Right Atrial Adaptation to Precapillary Pulmonary Hypertension: Pressure-Volume, Cardiomyocyte, and Histological Analysis.

BACKGROUND: Precapillary pulmonary hypertension (precPH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness. OBJECTIVES: This study aimed to investigate RA function using pressure-volume (PV) loops, isolated cardiomyocyte, and histological analyses. METHODS: RA PV loops were constructed in control subjects (n = 9) and precPH patients (n = 27) using magnetic resonance and catheterization data. RA stiffness (pressure rise during atrial filling) and right atrioventricular coupling index (RA minimal volume / RV end-diastolic volume) were compared in a larger cohort of patients with moderate (n = 39) or severe (n = 41) RV diastolic stiffness. Cardiomyocytes were isolated from RA tissue collected from control subjects (n = 6) and precPH patients (n = 9) undergoing surgery. Autopsy material was collected from control subjects (n = 6) and precPH patients (n = 4) to study RA hypertrophy, capillarization, and fibrosis. RESULTS: RA PV loops showed 3 RA cardiac phases (reservoir, passive emptying, and contraction) with dilatation and elevated pressure in precPH. PrecPH patients with severe RV diastolic stiffness had increased RA stiffness and worse right atrioventricular coupling index. Cardiomyocyte cross-sectional area was increased 2- to 3-fold in precPH, but active tension generated by the sarcomeres was unaltered. There was no increase in passive tension of the cardiomyocytes, but end-stage precPH showed reduced number of capillaries per mm2 accompanied by interstitial and perivascular fibrosis. CONCLUSIONS: RA PV loops show increased RA stiffness and suggest atrioventricular uncoupling in patients with severe RV diastolic stiffness. Isolated RA cardiomyocytes of precPH patients are hypertrophied, without intrinsic sarcomeric changes. In end-stage precPH, reduced capillary density is accompanied by interstitial and perivascular fibrosis.

Characterizing the Bone Marrow Environment in Advanced-Stage Myelofibrosis during Ruxolitinib Treatment Using PET/CT and MRI: A Pilot Study.

Current diagnostic criteria for myelofibrosis are largely based on bone marrow (BM) biopsy results. However, these have several limitations, including sampling errors. Explorative studies have indicated that imaging might form an alternative for the evaluation of disease activity, but the heterogeneity in BM abnormalities complicates the choice for the optimal technique. In our prospective diagnostic pilot study, we aimed to visualize all BM abnormalities in myelofibrosis before and during ruxolitinib treatment using both PET/CT and MRI. A random sample of patients was scheduled for examinations at baseline and after 6 and 18 months of treatment, including clinical and laboratory examinations, BM biopsies, MRI (T1-weighted, Dixon, dynamic contrast-enhanced (DCE)) and PET/CT ([15O]water, [18F]NaF)). At baseline, all patients showed low BM fat content (indicated by T1-weighted MRI and Dixon), increased BM blood flow (as measured by [15O]water PET/CT), and increased osteoblastic activity (reflected by increased skeletal [18F]NaF uptake). One patient died after the baseline evaluation. In the others, BM fat content increased to various degrees during treatment. Normalization of BM blood flow (as reflected by [15O]water PET/CT and DCE-MRI) occurred in one patient, who also showed the fastest clinical response. Vertebral [18F]NaF uptake remained stable in all patients. In evaluable cases, histopathological parameters were not accurately reflected by imaging results. A case of sampling error was suspected. We conclude that imaging results can provide information on functional processes and disease distribution throughout the BM. Differences in early treatment responses were especially reflected by T1-weighted MRI. Limitations in the gold standard hampered the evaluation of diagnostic accuracy.

Early Response Prediction of Multiparametric Functional MRI and 18F-FDG-PET in Patients with Head and Neck Squamous Cell Carcinoma Treated with (Chemo)Radiation.

