Reduction In Myocardial Blood Flow Research Articles

Impact of revascularization on non-flow limiting lesions

Abstract Background Physiology-guided decision-making markedly improves outcomes in patients with coronary artery disease (CAD). The fractional flow reserve (FFR) and the coronary flow reserve (CFR) can be used to estimate the reduction in myocardial blood flow by a stenosis and both were validated against non-invasive modalities to identify ischemia. Nevertheless, discordance between FFR and CFR in stenosis classification occurs in 30-40%. Recent studies showed that patients with non-flow limiting lesions (abnormal FFR, normal CFR) deferred from revascularization had similar outcomes to those vessels that underwent revascularization. However, the direct impact of revascularization in these vessels remains unclear. Purpose We aimed to identify the impact of revascularization in vessels with non-flow limiting lesions (abnormal FFR and normal CFR). Methods We selected those patients with non-flow limiting lesions from the global ILIAS Registry, a comprehensive pooled data set of patients whom underwent clinically indicated coronary angiography and complete physiological assessment. The primary outcomes consist of the composite endpoints of MACE and TVF at 5-year follow-up. Results A total of N=526 patients were included in the current analysis. Mean age was 64±10 and 74% were men. The mean FFR was 0.79±0.09 and the mean CFR 2.38±1.12. Of these, 53% (N=276) underwent revascularization and (47%) had no revascularization of the target vessel during the index procedure. Both groups had a similarly increased risk for MACE and TVF at 5-years (HR 2.4 [95% CI 1.6 – 3.5] and HR 2.2 [95% CI 1.5 – 3.4] respectively, p<0.005 for both, and p=0.787 for the difference between both). Conclusions We found that revascularization did not impact the association between non-flow limiting lesions and MACE or TVF at 5-year follow-up. Although these results should be interpreted with caution, it indicates the need for a more inclusive assessment of coronary hemodynamic when considering revascularization therapy.Figure 1

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

The diagnosis and prognosis of coronary microvascular disease using PET/CT.

This study aimed to evaluate the diagnostic and prognostic value of 13N-NH3·H2O positron emission tomography combined with computed tomography (PET/CT) for non-obstructive coronary microvascular disease (CMVD). A retrospective analysis was conducted on 70 patients with clinically suspected non-obstructive CMVD (35 males, 35 females) between March 2017 and August 2019. The average age of the patients was 53.32±7.82 years. The patients underwent 13N-NH3·H2O PET/CT and were divided into two groups based on diagnostic criteria: a CMVD group and a non-CMVD group. They were then followed up for 180-1,095 days. Data were analyzed using an χ2 test, the logistic regression model, the multiple linear regression model, the Kaplan-Meier method, the Cox proportional hazards regression model, and a receiver operating characteristic (ROC) curve. (1) The incidence of cardiovascular family history and a high calcification score (11-400) was higher in the CMVD group than in the non-CMVD group (58.8% vs. 20.8% and 29.4% vs. 5.7%, respectively; P < 0.05 for all), stress myocardial blood flow (MBF) and coronary flow reserve (CFR) values were lower in the CMVD group than in the non-CMVD group (2.280±0.693 vs. 3.641±1.365 and 2.142±0.339 vs. 3.700±1.123, respectively), and calcification score was higher in the CMVD group than in the non-CMVD group (110.18±165.07 vs. 13.21±41.68, respectively; P < 0.05 for all). Gender and diabetes were risk factors for stress MBF reduction (β= 1.287 and β= -0.636, respectively), calcification score and hypertension were risk factors for CFR reduction (β= -0.004 and β= -0.654, respectively), and hypertension, family history, and calcification score were risk factors in the CMVD group (OR = 7.323, OR = 5.108, OR = 1.012, respectively; P < 0.05 for all). (2) The prognosis of patients with CFR < 2.5 was worse than that of patients with CFR≥2.5 (x2 value: 27.404, P < 0.001). The risk of adverse cardiovascular events in diabetic patients was also increased (β= 0.328, P < 0.001). When CFR was set to 2.595, the prognostic sensitivity was 94% and the specificity was 80%. The technology of 13N-NH3·H2O PET/CT can be used for the diagnosis and prognosis of non-obstructive CMVD. Cardiovascular risk factors are related to the occurrence and prognosis of CMVD.

