Assessment of anthracycline-induced cardiotoxicity in childhood cancer survivors during long-term follow-up using strain analysis and intraventricular pressure gradient measurements.

BACKGROUND: Cardiac dysfunction due to cardiotoxicity from anthracycline chemotherapy is a leading cause of morbidity and mortality in childhood cancer survivors (CCS), and the cumulative incidence of cardiac events has continued to increase. This study identifies an adequate indicator of cardiac dysfunction during long-term follow-up. PROCEDURE: In total, 116 patients (median age: 15.5 [range: 4.7-40.2] years) with childhood cancer who were treated with anthracycline were divided into three age groups for analysis (C1: 4-12 years of age, C2: 13-18 years of age, C3: 19-40 years of age), and 116 control patients of similar ages were divided into three corresponding groups (N1, N2, and N3). Layer-specific strains were assessed for longitudinal strain (LS) and circumferential strain (CS). The total and segmental intraventricular pressure gradients (IVPG) were also calculated based on Doppler imaging of the mitral inflow using Euler's equation. RESULTS: Conventional echocardiographic parameters were not significantly different between the patients and controls. All layers of the LS and inner and middle layers of the basal and papillary CS in all ages and all IVPGs in C2 and C3 decreased compared to those of corresponding age groups. Interestingly, basal CS and basal IVPG in CCS showed moderate correlation and both tended to rapidly decrease with aging. Furthermore, basal IVPG and anthracycline dose showed significant correlations. CONCLUSIONS: Basal CS and total and basal IVPGs may be particularly useful indicators of cardiotoxicity in long-term follow-up.

Novel Findings of Early Cardiac Dysfunction in Patients With Childhood-Onset Inflammatory Bowel Disease Using Layer-Specific Strain Analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at a higher risk of developing cardiovascular diseases than healthy individuals, owing to persistent chronic inflammation and treatment effects. This study aimed to assess left ventricular function in patients with childhood-onset IBD using layer-specific strain analysis and to identify early indicators of cardiac dysfunction in them. METHODS: A total of 47 patients with childhood-onset ulcerative colitis (UC), 20 patients with Crohn's disease (CD), and 75 age- and sex-matched healthy control subjects were included in this study. Conventional echocardiographic measurements of layer-specific (ie, endocardium, midmyocardium, and epicardium) global longitudinal strain and global circumferential strain (GCS) were evaluated in these participants. RESULTS: Layer-specific strain analysis showed that global longitudinal strain was lower in all layers for the UC (P < .001) and CD (P < .001) groups, regardless of the age at onset, but that GCS was only lower in the midmyocardial (P = .032) and epicardial (P = .018) layers in the CD group than in the control group. Although the mean left ventricular wall thickness was not significantly different among the groups, it was significantly correlated with the GCS of the endocardial layer in the CD group (ρ= -0.615; P = .004), suggesting that thickening of the left ventricular wall occurred as a compensatory mechanism to maintain the endocardial strain in the CD group layer. CONCLUSIONS: Children and young adults with childhood-onset IBD displayed decreased midmyocardial deformation. Layer-specific strain could also be useful to identify indicators of cardiac dysfunction in patients with IBD.

Patients with inflammatory bowel disease are at a higher risk of developing cardiovascular disease than healthy individuals. Our study revealed that children and young adults with childhood-onset inflammatory bowel disease already have reduced myocardial deformability.

Intraventricular pressure gradients change during the development of left ventricular hypertrophy: Effect of salvianolic acid B and beta-blocker.

INTRODUCTION: Intraventricular pressure gradient is regarded as a non-invasive indicator of diastolic function. Salvianolic acid B (Sal-B), a traditional Asian medicine, revealed its usefulness in myocardial infarction models; however, the hemodynamic effect of salvianolic acid B is still unknown. The present study aimed to investigate the intraventricular pressure gradient changes during the development of left ventricular hypertrophy with or without salvianolic acid B and a beta-blocker. METHODS: In total, 48 rats were divided into four groups; Sham, Non-treatment, salvianolic acid B, and Carvedilol. Aortic coarctation-induced left ventricular hypertrophy was done in three groups and the treatment was started from the third to the sixth week. Blood pressure, conventional echocardiography, and color M-mode echocardiography for measurement of intraventricular pressure gradient were carried out for six consecutive weeks. RESULTS: At 4.5 weeks, the LV mass was elevated in the coarctation groups but the blood pressure was significantly lower in salvianolic acid B and Carvedilol groups (P < 0.05). In the Non-treatment group, the total intraventricular pressure gradient was increased at 4.5 and 6 weeks (2.60 and 2.65, respectively). Meanwhile, the basal intraventricular pressure gradient was elevated at 3 and 6 weeks (1.67 and 1.75) compared with the Sham group. Salvianolic acid B and Carvedilol significantly reduced the basal intraventricular pressure gradient at six weeks compared with the Non-treatment group (1.52 and 1.51 vs 1.75, respectively). CONCLUSIONS: Salvianolic acid B and Carvedilol promote cardiac function by decreasing the elevated basal intraventricular pressure gradient. The current preclinical results revealed the efficacy of salvianolic acid B as a potential therapy for left ventricular hypertrophy because of the non-blood pressure lowering effect.

