Serial Echocardiographic Examinations Research Articles

Core Laboratory Versus Center-Reported Echocardiographic Assessment of the Native and Bioprosthetic Aortic Valve.

Insights into quantitative differences between core laboratory and center-reported echocardiographic assessment of the native and bioprosthetic aortic valve are lacking. We aimed to explore clinically relevant differences between these evaluations. Data were used from the PERIcardial SurGical AOrtic Valve ReplacemeNt (PERIGON) Pivotal Trial for the Avalus valve. In this trial, patients with an indication for surgical aortic valve replacement (SAVR) due to aortic stenosis or regurgitation (AR) were enrolled. Serial echocardiographic examinations were performed at each center and blindly reanalyzed by an independent echocardiographic core laboratory (ECL). For the bioprosthetic valve analysis, postoperative data throughout the 5-year follow-up were pooled. Differences between the ECL and the centers in continuous parameters were quantified in mean differences and intraclass correlation coefficients (ICCs). Agreement on AR, paravalvular leak (PVL), and prosthesis-patient mismatch (PPM) classification was investigated using Cohen's kappa coefficients. The analysis on the native aortic valve was performed on 1118 echocardiograms. The relative mean difference was largest for the left ventricular outflow tract (LVOT) area, followed by stroke volume and effective orifice area (index), with center-reported values being 11%-7% higher. High ICCs of around 0.90 were observed for the parameters peak aortic jet velocity, mean pressure gradient, and the velocity-time integral across the aortic valve. Over 5000 echocardiograms were available for the bioprosthetic valve analysis. Therein, comparable results were observed. The kappa coefficient was 0.59 (95% confidence interval [CI] 0.56, 0.63) for agreement on native AR, 0.28 (95% CI 0.18, 0.37) for PVL, and 0.42 (95% CI 0.40, 0.44) for PPM. There is high agreement between the ECL and clinical centers on continuous-wave Doppler-related measurements. In contrast, agreement is low for parameters that involve measurement of the LVOT diameter. These results provide important context for the interpretation of aortic valve performance in studies that lack central ECL evaluation. ClinicalTrials.gov identifier: NCT02088554.

Core laboratory versus center-reported echocardiographic assessment of the native and bioprosthetic aortic valve

Abstract Background The use of a central echocardiographic core laboratory (ECL) is advised to minimize measurement variation and heterogeneity in clinical trials. Insights into quantitative differences between ECL and center-reported echocardiographic assessment of the native and bioprosthetic aortic valve are lacking. We aimed to explore clinically relevant differences between these evaluations. Methods Data were used from the PERIcardial SurGical AOrtic Valve ReplacemeNt (PERIGON) Pivotal Trial for the Avalus valve. In this trial, patients with an indication for surgical aortic valve replacement (SAVR) due to aortic stenosis or regurgitation (AR) were enrolled. Serial echocardiographic examinations were performed at each center and reanalyzed by an independent ECL. For the bioprosthetic valve analysis, postoperative data throughout 5-year follow-up were pooled. Differences between the ECL and the centers in continuous parameters were quantified in mean differences and intraclass correlation coefficients (ICCs). Between-center differences were illustrated by plotting standardized mean differences (SMDs) between centers and the ECL for the 10 sites that implanted the most prostheses. Agreement on AR, paravalvular leak (PVL), and prosthesis-patient mismatch (PPM) classification was investigated using Cohen’s kappa coefficients. Results The analysis on the native aortic valve was performed on 1118 patients. The relative mean difference was largest for the left ventricular outflow tract (LVOT) area, followed by stroke volume and effective orifice area (index), with center-reported values being 11-7% higher (Table 1). High ICCs of around 0.90 were observed for peak aortic jet velocity, mean pressure gradient, and the velocity-time integral across the aortic valve. More than 5000 echocardiograms were available for the bioprosthetic valve analysis. Therein, comparable results were observed. In Figure 1, differences in assessment on center level are illustrated. The SMDs for peak velocity were between 0 and 0.5 for all centers, while there was more heterogeneity between centers for other parameters. The kappa coefficient was 0.59 (95% confidence interval [CI] 0.56, 0.63) for agreement on native AR, 0.28 (95% CI 0.18, 0.37) for PVL, and 0.42 (95% CI 0.40, 0.44) for PPM. Conclusions For echocardiographic assessment of the native and bioprosthetic aortic valve, agreement between the ECL and the clinical centers varies by parameter and by center. There is high agreement on continuous-wave Doppler-related measurements. On the contrary, agreement is low for parameters that involve measurement of the LVOT diameter. These results provide important context for the interpretation of aortic valve performance in studies that lack central ECL evaluation.

