Amount Of Myocardium Research Articles

New Horizons in Cardioprotection

Coronary heart disease is the largest major killer of American men and women and accounted for 1 of every 6 deaths in the United States in 2007.1 The annual incidence of myocardial infarction in the United States is estimated to be 935 000, with 610 000 new cases and 325 000 recurrent attacks. Survivors have a much higher chance of suffering from congestive heart failure, arrhythmias, and sudden cardiac death. Prognosis after an acute myocardial ischemic injury is primarily dependent on the amount of myocardium that undergoes irreversible injury.2–4 Large transmural infarcts yield a higher probability of cardiogenic shock, arrhythmias, adverse remodeling, and development of late chronic heart failure. Although it has been known since the early 1970s that the size of a myocardial infarction can be modified by various therapeutic interventions,5 early coronary artery reperfusion by fibrinolysis or percutaneous coronary intervention, including balloon angioplasty with or without stenting, remains the only established intervention capable of consistently reducing infarct size in humans. Although reperfusion has led to significant advances in patient care and reduction in hospital mortality, delays in seeking medical attention and inherent limitations in initiating fibrinolysis or percutaneous coronary intervention dictate that additional substantive improvements in morbidity and mortality can be achieved only with the development of new adjunctive therapies coupled with reperfusion. In addition, reperfusion therapy itself may induce reperfusion injury, a phenomenon that may encompass stunned myocardium, no-reflow phenomenon, and lethal myocardial cell death. If this injury could be prevented or minimized by administration of adjunctive therapy, then the net benefit of reperfusion could be enhanced. The problem of acute ischemic injury and myocardial infarction is not limited to patients with acute coronary artery syndrome. It remains a major problem in cardiac surgery as well. It is well documented that the incidence of myocardial necrosis after surgery, as determined by creatine kinase MB enzyme release and troponin levels, ranges somewhere between 40% and 60%, and, depending on its clinical definition, the incidence of myocardial infarction after coronary artery bypass graft surgery may be as high as 19%. The intermediate and long-term implications are considerable. In a recent retrospective analysis of 18 908 patients who underwent coronary artery bypass graft surgery and in whom long-term follow-up was available, it was shown that myocardial enzyme elevation within the first 24 hours of surgery was associated with increasing mortality over the course of months to years. This study confirms earlier reports that even small enzyme elevations after surgery are associated with worse long-term outcomes.4

Complete versus incomplete revascularization for treatment of multivessel coronary artery disease in the drug-eluting stent era

Limited data exist regarding the impact of complete revascularization (CR) versus incomplete revascularization (IR) on the long-term outcomes of patients with multivessel coronary artery disease (MVD) who underwent percutaneous coronary intervention with drug-eluting stents. We compared major adverse cardiac events [MACE: death, myocardial infarction (MI), or any revascularization] in 873 patients and in 255 pairs generated by propensity-score matching. CR was performed in 427 patients (48.9%) and IR in 446 (51.1%). While the amount of myocardium at risk by the APPROACH score was similar between two groups (56.0 ± 14.4 vs. 56.7 ± 16.1, p = 0.49), the SYNTAX score was lower in the CR group than in the IR group (20.7 ± 9.4 vs. 23.3 ± 10.7, p < 0.01). MACE occurred in 203 patients (23.3%) during a median follow-up of 35 months. CR was associated with a lower incidence of MACE (HR 0.64; 95% CI 0.46-0.88; p < 0.01) and revascularization (HR 0.61; 95% CI 0.42-0.90; p = 0.01), but not of death (HR 0.87; 95% CI 0.48-1.57; p = 0.64) and MI (HR 0.62; 95% CI 0.23-1.67; p = 0.35). The incidence of periprocedural MI and stent thrombosis was similar in two groups (4.7% in the CR group vs. 3.6% in the IR group, p = 0.42; 1.6 vs. 1.3%, p = 0.72, respectively). After propensity-score matching, patients with CR had fewer MACE and revascularization than those with IR. In patients with MVD, CR strategy using drug-eluting stents could reduce repeat revascularization with similar death, MI, and stent thrombosis risk compared with IR strategy.

