Regional aortic distensibility and its relationship with age and aortic stenosis: a computed tomography study.

Aortic distensibility (AD) decreases with age and increased aortic stiffness is independently associated with adverse cardiovascular outcomes. The association of severe aortic stenosis (AS) with AD in different aortic regions has not been evaluated. Elderly subjects with severe AS and a cohort of patients without AS of similar age were studied. Proximal aortic cross-sectional-area changes during the cardiac cycle were determined using retrospective-ECG-gating on 128-detector row computed-tomography. Using oscillometric-brachial-blood-pressure measurements, the AD at the ascending-aorta (AA), proximal-descending-aorta (PDA) and distal-descending-aorta (DDA) was determined. Linear mixed effects modelling was used to determine the association of age and aortic stenosis on regional AD. 102 patients were evaluated: 36 AS patients (70-85 years), 24 AS patients (>85 years) and 42 patients without AS (9 patients <50 years, 20 patients between 51-70 years and 13 patients 70-85 years). When comparing patients 70-85 years, AA distensibility was significantly lower in those with AS compared to those without AS (0.9 ± 0.9 vs. 1.4 ± 1.1, P = 0.03) while there was no difference in the PDA (1.0 ± 1.1 vs. 1.0 ± 1.2, P = 0.26) and DDA (1.1 ± 1.2 vs. 1.2 ± 0.8, P = 0.97). In patients without AS, AD decreased with age in all aortic regions (P < 0.001). The AA in patients <50 years were the most distensible compared to other aortic regions. There is regional variation in aortic distensibility with aging. Patients with aortic stenosis demonstrated regional differences in aortic distensibility with lower distensibility demonstrated in the proximal ascending aorta compared to an age-matched cohort.

Incremental benefits of repeated mesenchymal stromal cell administration compared with solitary intervention after myocardial infarction.

BACKGROUND AIMS: Traditionally, stem cell therapy for myocardial infarction (MI) has been administered as a single treatment in the acute or subacute period after MI. These time intervals coincide with marked differences in the post-infarct myocardial environment, raising the prospect that repeat cell dosing could provide incremental benefit beyond a solitary intervention. This prospect was evaluated with the use of mesenchymal stromal cells (MSCs). METHODS: Three groups of rats were studied. Single-therapy and dual-therapy groups received allogeneic, prospectively isolated MSCs (1 × 10(6) cells) by trans-epicardial injection immediately after MI, with additional dosing 1 week later in the dual-therapy cohort. Control animals received cryopreservant solution only. Left ventricular (LV) dimensions and ejection fraction (EF) were assessed by cardiac magnetic resonance immediately before MI and at 1, 2 and 4 weeks after MI. RESULTS: Immediate MSC treatment attenuated early myocardial damage with EF of 35.3 ± 3.1% (dual group, n = 12) and 35.2 ± 2.2% (single group, n = 15) at 1 week after MI compared with 22.1 ± 1.9% in controls (n = 17, P < 0.01). In animals receiving a second dose of MSCs, EF increased to 40.7 ± 3.1% by week 4, which was significantly higher than in the single-therapy group (EF 35.9 ± 1.8%, P < 0.05). Dual MSC treatment was also associated with greater myocardial mass and arteriolar density, with trends toward reduced myocardial fibrosis. These incremental benefits were especially observed in remote (non-infarct) segments of LV myocardium. CONCLUSIONS: Repeated stem cell intervention in both the acute and the sub-acute period after MI provides additional improvement in ventricular function beyond solitary cell dosing, largely owing to beneficial changes remote to the area of infarction.

Impact of timing and dose of mesenchymal stromal cell therapy in a preclinical model of acute myocardial infarction.

