Evgeny Belyavskiy

Normal range and usefulness of right ventricular systolic strain to detect subtle right ventricular systolic abnormalities in patients with heart failure: a multicentre study

Aims The aim of the present multicentre study was to analyse a large cohort of healthy subjects and patients with a common condition such as heart failure (HF) with the purpose of determining the normal range and the usefulness of right ventricular (RV) systolic strain to detect subtle RV systolic abnormalities using 2D speckle-tracking echocardiography. Methods and results We analysed 238 healthy subjects and a cohort of 642 patients characterized by asymptomatic patients (n = 216) and patients with HF with preserved (HFpEF) and reduced (HFrEF) ejection fraction (n = 218 and n = 208, respectively) prospectively included in 10 centres. The normal range of RV systolic strain analysing the healthy subjects was as follows: RV global strain −24.5 ± 3.8 and RV free wall strain −28.5 ± 4.8 (lowest expected value −17 and −19%, respectively). Concerning the ability of these myocardial parameters to detect subtle RV systolic abnormalities, RV global and free wall systolic strain were able to detect subtle RV longitudinal systolic abnormalities in a significant proportion of patients with HFrEF and to a lesser extent in HFpEF despite preserved tricuspid annular plane systolic excursion, tricuspid lateral annular peak systolic velocity by pulsed tissue Doppler imaging, and RV fractional area change. In addition, RV global and free wall systolic strain were significantly linked to the symptomatic status of the patients. Conclusions The findings from this study provide important data regarding the normal range of RV global and free wall systolic strain and highlight the clinical relevance of these RV myocardial parameters to detect subtle RV systolic abnormalities in patients with HF.

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: results from the EPATH randomized, placebo-controlled trial

Background: Accumulating evidence points toward mutual interaction between parathyroid hormone (PTH) and aldosterone as potential mechanism for increasing cardiovascular risk in primary hyperparathyroidism (pHPT). Methods: The Eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism (EPATH) trial is a single-center, randomized, double-blind, parallel-group, placebo-controlled trial. The primary aim is to evaluate the effects of the mineralocorticoid receptor antagonist eplerenone on plasma intact PTH (iPTH) concentration in patients with pHPT. Secondary end points comprised surrogate parameters of cardiovascular health [24-h ambulatory SBP and DBP and echocardiographic parameters related to systolic/diastolic function as well as to cardiac dimensions]. Results: We enrolled 110 study participants with pHPT, 25-hydroxyvitamin D at least 20 ng/ml and estimated glomerular filtration rate more than 50 ml/min per 1.73 m2. Patients were 1 : 1 randomly assigned to receive either 25 mg eplerenone once daily (up-titration after 4 weeks to 50 mg/day) or matching placebo for a treatment period of 8 weeks. The study was completed by 97 participants [mean (SD) age: 67.5 ± 9.5 years; 78.4% women). The mean treatment effect (95% confidence interval) for iPTH was 1.0 (0.9–1.1; P = 0.777) pg/ml. Mean 24-h ambulatory SBP and DBP decreased significantly [mean change (95% confidence interval) −6.3 (−9.4 to −3.3) and −3.7 (−5.7 to −1.7) mmHg, respectively; P < 0.001]. No differences were seen in any further secondary outcomes or frequency of adverse events. Conclusion: In pHPT, treatment with eplerenone compared with placebo had no effect on circulating iPTH levels. Eplerenone treatment was well tolerated and safe and followed by significant decrease of ambulatory blood pressure.

Left ventricular longitudinal systolic function analysed by 2D speckle-tracking echocardiography in heart failure with preserved ejection fraction: a meta-analysis

