Spironolactone has antiarrhythmic activity in ischaemic cardiac patients without cardiac failure

Shah, Nimit; Pringle, Stuart D.; Donnan, Peter T.; Struthers, Allan D.

doi:10.1097/hjh.0b013e3282e9a72d

Cited by 34 publications

(25 citation statements)

References 27 publications

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“…spironolactone may not reduce vascular events by the magnitude that its blood pressure-lowering alone would suggest. On the other hand, spironolactone might exert favourable anti-arrhythmic effects by way of its apparently beneficial effects on myocardial collagen and on QT interval length, as has also been seen in other populations [46,47]. Further work is required to explore the full clinical consequences of the issues raised by this study.…”

Section: Discussionmentioning

confidence: 77%

Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles

et al. 2008

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Aims/hypothesis Aldosterone antagonism improves endothelial function (and reduces deaths) in chronic heart failure. It is not known whether similar effects occur in other high-risk groups such as patients with diabetes and hypertension. We therefore assessed the full effects of aldosterone blockade in poorly controlled hypertensive patients with type 2 diabetes, focussing on blood pressure, endothelial function, glycaemic control and key hormones. Methods We performed a randomised, placebo-controlled, double-blind, crossover study on 50 patients with type 2 diabetes and treated but poorly controlled hypertension, comparing spironolactone versus placebo. Patients had their endothelial function assessed by standard forearm venous occlusion plethysmography. Results There was no significant improvement in endotheliumdependent vasodilatation in response to acetylcholine, despite highly significant reductions in systolic and diastolic blood pressure. However, spironolactone significantly worsened glycaemic control, plasma angiotensin II and cortisol. Conclusions/interpretation Spironolactone is highly effective in lowering blood pressure in patients with type 2 diabetes and poorly controlled hypertension on standard treatment, but does not improve vascular endothelial function in this group. We speculate that any tendency for the spironolactoneinduced lowering of blood pressure to improve endothelial function is offset by its tendency to worsen glycaemic control and increase the levels of angiotensin II and even possibly cortisol.Trials Registry no.: ISRCTN 76558770

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Section: Discussionmentioning

confidence: 77%

Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles

et al. 2008

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“…[236][237][238][239][240][241][242][243][244][245][246][247] Aldosterone blockade by spironolactone was shown to reduce all-cause mortality in adults with symptomatic HF by 35% when it was added to standard HF therapy in the RALES trial (Randomized Aldactone Evaluation Study). 248 Subsequently, eplerenone was found to provide a similar survival benefit in adults with HF caused by LV dysfunction 249,250 In addition to improving survival and hospitalization rates, canrenone and spironolactone have been associated with reverse remodeling in adults with HF.…”

Section: Mineralocorticoid Antagonistsmentioning

confidence: 99%

Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association

Feingold¹,

Mahle²,

Auerbach³

et al. 2017

Circulation

220

195

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For many neuromuscular diseases (NMDs), cardiac disease represents a major cause of morbidity and mortality. The management of cardiac disease in NMDs is made challenging by the broad clinical heterogeneity that exists among many NMDs and by limited knowledge about disease-specific cardiovascular pathogenesis and course-modifying interventions. The overlay of compromise in peripheral muscle function and other organ systems, such as the lungs, also makes the simple application of endorsed adult or pediatric heart failure guidelines to the NMD population problematic. In this statement, we provide background on several NMDs in which there is cardiac involvement, highlighting unique features of NMD-associated myocardial disease that require clinicians to tailor their approach to prevention and treatment of heart failure. Undoubtedly, further investigations are required to best inform future guidelines on NMD-specific cardiovascular health risks, treatments, and outcomes. N euromuscular diseases (NMDs) encompass a broad spectrum of diagnoses with overlapping but distinct phenotypes. Common to many NMDs is cardiac involvement. Although the past 3 decades have seen marked advances in our understanding of many NMDs, significant gaps in knowledge remain on how best to approach cardiac care in these patients. For example, survival in Duchenne muscular dystrophy (DMD) has been extended through the use of glucocorticoid use and respiratory support, yet cardiac complications remain a significant cause of morbidity and mortality.1-3 To achieve further gains in care, we will need to improve our understanding of the pathophysiologies driving cardiac involvement in NMDs and advance treatments aimed at preventing the progression of heart failure (HF) and sudden death in NMDs. The recently published findings of an expert working group on cardiac involvement in DMD, which outlined key gaps in knowledge and made specific recommendations aimed at improving diagnosis and management, are a step toward this goal. 4 In this statement, we include a comprehensive overview of the major categories of NMDs with cardiac involvement. For each, a brief background of the gene defect(s), common clinical manifestations (particularly cardiac findings), and current therapies is summarized. Gaps in knowledge are highlighted, and where possible, clinical treatment suggestions are made by the expert writing group appointed by the American Heart Association to review the available literature. Selection of the writing group was performed in accordance with the American Heart Association's conflict-of-interest management policy. Participants volunteered to write sections relevant to their expertise and experience. CLINICAL STATEMENTS AND GUIDELINESconducted a general search of the literature, restricted to human subjects research published between 1980 and 2016. Drafts of each section were written and sent to the chair of the writing group for incorporation into a single document, which was then edited. The edited document was discussed electron...

