Prognostic Significance of LGE by CMR in Aortic Stenosis Patients Undergoing Valve Replacement

Background— Left ventricular (LV) remodeling after acute myocardial infarction is associated with adverse prognosis. MicroRNAs (miRNAs) regulate the expression of several genes involved in LV remodeling. Our aim was to identify miRNAs associated with LV remodeling after acute myocardial infarction.

Methods and Results— We studied 90 patients after first ST-segment–elevation acute myocardial infarction. A derivation cohort consisted of 60 patients characterized by echocardiography predischarge and at 6-month follow-up. Thirty patients characterized by magnetic resonance imaging predischarge and at 4-month follow-up were the validation cohort. Remodeling was defined as an increase in LV end-diastolic volume (ΔEDV>0) between discharge and follow-up. Circulating miRNAs were measured by microarrays and polymerase chain reaction. Using a systems-based approach, we identified several miRNAs potentially involved in LV remodeling. In the derivation cohort, one of these miRNAs, miR-150, was downregulated in patients with remodeling (ΔEDV>0) compared with patients without remodeling (ΔEDV≤0). In the validation cohort, patients with remodeling had 2-fold lower levels of miR-150 than those without ( P =0.03). miR-150 outperformed N-terminal pro-brain natriuretic peptide to predict remodeling (area under the receiver-operating characteristic curve of 0.74 and 0.60, respectively). miR-150 reclassified 54% (95% confidence interval, 5–102; P =0.03) of patients misclassified by N-terminal pro-brain natriuretic peptide and 59% (95% confidence interval, 9–108; P =0.02) of patients misclassified by a multiparameter clinical model, including age, sex, and admission levels of troponin I, creatine kinase, and N-terminal pro-brain natriuretic peptide.

Conclusions— Low circulating levels of miR-150 are associated with LV remodeling after first ST-segment–elevation acute myocardial infarction. miR-150 has potential as a novel biomarker in this setting.

MicroRNA-150 A Novel Marker of Left Ventricular Remodeling After Acute Myocardial Infarction

Background Recent recommendations suggest that in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation and coexistent significant coronary artery disease, the latter should be treated before the index procedure; however, the evidence basis for such an approach remains limited. We performed a systematic review and meta‐analysis to study the clinical outcomes of patients with coronary artery disease who did or did not undergo revascularization prior to transcatheter aortic valve implantation. Methods and Results We conducted a search of Medline and Embase to identify studies evaluating patients who underwent transcatheter aortic valve implantation with or without percutaneous coronary intervention. Random‐effects meta‐analyses with the inverse variance method were used to estimate the rate and risk of adverse outcomes. Nine studies involving 3858 participants were included in the meta‐analysis. Patients who underwent revascularization with percutaneous coronary intervention had a higher rate of major vascular complications (odd ratio [OR]: 1.86; 95% confidence interval [CI], 1.33–2.60; P =0.0003) and higher 30‐day mortality (OR: 1.42; 95% CI, 1.08–1.87; P =0.01). There were no differences in effect estimates for 30‐day cardiovascular mortality (OR: 1.03; 95% CI, 0.35–2.99), myocardial infarction (OR: 0.86; 95% CI, 0.14–5.28), acute kidney injury (OR: 0.89; 95% CI, 0.42–1.88), stroke (OR: 1.07; 95% CI, 0.38–2.97), or 1‐year mortality (OR: 1.05; 95% CI, 0.71–1.56). The timing of percutaneous coronary intervention (same setting versus a priori) did not negatively influence outcomes. Conclusions Our analysis suggests that revascularization before transcatheter aortic valve implantation confers no clinical advantage with respect to several patient‐important clinical outcomes and may be associated with an increased risk of major vascular complications and 30‐day mortality. In the absence of definitive evidence, careful evaluation of patients on an individual basis is of paramount importance to identify patients who might benefit from elective revascularization.

Transcatheter Aortic Valve Implantation With or Without Percutaneous Coronary Artery Revascularization Strategy: A Systematic Review and Meta‐Analysis

Aims Angiotensin-converting enzyme (ACE) inhibitors improve left ventricular (LV) remodelling and outcome in heart failure and hypertensive heart disease. They may be similarly beneficial in patients with aortic stenosis (AS), but historical safety concerns have limited their use, and no prospective clinical trials exist.

Methods and results We conducted a prospective, randomized, double-blind, placebo-controlled trial in 100 patients with moderate or severe asymptomatic AS to examine the physiological effects of ramipril, particularly LV mass (LVM) regression. Subjects were randomized to ramipril 10 mg daily ( n = 50) or placebo ( n = 50) for 1 year, and underwent cardiac magnetic resonance, echocardiography, and exercise testing at 0, 6, and 12 months, with follow-up data available in 77 patients. There was a modest but progressive reduction in LVM (the primary end point) in the ramipril group vs. the placebo group (mean change −3.9 vs. +4.5 g, respectively, P = 0.0057). There were also trends towards improvements in myocardial physiology: the ramipril group showed preserved tissue Doppler systolic velocity compared with placebo (+0.0 vs. −0.5 cm/s, P = 0.04), and a slower rate of progression of the AS (valve area 0.0 cm2 in the ramipril group vs. −0.2 cm2 in the placebo arm, P = 0.067). There were no significant differences in major adverse cardiac events.

Conclusion ACE inhibition leads to a modest, but progressive reduction in LVM in asymptomatic patients with moderate–severe AS compared with placebo, with trends towards improvements in myocardial physiology and slower progression of valvular stenosis. A larger clinical outcome trial to confirm these findings and explore their clinical relevance is required.

