Infarct-related Coronary Artery Research Articles

Different aspects of coronary microvascular damage during reperfusion of ST-elevation acute myocardial infarction

The beneficial effects of a timely recanalisation of the infarct-related coronary artery in ST-elevation myocardial infarction may be limited at the microvascular level by reperfusion injury and distal microembolisation. These complications carry ominous consequences for both prognosis and survival.The importance of reperfusion injury and microembolisation has been progressively more recognized and many different preventive and therapeutic interventions have been developed to minimise these complications. In the present contribution some simple elements of value in the understanding, recognition and differential diagnosis of reperfusion injury and coronary microembolisation are provided.

Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction – MiHeart/AMI study

BackgroundMyocardial infarction remains as a major cause of mortality worldwide and a high rate of survivors develop heart failure as a sequel, resulting in a high morbidity and elevated expenditures for health system resources. We have designed a multicenter trial to test for the efficacy of autologous bone marrow (ABM) mononuclear cell (MC) transplantation in this subgroup of patients. The main hypothesis to be tested is that treated patients will have a significantly higher ejection fraction (EF) improvement after 6 months than controls.MethodsA sample of 300 patients admitted with ST elevation acute myocardial infarction (STEMI) and left ventricle (LV) systolic dysfunction, and submitted to successful mechanical or chemical recanalization of the infarct-related coronary artery will be selected for inclusion and randomized to either treated or control group in a double blind manner. The former group will receive 100 × 106 MC suspended in saline with 5% autologous serum in the culprit vessel, while the latter will receive placebo (saline with 5% autologous serum).ImplicationsMany phase I/II clinical trials using cell therapy for STEMI have been reported, demonstrating that cell transplantation is safe and may lead to better preserved LV function. Patients with high risk to develop systolic dysfunction have the potential to benefit more. Larger randomized, double blind and controlled trials to test for the efficacy of cell therapies in patients with high risk for developing heart failure are required.Trial RegisterThis trial is registered at the NIH registry under the number NCT00350766.

Methylenetetrahydrofolate reductase (MTHFR) C677T genetic polymorphism and late infarct-related coronary artery patency after thrombolysis

In patients with acute myocardial infarction (AMI), a persistently occluded infarct-related artery (IRA) is associated with unfavorable prognosis and genetic factors may be contributing factors to thrombolysis failure. One-hundred and one consecutive patients treated with intravenous thrombolysis during AMI were blind-tested for methylenetetrahydrofolate reductase (MTHFR) and circulating homocysteine levels and underwent protocol angiography 14 +/- 6 days after the event. IRA was patent in 61 patients and occluded in 40. Overall MTHFR 677TT frequency was 22%. Patients with MTHFR 677TT homozygosis had higher prevalence of occluded IRA (73%) versus those with MTHFR 677CT/CC genotype (30%, P < 0.001); MTHFR 677TT genotype predicted independently the risk of IRA occlusion with a specificity of 90% (odds ratio 3.8, 95% confidence interval 1.1-9.1; P = 0.03). Moreover, patients with occluded IRA and MTHFR 677TT genotype had the highest homocysteine levels (21 +/- 7.6 micromol/l vs. < or =14.9 +/- 3.8 micromol/l; P = 0.011). In patients with AMI, MTHFR 677TT homozygosis is independently associated with a persistently occluded IRA after thrombolysis. This finding may have pathophysiological and therapeutic implications for recanalization strategies in patients with AMI.

Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia–reperfusion injury

Inhalation of hydrogen (H 2) gas has been demonstrated to limit the infarct volume of brain and liver by reducing ischemia–reperfusion injury in rodents. When translated into clinical practice, this therapy must be most frequently applied in the treatment of patients with acute myocardial infarction, since angioplastic recanalization of infarct-related occluded coronary artery is routinely performed. Therefore, we investigate whether H 2 gas confers cardioprotection against ischemia–reperfusion injury in rats. In isolated perfused hearts, H 2 gas enhances the recovery of left ventricular function following anoxia-reoxygenation. Inhaled H 2 gas is rapidly transported and can reach ‘at risk’ ischemic myocardium before coronary blood flow of the occluded infarct-related artery is reestablished. Inhalation of H 2 gas at incombustible levels during ischemia and reperfusion reduces infarct size without altering hemodynamic parameters, thereby preventing deleterious left ventricular remodeling. Thus, inhalation of H 2 gas is promising strategy to alleviate ischemia–reperfusion injury coincident with recanalization of coronary artery.

