Association of increased oncostatin M with adverse left ventricular remodeling in patients with myocardial infarction.

Background: The study of laboratory biomarkers that reflect the development of adverse cardiovascular events in the postinfarction period is of current relevance. The aim of the present study was evaluation of oncostatin M (OSM) concentration changes in the early and late stages of myocardial infarction and evaluation of the possibility of its use in prediction of adverse left ventricular (LV) remodeling in patients with myocardial infarction with ST-elevated segment (STEMI). Methods: The study involved 31 patients with STEMI admitted in the first 24 hours after the onset of MI and 30 patients with chronic coronary artery disease as a control group. Echocardiographic study was performed on day 3 and in 6 months after STEMI. The serum levels of biomarkers were evaluated on the day of hospital admission and 6 months after MI using multiplex immunoassay. Results: OSM level increased during the first 24 h after the onset of the disease, with the following decrease in 6 months. OSM concentration at admission had correlated with echocardiography parameters and Nt-proBNP, troponin I, CK-MB levels. Our study has demonstrated association of the increased levels of OSM at the early stages of STEMI with development of the adverse LV remodeling in 6 months after the event. Conclusions: Elevation of OSM levels in the first 24 h after STEMI is associated with the development of the adverse LV remodeling in the long-term post-infarction period.

Feasibility and value of two-dimensional volumetric stress echocardiography.

BACKGROUND: Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). METHODS: We enrolled 4735 patients (age 63.6±11.3 years, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (N.=1992 patients) and adenosine (N.=18); ≤2.0 for exercise (N.=2087) or dobutamine (N.=638). RESULTS: Force-based LVCR was obtained in all 4735 patients. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57% of patients with abnormal LVCR nevertheless showed increase in stroke volume. CONCLUSIONS: Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

Favorable effect of renal denervation on elevated renal vascular resistance in patients with resistant hypertension and type 2 diabetes mellitus.

Objective: To assess the effect of renal denervation (RDN) on renal vascular resistance and renal function in patients with drug-resistant hypertension (HTN) and type 2 diabetes mellitus (T2DM). Materials and methods: Fifty-nine patients (mean age 60.3 ± 7.9 years, 25 men) with resistant HTN [mean 24-h ambulatory blood pressure (BP) 158.0 ± 16.3/82.5 ± 12.7 mmHg, systolic/diastolic] and T2DM (mean HbA1c 7.5 ± 1.5%) were included in the single-arm prospective study and underwent RDN. Renal resistive index (RRI) derived from ultrasound Doppler; estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration formula), office and 24-h ambulatory BP were measured at baseline, 6, and 12 months after RDN to evaluate the respective changes in renal vascular resistance, renal function, and BP during treatment. Results: Forty-three patients completed 12 months follow-up. The RRI changed depending on the baseline value. Specifically, the RRI decreased significantly in patients with elevated baseline RRI values ≥ 0.7 {n = 23; -0.024 [95% confidence interval (CI): -0.046, -0.002], p = 0.035} and did not change in those with baseline RRI < 0.7 [n = 36; 0.024 (95% CI: -0.002, 0.050), p = 0.069]. No significant change was observed in eGFR whereas BP was significantly reduced at 12 months after RDN by -10.9 (95% CI: -16.7, -5.0)/-5.5 (95% CI: -8.7, -2.4) mmHg, systolic/diastolic. No relationship was found between the changes in RRI and BP. Conclusion: Our study shows that RDN can decrease elevated renal vascular resistance (RRI > 0.7) and stabilize kidney function in patients with RHTN and T2DM independently of its BP-lowering effect.

Prognostic value of stress echocardiography assessed by the ABCDE protocol.

