Christopher S. Johns

CT features of pulmonary arterial hypertension and its major subtypes: a systematic CT evaluation of 292 patients from the ASPIRE Registry

We evaluated the prevalence and prognostic value of CT-pulmonary angiographic (CTPA) measures in 292 treatment naive patients with pulmonary arterial hypertension (PAH). Pulmonary artery calcification (13%) and thrombus (10%) were exclusively seen in PAH-congenital heart disease. Oesophageal dilation (46%) was most frequent in PAH-systemic sclerosis. Ground glass opacification (GGO) (41%), pericardial effusion (38%), lymphadenopathy (19%) and pleural effusion (11%) were common. On multivariate analysis, inferior vena caval area, the presence of pleural effusion and septal lines predicted outcome. In PAH, CTPA provides diagnostic and prognostic information. In addition, the presence of GGO on a CT performed for unexplained breathlessness should alert the physician to the possibility of PAH.

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.

Lung perfusion: MRI vs. SPECT for screening in suspected chronic thromboembolic pulmonary hypertension: Lung Perfusion for CTEPH

To assess the diagnostic accuracy of magnetic resonance imaging (MRI) perfusion against perfusion single photon emission tomography (SPECT) screening for chronic thromboembolic pulmonary hypertension (CTEPH). Ventilation/perfusion (V/Q) scintigraphy is recommended to screen for suspected CTEPH. It has previously been shown that 3D dynamic contrast‐enhanced (DCE) lung perfusion MRI has a similar sensitivity for diagnosing CTEPH in comparison to planar perfusion scintigraphy; however, planar scintigraphy has now been largely replaced by SPECT, due to higher spatial resolution and sensitivity.

Non-invasive methods for estimating mPAP in COPD using cardiovascular magnetic resonance imaging

PurposePulmonary hypertension (PH) is associated with a poor outcome in chronic obstructive pulmonary disease (COPD) and is diagnosed invasively. We aimed to assess the diagnostic accuracy and prognostic value of non-invasive cardiovascular magnetic resonance (CMR) models.MethodsPatients with COPD and suspected PH, who underwent CMR and right heart catheter (RHC) were identified. Three candidate models were assessed: 1, CMR-RV model, based on right ventricular (RV) mass and interventricular septal angle; 2, CMR PA/RV includes RV mass, septal angle and pulmonary artery (PA) measurements; 3, the Alpha index, based on RV ejection fraction and PA size.ResultsOf 102 COPD patients, 87 had PH. The CMR-PA/RV model had the strongest diagnostic accuracy (sensitivity 92%, specificity 80%, positive predictive value 96% and negative predictive value 63%, AUC 0.93, p<0.0001). Splitting RHC-mPAP, CMR-RV and CMR-PA/RV models by 35mmHg gave a significant difference in survival, with log-rank chi-squared 5.03, 5.47 and 7.10. RV mass and PA relative area change were the independent predictors of mortality at multivariate Cox regression (p=0.002 and 0.030).ConclusionCMR provides diagnostic and prognostic information in PH-COPD. The CMR-PA/RV model is useful for diagnosis, the RV mass index and PA relative area change are useful to assess prognosis.Key Points• Pulmonary hypertension is a marker of poor outcome in COPD.• MRI can predict invasively measured mean pulmonary artery pressure.• Cardiac MRI allows for estimation of survival in COPD.• Cardiac MRI may be useful for follow up or future trials.• MRI is potentially useful to assess pulmonary hypertension in patients with COPD.