Longitudinal echocardiography in pediatric patients with hypermobile Ehlers-Danlos syndrome.

Vascular Ehlers-Danlos, Marfan and Loeys-Dietz syndromes have increased risk of aortic dilation and dissection. Previous early studies showed hypermobile Ehlers-Danlos syndrome (hEDS) may also have increased risk, with echocardiography screening recommended; subsequent studies have not confirmed the risk or recommended echocardiography. This pediatric-based study assessed aortic dilation prevalence in those with hEDS by serial echocardiographic examinations and assessed family history for aortic dissections. We retrospectively identified individuals with hEDS who had echocardiography studies from the electronic medical records at one pediatric center. Aortic root Z-scores >2.0 were found in 15/225 subjects (average age 12.9 years) on initial echocardiograms, with no Z-score >3.0. Subsequent studies (n = 68) found statistically significant decline in aortic root Z-scores. Repeat echocardiography in those with initial aortic root Z-score >2.0 (n = 10) demonstrated a decline in Z score <2.0 in seven. On final examination, 9/225 (4.0%) had a Z-score >2.0, not statistically different from the general population. No aortic dissection occurred in first- or second-degree relatives. In conclusion, aortic root dilation rate in hEDS is likely not different from the general population. We propose that in the absence of other cardiac findings or suspicion for another disorder, echocardiography is not required in hEDS.

Clinical presentation, management, and survival in dogs with persistent atrial standstill in the United Kingdom

ObjectivesTo investigate the clinical and echocardiographic presentation of dogs with persistent atrial standstill (PAS), identify variables measured at first presentation that could predict their survival, and document the progression of the disease after pacing. Materials and methodsRetrospective study of medical records of dogs diagnosed with PAS at three referral hospitals of the United Kingdom over seven years. ResultsTwenty-six dogs were diagnosed with PAS during the study period. Median age of the population was three years (range: seven months–12.5 years). The most common clinical sign was syncope (14/26). Twenty-four dogs received artificial pacemakers (PM). Major complications after PM implantation were observed in four dogs (four/24). Serial echocardiographic examinations showed that cardiac dimensions of PAS dogs with left atrial or left ventricular dilation at first presentation did not return to reference range after pacing. Further dilation of the cardiac chambers, recurrence of congestive heart failure (CHF), or development of new episodes of CHF were documented in seven, four, and 10 PAS dogs, respectively, despite pacing. Median survival time for cardiac-related deaths after PM implantation was 1512 days (18–3207). Neither CHF nor echocardiographic variables at presentation predicted survival after PM implantation in PAS dogs. ConclusionsPersistent atrial standstill (PAS) is an uncommon bradyarrhythmia, occurring in young adult dogs. Affected dogs were often presented with syncope. Whilst syncope resolved, cardiac remodeling persisted after PM implantation. Long-term survival was favorable after PM implantation and was not predicted by congestive status or cardiac chamber size at first presentation.

Echocardiographic function evaluation in adolescents following BNT162b2 Pfizer-BioNTech mRNA vaccination: A preliminary prospective study.

Vaccination against coronavirus disease 2019 (COVID-19) is crucial for preventing and minimizing illness. Myocarditis and pericarditis after messenger RNA (mRNA) COVID-19 vaccination in adolescents and young adult males have been reported. Most of the studies in this area rely on retrospective symptom reporting, especially for adolescents experiencing myocarditis as a potential side effect. However, prospective postvaccination echocardiographic evaluation is rare. The study enrolled adolescents aged 12 to 15 years who received the second dose of the BNT162b2 Pfizer-BioNTech mRNA (BNT) vaccine. Serial echocardiographic examinations were conducted at baseline before vaccination, followed by subsequent assessments on days 2, 7, 14, and 28 to identify any notable differences or abnormal changes in cardiac function. Clinical symptom assessments were also recorded during each follow-up. The study included 25 adolescents, comprising 14 males and 11 females, who completed the four follow-ups. Their mean age was 14 ± 1 years. The average interval between the first and second BNT vaccine doses was 90 ± 7 days. Ejection fraction values were 73.8% ± 5.2% at baseline, followed by 75.7% ± 5.3%, 75.5% ± 4.6%, 75.7% ± 4.5%, and 77.8% ± 5.8% at day 2, 7, 14, and 28, respectively. The cardiac function remained stable across all time points, with no significant differences observed between male and female participants. Within postvaccination 48 hours, 18 (72%) of the enrolled adolescents experienced temporary discomfort symptoms, which completely resolved by the final follow-up on the 28th day after vaccination. Although adolescents vaccinated with the second dose of BNT vaccine commonly experienced transient postvaccination discomfort, the serial echocardiographic examinations did not reveal any significant deterioration of cardiac function within 28 days. Further studies are required to investigate the incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccination-associated myocarditis in adolescents and the related mechanisms.

