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Percutaneous aortic valve replacement: patient selection is key

Studies among elderly populations demonstrate that conventional aortic valve replacement (AVR) remains the “gold standard” for the treatment of critical aortic stenosis compared with medical treatment. However, for those deemed too high-risk for conventional surgery, or among those who decline surgical intervention, percutaneous procedures such as transcatheter aortic valve implantation (TAVI) may be an option. Consequently, patients who were at one time considered inappropriate for intervention are now being referred for TAVI.

Dewey et al described the management and outcome of 105 patients referred to their centre (Medical City Dallas Hospital, Texas, USA) for consideration of TAVI. Patients had either previously been refused conventional surgical intervention or were considered to be at extreme risk with standard AVR. After multidisciplinary team assessment 52 (49.5%) patients received medical management (MM), 16 (15.2%) conventional AVR, 21 (20%) TAVI and 16 (15.2%) balloon aortic valvuloplasty (BAV). Significant differences were seen among the groups in the predicted risk of mortality score (using the Society of Thoracic Surgeons predicted risk of mortality): mean (SD) BAV 11.8 (6.5)%; MM 11.3 (6.7)%; TAVI 10.9 (3.5)%; AVR 6.3 (3.5)%. All-cause 30-day mortality was 1/16 (6.3%) patients for AVR, 2/21 (9.5%) with TAVI, 2/16 (12.5%) for BAV, and 7/52 (13.5%) for the MM cohort. Overall mortality during a mean (SD) follow-up of 159 (147) days was 42.3% (22/52 patients) for MM, 19.0% (4/21 patients) for TAVI, 12.5% (2/16 patients) for AVR, and 37.5% (6/16 patients) for BAV.

The decision to offer surgery to the elderly and high-risk patient populations remains complex. Evaluation of these unique populations can be improved by a multidisciplinary team approach involving surgeons and cardiologists. This study shows that TAVI and AVR can be performed in appropriately selected high-risk patients with good early and long-term outcomes.

▸ Dewey TM, Brown DL, Das TS, et al. High-risk patients referred for transcatheter aortic valve implantation: management and outcomes. Ann Thorac Surg 2008;86:1450–7.

Genetic study suggests CRP not causal in atherosclerosis

Increased levels of C-reactive protein (CRP) are associated with an increased risk of ischaemic heart and cerebrovascular disease. But is CRP a causal factor in atherosclerosis development or merely a marker for ischaemic vascular disease? Evidence to suggest a role for CRP in the pathogenesis of atherosclerosis comes predominantly from epidemiological studies. These have consistently observed an association between raised CRP and cardiovascular events. This relationship has the same statistical strength as for other cardiovascular risk factors such as hypertension and diabetes mellitus. However, statistical strength does not imply causality as alternative explanations may be offered by reverse causality or other confounding factors. Mendelian randomisation—the random assortment of genes that occurs during gamete formation—provides a relatively unbiased method of assessing whether risk factors that have a genetic component are causally related to clinical outcomes.

Four independent cohorts of white people of Danish descent were studied—a total of 50 816 subjects. These independent cohorts allowed independent confirmation of the findings in each group. The investigators used the fact that genetic variation in the CRP gene gives rise to variation in plasma CRP levels. The risks of ischaemic heart disease and ischaemic cerebrovascular disease were increased by a factor of 1.6 and 1.3, respectively, in patients with a CRP level >3 mg/l as compared with those with a CRP <1 mg/l. Genotype combinations of four CRP polymorphisms studied were associated with an increase in CRP levels of up to 64%. This theoretically predicts an increased risk of up to 32% for ischaemic heart disease and up to 25% for ischaemic vascular disease. However, these genotype combinations were not associated with an increased risk of ischaemic vascular disease either singly or in combination. A positive control was included in the study—variations in the apolipoprotein E level, which is known to affect cholesterol. The known association between apolipoprotein E levels and cardiovascular risk was confirmed for this cohort.

Limitation of this study include the use of cross-sectional and case–control cohorts as use of subjects recruited after the event may introduce survival bias. The possibility cannot be ruled out that the CRP polymorphisms studied are related to higher plasma levels of a less functionally active CRP. It assumes that genetically raised CRP levels behave in a similar fashion to acquired increases and that lifelong CRP elevation does not induce compensatory mechanisms in other systems. There may also be confounding from other genes in linkage disequilibrium with the CRP polymorphisms studied.

Nonetheless, the results appear to suggest that CRP is not causally implicated in the pathogenesis of atherosclerosis. More definitive answers may follow from trials involving agents aimed specifically at lowering CRP levels.

▸ Zacho J, Tybjaerg-Hansen A, Jensen JS, et al. Genetically elevated C-reactive protein and ischaemic vascular disease. N Engl J Med 2008;359:1897–908.

▸ Schunkert H, Samani NJ. Elevated C-reactive protein in atherosclerosis – chicken or egg? N Engl J Med 2008;359:1953–5.

Cardiogenic shock rates show evidence of decline

It remains uncertain whether the sweeping changes in the treatment of acute coronary syndromes (ACS) have had a substantial impact on the incidence of cardiogenic shock.

