Taco Kind

Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy.

OBJECTIVES The purpose of this study was to examine the relationship between changes in pulmonary vascular resistance (PVR) and right ventricular ejection fraction (RVEF) and survival in patients with pulmonary arterial hypertension (PAH) under PAH-targeted therapies. BACKGROUND Despite the fact that medical therapies reduce PVR, the prognosis of patients with PAH is still poor. The primary cause of death is right ventricular (RV) failure. One possible explanation for this apparent paradox is the fact that a reduction in PVR is not automatically followed by an improvement in RV function. METHODS A cohort of 110 patients with incident PAH underwent baseline right heart catheterization, cardiac magnetic resonance imaging, and 6-min walk testing. These measurements were repeated in 76 patients after 12 months of therapy. RESULTS Two patients underwent lung transplantation, 13 patients died during the first year, and 17 patients died in the subsequent follow-up of 47 months. Baseline RVEF (hazard ratio [HR]: 0.938; p = 0.001) and PVR (HR: 1.001; p = 0.031) were predictors of mortality. During the first 12 months, changes in PVR were moderately correlated with changes in RVEF (R = 0.330; p = 0.005). Changes in RVEF (HR: 0.929; p = 0.014) were associated with survival, but changes in PVR (HR: 1.000; p = 0.820) were not. In 68% of patients, PVR decreased after medical therapy. Twenty-five percent of those patients with decreased PVR showed a deterioration of RV function and had a poor prognosis. CONCLUSIONS After PAH-targeted therapy, RV function can deteriorate despite a reduction in PVR. Loss of RV function is associated with a poor outcome, irrespective of any changes in PVR.

Right ventricular ejection fraction is better reflected by transverse rather than longitudinal wall motion in pulmonary hypertension

BackgroundLongitudinal wall motion of the right ventricle (RV), generally quantified as tricuspid annular systolic excursion (TAPSE), has been well studied in pulmonary hypertension (PH). In contrast, transverse wall motion has been examined less. Therefore, the aim of this study was to evaluate regional RV transverse wall motion in PH, and its relation to global RV pump function, quantified as RV ejection fraction (RVEF).MethodsIn 101 PH patients and 29 control subjects cardiovascular magnetic resonance was performed. From four-chamber cine imaging, RV transverse motion was quantified as the change of the septum-free-wall (SF) distance between end-diastole and end-systole at seven levels along an apex-to-base axis. For each level, regional absolute and fractional transverse distance change (SFD and fractional-SFD) were computed and related to RVEF. Longitudinal measures, including TAPSE and fractional tricuspid-annulus-apex distance change (fractional-TAAD) were evaluated for comparison.ResultsTransverse wall motion was significantly reduced at all levels compared to control subjects (p < 0.001). For all levels, fractional-SFD and SFD were related to RVEF, with the strongest relation at mid RV (R2 = 0.70, p < 0.001 and R2 = 0.62, p < 0.001). For TAPSE and fractional-TAAD, weaker relations with RVEF were found (R2 = 0.21, p < 0.001 and R2 = 0.27, p < 0.001).ConclusionsRegional transverse wall movements provide important information of RV function in PH. Compared to longitudinal motion, transverse motion at mid RV reveals a significantly stronger relationship with RVEF and thereby might be a better predictor for RV function.

Progressive Changes in Right Ventricular Geometric Shortening and Long-term Survival in Pulmonary Arterial Hypertension

BACKGROUND Until now, many investigators have focused on describing right ventricular (RV) dysfunction in groups of patients with pulmonary arterial hypertension (PAH), but very few have addressed the deterioration of RV function over time. The aim of this study was to investigate time courses of RV geometric changes during the progression of RV failure. METHODS Forty-two patients with PAH were selected who underwent right-sided heart catheterization and cardiac MRI at baseline and after 1-year follow-up. Based on the survival after this 1-year run-in period, patients were classified into two groups: survivors (26 patients; subsequent survival of > 4 years) and nonsurvivors (16 patients; subsequent survival of < 4 years). Four-chamber cine imaging was used to quantify RV longitudinal shortening (apex-base distance change), RV transverse shortening (septum-free wall distance change), and RV fractional area change (RVFAC) between end diastole and end systole. RESULTS Longitudinal shortening, transverse shortening, and RVFAC measured at the beginning of the run-in period and 1 year later were significantly higher in subsequent survivors than in nonsurvivors (P < .05). Longitudinal shortening did not change during the run-in period in either patient group. Transverse shortening and RVFAC did not change during the run-in period in subsequent survivors but did decrease in subsequent nonsurvivors (P < .05). This decrease was caused by increased leftward septal bowing. CONCLUSIONS Progressive RV failure in PAH is associated with a parallel decline in longitudinal and transverse shortening until a floor effect is reached for longitudinal shortening. A further reduction of RV function is due to progressive leftward septal displacement. Because transverse shortening incorporates both free wall and septum movements, this parameter can be used to monitor the decline in RV function in end-stage PAH.

Accurate assessment of load-independent right ventricular systolic function in patients with pulmonary hypertension.

