Right superior pulmonary vein parameter determined by three-dimensional transesophageal echocardiography is an independent predictor of the outcome after cryoballoon isolation of the pulmonary veins.

BACKGROUND: A direct comparison of three-dimensional transesophageal echocardiography (3DTEE) and cardiac computed tomography imaging has demonstrated good inter-technique agreement for the following pulmonary vein (PV) parameters: the ostium area of the right superior PV (RSPV) and its major (a) and minor axis (b) diameters, the left lateral ridge and the minor axis (b) diameter of the left superior PV. Herein, under investigation, was the predictive value of these parameters for arrhythmia recurrence (AR) after PV isolation with the 28 mm second generation cryoballoon (CBG2). METHODS: One hundred eleven patients (67 men, mean age 58.06 ± 10.58 years) undergoing 3DTEE before PV isolation with the CBG2 for paroxysmal atrial fibrillation were followed. "Point by point" redo intervention was offered in case of AR and reconnected PVs were defined. RESULTS: During a mean follow-up of 617 ± 258.86 days, 65 (58.9%) patients remained free of AR. Longer RSPV b was found to be the only significant predictor for AR (hazard ratio [HR] 1.059; 95% confidence interval [CI] 1.000-1.121; p = 0.048). RSPV b ≥ 28 mm resulted in a threefold (HR 3.010; 95% CI 1.270-7.134, p = 0.012) increase in the risk of AR. The association of RSPV b with AR was independent of the biophysical parameters of cryoapplications. In 25 "redo" patients, reconnections were found 1.75 times more likely in the RSPV than in the other 3 PVs altogether. CONCLUSIONS: Right superior PV b measured with 3DTEE might be a significant predictor of AR after PV isolation with the CBG2. In case of RSPV b exceeding 28 mm, alternative PV isolation techniques or use of a larger balloon might be considered.

Three-dimensional transesophageal echocardiographic evaluation of pulmonary vein anatomy prior to cryoablation: validation with cardiac CT scan.

BACKGROUND: Anatomical characteristics of the left atrium and the pulmonary veins (PVs) may be relevant to the success rate of cryoballoon (CB)-ablation for atrial fibrillation (AF). Cardiac computed tomography (CCT) is considered as the gold standard for preablation imaging. Recently, three-dimensional transesophageal echocardiography (3DTOE) has been proposed for preprocedural assessment of cardiac structures relevant to CB-ablation. The accuracy of 3DTOE has not been validated by other imaging modalities. OBJECTIVE: We prospectively evaluated the feasibility and the accuracy of 3DTOE imaging for the assessment of left atrial and PV structures prior to pulmonary vein isolation (PVI). In addition, CCT was used to validate the measurements obtained with 3DTOE. METHODS: PV anatomy of 67 patients (59.7% men, mean age 58.5 ± 10.5 years) was assessed using both 3DTOE and CCT scan prior to PVI with the Arctic Front CB. The following parameters were measured bilaterally: PV ostium area (OA), the major and minor axis diameters of the ostium (a > b) and the width of the carina between the superior and the inferior PVs. In addition, the width of the left lateral ridge (LLR) between the left atrial appendage and the left superior PV. Evaluation of inter-technique agreement was based on linear regression with Pearson correlation coefficient (PCC) and Bland-Altman analysis of biases and limits of agreement. RESULTS: Moderate positive correlation (PCC 0.5-0.7) was demonstrated between the two imaging methods for the right superior PV's OA and both axis diameters, the width of the LLR and left superior PV (LSPV) minor axis diameter (b) with limits of agreement ˂50% and no significant biases. Low positive or negligible correlation (PCC < 0.5) was found for both inferior PV parameters. CONCLUSIONS: Detailed assessment of the right superior PV parameters, LLR and LSPV b is feasible with 3DTOE prior to AF ablation. This 3DTOE measurements demonstrated a clinically acceptable inter-technique agreement with those obtained with CCT.

Simplified coronary flow reserve calculations based on three-dimensional coronary reconstruction and intracoronary pressure data.

