Incremental prognostic value of a complex left ventricular remodeling classification in asymptomatic for heart failure hypertensive patients

Fabiani, Iacopo; Pugliese, Nicola Riccardo; Carrubba, Salvatore La; Conte, Lucia; Antonini‐Canterin, Francesco; Colonna, Paolo; Benedetto, Frank; Calogero, Enrico; Barletta, Valentina; Carerj, Scipione; Buralli, Simona; Taddei, Stefano; Romano, Maria Francesca; Bello, Vitantonio Di

doi:10.1016/j.jash.2017.05.005

Cited by 19 publications

(14 citation statements)

References 27 publications

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“…Ventricular remodeling often occurs as a consequence of chronic pressure overload, resulting in progressive alterations in size, mass, and structure of the heart. The process is associated with poor prognosis due to ventricular dysfunction 33. Animal studies and clinical implications of cardiac remodeling have provided strong evidence showing that stimulation of Ang II, production of reactive oxygen species, release of inflammatory mediators, and deposition of collagen are mostly implicated in the development of cardiac remodeling 34.…”

Section: Discussionmentioning

confidence: 99%

<p>Liraglutide attenuates cardiac remodeling and improves heart function after abdominal aortic constriction through blocking angiotensin II type 1 receptor in rats</p>

Zheng¹,

Bai²,

Zhang³

et al. 2019

DDDT

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Objective Angiotensin II (Ang II) is known to contribute to the pathogenesis of heart failure by eliciting cardiac remodeling and dysfunction. The glucagon-like peptide-1 (GLP-1) has been shown to exert cardioprotective effects in animals and patients. This study investigates whether GLP-1 receptor agonist liraglutide inhibits abdominal aortic constriction (AAC)-induced cardiac fibrosis and dysfunction through blocking Ang II type 1 receptor (AT1R) signaling. Methods Sprague-Dawley rats were subjected to sham operation and abdominal aortic banding procedure for 16 weeks. In treated rats, liraglutide (0.3 mg/kg) was subcutaneously injected twice daily or telmisartan (10 mg/kg/day), the AT1R blocker, was administered by gastric gavage. Results Relative to the animals with AAC, liraglutide reduced protein level of the AT1R and upregulated the AT2R, as evidenced by reduced ratio of AT1R/AT2R (0.59±0.04 vs. 0.91±0.06, p <0.05). Furthermore, the expression of angiotensin converting enzyme 2 was upregulated, tissue levels of malondialdehyde and B-type natriuretic peptide were reduced, and superoxide dismutase activity was increased. Along with a reduction in HW/BW ratio, cardiomyocyte hypertrophy was inhibited. In coincidence with these changes, liraglutide significantly decreased the populations of macrophages and myofibroblasts in the myocardium, which were accompanied by reduced protein levels of transforming growth factor beta1, Smad2/3/4, and upregulated smad7. The synthesis of collagen I and III was inhibited and collagen-rich fibrosis was attenuated. Consistent with these findings, cardiac systolic function was preserved, as shown by increased left ventricular systolic pressure (110±5 vs. 99±2 mmHg, p <0.05), ejection fraction (83%±2% vs. 69%±4%, p <0.05) and fraction shortening (49%±2% vs. 35%±3%, p <0.05). Treatment with telmisartan provided a comparable level of protection as compared with liraglutide in all the parameters measured. Conclusion Taken together, liraglutide ameliorates cardiac fibrosis and dysfunction, potentially via suppressing the AT1R-mediated events. These data indicate that liraglutide might be selected as an add-on drug to prevent the progression of heart failure.

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Section: Discussionmentioning

confidence: 99%

<p>Liraglutide attenuates cardiac remodeling and improves heart function after abdominal aortic constriction through blocking angiotensin II type 1 receptor in rats</p>

Zheng¹,

Bai²,

Zhang³

et al. 2019

DDDT

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show abstract

“…Moreover, the reduction in LV volumes, but not LVMI, resulted in an increased M/V ratio. This suggests a positive action on cardiac remodelling [48] and myocardial wall stress [49], with potential favourable prognostic implications [50].…”

Section: Discussionmentioning

confidence: 99%

Cardiac effects of 6 months' dietary nitrate and spironolactone in patients with hypertension and with/at risk of type 2 diabetes, in the factorial design, double‐blind, randomized controlled VaSera trial