BACKGROUND: Patients with locally-advanced head and neck squamous cell carcinoma (HNSCC) have variable responses to (chemo)radiotherapy. A reliable prediction of outcomes allows for enhancing treatment efficacy and follow-up monitoring. METHODS: Fifty-seven histopathologically-proven HNSCC patients with curative (chemo)radiotherapy were prospectively included. All patients had an MRI (DW,-IVIM, DCE-MRI) and 18F-FDG-PET/CT before and 10 days after start-treatment (intratreatment). Primary tumor functional imaging parameters were extracted. Univariate and multivariate analysis were performed to construct prognostic models and risk stratification for 2 year locoregional recurrence-free survival (LRFFS), distant metastasis-free survival (DMFS) and overall survival (OS). Model performance was measured by the cross-validated area under the receiver operating characteristic curve (AUC). RESULTS: The best LRFFS model contained the pretreatment imaging parameters ADC_kurtosis, Kep and SUV_peak, and intratreatment imaging parameters change (Δ) Δ-ADC_skewness, Δ-f, Δ-SUV_peak and Δ-total lesion glycolysis (TLG) (AUC = 0.81). Clinical parameters did not enhance LRFFS prediction. The best DMFS model contained pretreatment ADC_kurtosis and SUV_peak (AUC = 0.88). The best OS model contained gender, HPV-status, N-stage, pretreatment ADC_skewness, D, f, metabolic-active tumor volume (MATV), SUV_mean and SUV_peak (AUC = 0.82). Risk stratification in high/medium/low risk was significantly prognostic for LRFFS (p = 0.002), DMFS (p < 0.001) and OS (p = 0.003). CONCLUSIONS: Intratreatment functional imaging parameters capture early tumoral changes that only provide prognostic information regarding LRFFS. The best LRFFS model consisted of pretreatment, intratreatment and Δ functional imaging parameters; the DMFS model consisted of only pretreatment functional imaging parameters, and the OS model consisted ofHPV-status, gender and only pretreatment functional imaging parameters. Accurate clinically applicable risk stratification calculators can enable personalized treatment (adaptation) management, early on during treatment, improve counseling and enhance patient-specific post-therapy monitoring.

The REPAIR Study: Effects of Macitentan on RV Structure and Function in Pulmonary Arterial Hypertension.

OBJECTIVES: The REPAIR (Right vEntricular remodeling in Pulmonary ArterIal hypeRtension) study evaluated the effect of macitentan on right ventricular (RV) and hemodynamic outcomes in patients with pulmonary arterial hypertension (PAH), using cardiac magnetic resonance (CMR) and right heart catheterization (RHC). BACKGROUND: RV failure is the primary cause of death in PAH. CMR is regarded as the most accurate noninvasive method for assessing RV function and remodeling and CMR measures of RV function and structure are strongly prognostic for survival in patients with PAH. Despite this, CMR is not routinely used in PAH clinical trials. METHODS: REPAIR was a 52-week, open-label, single-arm, multicenter, phase 4 study evaluating the effect of macitentan 10 mg, with or without phosphodiesterase type-5 inhibition, on RV remodeling and function and cardiopulmonary hemodynamics. Primary endpoints were change from baseline to week 26 in RV stroke volume, determined by CMR; and pulmonary vascular resistance, determined by RHC. Efficacy measures were assessed for all patients with baseline and week 26 data for both primary endpoints. RESULTS: At a prespecified interim analysis in 42 patients, both primary endpoints were met, enrollment was stopped, and the study was declared positive. At final analysis (n = 71), RV stroke volume increased by 12 mL (96% confidence level: 8.4-15.6 mL; P < 0.0001) and pulmonary vascular resistance decreased by 38% (99% confidence level: 31%-44%; P < 0.0001) at week 26. Significant positive changes were also observed in secondary and exploratory CMR (RV and left ventricular), hemodynamic, and functional endpoints at week 26. Improvements in CMR RV and left ventricular variables and functional parameters were maintained at week 52. Safety (n = 87) was consistent with previous clinical trials. CONCLUSIONS: In the context of this study, macitentan treatment in patients with PAH resulted in significant and clinically-relevant improvements in RV function and structure and cardiopulmonary hemodynamics. At 52 weeks, improvements in RV function and structure were sustained. (REPAIR: Right vEntricular remodeling in Pulmonary ArterIal hypeRtension [REPAIR]; NCT02310672).

Repeatability of IVIM biomarkers from diffusion-weighted MRI in head and neck: Bayesian probability versus neural network.

