Cardiotrophin-1 plasma levels are associated with the severity of hypertrophy in hypertrophic cardiomyopathy

AimsAtrial fibrillation (AF) and thrombo‐embolism (TE) are associated with reduced survival in hypertrophic cardiomyopathy (HCM), but the absolute risk of TE in patients with and without AF is unclear. The primary aim of this study was to derive and validate a model for estimating the risk of TE in HCM. Exploratory analyses were performed to determine predictors of TE, the performance of the CHA2DS2‐VASc score, and outcome with vitamin K antagonists (VKAs).Methods and resultsA retrospective, longitudinal cohort of seven institutions was used to develop multivariable Cox regression models fitted with pre‐selected predictors. Bootstrapping was used for validation. Of 4821 HCM patients recruited between 1986 and 2008, 172 (3.6%) reached the primary endpoint of cerebrovascular accident (CVA), transient ischaemic attack (TIA), or systemic peripheral embolus within 10 years. A total of 27.5% of patients had a CHA2DS2‐VASc score of 0, of whom 9.8% developed TE during follow‐up. Cox regression revealed an association between TE and age, AF, the interaction between age and AF, TE prior to first evaluation, NYHA class, left atrial (LA) diameter, vascular disease, and maximal LV wall thickness. There was a curvilinear relationship between LA size and TE risk. The model predicted TE with a C‐index of 0.75 [95% confidence interval (CI) 0.70–0.80] and the D‐statistic was 1.30 (95% CI 1.05–1.56). VKA treatment was associated with a 54.8% (95% CI 31–97%, P = 0.037) relative risk reduction in HCM patients with AF.ConclusionsThe study shows that the risk of TE in HCM patients can be identified using a small number of simple clinical features. LA size, in particular, should be monitored closely, and the assessment and treatment of conventional vascular risk factors should be routine practice in older patients. Exploratory analyses show for the first time evidence for a reduction of TE with VKA treatment. The CHA2DS2‐VASc score does not appear to correlate well with the clinical outcome in patients with HCM and should not be used to assess TE risk in this population.

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“…Some patients from this cohort are reported in other recently published studies 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25…”

Section: Methodsmentioning

confidence: 88%

Prediction of thrombo‐embolic risk in patients with hypertrophic cardiomyopathy (HCMRisk‐CVA)

Guttmann

Pavlou

O’Mahony

et al. 2015

European J of Heart Fail

127

105

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“…In humans, elevated serum levels of CT-1 have been observed in patients with heart failure (HF) [33] and hypertensive heart disease [34]. While some authors have reported an association between circulating CT-1 and left ventricular structure and function [34][35][36][37][38][39], other studies could not confirm these findings [40]. Elevated CT-1 mRNA and protein were observed in the ventricles from rats with myocardial infarction, and in patients with ischemic heart disease, valvular heart disease or after myocardial infarction (MI) [41].…”

Section: Cardiovascularmentioning

confidence: 99%

Cardiotrophin-1: A multifaceted cytokine

López-Yoldi

Moreno-Aliaga

Bustos

2015

Cytokine & Growth Factor Reviews

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“…Interestingly, treatment-induced decrease of plasma cardiotrophin-1 paralleled LV hypertrophy regression in treated hypertension [19,25]. Data also support an association between cardiotrophin-1 and LV mass in other pathologic states, including hypertrophic [27] and dilated cardiomyopathy [28]. Other authors could not confirm, however, the above findings.…”

mentioning

confidence: 89%

“…Second, the limited sample size and the tiny number of normotensive controls (only 25 patients) make it difficult to draw definite conclusions on the independent contribution of cardiotrophin-1 in stratifying the risk of LV systolic dysfunction. Third, most of the published studies on the association between circulating cardiotrophin-1 and LV structure and function have been obtained by the same research group [19][20][21][22][24][25][26][27]30], whereas studies from other groups could not confirm the same findings [29]. Also, the inclusion of hypertensive patients under blood pressure-lowering drug treatment may be misleading in the interpretation of the study results.…”

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confidence: 98%

From hypertension to hypertrophy to heart failure

Schillaci

Pucci

Perlini

2013

Journal of Hypertension

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See original paper on page 587H eart failure is a major and growing public health issue, with high prevalence, poor clinical outcomes, and large healthcare costs [1]. Hypertension, a leading risk factor for congestive heart failure, represents the most common comorbidity in patients with heart failure [2], and carries an attributable risk of over 40% at the population level [3]. According to the American College of Cardiology/American Heart Association guidelines, all hypertensive patients without symptoms of heart failure and without structural heart disease should be classified as belonging to stage A, which denotes a high risk for heart failure, whereas those with structural heart involvement denoted, for instance, by left ventricular (LV) hypertrophy should be classified as belonging to stage B [4].Transition from hypertension to overt heart failure is characterized by a number of functional and structural alterations, which include LV hypertrophy and asymptomatic LV systolic and diastolic dysfunction [5]. Although LV systolic chamber function is almost invariably normal or even above normal in uncomplicated patients with essential hypertension [6,7], the use of the more physiologic midwall mechanic indexes identifies reduced myocardial systolic function in a large subgroup of hypertensive patients, whose chamber function is still preserved thanks to a more concentric LV geometry [8][9]. In individuals with untreated essential hypertension, the prevalence of asymptomatic LV systolic dysfunction is as low as 4% when considering traditional endocardial or chamber mechanics [10,11], and increases to 18% when assessed through midwall fractional shortening [10]. Also, midwall fractional shortening has a strong, independent, inverse relationship with a number of prognostically adverse markers including relative wall thickness as an index of LV concentric geometry [12], LV mass [12], and an inappropriately high LV mass, that is, beyond values required to compensate cardiac workload at a given body size and sex [13]. The coexistence of a low midwall fractional shortening and a high LV mass identifies a subgroup of hypertensive patients at a particularly high risk for cardiac morbidity and mortality [14]. Moreover, LV hypertrophy regression and normalization of chamber geometry during antihypertensive treatment are associated with improved midwall function [15].Epidemiological studies have identified clinical and demographic factors that increase the risk of developing LV systolic dysfunction in hypertension, including age, male sex, smoking, LV hypertrophy, and uncontrolled blood pressure [10,12,16]. However, knowledge of these risk factors alone cannot provide the means to predict the presence of systolic dysfunction, holds no real specificity and sensitivity, and is not useful in a clinically relevant context. As such, analytic measurements that would be easy to use and cost-effective for the detection of LV systolic dysfunction in an ambulatory setting would have significant clinical import. Although hemodynamic f...

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Cardiotrophin-1 plasma levels are associated with the severity of hypertrophy in hypertrophic cardiomyopathy

Cited by 26 publications

References 32 publications

Prediction of thrombo‐embolic risk in patients with hypertrophic cardiomyopathy (HCMRisk‐CVA)

Prediction of thrombo‐embolic risk in patients with hypertrophic cardiomyopathy (HCMRisk‐CVA)

Cardiotrophin-1: A multifaceted cytokine

From hypertension to hypertrophy to heart failure

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