RAnoLazIne for the Treatment of Diastolic Heart Failure in Patients With Preserved Ejection Fraction

Maier, Lars S.; Layug, Beth; Karwatowska‐Prokopczuk, Ewa; Belardinelli, Luiz; Lee, Stella; Sander, Julia; Lang, Christian; Wachter, Rolf; Edelmann, Frank; Hasenfuß, Gerd; Jacobshagen, Claudius

doi:10.1016/j.jchf.2012.12.002

Cited by 154 publications

(97 citation statements)

References 30 publications

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“…Furthermore, in a study of rats fed a high salt diet to induce hypertension, ranolazine therapy reduced oxidative stress and attenuated diastolic dysfunction (De Angelis, et al, 2016). Importantly, a 30-minute ranolazine infusion in patients with HFpEF reduced LVEDP in the RALI-DHF study (Maier, et al, 2013). In another study by Murray and Colombo, up to 70% of patients with HFrEF showed an improvement in EF when treated with ranolazine, compared to no improvement in the noradrenaline treatment arm (Murray & Colombo, 2014).…”

Section: Partial Fatty Acid Oxidation Inhibitionmentioning

confidence: 99%

Cardiac metabolism — A promising therapeutic target for heart failure

Noordali

Loudon

Frenneaux

et al. 2018

Pharmacology & Therapeutics

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Both heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF) are associated with high morbidity and mortality. Although many established pharmacological interventions exist for HFrEF, hospitalization and death rates remain high, and for those with HFpEF (approximately half of all heart failure patients), there are no effective therapies. Recently, the role of impaired cardiac energetic status in heart failure has gained increasing recognition with the identification of reduced capacity for both fatty acid and carbohydrate oxidation, impaired function of the electron transport chain, reduced capacity to transfer ATP to the cytosol, and inefficient utilization of the energy produced. These nodes in the genesis of cardiac energetic impairment provide potential therapeutic targets, and there is promising data from recent experimental and early-phase clinical studies evaluating modulators such as carnitine palmitoyltransferase 1 inhibitors, partial fatty acid oxidation inhibitors and mitochondrial-targeted antioxidants.Metabolic modulation may provide significant symptomatic and prognostic benefit for patients suffering from heart failure above and beyond guideline-directed therapy, but further clinical trials are needed.

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Section: Partial Fatty Acid Oxidation Inhibitionmentioning

confidence: 99%

Cardiac metabolism — A promising therapeutic target for heart failure

Noordali

Loudon

Frenneaux

et al. 2018

Pharmacology & Therapeutics

View full text Add to dashboard Cite

show abstract

“…Проведенный анализ показал, что прием препарата в течение 13 дней привел к улучшению показателей гемодинамики, но при этом отсутствовали изменения параметров релаксации [24].…”

Section: результаты и обсуждениеunclassified

Cardioprotective therapy in patients with atrial fibrillation and heart failure with preserved ejection fraction (Pilot study)

Tatarskiy¹,

Казеннова²,

Arutyunov³

2017

RHJ

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“…Nitroglycerin use also decreased in the treatment arm by one use per week vs. placebo ( P < 0.02). In a recent, small proof‐of‐concept RCT, ranolazine was further shown to improve haemodynamics [with decreases in left ventricular end‐diastolic pressure ( P = 0.04) and pulmonary capillary wedge pressure ( P = 0.04) in patients with HFpEF (Maier et al ., 2013)].…”

Section: Metabolic Dysfunction In Heart Failurementioning

confidence: 99%

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

Loudon

Noordali

Gollop

et al. 2016

British J Pharmacology

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Many conditions culminate in heart failure (HF), a multi‐organ systemic syndrome with an intrinsically poor prognosis. Pharmacotherapeutic agents that correct neurohormonal dysregulation and haemodynamic instability have occupied the forefront of developments within the treatment of HF in the past. Indeed, multiple trials aimed to validate these agents in the 1980s and early 1990s, resulting in a large and robust evidence‐base supporting their use clinically. An established treatment paradigm now exists for the treatment of HF with reduced ejection fraction (HFrEF), but there have been very few notable developments in recent years. HF remains a significant health concern with an increasing incidence as the population ages. We may indeed be entering the surgical era for HF treatment, but these therapies remain expensive and inaccessible to many. Newer pharmacotherapeutic agents are slowly emerging, many targeting alternative therapeutic pathways, but with mixed results. Metabolic modulation and manipulation of the nitrate/nitrite/nitric oxide pathway have shown promise and could provide the answers to fill the therapeutic gap between medical interventions and surgery, but further definitive trials are warranted. We review the significant evidence base behind the current medical treatments for HFrEF, the physiology of metabolic impairment in HF, and discuss two promising novel agents, perhexiline and nitrite.

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RAnoLazIne for the Treatment of Diastolic Heart Failure in Patients With Preserved Ejection Fraction

Abstract: Results of this proof-of-concept study revealed that ranolazine improved measures of hemodynamics but that there was no improvement in relaxation parameters. (Ranolazine in Diastolic Heart Failure [RALI-DHF]; NCT01163734).

Cited by 154 publications

References 30 publications

Cardiac metabolism — A promising therapeutic target for heart failure

Cardiac metabolism — A promising therapeutic target for heart failure

Cardioprotective therapy in patients with atrial fibrillation and heart failure with preserved ejection fraction (Pilot study)

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

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