Mechanisms by Which Late Coronary Reperfusion Mitigates Postinfarction Cardiac Remodeling

Although recanalization of the infarct-related artery late after myocardial infarction (MI) is known to reduce both cardiac remodeling and mortality, the mechanisms responsible are not yet fully understood. We compared infarcted rat hearts in which the infarct-related coronary artery was opened 24 hours after infarction (late reperfusion [LR] group) with those having a permanently occluded artery. Left ventricular dilatation and dysfunction were significantly mitigated in the LR group 1, 2, and 4 weeks post-MI. Attributable, in large part, to the greater number of cells present, the infarcted wall was significantly thicker in the LR group, which likely reduced wall stress and mitigated cardiac dysfunction. Granulation tissue cell proliferation was increased to a greater degree in the LR group 4 days post-MI, whereas the incidence of apoptosis was significantly lower throughout the subacute stage (4 days, 1 week, and 2 weeks post-MI), further suggesting preservation of granulation tissue cells contributes to the thick, cell-rich scar. Functionally, myocardial debris was more rapidly removed from the infarcted areas in the LR group during subacute stages, and stouter collagen was more rapidly synthesized in those areas. Direct acceleration of Fas-mediated apoptosis by hypoxia was confirmed in vitro using infarct tissue-derived myofibroblasts. In salvaged cardiomyocytes, degenerative changes, but not apoptosis, were mitigated in the LR group, accompanied by restoration of GATA-4 and sarcomeric protein expression. Along with various mechanisms proposed earlier, the present findings appear to provide an additional pathophysiological basis for the benefits of late reperfusion.

The value of fractional and coronary flow reserve in predicting myocardial recovery in patients with previous myocardial infarction

The aim of the study was to evaluate the relation between fractional flow reserve (FFR) and simultaneously evaluated coronary flow reserve by thermodilution (CFRthermo), with the improvement of left ventricular (LV) function in patients with previous myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). Study population consisted of 46 patients (mean age 53 +/- 7 years; 36 male) with previous MI and significant coronary stenosis undergoing PCI of infarct-related coronary artery. In all patients, we evaluated FFR and CFRthermo by single pressure/thermo wire during maximal hyperaemia before and immediately after PCI. We performed echocardiographic assessment of LV ejection fraction before and 6 months after PCI. Dobutamine stress echocardiography test was also performed before PCI. LV functional improvement was observed in 33/46 (72%) of patients. In patients with LV functional recovery in comparison with patients with no recovery, there was a significant difference in FFR before PCI (0.56 +/- 0.14 vs. 0.70 +/- 0.07, P < 0.001), improvement of FFR (0.35 +/- 0.14 vs. 0.21 +/- 0.07, P < 0.001), improvement of CFRthermo (1.3 +/- 0.6 vs. 0.5 +/- 0.3, P < 0.001), and CFRthermo after PCI (2.6 +/- 0.7 vs. 2.0 +/- 0.4, P < 0.001). When only parameters evaluated before PCI were taken into account, FFR before angioplasty (P = 0.001) and dobutamine-assessed viability (P = 0.006) were the most significant multivariate predictors of myocardial recovery. When all significant univariate parameters were evaluated, the most significant independent predictors for improvement in myocardial function were the improvement of CFRthermo during angioplasty (P < 0.001) and FFR before angioplasty (P = 0.002). Simultaneous evaluation of FFR and CFRthermo provide significant complementary data on the improvement in myocardial function in patients with previous MI. However, the evaluation of FFR before angioplasty identifies viable myocardium that may recover following revascularization and may be used as an alternative to non-invasive testing.

