High-resolution free-breathing automated quantitative myocardial perfusion by cardiovascular magnetic resonance for the detection of functionally significant coronary artery disease.

AIMS: Current assessment of myocardial ischaemia from stress perfusion cardiovascular magnetic resonance (SP-CMR) largely relies on visual interpretation. This study investigated the use of high-resolution free-breathing SP-CMR with automated quantitative mapping in the diagnosis of coronary artery disease (CAD). Diagnostic performance was evaluated against invasive coronary angiography (ICA) with fractional flow reserve (FFR) measurement. METHODS AND RESULTS: Seven hundred and three patients were recruited for SP-CMR using the research sequence at 3 Tesla. Of those receiving ICA within 6 months, 80 patients had either FFR measurement or identification of a chronic total occlusion (CTO) with inducible perfusion defects seen on SP-CMR. Myocardial blood flow (MBF) maps were automatically generated in-line on the scanner following image acquisition at hyperaemic stress and rest, allowing myocardial perfusion reserve (MPR) calculation. Seventy-five coronary vessels assessed by FFR and 28 vessels with CTO were evaluated at both segmental and coronary territory level. Coronary territory stress MBF and MPR were reduced in FFR-positive (≤0.80) regions [median stress MBF: 1.74 (0.90-2.17) mL/min/g; MPR: 1.67 (1.10-1.89)] compared with FFR-negative regions [stress MBF: 2.50 (2.15-2.95) mL/min/g; MPR 2.35 (2.06-2.54) P < 0.001 for both]. Stress MBF ≤ 1.94 mL/min/g and MPR ≤ 1.97 accurately detected FFR-positive CAD on a per-vessel basis (area under the curve: 0.85 and 0.96, respectively; P < 0.001 for both). CONCLUSION: A novel scanner-integrated high-resolution free-breathing SP-CMR sequence with automated in-line perfusion mapping is presented which accurately detects functionally significant CAD.

Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model.

To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5-6 weeks post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. Early LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories, 21 of which correlated with LV equatorial circumferential strain rate. The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2, and secreted frizzled-related protein 1 (sFRP1). This study shows that early changes in regional peak ACS persist at 5-6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. More studies are needed to ascertain if the observed increase in tissue levels of D-3PGDH and sFRP1 might be casually involved in the pathogenesis of adverse LV remodelling.

Quantitative assessment of myocardial scar heterogeneity using cardiovascular magnetic resonance texture analysis to risk stratify patients post-myocardial infarction.

AIM: To determine whether heterogeneity of cardiac scar, as assessed by cardiovascular magnetic resonance (CMR) texture analysis, may provide insight into better risk stratification for patients with previous myocardial infarction (MI). MATERIALS AND METHODS: Patients with previous MI (n=76) were followed for a median of 371.5 days after late gadolinium enhancement (LGE) CMR. The primary endpoint was a composite of ventricular tachycardia, ventricular fibrillation, or unexplained syncope. Areas of LGE were identified and manually segmented on a short-axis projection. The characteristics of the scar heterogeneity were evaluated via CMR texture analysis. This is a filtration-histogram technique, where images are filtered using the Laplacian of a Gaussian filter to extract features different sizes (2-6 mm in radius) corresponding to fine, medium, and coarse texture scales followed by a quantification step using histogram analysis (skewness and kurtosis). RESULTS: Patients suffering arrhythmic events during the follow-up period demonstrated significantly higher kurtosis (coarse-scale, p=0.005) and lower skewness (fine-scale, p=0.046) compared to those suffering no arrhythmic events. Furthermore, Kaplan-Meier analysis showed significantly higher coarse kurtosis (p=0.004), and lower fine skewness (p=0.035) were able to predict increased incidence of ventricular arrhythmic events. CONCLUSIONS: In this pilot study, indices of texture analysis reflecting textural heterogeneity were significantly associated with a greater incidence of arrhythmic events. Further work is required to delineate the role of texture analysis techniques in risk stratification post-MI.

Rest perfusion abnormalities in hypertrophic cardiomyopathy: correlation with myocardial fibrosis and risk factors for sudden cardiac death.