The feasibility of SPECT CZT measurement of myocardial blood flow and reserve in patients with acute coronary syndrome: comparison with cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: None. Background. Myocardial infarction with non-obstructive coronary arteries (MINOCA) is currently of interest in terms of diagnostic and treatment strategy. The diagnosis of MINOCA has been included in the STEMI guidelines of the European Society of Cardiology. However, there is lack of data regarding the relationship between myocardial damage according to cardiac magnetic resonance (CMR) and myocardial blood flow (MBF), myocardial flow reserve (MFR) obtained by dynamic SPECT. Purpose. To elucidate impairment of myocardial perfusion, MBF and MFR in patients with MINOCA. Methods. The study included 31 patients (21 men, age 62(56;70) years) with ASC. According to electrocardiography, cardiac biomarkers, invasive coronary angiography two groups were identified: with non-obstructive coronary arteries MINOCA (n = 10); MICAD (n = 21). Within 7-14 days after admission to the hospital all patients underwent dynamic SPECT on CZT gamma-camera with the assessment of standard indices of myocardial perfusion (SSS, SRS, SDS) and quantitative parameters (stress/rest myocardial blood flow (s/r MBF), myocardial flow reserve (MFR)). All patients underwent CMR with late gadolinium enhancement as well. Infarct size (IS), microvascular obstruction (MVO) and myocardial edema size (ME) were evaluated. Results. SSS and SRS differed significantly (p &amp;lt; 0.05) in MINOCA and MICAD patients: MINOCA: SSS 5.0(3.0;5.0), SRS 2.0(1.0;3.0); MICAD: SSS 9.0(5.0;13.0), SRS 6.0(3.0;11.0). However, SDS did not differ significantly in these two groups 2.5(1.0;4.0) vs 4.0(2.0;5.0). Moreover MINOCA patients in comparison with those with MIACD had higher values of quantitative parameters (p &amp;lt; 0.05): sMBF 2.02 (1.71;2.37) vs 0.86 (0.72;1.02) ml/min/g, rMBF 0.68 (0.66;0.86) vs 0.49 (0.4;0.57) ml/min/g, MFR 2.61 (2.23;3.14) vs 1.67 (1.1;1.9), respectively. Based on CMR, a total of 93 left ventricular vessel territories were analyzed. A total of 36(39%) vessel territories were considered as having acute myocardial injury (5 in MICAD, 31 in MINOCA). In patients with MICAD the values of IS, ME were significantly higher as compared to those with MINOCA (IS: 19.4(10.4;29.7)% vs1.8(0.0;6.9)%, ME: 19.5(12.0;30.0)% vs 3.0(0.0;12.0)% - p &amp;lt; 0.01). Based on regional analysis sMBF and MFR were significantly lower in vessel territories considering as CMR positive compared to those without MR signs of myocardial injury: regional sMBF 0.98(0.73;1.79) vs 1.33(0.94;2.08); regional MFR 0.58(0.43;0.9) vs 0.71(0.57;0.88), respectively. Conclusion. SPECT CZT is feasible in identifying both global and regional disturbances of myocardial blood flow and reserve in patients with acute coronary syndrome. MINOCA patients are characterized by mild reduction of myocardial blood flow and perfusion assessed visually and quantitatively. Therefore despite the absence of obstructive coronary artery lesion this group of patients has more pronounced risk of cardiac events and need more aggressive observation and treatment.

Extensive and balanced reduction of myocardial blood flow in patients with suspected obstructive coronary artery disease: 15O-water PET study

BackgroundDetection of obstructive coronary artery disease (CAD) by stress myocardial perfusion imaging (MPI) is conventionally based on relative differences in perfusion. This may lead to either underestimation of the extent of myocardial ischemia, or the ischemia might be completely missed in case of balanced perfusion reduction. Using absolute quantification of myocardial blood flow (MBF) by positron emission tomography (PET), we evaluated how common are extensive and balanced myocardial perfusion abnormalities in symptomatic patients with suspected obstructive CAD. Methods and resultsAmong 758 consecutive symptomatic patients undergone coronary computed tomography angiography (CTA), 286 patients subsequently underwent quantitative 15O-water adenosine-stress PET MPI to assess the hemodynamic significance of suspected obstructive stenosis. Out of these, 46 (16%) patients had reduced (≤2.3 ml/g/min) absolute stress MBF in all three standard coronary territories (LAD, LCX, RCA). Subsequently, relative stress MBF in each coronary territory was calculated, considering a territory with the highest absolute stress MBF as a reference region. Among the 46 patients, 72% had significant regional heterogeneity in myocardial perfusion (defined as having ≥1 territory with relative stress MBF <80%) while the remaining 28% (4.5% of the whole MPI cohort) showed balanced perfusion reduction (all relative MBF values ≥80%). ConclusionsAmong symptomatic patients with suspected obstructive stenosis on coronary CTA, quantitative PET revealed that 16% of patients had reduced stress MBF involving all three coronary artery territories, of whom approximately one third showed balanced reduction. Thus, in 4.5% of the patients the perfusion abnormalities could have been missed by conventional relative MPI analysis.

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

BackgroundQuantitative 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.MethodsWe 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.ResultsPerfusion 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.ConclusionsPerfusion 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.

