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Aims: We set out to assess the utility of endomyocardial biopsy (EMB) in cardiac sarcoidosis (CS). Historically, EMB sensitivity in CS is only ≤25%, but comprehensive analyses of its current diagnostic performance are not available., Methods and Results: The data of 260 consecutive patients with CS (mean age 49 years, 60% female) meeting the Heart Rhythm Society diagnostic criteria were analysed retrospectively. Overall, 216 patients (83%) had undergone EMB, 47 with repeat procedures. EMB overall sensitivity was 38%, rising to 49% after repeat biopsies. On logistic regression analysis, positive EMB was predicted independently by presentation with ventricular tachyarrhythmia with an odds ratio (OR) of 3.8 (95% confidence interval [CI] 1.2-12.0, p = 0.021), left ventricular ejection fraction ≤45% (OR 3.7, 95% CI 1.5-9.1, p = 0.004), elevation of cardiac troponins (OR 2.7, 95% CI 1.1-6.4, p = 0.024), and presence of late gadolinium enhancement in left ventricular mid-apical septal segments on magnetic resonance imaging (OR 4.1, 95% CI 1.2-13.8, p = 0.024). EMB sensitivity, counting in repeats, was 16% in patients (n = 37) without any independent predictor versus 38%, 60%, 79%, and 88% in those with 1 (n = 76), 2 (n = 62), 3 (n = 33), and 4/4 (n = 8) predictors, respectively. The rate of serious complications was 0.7% without mortality or permanent harm. Positive EMB was not an independent predictor of prognosis., Conclusion: The sensitivity of EMB in CS depends on the extent, activity, and location of myocardial involvement, being the higher the more severe CS is. Its use should rely on weighing the pre-test likelihood and individual value of positive biopsy against the procedural risks., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: There are no studies focusing on prognostic factors in giant cell myocarditis (GCM). We aimed to identify predictors of transplant-free survival in GCM., Methods and Results: We analysed the details of 46 patients with GCM (31 women, mean age 51 ± 12 years) seen at our hospital since 1991 and followed for the occurrence of cardiac death or transplantation till May 2015. The association of transplant-free survival with patient characteristics, laboratory data on admission, and myocardial histology in the 38 patients diagnosed prior to death or transplantation was examined. Altogether 26 patients died (n = 8) or underwent transplantation (n = 18) a median of 11 months following symptom onset. The 5-year estimate of transplant-free survival was 42% [95% confidence interval (CI) 35-48%]. By Cox regression analysis, the hazard ratio for death or transplantation was 0.87 (95% CI 0.75-0.99) per +5% difference in LVEF, 1.06 (95% CI 1.03-1.10) per + 1000 ng/L difference in NT-proBNP, and 4.57 (95% CI 1.63-11.28) for cardiac troponin-T above the median of 85 ng/L at presentation. The severity of necrosis and fibrosis in myocardial biopsy, graded by the consensus of two cardiac pathologists as none, mild, moderate, or severe, predicted the outcome with a hazard ratio of 7.17 (95% CI 2.29-22.40) for the presence of either necrosis or fibrosis of at least moderate extent., Conclusions: In GCM, the probability of transplant-free survival is 42% at 5 years from symptom onset. Markers of myocyte injury and cardiac dysfunction help predict the outcome., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Background: Osteoprotegerin (OPG) and the receptor activator of nuclear factor-kappaB ligand (RANKL), two cytokines regulating bone remodeling, have recently been raised as potential pathogenetic factors in cardiovascular diseases. We have studied circulating and myocardial OPG and RANKL in patients having severe aortic stenosis (AS) with or without heart failure (HF)., Methods: We studied 131 adults with AS. Blood was sampled from the aortic root, coronary sinus, and femoral vein at cardiac catheterization. LV myocardial biopsies were taken at surgery. Plasma OPG and soluble (s)RANKL were analyzed by ELISA, and myocardial OPG and RANKL by RT-PCR and immunohistochemistry., Results: Circulating OPG was elevated in AS patients with HF, the association being independent of age, sex, and presence of coronary artery disease (beta=0.17, p=0.033). Elevated plasma OPG decreased after valve replacement in patients with preoperative HF (p=0.0005). Relative to its concentration in the aortic root, plasma OPG was reduced in the coronary sinus (p<0.05) and in the femoral vein (p<0.001), these arteriovenous gradients being accentuated in HF (p=0.003)., Conclusions: HF due to LV pressure overload in AS increases circulating OPG and augments OPG extraction by the heart and peripheral tissues. OPG may be involved in the pathogenesis of HF and could serve as a useful biomarker in HF due to LV pressure overload.

