Background: Myocardial fibrosis in hypertrophic cardiomyopathy (HCM) is associated with worse clinical outcomes. The availability of circulating biomarkers of myocardial fibrosis and hypertrophy would be helpful in clinical practice. Objective: The aim of this study was to evaluate usefulness of various biomarkers of myocardial fibrosis and hypertrophy in HCM. Methods: Levels of biomarkers: soluble ST2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), NT-proBNP and high-sensitivity cardiac troponin T (hs-cTnT) were measured in 60 patients with HCM. All patients underwent cardiac magnetic resonance imaging to calculate parameters of hypertrophy and fibrosis. Results: We observed positive correlations among sST2 levels and left ventricular mass (LVM) (r = 0.32, p = 0.012), LV mass indexed for the body surface area (LVMI) (r = 0.27, p = 0.036) and maximal wall thickness (MWT) (r = 0.31, p = 0.015). No correlation was found between Gal-3 and GDF-15 levels and hypertrophy and fibrosis parameters. We observed positive correlations among hs-cTnT levels and LVM (r = 0.58, p < 0.0001), LVMI (r = 0.48, p = 0.0001), MWT (r = 0.31, p = 0.015) and late gadolinium enhancement (LGE) mass (r = 0.37, p = 0.003). There were positive correlations between NT-proBNP levels and LVM (r = 0.33, p = 0.01), LVMI (r = 0.41, p = 0.001), MWT (r = 0.42, p < 0.001) and LGE mass (r = 0.44, p < 0.001). Conclusions: Although no correlation between sST2 levels and myocardial fibrosis was found, sST2 may provide some additional information about hypertrophy extension. NT-proBNP and hs-cTnT are useful biomarkers in assessment of hypertrophy and fibrosis in HCM.

Background: Estimation of sudden cardiac death (SCD) risk is an integral part of clinical management of patients with hypertrophic cardiomyopathy (HCM). Identification of novel biomarkers of this disease can provide additional criteria for SCD risk stratification. Soluble suppression of tumorigenicity (sST2) and galectin-3 (Gal-3) are useful biomarkers for prognosis of heart failure (HF). Both of them appear to mediate cardiac fibrosis - an important pathogenetic process in HCM. Data about sST2 and Gal-3 usefulness in patients with HCM are limited. Aim: The aim of this study was to evaluate sST2 and Gal-3 as potential novel biomarkers for better risk stratification in HCM. Methods: Serum sST2 and serum Gal-3 levels were measured in 57 patients with HCM and 18 healthy controls. The patients with HCM underwent routine evaluation including medical history, physical examination, blood tests including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) measurements, 12-lead electrocardiography (ECG), 48-hour Holter monitoring and two-dimensional (2D) echocardiography with the assessment of the maximal left ventricular wall thickness (MWT), left atrial diameter (LAD), maximal left ventricular outflow tract (LVOT) gradient and LV ejection fraction (LVEF). Risk of sudden cardiac death (SCD) at 5 years according to HCM SCD-risk calculator was evaluated. The control group underwent ECG, 2D echocardiography and NT-proBNP measurements to exclude asymptomatic heart disease. Results: Concentrations of sST2 and Gal-3 were significantly higher in patients with HCM than in controls (14.9 +/- 5.8 ng/ml vs. 11.7 +/- 3.3 ng/ml, p=0.03 and 8.4 ng/ml [6.8 - 10.0] vs. 6.2 ng/ml [5.8 – 7.7], p=0.005, respectively). Levels of sST2 and Gal-3 were considerably different in the NYHA groups (p=0.008, p=0.009, respectively). Patients who presented non-sustained ventricular tachycardia (nsVT) on 48-hour Holter monitoring had higher levels of sST2 (19.1 ng/ml [12.2 - 24.2] vs. 13.2 ng/ml [10.0 – 17.1], p=0.02). There were no significant relationships between sST2 and Gal-3 levels and HCM SCD-risk, history of syncope presence, family history of SCD, and echocardiographic parameters. Conclusions: Gal-3 levels and sST2 levels were higher in patients with HCM than in control group. There were significant differences in Gal-3 levels between NYHA classes, but no correlations between Gal-3 levels and other parameters were found. Apart from differences in sST2 levels between NYHA classes, we demonstrated higher levels of sST2 in patients with nsVT. These findings suggest that sST2 may be useful as an additional biomarker for better risk stratification in HCM. Background: Estimation of sudden cardiac death (SCD) risk is an integral part of clinical management of patients with hypertrophic cardiomyopathy (HCM). Identification