BACKGROUND: Measurements of fractional flow reserve (FFR) and/or coronary flow reserve (CFR) are widely used for hemodynamic characterization of coronary lesions. The frequent combination of the epicardial and microvascular disease may indicate a need for complex hemodynamic evaluation of coronary lesions. This study aims at validating the calculation of CFR based on a simple hemodynamic model to detailed computational fluid dynamics (CFD) analysis. METHODS: Three-dimensional (3D) morphological data and pressure values from FFR measurements were used to calculate the target vessel. Nine patients with one intermediate stenosis each, measured by pressure wire, were included in this study. RESULTS: A correlation was found between the determined CFR from simple equations and from a steady flow simulation (r = 0.984, p < 10-5). There was a significant correlation between the CFR values calculated by transient and steady flow simulations (r = 0.94, p < 10-3). CONCLUSIONS: Feasibility was demonstrated of a simple hemodynamic calculation of CFR based on 3D-angiography and intracoronary pressure measurements. A simultaneous determination of both the FFR and CFR values provides the capability to diagnose microvascular dysfunction: the CFR/FFR ratio characterizes the microvascular reserve.

Novel Method to Detect Pitfalls of Intracoronary Pressure Measurements by Pressure Waveform Analysis.

Potential pitfalls of fractional flow reserve (FFR) measurements are well-known drawbacks of invasive physiology measurement, e.g., significant drift of the distal pressure trace may lead to the misclassification of stenoses. Thus, a simultaneous waveform analysis of the pressure traces may be of help in the quality control of these measurements by online detection of such artefacts as the drift or the wedging of the catheter. In the current study, we analysed the intracoronary pressure waveform with a dedicated program. In 130 patients, 232 FFR measurements were performed and derivative pressure curves were calculated. Local amplitude around the dicrotic notch was calculated from the distal intracoronary pressure traces (δdPn/dt). A unidimensional arterial network model of blood flow was employed to simulate the intracoronary pressure traces at different flow rates. There was a strong correlation between δdPn/dt values measured during hyperaemia and FFR (r = 0.88). Diagnostic performance of distal δdPn/dt ≤ 3.52 for the prediction of FFR ≤ 0.80 was 91%. The correlation between the pressure gradient and the corresponding δdPn/dt values obtained from all measurements independently of the physiological phase was also significant (r = 0.80). During simulation, the effect of flow rate on δdPn/dt further supported the close correlation between the pressure ratios and δdPn/dt. Discordance between the FFR and the δdPn/dt can be used as an indicator of possible technical problems of FFR measurements. Hence, an online calculation of the δdPn/dt may be helpful in avoiding some pitfalls of FFR evaluation.

Whole blood transcriptome characterization of young female triathlon athletes following an endurance exercise: a pilot study.

The vast majority of studies focusing on the effects of endurance exercise on hematological parameters and leukocyte gene expression were performed in adult men, so our aim was to investigate these changes in young females. Four young (age 15.3 ± 1.3 yr) elite female athletes completed an exercise session, in which they accomplished the cycling and running disciplines of a junior triathlon race. Blood samples were taken immediately before the exercise, right after the exercise, and then 1, 2, and 7 days later. Analysis of cell counts and routine biochemical parameters were complemented by RNA sequencing (RNA-seq) to whole blood samples. The applied exercise load did not trigger remarkable changes in either cardiovascular or biochemical parameters; however, it caused a significant increase in the percentage of neutrophils and a significant reduction in the ratio of lymphocytes immediately after exercise. Furthermore, endurance exercise induced a characteristic gene expression pattern change in the blood transcriptome. Gene set enrichment analysis (GSEA) using the Reactome database revealed that the expression of genes involved in immune processes and neutrophil granulocyte activation was upregulated, whereas the expression of genes important in translation and rRNA metabolism was downregulated. Comparison of a set of immune cell gene signatures (ImSig) and our transcriptomic data identified 15 overlapping genes related to T-cell functions and involved in podosome formation and adhesion to the vessel wall. Our results suggest that RNA-seq to whole blood together with ImSig analysis are useful tools for the investigation of systemic responses to endurance exercise.

