Right ventricular myocardial deoxygenation in patients with pulmonary artery hypertension.

BACKGROUND: In pulmonary arterial hypertension (PAH), progressive right ventricular (RV) dysfunction is believed to be largely secondary to RV ischaemia. A recent pilot study has demonstrated the feasibility of Oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) to detect in-vivo RV myocardial oxygenation. The aims of the present study therefore, were to assess the prevalence of RV myocardial ischaemia and relationship with RV myocardial interstitial changes in PAH patients with non-obstructive coronaries, and corelate with functional and haemodynamic parameters. METHODS: We prospectively recruited 42 patients with right heart catheter (RHC) proven PAH and 11 healthy age matched controls. The CMR examination involved standard functional imaging, OS-CMR imaging and native T1 mapping. An ΔOS-CMR signal intensity (SI) index (stress/rest signal intensity) was acquired at RV anterior, RV free-wall and RV inferior segments. T1 maps were acquired using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) at the inferior RV segment. RESULTS: The inferior RV ΔOS-CMR SI index was significantly lower in PAH patients compared with healthy controls (9.5 (- 7.4-42.8) vs 12.5 (9-24.6)%, p = 0.02). The inferior RV ΔOS-CMR SI had a significant correlation to RV inferior wall thickness (r = - 0.7, p < 0.001) and RHC mean pulmonary artery pressure (mPAP) (r = - 0.4, p = 0.02). Compared to healthy controls, patients with PAH had higher native T1 in the inferior RV wall: 1303 (1107-1612) vs 1232 (1159-1288)ms, p = 0.049. In addition, there was a significant difference in the inferior RV T1 values between the idiopathic PAH and systemic sclerosis associated PAH patients: 1242 (1107-1612) vs 1386 (1219-1552)ms, p = 0.007. CONCLUSION: Blunted OS-CMR SI suggests the presence of in-vivo microvascular RV dysfunction in PAH patients. The native T1 in the inferior RV segments is significantly increased in the PAH patients, particularly among the systemic sclerosis associated PAH group.

Left ventricular ischemia in pre-capillary pulmonary hypertension: a cardiovascular magnetic resonance study.

BACKGROUND: Prognosis in pulmonary arterial hypertension (PAH) is largely dependent on right ventricular (RV) function. However, recent studies have suggested the presence of left ventricular (LV) dysfunction in PAH patients. The potential role of LV ischemia, as a contributor to progressive LV dysfunction, has not been systematically studied in PAH. We aim to assess the presence and extent of LV myocardial ischemia in patients with known PH and without obstructive coronary artery disease (CAD), using oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) and stress/rest CMR T1 mapping. METHODS: We prospectively recruited 28 patients with right heart catheter-proven PH and no significant CAD, 8 patients with known CAD and 11 normal age-matched controls (NC). OS-CMR images were acquired using a T2* sequence and T1 maps were acquired using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) at rest and adenosine-induced stress vasodilatation; ΔOS-CMR signal intensity (SI) index (stress/rest SI) and ΔT1 reactivity (stress-rest/rest T1 mapping) were calculated. RESULTS: Global LV ΔOS SI index was significantly lower in PH patients compared with controls (11.1%±6.7% vs. 20.5%±10.5%, P=0.016), as was ΔT1 reactivity (5.2%±4.5% vs. 8.0%±2.9%, P=0.047). The ischemic segments of CAD patients had comparable ΔOS SI (10.3%±6.4% vs. 11.1%±6.7%, P=0.773) to PH patients, but lower ΔT1 reactivity (1.1%±4.2% vs. 5.2%±4.5%, P=0.036). CONCLUSIONS: Decreased OS-CMR SI and T1 reactivity signify the presence of impaired myocardial oxygenation and vasodilatory response in PH patients. Given their unobstructed epicardial coronary arteries, this is likely secondary to coronary microvascular dysfunction (CMD).

Advanced Echocardiographic Imaging for Prediction of SCD in Moderate and Severe LV Systolic Function.

