher in pre-capillary PH compared with post-capillary PH (0.37 vs 0.20; P <.001). Echocardiographic pulmonary to left atrial global strain ratio differentiated between isolated post-capillary PH and combined post- and pre-capillary PH (0.62 vs 0.32; P =.04) and was associated with pulmonary vascular resistance (r =0.28; P =.02) and transpulmonary gradient (r =0.30; P =.01). The diagnostic capability to distinguish pre-capillary and post-capillary PH favored echocardiographic pulmonary to left atrial global strain ratio (area under the curve [AUC] 0.80; 95% CI, 0.72-0.89; P <.001) over echocardiographic pulmonary to left atrial ratio (AUC 0.70; 95% CI, 0.61-0.80; P <.001). Limitations of this study included a lack of standard image acquisition, the absence of a control cohort, potential errors in the variable used to calculate echocardiographic pulmonary to left atrial global strain ratio, and the inclusion of symptomatic patients in the post-capillary PH cohort. The researchers concluded that "[t]he novel [echocardiographic pulmonary to left atrial global strain] ratio distinguishes pre-capillary from post-capillary PH and demonstrates a stronger differentiating capability as compared to [echocardiographic pulmonary to left atrial ratio]." Reference Venkateshvaran A, Manouras A, Kjellström B, Lund LH. The additive value of echocardiographic pulmonary to left atrial global strain ratio in the diagnosis of pulmonary hypertension [published online May 31, 2019]. Int J Cardiol. doi:10.1016/j.ijcard.2019.05.025  |
| Macitentan reduces pulmonary vascular resistance in portopulmonary hypertension: PORTICO - Healio Posted: 20 Jun 2019 12:03 PM PDT  Among patients with portopulmonary hypertension, treatment with macitentan, as compared with placebo, was associated with a 35% decrease in pulmonary vascular resistance, according to the PORTICO study published in The Lancet Respiratory Medicine. In the international, multicenter, double-blind, placebo-controlled phase 4 study, the researchers randomly assigned 85 adults with portopulmonary hypertension to macitentan 10 mg (n = 43; Opsumit, Actelion Pharmaceuticals) or placebo (n = 42) for 12 weeks, which was followed by a 12-week open-label period. Pulmonary vascular resistance at week 12, expressed as ratio of baseline in the full analysis set, served as the primary endpoint. At baseline, 64% of patients were being treated for pulmonary arterial hypertension; 59% were WHO functional class II; 39% were WHO functional class III; and the mean 6-minute walk distance was 384.5 m. After 12 weeks of treatment, the geometric mean ratio of baseline pulmonary vascular resistance decreased to 0.63 (95% CI, 0.58-0.67) in patients assigned macitentan and decreased to 0.98 (95% CI, 0.91-1.05) in patients assigned placebo. The ratio of geometric means was 0.65 (95% CI, 0.59-0.72), which translated to a 35% (95% CI, 28-41) reduction in pulmonary vascular resistance with macitentan vs. placebo. Results were consistent across predefined various subgroups, including in patients receiving PAH therapy at baseline, the researchers noted. Although there were no deaths or major changes in model for end-stage liver disease scores or Child-Pugh classification during the double-blind period, adverse events occurred in 84% of patients treated with macitentan and 79% of those treated with placebo. Twenty-one percent of events in the macitentan group and 14% in the placebo group were considered serious. Adverse events also prompted study discontinuation in 9% of patients assigned macitentan during the double-blind period. No patients assigned placebo discontinued the study. Peripheral edema was the most frequently reported adverse event — occurring in 26% of the macitentan group and 12% of the placebo group. Secondary outcomes In terms of secondary endpoints, macitentan was associated with a placebo-corrected decrease in mean pulmonary arterial pressure of –5.99 mm Hg (95% CI, –8.4 to –3.57) and total pulmonary resistance of –171.48 dyn/s/cm–5 (95% CI, –223.67 to –119.3). From baseline to 12 weeks, the change in cardiac index was greater in the macitentan group, with a treatment effect of 0.52 L/min/m2 (95% CI, 0.22-0.8). However, the macitentan and placebo groups did not differ significantly in change in right atrial pressure, mixed venous oxygen saturation and N-type pro-B-type natriuretic peptide (NT-proBNP). There also were no treatment effects observed in 6-minute walk distance and WHO functional class at 12 weeks. During the overall macitentan treatment period, including the 12-week open-label period, adverse events were similar to those observed during the double-blind period. Peripheral edema was