The feasibility of baroreflex sensitivity measurements in heart failure subjects: The role of slow-patterned breathing.

INTRODUCTION: Increased muscle sympathetic nerve activity (MSNA) indicates an adverse outcome in heart failure. Decreased baroreflex modulation of MSNA is a well-known feature of the disease. The determinability of cardiovagal baroreflex sensitivity (BRS) in heart failure is low, however, the determinability of sympathetic BRS is not known. METHODS: We have assessed the spontaneous, MSNA burst incidence-based baroreflex index (BRSsymp) in 33 stable heart failure patients and in 10 healthy controls using the traditional r ≥ .5 cutoff for acceptable individual diastolic pressure-burst incidence slopes, and also a more stringent r ≥ .7 cutoff. We have also assessed the influence of 6/min breathing. RESULTS: The determinability of BRSsymp in heart failure patients was 64% during spontaneous breathing with r ≥ .5 cutoff, and 39% using the r ≥ .7 cutoff. The determinability of these indices further decreased during 6/min breathing, dropping to 29% with the r ≥ .7 cutoff. In contrast, the determinability of the cardiovagal BRS indices increased significantly with 6/min breathing (from 24% to 66%; p < .001). Patients who still had determinable BRSsymp at the r ≥ .7 cutoff had a significantly lower baseline burst incidence than those with an undeterminable index (70 ± 14 vs. 89 ± 10 burst/100 cycles; p < .002). Neither the 6/min breathing, nor the r ≥ .7 cutoff limit influenced the high availability of BRSsymp in healthy subjects. CONCLUSION: The determinability of BRSsymp in heart failure patients is limited, especially with the 0.7 limit for correlation. Undeterminable BRSsymp in patients is associated with higher sympathetic activity. 6/min breathing improves the determinability of cardiovagal BRS indices, but not that of BRSsymp.

Sympathetic activation in heart failure with reduced and mildly reduced ejection fraction: the role of aetiology.

AIM: While sympathetic overactivity in heart failure (HF) with reduced ejection fraction (HFrEF; EF < 40%) is well-documented, it is ill-defined in patients with mildly reduced EF (HFmrEF; EF 40-49%). Furthermore, the significance of ischaemic versus non-ischaemic aetiology in sympathetic activation is also unclear and has yet to be studied in HF. Our goal was to compare muscle sympathetic nerve activity (MSNA) in HFmrEF and HFrEF patients and in healthy subjects, as well as to elucidate the influence of the underlying disease. METHODS AND RESULTS: Twenty-three HFrEF (age 58 ± 10 years), 33 HFmrEF patients (age 61 ± 10 years), including 11 subjects with non-ischaemic cardiomyopathy in each HF groups and 10 healthy controls (age 55 ± 10 years), were studied. MSNA-detected by peroneal microneurography, continuous arterial pressure, and ECG-was recorded. MSNA frequency (burst/min) and incidence (burst/100 cycles) were calculated. Association with the patients' characteristics were assessed, and aetiology-based comparisons were performed. Burst frequency demonstrated a significant stepwise increase in both HFmrEF (41 ± 11 burst/min) and HFrEF (58 ± 17 burst/min, P < 0.001) patients as compared with controls (27 ± 9; P < 0.001 for both HF groups). Similarly, burst incidences were 66 ± 17, 82 ± 15, and 36 ± 10 burst/100 cycles in HFmrEF, HFrEF patients, and in healthy controls, respectively (P < 0.001 for all). Burst frequencies in HF patients showed significant correlation with NT-proBNP levels, and significant inverse correlations with the subjects' mean RR intervals, stroke volumes, pulse pressures, and EF. CONCLUSIONS: Muscle sympathetic nerve activity parameters indicated significant sympathetic activation in both HFmrEF and HFrEF patients as compared with healthy controls with no difference in relation to ischaemic versus non-ischaemic aetiology.

