Characteristics and Outcome After Hospitalization for Acute Right Heart Failure in Patients With Pulmonary Arterial Hypertension

Haddad, François; Peterson, T.W.; Fuh, Eric; Kudelko, Kristina; Perez, Vinicio de Jesus; Skhiri, Mehdi; Vagelos, Randall H.; Schnittger, Ingela; Denault, André; Rosenthal, David N.; Doyle, Ramona L.; Zamanian, Roham T.

doi:10.1161/circheartfailure.110.949933

Cited by 118 publications

(115 citation statements)

References 36 publications

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“…Hospitalization for worsening pulmonary arterial hypertension is costly and is associated with a poor prognosis. [23][24][25] Rates of hospitalization for any cause did not differ significantly among the study groups, although these data were not collected prospectively and are thus subject to some uncertainty.…”

Section: Discussionmentioning

confidence: 99%

Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension

et al. 2015

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BACKGROUNDData on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce. METHODSIn this event-driven, double-blind study, we randomly assigned, in a 2:1:1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentanmonotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response. RESULTSThe primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooledmonotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval [CI], 0.35 to 0.72; P<0.001). At week 24, the combination-therapy group had greater reductions from baseline in N-terminal pro-brain natriuretic peptide levels than did the pooled-monotherapy group (mean change, −67.2% vs. −50.4%; P<0.001), as well as a higher percentage of patients with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 [95% CI, 1.05 to 2.32]; P = 0.03) and a greater improvement in the 6-minute walk distance (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events that occurred more frequently in the combination-therapy group than in either monotherapy group included peripheral edema, headache, nasal congestion, and anemia. CONCLUSIONSAmong participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.)

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Section: Discussionmentioning

confidence: 99%

Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension

et al. 2015

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“…Five investigations have confirmed and stressed the importance of renal dysfunction and changes in renal function as a marker of mortality risk in PAH patients. 8,20,35,[56][57][58] High levels of serum uric acid correlate with patient outcome, 59,60 as do changes in serum uric acid with therapy (ie, not simply baseline values) in patients with PAH. 61 Changes in albumin and total bilirubin are related to overall survival.…”

Section: Laboratorymentioning

confidence: 99%

Risk Assessment in Pulmonary Arterial Hypertension Patients: The Long and Short of it

Benza

Lohmueller

Kraisangka

et al. 2018

Advances in Pulmonary Hypertension

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Pulmonary arterial hypertension (PAH) is a chronic and rapidly progressive disease that is characterized by extensive narrowing of the pulmonary vasculature, leading to increases in pulmonary vascular resistance, subsequent right ventricular dysfunction, and eventual death. There are currently multiple approved drugs—developed as single or combination therapies in the last few years—that have improved outcome and functionality in PAH. However, despite improvement in short-term survival with these new effective therapies, PAH remains an incurable disease with a median survival of 7 years (Figure 1).1 This chronic disease state may be characterized by morbid events such as hospitalizations that herald rapid disease progression and account for a significant disease burden (Figure 2).23 Physician ability to predict PAH disease progression is critical for determining optimal care of patients. Accurate risk assessment allows clinicians to determine the patient's prognosis, identify treatment goals, and monitor disease progression and the patient's response to treatment. Risk assessment for PAH patients should include a range of clinical, hemodynamic, and exercise parameters, performed in a serial fashion over the treatment course. Patient risk stratification can also help physicians better allocate treatment resources in settings where they are scarce. If widely adopted, risk prediction can enhance the consistency of treatment approaches across PAH practitioners and improve the timeliness of referral for lung transplantation. Hence, along with advancing PAH treatment options, comprehensive risk prediction is essential to make individualized treatment decisions in the current treatment era. Several tools are currently available for assessing risk in PAH (Figure 3). These include the 2015 European Society of Cardiology/European Respiratory Society pulmonary hypertension guidelines' risk variables,4 the French registry equation,5 the National Institutes of Health risk equation,6 or a risk score such as the one derived from the Registry to Evaluate Early And Long-term PAH Disease Management.1 These registries and evaluations of clinical trial sets have provided important insights into the importance of both modifiable (eg, 6-minute walk distance, functional class, brain natriuretic peptide, and nonmodifiable (eg, age, gender, PAH etiology) risk factors that predict survival. The following review explores commonly cited risk factors, both modifiable and nonmodifiable, and their implications for patient outcomes.

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“…This natural stock of blood volume and endothelial mass can be stimulated by a proper pulsatile CAD, adaptable for right heart circuit's biophysics and physiopathology, for inducing shear stress-mediated endothelial function enhancement. Contrarily, to current evidence of high mortality of CHF patients associated with right heart failure (Haddad, 2011), the concept of the present therapeutic approach considers the right heart as a physiological backup for management of almost all types of hemodynamic and circulatory disorders, including CHF patients ). As been demonstrated on (Table 3), the right heart afterlaod could improve or deteriorates the global cardiac output (CO) and hemodynamic, for example nitrates therapies that could improve left ventricular MI by lowering the systemic afterload, may worsen and be fatal in case of RV ischemia (Haji, 2000).…”

Section: Aorta + Valsalva Highmentioning

confidence: 99%

“Flow and Rate”: Concept and Clinical Applications of a New Hemodynamic Theory

Nour¹

2012

Biophysics

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Characteristics and Outcome After Hospitalization for Acute Right Heart Failure in Patients With Pulmonary Arterial Hypertension

Cited by 118 publications

References 36 publications

Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension

Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension

Risk Assessment in Pulmonary Arterial Hypertension Patients: The Long and Short of it

“Flow and Rate”: Concept and Clinical Applications of a New Hemodynamic Theory

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