Use of quantitative myocardial perfusion mapping by CMR for characterisation of ischaemia in patients post coronary artery bypass graft surgery

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background Quantitative myocardial perfusion mapping using Cardiac Magnetic Resonance (CMR) imaging is used for evaluation of ischaemia in the context of native vessel coronary disease, but its diagnostic performance in patients with grafts is not well established. Perfusion defects are often detected in these patients, but whether these are a consequence of a technical limitation (delayed contrast arrival from graft conduits) or a true reflection of reduced myocardial blood flow is unclear. Methods 39 patients undergoing stress perfusion CMR with previous coronary artery bypass graft (CABG) surgery, unobstructed left internal mammary artery (LIMA) grafts to the left anterior descending (LAD) artery on coronary angiography and no CMR evidence of prior LAD infarction were included. Myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) were evaluated with quantitative perfusion mapping and the factors determining MBF in the LIMA-LAD territory (AHA segments 1,2,7,8,13,14), including the impact of delayed contrast arrival through the LIMA graft were evaluated. Results In 28 out of 39 cases a myocardial perfusion defect was reported on visual assessment in LIMA-LAD myocardial territory, despite the presence of unobstructed LIMA graft and no LAD infarction. Chronic total occlusion (CTO) of the native LAD was an independent predictor of stress MBF (B=-0.36, p =0.027) and the strongest predictor of MPR (B=-0.55, p 0.005) within the LIMA-LAD myocardial territory after adjusting for age, left ventricular (LV) ejection fraction, and presence of diabetes. CTO of the native LAD was associated with a reduction in stress MBF in the basal myocardial segments (-0.57ml/g/min, p = 0.002) but had no effect on the MBF of apical segments (-0.31ml/g/min, p = 0.084). Increasing the maximum value for allowable arterial delay (TA) of contrast in the quantitative mapping algorithm resulted in a small increase in myocardial blood flow in the LIMA-LAD territory both at stress (0.07 ± 0.08ml/g/min, p &amp;lt; 0.001) and rest (0.06 ± 0.05ml/g/min, p &amp;lt; 0.001). Conclusions Perfusion defects detected in LIMA-LAD subtended territories are common despite graft patency. These defects are likely to represent genuine reduction in MBF, resulting from native LAD coronary occlusion. Prolonged contrast transit time associated with LIMA grafts results in small underestimation of MBF as measured by quantitative CMR perfusion mapping, but does not account for the degree of MBF reduction seen in these patients. Figure 1. Study patient with unobstructed LIMA to LAD graft and evidence of inducible perfusion defect in LIMA-LAD territories. (A): First pass perfusion CMR imaging. (B): Perfusion mapping showing reduced stress MBF in mid antero-septum (0.85ml/g/min) compared to the apical septum (1.65ml/g/min). (C): Late gadolinium enhancement showing no evidence of previous infarction. (D,E): Coronary angiography demonstrating unobstructed LIMA graft (D) and anastomosis site (E). Abstract Figure 1.

Dynamic SPECT with assessment myocardial blood flow and coronary flow reserve in MINOCA patients: comparison with cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): grant of the President of the Russian Federation Background. In recent years a group of patients with acute myocardial infarction without obstructive coronary artery disease (MINOCA) is of interest. In this group of patients, there is a lack of information related to myocardial perfusion, blood flow and reserve, which could be important in term of risk and prognosis assessment. Purpose. To assess the global and regional myocardial blood flow and coronary flow reserve impairment in MINOCA patients compared to cardiac magnetic resonance (CMR). Methods. The study group comprised 28 patients (18 male, mean 62.9 ± 10.7years) with acute coronary syndrome. Based on ICA results all patients were divided into two groups: 1) MINOCA (n = 11); 2) patients with myocardial infarction with obstructive CAD (MICAD) (n = 17). A total of 12/17 (71%) MICAD patients underwent PCI with stenting; in 2/12 cases two arteries were revascularized. Within 7-10 days after admission to the hospital all patients underwent SPECT myocardial perfusion scintigraphy (MPS) with the assessment of standard indices (SSS, SRS, SDS) and quantitative parameters: rest MBF (rMBF), stress MBF (sMBF) and CFR (on CZT gamma-camera). Also, all patients underwent CMR with evaluation of infarct size (IF), microvascular obstruction (MVO), size of myocardial edema (ME) and transmural extent of myocardial infarction (TE). Results Visual analysis showed that SSS differed significantly (p = 0.001) among MINOCA and MICAD groups: 5 (3;6) vs 10 (5;13), respectively. According to the quantitative MPS data analysis, global sMBF and CFR values were significantly higher in MINOCA than in MICAD patients group: 1.2 (0.82;1.69) ml/min/g vs 0.62 (0.52;0.9) ml/min/g; 1.96 (1.23;2.42) vs 1.16 (0.98;1.64) , respectively. CMR indices such as IS, ME and TE were significantly lower in MINOCA compared to MICAD patients: 1.6 (0;7.8) vs 14.8 (6.3;22.6)%; 8(0;14) vs 18.5 (10;23)%; 0 (0;5) vs 18 (10;25), respectively. Seven(40%) MICAD group patients showed MVO, whereas there were no such patients in MINIOCA group. The regional analysis revealed that sMBF and CFR were significantly lower in LV regions characterized by myocardial injury compared to non-injured regions (based on CMR data): 0.78 (0.51;0.94) ml/min/g vs 1.11 (0.82;1.4) and 1.22 (0.91;1.74) vs 1.52 (1.14;2.42), respectively. Also, we found out significant correlation between regional quantitative SPECT indices and transmural extent of myocardial infarction evaluated by CMR: r=–0.4 for sMBF; r=–0.35 for CFR (p &amp;lt; 0.05). Conclusion. The analysis of quantitative MPS SPECT parameters showed that such approach allows identifying MBF and CFR disturbances both on global and regional level. These results showed that MINOCA patients characterized by mild reduction of myocardial blood flow and perfusion assessed visually and quantitatively. It means that despite the absence of obstructive coronary artery lesion this group of patients has more pronounced risk of cardiac events and need more aggressive observation and treatment.