Role of 3D echocardiography-determined atrial volumes in distinguishing between pre-capillary and post-capillary pulmonary hypertension.

AIMS: The current guidelines on pulmonary hypertension (PH) recommend the use of invasive examination for differentiating between left-sided heart disease-related (post-capillary) and pre-capillary PH. However, atrial sizes are considered markers of ventricular filling pressures. Therefore, we aimed to test the clinical applicability of atrial volumes measured by transthoracic three-dimensional echocardiography (3DE) in differentiating between pre-capillary and post-capillary PH. METHODS AND RESULTS: Seventy-five consecutive patients with PH were prospectively examined with transthoracic 3DE. After less than 24 h, the patients underwent right heart catheterization and 3DE and were classified as pre-capillary or post-capillary PH according to the recommendations of the ESC guidelines. The atrial volumes were measured offline with dedicated commercial software. Thirty-eight patients (13 men, age 65 ± 18 year) had pre-capillary PH, and 37 (23 men, age 62 ± year) had post-capillary PH. The mean pulmonary artery pressures were similar in patients with pre-capillary and post-capillary PH (38 [IQR 26, 54] mmHg vs. 41 [IQR 33, 48] mmHg, respectively, P = 0.49). The left atrial indexed maximum (LAVi max) and minimum (LAVi min) volumes were significantly larger in the post-capillary PH patient group than in the pre-capillary PH patient group (LAVi max: 64 ± 32 mL/m2 vs. 41 ± 25 mL/m2 , P = 0.001; LAVi min: 50 ± 22 mL/m2 vs. 26 ± 24 mL/m2 , P < 0.0001). The indexed right atrial minimum volume (RAVi min) was also higher in patients with post-capillary PH (51 ± 27 mL/m2 vs. 38 ± 26 mL/m2 ; P = 0.02). Both the left atrial (LA) and right atrial (RA) volumes, especially the LA minimum volume, correlated with the pulmonary artery wedge pressure (PAWP) (r = 0.62 (P < 0.0001) for LAV min vs. r = 0.49 (P < 0.0001) for LAV max; r = 0.32 (P = 0.005) for RAV min vs. r = 0.24 (P = 0.04) for RAV max). Multivariate logistic regression analysis showed that LAVi min was an independent predictor of post-capillary PH. In the receiver operating characteristic (ROC) curves of parameters predicting the post-capillary PH, the areas under the curve (AUC) for LAVi min, LAVi max, and RAVi min were 0.86 (95% CI, 0.76-0.95), 0.78 (95% CI, 0.67-0.89), and 0.66 (0.53-0.78), respectively. Concerning the performance of the atrial volume ratio for differentiating post-capillary PH, the AUC of the atrial volume ratio was significantly lower [AUC: 0.66 (95% CI, 0.53-0.78)]. The ROC analysis indicated a possible cutoff value of 27.7 mL/m2 for LAVi min to predict post-capillary PH (AUC = 0.86; sensitivity = 86%, specificity = 76%). CONCLUSIONS: The BSA-indexed left atrial minimum volume measured by transthoracic 3DE is a useful parameter for differentiating pre-capillary from post-capillary pulmonary hypertension.

The Holistic Coronary Physiology Display: Calculation of the Flow Separation Index in Vessel-Specific Individual Flow Range during Fractional Flow Reserve Measurement Using 3D Coronary Reconstruction.