Hemodynamic Comparison between the Avalus and the Perimount Magna Ease Aortic Bioprosthesis up to 5 Years.

We aimed to compare hemodynamic performance of the Avalus (Medtronic) and the Perimount Magna Ease (PME, Edwards Lifesciences) bioprosthesis up to 5 years by serial echocardiographic examinations. In patients undergoing aortic valve replacement, 58 received PME prostheses between October 2007 and October 2008, and another 60 received Avalus prostheses between October 2014 and November 2015. To ensure similar baseline characteristics, we performed a propensity score matching based on left ventricular ejection fraction, age, body surface area, and aortic annulus diameter measured by intraoperative transesophageal echocardiography. Thereafter, 48 patients remained in each group. Mean age at operation was 67 ± 6 years and mean EuroSCORE-II was 1.7 ± 1.1. Both values did not differ significantly between the two groups. At 1 year the mean pressure gradient (MPG) was 15.4 ± 4.3 mm Hg in the PME group and 14.7 ± 5.1 mm Hg in the Avalus group (p = 0.32). The effective orifice area (EOA) was 1.65 ± 0.45 cm2 in the PME group and 1.62 ± 0.45 cm2 in the Avalus group (p = 0.79). At 5 years the MPG was 16.6 ± 5.1 mm Hg in the PME group and 14.7 ± 7.1 mm Hg in the Avalus group (p = 0.20). The EOA was 1.60 ± 0.49 cm2 in the PME group and 1.51 ± 0.40 cm2 in the Avalus group (p = 0.38). Five-year survival was 88% in the PME group and 91% in the Avalus group (p = 0.5). In the PME group, there were no reoperations on the aortic valve, whereas in the Avalus group three patients required a reoperation due to endocarditis. Both bioprostheses exhibit similar hemodynamic performance during a 5-year follow-up.

NATURAL HISTORY OF CONGENITAL ISOLATED MILD AORTIC VALVE AND MILD PULMONARY VALVE STENOSIS: A SINGLE CENTER FOLLOW-UP STUDY

Objective: Most of the available information on the natural history of aortic stenosis (AS) and pulmonary stenosis (PS) in children is based on studies carried out over the past 35-40 years using cardiac catheterization. This study aimed to reveal the natural history of congenital isolated mild valvular AS and PS in children using serial Doppler echocardiographic examinations. Materials and Methods: A total of 125 children, 50 with mild AS and 75 with mild PS, who underwent Doppler echocardiography were included in this study. The prognoses of mild AS and PS were compared according to age, gender, and valvular gradient at the time of initial diagnosis. Results: The mean age of patients was 26.1±37.6 months at diagnosis. The mean follow-up duration was 27.65±21.60 (1- 120) months. There was a significant decrease in the final gradient of the PS group compared to the baseline (23.58±6.97 vs. 19.88±11.21 mmHg, p=0.001). In the AS group, there was an increase in the final gradient, which was more pronounced in patients ≤1-year-old (22.42±6.12 vs. 27.74±14.12 mmHg, p=0.002). Four percent of patients in the PS group and 12% of patients in the AS group progressed to moderate to severe stenosis. All patients who progressed in the PS group were ≤1-year-old and male. Conclusion: The results showed that mild PS had a better prognosis than mild AS and that the risk of progression in AS was higher. Careful follow-up should be performed in mild PS cases ≤1-year-old, especially in boys, since progression may be detected, even if infrequently. Mild AS should also be followed closely, as the disease may show progressive characteristics in all age groups.

