Pulmonary endarterectomy normalizes interventricular dyssynchrony and right ventricular systolic wall stress.

BACKGROUND: Interventricular mechanical dyssynchrony is a characteristic of pulmonary hypertension. We studied the role of right ventricular (RV) wall stress in the recovery of interventricular dyssynchrony, after pulmonary endarterectomy (PEA) in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: In 13 consecutive patients with CTEPH, before and 6 months after pulmonary endarterectomy, cardiovascular magnetic resonance myocardial tagging was applied. For the left ventricular (LV) and RV free walls, the time to peak (Tpeak) of circumferential shortening (strain) was calculated. Pulmonary Artery Pressure (PAP) was measured by right heart catheterization within 48 hours of PEA. Then the RV free wall systolic wall stress was calculated by the Laplace law. RESULTS: After PEA, the left to right free wall delay (L-R delay) in Tpeak strain decreased from 97 ± 49 ms to -4 ± 51 ms (P < 0.001), which was not different from normal reference values of -35 ± 10 ms (P = 0.18). The RV wall stress decreased significantly from 15.2 ± 6.4 kPa to 5.7 ± 3.4 kPa (P < 0.001), which was not different from normal reference values of 5.3 ± 1.39 kPa (P = 0.78). The reduction of L-R delay in Tpeak was more strongly associated with the reduction in RV wall stress (r = 0.69,P = 0.007) than with the reduction in systolic PAP (r = 0.53, P = 0.07). The reduction of L-R delay in Tpeak was not associated with estimates of the reduction in RV radius (r = 0.37,P = 0.21) or increase in RV systolic wall thickness (r = 0.19,P = 0.53). CONCLUSION: After PEA for CTEPH, the RV and LV peak strains are resynchronized. The reduction in systolic RV wall stress plays a key role in this resynchronization.

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

BACKGROUND: Longitudinal 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). METHODS: In 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. RESULTS: Transverse 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 (R(2) = 0.70, p < 0.001 and R(2) = 0.62, p < 0.001). For TAPSE and fractional-TAAD, weaker relations with RVEF were found (R(2) = 0.21, p < 0.001 and R(2) = 0.27, p < 0.001). CONCLUSIONS: Regional 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.

Detecting temporal lobe seizures from scalp EEG recordings: a comparison of various features.

OBJECTIVE: Sixteen different features are evaluated in their potential ability to detect seizures from scalp EEG recordings containing temporal lobe (TL) seizures. Features include spectral measures, non-linear methods (e.g. zero-crossings), phase synchronization and the recently introduced Brain Symmetry Index (BSI). Besides an individual comparison, several combinations of features are evaluated as well in their potential ability to detect TL seizures. METHODS: Sixteen long-term scalp EEG recordings, containing TL seizures from patients suffering from temporal lobe epilepsy (TLE), were analyzed. For each EEG, all 16 features were determined for successive 10s epochs of the recording. All epochs were labeled by experts for the presence or absence of seizure activity. In addition, triplet combinations of various features were evaluated using pattern recognition tools. Final performance was evaluated by the sensitivity and specificity (False Alarm Rate (FAR)), using ROC curves. RESULTS: In those TL seizures characterized by unilateral epileptiform discharges, the BSI was the best single feature. Except for one low-voltage EEG with many artifacts, the sensitivity found ranged from 0.55 to 0.90 at a FAR of approximately 1/h. Using three features increased the sensitivity to 0.77-0.97. In patients with bilateral electroencephalographic changes, the single best feature most often found was a measure for the number of minima and maxima (mmax) in the recording, yielding sensitivities of approximately 0.30-0.96 at FAR approximately 1/h. Using three features increased the sensitivity to 0.38-0.99, at the same FAR. In various recordings, it was even possible to obtain sensitivities of 0.70-0.95 at a FAR = 0. CONCLUSIONS: The Brain Symmetry Index is the most relevant individual feature to detect electroencephalographic seizure activity in TLE with unilateral epileptiform discharges. In patients with bilateral discharges, mmax performs best. Using a triplet of features significantly improves the performance of the detector. SIGNIFICANCE: Improved seizure detection can improve patient care in both the epilepsy monitoring unit and the intensive care unit.

The importance of trabecular hypertrophy in right ventricular adaptation to chronic pressure overload.

To assess the contribution of right ventricular (RV) trabeculae and papillary muscles (TPM) to RV mass and volumes in controls and patients with pulmonary arterial hypertension (PAH). Furthermore, to evaluate whether TPM shows a similar response as the RV free wall (RVFW) to changes in pulmonary artery pressure (PAP) during follow-up. 50 patients underwent cardiac magnetic resonance (CMR) and right heart catheterization at baseline and after one-year follow-up. Furthermore 20 controls underwent CMR. RV masses were assessed with and without TPM. TPM constituted a larger proportion of total RV mass and RV end-diastolic volume (RVEDV) in PAH than in controls (Mass: 35 ± 7 vs. 25 ± 5 %; p < 0.001; RVEDV: 17 ± 6 vs. 12 ± 6 %; p = 0.003). TPM mass was related to the RVFW mass in patients (baseline: R = 0.65; p < 0.001; follow-up: R = 0.80; p < 0.001) and controls (R = 0.76; p < 0.001). In PAH and controls, exclusion of TPM from the assessment resulted in altered RV mass, volumes and function than when included (all p < 0.01). Changes in RV TPM mass (ß = 0.44; p = 0.004) but not the changes in RVFW mass (p = 0.095) were independently related to changes in PAP during follow-up. RV TPM showed a larger contribution to total RV mass in PAH (~35 %) compared to controls (~25 %). Inclusion of TPM in the analyses significantly influenced the magnitude of the RV volumes and mass. Furthermore, TPM mass was stronger related to changes in PAP than RVFW mass. Our results implicate that TPM are important contributors to RV adaptation during pressure overload and cannot be neglected from the RV assessment.

