Anna-Maria J. Choy

Detection of left ventricular dysfunction after acute myocardial infarction: comparison of clinical, echocardiographic, and neurohormonal methods.

OBJECTIVE--The SAVE study showed that captopril improves mortality in patients with left ventricular dysfunction after myocardial infarction and that this benefit occurred even in patients with no clinically overt heart failure. On the basis of this, it seems important to identify correctly which patients have left ventricular dysfunction after a myocardial infarction. The objective was to compare various methods of identifying patients with left ventricular dysfunction (left ventricular ejection fraction, LVEF, < or = 40%) after acute myocardial infarction. The methods compared were echocardiography (quantitative and qualitative visual assessment), clinical evaluation (subjective assessment and three clinical score methods), and measurement of plasma concentrations of cardiac natriuretic peptide hormones (atrial and brain natriuretic peptides, ANP and BNP). DESIGN--Cross sectional study of left ventricular function in patients two to eight days after acute myocardial infarction. SETTING--Coronary care unit of a teaching hospital. PATIENTS--75 survivors of a recent myocardial infarction aged 40 to 88 with no history of cardiac failure and without cardiogenic shock at the time of entry to the study. MAIN OUTCOME MEASURES--Sensitivities and specificities of the various methods of detecting left ventricular dysfunction were calculated by comparing them with a cross sectional echocardiographic algorithm for LVEF. RESULTS--Clinical impression was poor at identifying LVEF < 40% (sensitivity 46%). Clinical scoring improved this figure somewhat (modified Peel index sensitivity 64%). Qualitative visual assessment echocardiography was a more sensitive method (sensitivity 82%) for detecting LVEF < 40%. Plasma BNP concentration was also a sensitive measure for detecting left ventricular dysfunction (sensitivity 84%) but plasma ANP concentration was much poorer (sensitivity 64%). CONCLUSION--Left ventricular dysfunction is easily and reliably detected by echocardiographic measurement of LVEF and also by a quick qualitative echocardiographic assessment but is likely to be missed by clinical assessment alone. High concentrations of plasma BNP maybe another useful indicator of left ventricular dysfunction, particularly in hospitals where not all patients can be screened by echocardiography or radionuclide ventriculography after myocardial infarction.

Diagnostic value of B-type natriuretic peptide concentrations in patients with acute myocardial infarction

Although elevations of plasma atrial natriuretic peptide (ANP) concentrations have been shown to have prognostic significance in patients after acute myocardial infarction (AMI), the relation between plasma levels of B-type natriuretic peptide (BNP) and cardiovascular mortality remains unknown. To test the prognostic value of plasma ANP and BNP after AMI, plasma concentrations were measured a mean of 3 days after infarction in 75 patients. During a median follow-up of 19.7 months, 14 patients (18.4%) died of cardiovascular causes. On univariate analysis, plasma ANP and BNP, Killip class, modified Peel index, left ventricular ejection fraction, and presence of left ventricular failure were all associated with cardiovascular mortality. In contrast, plasma ANP was the only variable that correlated with the development of symptomatic heart failure and hospitalization. For the combined end point of cardiovascular mortality, symptomatic heart failure, and hospitalization, plasma neurohormones were the only variables of predictive value. By stepwise regression analysis, plasma BNP was the only significant independent predictor of cardiovascular mortality (p = 0.001), whereas plasma ANP identified patients at risk of symptomatic heart failure and hospitalization (p = 0.002 and 0.019, respectively). This study indicates that plasma BNP measured after AMI is a powerful neurohormonal predictor of subsequent cardiovascular mortality, whereas plasma ANP correlates better with the development of symptomatic heart failure and hospitalization. Routine measurement of both of these peptides in the period immediately after an AMI may provide a simple means of risk stratification with different information gained from each peptide.

Impact of Renin-Angiotensin System Blockade Therapy on Outcome in Aortic Stenosis