Stepwise approach for diagnosis and management of Takotsubo syndrome with cardiac imaging tools.

Takotsubo syndrome is featured by transient left ventricle dysfunction in the absence of significant coronary artery disease, mainly triggered by emotional or physical stress. Its clinical presentation is similar to acute coronary syndrome; therefore, cardiac imaging tools have a crucial role. Coronary angiography is mandatory for exclusion of pathological stenosis. On the other side, transthoracic echocardiography is the first non-invasive imaging modality for an early evaluation of left ventricle systolic and diastolic function. Left ventricle morphologic patterns could be identified according to the localization of wall motion abnormalities. Moreover, an early identification of potential mechanical and electrical complications such as left ventricle outflow tract obstruction, mitral regurgitation, thrombus formation, right ventricular involvement, cardiac rupture, and cardiac rhythm disorders could provide additional information for clinical management and therapy. Because of the dynamic evolution of the syndrome, comprehensive serial echocardiographic examinations should be systematically performed. Advanced techniques, including speckle-tracking echocardiography, cardiac magnetic resonance, and nuclear imaging can provide mechanistic and pathophysiologic insights into this syndrome. This review focuses on these aspects and provide a stepwise approach of all cardiac imaging tools for the diagnosis and the management of Takotsubo syndrome.

Abstract 9890: HFpEF with Normal Natriuretic Peptides: An Earlier Stage of Disease or Fundamentally Different Phenotype?

Introduction: Many patients with heart failure with preserved ejection fraction (HFpEF) display normal N-terminal-pro-B type natriuretic peptide (NTproBNP)levels. Mortality and hospitalization rates are lower in this group compared to patients with high NTproBNP, but it remains unclear whether these patients represent a fundamentally different phenotype or an earlier stage of disease. Methods: 213 subjects with HFpEF defined by invasive hemodynamics underwent serial echocardiographic examinations &amp;gt;1 year apart. Clinical, cardiac structural, functional, and hemodynamic characteristics were examined. Results: Exam 2 was performed a median of 3.2 years (IQR 2.2-5.1) following Exam 1. From this cohort, 66 (33%) displayed normal NT-proBNP levels (≤125pg/ml, nBNP) and 147 (67%) displayed high NTproBNP (hBNP). Compared to hBNP, nBNP patients were younger (62±10 vs 71±9 years, p&amp;lt;0.0001) and more obese (35±8 vs 32±7 kg/m 2 , p=0.005). At Exam 1, approximately 50% of nBNP displayed left ventricular (LV) systolic dysfunction defined as LV longitudinal strain (GLS)&amp;lt;16% ( Figure A ) and LA dysfunction defined as left atrial (LA) reservoir strain&amp;lt;26% ( Figure B ), but right ventricular (RV) systolic function as relatively preserved ( Figure C ). At Exam 2, LV, LA, and RV strain decreased in both groups (Panels A-C), with no difference between nBNP and hBNP in the velocity of change (p&amp;gt;0.6 for all). More patients crossed the threshold definition for LV systolic and LA dysfunction in nBNP compared to hBNP ( Figure D and E ), but the prevalence of RV dysfunction increased more in hBNP ( Figure F ). Conclusions: In patients with HFpEF with normal NT-proBNP, biventricular systolic function and LA function deteriorate over time at similar pace. These data suggest that patients with HFpEF are not a fundamentally different disorder, but rather represent an earlier stage of disease that progresses from LV and LA dysfunction in early stages to RV dysfunction in advanced stages.

Spontaneous Degenerative Aortic Valve Disease in New Zealand Obese Mice.

