Large animal models of heart failure with preserved ejection fraction

Miyagi, Chihiro; Miyamoto, Takuma; Kuroda, Taiyo; Karimov, Jamshid H.; Starling, Randall C.

doi:10.1007/s10741-021-10184-9

Cited by 10 publications

(12 citation statements)

References 90 publications

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“…Nonetheless, a recent working group of the National Heart, Lung, and Blood Institute on HFpEF identified the need for “improved animal models, including large animal models, which incorporate the effects of aging and associated comorbid conditions.” 44 Several large animal models of HFpEF have been introduced of late. These include the Göttingen minipig administered a Western diet and subjected to deoxycorticosterone acetate‐salt pressure/volume stress, 45 aortic banding, or progressive aortic constriction in dogs and pigs, 46 , 47 and the Yorkshire×landrace swine with induction of diabetes (streptozotocin), hypercholesterolemia (high‐fat and high‐sugar diet with increasing salt), and chronic kidney disease (microembolization of the global right kidney). 48 As discussed here, small animal models are arguably perhaps better suited for an “omics” approach, involving genomics, proteomics, and metabolomics, to profile the changes in the heart occurring with HFpEF in a temporal and comorbidity‐dependent manner.…”

Section: Large Animal Models Of Hfpefmentioning

confidence: 99%

Genomic, Proteomic, and Metabolic Comparisons of Small Animal Models of Heart Failure With Preserved Ejection Fraction: A Tale of Mice, Rats, and Cats

Smith

Altara

Amin

et al. 2022

JAHA

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Heart failure with preserved ejection fraction (HFpEF) remains a medical anomaly that baffles researchers and physicians alike. The overall phenotypical changes of diastolic function and left ventricular hypertrophy observed in HFpEF are definable; however, the metabolic and molecular alterations that ultimately produce these changes are not well established. Comorbidities such as obesity, hypertension, and diabetes, as well as general aging, play crucial roles in its development and progression. Various animal models have recently been developed to better understand the pathophysiological and metabolic developments in HFpEF and to illuminate novel avenues for pharmacotherapy. These models include multi‐hit rodents and feline aortic constriction animals. Recently, genomic, proteomic, and metabolomic approaches have been used to define altered signaling pathways in the heart associated with HFpEF, including those involved in inflammation, cGMP‐related, Ca 2+ handling, mitochondrial respiration, and the unfolded protein response in endoplasmic reticulum stress. This article aims to present an overview of what has been learnt by these studies, focusing mainly on the findings in common while highlighting unresolved issues. The knowledge gained from these research models will not simply be of benefit for treating HFpEF but will undoubtedly provide new insights into the mechanisms by which the heart deals with external stresses and how the processes involved can fail.

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Section: Large Animal Models Of Hfpefmentioning

confidence: 99%

Genomic, Proteomic, and Metabolic Comparisons of Small Animal Models of Heart Failure With Preserved Ejection Fraction: A Tale of Mice, Rats, and Cats

Smith

Altara

Amin

et al. 2022

JAHA

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“…Consistently, all the methods developed to date fail to enable control over the severity of aortic constriction and, simultaneously, over the dynamics of disease progression and reversal, hindering fundamental and translational studies of human disease. In large animal models, aortic banding has been previously achieved through a variety of methods [11], including use of an inelastic sleeve in a juvenile swine that becomes constrictive during the animal's development [12], an on-demand inflatable cuff that can be pressurized to various levels [13], and a reduction stent that can be delivered percutaneously in the descending thoracic aorta [14]. Compared to large animals, small animal models are more time-and cost-effective due to the relatively faster dynamics of their associated cardiac remodeling processes.…”

Section: Introductionmentioning

confidence: 99%

Soft robotic platform for controlled, progressive and reversible aortic constriction in a small animal model