AIM: To measure the prevalence of abnormal rest perfusion in a population of consecutive patients with known hypertrophic cardiomyopathy (HCM) referred for cardiovascular MRI (CMR), and to assess any associations between abnormal rest perfusion and the presence, pattern, and severity of myocardial scar and the presence of risk factors for sudden death. MATERIALS AND METHODS: Eighty consecutive patients with known HCM referred for CMR underwent functional imaging, rest first-pass perfusion, and late gadolinium enhancement (LGE). RESULTS: Thirty percent of the patients had abnormal rest perfusion, all of them corresponding to areas of mid-myocardial LGE and to a higher degree of segmental hypertrophy. Rest perfusion abnormalities correlated with more extensive and confluent LGE. The subgroup of patients with myocardial fibrosis and rest perfusion abnormalities (fibrosis+/perfusion+) had more than twice the incidence of episodes of non-sustained ventricular tachycardia on Holter monitoring in comparison to patients with myocardial fibrosis and normal rest perfusion (fibrosis+/perfusion-) and patients with no fibrosis and normal rest perfusion (fibrosis-/perfusion-). CONCLUSIONS: First-pass perfusion CMR identifies abnormal rest perfusion in a significant proportion of patients with HCM. These abnormalities are associated with the presence and distribution of myocardial scar and the degree of hypertrophy. Rest perfusion abnormalities identify patients with increased incidence of episodes of non-sustained ventricular tachycardia on Holter monitoring, independently from the presence of myocardial fibrosis.

Quantitative myocardial perfusion imaging by cardiovascular magnetic resonance and positron emission tomography.

Recent studies have demonstrated that a detailed knowledge of the extent of angiographic coronary artery disease (CAD) is not a prerequisite for clinical decision making, and the clinical management of patients with CAD is more and more focused towards the identification of myocardial ischemia and the quantification of ischemic burden. In this view, non-invasive assessment of ischemia and in particular stress imaging techniques are emerging as preferred and non-invasive options. A quantitative assessment of regional myocardial perfusion can provide an objective estimate of the severity of myocardial injury and may help clinicians to discriminate regions of the heart that are at increased risk for myocardial infarction. Positron emission tomography (PET) has established itself as the reference standard for myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) quantification. Cardiac magnetic resonance (CMR) is increasingly used to measure MBF and MPR by means of first-pass signals, with a well-defined diagnostic performance and prognostic value. The aim of this article is to review the currently available evidence on the use of both PET and CMR for quantification of MPR, with particular attention to the studies that directly compared these two diagnostic methods.

Quantitative analysis of transmural gradients in myocardial perfusion magnetic resonance images.

Conventional quantitative assessments of myocardial perfusion analyze the temporal relation between the arterial input function and the myocardial signal intensity curves, thereby neglecting the important spatial relation between the myocardial signal intensity curves. The new method presented in this article enables characterization of sub-endocardial to sub-epicardial gradients in myocardial perfusion based on a two dimensional, "gradientogram" representation, which displays the evolution of the transmural gradient in myocardial contrast uptake over time in all circumferential positions of the acquired images. Moreover, based on segmentation in these gradientograms, several new measurements that characterize transmural myocardial perfusion distribution over time are defined. In application to clinical image data, the new two-dimensional representations, as well as the newly defined measurements revealed a clear distinction between normal perfusion and inducible ischaemia. Thus, the new measurements may serve as diagnostic markers for the detection and characterization of epicardial coronary and microvascular disease.

WITHDRAWN: Activity of endothelial factors on myocardial inotropy.

Ahead of Print article withdrawn by publisher.

Surgical revascularization in the ischemic heart disease. Long-term results in a series of consecutive patients selected according to the principles.

AIM: Ischemic heart disease can be treated with drugs, percutaneous coronary interventions (PCI) and surgical revascularization (CABG). In our institution the therapeutic decisions for non emergent cases have been regularly taken during a daily meeting attended by clinicians, interventionalists, and surgeons, who all adhere to the principles of Evidence Based Medicine. The purpose of the present report is to investigate the long-term results in a series of consecutive patients to whom surgical revascularization has been recommended following the abovementioned approach. METHODS: We selected 597 patients with no prior interventions, who were referred to our institution for coronary angiography between January 1991 and December 1997 and to whom surgical revascularization was recommended. The Kaplan-Meier method was adopted to evaluate survival and freedom from: non fatal acute myocardial infarction, PCI, repeat CABG. RESULTS: The results were compared to those of the randomized trials or of large follow-up reports. The mean observation period was 6.8 years. The results at 5 and 10 years were: overall survival 95.5% and 90.2%; freedom from acute myocardial infarction 95.5% and 90.2%; freedom from surgical reintervention 98.6% and 97.1%; freedom from PCI 91.2% and 79.8%; survival free from all events 79.3% and 58.1%. These rates were comparable to those reported by the most important clinical trials. CONCLUSIONS: If surgical treatment for patient with coronary artery disease is recommended according to the suggestions of the leading clinical trials and pertinent guidelines, the results in terms of mortality and morbidity are comparable to those of the trials themselves, even in the non selected patients of daily clinical practice.