BackgroundDegenerative aortic valve (AoV) disease and resulting aortic stenosis are major clinical health problems. Murine models of valve disease are rare, resulting in a translational knowledge gap on underlying mechanisms, functional consequences, and potential therapies. Naïve New Zealand obese (NZO) mice were recently found to have a dramatic decline of left ventricular (LV) function at early age. Therefore, we aimed to identify the underlying cause of reduced LV function in NZO mice.Methods and ResultsCardiac function and pulmonary hemodynamics of NZO and age‐matched C57BL/6J mice were monitored by serial echocardiographic examinations. AoVs in NZO mice demonstrated extensive thickening, asymmetric aortic leaflet formation, and cartilaginous transformation of the valvular stroma. Doppler echocardiography of the aorta revealed increased peak velocity profiles, holodiastolic flow reversal, and dilatation of the ascending aorta, consistent with aortic stenosis and regurgitation. Compensated LV hypertrophy deteriorated to decompensated LV failure and remodeling, as indicated by increased LV mass, interstitial fibrosis, and inflammatory cell infiltration. Elevated LV pressures in NZO mice were associated with lung congestion and cor pulmonale, evident as right ventricular dilatation, decreased right ventricular function, and increased mean right ventricular systolic pressure, indicative for the development of pulmonary hypertension and ultimately right ventricular failure.ConclusionsNZO mice demonstrate as a novel murine model to spontaneously develop degenerative AoV disease, aortic stenosis, and the associated end organ damages of both ventricles and the lung. Closely mimicking the clinical scenario of degenerative AoV disease, the model may facilitate a better mechanistic understanding and testing of novel treatment strategies in degenerative AoV disease.

Reproducibility of echocardiographic indices of left atrial size in dogs with subclinical myxomatous mitral valve disease.

BackgroundReliability of echocardiographic measurements of left atrial (LA) size, an important marker of disease severity, has not been reported in dogs with myxomatous mitral valve disease (MMVD).ObjectivesTo define and compare reliability of left atrial dimension/diameter (LAD), LAD indexed to aortic valve diameter (LAD/AoD), left atrium‐to‐aortic root ratio (LA/Ao), left atrial volume acquired from a right parasternal long‐axis (LAVRPLx), and left apical view (LAVLAP) in dogs with subclinical MMVD.AnimalsNine dogs with subclinical MMVD.MethodsProspective reproducibility study. Dogs underwent 12 echocardiographic examinations by 2 operators on the mornings and afternoons of 3 nonconsecutive days within 1 week. Reliability (measurement variability) was quantified using coefficients of variation (CV) and 95% repeatability/reproducibility coefficients (95% RC). A mixed‐model analysis of variance (ANOVA) was used to determine if time of day, day, and operator were significant sources of variability for each index.ResultsLinear measurements (LAD, LAD/AoD, and LA/Ao) exhibited less within‐day, between‐day, and interoperator variability (CVs, 3.9%‐12.5%) than did volume estimate measurements (LAVRPLx and LAVLAP; CVs, 11.8%‐17.9%). Of the linear measurements, LA/Ao exhibited greater variability (CVs, 9.9%‐12.5%) compared to LAD and LAD/AoD (CVs, 3.9%‐4.9%). Operator was a significant (P = .005) source of variability for LA/Ao.Conclusions and Clinical ImportanceCompared to other linear measurements, LA/Ao was the least reproducible and most dependent on operator. The 95% RC for each LA size index are provided to help identify clinically relevant changes (beyond intraoperator or interoperator variability) during serial echocardiographic examinations of dogs with subclinical MMVD.

Left Ventricular Dimension after Mitral Valve Surgery in Rheumatic Mitral Stenosis: The Impact of Myocardial Fibrosis.

Background: Patients with rheumatic mitral stenosis (MS) experience changes in left ventricular (LV) dimensions after mitral valve surgery. We sought to investigate changes in LV dimensional parameters after mitral valve surgery and find out whether the same changes occurred in different extents of myocardial fibrosis. Methods: This prospective observational study comprised 43 patients with rheumatic MS planned for mitral valve surgery between October 2017 and April 2018 in National Cardiovascular Center Harapan Kita (NCCHK) Jakarta. All the patients underwent cardiac magnetic resonance imaging based on the late gadolinium enhancement (LGE) protocol for myocardial fibrosis assessment prior to surgery. The patients were classified according to the estimated fibrosis volume considered to influence hemodynamic performance (myocardial fibrosis <5% and myocardial fibrosis ≥5%). Serial transthoracic echocardiographic examinations before and after surgery were performed to detect changes in LV dimensional parameters. Results: This study consisted of 31 (72.1%) women and 12 (27.9%) men at a mean age of 46±9 years. The LGE protocol revealed myocardial fibrosis of less than 5% in 32 (74.4%) patients. A significant increase was detected in the LV end-diastolic diameter postoperatively, specifically in the patients with myocardial fibrosis of less than 5% (44.0±4.8 mm vs 46.6±5.6 mm; P value=0.027). A similar significant increase was not found in the other group (45.0±6.6 mm vs 46.7±6.9 mm; P value=0.256). Other changes in echocardiographic parameters showed similar patterns in both groups. Conclusion: Our patients with rheumatic MS who had myocardial fibrosis of less than 5% demonstrated better improvements in terms of increased preload. Myocardial fibrosis of less than 5% is associated with more favorable improvements in LV geometry.

