Dave Capener

Noninvasive estimation of PA pressure, flow, and resistance with CMR imaging: derivation and prospective validation study from the ASPIRE registry.

OBJECTIVES The aim of this study was to develop a composite numerical model based on parameters from cardiac magnetic resonance (CMR) imaging for noninvasive estimation of the key hemodynamic measurements made at right heart catheterization (RHC). BACKGROUND Diagnosis and assessment of disease severity in patients with pulmonary hypertension is reliant on hemodynamic measurements at RHC. A robust noninvasive approach that can estimate key RHC measurements is desirable. METHODS A derivation cohort of 64 successive, unselected, treatment naive patients with suspected pulmonary hypertension from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) Registry, underwent RHC and CMR within 12 h. Predicted mean pulmonary arterial pressure (mPAP) was derived using multivariate regression analysis of CMR measurements. The model was tested in an independent prospective validation cohort of 64 patients with suspected pulmonary hypertension. Surrogate measures of pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were estimated by left atrial volumetry and pulmonary arterial phase contrast imaging, respectively. Noninvasive pulmonary vascular resistance (PVR) was calculated from the CMR-derived measurements, defined as: (CMR-predicted mPAP - CMR-predicted PCWP)/CMR phase contrast CO. RESULTS The following composite statistical model of mPAP was derived: CMR-predicted mPAP = -4.6 + (interventricular septal angle × 0.23) + (ventricular mass index × 16.3). In the validation cohort a strong correlation between mPAP and MR estimated mPAP was demonstrated (R(2) = 0.67). For detection of the presence of pulmonary hypertension the area under the receiver-operating characteristic (ROC) curve was 0.96 (0.92 to 1.00; p < 0.0001). CMR-estimated PVR reliably identified invasive PVR ≥3 Wood units (WU) with a high degree of accuracy, the area under the ROC curve was 0.94 (0.88 to 0.99; p < 0.0001). CONCLUSIONS CMR imaging can accurately estimate mean pulmonary artery pressure in patients with suspected pulmonary hypertension and calculate PVR by estimating all major pulmonary hemodynamic metrics measured at RHC.

Diagnostic accuracy of cardiovascular magnetic resonance imaging of right ventricular morphology and function in the assessment of suspected pulmonary hypertension results from the ASPIRE registry

BackgroundCardiovascular Magnetic Resonance (CMR) imaging is accurate and reproducible for the assessment of right ventricular (RV) morphology and function. However, the diagnostic accuracy of CMR derived RV measurements for the detection of pulmonary hypertension (PH) in the assessment of patients with suspected PH in the clinic setting is not well described.MethodsWe retrospectively studied 233 consecutive treatment naïve patients with suspected PH including 39 patients with no PH who underwent CMR and right heart catheterisation (RHC) within 48hours. The diagnostic accuracy of multiple CMR measurements for the detection of mPAP ≥ 25 mmHg was assessed using Fisher’s exact test and receiver operating characteristic (ROC) analysis.ResultsVentricular mass index (VMI) was the CMR measurement with the strongest correlation with mPAP (r = 0.78) and the highest diagnostic accuracy for the detection of PH (area under the ROC curve of 0.91) compared to an ROC of 0.88 for echocardiography calculated mPAP. Late gadolinium enhancement, VMI ≥ 0.4, retrograde flow ≥ 0.3 L/min/m2 and PA relative area change ≤ 15% predicted the presence of PH with a high degree of diagnostic certainty with a positive predictive value of 98%, 97%, 95% and 94% respectively. No single CMR parameter could confidently exclude the presence of PH.ConclusionCMR is a useful alternative to echocardiography in the evaluation of suspected PH. This study supports a role for the routine measurement of ventricular mass index, late gadolinium enhancement and the use of phase contrast imaging in addition to right heart functional indices in patients undergoing diagnostic CMR evaluation for suspected pulmonary hypertension.

Pulmonary artery relative area change detects mild elevations in pulmonary vascular resistance and predicts adverse outcome in pulmonary hypertension.

ObjectiveThe aim of this study was to evaluate the clinical use of magnetic resonance imaging measurements related to pulmonary artery stiffness in the evaluation of pulmonary hypertension (PH). Materials and MethodsA total of 134 patients with suspected PH underwent right heart catheterization (RHC) and magnetic resonance imaging on a 1.5-T scanner within 2 days. Phase contrast imaging at the pulmonary artery trunk and cine cardiac views were acquired. Pulmonary artery area change (AC), relative AC (RAC), compliance (AC/pulse pressure from RHC), distensibility (RAC/pulse pressure from RHC), right ventricular functional indices, and right ventricular mass were all derived. Regression curve fitting identified the statistical model of best fit between RHC measurements and pulmonary artery stiffness indices. The diagnostic accuracy and prognostic value of noninvasive AC and RAC were also assessed. ResultsThe relationship between pulmonary vascular resistance and pulmonary artery RAC was best reflected by an inverse linear model. Patients with mild elevation in pulmonary vascular resistance (<4 Woods units) demonstrated reduced RAC (P = 0.02) and increased right ventricular mass index (P < 0.0001) without significant loss of right ventricular function (P = 0.17). At follow-up of 0 to 40 months, 18 patients with PH had died (16%). Analysis of Kaplan-Meier plots showed that both AC and RAC predicted mortality (log-rank test, P = 0.046 and P = 0.012, respectively). Area change and RAC were also predictors of mortality using univariate Cox proportional hazards regression analysis (P = 0.046 and P = 0.03, respectively). ConclusionsNoninvasive assessment of pulmonary artery RAC is a marker sensitive to early increased vascular resistance in PH and is a predictor of adverse outcome.