In order to make optimal decisions on the treatment of atherosclerotic coronary heart disease (CHD), appropriate evaluation is necessary, including both the anatomical and physiological assessment of the coronary arteries. According to current guidelines, a fractional flow reserve (FFR)-based clinical decision is recommended, but coronary flow reserve (CFR) measurements and microvascular evaluation should also be considered in special cases for a detailed exploration of the coronary disease state. We aimed to generate an extended physiological evaluation during routine FFR measurement and define a new pathological flow-related prognostic factor. Fluid dynamic equations were applied to calculate CFR on the basis of the three-dimensional (3D) reconstruction of the invasively acquired coronary angiogram and the measured intracoronary pressure data. A new, potentially robust prognostic parameter of a coronary lesion called the "flow separation index" (FSi), which is thought to detect the pathological flow amount through a stenosis was introduced in a vessel-specific flow range. Correlations between FSi and the clinically established physiological indices (CFR and FFR) were determined. The FSi was calculated in 19 vessels of 16 patients, including data from the pre- and post-stent revascularization treatment of 3 patients. There was no significant correlation between the FSi and the CFR (r = -0.23, p = 0.34); however, there was significant negative correlation between the FSi and the FFR (r = -0.66, p = 0.002). An even stronger correlation was found between the FSi and the ratio of the resting pressure ratio and the FFR (r = 0.92, p < 0.0001). The diagnostic power of the FSi for predicting the FFR value of <0.80, as a gold standard prognostic factor, was tested by receiver operating characteristic analysis. FSi > 0.022 proved to be the cutoff value of the prediction of a pathologically low FFR with a 0.856 area under the curve (95% confidence interval: 0.620 to 0.972). The present flow-pressure-velocity display provides a comprehensive summary of patient-specific pathophysiology in CHD. The consequences of epicardial stenoses can be evaluated together with their complex relations to microvascular conditions. Based on these values, clinical decision-making concerning both pharmacological therapy and percutaneous or surgical revascularization may be more precisely guided.

The impact of hydrostatic pressure on the result of physiological measurements in various coronary segments.

The effect of hydrostatic pressure on physiological intracoronary measurements is usually ignored in the daily clinical practice. Our aim was to investigate this effect on Pd/Pa (distal/aortic pressure) and FFR (fractional flow reserve). 41 FFR measurements between 0.7 and 0.9 were selected. The difference in the height of the orifice and that of the sensor was defined in mm on the basis of 3D coronary reconstruction. Resting Pd/Pa and FFR were adjusted by subtracting the hydrostatic pressure gradient from the distal pressure. Height measurements were also performed from 2D lateral projections for each coronary segment (n = 305). In case of the LAD, each segment was located higher (proximal: - 13.69 ± 5.4; mid: - 46.13 ± 6.1; distal: - 56.80 ± 7.7 mm), whereas for the CX, each segment was lower (proximal: 14.98 ± 8.3; distal: 28.04 ± 6.3 mm) compared to the orifice. In case of the RCA, the distances from the orifice were much less (proximal: - 6.39 ± 2.9; mid: - 6.86 ± 7.0; distal: 17.95 ± 6.6 mm). The effect of these distances on pressure ratios at 100 Hgmm aortic pressure was between - 0.044 and 0.023. The correction for height differences changed the interpretation of the measurement (negative/positive result) in 5 (12%) and 11 (27%) cases for the FFR (cut-off value at 0.80) and the resting Pd/Pa (cut-off value at 0.92), respectively. The clinical implementation of hydrostatic pressure calculation should be considered during intracoronary pressure measurements. A correction for this parameter may become crucial in case of a borderline significant coronary artery stenosis, especially in distal coronary artery segments.

Three-Dimensional Echocardiographic Method for the Visualization and Assessment of Specific Parameters of the Pulmonary Veins.