Cone versus conventional repair for Ebstein's anomaly

ObjectivesWe aimed to investigate tricuspid valve function and adverse events after conventional repair and valve replacement for Ebstein's anomaly and compare them with cone repair. MethodsThe medical records of 151 patients (mean age, 25 years; 62% were female) who underwent operation in a single center from 1985 to 2018 were retrospectively analyzed. To determine tricuspid valve regurgitation during follow-up, serial echocardiographic examination was used (n = 2397, tricuspid regurgitation grades were graphed for every patient). ResultsThirty-nine patients underwent cone repair, 107 patients underwent other repair techniques, and 5 patients underwent valve replacement. The operative mortality was 1.3% (n = 2). Failed valve repair (defined as in-hospital death, conversion to replacement, or in-hospital reoperation) was less frequent after cone repair than after other repair techniques (5%, n = 2 vs 20%, n = 21, P = .039). Mean follow-up was 12.3 years (cone repair: 3.7 years). The 5-year cumulative incidence of moderate or greater recurrent tricuspid regurgitation was lower after cone repair than after other repair techniques (8% vs 32%, P = .03). Among the patients undergoing other repair techniques, the 15-year cumulative incidence of moderate or greater recurrent tricuspid regurgitation, severe tricuspid regurgitation, and reoperation was 58%, 37%, and 31%, respectively. During follow-up, 18 patients died (13 of cardiac and 5 of noncardiac causes). Among patients who died of cardiac causes, 10 of 13 had all 3 characteristics—moderate or greater tricuspid regurgitation, atrial fibrillation, and New York Heart Association classification III and IV—at their last medical evaluation. ConclusionsBefore cone repair, recurrent tricuspid regurgitation was considerable. Cone repair provided a higher rate of successful repair and a lower incidence of moderate or greater recurrent tricuspid regurgitation at the midterm follow-up.

ASE Statement on the Reintroduction of Echocardiographic Services during the COVID-19 Pandemic

• Echocardiography services have been interrupted by the COVID pandemic. • Services are being gradually reintroduced as healthcare facilities reopen. • Operational, workflow and prioritization considerations are suggested.

Does the right ventricle experiment morphologic and functional changes similarly to the left ventricle during pregnancy?

Morphological and functional right ventricular (RV) changes during normal pregnancy remain poorly characterized. Similar to left ventricle, RV load and function are expected to change, and establishing reference values for RV during a healthy pregnancy is critical for the evaluation of pregnancy-related heart disease. The aim of the study was to describe RV adaptation in a prospective cohort. Serial echocardiographic examinations were performed in second trimester (24±2weeks), third (32±2week) trimester, and postpartum (>3months after delivery). Nulliparous women were evaluated as control group. RV linear dimensions, areas, and function were assessed and compared. Forty-three pregnant women were evaluated and compared with nineteen nulliparous women as control. Function parameters decreased along gestation. RV fractional area fell from second to third trimester (52.01±0.92 vs 48.73±0.97, P<.05), as well as tricuspid annular plane systolic excursion (2.62±0.05 vs 2.41±0.05, P<.05); however, RV longitudinal strain (L) decreased earlier, showing main changes from second trimester (26.17±0.86 vs 22.71±0.57, P<.003, control vs second trimester). S'-wave velocity followed a different pattern without changes during pregnancy. RV diameters significantly increased during pregnancy: basal (3.65±0.06 vs 3.90±0.06, P<.05), mid- (2.70±0.06 vs 3.00±0.07, P<.05), longitudinal (6.90±0.09 vs 7.32±0.11, P<.05), and right ventricle outflow tract proximal diameter (3.20±0.06 vs 3.44±0.06, P<.05). RV areas also suffered early variation during pregnancy. In postpartum evaluation, all these changes were reversed. During pregnancy, RV experiments important variations. RV size increases, and its function decreases. Changes in LS were earlier compared with other function measures.

Myocardial deformation and acute cellular rejection after heart transplantation: Impact of inter-vendor variability in diagnostic effectiveness.