Background The purpose of this meta-analysis was to confirm if the global longitudinal systolic function of the left ventricle (LV) is altered in patients with heart failure with preserved ejection fraction (HFpEF). Methods We searched in different databases (Medline, Embase and Cochrane) studies that analysed LV global longitudinal systolic strain (GLS) in patients with HFpEF and in controls (such as healthy subjects or asymptomatic patients with arterial hypertension, diabetes mellitus or coronary artery disease). Results Twenty-two studies (2284 patients with HFpEF and 2302 controls) were included in the final analysis. Patients with HFpEF had significantly lower GLS than healthy subjects (mean −15.7% (range −12% to −18.9%) vs mean −19.9% (range −17.1% to −21.5%), weighted mean difference −4.2% (95% CI −3.3% to −5.0%), p < 0.001, respectively). In addition, patients with HFpEF had also significantly lower GLS than asymptomatic patients (mean −15.5% (range −13.4% to −18.4%) vs mean −18.3% (range −15.1% to −20.4%), weighted mean difference −2.8%(95% CI −1.9% to −3.6%), p < 0.001, respectively). In line, 10 studies showed that the rate of abnormal GLS was significantly higher in patients with HFpEF (mean 65.4% (range 37%–95%)) than in asymptomatic subjects (mean 13% (range 0%–29.6%)). Regarding the prognostic relevance of abnormal GLS in HFpEF, two multicentre studies with large sample size (447 and 348) and high number of events (115 and 177) showed that patients with abnormal GLS had worse cardiovascular (CV) outcomes than those with normal GLS (HR for CV mortality and HF hospitalisation 2.14 (95% CI 1.26 to 3.66) and 1.94 (95% CI 1.22 to 3.07)), even adjusting these analyses for multiples clinical and echocardiographic variables. Conclusion The present meta-analysis analysing 2284 patients with HFpEF and 2302 controls confirms that the longitudinal systolic function of the LV is significantly altered in high proportion of patients with HFpEF. Further large multicentre studies with the aim to confirm the prognostic role of abnormal GLS in HFpEF are warranted.

Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial

Observational studies suggested a link between bone disease and left ventricular (LV) dysfunction that may be pronounced in hyperparathyroid conditions. We therefore aimed to test the hypothesis that circulating markers of bone turnover correlate with LV function in a cohort of patients with primary hyperparathyroidism (pHPT). Cross-sectional data of 155 subjects with pHPT were analyzed who participated in the “Eplerenone in Primary Hyperparathyroidism” (EPATH) Trial. Multivariate linear regression analyses with LV ejection fraction (LVEF, systolic function) or peak early transmitral filling velocity (e’, diastolic function) as dependent variables and N-terminal propeptide of procollagen type 1 (P1NP), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), or beta-crosslaps (CTX) as the respective independent variable were performed. Analyses were additionally adjusted for plasma parathyroid hormone, plasma calcium, age, sex, HbA1c, body mass index, mean 24-hours systolic blood pressure, smoking status, estimated glomerular filtration rate, antihypertensive treatment, osteoporosis treatment, 25-hydroxy vitamin D and N-terminal pro-brain B-type natriuretic peptide. Independent relationships were observed between P1NP and LVEF (adjusted β-coefficient = 0.201, P = 0.035) and e’ (β = 0.188, P = 0.042), respectively. OC (β = 0.192, P = 0.039) and BALP (β = 0.198, P = 0.030) were each independently related with e’. CTX showed no correlations with LVEF or e’. In conclusion, high bone formation markers were independently and paradoxically related with better LV diastolic and, partly, better systolic function, in the setting of pHPT. Potentially cardio-protective properties of stimulated bone formation in the context of hyperparathyroidism should be explored in future studies.

Parathyroid hormone, aldosterone-to-renin ratio and fibroblast growth factor-23 as determinants of nocturnal blood pressure in primary hyperparathyroidism: the eplerenone in primary hyperparathyroidism trial

Objectives: The high prevalence of arterial hypertension in primary hyperparathyroidism (pHPT) is largely unexplained. Apart from parathyroid hormone (PTH), the mineral hormones fibroblast growth factor (FGF)-23 and aldosterone-to-renin ratio (ARR) are upregulated in pHPT. We aimed to determine whether nocturnal blood pressure (BP) is related with PTH, FGF-23 or ARR in a relatively large sample of pHPT patients. Methods: Cross-sectional data of the single-center “Eplerenone in Primary Hyperparathyroidism” trial were used. All patients with a biochemical diagnosis of pHPT who had both available 24-h ambulatory BP monitoring and valid laboratory data were included. Results: Full data were available in 136 patients (mean age 67 ± 10 years, 78% women). Median PTH was 99 (interquartile range: 82–124) pg/ml and mean calcium was 2.63 ± 0.15 mmol/l. ARR, but not PTH or FGF-23, was significantly and directly related with nocturnal SBP (Pearsons r = 0.241, P < 0.01) and DBP (r = 0.328, P < 0.01). In multivariate regression analyses, with adjustment for age, sex, PTH, FGF-23, traditional cardiovascular risk factors, antihypertensive medication and parameters of calcium metabolism ARR remained significantly and directly related with nocturnal BP (SBP: adjusted &bgr;-coefficient = 0.289, P < 0.01; DBP: &bgr; = 0.399, P < 0.01). The relationship between ARR and nocturnal SBP was exclusively present in patients with PTH levels above the median of 99 pg/ml. Conclusion: ARR, but not FGF-23 or PTH, was independently and directly related with nocturnal BP parameters in patients with pHPT, and this relationship was dependent on pHPT disease severity. Inappropriately, elevated aldosterone may partially explain the high prevalence of arterial hypertension in pHPT.