BACKGROUND End-systolic elastance (E(es)), a load-independent measure of ventricular function, is of clinical interest for studies of the right ventricle (RV) in patients with pulmonary arterial hypertension (PAH). The objective of this study was to determine whether, in PAH patients, E(es) can be estimated from mean pulmonary artery pressure (mPAP) and end-systolic volume (ESV) only. METHODS Right heart catheterization was used to measure mPAP. Maximal isovolumic pressure (P(iso)) was estimated from RV pressure curves with the so-called single-beat method. Cardiac magnetic resonance imaging (MRI) was used to assess RV end-diastolic and end-systolic volumes (EDV and ESV). E(es) was then calculated as: E(es) = (P(iso)-mPAP) / (EDV-ESV), and as E(es,V0 = 0) = mPAP/ESV (simplified method, with V0 = 0, is negligible volume at zero pressure). Right ventricular volume at zero pressure (V(0)) was then defined as the intercept of the end-systolic pressure-volume relation (single-beat method) with the horizontal axis. RESULTS E(es,V0 = 0) was significantly lower compared with E(es) (0.61 vs 1.34 mm Hg/ml, respectively, p<0.01). A modified Bland-Altman analysis showed a contractility-dependent difference between E(es,V0 = 0) and E(es). Moreover, V(0) ranged from-8 up to 171 ml, and a moderate and good correlation was found between V(0) and EDV, and V(0) and ESV, respectively (r = 0.65 and r = 0.87, p< 0.01). CONCLUSIONS These findings show that V(0) is dependent on RV dilation. Therefore, the assumption that V(0) is negligible in PAH is incorrect. Consequently, for an accurate assessment of load-independent RV systolic function, RV volumes and pressure curves are required.

Modeling the Instantaneous Pressure–Volume Relation of the Left Ventricle: A Comparison of Six Models

Simulations are useful to study the heart’s ability to generate flow and the interaction between contractility and loading conditions. The left ventricular pressure–volume (PV) relation has been shown to be nonlinear, but it is unknown whether a linear model is accurate enough for simulations. Six models were fitted to the PV-data measured in five sheep and the estimated parameters were used to simulate PV-loops. Simulated and measured PV-loops were compared with the Akaike information criterion (AIC) and the Hamming distance, a measure for geometric shape similarity. The compared models were: a time-varying elastance model with fixed volume intercept (LinFix); a time-varying elastance model with varying volume intercept (LinFree); a Langewouter’s pressure-dependent elasticity model (Langew); a sigmoidal model (Sigm); a time-varying elastance model with a systolic flow-dependent resistance (Shroff) and a model with a linear systolic and an exponential diastolic relation (Burkh). Overall, the best model is LinFree (lowest AIC), closely followed by Langew. The remaining models rank: Sigm, Shroff, LinFix and Burkh. If only the shape of the PV-loops is important, all models perform nearly identically (Hamming distance between 20 and 23%). For realistic simulation of the instantaneous PV-relation a linear model suffices.

Cardiac phase-dependent time normalization reduces load dependence of time-varying elastance

The time-varying elastance concept provides a comprehensive description of the intrinsic mechanical properties of the left ventricle that are assumed to be load independent. Based on pressure-volume measurements obtained with combined pressure conductance catheterization in six open-chest anesthetized sheep, we show that the time to reach end systole (defined as maximal elastance) is progressively prolonged for increasing ventricle pressures, which challenges the original (load-independent) time-varying elastance concept. Therefore, we developed a method that takes into account load dependency by normalization of time course of the four cardiac phases (isovolumic contraction, ejection, isovolumic relaxation, filling) individually. With this normalization, isophase lines are obtained that connect points in pressure-volume loops of different beats at the same relative time in each of the four cardiac phases, instead of isochrones that share points at the same time in a cardiac cycle. The results demonstrate that pressure curves can be predicted with higher accuracy, if elastance curves are estimated using isophase lines instead of using isochrones [root-mean-square error (RMSE): 3.8 +/- 1.0 vs. 14.0 +/- 7.4 mmHg (P < 0.001), and variance accounted for (VAF): 94.8 +/- 1.3 vs. 78.6 +/- 14.8% (P < 0.001)]. Similar results were found when the intercept volume was assumed to be time varying [RMSE: 1.7 +/- 0.3 vs. 13.4 +/- 7.4 mmHg (P < 0.001), and VAF: 97.4 +/- 0.5 vs. 81.8 +/- 15.5% (P < 0.001)]. In conclusion, phase-dependent time normalization reduces cardiac load dependency of timing and increases accuracy in estimating time-varying elastance.

Evaluation of model-independent deconvolution techniques to estimate blood perfusion

This report evaluates several methods to estimate blood perfusion and residue functions in dynamic contrast enhanced (DCE) MRI. Among these are model-dependent and model-independent techniques. All methods were applied to series of Monte Carlo simulations to evaluate the accuracy in order to reproduce different underlying vascular residue functions and blood perfusions. Of the model-independent approaches the use of B-splines with Tikhonov regularization was shown to have a reasonable accuracy in blood perfusion estimations and was less biased than all model-dependent approaches. This technique seems most promising for application to experimental data.