Effects of nebivolol on biomarkers in elderly patients with heart failure.

BACKGROUND: Heart failure activates neurohormones, and elevated levels of brain natriuretic peptide (BNP) are associated with adverse outcomes. The SENIORS trial showed that nebivolol, a highly selective beta-1 antagonist with vasodilating properties, reduced the composite outcome of all cause mortality or cardiovascular hospital admissions in older patients with heart failure. We explored the effects of nebivolol on a range of neurohormones, cytokines and markers of nitric oxide activity in heart failure. METHODS: In a subset of patients in SENIORS we measured N-terminal pro-brain natriuretic peptide (NT-BNP), pro atrial natriuretic peptide (Pro-ANP), endothelin-1 (ET-1), peripheral norepinephrine (PNE), soluble Fas (sFas), soluble Fas-ligand (sFas-L), tumour necrosis factor-alpha (TNF-α), serum uric acid (SUA), symmetrical dimethyl arginine (SDMA), arginine, citrulline and asymmetrical dimethyl arginine (ADMA) at baseline (before study drug), at 6 months and 12 months in a prespecified substudy. RESULTS: One hundred and six patients were enrolled and 75 had a baseline and at least one follow-up sample. There were no significant differences in neurohormone cytokines or nitric oxide markers measured between the two groups at six or twelve months. NT-ProBNP showed a numerical increase in the nebivolol group compared to placebo (P=0.08) and sFas showed a numerical increase in patients on placebo (P=0.08). Mean baseline LVEF was 35% in both groups and at 12 months was 43% on nebivolol group and 34% on placebo group (P=0.01). CONCLUSION: There were trends but no clear changes associated with nebivolol in neurohormones, cytokines or markers of nitric oxide activity in this study of elderly patients with heart failure. Further studies are needed to understand the mechanistic effects of beta blockers on biomarkers in heart failure.

Rates and causes of death from non-ST elevation acute coronary syndromes: ten year follow-up of the PRAIS-UK registry.

BACKGROUND: Long term nationally representative mortality rates following acute coronary syndrome (ACS) admissions are lacking beyond 5 years. We report rates and causes of mortality at approximately 10 years from PRAIS-UK. METHODS: PRAIS-UK was a prospective registry of 1046 non-ST-elevation ACS admissions to 56 UK hospitals between 1998 and 1999. 493 patients surviving to 6 months were consented to long term follow-up. We identified deaths and causes (ICD codes) via the UK central death register and examined the influence of baseline characteristics and early revascularisation procedures. A modified GRACE risk score was constructed to determine the association of baseline score with long term risk of death. RESULTS: The mean age was 66 years and 40% were women. After a median follow-up of 11.6 years (IQR 6.3-11.9), 46% (225) of patients had died with 55% being classified as cardiovascular. In a multivariate analysis, the following variables were associated with higher mortality (hazard ratio [HR] and 95% confidence intervals [CI]): age (10 years increase) 2.14 (1.87 to 2.45), ST depression or bundle branch block (compared to normal ECG) 1.68 (1.06 to 2.67), and history of heart failure (compared to no HF) 1.81 (1.28 to 2.56). The HR for risk of death in patients who received a revascularisation procedure (versus those who did not) in the first 6 months was 0.41 (0.24 to 0.69). The mean adapted GRACE score was 99.3 ± 26.4, associated with approximately 50% mortality at 10 years. CONCLUSIONS: Non-ST elevation ACS is associated with about 50% mortality over 10 years that may be improved by early revascularisation. Well designed long-term registries can provide key data to determine prognosis and burden of disease.

Antipsychotic-drug-induced dilated cardiomyopathy.

A man in his 30s presented with symptoms of shortness of breath (SOB). He was on clozapine for schizophrenic symptoms. From the initial two presentations it was thought to be and managed as a chest infection, and a perfusion ventilation scan was done to rule out pulmonary embolism. However, with worsening SOB on exertion, he presented for a third time, and was referred and seen in the Department of Medicine on this occasion. The ECG showed evidence of left atrial and ventricular enlargement. The chest x ray showed an increased cardiothoracic ratio. An urgent echocardiogram showed the presence of dilated cardiomyopathy with severe left ventricular systolic function impairment. The patient had a coronary angiogram and other relevant investigations to look for the cause of the dilated cardiomyopathy. These investigations did not reveal any significant abnormality. The cause appeared to be related to the drug clozapine. The patient was treated for heart failure, and clozapine was stopped. He improved and repeat echocardiogram at follow-up showed a definite improvement in the symptoms and the echocardiogram.

Right coronary artery (RCA) aneurysm as a collateral circulation in sub totally occluded mid RCA stenosis.