PURPOSE: The intravoxel incoherent motion (IVIM) model for DWI might provide useful biomarkers for disease management in head and neck cancer. This study compared the repeatability of three IVIM fitting methods to the conventional nonlinear least-squares regression: Bayesian probability estimation, a recently introduced neural network approach, IVIM-NET, and a version of the neural network modified to increase consistency, IVIM-NETmod . METHODS: Ten healthy volunteers underwent two imaging sessions of the neck, two weeks apart, with two DWI acquisitions per session. Model parameters (ADC, diffusion coefficient Dt , perfusion fraction fp , and pseudo-diffusion coefficient Dp ) from each fit method were determined in the tonsils and in the pterygoid muscles. Within-subject coefficients of variation (wCV) were calculated to assess repeatability. Training of the neural network was repeated 100 times with random initialization to investigate consistency, quantified by the coefficient of variance. RESULTS: The Bayesian and neural network approaches outperformed nonlinear regression in terms of wCV. Intersession wCV of Dt in the tonsils was 23.4% for nonlinear regression, 9.7% for Bayesian estimation, 9.4% for IVIM-NET, and 11.2% for IVIM-NETmod . However, results from repeated training of the neural network on the same data set showed differences in parameter estimates: The coefficient of variances over the 100 repetitions for IVIM-NET were 15% for both Dt and fp , and 94% for Dp ; for IVIM-NETmod , these values improved to 5%, 9%, and 62%, respectively. CONCLUSION: Repeatabilities from the Bayesian and neural network approaches are superior to that of nonlinear regression for estimating IVIM parameters in the head and neck.

Multiparametric functional MRI and 18F-FDG-PET for survival prediction in patients with head and neck squamous cell carcinoma treated with (chemo)radiation.

OBJECTIVES: To assess (I) correlations between diffusion-weighted (DWI), intravoxel incoherent motion (IVIM), dynamic contrast-enhanced (DCE) MRI, and 18F-FDG-PET/CT imaging parameters capturing tumor characteristics and (II) their predictive value of locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. METHODS: Between 2014 and 2018, patients with histopathologically proven HNSCC, planned for curative (chemo) radiotherapy, were prospectively included. Pretreatment clinical, anatomical, and functional imaging parameters (obtained by DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT) were extracted for primary tumors (PT) and lymph node metastases. Correlations and differences between parameters were assessed. The predictive value of LRFS and OS was assessed, performing univariable, multivariable Cox and CoxBoost regression analyses. RESULTS: In total, 70 patients were included. Significant correlations between 18F-FDG-PET parameters and DWI-/DCE volume parameters were found (r > 0.442, p < 0.002). The combination of HPV (HR = 0.903), intoxications (HR = 1.065), PT ADCGTV (HR = 1.252), Ktrans (HR = 1.223), and Ve (HR = 1.215) was predictive for LRFS (C-index = 0.546; p = 0.023). N-stage (HR = 1.058), HPV positivity (HR = 0.886), hypopharyngeal tumor location (HR = 1.111), ADCGTV (HR = 1.102), ADCmean (HR = 1.137), D* (HR = 0.862), Ktrans (HR = 1.106), Ve (HR = 1.195), SUVmax (HR = 1.094), and TLG (HR = 1.433) were predictive for OS (C-index = 0.664; p = 0.046). CONCLUSIONS: Functional imaging parameters, performing DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT, yielded complementary value in capturing tumor characteristics. More specific, intoxications, HPV-negative status, large tumor volume-related parameters, high permeability (Ktrans), and high extravascular extracellular space (Ve) parameters were predictive for adverse locoregional recurrence-free survival and adverse overall survival. Low cellularity (high ADC) and high metabolism (high SUV) were additionally predictive for decreased overall survival. These different predictive factors added to estimated locoregional and overall survival. KEY POINTS: • Parameters of DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT were able to capture complementary tumor characteristics. • Multivariable analysis revealed that intoxications, HPV negativity, large tumor volume and high vascular permeability (Ktrans), and extravascular extracellular space (Ve) were complementary predictive for locoregional recurrence. • In addition to predictive parameters for locoregional recurrence, also high cellularity (low ADC) and high metabolism (high SUV) were complementary predictive for overall survival.