The Utility of Intraventricular Pressure Gradient for Early Detection of Chemotherapy-Induced Subclinical Cardiac Dysfunction in Dogs.

Early detection of doxorubicin (DXR)-induced cardiomyopathy (DXR-ICM) is crucial to improve cancer patient outcomes and survival. In recent years, the intraventricular pressure gradient (IVPG) has been a breakthrough as a sensitive index to assess cardiac function. This study aimed to evaluate the usefulness of IVPG for the early detection of chemotherapy-related cardiac dysfunction. For this purpose, six dogs underwent conventional, speckle tracking, and color M-mode echocardiography concomitantly with pressure-and-volume analysis by conductance catheter. The cardiac function measurements were assessed before DXR administration (baseline, Pre), at the end of treatment protocol (Post), and at 1.5 years follow-up (Post2). The result showed a significant reduction in the left ventricular end-systolic pressure-volume (Emax: 4.4 ± 0.7, 6.1 ± 1.6 vs. 8.4 ± 0.8 mmHg/mL), total-IVPG (0.59 ± 0.12, 0.62 ± 0.15 vs. 0.86 ± 0.12 mmHg), and mid-IVPG (0.28 ± 0.12, 0.31 ± 0.11 vs. 0.48 ± 0.08 mmHg), respectively in Post2 and Post compared with the baseline (p < 0.05). Mid-to-apical IVPG was also reduced in Post2 compared with the baseline (0.29 ± 0.13 vs. 0.51 ± 0.11). Meanwhile, the fraction shortening, ejection fraction, and longitudinal strain revealed no change between groups. Total and mid-IVPG were significantly correlated with Emax (R = 0.49; p < 0.05, both) but only mid-IVPG was a predictor for Emax (R2 = 0.238, p = 0.040). In conclusion, this study revealed that impairment of contractility was the initial changes observed with DXR-ICM in dogs and only IVPG could noninvasively detect subclinical alterations in cardiac function. Color M-mode echocardiography-derived IVPG could be a potential marker for the early detection of doxorubicin cardiomyopathy.

Left atrial dysfunction and stiffness in pediatric and adult patients with Type 1 diabetes mellitus assessed with speckle tracking echocardiography.

BACKGROUND: Subclinical diastolic dysfunction in patients with Type 1 diabetes mellitus (T1DM) caused by myocardial injury due to diabetic cardiomyopathy leads to a high risk of death and heart failure. This myocardial injury extends not only to the left ventricle (LV) but also to the left atrium (LA). However, LA function in children and young adults with T1DM has not been extensively studied. OBJECTIVE: Therefore, the aim of this study was to assess LA dysfunction in pediatric and adult patients with T1DM using LA strain analysis with echocardiography. SUBJECTS: Fifty-three patients (median age: 23 [range: 5-41] years) with T1DM. METHODS: We divided the patients into three age groups (D1: 5-14 years, D2: 15-24 years, D3: 25-41 years); 53 age- and sex-matched controls were divided into three corresponding groups (C1, C2, and C3). LA and LV functions were evaluated using echocardiography. RESULTS: LA reservoir strain was lower in the D2 and D3 groups than in the C2 and C3 groups (P = 0.001, P = 0.004, respectively). LA conduit strain was lower in the D2 group than in the C2 group (P = 0.002). LA stiffness was significantly greater in the D3 group than in the C3 group (P < 0.001). CONCLUSIONS: In patients with T1DM, LA phasic function decreased in adolescents and young adults, and LA stiffness increased in adult patients aged >30 years. LA phasic function and LA stiffness can be potentially used as early markers for diastolic dysfunction.

In-Depth Insight Into the Mechanisms of Cardiac Dysfunction in Patients With Type 1 Diabetes Mellitus Using Layer-Specific Strain Analysis.