Preserved coronary endothelial function by inhibition of δ protein kinase C in a porcine acute myocardial infarction model

Background Previous studies demonstrate impairment of endothelial-dependent vasodilation after ischemia/reperfusion (I/R). Though we have demonstrated that inhibition of δ protein kinase C (δPKC) at reperfusion reduces myocyte damage and improves cardiac function in a porcine acute myocardial infarction (AMI) model, impact of the selective δPKC inhibitor on epicardial coronary endothelial function remains unknown. Methods Either δPKC inhibitor (δV1-1, n = 5) or saline ( n = 5) was infused into the left anterior descending artery at the last 1 min of the 30-min ischemia by balloon occlusion. In vivo responses to bradykinin (endothelium-dependent vasodilator) or nitroglycerin (endothelium-independent vasodilator) were analyzed at 24 h after I/R using intravascular ultrasound. Vascular responses were calculated as the ratio of vessel area at each time point (30, 60, 90 and 120 s after the infusion), divided by values at baseline (before the infusion). Results In control pigs, endothelial-dependent vasodilation following bradykinin infusion in infarct-related epicardial coronary artery was impaired, whereas in δPKC inhibitor-treated pigs the endothelial-dependent vasodilation was preserved. Nitroglycerin infusion caused similar vasodilatory responses in the both groups. Conclusions This is the first demonstration that a δPKC inhibitor preserves vasodilator capacity in epicardial coronary arteries in an in vivo porcine AMI model. Because endothelial dysfunction correlates with worse outcome in patients with AMI, this preserved endothelial function in epicardial coronary arteries might result in a better clinical outcome.

Diagnosis and discrimination of remote antero- and inferoseptal non-Q wave myocardial infarctions with body surface potential mapping

Previous studies have shown that the diagnosis and localization of previous non-Q wave myocardial infarction (NQMI) is possible by body surface potential mapping (BSPM), but the criteria for the discrimination between anteroseptal and inferoseptal middle regions remain to be determined. BSPM using 63 unipolar leads was recorded in 119 patients with previous NQMI (36 to 76 years of age, average 61 years; 85 men). Localization of anteroseptal or inferior middle NQMI occurred in 70 cases (44 to 76 years of age, average 61 years, 53 men) by determining early anterior minimum potential with only slight negativity. In these cases, isopotential maps obtained at additional time points were investigated to discriminate between anteroseptal and inferoseptal NQMI. The clinical localization was based on the concordance of two of the following tests: wall motion disturbances on echocardiography, coronary angiogram and repolarization changes in the acute-phase electrocardiogram. Two milliseconds before the appearance of the first anterior minimum, a more accentuated superior negativity indicated anteroseptal NQMI (32 of 70 cases), while a more pronounced inferior negativity indicated inferoseptal NQMI (38 of 70 cases). Fisher's exact test showed statistically significant associations between the above BSPM localizations and the clinical localizations (P<0.001). Occlusion or stenosis of the expected infarct-related coronary artery was detected in all patients either as a single lesion or together with other coronary artery lesions. The BSPM criteria proposed here are suitable to detect the most frequent NQMI localizations. The narrowing of the infarct-related coronary arteries, the left anterior descending or the posterior descending coronary artery, can be thus differentiated.

Acute myocardial infarction preceded by potential triggering activities: Angiographic and clinical characteristics

