Clinical decision-making and myocardial viability: current perspectives

Not all myocardium involved in a myocardial infarction is dead or irreversibly damaged. The balance between the amount of scar and live tissue, and the nature of the live tissue, determine the likelihood that contractile function will improve after revascularisation. This improvement (which defines viability) may be predicted with about 80% accuracy using several techniques. This review examines the determinants of functional recovery and how they may be integrated in making decisions regarding revascularisation. (Intern Med J 2005; 35: 118–125)

Comparison of specificity of quantitative myocardial contrast echocardiography for diagnosis of coronary artery disease in patients with versus without diabetes mellitus

Impaired coronary flow reserve is widely reported in diabetes mellitus (DM) but its effect on myocardial contrast echocardiography (MCE) is unclear. We sought to identify whether DM influences the accuracy of qualitative and quantitative assessment of coronary artery disease (CAD) using MCE in 83 patients who underwent coronary angiography (60 men, 27 with DM; 56 +/- 11 years;). Destruction replenishment imaging was performed at rest and after combined dipyridamole-exercise stress testing. Ischemia was identified by the development of new wall motion abnormalities, qualitative MCE (new perfusion defects apparent 1 second after flash during hyperemia), and quantitative MCE (myocardial blood flow reserve < 2.0 in the anterior circulation). Qualitative and quantitative assessment of perfusion was feasible in 100% and 92% of patients, respectively. Significant left anterior descending coronary stenosis (> 50% by quantitative angiography) was present in 28 patients (including 8 with DM); 55 patients had no CAD (including 19 with DM). The myocardial blood flow reserve was reduced in patients with coronary stenosis compared with those with no CAD (1.6 +/- 1.1 vs 3.8 +/- 2.5, p < 0.001). Among patients with no CAD, those with DM had an impaired flow reserve compared with control patients without DM (2.4 +/- 1.0 vs 4.5 +/- 2.8, p = 0.003). In conclusion, DM significantly influenced the quantitative, but not the qualitative, assessment of MCE, with a marked reduction in specificity in patients with DM. (c) 2005 Elsevier Inc. All rights reserved.

Myocardial blood volume and perfusion reserve responses to combined dipyridamole and exercise stress: A quantitative approach to contrast stress echocardiography

Background: Qualitative interpretation of myocardial contrast echocardiography (MCE) improves the accuracy of wall-motion analysis for assessment of coronary artery disease (CAD). We examined the feasibility and accuracy of quantitative MCE for diagnosis of CAD. Methods: Dipyridamole/exercise stress MCE (destruction-replenishment protocol with real-time imaging) was performed in 90 patients undergoing quantitative coronary angiography, 48 of whom had significant (> 50%) stenoses. MCE was repeated with exercise alone in 18 patients. Myocardial blood flow (A*beta) was obtained from blood volume (A) and time to refill (beta). Results: Quantification of flow reserve was feasible in 88%. The mean A*beta reserve in the anterior wall was significantly impaired for patients with left anterior descending coronary artery disease (n = 28) compared with those with no disease (1.6 +/- 1.2 vs; 4.0 +/- 2.5, P <=.001). This reflected impaired beta reserve, with no difference in the A reserve. Applying a receiver operating characteristic curve derived cutoff of 2.0 for A*beta reserve, quantitative MCE was 76% sensitive and 71% specific for the diagnosis of significant left anterior descending coronary artery stenosis. Posterior circulation results were similar, with 78% sensitivity and 59% specificity for detection of posterior CAD. Overall, quantitative MCE was similarly sensitive to qualitative approach for diagnosis of CAD (88% vs 93%), but with lower specificity (52% vs 65%, P =.07). In 18 patients restudied with pure exercise stress, the mean myocardial blood flow reserve was less than after combined stress (2.1 +/- 1.6 vs 3.7 +/- 1.9, P =.01). Conclusion: Quantitative MCE is feasible for the diagnosis of CAD with dipyridamole/exercise stress. Dipyridamole prolongs postexercise hyperemia, augmenting the degree of hyperemia at the time of imaging.