Optimal Intravascular Ultrasound Criteria and Their Accuracy for Defining the Functional Significance of Intermediate Coronary Stenoses of Different Locations

We performed this study to determine the optimal intravascular ultrasound (IVUS) criteria and to evaluate their accuracy for defining the functional significance of intermediate coronary stenoses in different locations of the coronary tree. Presence of myocardial ischemia is the most important prognostic factor in patients with coronary artery disease and is determined by both the lesion severity and the amount of myocardium supplied. IVUS and fractional flow reserve (FFR) measurements were performed in 267 intermediate lesions located at the proximal or mid part of major epicardial coronary arteries. Optimal IVUS criteria and their diagnostic accuracy for functionally significant stenoses (FFR <0.8) were assessed. FFR was <0.8 in 88 lesions (33%). The determinants of FFR were minimum lumen area (MLA) and lesion location. The diagnostic accuracy of MLA was highly variable according to the location of lesions. The best cutoff value of MLA to define the functional significance was 3.0 mm(2) (area under the curve [AUC]: 0.81, 95% confidence interval [CI]: 0.68 to 0.91) for proximal left anterior descending artery (LAD) lesions and 2.75 mm(2) for mid-LAD lesions located before the second diagonal branch (AUC: 0.76, 95% CI: 0.66 to 0.84). However, the appropriate MLA to predict the functional significance of lesions could not be found in other segments. When IVUS parameters are used to determine the functional significance of lesions in patients with intermediate coronary artery stenoses, different criteria should be used according to lesion location. In segments or vessels with anatomic variations, IVUS cannot be used for functional assessment of a stenosis. (Comparison of Fractional Flow Reserve and Intravascular Ultrasound; NCT01133015).

Correlation between an angiographic and a cardiac magnetic resonance score of myocardial jeopardy using standard and high-resolution perfusion sequences

Background High temporal resolution required for CMR perfusion imaging results in compromised spatial resolution. However, recent advances, including the use of the advanced acceleration method k-t sensitivity encoding, allow myocardial perfusion imaging with unprecedented spatial resolution. The associated benefits remain to be fully described. The BCIS-1 Myocardial Jeopardy Score (JS) quantifies the amount of myocardium in jeopardy from severe CAD (0= no jeopardy; 12 = maximum jeopardy). It accommodates patients with CABG and left main disease, is prognostically relevant and can easily be calculated by visual analysis of the X-ray coronary angiogram (XCA). Combined perfusion and scar CMR imaging should provide equivalent functional information on myocardial jeopardy. High-resolution perfusion imaging may improve the correlation between JS and CMR findings.

Gender and myocardial salvage after reperfusion treatment in acute myocardial infarction

The aim of this study was to investigate whether there are gender-associated differences in the amount of myocardial salvage after primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Despite having a more adverse cardiovascular risk profile, women with AMI have similar or even better outcomes after primary PCI compared with men. The reasons for these findings are unclear. In this study we included 202 women and 561 men with AMI who underwent primary PCI in the setting of three randomized trials. The primary end point of the study was myocardial salvage index (proportion of initial perfusion defect salvaged by reperfusion therapy), obtained by paired scintigraphic studies performed 7 to 10 days apart. The amount of myocardium at risk or initial perfusion defect (median [25th, 75th percentiles]) did not differ significantly between women and men (22.0% [12.0, 40.0] vs. 24.0% [14.0, 39.0] of the left ventricle [LV], p = 0.26). Final infarct size, measured in the follow-up scintigraphy, was significantly smaller in women than in men (6.0% [0.71, 18.7] vs. 10.0% [3.9, 21.8] of the LV, p = 0.001). Myocardial salvage index was 0.64 (0.35, 0.95) in women versus 0.50 (0.26, 0.77) in men (p < 0.001). After adjustment for baseline characteristics, female gender was an independent predictor of greater myocardial salvage after PCI (p = 0.002). The efficacy of primary PCI in patients with AMI appears to be gender-dependent. Myocardial salvage achieved by primary PCI is greater in women than in men.

