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QRS duration and ethnicity: implications for heart failure therapy
  1. Andrew Burden
  1. NHS Sandwell and West Birmingham Clinical Commissioning Group, West Bromwich, Sandwell, UK
  1. Correspondence to Dr Andrew Burden, Secondary Care Specialist member of the NHS Sandwell and West Birmingham Cinical Commissioning Group Board, Kingston House, 450 High Street, West Bromwich, B70 9LD, UK. a.burden{at}nhs.net, acfelix.burden{at}btinternet.com

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The article on ethnic differences in the association of QRS duration (QRSd) with ejection fraction (EF) and outcome in heart failure (HF)1 is a paradigm for epidemiological investigations of ethnic differences in disease.

Why is such an investigation of ethnic differences in disease important?

For the clinician, knowing about differences can improve the probability of diagnosis, treatment and prognosis. For the public health physician, it can highlight areas that need prevention programmes such as for type 2 diabetes or for coronary heart disease. For the physician concerned in ensuring equality, it encourages audit of access to treatments and outcomes for differing population groups.

For the researcher, differences can be used to formulate hypotheses to account for the disease variation: for example, why does the person who lives in or whose forefathers lived in the Indian subcontinent (here called Indo-Asian) have a high incidence of coronary artery disease but a low incidence of peripheral vascular disease? Clearly, such reasons could be genetic, epigenetic or more directly environmental.

For the publisher of international journals and or text books, differences in disease with differing ethnicity are very important to document for the readers. For too long observations have been made on Caucasians and for too long these observations have been assumed to be normal, even though access to equal care had been a popular subject for at least the past 20 years.2

What are the critical steps in an observational study looking at ethnicity disease variation?

The comparison needs to be based on an unbiased sample of each diseased population, or population-based, and the entry criteria must be the same, so that any differences are not due to an access problem to healthcare. In the present study, both populations of patients were from HF registers: one cohort of patients was from Sweden and the other from Singapore. Unfortunately, there were systematic differences between cohorts on the completeness of data: in the Swedish group only 11 221 people out of 20 073 (56%) were included when reasons such as missing data on EF, left bundle branch block or follow-up were considered; in Singapore 839 of 1084 (77.4%) were included. This lack of completeness suggests that the Caucasian patients may have had a reduced access to care in other areas which might lead, for example, to a worsened outcome.

In keeping with many such studies, the ethnic groups were ‘rounded’, that is, for Singapore, while 63% were Chinese, 27% were Malaysian and 9% were Indian, they were all analysed as ‘Asian’. Individual data on ethnicity are not collected in Sweden or many European countries other than the UK and therefore the cohort was described as Caucasian. The reason for such rounding is simply that, here, as in many studies, there was insufficient numbers to allow for comparisons in the smaller ethnic groups.

The cohorts were then analysed for demographic and underlying disease differences. Asian peoples were younger and shorter. Coronary heart disease, hypertension, current smoking and diabetes were more common in the Asian people (and presumably the diabetes was usually type 2 diabetes, type 1 diabetes being much more likely to be common in Sweden); atrial fibrillation (AF), valve surgery and chronic obstructive pulmonary disease more common in Caucasians.

These characteristics might have been thought to influence survival—people with concomitant diabetes and HF are known to have a worse prognosis than those without diabetes and on the other hand young people usually survive longer than old.

The unadjusted differences in HF between Caucasians and Asians are striking. Asians had worsened EF but less severe New York Heart Association (NYHA) symptoms and lower pro b-type natriuretic peptide (proBNP) values. They also had much less left bundle branch block (4.6% compared with 16%) and QRSd was shorter.

Finally the treatments received were different: of the usual ‘guardian’ drugs, β-blocker, statins and antiplatelet drugs were more commonly prescribed in Singapore as were diuretics.

These then are the reasons why the authors performed multivariate adjustment of QRSd.

In addition, QRSd increases with reducing EF; the authors therefore divided the population into those with HF with preserved EF and reduced EF, where the reduction was less than 50%. The authors looked to see if ethnicity affected the QRSd in either or both of these HF groups using multivariate adjustment.

The results showed no impact of ethnicity on QRSd in those with preserved EF, but in those with reduced EF, QRSd was longer in Asian people.

Next they examined the impact of ethnicity and QRSd on outcome of mortality and hospitalisation. Every 10 ms increase in QRSd gave a HR of 1.04 for all people, with no significant effect of ethnicity. Naturally given the number of differences in treatments, comorbidities and demography, this outcome of mortality had wide CIs and could mask actual but small differences.

The authors find that height was important in the results for the multivariate adjustments and suggest that this was because it is a marker for heart size.3 This important idea needs further work—not least because the study reporting the relationship between height and heart size was from a European clinic.

As well as the difference in QRSd, the study found that HF itself had ethnic differences; EF was different between the two ethnic groups, with Asian people having worsened EF, but lower N-terminal (NT)-proBNP values, and fewer symptoms as assessed by the NYHA.

The EF in Asian people without HF has higher values than in Caucasians.4 ,5 It seems likely that in future the definition of abnormal EF needs to be interpreted by ethnic group.

Could these differences in NTproBNP and NYHA have been mediated by the higher diuretic therapy? It may have contributed, but the relationship between EF and NTproBNP and NYHA symptoms in differing ethnic groups requires further research.

What are the implications from this study, for the patient, clinician and researcher?

The Asian patient may have been erroneously excluded from cardiac resynchronisation therapy (CRT). It is not clear if this lack of treatment would be a disadvantage, however, since randomised controlled trial evidence is lacking for this therapy in people with HF and non-left bundle branch block with wide QRS morphology of ≥120 ms.6 The trials included in this meta-analysis were not from Asia and consequently may not be applicable to Asian people. The clinician needs to be particularly careful in analysing patients from Asia to ensure that they are or are not appropriate for CRT.

The researcher needs first to investigate the natural history of HF in differing ethnic groups, in order to investigate the relationship more closely between EF, QRSd, left bundle branch block, NTproBNP and NYHA, with a definite incidence genotyped cohort and measurements of the cardiac variables with time. There are other aspects to investigate: why is treatment adherence more complete in the Singapore patients; is CRT effective in differing ethnic groups and why is left bundle branch block and AF uncommon in Asian people—this study suggests that the low incidence of AF found in African-Americans7 extends to other ethnic groups.

References

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Footnotes

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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