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Association of T-Wave Abnormalities With Major Cardiovascular Events in Patients With Diabetes
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This study evaluated the association between T-wave abnormalities (TWAs) and cardiovascular endpoints among individuals with diabetes who participated in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Among 8179 eligible participants, TWAs were associated with increased risks of all-cause mortality (HR, 1.45), cardiovascular mortality (HR, 1.93), congestive heart failure (HR, 2.04), and major coronary artery disease (HR, 1.40).
- The presence of TWAs was associated with hard cardiovascular outcomes among individuals with diabetes. Although TWAs are common and often nonspecific, their presence may reflect subclinical cardiovascular disease among individuals with diabetes.
abstract
This abstract is available on the publisher's site.
Access this abstract nowAIMS/HYPOTHESIS
T-wave abnormalities (TWA) are often found on ECG and signify abnormal ventricular repolarisation. While TWA have been shown to be associated with subclinical atherosclerosis, the relationship between TWA and hard cardiovascular endpoints is less clear and may differ in the presence of diabetes, so we sought to explore these associations in participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.
METHODS
TWA were operationally defined as the presence of any Minnesota Codes 5-1 through 5-4 in any lead distribution. Multivariable Cox proportional hazards models were constructed to examine relationships between TWA and clinical cardiovascular events. Secondary analyses explored the risks conferred by major vs minor TWA, differential effects of TWA by anatomic localisation (anterolateral, inferior or anterior lead distributions), and differing associations in those with or without prevalent CVD.
RESULTS
Among 8176 eligible participants (mean 62.1 ± 6.3 SD years, 61.4% male), there were 3759 cardiovascular events, including 1430 deaths (473 of a cardiovascular aetiology), 474 heart failure events, 1452 major CHD events and 403 strokes. Participants with TWA had increased risks of all-cause mortality (HR 1.45 [95% CI 1.30, 1.62], p < 0.0001), cardiovascular mortality (HR 1.93 [1.59, 2.34], p = 0.0001), congestive heart failure (HR 2.04 [1.69, 2.48], p < 0.0001) and major CHD (HR 1.40 [1.26, 1.57], p < 0.0001), but no increased risk of stroke (HR 0.99 [0.80, 1.23], p = 0.95). Major TWA conferred a higher risk than minor TWA. When TWA were added to the UK Prospective Diabetes Study risk engine, there was improved discrimination for incident CHD events, but only for those with prevalent CVD (area under the receiver operating characteristic curve 0.5744 and 0.6030 with p = 0.0067). Adding TWA to the risk engine yielded improvements in reclassification that were of greater magnitude in those with prevalent CVD (net reclassification improvement [NRI] 0.24 [95% CI 0.16, 0.32] in those with prevalent CVD, NRI 0.14 [95% CI 0.07, 0.22] in those without prevalent CVD).
CONCLUSIONS/INTERPRETATION
The presence and magnitude of TWA are associated with increased risk of clinical cardiovascular events and mortality in individuals with diabetes and may have value in refining risk, particularly in those with prevalent CVD.
Additional Info
Disclosure statements are available on the authors' profiles:
Association of T-Wave Abnormalities With Major Cardiovascular Events in Diabetes: The ACCORD Trial
Diabetologia 2021 Mar 01;64(3)504-511, SJ Mould, EZ Soliman, AG Bertoni, PD Bhave, J Yeboah, MJ SingletonFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Diabetes
The ACCORD trial was a negative trial among more than 10,000 patients with type 2 diabetes at high cardiovascular (CV) risk. It demonstrated that intensive therapy targeting a glycated hemoglobin level (A1c) below 6.0% not only failed to significantly reduce major CV events (the primary outcome) but also appeared to increase CV mortality.
This paper assessed the value of routine ECG in predicting major CV events based on T-wave abnormalities (TWAs) in 8176 patients from the ACCORD trial. The investigators used a validated, objective system (the Minnesota Code Classification System) to define TWAs and then thoughtfully classified minor and major TWAs. Unsurprisingly, patients with TWAs were older, more likely to have CV disease, had higher systolic blood pressure, longer-standing diabetes, higher A1c, and higher creatinine.
The investigators found that TWAs were associated with an increased risk of CV events and mortality, more so in those with prevalent CV disease and, to a larger degree, with major versus minor ECG changes. Moreover, these associations remained significant after multivariable adjustments.
It is interesting that anterior lead TWAs in patients with diabetes were not associated with increased mortality, whereas those in anterolateral or inferior leads were. The paper invokes ischemia as the explanation for TWAs, which seems reasonable in light of the findings. There is no mention, however, of the fact that TWAs can be seen in conditions other than ischemia, such as ventricular hypertrophy, electrolyte abnormalities, or as effects of drugs.
The routine ECG may still be a useful stratification tool in your type 2 diabetes patients at high CV risk. Seemingly minor changes, often referred to as "nonspecific," may indeed portend greater risk of future events. An additional lesson from this study is the apparently high negative predictive value of an entirely normal ECG.