Panax quinquefolius L. Saponins Protect Myocardial Ischemia Reperfusion No-Reflow Through Inhibiting the Activation of NLRP3 Inflammasome via TLR4/MyD88/NF-κB Signaling Pathway.

At present, many patients who undergo reperfusion immediately after percutaneous coronary intervention will undergo microvascular obstruction and reduction in myocardial blood flow. This phenomenon is called “no-reflow (NR),” and there is still no effective therapy for NR. Studies showed Panax quinquefolius L. saponins (PQS) have effect on MI/R injury, while the effect and mechanism of PQS on MI/R induced NR are not clear. In this study, we established a MI/R model to investigate whether PQS decrease NR phenomenon via suppression of inflammation. We found that PQS significantly alleviated the symptoms of NR by reducing ischemia, infarction, and NR area; improving cardiac function; preventing pathological morphology changes of myocardium; depressing leukocytes’ aggregation and adhesion; and suppressing the excessive inflammation. Further study demonstrated that PQS remarkably inhibited TLR4, MyD88, p-NF-κB, and NLRP3 inflammasome-associated protein, and these effects could be reversed by LPS. These results indicated that PQS may protect NR by inhibiting the activation of NLRP3 inflammasome via TLR4/MyD88/NF-κB signaling pathway in part, suggesting that PQS exist potential in preventing NR induced by MI/R.

A novel method for measuring absolute coronary blood flow and microvascular resistance in patients with ischaemic heart disease.

AimsIschaemic heart disease is the reduction of myocardial blood flow, caused by epicardial and/or microvascular disease. Both are common and prognostically important conditions, with distinct guideline-indicated management. Fractional flow reserve (FFR) is the current gold-standard assessment of epicardial coronary disease but is only a surrogate of flow and only predicts percentage flow changes. It cannot assess absolute (volumetric) flow or microvascular disease. The aim of this study was to develop and validate a novel method that predicts absolute coronary blood flow and microvascular resistance (MVR) in the catheter laboratory.Methods and resultsA computational fluid dynamics (CFD) model was used to predict absolute coronary flow (QCFD) and coronary MVR using data from routine invasive angiography and pressure-wire assessment. QCFD was validated in an in vitro flow circuit which incorporated patient-specific, three-dimensional printed coronary arteries; and then in vivo, in patients with coronary disease. In vitro, QCFD agreed closely with the experimental flow over all flow rates [bias +2.08 mL/min; 95% confidence interval (error range) −4.7 to +8.8 mL/min; R2 = 0.999, P < 0.001; variability coefficient <1%]. In vivo, QCFD and MVR were successfully computed in all 40 patients under baseline and hyperaemic conditions, from which coronary flow reserve (CFR) was also calculated. QCFD-derived CFR correlated closely with pressure-derived CFR (R2 = 0.92, P < 0.001). This novel method was significantly more accurate than Doppler-wire-derived flow both in vitro (±6.7 vs. ±34 mL/min) and in vivo (±0.9 vs. ±24.4 mmHg).ConclusionsAbsolute coronary flow and MVR can be determined alongside FFR, in absolute units, during routine catheter laboratory assessment, without the need for additional catheters, wires or drug infusions. Using this novel method, epicardial and microvascular disease can be discriminated and quantified. This comprehensive coronary physiological assessment may enable a new level of patient stratification and management.

Is Chemotherapy‐Induced Cardiomyopathy Caused by Myocardial Ischemia?