The dimensions of the pulmonary veins are important parameters when planning pulmonary vein isolation (PVI), especially with the cryoballoon ablation technique. Acknowledging the dimensions and anatomical variations of the pulmonary veins (PVs) may improve the outcome of the intervention. Conventional 2D transoesophageal echocardiography can only provide limited data about the dimensions of the PVs; however, 3D echocardiography can further evaluate relevant diameters and areas of the PVs, as well as their spatial relationship to surrounding structures. In previous literature data, parameters influencing the success rate of PVI have already been identified. These are the left lateral ridge, the intervenous ridge, the ostial area of the PVs and the ovality index of the ostium. Proper imaging of the PVs by 3D echocardiography is a technically challenging method. One crucial step is the collection of images. Three individual transducer positions are necessary to visualize the important structures; these are the left lateral ridge, the ostium of the PVs and the intervenous ridge of the left and right PVs. Next, 3D images are acquired and saved as digital loops. These datasets are cropped, which result in the en face views displaying spatial relationships. This step can also be employed to determine the anatomical variations of the PVs. Finally, multiplanar reconstructions are created to measure each individual parameter of the PVs. Optimal quality and orientation of the acquired images are paramount for the appropriate assessment of PV anatomy. In the present work, we examined the 3D visibility of the PVs and the suitability of the above method in 80 patients. The aim was to provide a detailed outline of the essential steps and potential pitfalls of PV visualization and assessment with 3D echocardiography.

Three-dimensional evaluation of the spatial morphology of stented coronary artery segments in relation to restenosis.

To investigate the correlations between the three-dimensional (3D) parameters of target coronary artery segments and restenosis after stent implantation. Sixty-four patients after single, cobalt chromium platform stent (27 BM stents and 37 DES) implantation were investigated retrospectively 12 ± 6 months after the index procedure. 3D coronary artery reconstruction was performed before and after the stent implantation using appropriate projections by a dedicated reconstruction software. The curve of the target segment was characterized by the ratio of the vessel length measured at midline (arc: A) and the distance between the edge points of the stent (chord: C): A/C ratio (ACr). Age, diabetes and hyperlipidaemia were taken into account for the statistical evaluation. 22 patients were diagnosed with ISR, while 42 patients without any restenosis served as controls. The two groups did not differ regarding major cardiovascular risk factors, proportion of the treated vessels or the type of stents. Higher initial ACr values were associated with greater straightening of the vessel curvature in all groups (p < 0.001). Significant negative correlations were found in cases of proximal or distal edge bending angles (p < 0.001). Pre-stent edge bending angles < 7° often showed an increase after the stent implantation, while in case of higher initial values, the bending angles generally decreased. Using multivariate logistic regression modelling we found that the pre-stent ACr was an independent predictor of in-stent restenosis (odds ratio for 1% increase of the ACr: 1.08; p = 0.012). Changes of angles at the stent edges following stent implantation correlate with the initial local bending angles. The ACr predispose to chronic shear stress in the vessel wall, which may contribute to the pathological intimal proliferation.

3-Dimensional Echocardiographic Analysis of the Tricuspid Annulus Provides New Insights Into Tricuspid Valve Geometry and Dynamics.

OBJECTIVES: The authors used transthoracic 3-dimensional transthoracic echocardiography (3DE) to characterize tricuspid annulus (TA) geometry and dynamics in healthy volunteers. BACKGROUND: Accurate sizing of the TA is essential for planning tricuspid annuloplasty and for implantation of new percutaneous tricuspid devices. METHODS: 3DE of the TA from 209 healthy volunteers was analyzed using custom software to measure TA area, perimeter, circularity, and dimensions at end diastole (equals tricuspid valve closure), mid-systole, end systole, and late diastole. TA intercommissural distances were measured at mid-systole. For comparison, TA diameters were measured at the same time points on multiplanar reconstruction of the 3DE datasets and on 2-dimensional transthoracic echocardiography (2DE) apical 4-chamber and right ventricular focused views. In 13 subjects with both 3DE and computed tomography, TA parameters were compared. RESULTS: 3DE TA area, perimeter, and dimensions were largest in late diastole and smallest at mid-systole/end systole. Normal tricuspid valve parameters in end diastole were 8.6 ± 2.0 cm2 for area; 10.5 ± 1.2 cm for perimeter; 36 ± 4 mm and 30 ± 4 mm for longest and shortest dimensions, respectively; and 0.83 ± 0.10 for circularity. There were no age-related changes in TA parameters. Women had larger indexed TA perimeter and longer long-axis dimensions compared with men. The longest 3DE TA dimension was significantly longer than diameters measured from both 2DE and 3D multiplanar reconstruction. 3DE TA area, perimeter, and dimensions correlated with both right atrial and right ventricular volumes, suggesting that both chambers may be determinants of TA size. TA fractional area change was 35 ± 10%. Fractional changes in both perimeter and dimensions were ≥20%. When compared with computed tomography, 3DE systematically underestimated TA parameters. CONCLUSIONS: Gender and body size should be taken into account to identify the reference values of TA dimensions. 2DE underestimates TA dimensions.