Roche

Rosalia

Wang

et al. 2023

Preprint

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Our understanding of cardiac remodeling processes due to left ventricular pressure overload derives largely from animal models of aortic banding. However, these studies fail to simultaneously enable control over disease progression and reversal, hindering their clinical relevance. Here, we describe a method for controlled, progressive, and reversible aortic banding based on an implantable expandable actuator that can be finely controlled to modulate aortic banding and debanding in a rat model. Through catheterization, imaging, and histologic studies, we demonstrate that our model can recapitulate the hemodynamic and structural changes associated with pressure overload in a controllable manner. We leverage the ability of our model to enable non-invasive aortic debanding to show that these changes can be partly reversed due to cessation of the biomechanical stimulus. By recapitulating longitudinal disease progression and reversibility, this model could elucidate fundamental mechanisms of cardiac remodeling and optimize timing of intervention for pressure overload.

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“…[ 30 ] A major limitation to the development of these devices and their market approval in the US is the lack of an adequate in vivo model of the HFpEF hemodynamics. [ 41,42 ] As a result, preclinical safety and functional evaluation of device‐based solutions for HFpEF can only be conducted on healthy animals, considerably hindering their reliability. [ 36,43 ]…”

Section: Introductionmentioning

confidence: 99%

“…[ 50 ] Another method currently under development involves reducing LV filling by the use of an intraventricular balloon; however, this technique is still lacking a post‐operative functional evaluation and may induce systolic dysfunction, which is only rarely associated with HFpEF. [ 42 ] Because of all these limitations, no such models are currently being used for the evaluation of medical devices for HFpEF.…”

Section: Introductionmentioning

confidence: 99%

“…[30] A major limitation to the development of these devices and their market approval in the US is the lack of an adequate in vivo model of the HF-pEF hemodynamics. [41,42] As a result, preclinical safety and functional evaluation of device-based solutions for HFpEF can only be conducted on healthy animals, considerably hindering their reliability. [36,43] Current large animal models of HFpEF suffer from a variety of shortcomings, including their limited hemodynamic fidelity, elevated costs, lengthy development times, and low throughput.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Modulating Cardiac Hemodynamics Using Tunable Soft Robotic Sleeves in a Porcine Model of HFpEF Physiology for Device Testing Applications

Rosalia,

Ozturk,

Wang

et al. 2023

Adv Funct Materials

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Heart failure with preserved ejection fraction (HFpEF) is a major challenge in cardiovascular medicine, accounting for ≈50% of all cases of heart failure. Despite the ongoing efforts, no medical device has yet received FDA approval. This is largely due to the lack of an in vivo model of the HFpEF hemodynamics, resulting in the inability to evaluate device effectiveness in vivo prior to clinical trials. Here, the development of a highly tunable porcine model of HFpEF hemodynamics is described using implantable soft robotic sleeves, where controlled actuation of a left ventricular and an aortic sleeve can recapitulate changes in ventricular compliance and afterload associated with a broad spectrum of HFpEF hemodynamic phenotypes. The feasibility of the proposed model in preclinical testing is demonstrated by evaluating the hemodynamic response of the model post‐implantation of an interatrial shunt device, which is found to be consistent with findings from in silico studies and clinical trials. This work overcomes limitations of prior HFpEF models, such as low hemodynamic accuracy, high costs, and long development phases. The versatile and adjustable platform introduced can transform HFpEF device development, aiming to enhance the lives of the 32 million people affected globally.

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Large animal models of heart failure with preserved ejection fraction

Cited by 10 publications

References 90 publications

Genomic, Proteomic, and Metabolic Comparisons of Small Animal Models of Heart Failure With Preserved Ejection Fraction: A Tale of Mice, Rats, and Cats

Genomic, Proteomic, and Metabolic Comparisons of Small Animal Models of Heart Failure With Preserved Ejection Fraction: A Tale of Mice, Rats, and Cats

Soft robotic platform for controlled, progressive and reversible aortic constriction in a small animal model

Modulating Cardiac Hemodynamics Using Tunable Soft Robotic Sleeves in a Porcine Model of HFpEF Physiology for Device Testing Applications

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