BACKGROUND: Although the subclinical left ventricular (LV) dysfunction caused by diabetes mellitus (DM) results in a high risk of death and heart failure, the details of cardiac dysfunction across a wide age range remain unclear. The aim of this study was to assess LV dysfunction in patients with type 1 DM (T1DM) using layer-specific strain analysis by echocardiography.Methods and Results:The 52 patients (median age: 23 [range: 5-40] years) with T1DM were divided into 3 age groups (D1: 5-14 years, D2: 15-24 years, D3: 25-40 years); 78 age- and sex-similar controls were divided into 3 corresponding groups (C1, C2, and C3). Layer-specific longitudinal strain (LS) and circumferential strain (CS) of the 3 myocardial layers (endocardium, midmyocardium, and epicardium) were determined using echocardiography. Strains did not decrease in D1. Epicardial and midmyocardial CS at the basal level and LS in all layers were decreased in D2 compared with C2. CS at the basal level and LS in all layers were lower in D3 than in C3. The strains correlated with the duration of T1DM and LV wall thickness. CONCLUSIONS: In patients with T1DM, longitudinal deformation in all layers and epicardial and midmyocardial circumferential deformation at the basal level decreased from the late teens, which correlated with the duration of the disease and LV hypertrophy.

Left ventricular vortex and intraventricular pressure difference in dogs under various loading conditions.

Restrictions on the conventional evaluation of diastolic function have been recognized, especially under various loading conditions. Recently, new noninvasive ventricular vortex indexes have been introduced and are expected to reflect the cardiac function. Physiologically, there is a hypothesis that the intraventricular pressure difference (IVPD) is related to the formation of vortexes. IVPD and vortex indexes were simultaneously measured, and the relationship between the two was investigated. To verify the possibility of diastolic vorticity as an index of diastolic relaxation, a correlation between diastolic vorticity and the load dependency of vorticity [time constant (τ)] was examined. Six healthy dogs were studied using transthoracic echocardiography, pressure, and a conductance catheter. Vorticity was analyzed using vector flow mapping (VFM). IVPD was determined using Euler's equation with color M-mode Doppler images. Data were obtained at baseline, at balloon dilatation in the thoracic aorta to alter afterload, at hydroxyethyl starch infusion to alter preload, and at milrinone administration to alter ventricular relaxation. Peak vorticity at early diastole (E-Vor) and IVPD of the midventricle (MIVPD) decreased under pressure loading, were unchanged under volume loading, and increased during milrinone administration. In multivariate analysis, the independent predictors of τ were global longitudinal strain, strain rate at early diastole, and E-Vor. MIVPD was strongly correlated with E-Vor ( r = 0.84). VFM-derived peak E vorticity was strongly related to IVPD, especially MIVPD, under various loading conditions. Both of these novel indexes are promising as reliable indexes of ventricular relaxation, independent from preload. NEW & NOTEWORTHY We showed the close relationship of vortex and intraventricular pressure difference and showed that both of them can become new markers of the left ventricular relaxation property. Our present study creates a paradigm for future studies in the field of intraventircular flow physiology and clinical diastology.

Cardiac Function in Infants Born to Mothers With Gestational Diabetes　- Estimation of Early Diastolic Intraventricular Pressure Differences.

Background: This study compared the myocardial performance of infants born to mothers with gestational diabetes mellitus (IGDM) and without GDM (controls) under the new GDM definitions. Methods and Results: The subjects consisted of 36 IGDM and 39 control infants. GDM diagnosis was based on oral glucose tolerance test during pregnancy or the presence of diabetes prior to the current pregnancy. Between-group infant cardiac function was determined and compared using 2-D speckle tracking analysis, intraventricular pressure difference (IVPD) and IVP gradient (IVPG), using color M-mode Doppler imaging. IVPD and IVPG were higher in IGDM than in the controls, particularly the mid-apical IVPG. The global circumferential strain (GCS) and endocardial GCS were higher in IGDM than in controls. Increased maternal glycated hemoglobin was correlated with reduced transmural and epicardial GCS in the IGDM. Maternal maximum fasting blood sugar had a mild, positive correlation with IVPD and IVPG. Conclusions: Ventricular sucking force, measured as the IVPD, IVPG, and endocardial GCS, were higher in IGDM than in the controls. A hyperglycemic environment during pregnancy leads to impaired cardiac performance in IGDM, compared with control infants. IGDM might have favorable systolic and diastolic cardiac performance due to cardiac metabolic adaptations occurring before poor glucose control causes impaired cardiac performance.