192 Predictive value of surface ECG on amount of myocardium with preserved perfusion in patients after Q-wave myocardial infarction: echo-contrast study

192 Predictive value of surface ECG on amount of myocardium with preserved perfusion in patients after Q-wave myocardial infarction: echo-contrast study

Value of echocardiography in predicting future cardiac events after acute myocardial infarction.

Short- and long-term survival after acute myocardial infarction mainly depends on three factors: the amount of myocardium that had become necrotic, the area of myocardium at further risk of becoming necrotic, and the patency of the infarct-related artery. Echocardiography is a low-cost, safe, bedside, repeatable tool, particularly useful for prognostic stratification after myocardial injury. Two-dimensional echocardiography analyzes left ventricular function, the most powerful predictor of survival immediately after acute myocardial infarction. Myocardial contrast echocardiography measures the infarct size and detects viable myocardium. Stress echocardiography stratifies patients with viable myocardium and/or multivessel coronary artery disease who need further diagnostic and therapeutic interventions. Transthoracic coronary Doppler ultrasonography assesses effective recanalization and coronary flow reserve of the left anterior descending coronary artery. Further technologic advances are needed to allow direct noninvasive measurement of flow by transthoracic Doppler ultrasonography in other coronary arteries.

P623 Long-term outcome of patients with high amount of myocardium at risk and stress-induced left-ventricular dysfunction

P623 Long-term outcome of patients with high amount of myocardium at risk and stress-induced left-ventricular dysfunction

Out-of-hospital ventricular fibrillation in patients with acute myocardial infarction: Coronary angiographic determinants

OBJECTIVESThe study intended to compare the acute coronary anatomy of patients with acute myocardial infarction (AMI) complicated by out-of-hospital ventricular fibrillation (VF) versus patients with AMI without this complication.BACKGROUNDMore than half of the deaths associated with AMI occur out of the hospital and within 1 h of symptom onset. The angiographic determinants of out-of-hospital VF in patients with AMI have not been investigated in detail.METHODSAcute coronary angiographic findings of 72 consecutive patients with AMI complicated by out-of-hospital VF were compared with findings from 144 matched patients with AMI without this complication.RESULTSPatients with an acute occlusion of the left anterior descending coronary artery (LAD) or left circumflex coronary artery (LCx) had a higher risk for out-of-hospital VF compared with patients with an acute occlusion of the right coronary artery (RCA) (odds ratio and 95% confidence interval, respectively, 4.82 [2.35 to 9.92] and 4.92 [2.34 to 10.39]). With regard to extent of coronary artery disease (CAD), the location of the culprit lesion in the coronary arteries (proximal vs. mid or distal), the flow in the infarct related artery (IRA), the presence or absence of collaterals to the IRA and chronic occlusions, there were no differences between the two groups.CONCLUSIONSAcute myocardial infarction due to occlusion in the left coronary artery (LCA) is associated with greater risk for out-of-hospital VF compared to the RCA. The location of occlusion within LCA (LAD, LCx, proximal or distal), amount of myocardium at risk for necrosis and extent of CAD are not related to out-of-hospital VF.

Evaluation of an active coronary perfusion balloon device using Doppler flow wire during PTCA.

