Arginine Metabolites as Biomarkers of Myocardial Ischaemia, Assessed with Cardiac Magnetic Resonance Imaging in Chronic Kidney Disease.

(1) Background: Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Myocardial oxygenation and perfusion response to stress, using oxygen-sensitive cardiovascular magnetic resonance (OS-CMR) and stress T1 mapping respectively, are impaired in CKD patients with and without known coronary artery disease (CAD). Endothelial dysfunction, assessed by circulating levels of asymmetric dimethylarginine (ADMA) and homoarginine (HMA), promotes atherosclerosis. We hypothesized that in CKD patients, worsening endothelial dysfunction is associated with worsening myocardial oxygenation and perfusion as assessed by change in OS-CMR signal intensity (Δ OS-CMR SI) and stress T1 (ΔT1) values. (2) Methods: 38 patients with advanced CKD underwent cardiovascular magnetic resonance (CMR) scanning at 3 Tesla. OS-CMR and T1 mapping images were acquired both at rest and after adenosine stress and analyzed semi-quantitatively. Serum ADMA and HMA concentrations were assessed using mass spectrometry. (3) Results: There was no significant correlation between Δ OS-CMR SI and ADMA or HMA. Interestingly, there was a significant negative correlation seen between Δ T1 and ADMA (r = -0.419, p = 0.037, n = 30) but not between Δ T1 and HMA. (4) Conclusions: Stress T1 response is impaired in CKD patients and is independently associated with higher circulating ADMA concentrations.

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).

The Role of Cardiac Imaging in the Diagnosis and Management of Anderson-Fabry Disease.

Anderson-Fabry disease (AFD) is a rare X-linked inherited metabolic disorder which results in a deficiency or absence of the enzyme α-galactosidase A, leading to the accumulation of glycosphingolipids in various cells and organs including the heart. Cardiac involvement is common and results in increased myocardial inflammation, left ventricular hypertrophy (LVH), and myocardial fibrosis. Echocardiography and cardiovascular magnetic resonance (CMR) offer distinctive and often complementary use to assist in the diagnosis and monitoring pharmacologic therapy in AFD, including detection of the AFD cardiac phenotype, differentiation from other forms of LVH, and patient selection for therapeutic intervention. Advanced cardiac imaging holds promise in subclinical detection of AFD-related abnormalities as well as disease staging and prognostication.

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.

Ascending Aorta and Myocardial Mechanics in Patients with "Clinically Normal" Bicuspid Aortic Valve.

Aortic valve dysfunction and aortic wall changes are well-known complications of bicuspid aortic valve (BAV) disease. The aim of the present study was to investigate whether a remodeling process of the left ventricle (LV) is present in patients with isolated BAV. Twenty-two consecutive patients (39 ± 15 years, 9 males) with clinically normal BAV and 18 age- and gender-matched control subjects (37 ± 10 years, 9 males) were included. Cardiovascular magnetic resonance (CMR) imaging was performed to evaluate LV function, aortic valve morphology, aortic orifice area, and ascending aorta (AA) dimensions. Tissue-tracking analysis was applied to assess LV systolic and diastolic myocardial mechanics in the longitudinal, circumferential, and radial direction and AA circumferential strain (CS). No significant difference was observed between BAV and controls regarding LV ejection fraction and LV mass index. Tissue-tracking analysis demonstrated that BAV patients had significantly impaired LV systolic and diastolic myocardial mechanics. BAV patients had also significantly lower AA CS compared with controls. At multivariate analysis, the presence of BAV was the only variable significantly and independently related to the impaired AA and LV systolic myocardial mechanics. In conclusion, LV myocardial deformation properties are impaired among BAV patients. The impairment of LV systolic mechanics observed in BAV patients appears to be related only to the congenital abnormality of the aortic valve itself.

Prognostic value of myocardial deformation imaging by cardiac magnetic resonance feature-tracking in patients with a first ST-segment elevation myocardial infarction.

