Role of Inotropic Agents in the Treatment of Heart Failure

Goldhaber, Joshua I.; Hamilton, Michèle A.

doi:10.1161/circulationaha.109.899294

Cited by 49 publications

(28 citation statements)

References 41 publications

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“…Following the analysis scheme of the main ESCAPE study, we initially calculated this endpoint with patients receiving transplant or assist devices coded as dead; then we coded these events as alive in a sensitivity analysis. The association between admission SBP, inotropes use, and outcomes was assessed by categorizing SBP into <100 vs. ≥100 mmHg based on previous literature 9, 10 and also by modeling SBP as a continuous variable. We followed a similar approach for cardiac index, using 1.8 L/min/m 2 for categorical analysis.…”

Section: Methodsmentioning

confidence: 99%

“…8 This discrepant trend is partially rooted in the limited options for management of advanced systolic HF. 9 However, it is also rooted in the belief that inotropes may be beneficial when systolic blood pressure (SBP) is relatively low even without clinical hypoperfusion, 10 or that benefits may outweigh risks in those patients who are in a low cardiac output state, since previous trials were conducted among hospitalized patients without the specific knowledge of central hemodynamics. 5 There are no data however to support these notions.…”

mentioning

confidence: 99%

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Inotrope Use and Outcomes Among Patients Hospitalized for Heart Failure: Impact of Systolic Blood Pressure, Cardiac Index, and Etiology

Καλογερόπουλος

Marti

Georgiopoulou

et al. 2014

Journal of Cardiac Failure

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Background Inotropes are widely used in hospitalized systolic heart failure (HF) patients, especially those with low systolic blood pressure (SBP) or cardiac index. Also inotropes are considered harmful in nonischemic HF. Methods and Results We examined the association of in-hospital inotrope use with (1) major events (death, ventricular assist device, or heart transplant) and (2) study days alive and out of hospital during the first 6 months in the ESCAPE trial, which excluded patients with immediate need for inotropic therapy. Predefined subgroups of interest were baseline SBP <100 vs. ≥100 mmHg, cardiac index <1.8 vs. ≥1.8 L/min/m2, and ischemic vs. nonischemic HF etiology. Inotropes were frequently used in both the <100-mmHg (88/165 [53.3%]) and the ≥100-mmHg (106/262 [40.5%]) SBP subgroups and were associated with higher risk for major events in both subgroups (adjusted HR 2.85, 95%CI 1.59–5.12, P<0.001 and HR 1.86, 95%CI 1.02–3.37; P=0.042, respectively). Risk with inotropes was more pronounced among those with cardiac index ≥1.8 L/min/m2 (N=114, HR 4.65, 95%CI 1.98–10.9, P<0.001) vs. <1.8 L/min/m2 (N=82, HR 1.48, 95%CI 0.61–3.58, P=0.39). Event rates were higher with inotropes both in ischemic (N=215, HR 2.64, 95%CI 1.49–4.68, P=0.001) and nonischemic patients (N=216, HR 2.19, 95%CI 1.18–4.07, P=0.012). Across all subgroups, patients who received inotropes spent fewer study days alive and out of hospital. Conclusion In the absence of cardiogenic shock or end-organ hypoperfusion, inotrope use during hospitalization for HF is associated with unfavorable 6-month outcomes, regardless of admission SBP, cardiac index, or HF etiology.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Inotrope Use and Outcomes Among Patients Hospitalized for Heart Failure: Impact of Systolic Blood Pressure, Cardiac Index, and Etiology

Καλογερόπουλος

Marti

Georgiopoulou

et al. 2014

Journal of Cardiac Failure

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“…While the early historical progression of the optimization of pharmacological therapy in HFrEF largely focused on improving left ventricular function through the use of positive inotropes (5,19), the introduction of vasodilator therapy in the 1980s was a therapeutic milestone (5,11). Indeed, the demonstrated beneficial effect of antihypertensive drugs, including nitrate-based medications (i.e., hydralazine) (12) and angiotensin-converting enzyme (ACE) inhibitors (1,12,16) on exercise intolerance and exercise-related symptoms has established important pleiotropic properties for these drug classes that are of significant value in the treatment of HFrEF.…”

Section: Perspectivesmentioning

confidence: 99%

Hemodynamic responses to small muscle mass exercise in heart failure patients with reduced ejection fraction

Barrett-O’Keefe

Lee

Berbert

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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To better understand the mechanisms responsible for exercise intolerance in heart failure with reduced ejection fraction (HFrEF), the present study sought to evaluate the hemodynamic responses to small muscle mass exercise in this cohort. In 25 HFrEF patients (64 ± 2 yr) and 17 healthy, age-matched control subjects (64 ± 2 yr), mean arterial pressure (MAP), cardiac output (CO), and limb blood flow were examined during graded static-intermittent handgrip (HG) and dynamic single-leg knee-extensor (KE) exercise. During HG exercise, MAP increased similarly between groups. CO increased significantly (+1.3 ± 0.3 l/min) in the control group, but it remained unchanged across workloads in HFrEF patients. At 15% maximum voluntary contraction (MVC), forearm blood flow was similar between groups, while HFrEF patients exhibited an attenuated increase at the two highest intensities compared with controls, with the greatest difference at the highest workload (352 ± 22 vs. 492 ± 48 ml/min, HFrEF vs. control, 45% MVC). During KE exercise, MAP and CO increased similarly across work rates between groups. However, HFrEF patients exhibited a diminished leg hyperemic response across all work rates, with the most substantial decrement at the highest intensity (1,842 ± 64 vs. 2,675 ± 81 ml/min; HFrEF vs. control, 15 W). Together, these findings indicate a marked attenuation in exercising limb perfusion attributable to impairments in peripheral vasodilatory capacity during both arm and leg exercise in patients with HFrEF, which likely plays a role in limiting exercise capacity in this patient population.

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“…Inotropic agents, particularly β-agonists, have been the mainstay of therapy for PEA 34 on the basis of considerations of molecular factors involved in contractile function and dysfunction. β-Agonists phosphorylate L-type Ca 2+ channels, ryanodine receptors, the sarcoplasmic reticulum calcium ATPase regulator phospholamban, and myofilaments not only to increase trigger Ca 2+ entry into the cell but also to synchronize Ca 2+ release from a loaded SR and improve myofilament Ca 2+ responsiveness.…”

Section: Cellular Mechanisms and Contractile Dysfunctionmentioning

confidence: 99%