Myocardial perfusion in cardiac amyloidosis.

AIMS: Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis and preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage. The aims of this study were to assess the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment. METHODS AND RESULTS: Ninety-three patients with cardiac amyloidosis (CA) (light-chain amyloidosis n = 42, transthyretin amyloidosis n = 51) and 97 without CA (three-vessel coronary disease [3VD] n = 47, unobstructed coronary arteries n = 26, healthy volunteers [HV] n = 24) underwent quantitative stress perfusion CMR with myocardial blood flow (MBF) mapping. Twenty-four myocardial biopsies and three explanted hearts with CA were analysed histopathologically. Stress MBF was severely reduced in patients with CA with lower values than patients with 3VD, unobstructed coronary arteries and HV (CA: 1.04 ± 0.51 ml/min/g, 3VD: 1.35 ± 0.50 ml/min/g, unobstructed coronary arteries: 2.92 ± 0.52 ml/min/g, HV: 2.91 ± 0.73 ml/min/g; CA vs. 3VD p = 0.011, CA vs. unobstructed coronary arteries p < 0.001, CA vs. HV p < 0.001). Myocardial perfusion abnormalities correlated with amyloid burden, systolic and diastolic function, structural parameters and blood biomarkers (p < 0.05). Biopsies demonstrated abnormal vascular endothelial growth factor staining in cardiomyocytes and endothelial cells, which may be related to hypoxia conditions. Amyloid infiltration in intramural arteries was associated with severe lumen reduction and severe reduction in capillary density. CONCLUSION: Cardiac amyloidosis is associated with severe inducible myocardial ischaemia demonstrable by histology and CMR stress perfusion mapping. Histological evaluation indicates a complex pathophysiology, where in addition to systolic and diastolic dysfunction, amyloid infiltration of the epicardial arteries and disruption and rarefaction of the capillaries play a role in contributing to myocardial ischaemia.

Quantitative cardiovascular magnetic resonance myocardial perfusion mapping to assess hyperaemic response to adenosine stress.

AIMS: Assessment of hyperaemia during adenosine stress cardiovascular magnetic resonance (CMR) remains a clinical challenge with lack of a gold-standard non-invasive clinical marker to confirm hyperaemic response. This study aimed to validate maximum stress myocardial blood flow (SMBF) measured using quantitative perfusion mapping for assessment of hyperaemic response and compare this to current clinical markers of adenosine stress. METHODS AND RESULTS: Two hundred and eighteen subjects underwent adenosine stress CMR. A derivation cohort (22 volunteers) was used to identify a SMBF threshold value for hyperaemia. This was tested in a validation cohort (37 patients with suspected coronary artery disease) who underwent invasive coronary physiology assessment on the same day as CMR. A clinical cohort (159 patients) was used to compare SMBF to other physiological markers of hyperaemia [splenic switch-off (SSO), heart rate response (HRR), and blood pressure (BP) fall]. A minimum SMBF threshold of 1.43 mL/g/min was derived from volunteer scans. All patients in the coronary physiology cohort demonstrated regional maximum SMBF (SMBFmax) >1.43 mL/g/min and invasive evidence of hyperaemia. Of the clinical cohort, 93% had hyperaemia defined by perfusion mapping compared to 71% using SSO and 81% using HRR. There was no difference in SMBFmax in those with or without SSO (2.58 ± 0.89 vs. 2.54 ± 1.04 mL/g/min, P = 0.84) but those with HRR had significantly higher SMBFmax (2.66 1.86 mL/g/min, P < 0.001). HRR >15 bpm was superior to SSO in predicting adequate increase in SMBF (AUC 0.87 vs. 0.62, P < 0.001). CONCLUSION: Adenosine-induced increase in myocardial blood flow is accurate for confirmation of hyperaemia during stress CMR studies and is superior to traditional, clinically used markers of adequate stress such as SSO and BP response.

Automated Pixel-Wise Quantitative Myocardial Perfusion Mapping by CMR to Detect Obstructive Coronary Artery Disease and Coronary Microvascular Dysfunction: Validation Against Invasive Coronary Physiology.

