Collateral-flow measurements in humans by myocardial contrast echocardiography: validation of coronary pressure-derived collateral-flow assessment

AIMS: Myocardial blood flow (MBF) is the gold standard to assess myocardial blood supply and, as recently shown, can be obtained by myocardial contrast echocardiography (MCE). The aims of this human study are (i) to test whether measurements of collateral-derived MBF by MCE are feasible during elective angioplasty and (ii) to validate the concept of pressure-derived collateral-flow assessment. METHODS AND RESULTS: Thirty patients with stable coronary artery disease underwent MCE of the collateral-receiving territory during and after angioplasty of 37 stenoses. MCE perfusion analysis was successful in 32 cases. MBF during and after angioplasty varied between 0.060-0.876 mL min(-1) g(-1) (0.304+/-0.196 mL min(-1) g(-1)) and 0.676-1.773 mL min(-1) g(-1) (1.207+/-0.327 mL min(-1) g(-1)), respectively. Collateral-perfusion index (CPI) is defined as the rate of MBF during and after angioplasty varied between 0.05 and 0.67 (0.26+/-0.15). During angioplasty, simultaneous measurements of mean aortic pressure, coronary wedge pressure, and central venous pressure determined the pressure-derived collateral-flow index (CFI(p)), which varied between 0.04 and 0.61 (0.23+/-0.14). Linear-regression analysis demonstrated an excellent agreement between CFI(p) and CPI (y=0.88 x +0.01; r(2)=0.92; P<0.0001). CONCLUSION: Collateral-derived MBF measurements by MCE during angioplasty are feasible and proved that the pressure-derived CFI exactly reflects collateral relative to normal myocardial perfusion in humans.

The relative myocardial blood volume differentiates between hypertensive heart disease and athlete's heart in humans

AIMS: The adaptation of the myocardial microcirculation in humans to pathologic and physiologic stress has not been examined in vivo so far. We sought to test whether the relative blood volume (rBV) measured by myocardial contrast echocardiography (MCE) can differentiate between left ventricular (LV) hypertrophy (LVH) in hypertensive heart disease and athlete's heart. METHODS AND RESULTS: Four groups were investigated: hypertensive patients with LVH (n = 15), semi-professional triathletes with LVH (n = 15), professional football players (n = 15), and sedentary control individuals without cardiovascular disease (n = 15). MCE was performed at rest and during adenosine-induced hyperaemia. The rBV (mL mL(-1)), its exchange frequency (beta, min(-1)), and myocardial blood flow (mL min(-1) g(-1)) were derived from steady state and refill sequences of ultrasound contrast agent. Hypertensive patients had lower rBV (0.093 +/- 0.013 mL mL(-1)) than triathletes (0.141 +/- 0.012 mL mL(-1), P < 0.001), football players (0.129 +/- 0.014 mL mL(-1), P < 0.001), and sedentary individuals (0.126 +/- 0.018 mL mL(-1), P < 0.001). Conversely, the exchange frequency (beta) was significantly higher in hypertensive patients (11.3 +/- 3.8 min(-1)) than in triathletes (7.4 +/- 1.8 min(-1)), football players (7.7 +/- 2.3 min(-1)), and sedentary individuals (9.0+/-2.5 min(-1)). An rBV below 0.114 mL mL(-1) distinguished hypertensive patients and triathletes with a sensitivity of 93% and a specificity of 100%. CONCLUSION: Pathologic and physiologic LVH were differentiated non-invasively and accurately by rBV, a measure of vascularisation assessed by MCE.

Safety and outcome of patients with an acute ST-elevation myocardial infarction transferred for primary coronary intervention: the Neuchâtel experience