Pulmonary MR angiography and perfusion imaging—A review of methods and applications

The pulmonary vasculature and its role in perfusion and gas exchange is an important consideration in many conditions of the lung and heart. Currently the mainstay of imaging of the vasculature and perfusion of the lungs lies with CT and nuclear medicine perfusion scans, both of which require ionizing radiation exposure. Improvements in MRI techniques have increased the use of MRI in pulmonary vascular imaging. Here we review MRI methods for imaging the pulmonary vasculature and pulmonary perfusion, both using contrast enhanced and non-contrast enhanced methodology. In many centres pulmonary MR angiography and dynamic contrast enhanced perfusion MRI are now well established in the routine workflow of patients particularly with pulmonary hypertension and thromboembolic disease. However, these imaging modalities offer exciting new directions for future research and clinical use in other respiratory diseases where consideration of pulmonary perfusion and gas exchange can provide insight in to pathophysiology.

CT derived left atrial size identifies left heart disease in suspected pulmonary hypertension: Derivation and validation of predictive thresholds

Background Patients with pulmonary hypertension due to left heart disease (PH-LHD) have overlapping clinical features with pulmonary arterial hypertension making diagnosis reliant on right heart catheterization (RHC). This study aimed to investigate computed tomography pulmonary angiography (CTPA) derived cardiopulmonary structural metrics, in comparison to magnetic resonance imaging (MRI) for the diagnosis of left heart disease in patients with suspected pulmonary hypertension. Methods Patients with suspected pulmonary hypertension who underwent CTPA, MRI and RHC were identified. Measurements of the cardiac chambers and vessels were recorded from CTPA and MRI. The diagnostic thresholds of individual measurements to detect elevated pulmonary arterial wedge pressure (PAWP) were identified in a derivation cohort (n = 235). Individual CT and MRI derived metrics were tested in validation cohort (n = 211). Results 446 patients, of which 88 had left heart disease. Left atrial area was a strong predictor of elevated PAWP>15 mm Hg and PAWP>18 mm Hg, area under curve (AUC) 0.854, and AUC 0.873 respectively. Similar accuracy was also identified for MRI derived LA volume, AUC 0.852 and AUC 0.878 for PAWP > 15 and 18 mm Hg, respectively. Left atrial area of 26.8 cm2 and 30.0 cm2 were optimal specific thresholds for identification of PAWP > 15 and 18 mm Hg, had sensitivity of 60%/53% and specificity 89%/94%, respectively in a validation cohort. Conclusions CTPA and MRI derived left atrial size identifies left heart disease in suspected pulmonary hypertension with high specificity. The proposed diagnostic thresholds for elevated left atrial area on routine CTPA may be a useful to indicate the diagnosis of left heart disease in suspected pulmonary hypertension.

The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension

Pulmonary endarterectomy (PEA) is the gold standard treatment for operable chronic thromboembolic pulmonary hypertension (CTEPH). However, a proportion of patients with operable disease decline surgery. There are currently no published data on this patient group. The aim of this study was to identify outcomes and prognostic factors in a large cohort of consecutive patients with CTEPH. Data were collected for consecutive, treatment-naive CTEPH patients at the Pulmonary Vascular Disease Unit of the Royal Hallamshire Hospital (Sheffield, UK) between 2001 and 2014. Of 550 CTEPH patients (mean±sd age 63±15 years, follow-up 4±3 years), 49% underwent surgery, 32% had technically operable disease and did not undergo surgery (including patient choice n=72 and unfit for surgery n=63), and 19% had inoperable disease due to disease distribution. The 5-year survival was superior in patients undergoing PEA (83%) versus technically operable disease who did not undergo surgery (53%) and inoperable due to disease distribution (59%) (p<0.001). Survival was superior in patients following PEA compared with those offered but declining surgery (55%) (p<0.001). In patients offered PEA, independent prognostic factors included mixed venous oxygen saturation, gas transfer and patient decision to proceed to surgery. Outcomes in CTEPH following PEA are excellent and superior to patients declining surgery, and strongly favour consideration of a surgical intervention in eligible patients. Outcomes for patients undergoing pulmonary endarterectomy are excellent and superior to patients declining surgery http://ow.ly/9UZw30kA28m