AIM: Scarce data are available whether cardiac magnetic resonance (CMR) assessment of myocardial deformation provides independent and incremental prognostic information in patients with ST-segment elevation myocardial infarction (STEMI). The aim of the present study was to investigate the prognostic utility of CMR feature-tracking derived left ventricular (LV) global circumferential strain (GCS) in STEMI patients. METHODS: A total of 180 patients (mean age 60 ±â€¯12 years, 72% male) admitted because of a first STEMI were included. CMR with late gadolinium enhancement (LGE) imaging was performed to assess LV function, infarct size, and microvascular obstruction. The feature-tracking analysis was applied to cine-CMR short-axis images to assess LV GCS. Patients were followed-up for a median of 95 months. The outcome event was a composite endpoint including cardiovascular death, aborted sudden cardiac death, and hospitalization for heart failure. RESULTS: During follow-up, 40 (22%) patients experienced at least 1 event. After adjustment for other clinical and CMR imaging characteristics, LV GCS remained significantly and independently associated with the outcome event (HR 1.16 per %; 95% CI 1.07-1.25; p < 0.001). A significant increase of global χ2 was observed when adding LV GCS to a model including clinical and non-contrast CMR variables (χ2 change = 8.2; p = 0.004) and to a model including clinical, non-contrast and LGE variables (χ2 change = 4.8; p = 0.028). CONCLUSION: LV GCS assessed by CMR feature-tracking can predict a worse long-term prognosis in patients admitted with a first STEMI. More importantly, the predictive ability of LV GCS is incremental to other clinical and CMR variables.

Noninvasive imaging in cardiac deposition diseases.

Infiltrative cardiomyopathy represents a heterogeneous group of diseases of the heart tissue with similar phenotypic expression. The condition is rare, but can be easily mistaken for other more common conditions of the heart. The diagnosis of infiltrative cardiomyopathy is therefore challenging and has often required the use of invasive procedures in the past. In the last decade there have been great advances in non-invasive cardiac imaging modalities like echocardiography, cardiovascular magnetic resonance and nuclear imaging. Although no single imaging modality abnormality on its own is pathognomic for infiltrative cardiomyopathy, a combination of these different modalities are synergistic, and can greatly aid in the clinical diagnosis. In this review, we describe these advancements in non-invasive cardiac imaging modalities with a particular focus on cardiovascular magnetic resonance imaging. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:44-59.

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.

Prevalence, Correlates, and Prognostic Relevance of Myocardial Mechanical Dispersion as Assessed by Feature-Tracking Cardiac Magnetic Resonance After a First ST-Segment Elevation Myocardial Infarction.

Postinfarction mechanical dispersion (MD), that is, the regional heterogeneity of myocardial contraction throughout the cardiac cycle, has detrimental effects on left ventricular (LV) function and is related to the occurrence of heart failure and ventricular arrhythmias. However, its prevalence, pathophysiological determinants, and clinical utility are still unknown. The aim of the present study is to clarify these issues. In total, 130 consecutive patients (mean age 60 ± 12 years, 75% male) with a first ST-segment elevation myocardial infarction (STEMI) were included. Cardiac magnetic resonance (CMR) with late gadolinium enhancement imaging was performed to assess LV function, infarct size, and microvascular obstruction. Feature-tracking analysis was applied to cine-CMR short-axis images to assess MD, defined as the SD of the time-to-peak circumferential strain of the LV segments expressed as percent cardiac cycle. For comparison purpose, 40 control subjects similar in age and gender to the STEMI group were also included. Patients were followed-up for a median of 95 months; the outcome event was defined as a composite of cardiovascular death, aborted sudden cardiac death, and hospitalization for heart failure. STEMI patients had significantly higher MD compared with controls (12.0 ± 5.35% vs 3.85 ± 0.99%, p <0.001). At multivariate analysis, heart rate (ß = 0.20, p = 0.008), LV end-systolic volume index (ß = 0.37, p <0.001), and infarct size (ß = 0.23, p = 0.017) were significantly and independently related to MD. The outcome event occurred in 26 (20%) patients. At multivariate Cox proportional hazards analysis, MD was significantly and independently related to the outcome event (p <0.001). MD provided significant incremental value over the other clinical and CMR variables in predicting the outcome event (p <0.001 for the chi-square change). In conclusion, MD after STEMI is a marker of the extent of myocardial damage; its assessment by feature-tracking CMR provides significant, independent, and incremental long-term prognostic information.