The AMIS (Acute Myocardial Infarction in Switzerland) Plus Registry analysed data from patients admitted to Swiss hospitals between 1997 and 2006. A total of 23 696 patients with ACS were enlisted. Although the rate of cardiogenic shock on admission remained constant at 2.3% in patients with ACS, rates of cardiogenic shock during hospitalisation decreased to 6.0%, leading to an overall decrease in the rate of cardiogenic shock to 8.3% of all patients with ACS. Overall, a decrease in in-hospital mortality was also seen (62.8% to 47.7%; p = 0.01), and percutaneous coronary intervention was independently associated with a lower risk for both in-hospital mortality (odds ratio = 0.47; p = 0.001) and cardiogenic shock development during admission (odds ratio = 0.59; p = 0.012).

Therefore both the incidence and mortality from cardiogenic shock seem to be declining in this select population. It should be noted that a higher rate of shock and mortality was seen in patients aged >75 (p<0.001), but that these patients also received fewer treatments (thrombolytic agents, percutaneous coronary intervention and intra-aortic ballon counterpulsation). The findings therefore underline the importance of following treatment guidelines in patients of all ages.

▸ Jeger RV, Radovanovic D, Hunziker PR, et al. Ten-year trends in the incidence and treatment of cardiogenic shock. Ann Intern Med 2008;149:618–26.

β Blockers: all are equal, but some more than others

Carvedilol, metoprolol and bisoprolol have all been shown to improve outcomes in patients with heart failure. These evidence based β blockers (EBBBs) are in contrast to atenolol, propranolol and timolol, which have not been directly tested in heart failure. Therefore if a patient receiving one of these agents develops heart failure, is it neccesary to switch them to an EBBB?

Kramer et al looked at patients in North Carolina aged >65 years who had been admitted for heart failure at least once. The primary outcome measure was survival from 30 days to 1 year. Of 11 959 patients, 40% were non-white and 79% were female. Twenty-three per cent were receiving EBBBs and 18% were receiving non-evidence-based β blockers (non-EBBBs). At 1 year, adjusted mortality rates were 24.2% for patients taking EBBB, compared with 22.8% for patients taking non-EBBBs (p = 0.43); those taking no β blockers had a mortality rate of 28.3% (p = 0.002 compared with patients taking β blockers). More rehospitalisations were seen in patients taking EBBBs than in patients taking no β blockers (p = 0.002) and non-EBBBs (p<0.001).

This is a retrospective study performed in an elderly cohort. Were similiar findings to arise from an analysis of a younger population with heart failure, then a randomised trial examining the effects of EBBBs versus non-EBBBs might be merited.

▸ Kramer JM, Curtis LH, Dupree CS, et al. Comparative effectiveness of β-blockers in elderly patients with heart failure. Arch Intern Med 2008;168:2422–8.

New MI diagnosis criteria, same old risk

The traditional diagnosis of myocardial infarction (MI) used the World Health Organization definition and required the concentration of a cardiac biomarker to be more than twice the upper limit of normal. However, more recent guidelines have defined a troponin level above the 99th centile of normal as being diagnostic of MI.

Using data from the AMIS (Acute Myocardial Infarction in Switzerland) registry, Urban investigated the outcomes of those patients with the “classic” definition of MI (creatine kinase (CK) or CK-MB above the upper limit of normal, or troponin T (TnT) >0.1 μg/l) compared with those with the “new” definition of myocardial infarction (TnT >0.01 μg/l).

Overall, 489 patients were diagnosed with the new criteria (a “new” MI) and 8701 with the old (a “classic” MI). In-hospital mortality was 3.5% in the “new” group and 6.7% in the “classic” group (p = 0.004). In as subset of patients with a longer follow-up, mortality at 3 and 12 months was 1% for the “new” group compared with 1.6% for the “classic” group at 3 months, and 5.6% compared with 4% at 12 months (p = NS).

By lowering the TnT threshold needed for the diagnosis of MI, the number of patients with this diagnosis will increase. In this study this population was represented by the “new” cases, and despite less aggressive treatment in hospital they had a better short-term prognosis than “classic” cases. However, the 3- and 12-month risk was the same in both patients (fig 1), suggesting that even a minor TnT leak identifies a group of patients at high risk in the long term.

Figure 1

Mortality: in-hospital, at 3 months and at 1 year.

▸ Urban P, Radovanovic D, Erne P, et al. Impact of changing definitions for myocardial infarction: a report from the AMIS registry. Am J Med 2008\;121:1065–71.

Journals scanned

American Journal of Medicine; American Journal of Physiology: Heart and Circulatory Physiology; Annals of Emergency Medicine; Annals of Thoracic Surgery; Archives of Internal Medicine; BMJ; Chest; European Journal of Cardiothoracic Surgery; JAMA; Journal of Clinical Investigation; Journal of Diabetes and its Complications; Journal of Immunology; Journal of Thoracic and Cardiovascular Surgery; Lancet; Nature Medicine; New England Journal of Medicine; Pharmacoeconomics; Thorax


Dr Alistair C Lindsay, Dr Katie Qureshi, Dr Jonathan Spiro