Our objective was to investigate the impact of inter-vendor variability in the ability of myocardial strain analysis to detect acute cellular rejection (ACR) in heart transplant recipients. We performed serial echocardiographic examinations in 18 consecutive adult heart transplanted patients, in their first year post-transplantation, within 3hours of the routine surveillance endomyocardial biopsies (EMB) in a single center. Myocardial strain was analyzed using two software in two different institutions, and inter-vendor variability of strain values and its association with ACR (any grade or grade ≥2R) was investigated. The parameter of comparison was the peak value of the average curve of strain during the entire cardiac cycle. A total of 147 pairs of EMB-echocardiogram were performed, 65 with no ACR, 63 with ACR grade 1R, and 19 with ACR grade ≥2R. Intra-class correlation coefficients for left ventricle longitudinal, radial, and circumferential strain were 0.38, 0.39, and 0.77, respectively, and 0.32 for right ventricular longitudinal strain. Neither software found significant association of left ventricular longitudinal strain with rejection. Grade ≥2R ACR was associated with left ventricular circumferential strain measured with the first software and with left ventricular radial strain with the other; and ACR of any grade was only significantly associated with right ventricle longitudinal strain measured with the first software. Inter-vendor reproducibility of strain values was low in this study. Some strain parameters were associated to ACR, although these results were inconsistent between two commercially available software. Specific validation of each software is warranted for this clinical indication.

Diastolic strain imaging: a new non-invasive tool to detect subclinical myocardial dysfunction in early cardiac allograft rejection.

Acute cellular rejection (ACR) remains a significant contributor to increased morbidity and mortality in heart transplant recipients. Early detection of ACR by non-invasive imaging is of potential clinical benefit. This study sought to investigate the use of non-invasive early global diastolic strain rate (GDSRe) and global longitudinal strain (GLS) in the detection of biopsy proven ACR. We retrospectively analysed 31 heart transplant patients (Mean age 52 ± 14years) with biopsy proven ACR who underwent serial transthoracic echocardiographic examination and 2D strain analysis. Traditional echocardiographic systolic and diastolic parameters and novel systolic and diastolic strain imaging were measured during (1) early rejection free period (0R); (2) pre-rejection period (pre-1R); and (3) grade 1R acute cellular rejection (1R-ACR). GDSRe was significantly reduced (p = 0.0001) during the pre-rejection period (pre-1R) (0.74/s) when compared with 0R (0.97/s). GLS was only significantly reduced during 1R-ACR (17.7%), p = 0.001 but could not detect pre-1R (19.9%). Global diastolic strain rate at isovolumic relaxation showed no significant differences between any of the rejection periods. Traditional systolic and diastolic indices showed no significant differences. In conclusion, early global diastolic strain rate is the most sensitive parameter to detect subclinical myocardial dysfunction during early periods of pre-1R prior to biopsy confirmed 1R-ACR. GDSRe is a potential new tool for non-invasive screening of early post-transplant cardiac allograft rejection.

Autoimmune myocarditis is not associated with left ventricular systolic dysfunction

BackgroundExperimental autoimmune myocarditis (EAM) is a common animal model for the investigation of the pathophysiology of myocarditis. Because of diverging findings from previous studies, we performed serial echocardiographic examinations throughout the course of the disease and investigated the dimensions of the murine heart and left ventricular (LV) systolic function.Materials and MethodsExperimental autoimmune myocarditis was induced in male Balb/c mice by subcutaneous injection of a fragment of the α‐myosin heavy chain (MyHC‐α 614‐629: Ac‐SLKLMATLFSTYASAD). Transthoracic echocardiography was performed on days 0, 7 and 21 in healthy animals and mice with EAM.ResultsExperimental autoimmune myocarditis was associated with a reduction in LV systolic function and an increase in LV internal diameter in diastole (LVIDd) and systole (LVIDs) 7 days postimmunization. After 21 days, EAM led to a significant increase in LV‐thickness (1.3‐fold increase in LV anterior wall diameter in diastole [LVAWDd]), but there was no difference in LV systolic function between immunized animals and healthy controls. LV‐thickness correlated well with the severity of myocarditis in the histopathological examination (LVAWDd: rs = 0.603, P = 0.003, LV anterior wall diameter in systole (LVAWDs): rs = 0.718, P < 0.0001).ConclusionOur results indicate that EAM leads to an initial dilatation of the LV that is followed by ventricular “hypertrophy.” On day 21, there was no significant difference in LV systolic function between immunized animals and controls. Furthermore, the ageing of the animals had a major impact on the echocardiographic parameters; therefore, the use of healthy age‐matched controls seems warranted when echocardiography is performed in rodents.