BACKGROUND: Although mesenchymal stem/stromal cells (MSC) have shown therapeutic promise after myocardial infarction (MI), the impact of cell dose and timing of intervention remains uncertain. We compared immediate and deferred administration of 2 doses of MSC in a rat model of MI. METHODS AND RESULTS: Sprague-Dawley rats were used. Allogeneic prospectively isolated MSC ("low" dose 1 × 10(6) or "high" dose 2 × 10(6) cells) were delivered by transepicardial injection immediately after MI ("early-low," "early-high"), or 1 week later ("late-low," "late-high"). Control subjects received cryopreservant solution alone. Left ventricular dimensions and ejection fraction (EF) were assessed by cardiac magnetic resonance. All 4 MSC-treatment cohorts demonstrated higher EF than control animals 4 weeks after MI (P values <.01 to <.0001), with function most preserved in the early-high group (absolute reduction in EF from baseline: control 39.1 ± 1.7%, early-low 26.5 ± 3.2%, early-high 7.9 ± 2.6%, late-low 19.6 ± 3.5%, late-high 17.9 ± 4.0%). Cell treatment also attenuated left ventricular dilatation and fibrosis and augmented left ventricular mass, systolic wall thickening (SWT), and microvascular density. Although early intervention selectively increased SWT and vascular density in the infarct territory, delayed treatment caused greater benefit in remote (noninfarct) myocardium. All outcomes demonstrated dose dependence for early MSC treatment, but not for later cell administration. CONCLUSIONS: The nature and magnitude of benefit from MSC after acute MI is strongly influenced by timing of cell delivery, with dose dependence most evident for early intervention. These novel insights have potential implications for cell therapy after MI in human patients.

Relationship of aortic annular eccentricity and paravalvular regurgitation post transcatheter aortic valve implantation with CoreValve.

BACKGROUND: Significant paravalvular aortic regurgitation (PAR) after transcatheter aortic valve implantation (TAVI) is associated with negative clinical consequences. We hypothesize that increased eccentricity of the aortic annulus is associated with greater PAR. METHODS: Patients with severe aortic stenosis underwent multidetector computed tomography (MDCT) before successful TAVI with the Medtronic CoreValve bioprosthesis. The smallest (D(min)) and largest (D(max)) orthogonal diameters in the basal ring of the aortic annulus were determined. We defined circularity of aortic annulus using the eccentricity index (1 - D(min)/D(max)). The primary endpoint was early occurrence of significant PAR, defined as > grade II PAR by postprocedural aortography. RESULTS: Eighty-four patients, mean age 83 ± 4 years with a mean aortic valve area of 0.7 ± 0.2 cm² were included. Twenty patients had postprocedural PAR > grade II. Using a receiver operating characteristic (ROC) analysis, eccentricity index correlated with significant PAR (AUC = 0.834; P=.034). A retrospectively determined eccentricity index cut-off of >0.25 was related to significant PAR with a sensitivity of 80%, specificity of 86%, and negative predictive value of 95% (P<.001). On univariate logistic regression, eccentricity index of >0.25 (P<.001) and device implantation depth (P=.015) correlated with significant PAR, while other parameters such as annular calcification and cover index did not. On multivariate analysis including only parameters with P<.1 on univariate analysis, eccentricity index >0.25 was the sole independent predictor of significant PAR. CONCLUSION: Eccentricity index is related to significant PAR after TAVI with Medtronic CoreValve. Further larger studies are required to determine the utility of this novel index in screening suitable patients for this procedure.

Prognostic value of adenosine stress perfusion cardiac MRI with late gadolinium enhancement in an intermediate cardiovascular risk population.

BACKGROUND: The high diagnostic accuracy of adenosine stress cardiac magnetic resonance (AS-CMR) for detecting coronary artery stenoses, with high sensitivity and specificity, is well documented. Prognostic data, particularly in non-low risk study populations and for greater than 12 months of follow up, is however lacking or variable in its findings. We present prognostic data, in an intermediate cardiovascular risk cohort undergoing adenosine stress perfusion CMR, over approximately 2 years of follow up. METHODS: The study population comprised 362 patients referred for a clinically indicated stress CMR and included patients with proven coronary artery disease (CAD; n=157) or unknown CAD status, yet an intermediate cardiovascular risk profile (n=205). Perfusion imaging was performed at stress (adenosine 140 µg/kg/min) and rest on a 1.5 T system. Patient records and state-wide hospital databases were reviewed. Major adverse cardiac events--death, myocardial infarction, revascularisation or ischaemic hospitalisation--were evaluated over a median follow up of 22 months. RESULTS: Of the 362 cases, 90 had a stress perfusion CMR positive for ischaemia and experienced a MACE rate of 24%. Of the 272 negative CMR scans, 225 were also negative for late gadolinium enhancement, and in this group MACE was encountered in only 6 (2.7%) patients. Accordingly a negative stress CMR afforded a freedom from MACE of 97.3%. Freedom from death/myocardial infarction was 99.6%. CONCLUSIONS: In patients with confirmed coronary artery disease or at intermediate risk for cardiovascular events, a negative stress perfusion CMR is associated with an excellent prognosis over nearly 2 years of follow up.