Plasma Parathyroid Hormone Is Independently Related to Nocturnal Blood Pressure in Hypertensive Patients: The Styrian Hypertension Study.

High parathyroid hormone (PTH) has been linked with high blood pressure (BP), but the relationship with 24‐hour ambulatory blood pressure monitoring is largely unknown. The authors therefore analyzed cross‐sectional data of 292 hypertensive patients participating in the Styrian Hypertension Study (mean age, 61±11 years; 53% women). Median plasma PTH (interquartile range) determined after an overnight fast was 49 pg/mL (39–61), mean daytime BP was 131/80±12/9 mm Hg, and mean nocturnal BP was 115/67±14/9 mm Hg. In multivariate regression analyses adjusted for BP and PTH‐modifying parameters, PTH was significantly related to nocturnal systolic and diastolic BP (adjusted β‐coefficient 0.140 [P=.03] and 0.175 [P<.01], respectively). PTH was not correlated with daytime BP readings. These data suggest a direct interrelationship between PTH and nocturnal BP regulation. Whether lowering high PTH concentrations reduces the burden of high nocturnal BP remains to be shown in future studies.

Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: the EPATH trial

Abstract Background: Primary hyperparathyroidism (pHPT) is associated with low-grade inflammation, left ventricular hypertrophy and increased cardiovascular mortality, but the association between inflammatory markers and parameters of adverse cardiac remodeling is unknown. We investigated the relationship between C-reactive protein (CRP), the essential amino acid tryptophan and its pro-inflammatory derivatives kynurenine and quinolinic acid (QUIN) with echocardiographic parameters. Methods: Cross-sectional baseline data from the “Eplerenone in Primary Hyperparathyroidism” trial were analyzed. Patients with any acute illness were excluded. We assessed associations between CRP, serum levels of tryptophan, kynurenine and QUIN and left ventricular mass index (LVMI), left atrial volume index (LAVI) and E/e′. Results: Among 136 subjects with pHPT (79% females), 100 (73%) had arterial hypertension and the prevalence of left ventricular hypertrophy was 52%. Multivariate linear regression analyses with LVMI, LAVI and E/e′ as respective dependent variables, and C-reactive protein and tryptophan, kynurenine and QUIN as respective independent variables were performed. Analyses were adjusted for age, sex, blood pressure, parathyroid hormone, calcium and other cardiovascular risk factors. LVMI was independently associated with CRP (adjusted β-coefficient=0.193, p=0.030) and QUIN (β=0.270, p=0.007), but not kynurenine. LAVI was related with CRP (β=0.315, p<0.001), kynurenine (β=0.256, p=0.005) and QUIN (β=0.213, p=0.044). E/e′ was related with kynurenine (β=0.221, p=0.022) and QUIN (β=0.292, p=0.006). Tryptophan was not associated with any of the remodeling parameters. [Correction added after online publication (22 April 2017: The sentence “Among 136 subjects with pHPT (79% females), 100 (73%) had left ventricular hypertrophy.” was corrected to “Among 136 subjects with pHPT (79% females), 100 (73%) had arterial hypertension and the prevalence of left ventricular hypertrophy was 52%.”] Conclusions: Cardiac remodeling is common in pHPT and is associated with low-grade inflammation and activation of the tryptophan-kynurenine pathway. The potential role of kynurenine and QUIN as cardiovascular risk factors may be further investigated in future studies.

Cardiac anomaly detection based on time and frequency domain features using tree-based classifiers