the most frequently reported adverse event, followed by headache and anemia. Thirty percent of patients had a serious adverse event and 12% had an event leading to study discontinuation. Four patients died, but the researchers determined the deaths were unrelated to treatment. Also during the overall treatment period, 37% of patients had a decrease in hemoglobin of 2 g/dL or more, which occurred in the first 8 weeks of receiving macitentan in the double-blind or open-label period and stabilized thereafter. Further study necessary Although the study met its primary endpoint, it also raised questions, according to Hossein-Ardeschir Ghofrani, MD, from the department of internal medicine, pulmonary hypertension division at University of Giessen and Marburg Lung Center in Germany and the department of medicine at Imperial College London. "Of note, besides the primary endpoint, no significant changes occurred in clinical parameters of exercise ability, symptoms or NT-proBNP concentrations. These findings could be explained in part by the fact that more than 60% of patients were pretreated with other pulmonary arterial hypertension-specific medications and NT-proBNP concentrations were rather low to begin with. However, one should keep in mind that improving pulmonary hemodynamics at the expense of a deteriorating myocardial function, in the absence of clinical improvements, would be too high a price to pay for these fragile patients," Ghofrani wrote in a linked comment. "In all previous pulmonary arterial hypertension treatment clinical trials, improvements in pulmonary hemodynamics and cardiac output were paralleled by reductions in NT-proBNP levels. The observations from PORTICO are the first time that these two indicators of cardiac function have not changed in parallel." Ghofrani also highlighted several other issues, including a rather high withdrawal rate due to adverse events for a study of PORTICO's duration. The possibility that endothelin receptor antagonists may lead to fluid overload that may promote peripheral edema, increases in right atrial pressure and the potential for gas exchange disturbances due to increased shunt perfusion when taking vasodilators are concerning for patients with severe pulmonary hypertension, he added. Due to these concerns, among others, Ghofrani emphasized the need for more research, noting that "in this particular patient population, assessment of the risk-benefit ratio of short-term hemodynamic improvements with macitentan therapy and long-term effects of morbidity or mortality warrant further studies." – by Melissa Foster Disclosures: This study was sponsored by Actelion Pharmaceuticals. Sitbon reports he has received grants, personal fees and nonfinancial support from Actelion, Bayer and Merck; he has received grants and personal fees from GlaxoSmithKline; and he has received personal fees from Acceloron and Arena Pharmaceuticals. Please see the study for all other authors' relevant financial disclosures. Ghofrani reports he has received personal fees from Actelion, Bayer, GlaxoSmithKline, Merck Sharp and Dohme, Novartis, Pfizer and United Therapeutics. Among patients with portopulmonary hypertension, treatment with macitentan, as compared with placebo, was associated with a 35% decrease in pulmonary vascular resistance, according to the PORTICO study published in The Lancet Respiratory Medicine. In the international, multicenter, double-blind, placebo-controlled phase 4 study, the researchers randomly assigned 85 adults with portopulmonary hypertension to macitentan 10 mg (n = 43; Opsumit, Actelion Pharmaceuticals) or placebo (n = 42) for 12 weeks, which was followed by a 12-week open-label period. Pulmonary vascular resistance at week 12, expressed as ratio of baseline in the full analysis set, served as the primary endpoint. At baseline, 64% of patients were being treated for pulmonary arterial hypertension; 59% were WHO functional class II; 39% were WHO functional class III; and the mean 6-minute walk distance was 384.5 m. After 12 weeks of treatment, the geometric mean ratio of baseline pulmonary vascular resistance decreased to 0.63 (95% CI, 0.58-0.67) in patients assigned macitentan and decreased to 0.98 (95% CI, 0.91-1.05) in patients assigned placebo. The ratio of geometric means was 0.65 (95% CI, 0.59-0.72), which translated to a 35% (95% CI, 28-41) reduction in pulmonary vascular resistance with macitentan vs. placebo. Results were consistent across predefined various subgroups, including in patients receiving PAH therapy at baseline, the researchers noted. Although there were no deaths or major changes in model for end-stage liver disease scores or Child-Pugh