OBJECTIVES: This study sought to determine the long-term prognostic value of myocardial deformation imaging by echocardiography in risk stratification of sudden cardiac death (SCD) and malignant ventricular arrhythmias (VAs) in a large consecutive cohort of patients with left ventricular (LV) systolic impairment, irrespective of its etiology. BACKGROUND: Left ventricular ejection fraction (LVEF) is limited for prediction of SCD. Echocardiographic strain-derived mechanical dispersion (MD) and global longitudinal strain (GLS) has been linked to VA and SCD. However, due to low event rates, the role of these parameters has not been fully elucidated. METHODS: Consecutive clinically stable patients who underwent echocardiographic study performed in an outpatient setting from 2008 to 2014 with a Simpson left ventricular ejection fraction (LVEF) ≤45% were included in the study. Strain analysis was performed in which the LV was separated into 16 segments for regional analysis. Mechanical dispersion (MD) was calculated as the SD of the time to peak of each of the 16 regions. Outcome data were obtained from medical records. RESULTS: A total of 939 patients were included in the study, with median LVEF of 37% (interquartile range 30% to 42%). At follow-up (91.4 ± 23.4 months), 96 VA events had occurred. Multivariate analysis demonstrated that only MD ≥75 ms (hazard ratio: 9.45; 95% confidence interval: 4.75 to 18.81; p < 0.0001) was predictive of VA events. Low MD predicted a low event rate, irrespective of LVEF. CONCLUSIONS: Using LVEF alone is inferior for prediction of VA and SCD, particularly in patients with moderately reduced LVEF. MD is easily obtained from standard echocardiographic images and can be used to improve risk prognosis, particularly in patients who are currently excluded from cardiac defibrillator insertion based on LVEF.

Feasibility of oxygen sensitive cardiac magnetic resonance of the right ventricle in pulmonary artery hypertension.

BACKGROUND: Progressive right ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH) which is contributed by RV ischemia leads to adverse clinical outcomes. Oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) has been used to determine the in vivo myocardial oxygenation of the left ventricle (LV). The aims of the present study were therefore to determine the feasibility of RV targeted rest/stress OS-CMR imaging in PAH patients and healthy volunteers. METHODS: We prospectively recruited 20 patients with right heart catheter proven PAH and 9 healthy age matched controls (NC). The CMR examination involved standard functional imaging and OS-CMR imaging. An OS-CMR signal intensity (SI) index (stress/rest SI) was acquired at RV anterior, RV free-wall and RV inferior segments. In the LV, the OS-CMR SI index was acquired globally. RESULTS: Reliable OS SI changes were only obtained from the RV inferior segment. As RV dysfunction in PAH is a global process, hence this segment was used in both patients and NC for further comparison. RV OS-CMR SI change between rest and stress in the NC was 17%±5% (mean ± SD). Nine of 20 (45%) of the PAH patients had a mean OS SI change of less than 9% (or ≥2 SD different from the mean values in NC). Overall, RV OS SI index between the PAH patients and NC was 11%±9% vs. 17%±5% (P=0.045) in the RV inferior segment. In the LV, the global OS-CMR SI index between the PAH patients and NC was 11%±7% vs. 21%±9% (P=0.019). There was a strong correlation between RV Inf OS-CMR SI and LV OS-CMR SI (r=0.86, P<0.001). CONCLUSIONS: In this small pilot study, pharmacological induced OS-CMR is a feasible and safe technique to identify and study myocardial oxygenation in the RV of PAH patients.

Long term prognostic importance of late gadolinium enhancement in first-presentation non-ischaemic dilated cardiomyopathy.