OBJECTIVE Recent advantages in mHealth-enabled ECG recorders boosted the demand for algorithms, which are able to automatically detect cardiac anomalies with high accuracy. APPROACH We present a combined method of classical signal analysis and machine learning which has been developed during the Computing in Cardiology Challenge (CinC) 2017. Almost 400 hand-crafted features have been developed to reflect the complex physiology of cardiac arrhythmias and their appearance in single-channel ECG recordings. For the scope of this article, we performed several experiments on the publicly available challenge dataset to improve the classification accuracy. We compared the performance of two tree-based algorithms-gradient boosted trees and random forests-using different parameters for learning. We assessed the influence of five different sets of training annotations on the classifiers performance. Further, we present a new web-based ECG viewer to review and correct the training labels of a signal data set. Moreover, we analysed the feature importance and evaluated the model performance when using only a subset of the features. The primary data source used in the analysis was the dataset of the CinC 2017, consisting of 8528 signals from four classes. Our best results were achieved using a gradient boosted tree model which worked significantly better than random forests. MAIN RESULTS Official results of the challenge follow-up phase provided by the Challenge organizers on the full hidden test set are 90.8% (Normal), 84.1% (AF), 74.5% (Other), resulting in a mean F1-score of 83.2%, which was only 1.6% behind the challenge winner and 0.2% ahead of the next-best algorithm. Official results were rounded to two decimal places which lead to the equal-second best F1 F -score of 83% with five others. SIGNIFICANCE The algorithm achieved the second-best score among 80 algorithms of the Challenge follow-up phase equal with five others.

Plasma parathyroid hormone and cardiovascular disease in treatment-naive patients with primary hyperparathyroidism: The EPATH trial

Patients with primary hyperparathyroidism are at increased risk for high blood pressure, vascular stiffening, and left ventricular hypertrophy, but previous studies have failed to demonstrate the direct associations with circulating parathyroid hormone (PTH) levels. The authors investigated cross‐sectional relationships between PTH and 24‐hour pulse wave velocity, nocturnal systolic blood pressure, and left ventricular mass index in patients with primary hyperparathyroidism who were treatment‐naive with cinacalcet, renin‐angiotensin‐aldosterone‐system inhibitors, and thiazide or loop diuretics. In 76 patients, mean±SD of pulse wave velocity, nocturnal systolic blood pressure, and left ventricular mass index values were 9.3±1.8 m/s, 116.6±17.0 mm Hg, and 92.8±23.0 g/m². In multivariate linear regression analyses with adjustment for potentially confounding parameters, PTH was independently associated with nocturnal systolic blood pressure (adjusted ß coefficient=.284, P=.040), mean 24‐hour pulse wave velocity (ß=.199, P=.001), and left ventricular mass index (ß=.252, P=.025). PTH may promote vascular and cardiac remodeling in primary hyperparathyroidism. Interventional trials are needed to test the antihypertensive and cardioprotective effects of PTH‐inhibitory treatment strategies.

9B.05: ASSOCIATION OF PLASMA PARATHYROID HORMONE WITH NIGHTTIME BLOOD PRESSURE IN PRIMARY HYPERPARATHYROIDISM-THE "EPLERENONE IN PRIMARY HYPERPARATHYROIDISM" TRIAL.

Objective: High parathyroid hormone (PTH) is a cardiovascular risk factor. Elevated plasma PTH levels are independently linked with high nighttime blood pressure (BP) in hypertensive patients. We therefore investigated the association between PTH and nighttime BP in patients with primary hyperparathyroidism (pHPT). Design and method: We analyzed patients with pHPT who participated in the “Eplerenone in Primary Hyperparathyroidism” (EPATH) Trial. Blood sampling was performed after an overnight fast and all laboratory parameters were determined immediately after blood sampling. 24-hour ambulatory BP monitoring was performed using a certified device (Mobil-O-Graph, I.E.M., Stolberg, Germany). Patients with regular use of the PTH modifying drug cinacalcet or with a reduced left ventricular ejection fraction <= 45% were excluded. Results: We enrolled 120 patients (mean age: 66 +/- 10 years, 98 were females [82%]). Median PTH (IQR) was 94 pg/mL (79 – 113), mean systolic and diastolic nighttime BP were 117 +/- 17 mmHg and 68 +/- 10 mmHg, respectively. PTH was directly correlated with mean systolic and mean diastolic nighttime BP (Spearman rho = 0.246, p = 0.007; rho = 0.214, p = 0.019, respectively). In multivariate linear regression analyses adjusted for age, sex, cholesterol, HbA1c, intake of antihypertensive drugs, 25-hydroxy vitamin D and glomerular filtration rate (CKDEPI), PTH remained significantly related to mean systolic nighttime BP (adjusted beta-coefficient = 0.194, p = 0.047), while the relationship with mean diastolic nighttime BP was not significant (beta = 0.260, p = 0.109). Conclusions: Plasma PTH was associated with mean systolic nighttime BP in patients with pHPT, independently of potential confounders. These novel data from the EPATH Trial further support the notion that PTH directly interferes with nighttime BP regulation. Whether lowering circulating PTH concentrations reduces the burden of high BP remains to be shown in future studies.