Systematic review and meta-analysis of incidence and correlates of recurrence of takotsubo cardiomyopathy.

AIM: Takotsubo cardiomyopathy (TTC) is a disorder of myocardial inflammation induced by high catecholamine levels and is associated with acute complications. In the long-term TTC is associated with a risk of single or multiple recurrences, but risk of such occurrences is not clear. We performed a systematic review and meta-analysis to identify and consolidate the evidence on the incidence and clinical correlates of cases of TTC recurrence. METHODS: A comprehensive search of four major databases (EMBASE, OVID Medline, PubMed and Google Scholar) was performed from their inception to first week of Jan 2014. We included original research studies, recruiting ≥ 5 participants, with ≥ 3 months follow-up, published in English language that reported data on recurrence in patients with TTC. RESULTS: Out of 298 studies searched, 31 cohorts (1664 TTC patients) were included in the analyses. Out of 74 cases of recurrence, with a mean follow-up of 24.5 months (95% CI, 19.3 to 33 months), extensive recurrence data were available for 23 cases. Cumulative incidence of recurrence was approximately 5% at 6 years. Annual rate of recurrence was approximately 1.5%. Furthermore, 14% of cases had recurrent chest pain and 11% reported dyspnea without definite evidence of recurrent TTC. Discharge medications at index admission included ß-adrenoceptor antagonists (BB) in 66.8% and ACE inhibitors (ACEi) and ARB in 67.4%. Recurrence rate was independent of clinic utilization of BB prescription, but inversely correlated (r=-0.45, p=0.016) with ACEi/ARB prescription. Patients with severe TTC at index admission were noted to have more recurrences. CONCLUSIONS: (1) TTC is associated with only 1-2% annual recurrence rate but substantially greater frequency of ongoing symptoms. (2) ACEi/ARB rather than BB may reduce risk of recurrence.

Meta-analysis of clinical correlates of acute mortality in takotsubo cardiomyopathy.

The incidence and clinical correlates of acute in-hospital mortality of takotsubo cardiomyopathy (TTC) are not clear. We performed a systematic review and meta-analysis to consolidate the current evidence on acute mortality in TTC. We then assessed the impact of "secondary" TTC, male gender, advancing age, and catecholamine use on mortality. A comprehensive search of 4 major databases (EMBASE, Ovid MEDLINE, PubMed, and Google Scholar) was performed from their inception to the first week of July 2013. We included original research studies, recruiting ≥10 participants, published in English language, and those that reported data on mortality and cause of death in patients with TTC. Of 382 citations, 37 studies (2,120 patients with TTC) from 11 different countries were included in the analyses. The mean age of the cohort was 68 years (95% confidence interval [CI] 67 to 69) with female predominance (87%). The in-hospital mortality rate among patients with TTC was 4.5% (95% CI 3.1 to 6.2, I2=60.8%). Among all deaths, 38% were directly related to TTC complications and rest to underlying noncardiac conditions. Male gender was associated with higher TTC mortality rate (odds ratio 2.6, 95% CI 1.5 to 4.6, p=0.0008, I2=0%) so was "secondary" TTC (risk difference -0.11, 95% CI -0.18 to -0.04, p=0.003, I2=84%). The mean age of patients dying tended to be greater than that in the whole cohort (72±7 vs 65±7 years). In conclusion, TTC is not as benign as once thought. To reduce the mortality rate, greater efforts need to be directed to the diagnosis, treatment, and ultimately prevention of "secondary" TTC.