AIM: The aim of this study was to assess the prognostic value of ABCDE-SE in a prospective, large scale, multicentre, international, effectiveness study. Stress echocardiography (SE) was recently upgraded to the ABCDE protocol: step A, regional wall motion abnormalities; step B, B lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in left anterior descending coronary artery; and step E, electrocardiogram-based heart rate reserve. METHODS AND RESULTS: From July 2016 to November 2020, we enrolled 3574 all-comers (age 65 ± 11 years, 2070 males, 58%; ejection fraction 60 ± 10%) with known or suspected chronic coronary syndromes referred from 13 certified laboratories. All patients underwent clinically indicated ABCDE-SE. The employed stress modality was exercise (n = 952, with semi-supine bike, n = 887, or treadmill, n = 65 with adenosine for step D) or pharmacological stress (n = 2622, with vasodilator, n = 2151; or dobutamine, n = 471). SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). All-cause death was the only endpoint. Rate of abnormal results was 16% for A, 30% for B, 36% for C, 28% for D, and 37% for E steps. During a median follow-up of 21 months (interquartile range: 13-36), 73 deaths occurred. Global X2 was 49.5 considering clinical variables, 50.7 after step A only (P = NS (not significant)) and 80.6 after B-E steps (P < 0.001 vs. step A). Annual mortality rate ranged from 0.4% person-year for score 0 up to 2.7% person-year for score 5. CONCLUSION: ABCDE-SE allows an effective prediction of survival in patients with chronic coronary syndromes.

Stress Echo 2030: The Novel ABCDE-(FGLPR) Protocol to Define the Future of Imaging.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021-2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Feasibility and functional correlates of left atrial volume changes during stress echocardiography in chronic coronary syndromes.

An enlarged left atrial volume index (LAVI) at rest mirrors increased LA pressure and/or impairment of LA function. A cardiovascular stress may acutely modify left atrial volume (LAV) within minutes. Aim of this study was to assess the feasibility and functional correlates of LAV-stress echocardiography (SE) Out of 514 subjects referred to 10 quality-controlled labs, LAV-SE was completed in 490 (359 male, age 67 ± 12 years) with suspected or known chronic coronary syndromes (n = 462) or asymptomatic controls (n = 28). The utilized stress was exercise in 177, vasodilator in 167, dobutamine in 146. LAV was measured with the biplane disk summation method. SE was performed with the ABCDE protocol. The intra-observer and inter-observer LAV variability were 5% and 8%, respectively. ∆-LAVI changes (stress-rest) were negatively correlated with resting LAVI (r = - 0.271, p < 0.001) and heart rate reserve (r = -.239, p < 0.001). LAV-dilators were defined as those with stress-rest increase ≥ 6.8 ml/m2, a cutoff derived from a calculated reference change value above the biological, analytical and observer variability of LAVI. LAV dilation occurred in 56 patients (11%), more frequently with exercise (16%) and dipyridamole (13%) compared to dobutamine (4%, p < 0.01). At multivariable logistic regression analysis, B-lines ≥ 2 (OR: 2.586, 95% CI = 1.1293-5.169, p = 0.007) and abnormal contractile reserve (OR: 2.207, 95% CI = 1.111-4.386, p = 0.024) were associated with LAV dilation. In conclusion, LAV-SE is feasible with high success rate and low variability in patients with chronic coronary syndromes. LAV dilation is more likely with reduced left ventricular contractile reserve and pulmonary congestion.

Serum Levels of Bone Morphogenetic Proteins 2 and 4 in Patients with Acute Myocardial Infarction.

BACKGROUND: Bone morphogenetic proteins-2 and -4 (BMPs) have been implicated in left ventricular remodeling (LVR) processes such as an inflammation and fibrogenesis. We hypothesized that this knowledge could be translated into clinics. METHODS: We studied the dynamics of serum levels of BMPs, its correlation with markers of LVR and with parameters of echocardiography in patients (n = 31) during the six-month follow-up period after myocardial infarction (MI). RESULTS: Elevated serum levels of BMPs decreased by the six-month follow-up period. BMP-2 decreased from the first day after MI, and BMP-4 decreased from the Day 14. The elevated level of BMP-2 at Day 1 was associated with a lower level of troponin I, reperfusion time and better left ventricular ejection fraction (LV EF) at the six-month follow-up. Elevated serum level of BMP-4 at Day 1 was associated with a lower level of a soluble isoform of suppression of tumorigenicity 2 (sST2), age and reperfusion time. An elevated level of BMP-2 at the six-month follow-up was associated with higher levels of BMP-4, high-sensitivity C-reactive protein (hCRP) and sST2. High serum level of BMP-2 correlated with high levels of hCRP and matrix metalloproteinase (MMP)-9 on Day 7. High serum level of BMP-4 correlated with low levels of hCRP, MMP-9 at Day 3, sST2 at Day 1 and with decreased LV EF on Day 7. The findings of multivariate analysis support the involvement of BMP-2 in the development of post-infarction LVR. CONCLUSIONS: Our research translates experimental data about the BMPs in the development of adverse LVR into the clinic. Elevated serum levels of BMPs decreased by the end of the six-month period after MI. BMP-2 decreased from the first day and BMP-4 decreased from Day 14. BMP-2 and BMP-4 were associated with the development of LVR. Their correlations with markers of inflammation, degradation of the extracellular matrix, hemodynamic stress and markers of myocardial damage further support our hypothesis. Diagnostic and predictive values of these BMPs at the development of post-infarction LVR in vivo should be investigated further.