Repeatability of arterial input functions and kinetic parameters in muscle obtained by dynamic contrast enhanced MR imaging of the head and neck.

BACKGROUND: Quantification of pharmacokinetic parameters in dynamic contrast enhanced (DCE) MRI is heavily dependent on the arterial input function (AIF). In the present patient study on advanced stage head and neck squamous cell carcinoma (HNSCC) we have acquired DCE-MR images before and during chemo radiotherapy. We determined the repeatability of image-derived AIFs and of the obtained kinetic parameters in muscle and compared the repeatability of muscle kinetic parameters obtained with image-derived AIF's versus a population-based AIF. MATERIALS AND METHODS: We compared image-derived AIFs obtained from the internal carotid, external carotid and vertebral arteries. Pharmacokinetic parameters (ve, Ktrans, kep) in muscle-located outside the radiation area-were obtained using the Tofts model with the image-derived AIFs and a population averaged AIF. Parameter values and repeatability were compared. Repeatability was calculated with the pre- and post-treatment data with the assumption of no DCE-MRI measurable biological changes between the scans. RESULTS: Several parameters describing magnitude and shape of the image-derived AIFs from the different arteries in the head and neck were significantly different. Use of image-derived AIFs led to higher pharmacokinetic parameters compared to use of a population averaged AIF. Median muscle pharmacokinetic parameters values obtained with AIFs in external carotids, internal carotids, vertebral arteries and with a population averaged AIF were respectively: ve (0.65, 0.74, 0.58, 0.32), Ktrans (0.30, 0.21, 0.13, 0.06), kep (0.41, 0.32, 0.24, 0.18). Repeatability of pharmacokinetic parameters was highest when a population averaged AIF was used; however, this repeatability was not significantly different from image-derived AIFs. CONCLUSION: Image-derived AIFs in the neck region showed significant variations in the AIFs obtained from different arteries, and did not improve repeatability of the resulting pharmacokinetic parameters compared with the use of a population averaged AIF. Therefore, use of a population averaged AIF seems to be preferable for pharmacokinetic analysis using DCE-MRI in the head and neck area.

Functional imaging early during (chemo)radiotherapy for response prediction in head and neck squamous cell carcinoma; a systematic review.

This systematic review gives an extensive overview of the current state of functional imaging during (chemo)radiotherapy to predict locoregional control (LRC) and overall survival (OS) for head and neck squamous cell carcinoma. MEDLINE and EMBASE were searched for literature until April 2018 assessing the predictive performance of functional imaging (computed tomography perfusion (CTp), MRI and positron-emission tomography (PET)) within 4 weeks after (chemo)radiotherapy initiation. Fifty-two studies (CTp: n = 4, MRI: n = 19, PET: n = 26, MRI/PET: n = 3) were included involving 1623 patients. Prognostic information was extracted according the PRISMA protocol. Pooled estimation and subgroup analyses were performed for comparable parameters and outcome. However, the heterogeneity of included studies limited the possibility for comparison. Early tumoral changes from (chemo)radiotherapy can be captured by functional MRI and 18F-FDG-PET and could allow for personalized treatment adaptation. Lesions showed potentially prognostic intratreatment changes in perfusion, diffusion and metabolic activity. Intratreatment ADCmean increase (decrease of diffusion restriction) and low SUVmax (persistent low or decrease of 18F-FDG uptake) were most predictive of LRC. Intratreatment persistent high or increase of perfusion on CT/MRI (i.e. blood flow, volume, permeability) also predicted LRC. Low SUVmax and total lesion glycolysis (TLG) predicted favorable OS. The optimal timing to perform functional imaging to predict LRC or OS was 2-3 weeks after treatment initiation.

Intravoxel incoherent motion magnetic resonance imaging in head and neck cancer: A systematic review of the diagnostic and prognostic value.

