Prevalence of Diastolic Dysfunction in Adult Survivors of Childhood Cancer: A Report From SJLIFE Cohort.

Background: The prevalence of diastolic dysfunction has not been systematically evaluated in a large population of survivors of childhood cancer using established guidelines and standards. Objectives: This study sought to assess the prevalence and progression of diastolic dysfunction in adult survivors of childhood cancer exposed to cardiotoxic therapy. Methods: Comprehensive, longitudinal echocardiographic examinations of adult survivors of childhood cancer ≥18 years of age and ≥10 years from diagnosis in SJLIFE (St. Jude Lifetime Cohort Study) were performed. Diastolic dysfunction was defined based on 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Results: Among 3,342 survivors, the median (25th-75th percentiles [quartile (Q)1-Q3]) age at diagnosis was 8.1 years (Q1-Q3: 3.6-13.7 years), 30.1 years (Q1-Q3: 24.4-37.0 years) at the baseline echocardiography evaluation (Echo 1), and 36.6 years (Q1-Q3: 30.8-43.6 years) at the last follow-up echocardiography evaluation (1,435 survivors) (Echo 2). The proportion of diastolic dysfunction was 15.2% (95% CI: 14.0%-16.4%) at Echo 1 and 15.7% (95% CI: 13.9%-17.7%) at Echo 2, largely attributable to concurrent systolic dysfunction. Less than 5% of survivors with preserved ejection fraction had diastolic dysfunction (2.2% at Echo 1, 3.7% at Echo 2). Using global longitudinal strain assessment in adult survivors with preserved ejection fraction (defined with a cutpoint worse than -15.9%), the proportion of diastolic dysfunction increased to 9.2% at baseline and 9.0% at follow-up. Conclusions: The prevalence of isolated diastolic dysfunction is low among adults who received cardiotoxic therapies for childhood cancer. The inclusion of left ventricular global longitudinal strain significantly increased the identification of diastolic dysfunction.

Impairment in quantitative microvascular function in non-ischemic cardiomyopathy as demonstrated using cardiovascular magnetic resonance.

BACKGROUND: Microvascular dysfunction (MVD) is present in various cardiovascular diseases and portends worse outcomes. We assessed the prevalence of MVD in patients with non-ischemic cardiomyopathy (NICM) as compared to subjects with preserved ejection fraction (EF) using stress cardiovascular magnetic resonance (CMR). METHODS: We retrospectively studied consecutive patients with NICM and 58 subjects with preserved left ventricular (LV) EF who underwent stress CMR between 2011-2016. MVD was defined visually as presence of a subendocardial perfusion defect and semiquantitatively by myocardial perfusion reserve index (MPRI<1.51). MPRI was compared between groups using univariate analysis and multivariable linear regression. RESULTS: In total, 41 patients with NICM (mean age 51 ± 14, 59% male) and 58 subjects with preserved LVEF (mean age 51 ± 13, 31% male) were identified. In the NICM group, MVD was present in 23 (56%) and 11 (27%) by semiquantitative and visual evaluation respectively. Compared to those with preserved LVEF, NICM patients had lower rest slope (3.9 vs 4.9, p = 0.05) and stress perfusion slope (8.8 vs 11.7, p<0.001), and MPRI (1.41 vs 1.74, p = 0.02). MPRI remained associated with NICM after controlling for age, gender, hypertension, ethnicity, diabetes, and late gadolinium enhancement (log MPR, ß coefficient = -0.19, p = 0.007). CONCLUSIONS: MVD-as assessed using CMR-is highly prevalent in NICM as compared to subjects with preserved LVEF even after controlling for covariates. Semiquantitative is able to detect a greater number of incidences of MVD compared to visual methods alone. Further studies are needed to determine whether treatment of MVD is beneficial in NICM.

Patent Ductus Arteriosus Stent Versus Surgical Aortopulmonary Shunt for Initial Palliation of Cyanotic Congenital Heart Disease with Ductal-Dependent Pulmonary Blood Flow: A Systematic Review and Meta-Analysis.