of novel biomarkers of this disease can provide additional criteria for SCD risk stratification. Soluble suppression of tumorigenicity (sST2) and galectin-3 (Gal-3) are useful biomarkers for prognosis of heart failure (HF). Both of them appear to mediate cardiac fibrosis - an important pathogenetic process in HCM. Data about sST2 and Gal-3 usefulness in patients with HCM are limited. Aim: The aim of this study was to evaluate sST2 and Gal-3 as potential novel biomarkers for better risk stratification in HCM. Methods: Serum sST2 and serum Gal-3 levels were measured in 57 patients with HCM and 18 healthy controls. The patients with HCM underwent routine evaluation including medical history, physical examination, blood tests including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) measurements, 12-lead electrocardiography (ECG), 48-hour Holter monitoring and two-dimensional (2D) echocardiography with the assessment of the maximal left ventricular wall thickness (MWT), left atrial diameter (LAD), maximal left ventricular outflow tract (LVOT) gradient and LV ejection fraction (LVEF). Risk of sudden cardiac death (SCD) at 5 years according to HCM SCD-risk calculator was evaluated. The control group underwent ECG, 2D echocardiography and NT-proBNP measurements to exclude asymptomatic heart disease. Results: Concentrations of sST2 and Gal-3 were significantly higher in patients with HCM than in controls (14.9 +/- 5.8 ng/ml vs. 11.7 +/- 3.3 ng/ml, p=0.03 and 8.4 ng/ml [6.8 - 10.0] vs. 6.2 ng/ml [5.8 – 7.7], p=0.005, respectively). Levels of sST2 and Gal-3 were considerably different in the NYHA groups (p=0.008, p=0.009, respectively). Patients who presented non-sustained ventricular tachycardia (nsVT) on 48-hour Holter monitoring had higher levels of sST2 (19.1 ng/ml [12.2 - 24.2] vs. 13.2 ng/ml [10.0 – 17.1], p=0.02). There were no significant relationships between sST2 and Gal-3 levels and HCM SCD-risk, history of syncope presence, family history of SCD, and echocardiographic parameters. Conclusions: Gal-3 levels and sST2 levels were higher in patients with HCM than in control group. There were significant differences in Gal-3 levels between NYHA classes, but no correlations between Gal-3 levels and other parameters were found. Apart from differences in sST2 levels between NYHA classes, we demonstrated higher levels of sST2 in patients with nsVT. These findings suggest that sST2 may be useful as an additional biomarker for better risk stratification in HCM.

Background: Transthyretin amyloidosis (ATTR) is a rare, life-threatening systemic disorder. We present first findings on the cardiac hereditary ATTR in Poland. Methods: Sixty-eight consecutive patients with suspected or known cardiac amyloidosis were evaluated, including blood tests, standard 12-lead electrocardiography (ECG) and transthoracic echocardiography. ATTR was confirmed histologically or non-invasively using 99mTc-DPD scintigraphy. Transthyretin (TTR) gene sequencing was performed. Results: In 2017–2019, 10 unrelated male patients were diagnosed with hereditary ATTR. All patients had very uncommon TTR gene mutations: 7 patients had p.Phe53Leu mutation, 2 patients had p.Glu109Lys mutation and 1 patient had p.Ala101Val mutation. The age of onset ranged from 49 to 67 years (mean [SD] age, 58.7 [6.4] years). On ECG, most patients (70%) had pseudoinfarct pattern and/or low QRS voltage. The maximal wall thickness (MWT) on echocardiography varied considerably among the patients from moderate (16 mm) to massively increased (30 mm). Most patients (90%) had decreased LV ejection fraction (mean [SD], 43 [11] %). On follow-up, we observed progressive heart failure in almost all cases. The first patient with p.Phe53Leu mutation died of heart failure, the second died suddenly, the third successfully underwent combined heart and liver transplant with 15 months survival from the surgery. The patient with p.Ala101Val mutation died of stroke. Conclusions: According to available research, this is the first time types of TTR mutations and clinical characteristics of Polish patients with cardiac hereditary ATTR have been reported. Previous literature data about Polish background in families with p.Phe53Leu mutation and the present results, suggest that this TTR mutation might be endemic in the Polish population. Background: Transthyretin amyloidosis (ATTR) is a rare, life-threatening systemic disorder. We present first findings on the cardiac hereditary ATTR in Poland. Methods: Sixty-eight consecutive patients with suspected or known cardiac amyloidosis were evaluated, including blood tests, standard 12-lead electrocardiography (ECG) and transthoracic echocardiography. ATTR was confirmed histologically or non-invasively using 99mTc-DPD scintigraphy. Transthyretin (TTR) gene sequencing was performed. Results: In 2017–2019, 10 unrelated male patients were diagnosed with hereditary ATTR. All patients had very uncommon TTR gene mutations: 7 patients had p.Phe53Leu mutation, 2 patients had p.Glu109Lys mutation and 1 patient had p.Ala101Val mutation. The age of onset ranged from 49 to 67 years (mean [SD] age, 58.7 [6.4] years). On ECG, most patients (70%) had pseudoinfarct pattern and/or low QRS voltage. The maximal wall thickness (MWT) on echocardiography varied considerably among the patients from moderate (16 mm) to massively increased (30 mm). Most patients (90%) had decreased LV ejection fraction (mean [SD], 43 [11] %). On follow-up, we observed progressive heart failure in almost all cases. The first patient with p.Phe53Leu mutation died of heart failure, the second died suddenly, the third successfully underwent combined heart and liver transplant with 15 months survival from the surgery. The patient with p.Ala101Val mutation died of stroke. Conclusions: According to available research, this is the first time types of TTR mutations and clinical characteristics of Polish patients with cardiac hereditary ATTR have been reported. Previous literature data about Polish background in families with p.Phe53Leu mutation and the present results, suggest that this TTR mutation might be endemic in the Polish population.

Cardiovascular magnetic resonance (CMR) imaging in patients with hypertrophic cardiomyopathy (HCM) enables the assessment of not only left ventricular (LV) hypertrophy and scarring but also the severity of mitral regurgitation. CMR assessment of mitral regurgitation is primarily based on the difference between LV stroke volume (LVSV) and aortic forward flow (Ao) measured using the phase-contrast (PC) technique. However, LV outflow tract (LVOT) obstruction causing turbulent, non-laminar flow in the ascending aorta may impact the accuracy of aortic flow quantification, leading to false conclusions regarding mitral regurgitation severity. Thus, we decided to quantify mitral regurgitation in patients with HCM using Ao or, alternatively, main pulmonary artery forward flow (MPA) for mitral regurgitation volume (MRvol) calculations. The analysis included 143 prospectively recruited subjects with HCM and 15 controls. MRvol was calculated as the difference between LVSV computed with either the inclusion (LVSVincl) or exclusion (LVSVexcl) of papillary muscles and trabeculations from the blood pool and either Ao (MRvolAoi or MRvolAoe) or MPA (MRvolMPAi or MRvolMPAe). The presence or absence of LVOT obstruction was determined based on Doppler echocardiography findings. MRvolAoi was higher than MRvolMPAi in HCM patients with LVOT obstruction [47.0 ml, interquartile range (IQR) = 31.5–60.0 vs. 35.5 ml, IQR = 26.0–51.0; p < 0.0001] but not in non-obstructive HCM patients (23.0 ml, IQR = 16.0–32.0 vs. 24.0 ml, IQR = 15.3–32.0; p = 0.26) or controls (18.0 ml, IQR = 14.3–21.8 vs. 20.0 ml, IQR = 14.3–22.0; p = 0.89). In contrast to controls and HCM patients without LVOT obstruction, in HCM patients with LVOT obstruction, aortic flow-based MRvol (MRvolAoi) was higher than pulmonary-based findings (MRvolMPAi) (bias = 9.5 ml; limits of agreement: −11.7–30.7 with a difference of 47 ml in the extreme case). The differences between aortic-based and pulmonary-based MRvol values calculated using LVSVexcl mirrored those derived using LVSVincl. However, MRvol values calculated using LVSVexcl were lower in all the groups analyzed (HCM with LVOT obstruction, HCM without LVOT obstruction, and controls) and with all methods of MRvol quantification used (p ≤ 0.0001 for all comparisons). In HCM patients, LVOT obstruction significantly affects the estimation of aortic flow, leading to its underestimation and, consequently, to higher MRvol values than those obtained with MPA-based MRvol calculations.

DOI: 10.20452/pamw.16877, Published online: October 29, 2024, Authors: Monika Gawor-Prokopczyk, Marta Lipowska, Grażyna Truszkowska, Joanna Ponińska, Maria Franaszczyk, Mateusz Ziarkiewicz, Marta Legatowicz-Koprowska, Renata Rajtar-Salwa, Przemysław Chmielewski, Zofia T. Bilińska, Anna Teresińska, Jacek Grzybowski