BACKGROUND: Transferring patients with ST-elevation myocardial infarction (STEMI) for primary percutaneous coronary intervention (PCI) from a community hospital to a PCI centre has been evaluated in randomised trials and shown to be safe and effective. A prolonged transfer time may restrict the benefit of this strategy. AIM: We sought to assess 1) safety of transfer from Neuchâtel to Berne, 2) time intervals of patients transferred either directly from on-site or after evaluation in the local emergency room, and 3) clinical long-term outcome. METHODS AND RESULTS: 42 patients with STEMI eligible for reperfusion therapy were prospectively included between January 2003 and June 2004. Twenty patients (48%, group 1) were directly transferred to the PCI centre from on-site. Twenty-two were transferred after initial treatment in the local emergency room: 11 patients (26%, group 2) presented spontaneously at the hospital and 11 patients (26%, group 3) were admitted by the rescue team. No major complication occurred during transport. Median transport time was 33 minutes. Median time from first healthcare contact to balloon consisted of 131 minutes in group 1, 158 minutes in group 2 and 174 minutes in group 3. The overall rate of Major Adverse Cardiac Events (MACE) at 6 months amounted to 9.5%. CONCLUSIONS: Transfer for primary PCI of our patients with acute STEMI was safe. Direct transfer from on-site to the PCI centre reduced the time of ischaemia. The overall MACE rate was low.

Postmortem unenhanced magnetic resonance imaging of myocardial infarction in correlation to histological infarction age characterization

AIMS: Postmortem magnetic resonance (MRI) imaging is currently evaluated as alternative to traditional autopsy and myocardial infarction plays a key role therein. The aim of this study is to determine the suitability of postmortem MRI in infarction age staging. METHODS AND RESULTS: In eight human forensic corpses presenting with a total of 11 myocardial infarcted areas, short-axis, transversal, and longitudinal long-axis images (T1, T2, stir, flair) were acquired in situ on a 1.5 T system. During subsequent autopsy, the section technique was adapted to short-axis images. Histological investigations were performed along the entire circumference of the left ventricle to correlate the signal alteration in MR to the histological appearance. Two peracute infarctions were not detected in MRI and autopsy. Four acute infarcted areas presented with decreased signal in necrotic centres and increased signal in marginal myocardial regions (T2-weighted). T1-weighted images showed local hyperintensities when intramyocardial haemorrhage occurred. Four cases showed subacute infarctions with hyperintense regions in T2-weighted images and no signal alteration in T1-weighted images. Four chronic myocardial infarctions showed distinctively decreased signals in all applied sequences. CONCLUSION: Postmortem MRI demonstrates myocardial infarction in situ and allows for an infarction age estimation based on the signal behaviour.

Myocardial infarction and post-traumatic stress disorder: frequency, outcome, and atherosclerotic mechanisms

BACKGROUND: Post-traumatic stress disorder (PTSD) may develop in the aftermath of an acute myocardial infarction (MI). Whether PTSD is a risk factor for cardiovascular disease (CVD) is elusive. The biological mechanisms linking PTSD with atherosclerosis are unclear. DESIGN: A critical review of 31 studies in the English language pursuing three aims: (i) to estimate the prevalence of PTSD in post-MI patients; (ii) to investigate the association of PTSD with cardiovascular endpoints; and (iii) to search for low-grade systemic inflammatory changes in PTSD pertinent to atherosclerosis. METHODS: We located studies by PubMed electronic library search and through checking the bibliographies of these sources. RESULTS: The weighted prevalence of PTSD after MI was 14.7% (range 0-25%; a total of 13 studies and 827 post-MI patients). Two studies reported a prospective association between PTSD and an increased risk of cardiovascular readmission in post-MI patients and of cardiovascular mortality in combat veterans, respectively. In a total of 11 studies, patients with PTSD had increased rates of physician-rated and self-reported cardiovascular diseases. Various cytokines and C-reactive protein were investigated in a total of seven studies suggesting that PTSD confers a pro-inflammatory state. CONCLUSIONS: Increasing evidence suggests that PTSD specifically related to MI develops considerably frequently in post-MI patients. More research is needed in larger cohorts applying a population design to substantiate findings suggesting PTSD is an atherogenic risk factor and to understand better the suspected behavioural and biological mechanisms involved.