Cardioprotective Effects of HSP72 Administration on Ischemia-Reperfusion Injury

BackgroundAlthough early reperfusion is the most desirable intervention after ischemic myocardial insult, it may add to damage through oxidative stress. ObjectivesThis study investigated the cardioprotective effects of a single intravenous dose of heat shock protein-72 (HSP72) coupled to a single-chain variable fragment (Fv) of monoclonal antibody 3E10 (3E10Fv) in a rabbit ischemia-reperfusion model. The Fv facilitates rapid transport of HSP72 into cells, even with intact membranes. MethodsA left coronary artery occlusion (40 min) reperfusion (3 h) model was used in 31 rabbits. Of these, 12 rabbits received the fusion protein (Fv-HSP72) intravenously. The remaining 19 control rabbits received a molar equivalent of 3E10Fv alone (n = 6), HSP72 alone (n = 6), or phosphate-buffered saline (n = 7). Serial echocardiographic examinations were performed to assess left ventricular function before and after reperfusion. Micro–single-photon emission computed tomography imaging of 99mTc-labeled annexin-V was performed with micro–computed tomography scanning to characterize apoptotic damage in vivo, followed by gamma counting of the excised myocardial specimens to quantify cell death. Histopathological characterization of the myocardial tissue and sequential cardiac troponin I measurements were also undertaken. ResultsMyocardial annexin-V uptake was 43% lower in the area at risk (p = 0.0003) in Fv-HSP72–treated rabbits compared with control animals receiving HSP72 or 3E10Fv alone. During reperfusion, troponin I release was 42% lower and the echocardiographic left ventricular ejection fraction 27% higher in the Fv-HSP72–treated group compared with control animals. Histopathological analyses confirmed penetration of 3E10Fv-containing molecules into cardiomyocytes in vivo, and treatment with Fv-HSP72 showed fewer apoptotic nuclei compared with control rabbits. ConclusionsSingle-dose administration of Fv-HSP72 fusion protein at the time of reperfusion reduced myocardial apoptosis by almost one-half and improved left ventricular functional recovery after myocardial ischemia-reperfusion injury in rabbits. It might have potential to serve as an adjunct to early reperfusion in the management of myocardial infarction.

Relationships Between Periventricular Epicardial Adipose Tissue Accumulation, Coronary Microcirculation, and Left Ventricular Diastolic Dysfunction

BackgroundObesity is related to left ventricular (LV) diastolic dysfunction, although its pathophysiological mechanism remains unclear. Epicardial adipose tissue (EAT) is an ectopic fat with paracrine effects on coronary circulation and myocardium. We hypothesized that left ventricle–specific (periventricular) EAT may deteriorate diastolic function by impairing coronary microcirculation. MethodsIn protocol 1, 74 patients without obstructive narrowing of the left anterior descending artery on multidetector computed tomography (MDCT) underwent coronary flow reserve (CFR) examination to evaluate the relationship between EAT and coronary microcirculation. In protocol 2, 372 patients who underwent both MDCT and serial transthoracic Doppler echocardiographic (TTDE) examinations were enrolled to investigate the impact of periventricular EAT on changes in diastolic function. EAT volume was measured by MDCT. CFR and diastolic function were assessed by TTDE. Deterioration of LV diastolic function was defined as a ≥ 20% decrease in early diastolic mitral annular velocity. ResultsCFR was significantly correlated with periventricular EAT volume (r = −0.37; P = 0.001), but not with total EAT volume (r = −0.21; P = 0.071). Periventricular EAT volume (P = 0.010) was significantly associated with CFR independent of cardiovascular risk factors. Among the 372 patients who had serial TTDE examinations, the frequency of deteriorated LV diastolic function was lowest in the lower tertile of periventricular EAT, intermediate in the middle tertile, and highest in the upper tertile (12.9%, 21.0%, and 25.8%, respectively; P = 0.037). Age, diabetes mellitus, and periventricular EAT volume were significantly associated with deterioration of LV diastolic function (all P < 0.05). ConclusionsThis study demonstrated the close association of periventricular EAT with impaired CFR and deteriorated LV diastolic function.