Background In patients with ductal-dependent pulmonary blood flow, initial palliation includes catheter-based patent ductus arteriosus (PDA) stent or surgical aortopulmonary shunt (APS). This meta-analysis aimed to compare outcomes between PDA stent and APS. Methods and Results A comprehensive literature search yielded six retrospective observational studies. Pooled adjusted hazard ratios (HR) were included to control for covariates and assess time to event analysis. Of 757 patients, 243 (32.1%) underwent PDA stent and 514 (67.9%) underwent APS. Pulmonary atresia with intact ventricular septum and expected biventricular repair were more common with PDA stent compared with APS (39.6% versus 21.2%, P<0.001 and 57.9% versus 46.6%, P=0.007, respectively). There was no statistically significant difference in mortality between PDA stent and APS (HR, 0.71; [95% CI, 0.26-1.93]; P=0.50). PDA stent was associated with lower risk of postprocedural complications (odds ratio [OR], 0.45; [95% CI, 0.25-0.81]; P=0.008), mechanical circulatory support (OR, 0.27; [95% CI, 0.09-0.79]; P=0.02), and shorter intensive care unit length of stay (-4.03 days; [95% CI, -5.99 to -2.07]; P<0.001), hospital length of stay (-5.54 days; [95% CI, -9.20 to -1.88]; P=0.003), and duration of mechanical ventilation (-3.41 days; [95% CI, -5.29 to -1.52]; P<0.001). There was no difference in pulmonary artery growth or hazard of unplanned reintereventions. Conclusions PDA stent has a similar hazard of mortality compared with APS. Benefits to PDA stent include shorter duration of mechanical ventilation, shorter hospital length of stay, and fewer complications. Differences in patient characteristics exist with more patients with pulmonary atresia with intact ventricular septum and expected biventricular repair undergoing PDA stent.

Prevalence and haemodynamic profiles of pulmonary hypertension in cardiac amyloidosis.

OBJECTIVES: While cardiac amyloidosis (CA) classically involves the left ventricle (LV), less is known about its impact on the right ventricle (RV) and pulmonary vasculature. We performed a retrospective analysis to identify the prevalence and types of pulmonary hypertension (PH) profiles in CA and to determine haemodynamic and cardiovascular magnetic resonance (CMR) predictors of major adverse cardiovascular events (MACE). METHODS: Patients with CA who underwent CMR and right heart catheterisation (RHC) within 1 year between 2010 and 2019 were included. Patients were assigned the following haemodynamic profiles based on RHC: no PH, precapillary PH, isolated postcapillary PH (IPCPH), or combined precapillary and postcapillary PH (CPCPH). The relationship between PH profile and MACE (death, heart failure hospitalisation) was assessed using survival analysis. CMR and RV parameters were correlated with MACE using Cox-regression analysis. RESULTS: A total of 52 patients were included (age 69±9 years, 85% men). RHC was performed during biopsy in 44 (85%) and for clinical indications in 8 (15%) patients. Rates of no PH, precapillary PH, IPCPH and CPCPH were 5 (10%), 3 (6%), 29 (55%) and 15 (29%), respectively. Haemodynamic PH profile did not correlate with risk of death (p=0.98) or MACE (p=0.67). Transpulmonary gradient (TPG) (HR 0.88, CI 0.80 to 0.97), RV, (HR 0.95, CI 0.92 to 0.98) and LV ejection fraction (HR 0.95, CI 0.92 to 0.98) were significantly associated with MACE. CONCLUSIONS: PH is highly prevalent in CA, even at the time of diagnosis. While IPCPH was most common, CPCPH is not infrequent. TPG and RV ejection fraction (RVEF) are prognostic markers in this population.

Application of machine learning in screening for congenital heart diseases using fetal echocardiography.

There is a growing body of literature supporting the utilization of machine learning (ML) to improve diagnosis and prognosis tools of cardiovascular disease. The current study was to investigate the impact that the ML framework may have on the sensitivity of predicting the presence or absence of congenital heart disease (CHD) using fetal echocardiography. A comprehensive fetal echocardiogram including 2D cardiac chamber quantification, valvar assessments, assessment of great vessel morphology, and Doppler-derived blood flow interrogation was recorded. The postnatal echocardiogram was used to ascertain the diagnosis of CHD. A random forest (RF) algorithm with a nested tenfold cross-validation was used to train models for assessing the presence of CHD. The study population was derived from a database of 3910 singleton fetuses with maternal age of 28.8 ± 5.2 years and gestational age at the time of fetal echocardiography of 22.0 weeks (IQR 21-24). The proportion of CHD was 14.1% for the studied cohort confirmed by post-natal echocardiograms. Our proposed RF-based framework provided a sensitivity of 0.85, a specificity of 0.88, a positive predictive value of 0.55 and a negative predictive value of 0.97 to detect the CHD with the mean of mean ROC curves of 0.94 and the mean of mean PR curves of 0.84. Additionally, six first features, including cardiac axis, peak velocity of blood flow across the pulmonic valve, cardiothoracic ratio, pulmonary valvar annulus diameter, right ventricular end-diastolic diameter, and aortic valvar annulus diameter, are essential features that play crucial roles in adding more predictive values to the model in detecting patients with CHD. ML using RF can provide increased sensitivity in prenatal CHD screening with very good performance. The incorporation of ML algorithms into fetal echocardiography may further standardize the assessment for CHD.

Atrial function and geometry differences in transthyretin versus immunoglobulin light chain amyloidosis: a cardiac magnetic resonance study.