Serum Soluble ST2 and Adverse Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: To assess the dynamics of serum levels of soluble isoform of suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) and their correlations with the development of adverse left ventricular remodeling (LVR) through 6 months in patients with primary myocardial infarction with ST-segment elevation (STEMI). METHODS: Subjects were 31 patients with STEMI (median age: 58 years), who underwent percutaneous coronary intervention (PCI) during the first 24 hours of the onset of myocardial infarction (MI). Blood samples and parameters of echocardiography were assessed at days 1, 3, 7, and 14 and 6 months after STEMI. RESULTS: Serum levels of sST2 and NT-proBNP decreased during the 6-month period. Levels of sST2 decreased by 48% from admission to day 7, and levels of NT-proBNP decreased by 40% from day 7 to 6 months after STEMI. Serum levels of sST2 at day 1 (r = 0.5, P < .05) and day 3 (r = 0.4, P < .05) were associated with adverse LVR by 6 months after STEMI. Logistic regression analysis showed that a high concentration of sST2 at day 7 increased the risk of adverse LVR (95% confidence interval [CI], 0.5-0.9; areas under curve [AUC] = 0.8; P = .002), with 92% sensitivity and 70% specificity. A multivariate analysis model revealed that adverse LVR was associated with the level of sST2 (P = .003) and with complete revascularization (P = .01) at the admission. CONCLUSIONS: The dynamics of serum levels of sST2 and NT-proBNP were different. The level of sST2 normalized by the 7th day; NT-proBNP decreased only by the end of the 6-month period after MI. Increased serum levels of sST2 by the 7th day of MI were associated with the development of adverse LVR by the end of the 6-month period.

Heart rate variability: the comparison between high tension and normal tension glaucoma.

RELEVANCE: Vascular factors may be involved in the development of both high tension glaucoma (HTG) and normal tension (NTG) glaucoma; however, they may be not exactly the same. Autonomic dysfunction characterized by heart rate variability (HRV) is one of the possible reasons of decrease in mean ocular perfusion pressure (MOPP). PURPOSE: To compare the shift of the HRV parameters in NTG and HTG patients after a cold provocation test (CPT). METHODS: MOPP, 24-hour blood pressure and HRV were studied in 30 NTG, 30 HTG patients, and 28 healthy subjects. The cardiovascular fitness assessment was made before and after the CPT. The direction and magnitude of the average group shifts of the HRV parameters after CPT were assessed using the method of comparing regression lines in order to reveal the difference between the groups. RESULTS: MOPP and minimum daily diastolic blood pressure were decreased in HTG and NTG patients compared to healthy subjects. There was no difference in MOPP between HTG and NTG before the CPT. However, all HRV parameters reflected the predominance of sympathetic innervation in glaucoma patients compared to healthy subjects (P < 0.05).Before the CPT, the standard deviation of NN intervals (SDNN) of HRV was lower in HTG compared to NTG, 27.2 ± 4.1 ms and 35.33 ± 2.43 ms (P = 0.02), respectively. After the CPT, SDNN decreased in NTG by 1.7 ms and increased in HTG and healthy subjects by 5.0 ms and 7.09 ms, respectively (P < 0.05). The analysis of relative shift of other HRV parameters after the CPT also revealed a significant difference between NTG and HTG in regard to the predominance of sympathetic innervation in NTG compared to HTG. CONCLUSION: Patients with NTG have more pronounced disturbance of autonomic nervous system than HTG patients, which is manifested with the activation of sympathetic nervous system in response to CPT. This finding refers to the NTG pathogenesis and suggests the use of HRV assessment in glaucoma diagnosis and monitoring.