The aim of this study was to assess whether active coronary perfusion catheters (APC) can provide a sufficient coronary flow in large caliber vessels during balloon inflation. To prevent myocardial ischemia during PTCA, these APC may be employed. However, it is as yet unknown whether the active flow rate of these devices approaches the flow rate prior to PTCA during balloon inflation. Therefore, we measured the efficacy of the APC during balloon inflation in vessels supplying a large amount of myocardium. In 12 patients (1 female, 11 males, 53 +/- 12.6 yr) with stenosed vessels (average diameter 3.4 +/- 0.26 mm), the coronary flow velocity was measured using a 0.014" Doppler guidewire, which was placed distally bypassing the balloon of the APC. The active perfusion balloon catheter was advanced through a 7F guiding catheter along a 0.014" guidewire. After removal of the guidewire, arterial blood being withdrawn from the side port of the femoral angioplasty sheath was pumped through the catheter to the distal coronary vessel. The perfusion volumes of the pump were set to different levels between 30 to 60 ml/min. Intracoronary flow rate was calculated by the angiographically assessed vessel luminal area [symbol: see text] average peak velocity [symbol: see text] 0.5. The mean coronary flow rate prior to PTCA was 43 +/- 17.7 ml/min. Maximum flow during PTCA was 55 +/- 19.6 ml/min. We found a good correlation between the preset external pump rate and the coronary flow in situ (r = 0.92). Pre-PTCA flow rates were achieved in 11 of 12 patients (92%) during balloon inflation. No relevant decrease in the arterial pressure occurred during dilation times of 4.6 +/- 1.63 min. Only two patients showed significant ECG changes during these balloon inflations. After an average follow-up period of 13 +/- 6.3 mo, only one patient (8%) had a significant re-stenosis requiring the implantation of a stent. The combination of intravascular Doppler velocity measurements with quantitative coronary angiography offers the opportunity of exact online flow registration during angioplasty. Using APC, It is possible to maintain a sufficient coronary flow in the distal vessel during balloon inflation even in large vessels. Therefore, as compared with mechanical circulatory assist devices, coronary assist by APC is a little invasive, but according to our measurements it might be a sufficient tool for performing PTCA also in high-risk patients.

Revisiting Reperfusion Therapy in Inferior Myocardial Infarction

Although thrombolytic therapy for acute myocardial infarction (MI) is recommended without regard for infarct location, treatment results are less impressive for inferior than for anterior MI because the amount of myocardium at risk is smaller and less strategically located, and the mortality risk is lower. Whereas the risks associated with anterior MI are relatively constant, high risk subsets of patients with an inferior MI can be identified by simple electrocardiographic criteria, including left precordial ST segment depression, complete atrioventricular heart block and right precordial ST segment elevation. Unfortunately, none of the placebo-controlled, randomized trials have analyzed the benefit of thrombolytic therapy for inferior MI in high risk versus low risk subsets.Thrombolytic therapy should be more successful in reducing infarct size and decreasing mortality in high risk patients with an inferior MI. Thrombolytic therapy may not decrease hospital mortality in low risk patients (baseline risk 2% to 4%) or those with symptom duration >6 h. Whereas it is arguable whether coronary angioplasty is superior to thrombolytic therapy in anterior MI, there are no mortality data to support using angioplasty as a primary or rescue reperfusion strategy instead of thrombolytic therapy in inferior MI, unless thrombolytic contraindications are present or the patient is in cardiogenic shock.

Dobutamine-induced wall motion abnormalities: Correlations with myocardial fractional flow reserve and quantitative coronary angiography

Objectives. This study evaluated both the relation between dobutamine-induced wall motion abnormalities and the physiologic and morphologic features of epicardial coronary artery stenoses and the impact of the extent of the area at risk on the sensitivity of dobutamine echocardiography.Background. The accuracy of dobutamine echocardiography has traditionally been assessed by comparing results with stenosis geometry. Myocardial fractional flow reserve is a functional index of coronary stenosis severity that takes into account both anterograde and collateral flow and may therefore be a more appropriate standard for comparison.Methods. Seventy-five patients with normal left ventricular function, good echocardiographic images and an isolated corenary stenosis underwent, within 6 h, debutamine echocardiography, quantitative coronary angiography and intracoronary pressure measurements. Myocardial fractional flow reserve was calculated as the ratio of mean hyperemic distal coronary to aortic pressure.Results. The degree of dobutamine-induced dyssynergy correlated significantly with percent diameter stenosis (r = 0.68), area stenosis (r = 0.68) and minimal lumen diameter (r = 0.60) and markedly better with myocardial fractional flow reserve (r = −0.77). However, marked dispersion of the individual data was observed. The sensitivity of dobutamine echocardiography in detecting lesions with a minimal lumen diameter ≤1 mm and diameter stenosis ≥50% was 83% and 80%, respectively. All but one patient with a myocardial fractional flow reserve >0.75 had a normal stress test result. Among patients with a myocardial fractional flow reserve ≤0.75, the sensitivity of dobutamine echocardiography was significantly lower for lesions in vessels with a reference diameter ≤2.6 mm than for lesions in larger vessels (58% vs. 90%, p = 0.008).Conclusions. 1) The magnitude of wall motion abnormalities induced by dobutamine infusion correlates with angiographic and, more closely, with functional indexes of stenosis severity, even though a wide scatter is observed. 2) In patients with a functionally significant stenosis, the amount of myocardium at risk is a critical determinant of the accuracy of debutamine echocardiography.