Prognostic value of cardiovascular magnetic resonance imaging measurements corrected for age and sex in idiopathic pulmonary arterial hypertension.

Background—There are limited data on the prognostic value of cardiovascular magnetic resonance measurements in idiopathic pulmonary arterial hypertension, with no studies investigating the impact of correction of cardiovascular magnetic resonance indices for age and sex on prognostic value. Methods and Results—Consecutive patients with idiopathic pulmonary arterial hypertension underwent cardiovascular magnetic resonance imaging at 1.5T. Steady-state free precession cardiac volumes and mass measurements were corrected for age, sex, and body surface area according to reference data and prognostic significance assessed. A total of 80 patients with idiopathic pulmonary arterial hypertension were identified, and 23 patients died during the mean follow-up of 32±14 months. Corrected for age, sex, and body surface area, right ventricular end-systolic volume (P=0.004) strongly predicted mortality, independent of World Health Organization functional class, mean right atrial pressure, cardiac index, and mixed venous oxygen saturations. Conclusions—Consideration should be given to correcting cardiovascular magnetic resonance measures for age, sex, and body surface area, particularly given the changing demographics of patients with idiopathic pulmonary arterial hypertension. Corrected right ventricular end-systolic volume is a strong prognostic marker in idiopathic pulmonary arterial hypertension, independent of invasively derived measurements, mean right atrial pressure cardiac index, and mixed venous oxygen saturations.

Quantitative magnetic resonance imaging of pulmonary hypertension: a practical approach to the current state of the art.

Pulmonary hypertension is a condition of varied etiology, commonly associated with poor clinical outcome. Patients are categorized on the basis of pathophysiological, clinical, radiologic, and therapeutic similarities. Pulmonary arterial hypertension (PAH) is often diagnosed late in its disease course, with outcome dependent on etiology, disease severity, and response to treatment. Recent advances in quantitative magnetic resonance imaging (MRI) allow for better initial characterization and measurement of the morphologic and flow-related changes that accompany the response of the heart-lung axis to prolonged elevation of pulmonary arterial pressure and resistance and provide a reproducible, comprehensive, and noninvasive means of assessing the course of the disease and response to treatment. Typical features of PAH occur primarily as a result of increased pulmonary vascular resistance and the resultant increased right ventricular (RV) afterload. Several MRI-derived diagnostic markers have emerged, such as ventricular mass index, interventricular septal configuration, and average pulmonary artery velocity, with diagnostic accuracy similar to that of Doppler echocardiography. Furthermore, prognostic markers have been identified with independent predictive value for identification of treatment failure. Such markers include large RV end-diastolic volume index, low left ventricular end-diastolic volume index, low RV ejection fraction, and relative area change of the pulmonary trunk. MRI is ideally suited for longitudinal follow-up of patients with PAH because of its noninvasive nature and high reproducibility and is advantageous over other biomarkers in the study of PAH because of its sensitivity to change in morphologic, functional, and flow-related parameters. Further study on the role of MRI image based biomarkers in the clinical environment is warranted.

Magnetic Resonance Imaging in the Prognostic Evaluation of Patients with Pulmonary Arterial Hypertension

&NA; Rationale: Prognostication is important when counseling patients and defining treatment strategies in pulmonary arterial hypertension (PAH). Objectives: To determine the value of magnetic resonance imaging (MRI) metrics for prediction of mortality in PAH. Methods: Consecutive patients with PAH undergoing MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) pulmonary hypertension registry. Measurements and Main Results: During the follow‐up period of 42 (range, 17‐142) months 576 patients were studied and 221 (38%) died. A derivation cohort (n = 288; 115 deaths) and validation cohort (n = 288; 106 deaths) were identified. We used multivariate Cox regression and found two independent MRI predictors of death (P < 0.01): right ventricular end‐systolic volume index adjusted for age and sex, and the relative area change of the pulmonary artery. A model of MRI and clinical data constructed from the derivation cohort predicted mortality in the validation cohort at 1 year (sensitivity, 70 [95% confidence interval (CI), 53‐83]; specificity, 62 [95% CI, 62‐68]; positive predictive value [PPV], 24 [95% CI, 16‐32]; negative predictive value [NPV], 92 [95% CI, 87‐96]) and at 3 years (sensitivity, 77 [95% CI, 67‐85]; specificity, 73 [95% CI, 66‐85]; PPV, 56 [95% CI, 47‐65]; and NPV, 87 [95% CI, 81‐92]). The model was more accurate in patients with idiopathic PAH at 3 years (sensitivity, 89 [95% CI, 65‐84]; specificity, 76 [95% CI, 65‐84]; PPV, 60 [95% CI, 46‐74]; and NPV, 94 [95% CI, 85‐98]). Conclusions: MRI measurements reflecting right ventricular structure and stiffness of the proximal pulmonary vasculature are independent predictors of outcome in PAH. In combination with clinical data MRI has moderate prognostic accuracy in the evaluation of patients with PAH.