To determine the differences in left atrial (LA) function and geometry assessed by cardiac magnetic resonance (CMR) between transthyretin (ATTR) and immunoglobulin light chain (AL) cardiac amyloidosis (CA). We performed a retrospective analysis of 54 consecutive patients (68.5% male, mean age 67 ± 11 years) with confirmed CA (24 ATTR, 30 AL) who underwent comprehensive CMR examinations. LA structural and functional assessment including LA volume, LA sphericity index, and LA strain parameters were compared between both subtypes. In addition, 15 age-matched controls were compared to all groups. Patients with ATTR-CA were older (73 ± 9 vs. 62 ± 10 years, p < 0.001) and more likely to be male (83.3% vs. 56.7%, p = 0.036) when compared to AL-CA. No significant difference existed in LA maximum volume and LA sphericity index between ATTR-CA and AL-CA. LA minimum volumes were larger in ATTR-CA when compared with AL-CA. There was a significant difference in LA function with worse strain values in ATTR vs AL: left atrial reservoir [7.4 (6.3-12.8) in ATTR vs. 13.8 (6.90-24.8) in AL, p = 0.017] and booster strains [3.6 (2.6-5.5) in ATTR vs. 5.2 (3.6-12.1) in AL, p = 0.039]. After adjusting for age, LA reservoir remained significantly lower in ATTR-CA compared to AL-CA (p = 0.03), but not LA booster (p = 0.16). We demonstrate novel differences in LA function between ATTR-CA and AL-CA despite similar LA geometry. Our findings of more impaired LA function in ATTR may offer insight into higher AF burden in these patients.

Left Ventricular End-Diastolic Dimension and Clinical Outcomes After Centrifugal Flow Left Ventricular Assist Device Implantation.

The impact of preoperative end-diastolic left ventricular dimension (preLVEDD) on long-term outcomes with centrifugal continuous-flow left ventricular assist device (CF-LVAD) is not well established. Accordingly, we performed an analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry to study this relationship. All patients with centrifugal CF-LVAD in the INTERMACS registry from June 2006 to December 2017 were screened. The final study group consisted of 3,304 patients. After a median follow-up of 9.0 months (interquartile range [IQR], 4.2-18.8 months), 2,596 (79%) patients were alive. After adjusting for significant covariates, increased preLVEDD was associated with lower mortality (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84-0.98; p = 0.01), stroke (HR, 0.85; 95% CI, 0.77-0.93; p < 0.001), and gastrointestinal bleeding (HR, 0.88; 95% CI, 0.80-0.97; p = 0.01), although there were more arrhythmias (HR, 1.14; 95% CI, 1.05-1.24; p = 0.003). Our study suggests that preLVEDD is an independent predictor of mortality and adverse events in patients treated with centrifugal CF-LVAD. preLVEDD should be considered an important preimplant variable for risk stratification when considering a CF-LVAD.

Infarct size and long-term left ventricular remodelling in acute myocardial infarction patients subjected to transcoronary delivery of progenitor cells.

Introduction: Infarct size (IS) is a fundamental determinant of left-ventricular (LV) remodelling (end-systolic and end-diastolic volume change, ΔESV, ΔEDV) and adverse clinical outcomes after myocardial infarction (MI). Our prior work found that myocardial uptake of transcoronary-delivered progenitor cells is governed by IS. Aim: To evaluate the relationship between IS, stem cell uptake, and the magnitude of LV remodelling in patients receiving transcoronary administration of progenitor cells shortly after MI. Material and methods: Thirty-one subjects (age 36-69 years) with primary percutaneous coronary intervention (pPCI)-treated anterior ST-elevation MI (peak CK-MB 584 [181-962] U/l, median [range]) and sustained left ventricle ejection fraction (LVEF) ≤ 45% were studied. On day 10 (median) 4.3 × 106 (median) autologous CD34+ cells (50% labelled with 99mTc-extametazime) were administered via the infarct-related artery (left anterior descending). ΔESV, ΔEDV, and mid circumferential myocardial strain (mCS) were evaluated at 24 months. Results: Infarct mass (cMRI) was 57 [11-112] g. Cell label myocardial uptake (whole-body γ-scans) was proportional to IS (r = 0.62), with a median 2.9% uptake in IS 1st tercile (≤ 45 g), 5.2% in 2nd (46-76 g), and 6.7% in 3rd (> 76 g) (p = 0.0006). Cell uptake in proportion to IS attenuated the IS-ΔESV (p = 0.41) and IS-ΔEDV (p = 0.09) relationship. At 24 months, mCS improved in IS 2nd tercile (p = 0.028) while it showed no significant change in smaller (p = 0.87) or larger infarcts (p = 0.58). Conclusions: This largest human study with labelled CD34+ cell transplantation shortly after MI suggests that cell uptake (proportional to IS) may attenuate the effect of IS on LV adverse remodelling. To boost this effect, further strategies should involve cell types and delivery techniques to maximize myocardial uptake.