Heart rate variability in normal tension glaucoma: A case-control study.

Primary vascular dysregulation (PVD) is believed to be a main cause of local vasospasm and impaired autoregulation as a possible contributing factor in the pathogenesis of normal tension glaucoma (NTG). Subjects with PVD respond stronger to psychological stress. Autonomic dysfunction is another reason of instable ocular blood flow and may be studied by means of assessment of heart rate variability (HRV) especially during a hand-cold provocation test (CPT).To compare the shift of HRV parameters in NTG and healthy subjects after a cold provocation test and to assess the relation between structural damage, circulatory parameters and autonomic dysfunction in NTG.HRV was studied using CPT in 78 NTG patients and 60 health control matches. The ocular blood flow was measured using color Doppler imaging (CDI). The 24 hours blood pressure (BP) monitoring was carried out. The cardiovascular fitness assessment was made to all patients before and after CPT. Mean group difference of HRV parameters was compared between NTG and healthy subjects using the Euclidean metric. The mean ocular perfusion pressure (MOPP) was measured. Optic nerve head and retinal nerve fiber layer (RNFL) were evaluated using spectral-domain optic coherence tomography (SD-OCT). The relation between HRV, CDI, and SD-OCT-parameters was assessed.In contrast to healthy subjects, a predominance of the sympathetic activity after the CPT was revealed in the NTG group. The end diastolic velocity (EDV) in central retinal artery (CRA) and short posterior ciliary artery (SPCA) was significantly reduced in NTG compared to healthy eyes. In NTG, the main HRV parameter characterizing the total effect of autonomic blood circulation regulation (SDNN) correlated with MOPP (0.75, P = .035), SPCA EDV (0.93, P < .001), and CRA EDV (0.9, P < .001). The average daily diastolic BP correlated with RNFL (0.67, P = .009).The NTG patients have the disturbance of the autonomic nervous system, which increases in response to stress provocation and is related to ocular blood flow and structural damage.

Predictors of Renal Denervation Efficacy in the Treatment of Resistant Hypertension.

UNLABELLED: The aims of the study were to evaluate the effects of renal sympathetic denervation (RSD) on the heart and to identify the predictors of RSD efficacy in patients with resistant arterial hypertension. The study comprised 60 RSD patients (54.6 ± 9.5 years) who received full-dose antihypertensive therapy (4.1 drugs) including diuretics. Initially, 58.6% of patients had abnormal left ventricular (LV) diastolic function. All patients received echocardiography before and 24 weeks after RSD. Renal sympathetic denervation was achieved through the endovascular radiofrequency ablation (RFA) of the renal arteries. Drug therapy continued for the entire period of observation. After RSD, all patients were retrospectively assigned to two groups: group 1 comprised patients (n = 22; 36.7%) in whom the myocardial mass (MM) of the left ventricle decreased by more than 10 g after RSD; group 2 comprised patients (n = 38; 63.3%) in whom LV MM increased or decreased by less than 10 g. Anthropometry, arterial blood pressure, heart rate, therapy, and LV end-diastolic dimensions (EDD) were comparable in these groups. After RSD, the values of office blood pressure significantly decreased and MM regressed by more than 10 g in 36.7% of patients; LV diastolic function normalized in 31% of patients, and diastolic dysfunction improved in 14% of patients. The study found the associations between the initial LV wall dimensions and LV MM changes. Unlike LV EDD, arterial blood pressure, or heart rate, the initial values of LV wall thickness predicted LV MM regress. TRIAL REGISTRATION: #NCT01499810 https://clinicaltrials.gov/ct2/show/NCT01499810.