Over the last 50 years progress has been made in treating childhood and adult solid and hematological tumors. One commonly used chemotherapeutic agent is doxorubicin (DOX), an anthracycline antitumor antibiotic, which was discovered in early 1960s. Anthracycline (ANT) chemotherapy alone or in combination with other chemotherapeutic agents markedly improves the survival rate of cancer patients, particularly among children, where survival rates have more than doubled over 5 decades. However, the use of ANT chemotherapy is a double‐edged sword in that it can produce chemotherapy induced cardiac dysfunction (CRCD), which can cause death in 50% of the patients with who present with the cardiomyopathy. We hypothesized, that one of the causes for CRGD is a reduction in myocardial blood flow (MBF) that leads to cardiac myocyte hypoxia, producing small areas of ischemia and myocyte damage. We also hypothesize that increasing MBF by the coronary vasodilator chromonar prevents cardiomyocytes from hypoxic damage.To test these hypotheses, we treated mice genetically engineered to show cardiac myocyte fluorescence if the cells are hypoxic (hypoxia fate mapping [HFM]) with DOX for 6 weeks (group 1, N=8) and Dox + Chromonar for 6 weeks (group 2 N=8). Five weeks after treatment we started tamoxifen for 5 days to activate the HFM protocol. Tamoxifen induces Cre in cardiac myocytes and hypoxia activates a program that results in the expression of td‐tomato only in hypoxic cardiac myocytes. In tissue sections, hypoxic cardiac myocytes are visualized by fluorescence microscopy. Cardiac function was measured by ultrasound and MBF was measured with contrast echocardiography.Six weeks after DOX treatment many hypoxic myocytes were observed in the myocardium. Cardiac function was significantly decreased at the end of DOX treatment (% ejection fraction EF=39±3) compared to baseline (62±5.8%). Simultaneous administration of chromonar prevents the cardiomyocytes from hypoxic damage and prevents cardiac dysfunction development. %EF was 58±6 at the end of the chemotherapy. Chromonar also significantly increased MBF in group 2 mice compared to group 1 (P&lt;0.05).Based on these data CRCD may be a type of ischemic heart disease where the treatment reduces MBF, which leads cardiomyocyte hypoxia, and causes progressive, accumulative cardiac injury. Moreover, increasing myocardial blood flow by chromonar prevents the cardiomyocytes from hypoxic damage and development of CRCD.Support or Funding InformationNIH, NHLBIPanel A shows the relationship between myocardial blood flow and cardiac work 6 weeks after DOX and DOX + Chromonar treatment. Panel B shows ejection fraction changes in DOX +Chromonar (Group 2 mice)Figure 1

Serum Level of Interleukin-33, C-Reactive Protein, and Troponin in Iraqi Coronary Artery Disease Patients

Coronary artery disease (CAD) is a condition of an inadequate supply of oxygenated blood to a portion of the myocardium. It typically occurs when there is an imbalance between supply and demand of myocardial oxygen. The most common cause of myocardial ischemia is atherosclerotic disease of an epicardial coronary artery or arteries which is sufficient to cause a regional reduction in myocardial blood flow and inadequate perfusion of the myocardium supplied by the involved coronary artery. Fifty CAD subjects (23 females and 27 males) were enrolled in this study in addition to thirty healthy control subjects (13 female and 17 male). This study aimed to measure the serum levels of interleukin IL- 33, C- reactive protein and troponin in CAD and their association with lipid profile by using enzyme-linked immune sorbent assay (ELISA). T results showed that high-density lipoprotein (HDL) was statistically high while differences in cholesterol, triglyceride and low-density lipoprotein (LDL) were statistically non-significant between CAD patients and controls. Moreover, the serum level of IL-33 and CRP were statistically higher in patients than controls, while troponin levels were not significantly different. In addition, the present study demonstrates that IL-33, CRP, and Troponin were not associated with lipid profile. The relationship of IL-33 with CRP and troponin was non-significant.

Effects of a novel peptide Ac-SDKP in radiation-induced coronary endothelial damage and resting myocardial blood flow

BackgroundCancer survivors treated with thoracic ionizing radiation are at higher risk of premature death due to myocardial ischemia. No therapy is currently available to prevent or mitigate these effects. We tested the hypothesis that an endogenous tetrapeptide N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) counteracts radiation-induced coronary vascular fibrosis and endothelial cell loss and preserves myocardial blood flow.MethodsWe examined a rat model with external-beam-radiation exposure to the cardiac silhouette. We treated a subgroup of irradiated rats with subcutaneous Ac-SDKP for 18-weeks. We performed cardiac MRI with Gadolinium contrast to examine resting myocardial blood flow content. Upon sacrifice, we examined coronary endothelial-cell-density, fibrosis, apoptosis and endothelial tight-junction proteins (TJP). In vitro, we examined Ac-SDKP uptake by the endothelial cells and tested its effects on radiation-induced reactive oxygen species (ROS) generation. In vivo, we injected labeled Ac-SDKP intravenously and examined its endothelial localization after 4-h.ResultsWe found that radiation exposure led to reduced resting myocardial blood flow content. There was concomitant endothelial cell loss and coronary fibrosis. Smaller vessels and capillaries showed more severe changes than larger vessels. Real-time PCR and confocal microscopy showed radiation-induced loss of TJ proteins including- claudin-1 and junctional adhesion molecule-2 (JAM-2). Ac-SDKP normalized myocardial blood flow content, inhibited endothelial cell loss, reduced coronary fibrosis and restored TJ-assembly. In vitro, Ac-SDKP localized to endothelial cells and inhibited radiation-induced endothelial ROS generation. In vivo, labeled Ac-SDKP was visualized into the endothelium 4-h after the intravenous injection.ConclusionsWe concluded that Ac-SDKP has protective effects against radiation-induced reduction of myocardial blood flow. Such protective effects are likely mediated by neutralization of ROS-mediated injury, preservation of endothelial integrity and inhibition of fibrosis. This demonstrates a strong therapeutic potential of Ac-SDKP to counteract radiotherapy-induced coronary disease.