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“…For instance, it has been reported that serum PICP decreases in hypertensive patients being treated with angiotensin type 1 receptor antagonists 28,[61][62][63][64] or HF patients treated with the loop diuretic torasemide, 27,29 PIIINP decreases in HF patients treated with aldosterone antagonists, [65][66][67][68] CITP and MMP-1 increase in hypertensive patients treated with angiotensin-converting enzyme inhibitors, 69,70 and CITP decreases in hypercholesterolemic patients treated with statins. 71 Thus, the potential influence of previous pharmacological treatment must be carefully considered in studies assessing serum biomarkers of collagen metabolism in cardiac patients.…”

Section: Aspects Related To the Effects Of Pharmacological Treatmentmentioning

confidence: 99%

“…De ce fait, en dépit des nombreuses publications faisant état d'altérations de ces marqueurs dans les maladies cardiaques responsables de la survenue d'une fibrose ou de la destruction du réseau de collagène au niveau du myocarde, seuls quelques uns d'entre eux satisfont à cette exigence et apportent donc des informations quant à leur utilité clinique potentielle (Tableau 4 [20][21][22][23][24][25][28][29][30][31]40,[61][62][63][64][65][66][67][68] ). Il est à noter que certaines de ces études font état d'altérations intéressant plus d'un biomarqueur, ce qui permet d'envisager l'emploi combiné de plusieurs marqueurs afin de recueillir davantage de renseignements sur les perturbations du métabolisme du collagène dont il est ici question.…”

Section: Aspects Liés à L'analyse Coût/bénéficeunclassified

Circulating Biomarkers of Collagen Metabolism in Cardiac Diseases

2010

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A lterations of the structure and composition of cardiomyocyte and noncardiomyocyte compartments of the myocardium appear to play a central role in the pathogenesis of heart failure (HF) associated with a number of cardiac diseases. Among these alterations, changes in the quantity and quality of the extracellular matrix, including the collagen network, have been characterized that induce remodeling of the myocardium and ultimately deteriorate left ventricular (LV) function and facilitate the development of HF. Studies on circulating biomarkers of collagen metabolism have attracted the attention of the medical community, and some circulating biomarkers have been proposed as potential useful tools to improve diagnosis, prognosis, and therapy in cardiac diseases that develop HF. 1 However, the available data are far from conclusive and from affording incremental value to the knowledge provided by more classic diagnostic tools. This is due mainly to 3 limitations. First, collagen is the most abundant protein in the body, and its turnover is so dynamic that not all circulating molecules proposed as biomarkers actually reflect changes in collagen metabolism, namely at the cardiac level. Second, a thorough understanding of the association of a given biomarker with the pathological features of the collagen network in the cardiac disease under study has not been considered essential, thus weakening its pathophysiological meaning. Third, several methodological issues may introduce a number of confounding factors into the measurements of circulating biomarkers of collagen metabolism, thus bringing into question the validity of the available results. Therefore, this article is not aimed at providing a systematic review of all the published information on circulating biomarkers of collagen metabolism in cardiac diseases but at analyzing the biochemical, pathophysiological, and methodological aspects to be taken into account to overcome the above limitations and to improve the clinical applicability of such molecules. Circulating Biomarkers of Collagen Metabolism Collagen MetabolismThe extracellular matrix contains a fibrillar collagen network, a basement membrane, proteoglycans and glycosaminoglycans, and bioactive signaling molecules. The collagen network is a metabolically active structure in the sense that the balance between the synthesis and degradation of collagen determines its turnover, which is estimated to be from 80 to 120 days. 2 The turnover is regulated by fibroblasts and by fibroblasts differentiated to myofibroblasts (Figure 1). 3 These cells respond to mechanical stretch, autocrine and paracrine factors generated locally (eg, vasoactive peptides such as angiotensin II and growth factors such as transforming growth factor-␤ or connective tissue growth factor), and hormones derived from the circulation (eg, aldosterone). In addition, a number of proinflammatory cytokines (eg, tumor necrosis factor-␣, interleukin-1 and -6) secreted by monocytes and macrophages also influence the function of fibroblasts and my...

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Spironolactone has antiarrhythmic activity in ischaemic cardiac patients without cardiac failure

Cited by 34 publications

References 27 publications

Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles

Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles

Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association

Circulating Biomarkers of Collagen Metabolism in Cardiac Diseases

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