The sound of silence

In January, 2011, a previously well 68-year-old woman, presented to our neurology outpatients department with a 6 week history of hearing a male voice singing and gradual bilateral hearing loss over the course of 1 year. The singing started suddenly with songs she knew from her childhood, and more recently she also reported hearing a choir. The singing was perceived as external, heard only in the left ear, and continued all day and night. She reported that the voices were irritating, particularly when trying to sleep. They stopped when she fell asleep and did not interfere with her daytime activities. She had insight that the voices were imaginary but said that she could not “switch them off ” and did not recall any specifi c triggers. There was no alteration of the symptoms with her mood or tiredness. There was no reported change in her mood, with no signs of depression or mania, nor thoughts or intentions of self harm. She did not report tinnitus, other sensory hallucinations, or any symptoms of epileptic seizures such as vacant attacks, odd tastes or smells, incontinence, tongue biting at night, or psychomotor automatisms. She had no history of thought insertion, withdrawal, broadcasting, or any other features of schizophrenia. She had a medical history of hypertension, and was on aspirin, atenolol, and olmesartan. Amitriptyline was prescribed for insomnia. She did not smoke, drink alcohol, or use recreational drugs. On examination she was anxious, but alert and oriented with no cognitive impairment. A full mini-mental state examination could not be done because her hearing loss made the repetition of a sentence impossible. However, she scored 27/27 points on the incomplete test. She was oriented in time, person, and place, with no evidence of alteration of consciousness. She had bilateral hearing loss. Neurological examination was unremarkable other than absent vibration sensation and ankle refl exes. Routine blood tests were normal. An electroencephalogram done whilst she was experiencing the singing, did not show epileptic activity or any other focal or generalised brain abnormalities. CT of the head was normal. MRI of the head (with T1, T2, and FLAIR sequences) showed only a few white matter hyper intensities of the T2 and FLAIR sequences, which can be associated with smallvessel disease secondary to hyper tension. Ear, nose, and throat examination and pure tone audiogram showed bilateral sensorineural hearing loss only. Psychiatric assessment ruled out the possibility of mental illness. Our patient was diagnosed with musical ear syndrome because there was no evidence of neurological or psychiatric disease. This is a syndrome comparable to Charles Bonnet Syndrome in which people with visual impairment have visual hallucinations. Our patient was reassured about the benign nature of her condition. Multiple anticonvulsants were tried with mixed results. In February, 2012, at last follow-up, she had marked improvement of her symptoms after starting Clonazepam. Charles Bonnet was a Swiss scientist who documented complex visual hallucinations in his blind but otherwise healthy grandfather in 1760. Later the blind Charles Bonnet also had similar hallu cinations. Diagnostic criteria have since been developed for the disorder fi rst described as Charles Bonnet Syndrome by a Swiss neurologist George de Morsier, in 1967. Clinical features are often stereotyped, complex visual hallucin ations in a partially sighted patient. The patient has insight that the hallucinations are not real, and there is no psychosis, neurological or cognitive impairment, intox ication, or metabolic abnormality. No other sensory hallu cinations should be present. Generally the hallucinations are self limiting. No clear evidence for treatment exists. The mechanism of Charles Bonnet Syndrome is poorly understood. Few reports about complex auditory hallucinations in people with hearing impairment exist; however, some have suggested that they are quite common. Whether the diagnostic criteria of Charles Bonnet Syndrome should be extended to include complex auditory hallucinations, or these considered separately as Musical Ear Syndrome, is debatable. Our patient’s case is a reminder that hallucinations are not always due to delirium or to psychological or neurodegenerative conditions. Other conditions, such as Charles Bonnet Syndrome or musical ear syndrome, should also be considered.