Magnesium in Acute MI

It is an axiom of coronary care medicine that infarct size is a pivotal determinant of the prognosis of patients with acute myocardial infarction (AMI). When one is able to limit the size of an AMI, one is rewarded with a reduction in the number of potentially life-threatening complications such as pulmonary edema, cardiogenic shock, ventricular septal defects, papillary muscle rupture, and ventricular tachyarrhythmias.1 Salvage of even a rim of epicardial tissue as the wave front of necrosis spreads from the endocardium might prevent infarct expansion, ventricular remodeling, and congestive heart failure.2 3 Reperfusion that is sufficiently early (within 15 to 20 minutes) after AMI may prevent ischemic zones of myocardium from progressing to infarction. However, with the possible exceptions of an AMI that develops during cardiac catheterization, of patients who receive prehospital thrombolysis, or of the rare patient who occludes a coronary artery in the Emergency Department or coronary care unit and receives extraordinarily prompt and successful thrombolysis, reperfusion in cases of human AMI results in a mixture of necrotic and salvaged myocytes. The amount of myocardium that is irreversibly damaged (area of necrosis divided by area at risk) is directly related to the duration of occlusion. Interventions that delay cell death (eg, β-blockers) may help to protect ischemic myocytes and leave a greater quantity of viable cells that can subsequently be rescued by reperfusion. More than a decade ago, Braunwald and Kloner2 emphasized that reperfusion therapy, while beneficial in terms of myocardial salvage, may come at a cost because of a process referred to as reperfusion injury. Four aspects of reperfusion injury have been recognized4 : (1) lethal reperfusion injury (reperfusion-induced death of cells that were still viable at the moment of restoration of blood flow), (2) vascular reperfusion injury (no-reflow phenomenon and loss …

Magnitude of myocardial dysfunction is greater in painful than in painless myocardial ischemia: An exercise echocardiographic study

Objectives. This study sought to assess the presence and extent of inducible myocardial dysfunction during painful and painless (silent) myocardial ischemia in a homogeneous patient cohort with coronary artery disease and no previous myocardial infarction.Background. The functional significance of painless versus painful demand-driven ischemia remains controversial, with conflicting results in published reports regarding the amount of myocardium in jeopardy.Methods. Exercise echocardiography was performed in 89 patients (mean [±SD] age 59.3 ± 8.2 years) with significant coronary artery disease and positive exercise stress test results. Patients were taking no antianginal medications and were classified into painless and painful cohorts after the outcome of a symptom-limited treadmill exercise test. No patients had previous coronary artery bypass surgery. Images were acquired in digital format before and immediately after treadmill exercise testing.Results. Fifty-eight patients had painful and 31 painless myocardial ischemia. Clinical and demographic characteristics as well as coronary artery anatomy were similar in both groups. Patients with painless ischemia achieved better exercise performance with greater exercise duration (p < 0.001) and higher maximal rate-blood pressure product (p < 0.001) than those with painful ischemia. New wall motion abnormalities were seen in 54 patients (93%) with painful versus 17 (55%) with painless ischemia (p < 0.001). Total ischemic score was greater in patients with painful than in those with painless ischemia (15.9 ± 3.7 vs. 12 ± 1.4, p < 0.001, respectively), with a greater number of ischemic myocardial segments in painful than in painless ischemia (101 [16%] vs. 21 [6%], p < 0.001, respectively).Conclusions. Patients with painless ischemia frequently have regional myocardial dysfunction on exertion detected by echocardiography, but painful episodes are accompanied by a greater magnitude of myocardial dysfunction.