Fatty acids are important for the Frank-Starling mechanism and Gregg effect but not for catecholamine response in isolated rat hearts.

In some pathophysiological conditions myocardial metabolism can switch from mainly long chain fatty acid (LCFA) oxidation to mainly glucose oxidation. Whether the predominant fatty acid or glucose oxidation affects cardiac performance has not been defined. In a buffer perfused isovolumetrically contracting rat heart, oxidation of endogenous pool LCFA was avoided by inhibiting carnitine-palmitoyl-transferase I (CPT-I) with oxfenicine (2 mM). In order to restore fatty acid oxidation, hexanoate (1 mM), which bypasses CPT-I inhibition, was added to the perfusate. Three groups of hearts were subjected to either an increase in left ventricular volume (VV, +25%) or an increase in coronary flow (CF, +50%), or inotropic stimulation with isoproterenol (10(-8) and 10(-6) m). The increase in VV (the Frank-Starling mechanism) increased rate-pressure product (RPP) by 21 +/- 2% under control conditions, but only by 6 +/- 2% during oxfenicine-induced CPT-I inhibition. The contractile response to changes in VV recovered after the addition of hexanoate. Similar results were obtained in hearts, in which an increase in CF was elicited (the Gregg phenomenon). Isoproterenol caused a similar increase in contractility regardless of the presence of oxfenicine or hexanoate. In all groups, a commensurate increase in oxygen consumption accompanied the increase in contractility. The fatty acid oxidation is necessary for an adequate contractile response of the isolated heart to increased pre-load or flow, whereas the inotropic response to adrenergic beta-receptor stimulation is insensitive to changes in substrate availability.

Cytochrome P-450 metabolite of arachidonic acid mediates bradykinin-induced negative inotropic effect.

This study focused on the mechanisms of the negative inotropic response to bradykinin (BK) in isolated rat hearts perfused at constant flow. BK (100 nM) significantly reduced developed left ventricular pressure (LVP) and the maximal derivative of systolic LVP by 20-22%. The cytochrome P-450 (CYP) inhibitors 1-aminobenzotriazole (1 mM and 100 microM) or proadifen (5 microM) abolished the cardiodepression by BK, which was not affected by nitric oxide and cyclooxygenase inhibitors (35 microM NG-nitro-L-arginine methyl ester and 10 microM indomethacin, respectively). The CYP metabolite 14,15-epoxyeicosatrienoic acid (14,15-EET; 50 ng/ml) produced effects similar to those of BK in terms of the reduction in contractility. After the coronary endothelium was made dysfunctional by Triton X-100 (0.5 microl), the BK-induced negative inotropic effect was completely abolished, whereas the 14,15-EET-induced cardiodepression was not affected. In hearts with normal endothelium, after recovery from 14,15-EET effects, BK reduced developed LVP to a 35% greater extent than BK in the control. In conclusion, CYP inhibition or endothelial dysfunction prevents BK from causing cardiodepression, suggesting that, in the rat heart, endothelial CYP products mediate the negative inotropic effect of BK. One of these mediators appears to be 14,15-EET.

Coronary reactive hyperaemia after two periods of coronary occlusion in the anaesthetized goat.

In the coronary circulation an ischaemic preconditioning obtained with two periods of 2.5 min each of occlusion of the left circumflex coronary artery alters the pattern of a coronary reactive hyperaemia which follows 15 s only of occlusion of the studied artery. The most remarkable change consists of a reduction of 40-45% of the time required by the flow to reach the maximum hyperaemic peak (time to peak) after the brief occlusion. The present investigation was planned to study whether the time to peak of the hyperaemia following the second 2.5 min preconditioning occlusion was shorter than the hyperaemia following the first occlusion. Experiments performed in the anaesthetized goat, in which coronary flow was measured with an electromagnetic flow-probe placed around the left circumflex coronary artery showed that in the hyperaemia occurring after the second preconditioning occlusion the time to peak was reduced by 18% only. The moderate effect of the second preconditioning occlusion in reducing the time to peak is attributed to the fact that the heart was already partially preconditioned after the first occlusion and that after relatively long periods (2.5 min) of occlusion the metabolic component of the hyperaemic response was so predominant to partially mask the role of the vascular mechanisms presumably responsible for the reduction of the time to peak.