classification during the double-blind period, adverse events occurred in 84% of patients treated with macitentan and 79% of those treated with placebo. Twenty-one percent of events in the macitentan group and 14% in the placebo group were considered serious. Adverse events also prompted study discontinuation in 9% of patients assigned macitentan during the double-blind period. No patients assigned placebo discontinued the study. Peripheral edema was the most frequently reported adverse event — occurring in 26% of the macitentan group and 12% of the placebo group. Secondary outcomes In terms of secondary endpoints, macitentan was associated with a placebo-corrected decrease in mean pulmonary arterial pressure of –5.99 mm Hg (95% CI, –8.4 to –3.57) and total pulmonary resistance of –171.48 dyn/s/cm–5 (95% CI, –223.67 to –119.3). From baseline to 12 weeks, the change in cardiac index was greater in the macitentan group, with a treatment effect of 0.52 L/min/m2 (95% CI, 0.22-0.8). However, the macitentan and placebo groups did not differ significantly in change in right atrial pressure, mixed venous oxygen saturation and N-type pro-B-type natriuretic peptide (NT-proBNP). There also were no treatment effects observed in 6-minute walk distance and WHO functional class at 12 weeks. PAGE BREAK During the overall macitentan treatment period, including the 12-week open-label period, adverse events were similar to those observed during the double-blind period. Peripheral edema was the most frequently reported adverse event, followed by headache and anemia. Thirty percent of patients had a serious adverse event and 12% had an event leading to study discontinuation. Four patients died, but the researchers determined the deaths were unrelated to treatment. Also during the overall treatment period, 37% of patients had a decrease in hemoglobin of 2 g/dL or more, which occurred in the first 8 weeks of receiving macitentan in the double-blind or open-label period and stabilized thereafter. Further study necessary Although the study met its primary endpoint, it also raised questions, according to Hossein-Ardeschir Ghofrani, MD, from the department of internal medicine, pulmonary hypertension division at University of Giessen and Marburg Lung Center in Germany and the department of medicine at Imperial College London. "Of note, besides the primary endpoint, no significant changes occurred in clinical parameters of exercise ability, symptoms or NT-proBNP concentrations. These findings could be explained in part by the fact that more than 60% of patients were pretreated with other pulmonary arterial hypertension-specific medications and NT-proBNP concentrations were rather low to begin with. However, one should keep in mind that improving pulmonary hemodynamics at the expense of a deteriorating myocardial function, in the absence of clinical improvements, would be too high a price to pay for these fragile patients," Ghofrani wrote in a linked comment. "In all previous pulmonary arterial hypertension treatment clinical trials, improvements in pulmonary hemodynamics and cardiac output were paralleled by reductions in NT-proBNP levels. The observations from PORTICO are the first time that these two indicators of cardiac function have not changed in parallel." Ghofrani also highlighted several other issues, including a rather high withdrawal rate due to adverse events for a study of PORTICO's duration. The possibility that endothelin receptor antagonists may lead to fluid overload that may promote peripheral edema, increases in right atrial pressure and the potential for gas exchange disturbances due to increased shunt perfusion when taking vasodilators are concerning for patients with severe pulmonary hypertension, he added. Due to these concerns, among others, Ghofrani emphasized the need for more research, noting that "in this particular patient population, assessment of the risk-benefit ratio of short-term hemodynamic improvements with macitentan therapy and long-term effects of morbidity or mortality warrant further studies." – by Melissa Foster Disclosures: This study was sponsored by Actelion Pharmaceuticals. Sitbon reports he has received grants, personal fees and nonfinancial support from Actelion, Bayer and Merck; he has received grants and personal fees from GlaxoSmithKline; and he has received personal fees from Acceloron and Arena Pharmaceuticals. Please see the study for all other authors' relevant financial disclosures. Ghofrani reports he has received personal fees from Actelion, Bayer, GlaxoSmithKline, Merck Sharp and Dohme, Novartis, Pfizer and United Therapeutics.  |
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