My four-year-old nephew from New York City came to visit me a few weeks ago in Denver, and we spent a weekend catching up on all his favorite Batman episodes. In one particularly engaging adventure, the Joker and the Penguin joined forces to plot Batman's demise, and that got me thinking about how two formidable powers, each mighty in its own right, can combine to make matters worse.

This is the case for diabetes and hypertension, which can work in tandem to worsen left ventricular hypertrophy (LVH). Individually, both hypertension and diabetes impose an enormous public health burden, and their incidence is rising. Diabetes is estimated to affect approximately 34 million Americans,1 while hypertension is estimated to affect 108 million Americans,2 nearly half of the adult population in the U.S.

When both of these conditions occur in the same patient, the risk of LVH increases considerably.

LVH and Structural Changes in the Heart

Left ventricular hypertrophy develops when the myocardial cells experience growth, or hypertrophy, resulting in structural changes in the heart. The condition is associated with arrhythmias, increased myocardial oxygen demand, diastolic dysfunction, and heart failure. Individually, LVH carries an independent prognosis of adverse cardiac events. It can develop as a result of either diabetes or hypertension; when both are present, the adverse manifestations can be compounded.

Many structural changes can take place as a result of hypertension. For example, increased filling pressures and hypertension in the heart can go hand in hand with the development of left atrial dilation. The left atrium is often called the "pressure sensor" of the heart, and when hypertension affects this area, LVH, left atrial enlargement, or degenerative conditions such as right or left bundle branch blocks can occur as sequelae.

Electrocardiographic Correlates of LVH Structural Changes

These structural changes have correlating electrical manifestations on an ECG. These are not necessarily the result of LVH but rather how the ECG propagates through tissue that has changed due to hypertension and diabetes. However, ECG alone lacks both sensitivity and specificity for the diagnosis of LVH on echo, with the Cornell voltage product criteria being the most sensitive (50%), the Sokolow-Lyon having intermediate sensitivity (29%), and the Romhilt-Estes criteria being the least sensitive (22%). In other words, although ECG alone lacks the sensitivity for detection of LVH via echo, it measures different aspects of the disease. Both are independently predictive of outcome. In particular, ST changes associated with LVH have a poor prognosis and can normalize given proper treatment.

Many of the sequelae, such as left atrial enlargement, are "late" manifestations of LVH that appear once the structural changes have taken hold. However, research asserts that "ventricular activation time, in milliseconds, on the surface electrocardiogram from the onset of the QRS complex to the peak of the R wave (QR interval) predicts diastolic dysfunction and left ventricular stiffness."3 This QR interval represents a potentially novel marker for early detection of diastolic dysfunction, which can manifest as heart failure, a leading cause of death in diabetic patients.

LVH and Diabetes: Molecular and Clinical Implications

Research has identified that the hormone fibroblast growth factor (FGF) 21 is elevated and dysfunctional in diabetics, resulting in direct hypertrophy of myocardial cells and LVH in mice4. Research to determine whether blocking the effects of FGF21 can protect diabetic mice from developing LVH is ongoing.

From a clinical perspective, the presence of diabetes was found to be associated with a significantly higher left ventricular mass index in a normotensive population compared to age-matched and sex-matched controls in a healthy population. One study suggested the risk was three times greater for diabetics who had type 1 diabetes for an average of more than thirty years.5

Obesity can also play a role in the development of LVH. Elevated BMI is "significantly associated with LVH," and the duration and the degree of glycemic control (as reflected by the HbA1c) was also significantly associated with the degree of LVH.6 These findings suggest that all diabetic patients should be considered for LVH screening using all available diagnostic tools, especially electrocardiogram and echocardiogram.

To learn more about the power of the ECG in today's clinical landscape, browse our Diagnostic ECG Clinical Insights Center.

ECG for Diabetic Patients

A diabetic patient's ECG readings are critical to both diagnosis and prognosis of LVH. As discussed above, ECG changes that suggest LVH, as well as abnormalities in the QR interval, can provide key information on the disease process for a diabetic patient.

There are many additional nuanced findings on the ECGs of diabetic patients to consider, even some that vary by sex. For example, in diabetic patients with normal QTc at baseline, female sex was associated with a risk of prolonged QTc, with the mechanism of QTc prolongation thought to be due to hyperinsulinemia-induced hypoglycemia. ECG can also be used to detect silent ischemia. In the course of diabetes, additional alterations such sinus tachycardia, changes in heart rate variability, and ST-T changes may also be observed.

QT duration has been found to correlate with coronary calcium.7 ECG findings can provide valuable prognostic information for diabetics with both QTc prolongation and ST depression, predicting risk of all-cause mortality in type 2 diabetics. QT dispersion can predict not just total mortality, but also cardiac and cerebrovascular mortality.

Diabetes and hypertension, with their rapidly rising prevalence and incidence, are two of the most formidable contributors to heart disease morbidity and mortality. Both can manifest with LVH and diastolic dysfunction, and every clinician should stay up-to-date on the diagnostic and prognostic ECG changes associated with diabetes and hypertension. Being well versed in the applicable criteria for this simple bedside tool can help physicians substantially enhance the clinical care of diabetic patients.

Dr. Payal Kohli, MD, FACC is a top graduate of MIT and Harvard Medical School (magna cum laude) and, as a practicing noninvasive cardiologist, is the managing partner of Cherry Creek Heart in Denver, Colorado.

The opinions, beliefs and viewpoints expressed in this article are solely those of the author and do not necessarily reflect the opinions, beliefs and viewpoints of GE Healthcare. The author is a paid consultant for GE Healthcare and was compensated for creation of this article.

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