BACKGROUND: Presence of myocardial fibrosis in well-established non-ischaemic dilated cardiomyopathy (NIDCM) is associated with adverse clinical outcomes. However, the impact of myocardial fibrosis at first presentation in NIDCM, and its long-term association with left ventricular (LV) dysfunction, heart failure (HF) and ventricular arrhythmia (VA) remains unclear. We investigated whether the presence of myocardial fibrosis quantified by late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) at presentation, is independently associated with long-term major adverse cardiovascular events (MACE) in patients with first presentation NIDCM. METHODS: Consecutive patients with a first diagnosis of NIDCM were recruited. Patients underwent LGE-CMR at baseline. Replacement myocardial fibrosis by LGE-CMR was quantified by experienced observers blinded to patient outcome. MACE was defined as a composite end-point including cardiac death, HF rehospitalisation and the occurrence of sustained VA. RESULTS: Fifty-one patients with first presentation NIDCM were included, of which 49 (96%) had follow up and outcome data. Median follow up was 8.2 years. Both the LGE positive and LGE negative groups had similar clinical characteristics at follow up. In univariate Cox regression analysis, positive LGE was associated with MACE (HR:3.44; 95% CI:1.89 to 6.24, p-value < 0.001) and HF rehospitalisation (HR:2.89; 95% CI:1.42 to 5.85, p-value = 0.003). In multivariate Cox regression, positive LGE-CMR was independently associated with MACE (HR:3.53; 95% CI:1.51 to 8.27, p-value = 0.004) and HF rehospitalisation (HR:3.07; 95% CI:1.24 to 7.59, p-value = 0.015). CONCLUSIONS: The presence of myocardial fibrosis in first presentation NIDCM is independently associated with an increased risk of HF rehospitalisation, at long term follow-up.

Novel cardiovascular magnetic resonance oxygenation approaches in understanding pathophysiology of cardiac diseases.

Cardiovascular magnetic resonance imaging (CMR) permits accurate phenotyping of many cardiac diseases. CMR's inherent advantages are its non-invasive nature, lack of ionizing radiation and high accuracy and reproducibility. Furthermore, it is able to assess many aspects of cardiac anatomy, structure and function. Specifically, it can characterize myocardial tissue, myocardial function, myocardial mass, myocardial blood flow/perfusion, irreversible and reversible injury, all with a high degree of accuracy and reproducibility. Hence, CMR is a powerful tool in clinical and pre-clinical research. In recent years there have been novel advances in CMR myocardial tissue characterization. Oxygenation-sensitive CMR (OS-CMR) is a novel non-invasive, contrast independent technique that permits direct quantification of myocardial tissue oxygenation, both at rest and during stress. In this review, we will address the principles of the OS-CMR technique, its recent advances and summarize the studies in the effects of oxygenation on cardiac diseases.

Cardiac magnetic resonance evaluation of left ventricular functional, morphological, and structural features in children and adolescents vs. young adults with isolated left ventricular non-compaction.

AIM: To investigate the left ventricular (LV) functional, morphological, and structural features revealed by cardiac magnetic resonance (CMR) in children/adolescents with isolated LV non-compaction (iLVNC), and to compare them with those observed in young adults with iLVNC and healthy controls. METHODS: 56 subjects were included: 12 children/adolescents (mean age 15±3years, 75% male) and 20 young adults (mean age 35±7years, 75% male) with first diagnosis of iLVNC, 12 healthy children/adolescents (mean age 15±3years, 75% male) and 12 healthy young adults (mean age 34±8years, 75% male). CMR with late gadolinium enhancement (LGE) imaging was performed to evaluate LV function, extent of LV trabeculation, and presence/extent of LV LGE, a surrogate of myocardial fibrosis. Tissue-tracking analysis was applied to assess LV global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain. RESULTS: The extent of LVNC and the presence/extent of LV LGE in children/adolescents and young adults with iLVNC were similar. Compared to healthy subjects, young adults with iLVNC had significantly lower LVEF; conversely, no significant difference in this parameter was observed between children/adolescents with iLVNC and healthy subjects. However, compared to healthy subjects, LV strain parameters were lower in both children/adolescents and young adults with iLVNC. CONCLUSIONS: Complete phenotypic expression, subclinical impairment of myocardial deformation properties, and cardiac injury occur early in iLVNC patients, being already noticeable in the pediatric age group. The application of CMR myocardial deformation imaging permits earlier detection of LV functional impairment in children/adolescents with iLVNC, which would otherwise be missed with standard CMR imaging.