Effect of pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension on stroke volume response to exercise.

In pulmonary hypertension, exercise is limited by an impaired right ventricular (RV) stroke volume response. We hypothesized that improvement in exercise capacity after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) is paralleled by an improved RV stroke volume response. We studied the extent of PEA-induced restoration of RV stroke volume index (SVI) response to exercise using cardiac magnetic resonance imaging (cMRI). Patients with CTEPH (n = 18) and 7 healthy volunteers were included. Cardiopulmonary exercise testing and cMRI were performed before and 1 year after PEA. For cMRI studies, pre- and post-operatively, all patients exercised at 40% of their preoperative cardiopulmonary exercise testing-assessed maximal workload. Post-PEA patients (n = 13) also exercised at 40% of their postoperative maximal workload. Control subjects exercised at 40% of their predicted maximal workload. Preoperatively, SVI (n = 18) decreased during exercise from 35.9 ± 7.4 to 33.0 ± 9.0 ml·m(2) (p = 0.023); in the control subjects, SVI increased (46.6 ± 7.6 vs 57.9 ± 11.8 ml·m(-2), p = 0.001). After PEA, the SVI response (ΔSVI) improved from -2.8 ± 4.6 to 4.0 ± 4.6 ml·m(2) (p <0.001; n = 17). On exercise at 40% of the postoperative maximal workload, SVI did not increase further and was still significantly lower compared with controls. Moreover, 4 patients retained a negative SVI response, despite (near) normalization of their pulmonary hemodynamics. The improvement in SVI response was accompanied by an increased exercise tolerance and restoration of RV remodeling. In conclusion, in CTEPH, exercise is limited by an impaired stroke volume response. PEA induces a restoration of SVI response to exercise that appears, however, incomplete and not evident in all patients.

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.

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.

Proportional Relations Between Systolic, Diastolic and Mean Pulmonary Artery Pressure are Explained by Vascular Properties.

Recently, it was shown that proportional relationships exist between systolic, diastolic and mean pulmonary artery pressure (P(sys), P(dia) and P(mean)) and that they are maintained under various conditions in both health and disease. An arterial-ventricular interaction model was used to study the contribution of model parameters to the ratios P(sys)/P(mean), and P(dia)/P(mean). The heart was modeled by a time-varying elastance function, and the arterial system by a three-element windkessel model consisting of peripheral resistance, R(p), arterial compliance C(a), and pulmonary artery characteristic impedance Z(0). Baseline model parameters were estimated in control subjects and compared to values estimated in patients with pulmonary hypertension. Results indicate that experimentally derived ratios P(sys)/P(mean) and P(dia)/P(mean) could be accurately reproduced using our model (1.59 and 0.61 vs. 1.55 and 0.64, respectively). Sensitivity analysis showed that the (empirical) constancy of P(sys)/P(mean) and P(dia)/P(mean) was primarily based on the inverse hyperbolic relation between total vascular resistance (R(T); calculated as R(p) + Z(0)) and C(a), (i.e. constant R(T)C(a) product). Of the cardiac parameters, only heart rate affected the pressure ratios, but the contribution was small. Therefore, we conclude that proportional relations between systolic, diastolic and mean pulmonary artery pressure result from the constancy of R(T)C(a) thus from pulmonary arterial properties, with only little influence of heart rate.

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.

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.

Estimation of three- and four-element windkessel parameters using subspace model identification.

A windkessel model is widely used to operationalize vascular characteristics. In this paper, we employ a noniterative subspace model identification (SMI) algorithm to estimate parameters in a three- and four-element windkessel model by application of physical foreknowledge. Simulation data of the systemic circulation were used to investigate systematic and random errors in the parameter estimations. Results were compared with different methods as proposed in the literature: one closed-loop and two iterative methods for the three-element model, and one iterative method for the four-element model. For the three-element model, no significant systematic errors were observed using SMI. Concerning random errors, SMI appeared more robust in parameter estimations compared with the other methods (P < 0.05 for a signal-to-noise ratio of 18 dB). For the four-element model, a significant systematic error in the estimate of the arterial inertance L was observed (P = 0.011). However, for all methods, an increasing number of outliers in parameter estimates were observed at increased noise levels. These outliers were almost exclusive due to errors in estimates of L. In conclusion, with SMI physical parameters can mathematically be derived by application of physiological foreknowledge. For a three-element windkessel model, SMI appeared a very robust method to estimate parameters. However, application to a four-element windkessel model was less accurate because of low identifiability of L. Therefore, based on the simulation results, the use of the four-element windkessel model is questionable.

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.

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.