Myocardial and vascular dysfunction and exercise capacity in the metabolic syndrome

The metabolic syndrome (MS) is associated with cardiovascular risk exceeding that expected from atherosclerotic risk factors, but the mechanism of this association is unclear. We sought to determine the effects of the MS on myocardial and vascular function and cardiorespiratory fitness in 393 subjects with significant risk factors but no cardiovascular disease and negative stress echocardiographic findings. Myocardial function was assessed by global strain rate, strain, and regional systolic velocity (s(m)) and diastolic velocity (e(m)) using tissue Doppler imaging. Arterial compliance was assessed using the pulse pressure method, involving simultaneous radial applanation tonometry and echocardiographic measurement of stroke volume. Exercise capacity was measured by expired gas analysis. Significant and incremental variations in left ventricular systolic (s(m), global strain, and strain rate) and diastolic (e(m)) function were found according to the number of components of MS (p <0.001). MS contributed to reduced systolic and diastolic function even in those without left ventricular hypertrophy (p <0.01). A similar dose-response association was present between the number of components of the MS and exercise capacity (p <0.001) and arterial compliance. The global strain rate and em were independent predictors of exercise capacity. In conclusion, subclinical left ventricular dysfunction corresponded to the degree of metabolic burden, and these myocardial changes were associated with reduced cardiorespiratory fitness.' Subjects with MS who also have subclinical myocardial abnormalities and reduced cardiorespiratory fitness may have a higher risk of cardiovascular disease events and heart failure. (C) 2005 Elsevier Inc. All rights reserved.

Reduced between-hospital variation in short term survival after acute myocardial infarction: the result of improved cardiac care?

Objectives: To re-examine interhospital variation in 30 day survival after acute myocardial infarction ( AMI) 10 years on to see whether the appointment of new cardiologists and their involvement in emergency care has improved outcome after AMI. Design: Retrospective cohort study. Setting: Acute hospitals in Scotland. Participants: 61 484 patients with a first AMI over two time periods: 1988 - 1991; and 1998 - 2001. Main outcome measures: 30 day survival. Results: Between 1988 and 1991, median 30 day survival was 79.2% ( interhospital range 72.1 - 85.1%). The difference between highest and lowest was 13.0 percentage points ( age and sex adjusted, 12.1 percentage points). Between 1998 and 2001, median survival rose to 81.6% ( and range decreased to 78.0 - 85.6%) with a difference of 7.6 ( adjusted 8.8) percentage points. Admission hospital was an independent predictor of outcome at 30 days during the two time periods ( p< 0.001). Over the period 1988 - 1991, the odds ratio for death ranged, between hospitals, from 0.71 ( 95% confidence interval ( CI) 0.58 to 0.88) to 1.50 ( 95% CI 1.19 to 1.89) and for the period 1998 - 2001 from 0.82 ( 95% CI 0.60 to 1.13) to 1.46 ( 95% CI 1.07 to 1.99). The adjusted risk of death was significantly higher than average in nine of 26 hospitals between 1988 and 1991 but in only two hospitals between 1998 and 2001. Conclusions: The average 30 day case fatality rate after admission with an AMI has fallen substantially over the past 10 years in Scotland. Between-hospital variation is also considerably less notable because of better survival in the previously poorly performing hospitals. This suggests that the greater involvement of cardiologists in the management of AMI has paid dividends.

Renal endothelial dysfunction and impaired autoregulation after ischemia-reperfusion injury result from excess nitric oxide