Diagnosis of Pulmonary Hypertension with Cardiac MRI: Derivation and Validation of Regression Models

Purpose To derive and test multiparametric cardiac MRI models for the diagnosis of pulmonary hypertension (PH). Materials and Methods Images and patient data from consecutive patients suspected of having PH who underwent cardiac MRI and right-sided heart catheterization (RHC) between 2012 and 2016 were retrospectively reviewed. Of 2437 MR images identified, 603 fit the inclusion criteria. The mean patient age was 61 years (range, 18–88 years; mean age of women, 60 years [range, 18–84 years]; mean age of men, 62 years [range, 22–88 years]). In the first 300 patients (derivation cohort), cardiac MRI metrics that showed correlation with mean pulmonary arterial pressure (mPAP) were used to create a regression algorithm. The performance of the model was assessed in the 303-patient validation cohort by using receiver operating characteristic (ROC) and χ2 analysis. Results In the derivation cohort, cardiac MRI mPAP model 1 (right ventricle and black blood) was defined as follows: −179 + loge interventricular septal angle × 42.7 + log10 ventricular mass index (right ventricular mass/left ventricular mass) × 7.57 + black blood slow flow score × 3.39. In the validation cohort, cardiac MRI mPAP model 1 had strong agreement with RHC-measured mPAP, an intraclass coefficient of 0.78, and high diagnostic accuracy (area under the ROC curve = 0.95; 95% confidence interval [CI]: 0.93, 0.98). The threshold of at least 25 mm Hg had a sensitivity of 93% (95% CI: 89%, 96%), specificity of 79% (95% CI: 65%, 89%), positive predictive value of 96% (95% CI: 93%, 98%), and negative predictive value of 67% (95% CI: 53%, 78%) in the validation cohort. A second model, cardiac MRI mPAP model 2 (right ventricle pulmonary artery), which excludes the black blood flow score, had equivalent diagnostic accuracy (ROC difference: P = .24). Conclusion Multiparametric cardiac MRI models have high diagnostic accuracy in patients suspected of having pulmonary hypertension. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Colletti in this issue.

Identifying At-Risk Patients with Combined Pre- and Postcapillary Pulmonary Hypertension Using Interventricular Septal Angle at Cardiac MRI

Purpose To assess interventricular septal (IVS) angle in the identification of combined pre- and postcapillary pulmonary hypertension (Cpc-PH) in patients with pulmonary hypertension (PH) due to left-sided heart disease. Materials and Methods In this retrospective study, consecutive, incident patients suspected of having PH underwent same-day right-sided heart catheterization (RHC) and MRI at a PH referral center between April 2012 and April 2017. The diagnostic accuracy of the IVS angle to identify Cpc-PH in patients with pulmonary arterial wedge pressure (PAWP) greater than 15 mmHg was assessed by using receiver operator characteristic curves, sensitivity, specificity, and negative and positive predictive values. IVS angle also was assessed as a predictor of all-cause mortality by using Cox uni- and multivariable proportional hazards regression. Results A total of 708 patients underwent same-day MRI and RHC, and 171 patients had PAWP greater than 15 mmHg. Mean age was 70 years (range, 21–90 years) (women: mean age, 69 years; range, 21–88 years) (men: mean age, 71 years; range, 43–90 years). Systolic IVS angle correlated with diastolic pulmonary gradient (DPG) (r = 0.739, P < .001). Receiver operating characteristic curve analysis showed septal angle enabled identification of Cpc-PH (DPG ≥ 7), with an area under the receiver operating characteristic curve of 0.911 (P < .001). A 160° threshold, derived from the first half of patients with raised PAWP, enabled identification of a DPG of at least 7 mmHg with 67% sensitivity and 93% specificity (P < .001) in the second cohort of patients with raised PAWP. IVS angle was predictive of all-cause mortality (standardized univariable hazard ratio, 1.615; P < .01). Conclusion The systolic interventricular septal angle is elevated in patients with combined pre- and postcapillary pulmonary hypertension and enables one to predict those patients who have PH due to left-sided heart disease who have an increased risk of death. Published under a CC BY 4.0 license. Online supplemental material is available for this article.