Intravoxel incoherent motion (IVIM) imaging is increasingly applied in the assessment of head and neck cancer (HNC). Our purpose was to determine the diagnostic and prognostic performance of IVIM in HNC by performing a critical review of the literature. Pubmed and EMBASE were searched until May 2016. Study and patients characteristics, imaging protocol and diagnostic or prognostic outcomes were extracted by 2 independent reviewers. The studied IVIM parameters were diffusion coefficient (D), pseudodiffusion coefficient (D∗), and perfusion fraction (f). We included 10 diagnostic studies, 5 prognostic studies and 2 studies assessing both. Studies were very heterogeneous in terms of applied b-values, imaging protocols, outcome measurements and reference standards; therefore we did not perform a meta-analysis. The most commonly used sequence was "spin-echo planar imaging". A median of 10.5 b-values (range, 3-17) were used. All but three studies included at least 4 b-values below b=200s/mm2. By combining IVIM-parameters squamous cell carcinomas, lymphomas, malignant salivary gland tumors, Warthin's tumors and pleomorphic adenomas could be differentiated with a sensitivity of 85-87% and specificity of 80-100%. Low pre-treatment D or f and an increase in D during treatment were associated with a favorable response to treatment. D∗ appeared to be the parameter with the lowest prognostic value. Future research should focus on finding the optimal IVIM protocol, using uniformly accepted study methods and larger patient populations.

Inter-reader reproducibility of dynamic contrast-enhanced magnetic resonance imaging in patients with non-small cell lung cancer treated with bevacizumab and erlotinib.

UNLABELLED: Objectives When evaluating anti-tumor treatment response by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) it is necessary to assure its validity and reproducibility. This has not been well addressed in lung tumors. Therefore we have evaluated the inter-reader reproducibility of response classification by DCE-MRI in patients with non-small cell lung cancer (NSCLC) treated with bevacizumab and erlotinib enrolled in a multicenter trial. MATERIALS AND METHODS: Twenty-one patients were scanned before and 3 weeks after start of treatment with DCE-MRI in a multicenter trial. The scans were evaluated by two independent readers. The primary lung tumor was used for response assessment. Responses were assessed in terms of relative changes in tumor mean trans endothelial transfer rate (K(trans)) and its heterogeneity in terms of the spatial standard deviation. Reproducibility was expressed by the inter-reader variability, intra-class correlation coefficient (ICC) and dichotomous response classification. RESULTS: The inter-reader variability and ICC for the relative K(trans) were 5.8% and 0.930, respectively. For tumor heterogeneity the inter-reader variability and ICC were 0.017 and 0.656, respectively. For the two readers the response classification for relative K(trans) was concordant in 20 of 21 patients (k=0.90, p<0.0001) and for tumor heterogeneity in 19 of 21 patients (k=0.80, p<0.0001). CONCLUSIONS: Strong agreement was seen with regard to the inter-reader variability and reproducibility of response classification by the two readers of lung cancer DCE-MRI scans.

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.

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.

Use of H2(15)O-PET and DCE-MRI to measure tumor blood flow.

Positron emission tomography (PET) with H2(15)O and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provide noninvasive measurements of tumor blood flow. Both tools offer the ability to monitor the direct target of antiangiogenic treatment, and their use is increasingly being studied in trials evaluating such drugs. Antiangiogenic therapy offers great potential and, to an increasing extent, benefit for oncological patients in a variety of palliative and curative settings. Because this type of targeted therapy frequently results in consolidation of the tumor mass instead of regression, monitoring treatment response with the standard volumetric approach (Response Evaluation Criteria in Solid Tumors) leads to underestimation of the response rate. Monitoring direct targets of anticancer therapy might be superior to indirect size changes. In addition, measures of tumor blood flow contribute to a better understanding of tumor biology. This review shows that DCE-MRI and H2(15)O-PET provide reliable measures of tumor perfusion, provided that a certain level of standardization is applied. Heterogeneity in scan acquisition and data analysis complicates the interpretation of study results. Also, limitations inherent to both techniques must be considered when interpreting DCE-MRI and H2(15)O-PET results. This review focuses on the technical and physiological aspects of both techniques and aims to provide the essential information necessary to critically evaluate the use of DCE-MRI and H2(15)O-PET in an oncological setting.