Background: Vasoactive intestinal peptide (VIP) is a peptidergic neurotransmitter and a vasodilator with positive inotropic and chronotropic properties. Whether and how VIP contributes to the neuroendocrine response in heart failure (HF) is disputed, and there are no data on VIP in pressure overload-induced HF., Methods: We studied 129 adults with isolated aortic valve stenosis (AS). Blood was sampled from the aortic root and, in a subset of 48 patients, also from the coronary sinus for determination of VIP by radioimmunoassay. HF was diagnosed according to the European Society of Cardiology criteria., Results: Plasma VIP (mean+/-S.E.M.) was slightly higher in patients with HF (22.6+/-0.9 pmol/l, n=41) than in patients free of HF (21.1+/-0.5 pmol/l, n=88) or in 11 control patients without structural heart disease (20.0+/-1.3 pmol/l, n=11) (p=0.030 across the groups). VIP did not correlate with any measurement of cardiac structure or function in AS. The change in plasma VIP from aortic root to coronary sinus averaged +1.2+/-0.4 pmol/l in the 11 control patients (p=0.021), +1.2+/-0.2 pmol/l in 33 AS patients free of HF (p<0.001) and +0.8+/-0.3 pmol/l in 15 AS patients with HF (p=0.037)., Conclusions: Both structurally normal and diseased hearts release VIP into the coronary sinus. Although marginally elevated in the systemic circulation, VIP is unlikely to contribute significantly to the neuroendocrine activation in HF due to pressure overload.

Background: Plasma B-type natriuretic peptide (BNP), as well as the N-terminal part of the prohormone (Nt-BNP), are frequently elevated in aortic valve stenosis (AS). Yet, their release from the heart into the circulation has never been directly studied in AS., Aim: To assess the release of Nt-BNP in AS with focus on the identification of its main determinants., Methods: We studied 49 adult patients undergoing preoperative cardiac catheterization for isolated AS. Blood was sampled from the aortic root and the coronary sinus for Nt-BNP determination by immunoassay., Results: The mean (+/-S.E.) transcardiac Nt-BNP step-up averaged 79+/-53 pmol/l in 11 control patients free of structural heart disease, 75+/-32 pmol/l in 31 AS patients free of heart failure (HF), 236+/-62 pmol/l in 8 AS patients with diastolic HF (ejection fraction > or = 50%, pulmonary wedge pressure > 14 mm Hg) and 469+/-66 pmol/l in 7 AS patients with systolic HF (ejection fraction < 50%, wedge pressure > 14 mm Hg) (p<0.001). The transcardiac Nt-BNP gradient was independently associated with left ventricular (LV) end-diastolic pressure (beta=0.47, p<0.001) and ejection fraction (beta=-0.29, p<0.019) and with co-existent coronary artery disease (beta=0.23, p=0.050)., Conclusion: LV diastolic and systolic dysfunction along with coronary artery disease are likely to be the key determinants of cardiac Nt-BNP release in AS. The transcardiac Nt-BNP gradient increases on average three-fold with the development of diastolic HF and six-fold in systolic HF.

Background: The pregnancy hormone relaxin has been raised as a new compensatory mediator of cardiac origin in heart failure (HF). We set out to assess the role of relaxin in pressure overload-induced human HF., Methods: We studied 129 adult patients undergoing cardiac catheterization for isolated aortic valve stenosis (AS). Blood was sampled from the aortic root and, in a subset of 49 patients, from the coronary sinus for the determination of plasma relaxin by enzyme immunoassay. HF was diagnosed when the patient had dyspnea or fatigue on ordinary effort in association with pulmonary wedge pressure >14 mm Hg at catheterization., Results: Forty-one patients had HF, which was systolic (ejection fraction <50%) in 16 patients and diastolic in 25 patients. The median plasma relaxin was 32 pg/ml (<12-297 pg/ml) in 88 AS patients without HF, 28 pg/ml (<12-825 pg/ml) in the 41 AS patients with HF, and 42 pg/ml (range, <12-100 pg/ml) in 11 control patients free of heart disease (p=0.82). Plasma relaxin did not correlate with any measurement of cardiac structure or function. The concentration gradients of relaxin from the aortic root to the coronary sinus indicated relaxin extraction by the heart in the control patients (median change, -5 pg/ml, p=0.038) vs. relaxin production in patients with systolic HF (median change, +6 pg/ml, p=0.028) (p=0.002 between groups)., Conclusions: Although the heart may release relaxin into the circulation in certain forms of HF, this does not translate into elevated systemic concentrations. Relaxin is not a major player in human HF.