The Impact of Bariatric Surgery on Coronary Microvascular Function Assessed Using Automated Quantitative Perfusion CMR.

BACKGROUND: Coronary microvascular function is impaired in patients with obesity, contributing to myocardial dysfunction and heart failure. Bariatric surgery decreases cardiovascular mortality and heart failure, but the mechanisms are unclear. OBJECTIVES: The authors studied the impact of bariatric surgery on coronary microvascular function in patients with obesity and its relationship with metabolic syndrome. METHODS: Fully automated quantitative perfusion cardiac magnetic resonance and metabolic markers were performed before and 6 months after bariatric surgery. RESULTS: Compared with age- and sex-matched healthy volunteers, 38 patients living with obesity had lower stress myocardial blood flow (MBF) (P = 0.001) and lower myocardial perfusion reserve (P < 0.001). A total of 27 participants underwent paired follow-up 6 months post-surgery. Metabolic abnormalities reduced significantly at follow-up including mean body mass index by 11 ± 3 kg/m2 (P < 0.001), glycated hemoglobin by 9 mmol/mol (Q1-Q3: 4-19 mmol/mol; P < 0.001), fasting insulin by 142 ± 131 pmol/L (P < 0.001), and hepatic fat fraction by 5.6% (2.6%-15.0%; P < 0.001). Stress MBF increased by 0.28 mL/g/min (-0.02 to 0.75 mL/g/min; P = 0.003) and myocardial perfusion reserve by 0.13 (-0.25 to 1.1; P = 0.036). The increase in stress MBF was lower in those with preoperative type 2 diabetes mellitus (0.1 mL/g/min [-0.09 to 0.46 mL/g/min] vs 0.75 mL/g/min [0.31-1.25 mL/g/min]; P = 0.002). Improvement in stress MBF was associated with reduction in fasting insulin (beta = -0.45 [95% CI: -0.05 to 0.90]; P = 0.03). CONCLUSIONS: Coronary microvascular function is impaired in patients with obesity, but can be improved significantly with bariatric surgery. Improvements in microvascular function are associated with improvements in insulin resistance but are attenuated in those with preoperative type 2 diabetes mellitus.

[11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial.

Primary aldosteronism (PA) due to a unilateral aldosterone-producing adenoma is a common cause of hypertension. This can be cured, or greatly improved, by adrenal surgery. However, the invasive nature of the standard pre-surgical investigation contributes to fewer than 1% of patients with PA being offered the chance of a cure. The primary objective of our prospective study of 143 patients with PA ( NCT02945904 ) was to compare the accuracy of a non-invasive test, [11C]metomidate positron emission tomography computed tomography (MTO) scanning, with adrenal vein sampling (AVS) in predicting the biochemical remission of PA and the resolution of hypertension after surgery. A total of 128 patients reached 6- to 9-month follow-up, with 78 (61%) treated surgically and 50 (39%) managed medically. Of the 78 patients receiving surgery, 77 achieved one or more PA surgical outcome criterion for success. The accuracies of MTO at predicting biochemical and clinical success following adrenalectomy were, respectively, 72.7 and 65.4%. For AVS, the accuracies were 63.6 and 61.5%. MTO was not significantly superior, but the differences of 9.1% (95% confidence interval = -6.5 to 24.1%) and 3.8% (95% confidence interval = -11.9 to 9.4) lay within the pre-specified -17% margin for non-inferiority (P = 0.00055 and P = 0.0077, respectively). Of 24 serious adverse events, none was considered related to either investigation and 22 were fully resolved. MTO enables non-invasive diagnosis of unilateral PA.

Use of quantitative cardiovascular magnetic resonance myocardial perfusion mapping for characterization of ischemia in patients with left internal mammary coronary artery bypass grafts.