Electro-mechanical characteristics of myocardial infarction border zones and ventricular arrhythmic risk: novel insights from grid-tagged cardiac magnetic resonance imaging.

OBJECTIVE: To investigate whether grid-tag myocardial strain evaluation can characterise 'border-zone' peri-infarct region and identify patients at risk of ventricular arrhythmia as the peri-infarct myocardial zone may represent an important contributor to ventricular arrhythmia following ST-segment elevation myocardial infarction (STEMI). METHODS: Forty-five patients with STEMI underwent cardiac magnetic resonance (CMR) imaging on days 3 and 90 following primary percutaneous coronary intervention (PCI). Circumferential peak circumferential systolic strain (CS) and strain rate (CSR) were calculated from grid-tagged images. Myocardial segments were classified into 'infarct', 'border-zone', 'adjacent' and 'remote' regions by late-gadolinium enhancement distribution. The relationship between CS and CSR and these distinct myocardial regions was assessed. Ambulatory Holter monitoring was performed 14 days post myocardial infarction (MI) to estimate ventricular arrhythmia risk via evaluation of heart-rate variability (HRV). RESULTS: We analysed 1,222 myocardial segments. Remote and adjacent regions had near-normal parameters of CS and CSR. Border-zone regions had intermediate CS (-9.0 ± 4.6 vs -5.9 ± 7.4, P < 0.001) and CSR (-86.4 ± 33.3 vs -73.5 ± 51.4, P < 0.001) severity compared with infarct regions. Patients with 'border-zone' peri-infarct regions had reduced very-low-frequency power on HRV analysis, which is a surrogate for ventricular arrhythmia risk (P = 0.03). CONCLUSION: Grid-tagged CMR-derived myocardial strain accurately characterises the mechanical characteristics of 'border-zone' peri-infarct region. Presence of 'border-zone' peri-infarct region correlated with a surrogate marker of heightened arrhythmia risk following STEMI. KEY POINTS: • Grid-tagged cardiac magnetic resonance (CMR) offers new insights into myocardial mechanical function. • Grid-tagged CMR identified different characteristics in 'border-zone' and 'adjacent' peri-infarct myocardial regions. • Reduced very-low-frequency (VLF) power is associated with arrhythmic and mortality risk. • The presence of 'border-zone' peri-infarct region correlated with reduced VLF power.

The role of cardiac magnetic resonance imaging following acute myocardial infarction.

BACKGROUND: Advances in the management of myocardial infarction have resulted in substantial reductions in morbidity and mortality. METHODS: However, after acute treatment a number of diagnostic and prognostic questions often remain to be answered, whereby cardiac imaging plays an essential role. RESULTS: For example, some patients will sustain early mechanical complications after infarction, while others may develop significant ventricular dysfunction. Furthermore, many individuals harbour a significant burden of residual coronary disease for which clarification of functional ischaemic status and/or viability of the suspected myocardial territory is required. CONCLUSION: Cardiac magnetic resonance (CMR) imaging is well positioned to fulfil these requirements given its unparalleled capability in evaluating cardiac function, stress ischaemia testing and myocardial tissue characterisation. This review will focus on the utility of CMR in resolving diagnostic uncertainty, evaluating early complications following myocardial infarction, assessing inducible ischaemia, myocardial viability, ventricular remodelling and the emerging role of CMR-derived measures as endpoints in clinical trials. KEY POINTS: Cardiac magnetic resonance (CMR) imaging identifies early complications after myocardial infarction. • Adenosine stress CMR can reliably assess co-existing disease in non-culprit arteries. • Assessment of infarct size and microvascular obstruction a robust prognostic indicator. • Assessment of myocardial viability is important to guide revascularisation decision-making.

