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 intraventricular pressure gradient in hypertrophic cardiomyopathy patients receiving implantable cardioverter-defibrillators for primary prevention

Background Conventional risk factors for sudden cardiac death (SCD) justify primary prevention through implantable cardioverter-defibrillator (ICD) implantation in hypertrophic cardiomyopathy (HCM) patients. However, the positive predictive values for these conventional SCD risk factors are low. Left ventricular outflow tract obstruction (LVOTO) and midventricular obstruction (MVO) are potential risk modifiers for SCD. The aims of this study were to evaluate whether an elevated intraventricular pressure gradient (IVPG), including LVOTO or MVO, is a potential risk modifier for SCD and ventricular arrhythmias requiring ICD interventions in addition to the conventional risk factors among HCM patients receiving ICDs for primary prevention. Methods We retrospectively studied 60 HCM patients who received ICDs for primary prevention. An elevated IVPG was defined as a peak instantaneous gradient ≥ 30 mmHg at rest, as detected by continuous-wave Doppler echocardiography. The main outcome was a composite of SCD and appropriate ICD interventions, which were defined as an antitachycardia pacing or shock therapy for ventricular tachycardia or fibrillation. The Cox proportional hazards model was used to assess the relationships between risk factors and the occurrence of SCD and appropriate ICD interventions. Results Thirty patients met the criteria of elevated IVPG (50%). During the median follow-up period of 66 months, 2 patients experienced SCD, and 10 patients received appropriate ICD interventions. Kaplan–Meier curves showed that the incidence of the main outcome was higher in patients with an IVPG ≥ 30 mmHg than in those without an IVPG ≥ 30 mmHg (log-rank P = 0.03). There were no differences in the main outcome between patients with LVOTO and patients with MVO. The combination of nonsustained ventricular tachycardia (NSVT) and IVPG ≥ 30 mmHg was found to significantly increase the risk of the main outcome (HR 6.31, 95% CI 1.36–29.25, P = 0.02). Five patients experienced ICD implant-related complications. Conclusions Our findings showed that a baseline IVPG ≥ 30 mmHg was associated with an increased risk of experiencing SCD or appropriate ICD interventions among HCM patients who received ICDs for primary prevention. Combined with NSVT, which is a conventional risk factor, a baseline IVPG ≥ 30 mmHg may be a potential modifier of SCD risk in HCM patients.

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.

Abstract 20360: MRI Assessment of Diastolic and Systolic Intraventricular Pressure Gradients in Heart Failure

Background: Non-invasive assessment of left ventricular (LV) diastolic function is an important goal to better understand physiologic abnormalities in heart failure. The spatiotemporal pattern of LV blood flow velocities during early filling can be used to estimate intraventricular pressure gradients driving early filling. MRI can provide accurate flow velocity information in the LV, but this method has not been exploited to assess diastolic function in heart failure (HF). Aim: To assess differences in intraventricular pressure gradients in heart failure and preserved ejection fraction (HFPEF) and heart failure with reduced ejection fraction (HFREF), compared to subjects without HF. Methods: We studied 23 subjects without HF, 13 subjects with HFREF and 14 subjects with HFPEF. Intraventricular flow during diastole was measured using 2D in-plane phase-contrast MRI. We solved the Eulier equations to compute intraventricular pressure gradients during LV early filling (figure) and during ejection. Results: Whereas the initial velocity of wave propagation (was not significantly different between the groups, the terminal diastolic propagation velocity during early diastolic filling was significantly slower (P=0.004) in HFREF (5.2 m/s; 95%CI=3.9-6.8) than in patients with HFPEF (9.5; 95%CI=6.6-13.6) or subjects without HF (8.9; 95%CI=7.3-10.7). In contrast, HFPEF was associated with a greater amplitude of the reversal of the base-to-apex intraventricular pressure gradient during early filling (β=-0.34; P=0.04), which was driven by the inertial component. Conclusions: HFPEF and HFREF are associated with distinct patterns of intraventricular pressure gradient abnormalities during early diastolic filling. Our findings support fundamental differences in the nature of diastolic dysfunction in these 2 conditions.