The SEISICAT study: a pilot study assessing efficacy and safety of spironolactone in cats with congestive heart failure secondary to cardiomyopathy

323

264

Chronic activation of the renin‐angiotensin‐aldosterone system (RAAS) promotes and perpetuates the syndromes of congestive heart failure, systemic hypertension, and chronic kidney disease. Excessive circulating and tissue angiotensin II (AngII) and aldosterone levels lead to a pro‐fibrotic, ‐inflammatory, and ‐hypertrophic milieu that causes remodeling and dysfunction in cardiovascular and renal tissues. Understanding of the role of the RAAS in this abnormal pathologic remodeling has grown over the past few decades and numerous medical therapies aimed at suppressing the RAAS have been developed. Despite this, morbidity from these diseases remains high. Continued investigation into the complexities of the RAAS should help clinicians modulate (suppress or enhance) components of this system and improve quality of life and survival. This review focuses on updates in our understanding of the RAAS and the pathophysiology of AngII and aldosterone excess, reviewing what is known about its suppression in cardiovascular and renal diseases, especially in the cat and dog.

Section: Suppression Of Raasmentioning

confidence: 99%

The renin‐angiotensin‐aldosterone system and its suppression

Ames

Atkins

Pitt

2019

323

264

“…Torsemide may be considered in place of furosemide in cats with persistent CHF despite high doses of furosemide (>6 mg/kg/day PO), at a starting dose of 0.1 to 0.2 mg/kg PO q24h and uptitrating to effect (LOE low). Spironolactone 1 to 2 mg/kg PO q12h to q24h also can be considered for management of chronic CHF . Adverse reactions (eg, ulcerative dermatitis) have been reported in Maine Coon cats treated with spironolactone at a dosage of 2 mg/kg q12h (LOE medium) .…”

Section: Treatmentmentioning

confidence: 99%

ACVIM consensus statement guidelines for the classification, diagnosis, and management of cardiomyopathies in cats

Fuentes

Abbott

Chetboul

et al. 2020

191

236

Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide the veterinary community with up-to-date information on the pathophysiology, diagnosis, and treatment of clinically important animal diseases. The ACVIM Board of Regents oversees selection of relevant topics, identification of panel members with the expertise to draft the statements, and other aspects of assuring the integrity of the process. The statements are derived from evidence-based medicine whenever possible and the panel offers interpretive comments when such evidence is inadequate or contradictory. A draft is prepared by the panel, followed by solicitation of input by the ACVIM membership that may be incorporated into the statement. It is then submitted to the Journal of Veterinary Internal Medicine, where it is edited before publication. The authors are solely responsible for the content of the statements. AbstractCardiomyopathies are a heterogeneous group of myocardial disorders of mostly unknown etiology, and they occur commonly in cats. In some cats, they are welltolerated and are associated with normal life expectancy, but in other cats they can result in congestive heart failure, arterial thromboembolism or sudden death.Cardiomyopathy classification in cats can be challenging, and in this consensus statement we outline a classification system based on cardiac structure and function (phenotype). We also introduce a staging system for cardiomyopathy that includes subdivision of cats with subclinical cardiomyopathy into those at low risk

“…7,8 Unlike ACE, which cleaves 2 amino acids, ACE2 removes a single amino acid from AT1 and AT2, forming angiotensin 1-9 (Ang1-9) and angiotensin 1-7 (Ang1-7), respectively ( Figure 1). Despite a structural difference of just 1 amino acid, Ang1-7, Ang1-9, and other APs such as angiotensin [1][2][3][4][5] are vasodilatory, natriuretic, and cardioprotective. 9 This discovery has expanded our understanding of the AP system and use of traditional RAASi drugs, such as ACEI, beyond just AT1 and AT2.…”

Section: Introductionmentioning

confidence: 99%

Effect of angiotensin receptor blockers and angiotensin‐converting enzyme 2 on plasma equilibrium angiotensin peptide concentrations in cats with heart disease

Larouche‐Lebel

Loughran

Huh

et al. 2020

Background Little is known about the effect of renin angiotensin aldosterone system‐inhibiting (RAASi) drugs on alternative angiotensin peptides (APs) such as angiotensin 1‐7 (Ang1‐7), which are mediated by angiotensin‐converting enzyme 2 (ACE2). Hypothesis/Objectives Angiotensin receptor blockers (ARBs) would alter balance of APs and differences would be magnified in vitro by incubation of plasma samples with recombinant human ACE2 (rhACE2). Animals Six cats with cardiomyopathy (CM), 8 healthy cats. Methods Prospective open label trial. Plasma equilibrium concentrations of APs were measured in healthy cats as well as in CM cats that first received no RAASi drugs (CMnoRAASi) and then after 14 days of PO telmisartan (CMARB). Plasma APs also were measured after in vitro incubation with rhACE2. Results No significant differences were found between healthy and CMnoRAASi groups. Concentrations of several APs, including angiotensin I (AT1) and angiotensin II (AT2) were significantly different between CMnoRAASi and CMARB groups. Incubation with rhACE2 decreased AT1 and AT2 in both groups. The geometric mean concentration of Ang1‐7 was significantly higher in CMARB (4.9 pg/mL; 95% confidence interval [CI], 3.7‐6.4 pg/mL) vs CMnoRAASi (3.2 pg/mL; 95% CI, 2.2‐4.7 pg/mL; P = .01) and in CMARB + ACE2 (5.0 pg/mL; 95% CI, 3.9‐6.4 pg/mL) vs CMnoRAASi + ACE2 (3.0 pg/mL; 95% CI, 1.7‐5.5 pg/mL; P = .01). The most favorable theoretical AP profile that maximized Ang1‐7 and other alternative APs was CMARB + ACE2. Conclusions and Clinical Importance Balance between traditional and alternative APs can be favorably shifted using ARBs and in vitro incubation with rhACE2. These data shed light on new AP‐targeting strategies in cats with CM.