Background In an investigation of the relationship between myocardial infarction (MI) preceded by certain activities or events and coronary angiographic data, including the extent of atherothrombotic involvement during acute MI, we hypothesized that when comparing patients with MI that was preceded by potential triggering activities (PTA “+”) to MI without PTA, the former might have a distinct pathogenic basis exhibiting different angiographic and clinical features. Methods In the framework of a national survey on acute coronary syndromes conducted during a 2-month period in 2002, 662 acute MI patients with complete angiographic data were divided into two groups, according to whether or not they reported the presence of specific unusual events or activities immediately preceding the onset of MI. Results One hundred and one patients with PTA “+” MI were younger, and included a higher proportion of smokers than their counterparts ( n = 561), who were characterized by a higher frequency of hypertension and diabetes. After adjustment for age, gender, prior MI or CABG, diabetes, hypertension, current smoking, serum creatinine level, left ventricular ejection fraction less than 30%, re-ischemia and Killip class II+, 30-day, 6 month and 1-year mortality was similar between the two groups. The incidence of LAD disease ( P < 0.01), 3-vessel coronary disease ( P < 0.03) and TIMI flow 0 or 1 after coronary angioplasty was significantly lower ( P < 0.02) in patients with PTA “+” MI, while infarct-related right coronary artery (RCA) obstruction was significantly higher (OR: 1.7; 95% CI: 1.0–2.9). Conclusion Further investigation is needed in order to confirm the association between angiographic data and potential triggering activities observed in our study, and to determine the mechanisms responsible for this finding.

The Late Open-Coronary Artery Hypothesis: Dead, or Not Definitively Tested?

Continued controversy surrounds the optimal therapeutic approach to the patient who does not undergo percutaneous coronary intervention (PCI) early during acute myocardial infarction, when ischemic myocardium could still be salvaged, and who presents days to weeks after the acute event with persistent total occlusion of the infarct-related coronary artery. The Occluded Artery Trial (OAT) demonstrated no measurable effect of PCI on outcome. There were trends, however, for more frequent reinfarctions and a higher estimated 4-year cumulative primary event rate. Because patient selection included only patients with 1- or 2-vessel coronary disease, and because interventionalists were permitted to perform PCI on the noninfarct-related arteries, >85% of patients in the intervention group had no coronary arteries with significant obstructions after PCI, a situation that would cause the functional regression of existing collaterals. If subsequent plaque rupture and total occlusion of any of the 3 coronary arteries occurred (expected in 5% to 15% of patients with acute coronary syndromes over the first 1 to 2 years), the impaired collateral flow immediately after new acute occlusion would predispose to greater myocardial injury and therefore greater patient risk, which could explain the negative effects of the OAT study, and which raises the disturbing possibility that complete revascularization in patients with recent acute coronary syndromes could possibly lead to greater risks in the following 1 to 2 years in those patients who experience recurrent acute coronary occlusion. Conversely, late opening of the culprit artery in patients with multivessel coronary disease, without all arteries being patent, may favorably alter late outcomes. In conclusion, the therapeutic implications of the OAT study apply to a specific patient cohort; whether late opening of the culprit artery improves or impairs outcome appears critically to depend on the specific cohort treated.

Transient myocardial bridging of the left anterior descending coronary artery in acute inferior myocardial infarction

We observed transient myocardial bridging of left anterior descending coronary artery (LAD) in 18.75% (12 of the total 64) of the patients during acute inferior myocardial infarction (MI). Myocardial bridging occurred only in the acute phase of inferior MI and not in the chronic phase. In the acute phase of inferior MI, compensatory hypercontraction of the anterior wall is assumed to occur in response to the decrease in the movement of the infarct-related walls. In the chronic phase, disappearance of the myocardial bridging observed due to the resolution of compensatory anterior wall hypercontraction, as a result of the reperfusion of infarct-related coronary artery. Most of the myocardial bridges seen in autopsy series are not seen angiographically. Variation at angiography may in part be attributable to small and thin bridges causing little compression. Adrenergic stimulation or afterload reduction by nitroglycerin facilitates diagnosis of myocardial bridging by increasing coronary compression. Both of these conditions are almost always present in acute MI. We concluded that transient myocardial bridging of LAD can be observed in some patients with acute inferior MI during acute stage.