Less invasive fractional flow reserve measurement from 3-dimensional quantitative coronary angiography and classic fluid dynamic equations.

AIMS: The aim of this study was to develop a simplified model of FFR calculation (FFRsim) derived from three-dimensional (3D) coronary angiographic data and classic fluid dynamic equations without using finite element analysis. METHODS AND RESULTS: Intracoronary pressure measurements were performed by pressure wire sensors. The lumens of the interrogated vessel segments were reconstructed in 3D. The coronary artery volumetric flow was calculated based on the velocity of the contrast material. Pressure gradients were computed by classic fluid dynamic equations. The diagnostic power of the simplified computation of the FFR (FFRsim) was assessed by comparing the results with standard invasive FFR measurements (FFRmeas) in 68 vessels with a single stenosis. We found a strong correlation between the FFRsim and the FFRmeas (r=0.86, p<0.0001). The sensitivity and specificity for predicting the abnormal FFR of ≤0.80 (indicating haemodynamically significant stenosis) were 90% and 100%, respectively. The area under the curve (AUC) was 0.96. To achieve 100% negative and positive predictive values we defined the FFRsim >0.88 and the FFRsim ≤0.8 ranges. In our patient population, these ranges were found in 69% of the cases. CONCLUSIONS: According to our simplified model, the invasive FFR measurement can be omitted without misclassification in pre-specified ranges of the calculated FFRsim.

Circulating ACE2 activity correlates with cardiovascular disease development.

It was shown recently that angiotensin-converting enzyme activity is limited by endogenous inhibition in vivo, highlighting the importance of angiotensin II (ACE2) elimination. The potential contribution of the ACE2 to cardiovascular disease progression was addressed. Serum ACE2 activities were measured in different clinical states (healthy, n=45; hypertensive, n=239; heart failure (HF) with reduced ejection fraction (HFrEF) n=141 and HF with preserved ejection fraction (HFpEF) n=47). ACE2 activity was significantly higher in hypertensive patients (24.8±0.8 U/ml) than that in healthy volunteers (16.2±0.8 U/ml, p=0.01). ACE2 activity further increased in HFrEF patients (43.9±2.1 U/ml, p=0.001) but not in HFpEF patients (24.6±1.9 U/ml) when compared with hypertensive patients. Serum ACE2 activity negatively correlated with left ventricular systolic function in HFrEF, but not in hypertensive, HFpEF or healthy populations. Serum ACE2 activity had a fair diagnostic value to differentiate HFpEF from HFrEF patients in this study. Serum ACE2 activity correlates with cardiovascular disease development: it increases when hypertension develops and further increases when the cardiovascular disease further progresses to systolic dysfunction, suggesting that ACE2 metabolism plays a role in these processes. In contrast, serum ACE2 activity does not change when hypertension progresses to HFpEF, suggesting a different pathomechanism for HFpEF, and proposing a biomarker-based identification of these HF forms.

Wall shear stress in the development of in-stent restenosis revisited. A critical review of clinical data on shear stress after intracoronary stent implantation.

The average wall shear stress (WSS) is in 1 Pa range in coronary arteries, while the stretching effect of an implanted coronary stent can generate up to 3 × 105 times higher circumferential stress in the vessel wall. It is widely accepted that WSS plays a critical role in the development of restenosis after coronary stent implantation, but relevant clinical endpoint studies are lack-ing. Fluid dynamics modeling suggests an association between WSS and intimal hyperplasia, however, such an association is not established when the compensating healing process becomes an overshoot phenomenon. This review summarizes available clinical results and concepts of potential clinical importance.