Brain natriuretic peptide as noninvasive marker of the severity of right ventricular dysfunction in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Right ventricular (RV) dysfunction is associated with increased morbidity and mortality in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo pulmonary endarterectomy (PEA). We studied whether plasma brain natriuretic peptide (BNP) levels can be used to identify RV dysfunction in CTEPH patients. Therefore, plasma BNP levels were studied in relation to cardiac remodeling and function as determined by cardiac magnetic resonance imaging (MRI). METHODS: Thirty-eight patients with CTEPH (55 +/- 15 years), and ten healthy controls (46 +/- 15 years) were studied. The BNP was determined by an immunoradiometric assay. RESULTS: The CTEPH patients had a mean pulmonary artery pressure of 49 +/- 13 mm Hg, cardiac index 2.1 +/- 0.7 l x min(-1) x m(-2), and pulmonary vascular resistance of 867 +/- 432 dynes x s x cm(-5). In CTEPH patients, compared with controls, right ventricular (RV) remodeling was demonstrated. In the patients, BNP was increased and correlated (all p < 0.0001; Spearman rank test) with MRI parameters of RV remodeling and function: end diastolic (r = 0.71) and end systolic (r = 0.74) volumes, RV mass (r = 0.68), leftward ventricular septal bowing (r = -0.80) and ejection fraction (EF; r = -0.81). By receiver operating curve analysis, BNP levels of 11.5 picomole (pmol)/L and 48.5 pmol/L, respectively, detected RV dysfunction as defined by RVEF less than 0.45 and less than 0.30, respectively, with high sensitivity and specificity. Hemodynamically, BNP levels greater than 48.5 pmol/L identified the most severely affected patients. CONCLUSIONS: In CTEPH patients, BNP levels correlate with RV remodeling and can be used to identify RV dysfunction. Future studies are warranted on the role of BNP to identify "high risk" CTEPH patients and its relation to postoperative hemodynamic outcome, RV failure, and mortality.

Cardiac function and position more than 5 years after pneumonectomy.

BACKGROUND: Pneumonectomy not only reduces the pulmonary vascular bed but also changes the position of the heart and large vessels, which may affect the function of the heart. We investigated long-term effects of pneumonectomy on right ventricular (RV) and left ventricular (LV) function and whether this function is influenced by the side of pneumonectomy or the migration of the heart to its new position. METHODS: In 15 patients who underwent pneumonectomy and survived for more than 5 years, we evaluated by dynamic magnetic resonance imaging the function of the RV and LV and the position of the heart within the thorax. RESULTS: Long-term effect of pneumonectomy on the position of the heart is characterized by a lateral shift after right-sided pneumonectomy and rotation of the heart after left-sided pneumonectomy. Postoperatively, heart rate was high (p = 0.006) and stroke volume was low (p = 0.001), compared with the reference values, indicating impaired cardiac function. Patients after right-sided pneumonectomy had an abnormal low RV end-diastolic volume of 99 +/- 29 mL together with a normal LV function. No signs of RV hypertrophy were found. In left-sided pneumonectomy patients, RV volumes were normal whereas LV ejection fraction was abnormally low. CONCLUSIONS: The long-term effects of pneumonectomy on the position of the heart are characterized by a lateral shift in patients after right-sided pneumonectomy and rotation of the heart in patients after left-sided pneumonectomy. Overall, cardiac function in long-term survivors after pneumonectomy is compromised, and might be explained by the altered position of the heart.

Reverse right ventricular remodeling after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension: utility of magnetic resonance imaging to demonstrate restoration of the right ventricle.