Abstract 3336: Fractional and Coronary Flow Reserve in Prediction of Functional Recovery of Myocardium in Patients with Previous Myocardial Infarction

Background: Fractional flow reserve (FFR) may provide clinically useful diagnostic information both in patients (pts) with normal left ventricular (LV) function as well as in pts with previous myocardial infarction (MI). However, the question remains to the relation between improvement of FFR and improvement of LV function in pts with previous MI undergoing percutaneous coronary intervention (PCI). Aim: The aim of the study was to evaluate the relation between FFR and simultaneously evaluated coronary flow reserve by thermodilution (CFRthermo), with functional improvement of LV function in pts with previous MI undergoing PCI. Methods: Study population consisted of 50 pts (mean age 53±8 years; 40 male) with previous MI and significant coronary stenosis in one-vessel CAD (33 LAD, 4 Cx, 13 RCA) undergoing PCI of infarct-related coronary artery. In all pts we have evaluated by single pressure/thermo wire FFR and CFRthermo before and immediately after PCI. In all pts, we have evaluated LV ejection fraction by echo and wall motion score index (WMSI) before and 3 months after PCI. Results: Coronary lesions were successfully treated in all pts with decrease of diameter stenosis from 63±7% to 18±9% (p&lt;0.001). FFR increased significantly (p&lt;0.001) from 0.62±0.15 to 0.91±0.06 after PCI, whereas CFRthermo increased significantly (p&lt;0.01) from 1.5±0.3 to 2.5±0.7. LV ejection fraction increased from 49±6% to 55±8% (p&lt;0.0001), and WMSI decreased from 1.44±0.24 to 1.29±0.29 (p&lt;0.0001). LV functional improvement was observed in 33/50 (66%) of pts. In pts with LV functional recovery in comparison to pts with no recovery there was significant difference in FFR before PCI (0.57±0.15 vs. 0.71±0.11, p=0.001), improvement of FFR during PCI (0.34±0.15 vs. 0.21±0.13, p=0.004), improvement of CFRthermo during PCI (1.2±0.6 vs. 0.6±0.5, p=0.001) and CFRthermo after PCI (2.7±0.7 vs. 2.1±0.6, p=0.008), respectively. Conclusion: Evaluation of FFR and CFRthermo provide significant prognostic information on LV functional recovery in pts with previous MI undergoing PCI. Lower FFR before PCI, higher CFRthermo after PCI, as well as higher improvement of FFR and CFRthermo during PCI are indicative of left ventricular functional improvement in pts with previous MI.

Abstract 2986: Did Early Hazard of PCI Offset Late Benefit in the Occluded Artery Trial (OAT)?

Background: The Occluded Artery Trial (OAT) showed no reduction in death, MI or class IV CHF with routine PCI in occluded infarct-related coronary arteries in stable patients identified up to 28 days post MI. PCI of non-acute coronary occlusions can be complex and hazardous. We report the magnitude and nature of PCI-related early hazard in OAT and its contribution to overall trial results. Methods: All 1101 PCI and 1100 medical therapy (MED) assigned patients were examined by intention-to-treat. Pre-specified events (death, MI, class III or IV HF) and procedural complications during the first 48 hours after OAT enrollment (including at least 24 hours post protocol-driven PCI) were analyzed, and the OAT primary composite outcome (death, adjudicated MI, or new class IV HF) was examined at 5 and 30 days, and 60 months. Results: Events or complications within 48 hours of enrollment occurred in 55 PCI patients (5.0%) versus 29 MED patients (2.6%) (p=0.01). PCI patients experienced more class III or IV HF events (5 vs. 2), coronary perforation (4 vs. 1), ventricular arrhythmias (6 vs. 2), CNS complications (3 vs. 2), major hemorrhage (8 vs. 1), and vascular complications (5 vs. 1). Cardiac rupture occurred in 4 patients; 2 in each arm. Events/complications were deemed PCI-related by sites in 35 of 55 patients, and by central review in 30 of 55. Attribution by sites and central review were generally concordant and indicate that the observed events excess was causally related to PCI procedures. Conclusion: While there was no excess mortality in the PCI-treated group, events and complications during the first 48 hours were significantly more common in OAT patients assigned PCI than in those assigned MED. This early procedural hazard, however, was small in magnitude and was not followed by convergence of event rates through 60 months. We conclude the absence of net benefit for routine PCI in OAT cannot be explained by early hazard offsetting late benefit. Primary Outcome Life Table Event Rates: 48 hrs, 5 and 30 days, and 60 months