OBJECTIVES The purpose of this study was to investigate the impact of renin-angiotensin system blockade therapy on outcomes in aortic stenosis (AS). BACKGROUND Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are perceived to be relatively contraindicated in AS. However, inhibitors of the renin-angiotensin system may be beneficial in AS through their cardioprotective and beneficial effects on left ventricular remodeling. METHODS The Health Informatics dispensed prescribing, morbidity, and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database (>110,000 scans). Patients with a diagnosis of AS from 1993 to 2008 were identified. Cox regression model (adjusted for confounding variables) and propensity score analysis were used to assess the impact of ACEIs or ARBs on all-cause mortality and cardiovascular (CV) events (CV death or hospitalizations). RESULTS A total of 2,117 patients with AS (mean age 73 ± 12 years, 46% men) were identified and 699 (33%) were on ACEI or ARB therapy. Over a mean follow-up of 4.2 years, there were 1,087 (51%) all-cause deaths and 1,018 (48%) CV events. Those treated with ACEIs or ARBs had a significantly lower all-cause mortality with an adjusted hazard ratio of 0.76 (95% confidence interval: 0.62 to 0.92, p < 0.0001) and fewer CV events with an adjusted hazard ratio of 0.77 (95% confidence interval: 0.65 to 0.92, p < 0.0001). The outcome benefits of ACEIs/ARBs were further supported by propensity score analysis. CONCLUSIONS This large observational study suggests that ACEI/ARB therapy is associated with an improved survival and a lower risk of CV events in patients with AS.

Insulin Resistance Is Highly Prevalent and Is Associated With Reduced Exercise Tolerance in Nondiabetic Patients With Heart Failure

OBJECTIVES The purpose of this study was to establish the prevalence of insulin resistance (IR) among nondiabetic chronic heart failure (CHF) patients and to seek factors associated with IR in CHF, including the relationship of IR to functional class, exercise capacity, and disease severity in CHF. BACKGROUND Several lines of evidence suggest that CHF is an IR state. The prevalence of IR in CHF and its relation to CHF have not been fully defined. METHODS Fasting insulin resistance index (FIRI) was assessed in a cohort of 129 consecutive CHF patients (mean age 69.2 +/- 10.4 years; 76% males; body mass index 27.4 +/- 4.4 kg/m(2)). Patients underwent cardiopulmonary exercise testing and peripheral endothelial function testing by reactive hyperemia peripheral arterial tonometry (RH-PAT). RESULTS Prevalence of IR as defined by FIRI > or =2.7 was 61% in our cohort of CHF patients. There was a significant correlation between IR and waist circumference (r = 0.37; p < 0.01), serum triglycerides (r = 0.34; p < 0.01), high-density lipoprotein cholesterol (r = -0.22; p = 0.02), and serum leptin (r = 0.39; p = 0.03). Insulin resistance increased significantly with worsening New York Heart Association functional class (p < 0.01). The CHF patients with IR had a significantly lower exercise capacity and peak oxygen consumption than patients with an FIRI <2.7. The RH-PAT ratio was significantly lower in CHF patients with IR compared with CHF patients with an FIRI <2.7 (1.6 +/- 0.3 vs. 2.0 +/- 0.5; p < 0.05). CONCLUSIONS Insulin resistance is highly prevalent among nondiabetic CHF patients and is associated with decreased exercise capacity in patients with CHF. (Insulin Resistance: Heart Failure; NCT00486967).

The effect of metformin on insulin resistance and exercise parameters in patients with heart failure

Chronic heart failure (CHF) is an insulin‐resistant state. The degree of insulin resistance (IR) correlates with disease severity and is associated with reduced exercise capacity. In this proof of concept study, we have examined the effect of metformin on IR and exercise capacity in non‐diabetic CHF patients identified to have IR.

The effect of intravenous saline loading on plasma levels of brain natriuretic peptide in man.

Objective: Recent evidence suggests the presence of a dual natriuretic peptide system consisting of atrial natriuretic factor (ANF) from the atrium and brain natriuretic peptide (BNP) from the ventricle. Discrete roles have been postulated for these two natriuretic peptides in the control of circulatory homeostasis. We have therefore compared the release of ANF and BNP in response to an acute saline load to explore a differential pattern of release for the two natriuretic peptides in man. Design: The effects of an acute saline infusion on plasma ANF and BNP concentrations were studied in 10 normal male volunteers. Methods: Subjects were studied on two study days in the semirecumbent position. An acute intravenous saline infusion (250ml/min) of 18 ml/kg isotonic sodium chloride-potassium chloride solution was administered on one of the two study days. No infusion was administered on the other day as a control. Results: Plasma ANF concentrations increased significantly (P<0.01) with saline loading without any detectable changes in plasma BNP concentrations up to 60 min following infusion. Heart rate and systolic and diastolic blood pressure were unchanged after saline loading. Conclusions: We have shown that an acute intravenous saline load causes an increase in plasma ANF concentrations with no detectable increase in plasma BNP at least up to 60 min after the acute saline load in man. These results support the view that the release of ANF and BNP may be regulated differently, especially with regard to the time required for the acute release of each peptide.