BACKGROUND: Quantitative myocardial perfusion mapping using cardiovascular magnetic resonance (CMR) is validated for myocardial blood flow (MBF) estimation in native vessel coronary artery disease (CAD). Following coronary artery bypass graft (CABG) surgery, perfusion defects are often detected in territories supplied by the left internal mammary artery (LIMA) graft, but their interpretation and subsequent clinical management is variable. METHODS: We assessed myocardial perfusion using quantitative CMR perfusion mapping in 38 patients with prior CABG surgery, all with angiographically-proven patent LIMA grafts to the left anterior descending coronary artery (LAD) and no prior infarction in the LAD territory. Factors potentially determining MBF in the LIMA-LAD myocardial territory, including the impact of delayed contrast arrival through the LIMA graft were evaluated. RESULTS: Perfusion defects were reported on blinded visual analysis in the LIMA-LAD territory in 27 (71%) cases, despite LIMA graft patency and no LAD infarction. Native LAD chronic total occlusion (CTO) was a strong independent predictor of stress MBF (B = - 0.41, p = 0.014) and myocardial perfusion reserve (MPR) (B = - 0.56, p = 0.005), and was associated with reduced stress MBF in the basal (1.47 vs 2.07 ml/g/min; p = 0.002) but not the apical myocardial segments (1.52 vs 1.87 ml/g/min; p = 0.057). Extending the maximum arterial time delay incorporated in the quantitative perfusion algorithm, resulted only in a small increase (3.4%) of estimated stress MBF. CONCLUSIONS: Perfusion defects are frequently detected in LIMA-LAD subtended territories post CABG despite LIMA patency. Although delayed contrast arrival through LIMA grafts causes a small underestimation of MBF, perfusion defects are likely to reflect true reductions in myocardial blood flow, largely due to proximal native LAD disease.

Prognostic Value of Pulmonary Transit Time and Pulmonary Blood Volume Estimation Using Myocardial Perfusion CMR.

OBJECTIVES: The purpose of this study was to explore the prognostic significance of PTT and PBVi using an automated, inline method of estimation using CMR. BACKGROUND: Pulmonary transit time (PTT) and pulmonary blood volume index (PBVi) (the product of PTT and cardiac index), are quantitative biomarkers of cardiopulmonary status. The development of cardiovascular magnetic resonance (CMR) quantitative perfusion mapping permits their automated derivation, facilitating clinical adoption. METHODS: In this retrospective 2-center study of patients referred for clinical myocardial perfusion assessment using CMR, analysis of right and left ventricular cavity arterial input function curves from first pass perfusion was performed automatically (incorporating artificial intelligence techniques), allowing estimation of PTT and subsequent derivation of PBVi. Association with major adverse cardiovascular events (MACE) and all-cause mortality were evaluated using Cox proportional hazard models, after adjusting for comorbidities and CMR parameters. RESULTS: A total of 985 patients (67% men, median age 62 years [interquartile range (IQR): 52 to 71 years]) were included, with median left ventricular ejection fraction (LVEF) of 62% (IQR: 54% to 69%). PTT increased with age, male sex, atrial fibrillation, and left atrial area, and reduced with LVEF, heart rate, diabetes, and hypertension (model r2 = 0.57). Over a median follow-up period of 28.6 months (IQR: 22.6 to 35.7 months), MACE occurred in 61 (6.2%) patients. After adjusting for prognostic factors, both PTT and PBVi independently predicted MACE, but not all-cause mortality. There was no association between cardiac index and MACE. For every 1 × SD (2.39-s) increase in PTT, the adjusted hazard ratio for MACE was 1.43 (95% confidence interval [CI]: 1.10 to 1.85; p = 0.007). The adjusted hazard ratio for 1 × SD (118 ml/m2) increase in PBVi was 1.42 (95% CI: 1.13 to 1.78; p = 0.002). CONCLUSIONS: Pulmonary transit time (and its derived parameter pulmonary blood volume index), measured automatically without user interaction as part of CMR perfusion mapping, independently predicted adverse cardiovascular outcomes. These biomarkers may offer additional insights into cardiopulmonary function beyond conventional predictors including ejection fraction.

Advanced Imaging Modalities to Monitor for Cardiotoxicity.

OPINION STATEMENT: Early detection and treatment of cardiotoxicity from cancer therapies is key to preventing a rise in adverse cardiovascular outcomes in cancer patients. Over-diagnosis of cardiotoxicity in this context is however equally hazardous, leading to patients receiving suboptimal cancer treatment, thereby impacting cancer outcomes. Accurate screening therefore depends on the widespread availability of sensitive and reproducible biomarkers of cardiotoxicity, which can clearly discriminate early disease. Blood biomarkers are limited in cardiovascular disease and clinicians generally still use generic screening with ejection fraction, based on historical local expertise and resources. Recently, however, there has been growing recognition that simple measurement of left ventricular ejection fraction using 2D echocardiography may not be optimal for screening: diagnostic accuracy, reproducibility and feasibility are limited. Modern cancer therapies affect many myocardial pathways: inflammatory, fibrotic, metabolic, vascular and myocyte function, meaning that multiple biomarkers may be needed to track myocardial cardiotoxicity. Advanced imaging modalities including cardiovascular magnetic resonance (CMR), computed tomography (CT) and positron emission tomography (PET) add improved sensitivity and insights into the underlying pathophysiology, as well as the ability to screen for other cardiotoxicities including coronary artery, valve and pericardial diseases resulting from cancer treatment. Delivering screening for cardiotoxicity using advanced imaging modalities will however require a significant change in current clinical pathways, with incorporation of machine learning algorithms into imaging analysis fundamental to improving efficiency and precision. In the future, we should aspire to personalized rather than generic screening, based on a patient's individual risk factors and the pathophysiological mechanisms of the cancer treatment they are receiving. We should aspire that progress in cardiooncology is able to track progress in oncology, and to ensure that the current 'one size fits all' approach to screening be obsolete in the very near future.