[10.1093/ehjci/jev082][1]

 [1]: /lookup/doi/10.1093/ehjci/jev082

A prospective, double-blind, randomized controlled trial of the angiotensin-converting enzyme inhibitor Ramipril In Aortic Stenosis (RIAS trial).

Myocardial T1 relaxation times have been reported to be markedly abnormal in diverse myocardial pathologies, ascribed to interstitial changes, evaluated by T1 mapping and calculation of extracellular volume (ECV). T1 mapping is sensitive to myocardial water content of both intra- and extracellular in origin, but the effect of intravascular compartment changes on T1 has been largely neglected. We aimed to assess the role of intravascular compartment on native (pre-contrast) T1 values by studying the effect of adenosine-induced vasodilatation in patients with severe aortic stenosis (AS) before and after aortic valve replacement (AVR). 42 subjects (26 patients with severe AS without obstructive coronary artery disease and 16 controls) underwent cardiovascular magnetic resonance at 3 T for native T1-mapping (ShMOLLI), first-pass perfusion (myocardial perfusion reserve index-MPRI) at rest and during adenosine stress, and late gadolinium enhancement (LGE). AS patients had increased resting myocardial T1 (1196 ± 47 ms vs. 1168 ± 27 ms, p = 0.037), reduced MPRI (0.92 ± 0.31 vs. 1.74 ± 0.32, p < 0.001), and increased left ventricular mass index (LVMI) and LGE volume compared to controls. During adenosine stress, T1 in AS was similar to controls (1240 ± 51 ms vs. 1238 ± 54 ms, p = 0.88), possibly reflecting a similar level of maximal coronary vasodilatation in both groups. Conversely, the T1 response to stress was blunted in AS (ΔT1 3.7 ± 2.7% vs. 6.0 ± 4.2% in controls, p = 0.013). Seven months after AVR (n = 16) myocardial T1 and response to adenosine stress recovered towards normal. Native T1 values correlated with reduced MPRI, aortic valve area, and increased LVMI. Our study suggests that native myocardial T1 values are not only influenced by interstitial and intracellular water changes, but also by changes in the intravascular compartment. Performing T1 mapping during or soon after vasodilator stress may affect ECV measurements given that hyperemia alone appears to substantially alter T1 values.

/pdf/adenosine-stress-native-t1-mapping-in-severe-aortic-stenosis-1titpt2jes.pdf

Adenosine stress native T1 mapping in severe aortic stenosis: evidence for a role of the intravascular compartment on myocardial T1 values

Objectives The purpose of this study was to assess the functional significance of cardiac magnetic resonance (CMR) measures of left ventricular (LV) remodeling and myocardial perfusion reserve (MPR) in patients with severe aortic stenosis (AS), without obstructive coronary artery disease. Background Measures of stenosis severity do not correlate well with exercise intolerance in AS. LV remodeling in AS is associated with myocardial fibrosis and impaired MPR. The functional significance and determinants of MPR in AS are unclear. Methods Forty-six patients with isolated severe AS were prospectively studied before aortic valve replacement. The following investigations were undertaken: cardiopulmonary exercise testing to measure aerobic exercise capacity (peak VO2); CMR to assess left ventricular mass index (LVMI), myocardial fibrosis with late gadolinium enhancement (LGE), myocardial blood flow (MBF), and MPR; and transthoracic echocardiography to assess stenosis severity and diastolic function. Results Peak VO2 was associated with sex (β = −0.41), age (β = −0.32), MPR (β = 0.45), resting MBF (β = −0.53), and septal transmitral flow velocity to annular velocity ratio (E/E′) (β = −0.34), but not with LVMI, LGE, or echocardiographic measures of AS severity. On stepwise regression analysis, only MPR was independently associated with age- and sex-corrected peak VO2 (β = 0.46, p = 0.001). MPR was also inversely related to New York Heart Association functional class (p = 0.001). Univariate associations with MPR were sex (β = 0.38, p = 0.02), septal E/E′ (β = −0.30, p = 0.03), peak aortic valve velocity (β = −0.34, p = 0.02), LVMI (β = −0.51, p Conclusions CMR-quantified MPR is independently associated with aerobic exercise capacity in severe AS. LV remodeling appears to be a more important determinant of impaired MPR than stenosis severity per se. Further work is required to determine how CMR assessment of MPR can aid clinical management of patients with AS.

Determinants and Functional Significance of Myocardial Perfusion Reserve in Severe Aortic Stenosis

Objective The use of stress cardiovascular MR (CMR) to evaluate myocardial ischaemia has increased significantly over recent years. We aimed to assess the indications, incidental findings, tolerance, safety and accuracy of stress CMR in routine clinical practice. Methods We retrospectively examined all stress CMR studies performed at our tertiary referral centre over a 20-month period. Patients were scanned at 1.5 T, using a standardised protocol with routine imaging for late gadolinium enhancement. Angiograms of patients were assessed by an interventional cardiologist blinded to the CMR data. Results 654 patients were scanned (mean age 65±29 years; 63 inpatients; 9.6%). 14% of patients had incidental extracardiac findings, the commonest being liver or renal cysts (6%) and pulmonary nodules (4%). 639 patients (97.7%) received intravenous adenosine, 10 received intravenous dobutamine and 5 patients had both. Of the 15 patients who received dobutamine, 12 had no side-effects/complications, 2 experienced nau...

/pdf/stress-cardiovascular-mr-in-routine-clinical-practice-tmv8198p7d.pdf

Benjamin Grundy

Papers

Determinants and Functional Significance of Myocardial Perfusion Reserve in Severe Aortic Stenosis

Stress cardiovascular MR in routine clinical practice: referral patterns, accuracy, tolerance, safety and incidental findings