OBJECTIVES: Pulmonary arterial hypertension causes right ventricular remodeling; that is, right ventricular dilatation, hypertrophy, and leftward ventricular septal bowing. We studied the effect of pulmonary endarterectomy on the restoration of right ventricular remodeling in patients with chronic thromboembolic pulmonary hypertension by magnetic resonance imaging. METHODS: In 17 patients with chronic thromboembolic pulmonary hypertension, before and at least 4 months after pulmonary endarterectomy, and in 12 healthy controls, right ventricular and left ventricular end-diastolic and end-systolic volumes (milliliters) and mass (grams per meter squared) and leftward ventricular septal bowing (1 divided by the radius of curvature in centimeters) were determined by magnetic resonance imaging. RESULTS: Before pulmonary endarterectomy, right ventricular volumes, left ventricular end-diastolic volume, right ventricular mass, and leftward ventricular septal bowing differed significantly between patients with chronic thromboembolic pulmonary hypertension and healthy control subjects. After pulmonary endarterectomy, pulmonary hemodynamics improved, and right and left ventricular volumes and leftward ventricular septal bowing normalized; right ventricular mass decreased significantly (46 +/- 14 to 31 +/- 9 g x m(-2), P< .0005), but did not completely normalize. The change in total pulmonary resistance correlated with the change in right ventricular ejection fraction (r = 0.50, P < .05), right ventricular mass (r = 0.63, P < .01), and leftward ventricular septal bowing (r = 0.50, P < .05). CONCLUSIONS: Right ventricular remodeling was observed in patients with chronic thromboembolic pulmonary hypertension and restored almost completely after a hemodynamically successful pulmonary endarterectomy. Magnetic resonance imaging is a valuable tool to evaluate cardiac remodeling and function in patients with chronic thromboembolic pulmonary hypertension, both before and after pulmonary endarterectomy.

Early changes of cardiac structure and function in COPD patients with mild hypoxemia.

BACKGROUND: COPD is often associated with changes of the structure and the function of the heart. Although functional abnormalities of the right ventricle (RV) have been well described in COPD patients with severe hypoxemia, little is known about these changes in patients with normoxia and mild hypoxemia. STUDY OBJECTIVES: To assess the structural and functional cardiac changes in COPD patients with normal Pa(O2) and without signs of RV failure. METHODS: In 25 clinically stable COPD patients (FEV1, 1.23 +/- 0.51 L/s; Pa(O2), 82 +/- 10 mm Hg [mean +/- SD]) and 26 age-matched control subjects, the RV and left ventricular (LV) structure and function were measured by MRI. Pulmonary artery pressure (PAP) was estimated from right pulmonary artery distensibility. RESULTS: RV mass divided by RV end-diastolic volume as a measure of RV adaptation was 0.72 +/- 0.18 g/mL in the COPD group and 0.41 +/- 0.09 g/mL in the control group (p < 0.01). LV and RV ejection fractions were 62 +/- 14% and 53 +/- 12% in the COPD patients, and 68 +/- 11% and 53 +/- 7% in the control subjects, respectively. PAP estimated from right pulmonary artery distensibility was not elevated in the COPD group. CONCLUSION: From these results, we conclude that concentric RV hypertrophy is the earliest sign of RV pressure overload in patients with COPD. This structural adaptation of the heart does not alter RV and LV systolic function.

Impact of head movements on morphology and flow in the internal carotid artery after carotid angioplasty and stenting versus endarterectomy.

OBJECTIVE: Because stents can cause vessel angulation during movement, we hypothesized that internal carotid artery (ICA) stents might lead to alterations of cerebropetal blood flow. This study assessed three-dimensional anatomy and volumetric flow rate (VFR) in the ICA in various head positions by comparing patients treated with carotid angioplasty and stenting (CAS) with patients treated with carotid endarterectomy (CEA). METHODS: Three-dimensional time-of-flight magnetic resonance angiography and magnetic resonance flow quantification were performed on six subjects after CAS (median age, 70 years) and on six subjects after CEA (median age, 67 years). All investigations were performed in five head positions: neutral, bent forward, bent backward, and turned to the treated, ipsilateral side and to the contralateral side. Maximum-intensity projection reconstructions were obtained to measure maximal angulation of the ICA in the forward, backward, ipsilateral, and contralateral positions compared with neutral. Subsequently, the plane perpendicular to the ICA, 1 cm distal to the stent or 4 cm distal to the carotid bifurcation (CEA patients), was established. The VFR through this plane was measured for each position, and the forward, backward, ipsilateral, and contralateral positions were compared with neutral. RESULTS: In CAS patients, there was a median change in ICA angulation of +10.2 degrees (interquartile range, +7.3 degrees to +17.9 degrees ) in the forward position, compared with +0.2 degrees (-1.0 degrees to +2.4 degrees ) in CEA patients ( P = .016). In all other head positions, there was no statistically significant difference in angulation change. There was no statistically significant difference in VFR change between groups in any of the head positions tested. CONCLUSIONS: There was a significant increase in ICA angulation in CAS patients if the head was bent forward; this was not observed in CEA patients. This angulation change did not lead to significant acute changes in cerebropetal blood flow, but it might have chronic effects not yet tested.