Endothelial dysfunction in ischemic acute renal failure (IARF) has been attributed to both direct endothelial injury and to altered endothelial nitric oxide synthase ( eNOS) activity, with either maximal upregulation of eNOS or inhibition of eNOS by excess nitric oxide ( NO) derived from iNOS. We investigated renal endothelial dysfunction in kidneys from Sprague-Dawley rats by assessing autoregulation and endothelium-dependent vasorelaxation 24 h after unilateral ( U) or bilateral ( B) renal artery occlusion for 30 (U30, B30) or 60 min (U60, B60) and in sham-operated controls. Although renal failure was induced in all degrees of ischemia, neither endothelial dysfunction nor altered facilitation of autoregulation by 75 pM angiotensin II was detected in U30, U60, or B30 kidneys. Baseline and angiotensin II-facilitated autoregulation were impaired, methacholine EC50 was increased, and endothelium-derived hyperpolarizing factor ( EDHF) activity was preserved in B60 kidneys. Increasing angiotensin II concentration restored autoregulation and increased renal vascular resistance ( RVR) in B60 kidneys; this facilitated autoregulation, and the increase in RVR was abolished by 100 mu M furosemide. Autoregulation was enhanced by N-omega-nitro-L-arginine methyl ester. Peri-ischemic inhibition of inducible NOS ameliorated renal failure but did not prevent endothelial dysfunction or impaired autoregulation. There was no significant structural injury to the afferent arterioles with ischemia. These results suggest that tubuloglomerular feedback is preserved in IARF but that excess NO and probably EDHF produce endothelial dysfunction and antagonize autoregulation. The threshold for injury-producing, detectable endothelial dysfunction was higher than for the loss of glomerular filtration rate. Arteriolar endothelial dysfunction after prolonged IARF is predominantly functional rather than structural.

Complement factor 5a as a therapeutic target

The complement system is an innate immune defense mechanism that protects the host from infection and injury. Complement activation results in the formation of anaphylatoxins, including the biologically active protein C5a. This anaphylatoxin is a potent chemotactic agent for immune and inflammatory cells and induces cell activation. In situations of excessive or uncontrolled complement activation, the overproduction of C5a can cause deleterious effects to the host, and this process is implicated in the pathogenesis of numerous immunoinflammatory disease states, including rheumatoid arthritis, psoriasis, inflammatory bowel disease, ischemia-reperfusion injuries and others. The presence of C5a in a wide variety of condition's has prompted many groups to examine the potential of inhibiting this complement activation product, with the aim of controlling these diseases and reducing the pathologic process. However, to date there is no clinically available specific C5a inhibitor and development of this new drug class is still in a relatively early stage, although limited phase I and phase II human clinical trials have been undertaken in the last few years with selected agents. In this review, examination of the current evidence supporting a specific role of C5a in selected disease states and an overview of potential therapeutic C5a inhibitors will enable the critical evaluation of the potential for C5a as a therapeutic target.

Insulin resistance is a determinant of myocardial dysfunction in apparently healthy obese subjects

Background. Obese pts have subclinical myocardial dysfunction that may account for their risk of heart failure. We sought the contribution of insulin resistance (IR) to myocardial dysfunction in obesity. Methods. Asymptomatic obese subjects without known cardiac disease underwent clinical evaluation, homeostasis model assessment (HOMA score) as a measure of insulin sensitivity and echocardiographic assessment. After exclusion of DM, overt myocardial dysfunction or ischemia, subclinical myocardial function was assessed by myocardial systolic (Sm) and diastolic velocity (Em) in 79 pts. Association was sought between myocardial function with clinical and biochemical characteristics. Results HOMA score categorized 36 pts as non-IR (HOMA

B-type natriuretic peptide concentrations and myocardial dysfunction in critical illness

B-type natriuretic peptide (BNP) is the first biomarker of proven value in screening for left ventricular dysfunction. The availability of point-of-care testing has escalated clinical interest and the resultant research is defining a role for BNP in the investigation and treatment of critically ill patients. This review was undertaken with the aim of collecting and assimilating current evidence regarding the use of BNP assay in the evaluation of myocardial dysfunction in critically ill humans. The information is presented in a format based upon organ system and disease category. BNP assay has been studied in a spectrum of clinical conditions ranging from acute dyspnoea to subarachnoid haemorrhage. Its role in diagnosis, assessment of disease severity, risk stratification and prognostic evaluation of cardiac dysfunction appears promising, but requires further elaboration. The heterogeneity of the critically ill population appears to warrant a range of cut-off values. Research addressing progressive changes in BNP concentration is hindered by infrequent assay and appears unlikely to reflect the critically ill patient's rapidly changing haemodynamics. Multi-marker strategies may prove valuable in prognostication and evaluation of therapy in a greater variety of illnesses. Scant data exist regarding the use of BNP assay to alter therapy or outcome. It appears that BNP assay offers complementary information to conventional approaches for the evaluation of cardiac dysfunction. Continued research should augment the validity of BNP assay in the evaluation of myocardial function in patients with life-threatening illness.