Myoblast-seeded biodegradable scaffolds to prevent post-myocardial infarction evolution toward heart failure

OBJECTIVE(S): Even though the mechanism is not clearly understood, direct intramyocardial cell transplantation has demonstrated potential to treat patients with severe heart failure. We previously reported on the bioengineering of myoblast-based constructs. We investigate here the functional outcome of infarcted hearts treated by implantation of myoblast-seeded scaffolds. METHODS: Adult Lewis rats with echocardiography-confirmed postinfarction reduced ejection fraction (48.3% +/- 1.1%) were randomized to (1) implantation of myoblast-seeded polyurethane patches at the site of infarction (PU-MyoB, n = 11), (2) implantation of nonseeded polyurethane patches (PU, n = 11), (3) sham operation (Sham, n = 12), and (4) direct intramyocardial myoblast injection (MyoB, n = 11). Four weeks later, the functional assessment by echocardiography was repeated, and we additionally performed left ventricular catheterization plus histologic studies. RESULTS: The ejection fraction significantly decreased in the PU (39.1% +/- 2.3%; P = .02) and Sham (39.9% +/- 3.5%; P = .04) groups, whereas it remained stable in the PU-MyoB (48.4% +/- 3.1%) and MyoB (47.9% +/- 3.0%) groups during the observation time. Similarly, left ventricular contractility was significantly higher in groups PU-MyoB (4960 +/- 266 mm Hg/s) and MyoB (4748 +/- 304 mm Hg/s) than in groups PU (3909 +/- 248 mm Hg/s, P = .01) and Sham (4028 +/- 199 mm Hg/s, P = .01). Immunohistology identified a high density of myoblasts within the seeded scaffolds without any migration toward the host cardiac tissue and no evidence of cardiac cell differentiation. CONCLUSIONS: Myoblast-seeded polyurethane scaffolds prevent post-myocardial infarction progression toward heart failure as efficiently as direct intramyocardial injection. The immunohistologic analysis suggests that an indirect mechanism, potentially a paracrine effect, may be assumed.

Noninvasive Doppler-derived myocardial performance index in rats with myocardial infarction: validation and correlation by conductance catheter

The rodent model of myocardial infarction (MI) is extensively used in heart failure studies. However, long-term follow-up of echocardiographic left ventricular (LV) function parameters such as the myocardial performance index (MPI) and its ratio with the fractional shortening (LVFS/MPI) has not been validated in conjunction with invasive indexes, such as those derived from the conductance catheter (CC). Sprague-Dawley rats with left anterior descending coronary artery ligation (MI group, n = 9) were compared with a sham-operated control group (n = 10) without MI. Transthoracic echocardiography (TTE) was performed every 2 wk over an 8-wk period, after which classic TTE parameters, especially MPI and LVFS/MPI, were compared with invasive indexes obtained by using a CC. Serial TTE data showed significant alterations in the majority of the noninvasive functional and structural parameters (classic and novel) studied in the presence of MI. Both MPI and LVFS/MPI significantly (P < 0.05 for all reported values) correlated with body weight (r = -0.58 and 0.76 for MPI and LVFS/MPI, respectively), preload recruitable stroke work (r = -0.61 and 0.63), LV end-diastolic pressure (LVEDP) (r = 0.82 and -0.80), end-diastolic volume (r = 0.61 and -0.58), and end-systolic volume (r = 0.46 and -0.48). Forward stepwise linear regression analysis revealed that, of all variables tested, LVEDP was the only independent determinant of MPI (r = 0.84) and LVFS/MPI (r = 0.83). We conclude that MPI and LVFS/MPI correlate strongly and better than the classic noninvasive TTE parameters with established, invasively assessed indexes of contractility, preload, and volumetry. These findings support the use of these two new noninvasive indexes for long-term analysis of the post-MI LV remodeling.