Comparison using dynamic vectorcardiography and MIBI SPECT of ST-segment changes and myocardial MIBI uptake during percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery

The quantitative relation between ST-segment changes and the severity and extent of myocardial ischemia during coronary occlusion remains unclear. This study assesses whether ST-segment changes during percutaneous transluminal coronary angioplasty (PTCA) correlate with the amount of myocardium at risk, measured with technetium-99m hexakis 2-methoxyisobutyl isonitrile (MIBI; also called sestamibi) single-photon emission computed tomography (SPECT). Quantitative continuous dynamic vectorcardiography was performed during PTCA of the left anterior descending coronary artery in 11 patients (mean age 64.3 years) without previous myocardial infarction. Change in the magnitude of the ST vector (STc-VM) was continuously recorded. A standardized protocol of balloon inflations was used and technetium-99m MIBI was injected intravenously at the onset of the third inflation. SPECT imaging was performed 60 minutes later and compared to a rest acquisition. SPECT was quantified by bull's-eye analysis using: (1) the change in the pathologic/normal area count ratio ( ΔP N ) as an index of the severity of ischemia; and (2) planimetered defect size during PTCA as an indicator of the size of the area at risk. The ΔP N from baseline to balloon occlusion (22 ± 11%) was correlated, albeit loosely, ta the maximum value of STc-VM (245 ± 186 μV, r = 0.62, p < 0.05), but there was no correlation between the size of the scintigraphic defect and STc-VM. Likewise, the sum of ST-segment elevation was correlated to ΔP N (r = 0.72, p < 0.02), but not ta the size of the scintigraphic defect. In conclusion, ST changes induced by coronary occlusion during PTCA are mostly related to the severity of ischemia rather than to the size of the area at risk. During coronary occlusion, ST changes provide only a crude estimate of the amount of jeopardized myocardium.

Prodromal angina limits infarct size. A role for ischemic preconditioning.

In the experimental setting, it has been demonstrated that preconditioning myocardium before prolonged occlusion with brief ischemic episodes affords substantial protection to the cells by delaying lethal injury, thereby limiting infarct size. Whether the same occurs in humans remains unknown. This study was undertaken to determine whether new-onset prodromal angina, defined as chest pain episodes limited to the 24 hours before myocardial infarction, is the clinical correlate of the ischemic preconditioning phenomenon. Twenty-five patients with their first anterior myocardial infarction treated with thrombolysis (recombinant tissue plasminogen activator [r-TPA], 100 mg/3 hours) were retrospectively included in the study because they met the following criteria: (1) < 120 minutes from onset of symptoms to reperfusion therapy, (2) < 90 minutes from the beginning of thrombolytic therapy to reperfusion (defined as rapid ST elevation reduction > 50%), (3) a patient infarct-related coronary artery with TIMI 3 flow and complete absence of collateral circulation to the infarct related artery (assessed at 24 +/- 5 days), and (4) the presence of new-onset prodromal angina, ie, typical chest pain episodes occurring at rest within 24 hours or, alternatively, a complete absence of symptoms before onset of infarction. Therefore, on the basis of their clinical status before infarction, the patients were divided into two groups: group 1, 13 patients without prodromal angina, and group 2, 12 patients with prodromal angina. Despite no difference in time to treatment (81 +/- 19 versus 75 +/- 21 minutes in group 1 and group 2, respectively; P = NS) and time to reperfusion (58 +/- 34 versus 46 +/- 24 minutes; P = NS), the peak of CKMB release was markedly lower in group 2 (86.3 +/- 66 versus 192.3 +/- 108.3 IU/L; P < .01). In addition, although both groups were comparable in terms of area at risk (amount of myocardium beyond the infarct-related stenosis; 15.1 +/- 4.6 versus 13.7 +/- 4.6 hypokinetic segments in group 1 and group 2, respectively, P = NS), the final infarct size (11 +/- 7.5 versus 5.6 +/- 4 hypokinetic segments, P < .04) was smaller in group 2. Thus, the limitation of the infarct size was significantly greater in group 2 (69% versus 36%; P < .05), and this represents an additional 33% reduction (95% confidence intervals, 7.1% to 58.9%; P = .01) in the group of patients with prodromal angina. Also, the third index, that is, the ECG, showed a favorable trend toward a lesser number of Q waves and a higher sigma R waves, although the values did not reach statistical significance. Despite a similar area at risk, patients with new-onset prodromal angina showed a significantly smaller infarct size compared with patients without prodromal symptoms. Since the two groups had similar times to reperfusion and no evidence of collateral circulation to the infarct related artery, the protection afforded by angina in group 2 patients might be explained by the occurrence of ischemic preconditioning.