The Impact of Renin-Angiotensin-Aldosterone System Blockade on Heart Failure Outcomes and Mortality in Patients Identified to Have Aortic Regurgitation : A Large Population Cohort Study

OBJECTIVES The aim of this study was to investigate the effect of renin-angiotensin system blockade on outcomes in patients with aortic regurgitation (AR). BACKGROUND Angiotensin-converting enzyme (ACE) inhibitors have the potential to reduce afterload, blunt left ventricular wall stress, and limit left ventricular dilation and hypertrophy. However, long-term studies have yielded inconsistent results, and very few have assessed clinical outcomes. METHODS The Health Informatics Centre dispensed prescription and morbidity and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database. Patients diagnosed with at least moderate AR from 1993 to 2008 were identified. Cox regression analysis was used to assess differences in all-cause mortality and cardiovascular (CV) and AR events (heart failure hospitalizations, heart failure deaths, or aortic valve replacement) between those treated with and without ACE inhibitors or angiotensin receptor blockers (ARBs). RESULTS A total of 2,266 subjects with AR (median age 74 years; interquartile range: 64 to 81 years) were studied, with a mean follow-up period of 4.4 ± 3.7 years. Seven hundred and five patients (31%) received ACE inhibitor or ARB therapy. There were 582 all-cause deaths (25.7%). Patients treated with ACE inhibitors or ARBs had significantly lower all-cause mortality and fewer CV and AR events, with adjusted hazard ratios of 0.56 (95% confidence interval [CI]: 0.64 to 0.89; p < 0.01) for all-cause mortality, 0.77 (95% CI: 0.67 to 0.89; p < 0.01) for CV events, and 0.68 (95% CI: 0.54 to 0.87; p < 0.01) for AR events. CONCLUSIONS This large retrospective study shows that the prescription of ACE inhibitors or ARBs in patients with moderate to severe AR was associated with significantly reduced all-cause mortality and CV and AR events. These data need to be confirmed by a prospective randomized controlled outcome trial.

Insulin resistance: a potential new target for therapy in patients with heart failure.

There is increasing evidence to suggest that chronic heart failure (CHF) is an insulin resistant (IR) state and that the degree of IR correlates with the severity and mortality of CHF. The pathophysiology of IR in CHF has yet to be fully defined. Additionally, it remains to be determined if IR is merely a marker reflecting the severity of CHF or whether it contributes to the disease in CHF. If IR is truly a culprit that worsens CHF, it will potentially be a new target for therapy as strategies that can reverse IR in CHF may potentially result in an improvement in symptoms and even mortality in these patients. However, there are concerns regarding the use of certain insulin sensitizers, most notably, the thiazolidinediones (TZDs) which have been associated with increased risk of hospitalizations for CHF. Despite previous concerns of lactic acidosis (LA), there is now evidence that metformin may not only be safe but could potentially be useful in the setting of CHF. There are now ongoing prospective studies, including the TAYSIDE study, to determine if reversing IR with metformin will have beneficial effects in patients with CHF.

Mean HbA1c and mortality in diabetic individuals with heart failure: a population cohort study.

Controversy exists regarding the importance of glycaemic control in patients with type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF) based on conflicting reports using single baseline glycosyated haemoglobin (HbA1c). Using the time‐weighted mean of serial HbA1c measurements has been found to be a better predictor of diabetic complications as it reflects the glycaemic burden for that individual over time. We therefore sought to confirm this in a large cohort of patients with T2DM and incident CHF.

Therapeutic development in cardiac syndrome X: a need to target the underlying pathophysiology.

Morbidity of patients with cardiac syndrome X (typical anginal-like chest pain and normal coronary arteriogram) is high with continuing episodes of chest pain and frequent hospital readmissions. Management of this syndrome represents a major challenge for the treating physician. Conventional therapies with antianginal agents such as nitrates, calcium channel antagonists, classic beta-adrenoceptor blockers and nicorandil have been tried, with variable success. However, this might be related to a failure to target the underlying pathophysiology and, clearly, more effective therapies are needed. Supporting evidence for the important role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X has come from the recent observation that basal superoxide production predicts future cardiovascular events in this patient group. This review will discuss the pathophysiology, current medical management and potential new pharmacological treatment for patients with cardiac syndrome X which target endothelial dysfunction and oxidative stress. Whats already known about this topic? Morbidity of patients with cardiac syndrome X is high. The important role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X. What does this article add? This review will discuss the pathophysiology, current medical management and potential new pharmacological treatment for patients with cardiac syndrome X which target endothelial dysfunction and oxidative stress.