Abstract 2393: Similar Long-Term Outcomes After PCI Success, PCI Failure, and no PCI in the Occluded Artery Trial (OAT)

Background: The Occluded Artery Trial (OAT) showed that a strategy of routine percutaneous coronary interventions (PCI) for occluded infarct-related coronary arteries identified up to 28 days post-MI does not reduce the primary end point of death, MI or class IV CHF compared to medical therapy alone (MED). However, PCI was not universally attempted in patients assigned PCI, and was not always successful when attempted. Moreover, some MED patients underwent early PCI. Using an as-treated analysis, we compared the outcomes of (1) successfully-treated PCI patients to medically-treated MED patients, and (2) PCI-assigned patients according to PCI success versus failure. Methods: Of 2201 patients randomized in OAT (2166 + 35 substudy), 1101 were assigned PCI and 1100 to MED. PCI assignment was categorized as attempted and successful (Success), attempted and unsuccessful (Fail), or No Attempt. MED assignment was categorized as medical only (Med Only) or crossover (X-Over) if PCI of the occlusion was performed in ≤30 days. Life table estimates of primary and secondary outcomes were calculated to compare as-treated categories. Results: Baseline characteristics of PCI Success and MED Only groups were similar. Compared to PCI Success, PCI Fail patients were more likely to be male, with higher rates of prior PCI, Killip Class 2– 4, and higher LV end-systolic sphericity index. No significant differences in primary or secondary outcomes were observed between PCI Success versus MED Only, or between PCI Success and PCI Fail. Med X-Over and PCI No Attempt groups were small. Conclusions: As-treated analysis does not reveal important differences in outcome, whether the comparison is between those with PCI success versus medical therapy alone, or between PCI success and PCI failure. These data indicate that the primary intention-to-treat results of OAT would not be altered by higher PCI success rates. 60-Month Life Table Event Rate Estimates

Sirolimus-Eluting Stent Implantation Aggravates Endothelial Vasomotor Dysfunction in the Infarct-Related Coronary Artery in Patients With Acute Myocardial Infarction

This study examined whether sirolimus-eluting stent (SES) implantation may affect endothelial vasomotor dysfunction in resistance and epicardial infarct-related coronary arteries in acute myocardial infarction (AMI). Myocardial ischemia-reperfusion causes endothelial injury entirely in the vasculature of the infarct-related coronary artery. Sirolimus-eluting stent implantation inhibits re-endothelialization at the site of stenting. This study included 29 patients with a first AMI due to occlusion of the left anterior descending coronary artery (LAD) and successful reperfusion therapy using a SES (n = 13) or bare-metal stent (BMS) (n = 16). The diameter of the epicardial segment distal to the site of SES deployment and coronary blood flow in the LAD in response to an intracoronary infusion of acetylcholine were measured at 2 weeks after AMI. Levels of vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunoadsorbent assay in plasma obtained from the aortic root (AO) and the anterior interventricular vein (AIV) in all patients. The epicardial coronary artery was more severely constricted in response to acetylcholine in the SES than in the BMS group. The increase in coronary blood flow in response to acetylcholine was lower in the SES than in the BMS group. Vascular endothelial growth factor levels in the AIV were significantly lower than in the AO in the SES group but not in the BMS group. During the course of AMI, SES implantation adversely affects endothelium-dependent vasomotor function in resistance and epicardial coronary arteries after the ischemia-reperfusion in association with a reduction in myocardial VEGF secretion.