The impact of prompt gamma compensation on myocardial blood flow measurements with rubidium-82 dynamic PET

BackgroundRubidium-82 myocardial perfusion imaging is a well-established technique for assessing myocardial ischemia. With continuing interest on myocardial blood flow (MBF) and myocardial flow reserve (MFR) measurements, there is a requirement to fully appreciate the impact of technical aspects of the process. One such factor for rubidium-82 is prompt gamma compensation (PGC). This study aims to assess the impact of PGC on MBF and MFR calculated from dynamic Rb-82 data. MethodsDynamic rest and stress images were acquired on a Siemens Biograph mCT and reconstructed with and without PGC in 50 patients (29 male). MBF and MFR were measured in the three main coronary territories as well as globally. ResultsWith PGC, statistically significant reductions in MBF were observed in LAD (−6.9%), LCx (−4.8%), and globally (−6.5%) but only in obese patients. Significant increases in MBF were observed in RCA (+6.4%) in only nonobese patients. In very obese patients, differences of up to 40% in MBF were observed between PGC and non-PGC images. In nearly all cases, similar PGC differences were observed at stress and rest so there were no significant differences in MFR; however, in a small number of very obese patients, differences in excess of 20% were observed. ConclusionPGC results in statistically significant changes in MBF, with the greatest reductions observed in the LAD and LCx territories of obese patients. In most cases, the impact on stress and rest data is of similar relative magnitudes and changes to MFR are small.

Non-contrast assessment of microvascular integrity using arterial spin labeled cardiovascular magnetic resonance in a porcine model of acute myocardial infarction

BackgroundFollowing acute myocardial infarction (AMI), microvascular integrity and function may be compromised as a result of microvascular obstruction (MVO) and vasodilator dysfunction. It has been observed that both infarcted and remote myocardial territories may exhibit impaired myocardial blood flow (MBF) patterns associated with an abnormal vasodilator response. Arterial spin labeled (ASL) CMR is a novel non-contrast technique that can quantitatively measure MBF. This study investigates the feasibility of ASL-CMR to assess MVO and vasodilator response in swine.MethodsThirty-one swine were included in this study. Resting ASL-CMR was performed on 24 healthy swine (baseline group). A subset of 13 swine from the baseline group underwent stress ASL-CMR to assess vasodilator response. Fifteen swine were subjected to a 90-min left anterior descending (LAD) coronary artery occlusion followed by reperfusion. Resting ASL-CMR was performed post-AMI at 1–2 days (N = 9, of which 6 were from the baseline group), 1–2 weeks (N = 8, of which 4 were from the day 1–2 group), and 4 weeks (N = 4, of which 2 were from the week 1–2 group). Resting first-pass CMR and late gadolinium enhancement (LGE) were performed post-AMI for reference.ResultsAt rest, regional MBF and physiological noise measured from ASL-CMR were 1.08 ± 0.62 and 0.15 ± 0.10 ml/g/min, respectively. Regional MBF increased to 1.47 ± 0.62 ml/g/min with dipyridamole vasodilation (P < 0.001). Significant reduction in MBF was found in the infarcted region 1–2 days, 1–2 weeks, and 4 weeks post-AMI compared to baseline (P < 0.03). This was consistent with perfusion deficit seen on first-pass CMR and with MVO seen on LGE. There were no significant differences between measured MBF in the remote regions pre and post-AMI (P > 0.60).ConclusionsASL-CMR can assess vasodilator response in healthy swine and detect significant reduction in regional MBF at rest following AMI. ASL-CMR is an alternative to gadolinium-based techniques for assessment of MVO and microvascular integrity within infarcted, as well as salvageable and remote myocardium. This has the potential to provide early indications of adverse remodeling processes post-ischemia.