Faconti

Mills

Govoni

et al. 2018

Brit J Clinical Pharma

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Aims The aims of the present study were to explore whether a long‐term intervention with dietary nitrate [(NO3−), a potential tolerance‐free source of beneficial vasoactive nitric oxide] and spironolactone (to oppose aldosterone's potential deleterious cardiovascular effects) improve cardiac structure/function, independently of blood pressure (BP), in patients with/at risk of type 2 diabetes (a population at risk of heart failure). Methods A subsample of participants in our double‐blind, randomized, factorial‐design intervention (VaSera) trial of active beetroot juice as a nitrate source (≤11.2 mmol) or placebo (nitrate depleted) beetroot juice, and either ≤50 mg spironolactone or ≤16 mg doxazosin (control), had transthoracic cardiac ultrasounds at baseline (n = 105), and at 3 months and 6 months (n = 87) after the start of the intervention. Analysis was by modified intent‐to‐treat. Results Nitrate‐containing juice (n = 40) decreased left ventricular (LV) end‐diastolic volume {−6.3 [95% confidence interval (CI) –11.1, –1.6] ml} and end‐systolic volume [−3.2 (95% CI −5.9, –0.5) ml], and increased end‐diastolic mass/volume ratio [+0.04 (95% CI 0.00, 0.07)], relative to placebo juice (n = 47). Spironolactone (n = 44) reduced relative wall thickness compared with doxazosin (n = 43) [−0.01 (95% CI −0.02, –0.00)]. Although spironolactone reduced LV mass index relative to baseline [−1.48 (95% CI −2.08, –0.88) g m–2.7], there was no difference vs. doxazosin [−0.85 (95% CI −1.76, 0.05) g m–2.7]. Spironolactone also decreased the E/A ratio [−0.12 (95% CI −0.19, –0.04)] and increased S′ (a tissue‐Doppler systolic function index) by 0.52 (95% CI 0.05, 1.0) cm s–1. BP did not differ between the juices, or between the drugs. Conclusions Six months' dietary nitrate decreased LV volumes ~5%, representing new, sustained, BP‐independent benefits on cardiac structure, extending mechanisms characterized in preclinical models of heart failure. Spironolactone's effects on cardiac remodelling and systolic–diastolic function, although confirmatory, were independent of BP.

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“…The immunized mice showed the absence of hypertrophy and dilation as indicated by the lack of significant increase in the diastolic septal/posterior wall thickness indices and end-diastolic volume. However, the RWT of 0.43 in the immunized mice (normal RWT = 0.32–0.42) identifies concentric remodeling without hypertrophy whereas RWT of 0.39 identifies a normal morphology as seen in the naive mice ( 51 ). No differences with body weight (19.20 ± 0.32 vs. 18.23 ± 0.44 g), heart weight (87.25 ± 1.11 vs. 84.00 ± 1.73 mg) or heart/body weight ratio (4.55 ± 0.03 vs. 4.61 ± 0.07 mg/g) were observed between immunized and control groups (Figure S2 in Supplementary Material).…”

Section: Resultsmentioning

confidence: 99%

β1-Adrenergic Receptor Contains Multiple IAk and IEk Binding Epitopes That Induce T Cell Responses with Varying Degrees of Autoimmune Myocarditis in A/J Mice

et al. 2017

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Myocarditis/dilated cardiomyopathy (DCM) patients can develop autoantibodies to various cardiac antigens and one major antigen is β1-adrenergic receptor (β1AR). Previous reports indicate that animals immunized with a β1AR fragment encompassing, 197–222 amino acids for a prolonged period can develop DCM by producing autoantibodies, but existence of T cell epitopes, if any, were unknown. Using A/J mice that are highly susceptible to lymphocytic myocarditis, we have identified β1AR 171–190, β1AR 181–200, and β1AR 211–230 as the major T cell epitopes that bind major histocompatibility complex class II/IAk or IEk alleles, and by creating IAk and IEk dextramers, we demonstrate that the CD4 T cell responses to be antigen-specific. Of note, all the three epitopes were found also to stimulate CD8 T cells suggesting that they can act as common epitopes for both CD4 and CD8 T cells. While, all epitopes induced only mild myocarditis, the disease-incidence was enhanced in animals immunized with all the three peptides together as a cocktail. Although, antigen-sensitized T cells produced mainly interleukin-17A, their transfer into naive animals yielded no disease. But, steering for T helper 1 response led the T cells reacting to one epitope, β1AR 181–200 to induce severe myocarditis in naive mice. Finally, we demonstrate that all three β1AR epitopes to be unique for T cells as none of them induced antibody responses. Conversely, animals immunized with a non-T cell activator, β1AR 201–220, an equivalent of β1AR 197–222, had antibodies comprising of all IgG isotypes and IgM except, IgA and IgE. Thus, identification of T cell and B cell epitopes of β1AR may be helpful to determine β1AR-reactive autoimmune responses in various experimental settings in A/J mice.

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Incremental prognostic value of a complex left ventricular remodeling classification in asymptomatic for heart failure hypertensive patients

Cited by 19 publications

References 27 publications

<p>Liraglutide attenuates cardiac remodeling and improves heart function after abdominal aortic constriction through blocking angiotensin II type 1 receptor in rats</p>

<p>Liraglutide attenuates cardiac remodeling and improves heart function after abdominal aortic constriction through blocking angiotensin II type 1 receptor in rats</p>

Cardiac effects of 6 months' dietary nitrate and spironolactone in patients with hypertension and with/at risk of type 2 diabetes, in the factorial design, double‐blind, randomized controlled VaSera trial

β1-Adrenergic Receptor Contains Multiple IAk and IEk Binding Epitopes That Induce T Cell Responses with Varying Degrees of Autoimmune Myocarditis in A/J Mice

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