Coronary aneurysms are rare occurrences but are known to be associated with complications. Controversies persist regarding the use of medical or surgical management, especially in the presence of obstructive coronary artery disease. This information is further lacking in cases of coronary aneurysm that appears to be working as collaterals/bypass blood across a suboccluded stenosis.

A randomized trial of exercise treadmill ECG versus stress SPECT myocardial perfusion imaging as an initial diagnostic strategy in stable patients with chest pain and suspected CAD: cost analysis.

BACKGROUND: Exercise electrocardiography (ETT) is frequently used in patients with suspected coronary artery disease (CAD). Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) improves diagnostic stratification. There are no randomized trials comparing ETT and MPI. We hypothesized that first-line MPI would be effective and cost-saving versus ETT. METHODS AND RESULTS: We randomized 457 outpatients with stable chest pain and suspected CAD to either treadmill electrocardiography or MPI. The post-test likelihood incorporated the pretest likelihood and the test result, with clinically driven testing. The primary endpoint was cost to diagnosis based on institutional and National Institute for Clinical Excellence costs. MPI significantly reduced the intermediate post-test likelihood of CAD (30% for ETT vs 3% for MPI, P < .0001) and further investigations (71% for ETT vs 16% for MPI, P < .0001). Despite the reduction in downstream resource utilization after MPI, mean costs were not different between the 2 initial strategies: 490.44 pounds sterling (95% confidence interval, 453.80-527.08) for ETT versus 512.41 pounds sterling (95% confidence interval, 481.41-543.41) for MPI. MPI cost was no different from ETT cost in patients with an intermediate or high pretest likelihood (P = not significant). ETT was less expensive in low-risk patients. CONCLUSIONS: In this study there was no difference in cost to diagnosis between initial ETT and MPI. In low-likelihood patients ETT was less costly, whereas there was no cost difference in intermediate- or high-likelihood patients.

Mortality following non-ST elevation acute coronary syndrome: 4 years follow-up of the PRAIS UK Registry (Prospective Registry of Acute Ischaemic Syndromes in the UK).

AIM: To present information on long-term prognosis and risk factors following an admission with non-ST elevation acute coronary syndrome. METHODS: A cohort of 653 patients was followed for mortality and causes of death using data from the UK Office of National Statistics (ONS). Cox proportional hazards model was used to identify the prognostic factors. RESULTS: Overall survival at a maximum follow-up of 45 months was 77.8% (95% CI 74.1-81.1%). Seventy-three per cent of the deaths were clearly due to a cardiovascular cause. Age, male gender, heart failure, ST depression or bundle branch block were all associated with higher short- and long-term risk. Taking aspirin or having a revascularization procedure, over the period of six months following initial hospitalisation were both associated with a lower long-term risk. CONCLUSION: Non-ST elevation acute coronary syndromes carry a high risk of death over a 4-year period. Conventional risk factors can predict both short- and long-term risk. More invasive management and the use of evidence-based therapies appear to be associated with a lower risk.

The pathologic basis of Q-wave and non-Q-wave myocardial infarction: a cardiovascular magnetic resonance study.

OBJECTIVES: The purpose of this study was to determine the pathologic basis of Q-wave (QW) and non-Q-wave (NQW) myocardial infarction (MI). BACKGROUND: The QW/NQW distinction remains in wide clinical use but the meaning of the difference remains controversial. We hypothesized that measurement of total MI size and transmural extent by late gadolinium enhancement cardiovascular magnetic resonance (CMR) would identify the pathologic basis of QWs. METHODS: A total of 100 consecutive patients with documented previous MI had electrocardiogram and CMR on the same day. Patients with acute MI within seven days were excluded. Left ventricular function and the size and transmural extent of MI were quantified in the three major arterial territories and correlated with the presence of QW. RESULTS: Subendocardial MI showed QW in 28%. Transmural MI showed NQW in 29%. Of all MIs, 48% were at some point transmural, and 99% of these were at some point non-transmural. As MI size and number of transmural segments increased, the probability of QW increased (anterior: total size chi-square = 53, p < 0.0001, transmural extent chi-square = 36, p < 0.0001; inferior: total size chi-square = 16, p = 0.001, transmural extent chi-square = 10, p = 0.001). These findings did not hold for lateral MI. In a multivariate model, the transmural extent of MI was not an independent predictor of QW when total size of MI was removed. The QW/NQW classification was a good test for size of MI (area under receiver operating characteristic curve: anterior 0.90, inferior 0.77). CONCLUSIONS: The QW/NQW distinction is useful, but it is determined by the total size rather than transmural extent of underlying MI.