New speckle-tracking algorithm for right ventricular volume analysis from three-dimensional echocardiographic data sets: validation with cardiac magnetic resonance and comparison with the previous analysis tool.

AIMS: (i) To validate a new software for right ventricular (RV) analysis by 3D echocardiography (3DE) against cardiac magnetic resonance (CMR); (ii) to assess the accuracy of different measurement approaches; and (iii) to explore any benefits vs. the previous software. METHODS AND RESULTS: We prospectively studied with 3DE and CMR 47 patients (14-82 years, 28 men) having a wide range of RV end-diastolic volumes (EDV 82-354 mL at CMR) and ejection fractions (EF 34-81%). Multi-beat RV 3DE data sets were independently analysed with the new software using both automated and manual editing options, as well as with the previous software. RV volume reproducibility was tested in 15 random patients. RV volumes and EF measurements by the new software had an excellent accuracy (bias ± SD: -15 ± 24 mL for EDV; 1.4 ± 4.9% for EF) and reproducibility compared with CMR, provided that the RV borders automatically tracked by software were systematically edited by operator. The automated analysis option underestimated the EDV, overestimated the ESV, and largely underestimated the EF (bias ± SD: -17 ± 10%). RV volumes measured with the new software using manual editing showed similar accuracy, but lower inter-observer variability and shorter analysis time (3-5') in comparison with the previous software. CONCLUSION: Novel vendor-independent 3DE software enables an accurate, reproducible and faster quantitation of RV volumes and ejection fraction. Rather than optional, systematic verification of border tracking quality and manual editing are mandatory to ensure accurate 3DE measurements. These findings are relevant for echocardiography laboratories aiming to implement 3DE for RV analysis for both research and clinical purposes.

Relationship between reversibility score on corresponding left ventricular segments and fractional flow reserve in coronary artery disease.

OBJECTIVE: The objective of this study was to find the correlation between the severity of perfusion abnormality detected by scintigraphy and the FFR value, as well as the localization of a particular coronary lesion. On the basis of FFR values and the corresponding left ventricular segments, we proposed a combined index to aim for better correlation with myocardial ischemia than the FFR parameter alone. METHODS: Twenty-eight patients (male: 22, female: 6, age 62±7.62) having FFR measurements and myocardial perfusion SPECT studies were enrolled in our retrospective analysis. FFR measurements on 36 vessels (20 LAD, 6 LCx, 10 RCA) with intermediate stenosis (40%-60%) were compared to the Tc-99m SestaMIBI myocardial perfusion SPECT studies. SPECT studies were performed before the invasive procedure in all cases. We introduced a new ischemic index, the left ventricular ischemic index (LVIi), by combining FFR values with the number of corresponding myocardial segments (N) [LVIi=N x (1-FFR)]. This index correlated with the regional myocardial perfusion defects identified on the scintigrams. A perfusion reversibility score of 2 or above was considered indicative of active ischemia (regional difference score: rDSc). For the statistical analysis, we used linear regression analysis and receiver operating characteristic (ROC) curve analysis to compare the different parameters. RESULTS: A close linear relationship was found between the LVIi and rDSc values (p<0.001) with linear regression analysis. When analyzing all FFR values independently of the localization of the lesions, they also correlated significantly to the rDSc, but this relation was not as close. LVIi predicted active ischemia (≥2 rDSc) on myocardial scintigraphy with 78% sensitivity and 94% specificity when the cutoff value was set to 0.96. FFR alone predicted ischemia on scintigraphy with 72% sensitivity and 94% specificity at the best 0.8 cut-off value. The area under the ROC curve was significantly higher for LVIi than FFR (0.94 vs. 0.87; p<0.05). CONCLUSION: The scintigraphic data indicate that an LVIi >0.96 implies a clinically relevant stenotic lesion. In our opinion, FFR values, weighted with the corresponding left ventricular segments, should be taken into consideration for the best clinical decision-making.