OBJECTIVES: This study sought to assess the performance of cardiovascular magnetic resonance (CMR) myocardial perfusion mapping against invasive coronary physiology reference standards for detecting coronary artery disease (CAD, defined by fractional flow reserve [FFR] ≤0.80), microvascular dysfunction (MVD) (defined by index of microcirculatory resistance [IMR] ≥25) and the ability to differentiate between the two. BACKGROUND: Differentiation of epicardial (CAD) and MVD in patients with stable angina remains challenging. Automated in-line CMR perfusion mapping enables quantification of myocardial blood flow (MBF) to be performed rapidly within a clinical workflow. METHODS: Fifty patients with stable angina and 15 healthy volunteers underwent adenosine stress CMR at 1.5T with quantification of MBF and myocardial perfusion reserve (MPR). FFR and IMR were measured in 101 coronary arteries during subsequent angiography. RESULTS: Twenty-seven patients had obstructive CAD and 23 had nonobstructed arteries (7 normal IMR, 16 abnormal IMR). FFR positive (epicardial stenosis) areas had significantly lower stress MBF (1.47 ± 0.48 ml/g/min) and MPR (1.75 ± 0.60) than FFR-negative IMR-positive (MVD) areas (stress MBF: 2.10 ± 0.35 ml/g/min; MPR: 2.41 ± 0.79) and normal areas (stress MBF: 2.47 ± 0.50 ml/g/min; MPR: 2.94 ± 0.81). Stress MBF ≤1.94 ml/g/min accurately detected obstructive CAD on a regional basis (area under the curve: 0.90; p < 0.001). In patients without regional perfusion defects, global stress MBF <1.82 ml/g/min accurately discriminated between obstructive 3-vessel disease and MVD (area under the curve: 0.94; p < 0.001). CONCLUSIONS: This novel automated pixel-wise perfusion mapping technique can be used to detect physiologically significant CAD defined by FFR, MVD defined by IMR, and to differentiate MVD from multivessel coronary disease. A CMR-based diagnostic algorithm using perfusion mapping for detection of epicardial disease and MVD warrants further clinical validation.

Functional coronary stenosis severity assessed from the mean pressure gradient-velocity relationship obtained by contrast medium-induced submaximal hyperaemia.

AIMS: First, to establish the diagnostic performance of the pressure gradient at a standardised mean velocity (dPv) as derived from the cycle-averaged stenosis pressure gradient-velocity (dP-v) relationship obtained by administration of adenosine and, second, to determine whether dPv can be assessed from contrast medium-induced submaximal hyperaemia. METHODS AND RESULTS: Distal coronary pressure and velocity were simultaneously recorded in 64 patients during the response to intracoronary injection of adenosine. dPv was assessed at velocities between 20 and 50 cm/s. The pressure gradient at a mean flow velocity of 30 cm/s (dPv30) yielded an excellent diagnostic performance against FFR ≤0.8 (area under the curve 0.96; sensitivity 84%; specificity 96%; accuracy 89%). In a subgroup of 21 patients, measurements were repeated throughout contrast medium-induced reactive hyperaemia. Peak velocity and pressure gradient were lower compared to adenosine, but the course of the corresponding dP-v relationships coincided very well over the common velocity range, with no difference in dPv30. CONCLUSIONS: dPv30 reliably detects functionally significant coronary lesions. It derives from stenosis haemodynamics and can be obtained with submaximal hyperaemia, such as following injection of contrast medium, thereby obviating the maximal vasodilation by adenosine required for FFR or other established hyperaemic parameters of functional stenosis severity.

Hemodynamic response to intravenous adenosine and its effect on fractional flow reserve assessment: results of the Adenosine for the Functional Evaluation of Coronary Stenosis Severity (AFFECTS) study.

