A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST)

Califf, Robert M.; Adams, Kirkwood F.; McKenna, William J.; Gheorghiade, Mihai; Uretsky, Barry F.; McNulty, Steven E.; Darius, Harald; Schulman, Kevin A.; Zannad, Faı̈ez; Handberg, Eileen M.; Harrell, Frank E.; Wheeler, William; Soler‐Soler, Jordi; Swedberg, Karl

doi:10.1016/s0002-8703(97)70105-4

Cited by 606 publications

(326 citation statements)

References 32 publications

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“…Outcomes are worse when PH complicates left heart disease and there are no specific treatments (1)(2)(3)(4). Further, in patients with left heart disease, therapies indicated for PAH, such as prostacyclins and endothelin receptor antagonists have been unsuccessful, while phosphodiesterase type 5 inhibitors have met with mixed results (5)(6)(7)(8)(9). Therefore, a great need exists to develop targeted therapies and to identify the patient population that can benefit.…”

Section: Methodsmentioning

confidence: 99%

Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction

Simon

Vanderpool²,

Nouraie³

et al. 2016

JCI Insight

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Section: Methodsmentioning

confidence: 99%

Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction

Simon

Vanderpool²,

Nouraie³

et al. 2016

JCI Insight

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“…10 To our knowledge, this is the first study to examine the potential role of an inhaled prostanoid, in this case iloprost, in the management of patients with PH associated with HFpEF. The current pilot study suggests that alteration of the delivery (systemic vs. inhaled) of these molecules may make a substantial difference in their effect and tolerability.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Hypertension Associated with Heart Failure with Preserved Ejection Fraction: Acute Hemodynamic Effects of Inhaled Iloprost

et al. 2015

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Iloprost, an inhaled synthetic prostacyclin analogue, improves hemodynamic and clinical status with minimal systemic adversity in patients with pulmonary arterial hypertension. Our single-site, prospective case series aimed to determine the effects of iloprost in subjects with group 2 pulmonary hypertension and heart failure with preserved ejection fraction. Patients referred to Boston Medical Center for initial evaluation of suspected pulmonary hypertension received a test dose of 2.5 μg inhaled iloprost, followed by two subsequent doses of 5 μg. Hemodynamic measurements were recorded for each inhalation after 15, 30, 60, and 90 minutes. Results were analyzed via paired t test and signed-rank test. Eight subjects fulfilled criteria and elected to enter the study. There was a reduction of pulmonary arterial pressure (by an average of 7.0 mmHg [P ¼ 0.005] and 4.7 mmHg [P ¼ 0.021] with the first and second 5-μg inhalations, respectively) and pulmonary vascular resistance (by an average of 161.9 dyn·s/cm 5 [P ¼ 0.019] and 95.0 dyn·s/cm 5 [P ¼ 0.014] with the first and second 5-μg inhalations, respectively). There were trends for increased cardiac output and decreased oxygen saturation. There were no changes in other vital or hemodynamic parameters, including pulmonary capillary wedge pressure. All patients completed each cycle of iloprost administration without preestablished termination criteria. In patients with pulmonary hypertension and heart failure with preserved ejection fraction, inhaled iloprost resulted in acute reduction of pulmonary arterial pressure and pulmonary vascular resistance. Further evaluation of iloprost in this subset of patients is warranted.

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“…The Flolan International Randomized Survival Trial trial, in which epoprostanol was given to patients with LV dysfunction, is illustrative. 153 Both PAP and PVR were significantly reduced, but the study was halted early because of increased mortality among treated subjects.…”

Section: Treating Pvh-phmentioning

confidence: 99%

Pulmonary Hypertension Caused by Pulmonary Venous Hypertension

Kulik

2014

Pulm. circ.

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The effect of pulmonary venous hypertension (PVH) on the pulmonary circulation is extraordinarily variable, ranging from no impact on pulmonary vascular resistance (PVR) to a marked increase. The reasons for this are unknown. Both acutely reversible pulmonary vasoconstriction and pathological remodeling (especially medial hypertrophy and intimal hyperplasia) account for increased PVR when present. The mechanisms involved in vasoconstriction and remodeling are not clearly defined, but increased wall stress, especially in small pulmonary arteries, presumably plays an important role. Myogenic contraction may account for increased vascular tone and also indirectly stimulate remodeling of the vessel wall. Increased wall stress may also directly cause smooth muscle growth, migration, and intimal hyperplasia. Even long-standing and severe pulmonary hypertension (PH) usually abates with elimination of PVH, but PVH-PH is an important clinical problem, especially because PVH due to left ventricular noncompliance lacks definitive therapy. The role of targeted PH therapy in patients with PVH-PH is unclear at this time. Most prospective studies indicate that these medications are not helpful or worse, but there is ample reason to think that a subset of patients with PVH-PH may benefit from phosphodiesterase inhibitors or other agents. A different approach to evaluating possible pharmacologic therapy for PVH-PH may be required to better define its possible utility.Keywords: pulmonary hypertension, pulmonary venous hypertension. As a perfect example of how clinical imperative can drive basic physiological investigation, studies of the effect of pulmonary venous hypertension (PVH) on the lung's circulation were in full swing by the very early 1950s, 1 close on the heels of the development of surgical relief of mitral valve stenosis. Cardiac catheterization of patients with mitral valve disease has characterized the physiology of PVH, and histological investigations demonstrated the microvascular changes provoked by PVH. Just as important, the effect of relief of left atrial (LA) hypertension on the circulation has been extensively reported, usually for patients who have had mitral valve intervention. We have learned that the circulatory alterations provoked by PVH share some characteristics with other forms of pulmonary hypertension (PH), such as the idiopathic variety, PH due to chronic alveolar hypoxia, and PH secondary to congenital cardiac shunting lesions. For example, acute "reactivity" to vasodilators may be observed, and there is overlap in the microarchitectural abnormalities seen. On the other hand, the "natural history" of PVH-PH is very different than that of the idiopathic variety or that seen with shunting defects: in the former (as demonstrated with mitral valve disease), PH is likely to largely or completely resolve if PVH is relieved, even with long-standing and severely increased pulmonary vascular resistance (PVR), 2,3 while in the latter two, PH is more likely to inexorably increase. PVH-PH is ther...

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A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST)

Cited by 606 publications

References 32 publications

Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction

Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction

Pulmonary Hypertension Associated with Heart Failure with Preserved Ejection Fraction: Acute Hemodynamic Effects of Inhaled Iloprost

Pulmonary Hypertension Caused by Pulmonary Venous Hypertension

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