Fractional flow reserve after previous myocardial infarction

Marques and colleagues have conducted an interesting study on microvascular resistance of viable tissue within an infarcted area.1 This study is important, not only from a conceptual point of view, but also because it has several relevant implications for the applicability of MIBI spect and fractional flow reserve (FFR) measurement in patients with previous myocardial infarction and a residual or recurrent stenosis in the infarct-related coronary artery. The use of these methods, one non-invasive and the other invasive, has been supported by theoretical and empirical data, but the present study corroborates their usefulness in patients with previous myocardial infarctions. To understand the clinical implications of the study by Marques et al. , it is paramount to understand microvascular resistance, which so far has been hard to assess in conscious humans. Microvascular resistance equals the ratio of distal coronary pressure divided by myocardial blood flow. As surrogates for the numerator and denominator of that ratio, sometimes aortic pressure and coronary blood flow or flow velocity, respectively, have been used, which might be correct in healthy persons. However, in patients with coronary artery disease, the first number overestimates distal coronary pressure and the second one underestimates myocardial blood flow, and therefore use of these surrogates leads to progressive overestimation of myocardial resistance in the case of a stenotic coronary artery.2–4 As a consequence, our knowledge about microvascular resistance in patients with coronary disease, and especially after previous myocardial infarction, has remained questionable. Furthermore, from a clinical point of view, i.e. the question of whether inducible ischaemia is still present or present again, the interesting index to study is hyperaemic blood flow, corresponding to minimal resistance of the viable myocardium within the infarcted zone, not the resistance of the scar tissue. … Corresponding author. Tel: +31 (40) 239 7004; fax: +31 (40) 244 7885. E-mail address: nico.pijls{at}inter.nl.net

Intracoronary delivery of autologous bone marrow mononuclear cells radiolabeled by 18F‐fluoro‐deoxy‐glucose: Tissue distribution and impact on post‐infarct swine hearts

Intracoronary injection of the bone marrow-derived mononuclear cells (MNCs) is emerging as a potentially novel therapy for ischemic heart failure. This study was aimed at assessing the efficacy of intracoronary MNC delivery in the myocardium. The in vivo distribution and myocardial homing of intracoronarily delivered MNCs in experimental Chinese swine with acute myocardial infarction (AMI) created by occlusion of left anterior descending (LAD) coronary artery for 90 min. MNCs radiolabeled with 18F-fluoro-deoxy-glucose (18F-FDG) were delivered using a coronary catheter into the infarct-related coronary artery 1 week after AMI. Dual-nuclide single photon emission computed tomography (SPECT) revealed that 1 h after cell infusion, 6.8 +/- 1.8% of 18F-FDG-labeled MNCs occurred in the infarcted myocardium with the remaining activity found primarily in the liver and spleen. In the heart, MNCs were detected predominantly in the under-perfused myocardium. The infused cells retained in the hearts at a rate highly correlated with the under-perfused lesional sizes. Pathological examination further demonstrated that 6 weeks after infusion, compared to controls, the hearts receiving MNCs exhibited less fibrosis and inflammatory infiltrate, more viable tissue, and higher vascular density. Cardiac function was significantly improved in the MNC-infused hearts. Thus, 18F-FDG labeling and dual-nuclide SPECT imaging is capable of monitoring in vivo distribution and homing of MNCs after intracoronary infusion. MNC coronary delivery may improve cardiac function and positive ventricular remodeling in the heart with AMI.

The Open Artery Hypothesis: Beneficial Effects and Long-term Prognostic Importance of Patency of the Infarct-Related Coronary Artery

There seem to be additional mechanisms of benefit in patients receiving late reperfusion therapy in a time when the opportunity for myocardial salvage has been missed. Previous studies have demonstrated that the restoration of blood flow in the infarct-related coronary artery in patients with acute myocardial infarction improves left ventricular function and reduces mortality. Initially, it was thought that survival was improved because viable myocardium was salvaged. However, data obtained over the past several years have suggested that the restoration of antegrade flow in the infarct-related artery may improve survival via a mechanism independent of the influence on left ventricular function. Clinical interest in the open artery hypothesis has recently resurfaced owing to a substantial improvement in technical aspects of percutaneous coronary interventions (PCI). Observational data suggest a role for late intervention as safer and more effective mechanical reperfusion practices have emerged. Long-term clinical benefits have been shown from balloon angioplasty late after myocardial infarction (MI). Therefore, patients with failed thrombolysis or those with late-presenting MI may still benefit from PCI by mechanisms independent of myocardial salvage. There is accumulative evidence on this matter. Possible mechanisms include reduction of ventricular remodeling, diminished ventricular instability reducing the incidence of arrhythmias, and provision of collaterals to other territories in the event of further coronary artery occlusion. However, caution must be exercised in interpreting the results of studies examining the open artery hypothesis. This hypothesis can be tested in its purest sense in animal experiments; however, the clinical situation is much more complex. Patients may have acute-on-chronic coronary artery occlusion in the presence of multivessel disease and well-developed collateral channels. The pattern of necrosis may also be different with areas of necrosis separated by islands of ischemic, stunned, hibernating, or normal cells. Therefore, the patency of the infarct-related coronary artery in single or multivessel disease days to weeks after infarction markedly influences long-term prognosis unrelated to improvement of left ventricular function. Current technology has made it feasible to open and maintain patency of most occluded infarct-related arteries. However, the hypothesis that late mechanical reperfusion in patients with asymptomatic occluded infarct-related artery will improve long-term clinical outcomes remains to be proved and is currently being tested in a large randomized trial.