Does ambulatory monitoring contribute to exercise testing and myocardial perfusion scintigraphy in the prediction of the extent of coronary artery disease in stable angina?

The role of ambulatory myocardial ischemia detection, in addition to exercise testing and myocardial perfusion scintigraphy, in the prediction of the angiographic severity of coronary artery disease in patients with stable angina was examined. Ninety-seven patients underwent ambulatory electrocardiographic monitoring, exercise testing with scintigraphy, and coronary angiography. In addition to the number of diseased vessels involved, proximal arterial segment and coronary artery jeopardy scores were calculated to evaluate the extent of disease and amount of myocardium at risk. Thirty patients (31%) had 1.8 ± 1.8 episodes/24 hours of ambulatory ischemia (94% of episodes were asymptomatic) and were similar to 67 without ambulatory ischemia in regard to clinical characteristics, left ventricular function and mean number of diseased vessels involved. Proximal arterial segment and coronary artery jeopardy scores were greater in: (1) 30 patients with versus 67 without ambulatory ischemia (3.3 ± 1.8 vs 1.9 ± 1.5 [p = 0.0002] and 6.6 ± 3.6 vs 5.0 ± 3.4 [p = 0.03], respectively); (2) 78 with versus 19 without a positive exercise test (2.6 ± 1.8 vs 1.4 ± 0.8 [p = 0.0001] and 6.1 ± 3.5 vs 3.0 ± 2.5 [p = 0.0003], respectively); and (3) 69 with versus 6 without a positive perfusion scan (2.4 ± 1.8 vs 1.0 ± 0 [p = 0.0008] and 5.5 ± 3.6 vs 2.3 ± 2.0 [p = 0.03], respectively). In multivariate analysis, ambulatory ischemia was the best predictor of the proximal segment score, whereas exercise testing and myocardial perfusion imaging were predictive of the coronary jeopardy score.

Reperfusion in acute myocardial infarction: Effect of timing and modulating factors in experimental models

Timely reperfusion of ischemic myocardium in experimental animals halts the advancing transmural “wavefront” of ischemic cell death and thereby limits myocardial infarct size by limiting its transmural extent. The time window of opportunity for such salvage in most experimental models of regional ischemia is the first 3 hours. The number of myocytes that can be salvaged by reperfusion decreases exponentially during this period, such that at 3 hours, reperfusion limits infarct size by only about 10%. The rate of lethal ischemic cell injury and therefore the amount of myocardium that can be salvaged by reperfusion after a particular duration of ischemia is dependent both on the degree of blood flow deficit and the rate of ischemic metabolism. In experimental animal models, several interventions, including hypothermia, calcium antagonists, and “ischemic preconditioning,” have been shown to reduce the rate of ischemic metabolism and to limit myocardial infarct size when assessed after a defined period of ischemia and reperfuslon. Hypothetically, interventions that could prevent additional myocyte necrosis caused by some deleterious aspects of reperfusion (“lethal reperfusion injury”) also could serve as valuable adjunctive therapy. However, studies of therapies designed to prevent lethal reperfusion injury have produced conflicting results. Thus, the concept that lethal reperfusion injury occurs remains controversial. Experimental evidence indicates that reperfusion accelerates both the initial inflammatory response and later process of infarct repair. Late reperfusion of infarcts in dogs, which does not limit myocardial infarct size, appears to accelerate the replacement of necrotic myocardium by scar without altering the size of the final scar.