BACKGROUND: We studied the hemodynamic response to intravenous adenosine on calculation of fractional flow reserve (FFR). Intravenous adenosine is widely used to achieve conditions of stable hyperemia for measurement of FFR. However, intravenous adenosine affects both systemic and coronary vascular beds differentially. METHODS AND RESULTS: A total of 283 patients (310 coronary stenoses) underwent coronary angiography with FFR using intravenous adenosine 140 mcg/kg per minute via a central femoral vein. Offline analysis was performed to calculate aortic (Pa), distal intracoronary (Pd), and reservoir (Pr) pressure at baseline, peak, and stable hyperemia. Seven different hemodynamic patterns were observed according to Pa and Pd change at peak and stable hyperemia. The average time from baseline to stable hyperemia was 68.2±38.5 seconds, when both ΔPa and ΔPd were decreased (ΔPa, -10.2±10.5 mm Hg; ΔPd, -18.2±10.8 mm Hg; P<0.001 for both). The fall in Pa closely correlated with the reduction in peripheral Pr (ΔPr, -12.9±15.7 mm Hg; P<0.001; r=0.9; P<0.001). ΔPa and ΔPd were closely related under conditions of peak (r=0.75; P<0.001) and stable hyperemia (r=0.83; P<0.001). On average, 56% (10.2 mm Hg) of the reduction in Pd was because of fall in Pa. FFR lesion classification changed in 9% using an FFR threshold of ≤0.80 and 5.2% with FFR threshold <0.75 when comparing Pd/Pa at peak and stable hyperemia. CONCLUSIONS: Intravenous adenosine results in variable changes in systemic blood pressure, which can lead to alterations in FFR lesion classification. Attention is required to ensure FFR is measured under conditions of stable hyperemia, although the FFR value at this point may be numerically higher.

Dynamic damping of the aortic pressure trace during hyperemia: the impact on fractional flow reserve measurement.

We report on two cases that illustrate an important caveat in the measurement of fractional flow reserve (FFR) in coronary arteries. To obtain accurate FFR measurements, two fundamental requirements must be fulfilled. One is to minimize microvascular resistance; the other is that there is no damping of the proximal aortic pressure trace. A problem with either of these requirements can be a source of serious error in the measurement of FFR. In each case we present here, despite a good aortic pressure trace at the start of the procedure, there is dynamic damping of the pressure trace during hyperemia, secondary to axial migration of the guiding catheter into the left main stem (LMS). In both cases, a normal aortic pressure trace (Pa) is present at baseline. After intracoronary adenosine injection, there was a fall in both mean Pa and distal coronary pressure (Pd) concomitant with damping of Pa, evidenced by loss of the dicrotic notch and ventricularization of the pressure trace. The resultant FFR value is underestimated. As hyperemia wears off, both pressure traces return to normal with good articulation of the dicrotic notch. When the procedure was repeated taking care to ensure that the guide did not move into the LMS during hyperemia, the Pa trace remained stable following intracoronary adenosine, while mean Pd decreased as before. In both cases, hemodynamically significant lesions were demonstrated that had been masked by the artifactual drop in Pa during the first attempt.

Impact of measuring fractional flow reserve on decision-making in the cath lab in a cohort of patients being considered for coronary revascularization.

BACKGROUND: Fractional flow reserve (FFR) is an accepted standard to detect the functional significance of coronary stenoses. Recent trials suggest that revascularization of moderate coronary stenoses can be safely deferred if the FFR is > or = 0.75 and FFR can be used to guide therapy in multivessel disease. AIM: In a cohort of patients with moderate angiographic coronary disease, we sought to examine the influence of FFR on lesion revascularization and the impact of multivessel FFR assessment on revascularization strategy. METHODS AND RESULTS: Patients with FFR measurements taken between April 2005 to October 2007 were included. Out of 300 cases performed in this time, 264 patients were included. Patients were 62 +/- 11 years and 1.3 +/- 0.54 vessels were examined per case. 92.7% of lesions with a FFR < 0.75 underwent revascularizati on an d 93% of lesions with a FFR > or = 0.75 had intervention deferred. FFR was 0.71 +/- 0.07 in the revascularization group (9 coronary artery bypass graft surgery, 64 percutaneous coronary interventions) and 0.86 +/- 0.06 in the deferred group (p < 0.001). Overall, 75% of patients avoided revascularization of at least one vessel on the basis of the FFR. CONCLUSIONS: Measurement of FFR is clinically useful with a high impact on clinical decision-making in the catheterization laboratory. FFR can be used to reclassify patients with multivessel stenoses, reducing the need for revascularization in the majority of cases.