Intravenous magnesium for acute myocardial infarction

BACKGROUND: Mortality and morbidity from acute myocardial infarction (AMI) remain high. Intravenous magnesium started early after the onset of AMI is thought to be a promising adjuvant treatment. Conflicting results from earlier trials and meta-analyses warrant a systematic review of available evidence. OBJECTIVES: To examine the effect of intravenous magnesium versus placebo on early mortality and morbidity. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library Issue 3, 2006), MEDLINE (January 1966 to June 2006) and EMBASE (January 1980 to June 2006), and the Chinese Biomedical Disk (CBM disk) (January 1978 to June 2006). Some core Chinese medical journals relevant to the cardiovascular field were hand searched from their starting date to the first-half year of 2006. SELECTION CRITERIA: All randomized controlled trials that compared intravenous magnesium with placebo in the presence or absence of fibrinolytic therapy in addition to routine treatment were eligible if they reported mortality and morbidity within 35 days of AMI onset. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the trial quality and extracted data using a standard form. Odds ratio (OR) were used to pool the effect if appropriate. Where heterogeneity of effects was found, clinical and methodological sources of this were explored. MAIN RESULTS: For early mortality where there was evidence of heterogeneity, a fixed-effect meta-analysis showed no difference between magnesium and placebo groups (OR 0.99, 95%CI 0.94 to 1.04), while a random-effects meta-analysis showed a significant reduction comparing magnesium with placebo (OR 0.66, 95% CI 0.53 to 0.82). Stratification by timing of treatment (< 6 hrs, 6+ hrs) reduced heterogeneity, and in both fixed-effect and random-effects models no significant effect of magnesium was found. In stratified analyses, early mortality was reduced for patients not treated with thrombolysis (OR=0.73, 95% CI 0.56 to 0.94 by random-effects model) and for those treated with less than 75 mmol of magnesium (OR=0.59, 95% CI 0.49 to 0.70) in the magnesium compared with placebo groups.Meta-analysis for the secondary outcomes where there was no evidence of heterogeneity showed reductions in the odds of ventricular fibrillation (OR=0.88, 95% CI 0.81 to 0.96), but increases in the odds of profound hypotension (OR=1.13, 95% CI 1.09 to 1.19) and bradycardia (OR=1.49, 95% CI 1.26 to 1.77) comparing magnesium with placebo. No difference was observed for heart block (OR=1.05, 95% CI 0.97-1.14). For those outcomes where there was evidence of heterogeneity, meta-analysis with both fixed-effect and random-effects models showed that magnesium could decrease ventricular tachycardia (OR=0.45, 95% CI 0.31 to 0.66 by fixed-effect model; OR=0.40, 95% CI 0.19 to 0.84 by random-effects model) and severe arrhythmia needing treatment or Lown 2-5 (OR=0.72, 95% CI 0.60 to 0.85 by fixed-effect model; OR=0.51, 95% CI 0.33 to 0.79 by random-effects model) compared with placebo. There was no difference on the effect of cardiogenic shock between the two groups. AUTHORS' CONCLUSIONS: Owing to the likelihood of publication bias and marked heterogeneity of treatment effects, it is essential that the findings are interpreted cautiously. From the evidence reviewed here, we consider that: (1) it is unlikely that magnesium is beneficial in reducing mortality both in patients treated early and in patients treated late, and in patients already receiving thrombolytic therapy; (2) it is unlikely that magnesium will reduce mortality when used at high dose (>=75 mmol); (3) magnesium treatment may reduce the incidence of ventricular fibrillation, ventricular tachycardia, severe arrhythmia needing treatment or Lown 2-5, but it may increase the incidence of profound hypotension, bradycardia and flushing; and (4) the areas of uncertainty regarding the effect of magnesium on mortality remain the effect of low dose treatment (< 75 mmol) and in patients not treate...

Effects of percutaneous coronary interventions in silent ischemia after myocardial infarction: the SWISSI II randomized controlled trial

CONTEXT: The effect of a percutaneous coronary intervention (PCI) on the long-term prognosis of patients with silent ischemia after a myocardial infarction (MI) is not known. OBJECTIVE: To determine whether PCI compared with drug therapy improves long-term outcome of asymptomatic patients with silent ischemia after an MI. DESIGN, SETTING, AND PARTICIPANTS: Randomized, unblinded, controlled trial (Swiss Interventional Study on Silent Ischemia Type II [SWISSI II]) conducted from May 2, 1991, to February 25, 1997, at 3 public hospitals in Switzerland of 201 patients with a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease. Follow-up ended on May 23, 2006. INTERVENTIONS: Percutaneous coronary intervention aimed at full revascularization (n = 96) or intensive anti-ischemic drug therapy (n = 105). All patients received 100 mg/d of aspirin and a statin. MAIN OUTCOME MEASURES: Survival free of major adverse cardiac events defined as cardiac death, nonfatal MI, and/or symptom-driven revascularization. Secondary measures included exercise-induced ischemia and resting left ventricular ejection fraction during follow-up. RESULTS: During a mean (SD) follow-up of 10.2 (2.6) years, 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group (adjusted hazard ratio, 0.33; 95% confidence interval, 0.20-0.55; P<.001), which corresponds to an absolute event reduction of 6.3% per year (95% confidence interval, 3.7%-8.9%; P<.001). Patients in the PCI group had lower rates of ischemia (11.6% vs 28.9% in patients in the drug therapy group at final follow-up; P = .03) despite fewer drugs. Left ventricular ejection fraction remained preserved in PCI patients (mean [SD] of 53.9% [9.9%] at baseline to 55.6% [8.1%] at final follow-up) and decreased significantly (P<.001) in drug therapy patients (mean [SD] of 59.7% [11.8%] at baseline to 48.8% [7.9%] at final follow-up). CONCLUSION: Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00387231.