Cardiovascular Magnetic Resonance T2-weighted Imaging of Myocardial Edema in Acute Myocardial Infarction

Technical advances in cardiovascular magnetic resonance (CMR) T2-weighted imaging have allowed in-vivo visualization and accurate quantification of myocardial edema, a substantial feature of myocardial ischemic/reperfusion injury. In acute myocardial infarction, myocardial edema imaging can be used to differentiate acute from chronic irreversible injury. This can also be of particular importance in the sub-acute phase in which laboratory markers are equivocal or in the setting of missed infarction. Furthermore, CMR-T2-weighted edema imaging identifies the area at risk and thus can be used to quantify the area of salvaged myocardium after coronary reperfusion by comparing the area of irreversible injury to that of the myocardium at risk. Another exciting area of research employs edema imaging to monitor the effect of interventions that target reduction of myocardial edema. The premise is that myocardial edema results in vascular compression, and may thus contribute to failure of myocardial tissue reperfusion even after reestablishing the patency of the infarct related coronary artery. This can be used to monitor the efficiency of novel therapeutic strategies targeting post-infarction myocardial edema. This mini review will address the pathophysiological, clinical and some technical issues related to edema imaging in acute myocardial infarction. Some recent patents on myocardial edema, Magnetic resonance imaging and myocardial infarction are also addressed.

Early Changes in Ventricular Repolarization after Thrombolytic Therapy in Patients with Acute Myocardial Infarction as Indicators for Prediction of Epicardial Coronary Artery Reperfusion

Objectives: To investigate the relationship between early T-wave inversion after thrombolytic therapy and the likelihood of successful epicardial coronary reperfusion. Subjects and Methods: Thrombolytic therapy was given to 195 patients with ST segment elevation due to acute anterior myocardial infarction (AMI). Coronary angiography was performed. Receiver operating characteristic (ROC) curve (grade of sensitivity versus false positive) was calculated using likelihood ratio method to identify the ideal cut-off values of the ventricular repolarization variables. Results: Predictive indices showed 80% sensitivity, 83% specificity, 81% accuracy, 88% positive predictive value and 71% negative predictive value for early T-wave inversion after thrombolytic therapy. A good concordant agreement was noted between the data of coronary angiography and early T-wave inversion in the infarct-related ECG leads after thrombolysis (kappa coefficient ĸ= 0.876). Stepwise multivariate analysis revealed that early T-wave inversion after thrombolytic therapy of AMI was significantly associated with a history of preinfarction angina, residual infarct-related coronary artery stenosis >50%, short time to thrombolytic therapy <90 min, and evening time for occurrence of thrombolysis (p < 0.05). The ROC curve data analysis showed that early T-wave inversion amplitude after AMI had 87% sensitivity and 84% specificity for predicting successful reperfusion, with an ideal cut-off value of 7.2 mm, while time of T-wave inversion had 80% sensitivity and 79% specificity, with an ideal cut-off value of 120 min. Conclusion: The data indicate that early inversion of T wave after AMI is a statistically significant independent variable in predicting successful epicardial coronary thrombolysis status.