Ischemia Modified Albumin –An Early Marker of Myocardial Ischemia

INTRODUCTION Myocardial Ischemia occurs when there is an inadequate supply of blood to the myocardium resulting in an imbalance between myocardial oxygen supply and demand. The most common cause of Myocardial ischemia is an atherosclerotic disease of an epicardial coronary artery leading to a regional reduction in myocardial blood flow, followed by spasm, arterial thrombi, and rarely coronary emboli. Episodes of defective perfusion result in decreased myocardial tissue oxygen tension, and cause transient disturbance of mechanical, biochemical and electrical functions of the myocardium. More severe the block, more the damage to the myocardium, also in relation to the duration of oxygen supply. Early diagnosis of Myocardial Infarction at this stage itself can prevent morbidity and mortality. Though we have various myocardial proteins in the serum like CK-MB, LDH, AST and Troponins I and T for diagnosing Acute Myocardial Infarction, along with ECG, we should be able to identify myocardial ischemia before it progresses to irreversible myocardial cell damage. These markers are not elevated in the absence of necrosis when measured in the first 2 to 6 hours following an ischemic event. The present study on ischemia modified albumin has been found to be very useful for the detection of myocardial ischemia within 6 hours of onset of chest pain. Ischemia Modified Albumin (IMA) is measured by Albumin Cobalt Binding assay. It is based on the reduced binding affinity of human serum albumin for metal ions like Cobalt attributed to the free radical damage to the N - terminal region of albumin in patients with myocardial ischemia. The values are correlated with CK-MB and lipid profile. AIM OF THE STUDY : Aim of the study is to measure the Ischemia Modified Albumin by Albumin Cobalt Binding assay in patients, within 6 hours of onset of chest pain. OBJECTIVE : (1) To correlate the IMA values with CK-MB (2) Correlation of other markers of atherosclerosis like: (a) Total cholesterol, (b) Triacylglycerol, (c) High density lipoprotein, (d) Low density lipoprotein, (e) Very low density lipoprotein with IMA, (3) To prove the use of IMA as an early marker of myocardial ischemia. CONCLUSION : Biochemical markers such as CK-MB, Cardiac Troponin-I and Myoglobin are suitable only for assessing myocardial infarction. The results of the present study confirm the findings of previous studies, that reported that the Albumin Cobalt colorimetric assay distinguishes myocardial ischemic patients from non ischemic patients (p<0.001) Introduction of IMA assay for the first time provides emergency physicians with an objective diagnostic study to determine the presence of myocardial ischemia completely within the control of the emergency department. IMA assay presents a quantitative accurate laboratory determination of the occurrence of an Ischemic myocardial event, Angina of various types. Unlike the previous laboratory parameters that identify myocardial damage, only after it is well established, this test (Albumin Cobalt binding assay) helps to determine which patients will go in for severe occlusion. The introduction of IMA is a welcome event and based on the results obtained, the present study supports the hypothesis that Ischemia Modified Albumin is a useful marker for the early diagnosis of myocardial ischemia before any significant increase in CK-MB levels.

17 A case-control study with computational modelling of acute left ventricular dysfunction

Introduction The pathophysiology of acute left ventricular dysfunction after acute ST-elevation myocardial infarction (STEMI) is incompletely understood. In this study, we carried out a case-control study of left ventricular (LV) biomechanical behaviour in vivo using an immersed boundary-finite element (IB/FE) method. Methods Cardiac magnetic resonance images were acquired from six healthy volunteers (the healthy group) and six patients with acute LV dysfunction post-acute STEMI (the MI group) with no-reflow, defined as an acute reduction in myocardial blood flow despite a patent epicardial coronary artery. The two groups were age matched. The passive and active myocardial parameters were determined from the measured in vivo data (LV cavity volume and strain) to match the LV dynamics in diastole and systole. Results Student’s t-test was used for significance test. Our results show that even though the average measured peak cuff-pressure in the MI group is much lower than the healthy group (122 ± 21 vs. 150 ± 20mmHg, p Conclusions In summary, we have shown for the first time that, compared with controls, patients with recent ST-elevation myocardial infarction exhibit increased active tension generation in combination with predictable changes in end-diastolic volume and ejection fraction. Active tension generation is a novel biomechanical index, and its clinical and prognostic significance merits further study. Funding British Heart Foundation (PG/14/64/31043)

Endotoxemic myocardial dysfunction: subendocardial collagen deposition related to coronary driving pressure.

Sepsis impairs the autoregulation of myocardial microcirculatory blood flow, but whether this impairment is correlated with myocardial remodeling is unknown. This study investigated the role of coronary driving pressure (CDP) as a determinant of microcirculatory blood flow and myocardial fibrosis in endotoxemia and sepsis. The study is composed of two parts: a prospective experimental study and an observational clinical study. The experimental study was performed on male Wistar rats weighing 300 to 320 g. Endotoxemia was induced in rats by lipopolysaccharide (LPS) injection (10 mg·kg intraperitoneally). Hemodynamic evaluation was performed 1.5 to 24 h after LPS injection by measuring the mean arterial pressure, CDP, left ventricular end-diastolic pressure, dP/dtmax, and dP/dtmin. Microspheres were also infused into the left ventricle to measure myocardial blood flow, and myocardial tissue was histologically assessed to analyze collagen deposition. The CDP, mean arterial pressure, and myocardial blood flow were reduced by 55%, 30%, and 70%, respectively, in rats 1.5 h after LPS injection compared with phosphate buffer saline injection (P < 0.05). The CDP was significantly correlated with subendocardial blood flow (r = 0.73) and fibrosis (r = 0.8). Left ventricular function was significantly impaired in the LPS-treated rats, as demonstrated by dP/dtmax (6,155 ± 455 vs. 3,746 ± 406 mmHg·s, baseline vs. LPS; P < 0.05) and dP/dtmin (-5,858 ± 236 vs. -3,516 ± 436 mmHg·s, baseline vs. LPS; P < 0.05). The clinical study was performed on 28 patients with septic shock analyzed for CDP. The CDP data and histological slices were collected from septic patients. In addition, the clinical data demonstrated fibrosis and 45% CDP reduction in nonsurvivors compared with survivors. In conclusion, the left ventricular subendocardial blood flow was positively correlated with CDP, and higher CDP was negatively correlated with myocardial collagen deposition. Thus, early reductions in myocardial blood flow and CDP facilitate late myocardial fibrosis in rats and likely in humans.