Interventricular septal configuration at mr imaging and pulmonary arterial pressure in pulmonary hypertension.

PURPOSE: To investigate whether a relationship exists between septum shape and systolic pulmonary arterial pressure (PAP) in patients with pulmonary hypertension. MATERIALS AND METHODS: Study protocol was approved by institutional ethics review committee; all patients gave informed consent. Right-sided heart catheterization with vasodilator testing was performed in 39 adult subjects suspected of having pulmonary hypertension. There were 11 men and 28 women, aged 21-75 years (mean, 46 years). Only two patients showed favorable response to vasodilators, defined by a decrease in PAP of more than 20%. Synchronous right- and left-ventricular pressure measurements and four-chamber magnetic resonance (MR) imaging were used to identify timing of maximal leftward ventricular septal bowing within cardiac cycle. Septal bowing was evaluated with MR, measured on short-axis cine heart images, and expressed as curvature (reciprocal of radius). Curvature was quantified on one image (the one that showed the most severe distortion of normal septal shape). The relationship between systolic PAP and septal curvature was tested with linear regression analysis. P <.05 was considered to indicate a statistically significant difference. RESULTS: Of 39 subjects, 37 had pulmonary hypertension. Maximal distortion of normal septal shape was found during right ventricular relaxation phase. Systolic PAP was proportional to septal curvature: r=0.77 (P < .001), slope=-114.7, and intercept=67.2. In the two vasodilator responsive subjects, a significant reduction of leftward ventricular septal bowing was observed in response to reduction of right ventricular pressure. CONCLUSION: In 37 patients with pulmonary hypertension, systolic PAP higher than 67 mm Hg may be expected when leftward curvature is observed.

Pulmonary vascular responses to hypoxia and hyperoxia in healthy volunteers and COPD patients measured by electrical impedance tomography.

BACKGROUND: Electrical impedance tomography (EIT) is a noninvasive imaging technique using impedance to visualize and measure blood volume changes. STUDY OBJECTIVE: To examine the validity of EIT in the measurement of hypoxic pulmonary vasoconstriction (HPV) and hyperoxic pulmonary vasodilation in healthy volunteers and COPD patients. PARTICIPANTS: Group 1 consisted of seven healthy volunteers (mean age, 46 years; age range, 36 to 53 years). Group 2 comprised six clinically stable COPD patients (mean age, 65 years; age range, 50 to 74 years). INTERVENTIONS: EIT measurements were performed in healthy subjects while they were breathing room air, 14% oxygen (ie, hypoxia), and 100% oxygen (ie, hyperoxia) through a mouthpiece. Maximal impedance change during systole (DeltaZsys) was used as a measure of pulmonary perfusion-related impedance changes. Stroke volume (SV) was measured by means of MRI. In the COPD group, EIT and SV also were determined, but only in room air and under hyperoxic conditions. RESULTS: The data were statistically compared to data for the room air baseline condition. In the volunteers, the mean (+/- SD) DeltaZsys for the group was 352 +/- 53 arbitrary units (AU) while breathing room air, 309 +/- 75 AU in hypoxia (p < 0.05), and 341 +/- 69 AU in hyperoxia (not significant [NS]). The mean MRI-measured SV was 83 +/- 21 mL while breathing room air, 90 +/- 29) mL in hypoxia (NS), and 94 +/- 19 mL in hyperoxia (p < 0.05). In the COPD patients, the mean DeltaZsys for this group was 222 +/- 84 AU while breathing room air and 255 +/- 83 AU in hyperoxia (p < 0.05). In this group, the SV was 59 +/- 16 mL while breathing room air and 61 +/- 13 mL in hyperoxia (NS). Thus, the volunteer EIT response to hypoxia is not caused by decreased SV, because SV did not show a significant decrease. Similarly, in COPD patients the EIT response to hyperoxia is not caused by increased SV, because SV showed only a minor change. CONCLUSION: EIT can detect blood volume changes due to HPV noninvasively in healthy subjects and hyperoxic vasodilation in COPD patients.