MRI for patients with cardiac implantable electronic devices: simplifying complexity with a 'one-stop' service model.

BACKGROUND: Patients with cardiac pacemakers and defibrillators are disadvantaged because of poor access to MRI scans, leading to late and misdiagnosis particularly for cancer and neurological disease. New technology allied to tested protocols now allows safe MRI scanning of such patients; however, logistical barriers persist. AIM: To deliver a streamlined sustainable service that provides timely MRI scans to patients with cardiac implantable electronic devices (CIEDs). METHODS: Patients requested a 'one-stop' service for MRI, whereby devices could be reprogrammed and scans acquired at a single location and visit. To provide this 'one-stop' service, we trained a team including administrators, physicians, cardiac physiologists and radiographers. A standard protocol was used to prevent unnecessary request refusals and delays to scheduling. Service volume, waiting time and safety were analysed 6 months before and 2 years after service redesign. Waiting times for internal and external inpatient referrals plus time to treatment for patients on a cancer pathway were analysed. RESULTS: 215 MRI scans were performed over 2 years. After service redesign, MRI provision increased six-fold to 20 times the national average with reduced waiting time from 60 to 15 days and no adverse events. Departmental throughput was maintained. 85 (40%) referrals were external. 41 (19%) inpatients were scanned, reducing bed-stay by 3 days for internal referrals. 24 (11%) scans were for suspected cancer, 83% allowed treatment within the national standard of 62 days. There was no preintervention service for either inpatients or suspected cancer investigation. CONCLUSION: Implementation of a 'one-stop' service model to provide MRI for patients with CIEDs is safe, streamlined, scalable and has reduced delays making economic and clinical sense. Protocols and checklists are available at mrimypacemaker.com.

Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis.

BACKGROUND: Left ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis). OBJECTIVES: This study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress. METHODS: Patients with symptomatic, severe AS (n = 181; aortic valve area index 0.4 ± 0.1 cm2/m2) were assessed pre-aortic valve replacement (AVR) by echocardiography (AS severity, diastology), cardiovascular magnetic resonance (CMR) (for volumes, function, and focal or diffuse fibrosis), biomarkers (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T), and the 6-min walk test. CMR was used to measure the extracellular volume fraction (ECV), thereby deriving matrix volume (LV mass × ECV) and cell volume (LV mass × [1 - ECV]). Biopsy excluded occult bystander disease. Assessment was repeated at 1 year post-AVR. RESULTS: At 1 year post-AVR in 116 pacemaker-free survivors (age 70 ± 10 years; 54% male), mean valve gradient had improved (48 ± 16 mm Hg to 12 ± 6 mm Hg; p < 0.001), and indexed LV mass had regressed by 19% (88 ± 26 g/m2 to 71 ± 19 g/m2; p < 0.001). Focal fibrosis by CMR late gadolinium enhancement did not change, but ECV increased (28.2 ± 2.9% to 29.9 ± 4.0%; p < 0.001): this was the result of a 16% reduction in matrix volume (25 ± 9 ml/m2 to 21 ± 7 ml/m2; p < 0.001) but a proportionally greater 22% reduction in cell volume (64 ± 18 ml/m2 to 50 ± 13 ml/m2; p < 0.001). These changes were accompanied by improvement in diastolic function, N-terminal pro-B-type natriuretic peptide, 6-min walk test results, and New York Heart Association functional class. CONCLUSIONS: Post-AVR, focal fibrosis does not resolve, but diffuse fibrosis and myocardial cellular hypertrophy regress. Regression is accompanied by structural and functional improvements suggesting that human diffuse fibrosis is plastic, measurable by CMR and a potential therapeutic target. (Regression of Myocardial Fibrosis After Aortic Valve Replacement; NCT02174471).