Aortic annulus dimension assessment by computed tomography for transcatheter aortic valve implantation: differences between systole and diastole.

Accurate assessment of aortic annular dimensions is essential for successful transcatheter aortic valve implantation (TAVI). Annular dimensions are conventionally measured in mid-systole by multidetector computed tomography (MDCT), echocardiography and angiography. Significant differences in systolic and diastolic aortic annular dimensions have been demonstrated in cohorts without aortic stenosis (AS), but it is unknown whether similar dynamic variation in annular dimensions exists in patients with severe calcific AS in whom aortic compliance is likely to be substantially reduced. We investigated the variation in aortic annular dimensions between systole and diastole in patients with severe calcific AS. Patients with severe calcific AS referred for TAVI were evaluated by 128-slice MDCT. Aortic annular diameter was measured during diastole and systole in the modified coronal, modified sagittal, and basal ring planes (maximal, minimal and mean diameters). Differences between systole and diastole were analysed by paired t test. Fifty-nine patients were included in the analysis. Three of the five aortic dimensions measured increased significantly during systole. The largest change was a 0.75 mm (3.4%) mean increase in the minimal diameter of the basal ring during systole (p = 0.004). This corresponds closely to the modified sagittal view, which also increased by mean 0.42 mm (1.9%) during systole (p = 0.008). There was no significant change in the maximal diameter of the basal ring or the modified coronal view during systole (p > 0.05). There is a small magnitude but statistically significant difference in aortic annulus dimensions of patients with severe AS referred for TAVI when measured in diastole and systole. This small difference is unlikely to alter clinical decisions regarding prosthesis size or suitability for TAVI.

An unusual cause of cardiac failure.

Left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized by deep intertrabecular recesses communicating with the main ventricular chamber. Cardiac magnetic resonance offers high spatial resolution, and thereby substantial aptitude for the diagnosis of LVNC. Additional clinically relevant information, including thrombus and myocardial fibrosis evaluation, can be readily acquired. These images demonstrate classical LVNC morphology in conjunction with its potential sequelae.

Cardiac magnetic resonance derived late microvascular obstruction assessment post ST-segment elevation myocardial infarction is the best predictor of left ventricular function: a comparison of angiographic and cardiac magnetic resonance derived measurements.

Microvascular obstruction (MVO) is a strong independent predictor of left ventricular remodelling and mortality following ST-segment elevation myocardial infarction (STEMI). Microvascular obstruction can be identified at angiography or with gadolinium-enhanced cardiac MRI (CMR). First-pass perfusion CMR also allows a novel quantitative evaluation of myocardial blood flow (MBF) that might provide superior predictive data in the assessment of MVO. We sought to compare angiographic and CMR derived methodologies in the assessment of MVO to determine the optimal methodology that best predicts the surrogate outcome marker of left ventricular function post STEMI. Following primary-PCI angiographic assessment of 'no-reflow' with TIMI myocardial perfusion grade (TMPG) and myocardial blush grade (MBG) were documented. Assessment of CMR derived MVO was assessed on day 3, with MVO on first-pass perfusion imaging termed 'early MVO' and on late gadolinium enhancement, 'late MVO'. Furthermore on the same day 3 CMR scan, myocardial blood flow in the infarct region was quantified at adenosine stress and rest utilizing standard perfusion imaging sequences. Assessment of remodelling, structure and function was undertaken via standard CMR imaging assessment on day 90 post-STEMI and was used as the surrogate marker for long term clinical outcome. Forty patients (age 59 ± 12 years, 84% males) were appraised. Late MVO had the strongest correlation with LVEF at 90 days compared to the CMR parameters of early MVO, stress infarct region MBF and rest infarct region MBF (r = -0.754, r = -0.588, r = 0.595 and r = 0.345 respectively). Of the angiographic parameters used to assess MVO, TMPG had the strongest relationship with MVO when assessed via CMR. Myocardial blush grade however showed no relationship to CMR derived assessment of MVO. On multivariate analysis, of all angiographic and CMR variables, late MVO was the strongest predictor of LVEF at 90 days (p = 0.004). Cardiac magnetic resonance imaging derived assessment of microvascular obstruction on late gadolinium enhancement strongly predicts left ventricular function following STEMI at 90 days.