Dynamic contrast–enhanced magnetic resonance imaging in patients with pulmonary arterial hypertension

Dynamic contrast–enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for detecting reduced CI (FWHM area under the curve [AUC] at receiver operating characteristic analysis = 0.91 and PTT AUC = 0.92, respectively) and for detecting elevated PVRI (FWHM AUC = 0.88 and PTT AUC = 0.84, respectively). During the follow-up period, 25 patients died. Patients with longer measurements of FWHM (P = 0.0014) and PTT (P = 0.004) were associated with poor outcome at Kaplan-Meier analysis, and both parameters were strong predictors of adverse outcome from Cox proportional hazards analysis (P = 0.013 and 0.010, respectively). At bivariate analysis, DCE measurements predicted mortality independent of age, gender, and World Health Organization functional class; however, invasive hemodynamic indexes CI, PVRI, and DCE measurements were not independent of one another. In conclusion, DCE-MR transit times predict mortality in patients with PAH and are closely associated with clinical gold standards CI and PVRI.

Right Ventricular Sex Differences in Patients with Idiopathic Pulmonary Arterial Hypertension Characterised by Magnetic Resonance Imaging: Pair-Matched Case Controlled Study

Purpose Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently affected by the condition but have worse outcome as compared to females. We sought to characterise the sex related differences in right ventricular remodelling in age matched male and female patients with IPAH using cardiac magnetic resonance imaging (MRI). Methods A case controlled pair-matched study was conducted with patients matched by age and sex. Steady state free precession (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass measurements were corrected for age, sex and BSA according to reference data. Results 40 age and sex matched patients with IPAH were identified. The mean age was 57 (SD 17) in both male and female cohorts. Men had proportionally lower right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no significant difference in RV mass or haemodynamic indices of mPAP and PVR between males and females. Conclusion Male patients with IPAH have proportionally worse RV function despite similar afterload. We hypothesise that adaptive remodelling of the RV in response to increased afterload in IPAH is more effective in females.

Longitudinal and transverse right ventricular function in pulmonary hypertension: cardiovascular magnetic resonance imaging study from the ASPIRE registry

Right ventricular (RV) function is a strong predictor of outcome in cardiovascular diseases. Two components of RV function, longitudinal and transverse motion, have been investigated in pulmonary hypertension (PH). However, their individual clinical significance remains uncertain. The aim of this study was to determine the factors associated with transverse and longitudinal RV motion in patients with PH. In 149 treatment-naive patients with PH and 16 patients with suspected PH found to have mean pulmonary arterial pressure of <20 mmHg, cardiovascular magnetic resonance imaging was performed within 24 hours of right heart catheterization. In patients with PH, fractional longitudinal motion (fractional tricuspid annulus to apex distance [f-TAAD]) was significantly greater than fractional transverse motion (fractional septum to free wall distance [f-SFD]; P = 0.002). In patients without PH, no significant difference between f-SFD and f-TAAD was identified (P = 0.442). Longitudinal RV motion was singularly associated with RV ejection fraction independent of age, invasive hemodynamics, and cardiac magnetic resonance measurements (P = 0.024). In contrast, transverse RV motion was independently associated with left ventricular eccentricity (P = 0.036) in addition to RV ejection fraction (P = 0.014). In conclusion, RV motion is significantly greater in the longitudinal direction in patients with PH, whereas patients without PH have equal contributions of transverse and longitudinal motion. Longitudinal RV motion is primarily associated with global RV pump function in PH. Transverse RV motion not only reflects global pump function but is independently influenced by ventricular interaction in patients with PH.

Right ventricular mass has better reproducibility in systole than diastole in patients with suspected pulmonary hypertension

Results 30 consecutive patients with suspected pulmonary hypertension were studied by both independent observers. RV mass measured in systole had higher ICC agreement than diastole (0.983 verses 0.947) and showed less bias at Bland-Altman analysis, 1.9g compared to 8.7g, Figure 1. Of note, RV mass measurements were significantly higher when measured in systole than diastole, with a mean difference of 10g (95% confidence interval of 6.6 to 13.2, p<0.0001). Bland Altman analysis shows RV mass measured in systole to be systematically higher than in diastole with a bias of 9.9g, with limits of agreement ranging from -27.4g to 7.6g. Figure 2 illustrates that the RV endocardial border is more easily appreciated in systole compared to diastole in patients with and without pulmonary hypertension. Conclusions RV mass possess a higher reproducibility profile at endsystole than end-diastole in patients with suspected pulmonary hypertension, this finding is of clinical relevance as mass measurements are typically measured in diastole.