Redefining viability by cardiovascular magnetic resonance in acute ST-segment elevation myocardial infarction.

In chronic myocardial infarction (MI), segments with a transmural extent of infarct (TEI) of ≤50% are defined as being viable. However, in the acute phase of an ST-segment elevation myocardial infarction (STEMI), late gadolinium enhancement (LGE) has been demonstrated to overestimate MI size and TEI. We aimed to identify the optimal cut-off of TEI by cardiovascular magnetic resonance (CMR) for defining viability during the acute phase of an MI, using ≤50% TEI at follow-up as the reference standard. 40 STEMI patients reperfused by primary percutaneous coronary intervention (PPCI) underwent a CMR at 4 ± 2 days and 5 ± 2 months. The large majority of segments with 1-25%TEI and 26-50%TEI that were viable acutely were also viable at follow-up (59/59, 100% and 75/82, 96% viable respectively). 56/84(67%) segments with 51-75%TEI but only 4/63(6%) segments with 76-100%TEI were reclassified as viable at follow-up. TEI on the acute CMR scan had an area-under-the-curve of 0.87 (95% confidence interval of 0.82 to 0.91) and ≤75%TEI had a sensitivity of 98% but a specificity of 66% to predict viability at follow-up. Therefore, the optimal cut-off by CMR during the acute phase of an MI to predict viability was ≤75% TEI and this would have important implications for patients undergoing viability testing prior to revascularization during the acute phase.

Residual Myocardial Iron Following Intramyocardial Hemorrhage During the Convalescent Phase of Reperfused ST-Segment-Elevation Myocardial Infarction and Adverse Left Ventricular Remodeling.

BACKGROUND: The presence of intramyocardial hemorrhage (IMH) in ST-segment-elevation myocardial infarction patients reperfused by primary percutaneous coronary intervention has been associated with residual myocardial iron at follow-up, and its impact on adverse left ventricular (LV) remodeling is incompletely understood and is investigated here. METHODS AND RESULTS: Forty-eight ST-segment-elevation myocardial infarction patients underwent cardiovascular magnetic resonance at 4±2 days post primary percutaneous coronary intervention, of whom 40 had a follow-up scan at 5±2 months. Native T1, T2, and T2* maps were acquired. Eight out of 40 (20%) patients developed adverse LV remodeling. A subset of 28 patients had matching T2* maps, of which 15/28 patients (54%) had IMH. Eighteen of 28 (64%) patients had microvascular obstruction on the acute scan, of whom 15/18 (83%) patients had microvascular obstruction with IMH. On the follow-up scan, 13/15 patients (87%) had evidence of residual iron within the infarct zone. Patients with residual iron had higher T2 in the infarct zone surrounding the residual iron when compared with those without. In patients with adverse LV remodeling, T2 in the infarct zone surrounding the residual iron was also higher than in those without (60 [54-64] ms versus 53 [51-56] ms; P=0.025). Acute myocardial infarct size, extent of microvascular obstruction, and IMH correlated with the change in LV end-diastolic volume (Pearson's rho of 0.64, 0.59, and 0.66, respectively; P=0.18 and 0.62, respectively, for correlation coefficient comparison) and performed equally well on receiver operating characteristic curve for predicting adverse LV remodeling (area under the curve: 0.99, 0.94, and 0.95, respectively; P=0.19 for receiver operating characteristic curve comparison). CONCLUSIONS: The majority of ST-segment-elevation myocardial infarction patients with IMH had residual myocardial iron at follow-up. This was associated with persistently elevated T2 values in the surrounding infarct tissue and adverse LV remodeling. IMH and residual myocardial iron may be potential therapeutic targets for preventing adverse LV remodeling in reperfused ST-segment-elevation myocardial infarction patients.

T1 mapping: non-invasive evaluation of myocardial tissue composition by cardiovascular magnetic resonance.

Cardiovascular magnetic resonance is an important tool for patient care and is the best test for myocardial structure and function. Ischemia and scar imaging also provide key insights and focus attention on heart muscle - the site of most cardiac diseases. New ways of measuring abnormal muscle have been developed, including T1 mapping. Abnormal signal can be distinguished either without contrast (native T1), or post-contrast (extracellular volume measurement). Large changes occur in rare diseases (cardiac amyloidosis, Anderson-Fabry disease and iron overload) even at an early stage, while more subtle changes are seen in diffuse fibrosis where a robust test would be of major impact. This review presents the potential future clinical utility of T1 mapping - a technology to watch.