Outcome of elderly patients undergoing primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

AIM: To investigate the outcome of primary percutaneous coronary interventions (PCI) in elderly patients (>/=>/=75 years) with ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Between 1995 and 2003, a total of 319 consecutive patients with acute ST-elevation myocardial infarction presenting within 6-12 hr after onset of symptoms were prospectively enrolled in a registry. Of 296 patients undergoing primary PCI, 40 patients were >/=>/=75 years old (group A) and 256 patients younger than 75 years (group B). Elderly patients presented with a lower ejection fraction (49 +/- 14% vs. 53 +/- 13%, P = 0.046) and a higher number of cardiovascular risk factors. PCI success was achieved in 80% (group A) and 91% (group B, P = 0.031), respectively with comparable door-to-balloon times (87 +/- 49 and 95 +/- 79 min, P = ns). Periprocedural complications in both groups were low and major adverse cardiac events (death, myocardial infarction, target vessel revascularization and cardiac rehospitalization) after 6 months amounted to 23% (group A) and 20% (group B, P = ns), respectively. CONCLUSIONS: Clinical outcome of elderly patients (>/=>/=75 years) with acute STEMI is favorable and comparable with the middle-aged population. However, procedural success was significantly lower in elderly (80%) compared to younger patients (90%). Acute percutaneous coronary intervention appears to be safe and not associated with higher periprocedural complications, in elderly patients.

Paradoxical emboli through the patent foramen ovale as the suspected cause of myocardial and renal infarction in a 48-year-old woman

We review the case of a 48-year-old woman who underwent elective percutaneous patent foramen ovale closure following successive renal and myocardial infarction with normal renal and coronary arteries, probably as a consequence of paradoxical emboli.

Attenuation of myocardial reperfusion injury in pigs by Mirococept, a membrane-targeted complement inhibitor derived from human CR1

OBJECTIVES: Membrane-targeted application of complement inhibitors may ameliorate ischemia/reperfusion (I/R) injury by directly targeting damaged cells. We investigated whether Mirococept, a membrane-targeted, myristoylated peptidyl construct derived from complement receptor 1 (CR1) could attenuate I/R injury following acute myocardial infarction in pigs. METHODS: In a closed-chest pig model of acute myocardial infarction, Mirococept, the non-tailed derivative APT154, or vehicle was administered intracoronarily into the area at risk 5 min pre-reperfusion. Infarct size, cardiac function and inflammatory status were evaluated. RESULTS: Mirococept targeted damaged vasculature and myocardium, significantly decreasing infarct size compared to vehicle, whereas APT154 had no effect. Cardioprotection correlated with reduced serum troponin I and was paralleled by attenuated local myocardial complement deposition and tissue factor expression. Myocardial apoptosis (TUNEL-positivity) was also reduced with the use of Mirococept. Local modulation of the pro-inflammatory and pro-coagulant phenotype translated to improved left ventricular end-diastolic pressure, ejection fraction and regional wall motion post-reperfusion. CONCLUSIONS: Local modification of a pro-inflammatory and pro-coagulant environment after regional I/R injury by site-specific application of a membrane-targeted complement regulatory protein may offer novel possibilities and insights into potential treatment strategies of reperfusion-induced injury.