Severity of blood flow reduction associated with detectable T2 enhancement in the area at risk of a reperfused canine model of acute myocardial infarction

Background T2-weighted enhancement depicts the myocardial area at risk (AAR) associated with coronary occlusion. However, the severity of blood flow abnormality required to cause a detectable elevation in myocardial T2 is unknown. The aim of this study was to use microspheres to determine the severity of reduction in myocardial blood flow that results in visually detectable T2 weighted enhancement. Methods Surface coil intensity corrected T2 prepared SSFP at 1.5T was performed after 2 hours of coronary occlusion followed by 4 hours of reperfusion in a canine model. Myocardial blood flow during ischemia was determined by administering microspheres. A mid-ventricular short axis slice of the heart was divided into 16 transmural sectors for microsphere analysis. MR images were matched to the pathological slices at the sector level using papillary muscles and RV insertion as landmarks. ROIs delineated T2-enhanced and remote regions of the MR images and measurements were compared with microsphere blood flows. Results were reported as median (interquartile range [IQ]) and compared using the signed Wilcoxon rank test. Each T2-prepared sector was classified as bright (AAR) or normal (remote) by 2 independent readers and compared with absolute microsphere blood

Dialysis-induced segmental wall motion abnormalities, post-dialysis fatigue and cardiovascular mortality: the new Bermuda triangle?

Dialysis patients exhibit higher rates of death compared withthe general population [1], with an almost similar increase inthe proportion of cardiovascular (CV) and non-CV deaths[1]; however, the CV mortality risk in patients starting dialy-sis is much higher compared with the general population(unstandardized CV risk—15-fold higher/age-standardizedCV risk—8.8 higher than in matched individuals from thegeneral population) [1] and is not determined by the samerisk factors. Indeed, classical atherosclerotic disease is not themost important and common cause of death in a moderndialysis population. Sudden cardiac death (SCD) [2] andheart failure are the most frequent forms of death in dialysispatients; the overall incidence of these events is much greaterthan the incidence of coronary events [3]. Moreover, the riskpersists after coronary vascularization [4]. Important factorsfor this significant CV morbidity include left ventricular (LV)hypertrophy, electrolyte shifts during haemodialysis (HD),poor volume control [5] and abnormalities in myocardialultra-structure and function, including endothelial dysfunc-tion, interstitial fibrosis, impaired coronary flow reserve anddiminished ischaemia tolerance.One potential important player in the mechanisms behindthis excess mortality is the HD procedure. It is obvious thatthe HD procedure is stressful for the CV system; almost 30%of HD sessions are associated with significant intra-dialytic hy-potension [6]. Intermittent HD treatments may induce globaland segmental myocardial ischaemia [7, 8]. This was suggestedby Selby’s studies using echocardiography [9, 10] and cardiactroponin levels [11] and by Singh et al.[12] using 99Tc-sesta-mibi single-photon emission computed tomography. Confir-mation that an HD session is undeniably capable of inducingregional myocardial ischaemia was provided recently by McIn-tyre et al. [7]. Using intra-dialytic H215O positron emissiontomography and echocardiography, they showed that HDtreatment elicited reversible (LV) regional wall motion ab-normalities (RWMAs) with matched reductions in myocardialblood flow (MBF). Dasselaar et al.[8] reconfirmed 1 year laterthese results in non-diabetic non-cardiac-compromisedpatients. They observed a significant reduction in MBF, earlyduring dialyses that were not accompanied by significant fluidremoval.In the general population, repeated episodes of transientmyocardial ischaemia lead to a spectrum of disease encom-passing myocardial stunning, myocardial hibernation andending in myocardial remodelling and scarring, with irrevers-ible loss of contractile function. Myocardial stunning isdefined as a prolonged LV dysfunction without histologicalsigns of irreversible injury to cardiomyocytes. It occurs eachtime when ischaemia and reperfusion are present: in patientswith coronary artery disease, after percutaneous transluminalcoronary angioplasty, after coronary bypass or cardiac trans-plantation or following resuscitation. Myocardial stunninghas been well described in the general population as a causa-tive mechanism for heart failure [9]. Myocardial hibernationis described also as depressed myocardial contractility, butthe ischaemic myocardium remains viable and the LV dys-function can be partially or completely restored to normality,by improving/restoring blood flow. In pathophysiologicalterms, a severe reduction in coronary flow reserve is commonfor both conditions, and recovery of function is paralleled byrestoration of an adequate coronary flow reserve.The reduction in MBF during HD is associated with myo-cardial remodelling and eventually non-viable myocardiumwith irreversible reduction in LV function. This processbecomes increasingly appreciated as a principal pathophysio-logic contributor to the excess CV mortality in HD patients