The relationship of inferior ST depression, lateral ST elevation, and left precordial ST elevation to myocardium at risk in acute anterior myocardial infarction

The purpose of this study was to examine the relationship between the presence or absence of ST segment depression in inferior leads (II, III, and aV F) and ST segment elevation in lateral (I and aV L) or left precordial (V 5 and V 6) leads with the amount and location of myocardium at risk for infarction in patients with acute anterior myocardial infarction. Forty-three patients with anterior infarctions were injected with technetium 99m-sestamibi when they were first seen and underwent tomographic imaging to measure the amount and location of myocardium at risk. Patients with inferior ST depression ( n = 10) compared with those without ST depression ( n = 33) had perfusion defects that extended significantly further into the lateral wall (47 degrees vs 20 degrees, p = 0.04) and larger anterior injury vectors (6.47 vs 4.92, p = 0.008). There was no significant association with the percentage of myocardium at risk, disease of the right coronary artery, the presence of an inferior perfusion defect, or the size of the inferior injury vector. Among the patients with ST elevation in lateral leads ( n = 16) compared with those without ( n = 27), there was a significantly more lateral defect border (47 degrees vs 25 degrees, p = 0.007) and a larger anterior injury vector (6.07 vs 4.81, p = 0.01). There was no significant correlation with the percentage of myocardium at risk. A significant relationship could not be demonstrated between the presence of ST elevation in the left precordial leads and any measure of the amount or location of myocardium at risk. These data support the theory that inferior ST depression in patients with transmural anterior ischemia is a “reciprocal” finding and does not represent inferior ischemia. The presence of inferior ST depression or lateral ST elevation is associated with a more lateral perfusion defect. Neither of these ECG findings is associated with the amount of myocardium at risk for infarction.

Inter-relationships between hypertension, left ventricular hypertrophy and coronary heart disease

Increased left ventricular mass predicts myocardial infarction: Recent studies have demonstrated that increased left ventricular mass is a more potent predictor than is elevated blood pressure of myocardial infarction or death due to coronary heart disease in hypertensive patients. Other research has shown that hypertensive patients commonly have episodes of asymptomatic ischemic ST-segment depression. Several different factors appear to account for this close relationship between myocardial muscle mass and the occurrence of ischemia and vascular morbid events. These include an increased resting demand for coronary blood flow (to supply the greater amount of myocardium), atherosclerotic obstruction of large coronary arteries and reduced vasodilatory capacity of the coronary microcirculation due to arteriolar hypertrophy and dysregulation, each of which reduces the capacity of the coronary circulation to increase its blood flow during stress (coronary reserve). Increased risk in population with more severe hypertension: Increased ventricular mass and coronary arteriolar abnormalities appear especially important as mechanisms of myocardial ischemia in populations with more severe hypertension, whereas conventional coronary disease predominates in patients with mild hypertension and multiple standard risk factors. Need for further research to optimize therapy: To develop optimal therapeutic approaches, further research is needed to clarify the basis of the inter-relationships between left ventricular hypertrophy and arterial abnormalities, to determine whether cardiac microvascular abnormalities parallel systemic hemodynamic patterns in hypertension and to ascertain the relative importance of reversing or preventing cardiovascular hypertrophy and myocardial ischemia for improving the prognosis of hypertensive patients.