Global Hypokinesis in Resting Transthoracic Echocardiography Diagnosis of Heart Failure and Coronary Artery Disease

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J INVASIVE CARDIOL 2024. doi:10.25270/jic/24.00192. Epub July 25, 2024.

Objectives. Although coronary artery disease (CAD) and heart failure (HF) are separate entities, HF is a common complication of CAD, and both CAD and HF are known causes of wall motion abnormalities (WMA) of transthoracic echocardiography (TTE). Specifically, global hypokinesis on TTE could logically be due to multivessel CAD or non-ischemic cardiomyopathy. The purpose of this study was to investigate the relationship between CAD, HF, and WMA on TTE.

Methods. A single-center retrospective chart review was conducted of adults who had a resting TTE and cardiac catheterization within 30 days. We analysed the association between global hypokinesis, triple-vessel CAD, and HF diagnosis.

Results. Across 754 included patients, there was a positive association between global hypokinesis on TTE and HF diagnosis (P < .001). There was no association between global hypokinesis on TTE and triple-vessel CAD (P = .341), possibly an inverse correlation. The sensitivity of regional (R) WMAs on TTE for diagnosing CAD was generally lower in patients without heart failure (44%), while specificity was higher in these same patients (89%).

Conclusions. There was a positive association between global hypokinesis and HF, and a possible inverse correlation between global hypokinesis and triple-vessel CAD. This could be explained by heart failure diagnosis and other diagnoses having a stronger effect on global hypokinesis than any potential effect from triple-vessel CAD. These sensitivity and specificity results for RWMA on CAD, stratified by HF diagnosis and/or global hypokinesis, can be used to inform clinical decision-making in an acute coronary syndrome case with borderline electrocardiography and/or troponin findings.

Cardiovascular disease remains the most prevalent cause of death in the United States, and coronary artery disease (CAD) and heart failure (HF) account for approximately 42% and 10% of all cardiovascular-related deaths, respectively.^1,2 Therefore, the diagnosis and treatment of CAD and HF are of significant clinical importance to address their associated morbidity and mortality.

The diagnosis of CAD is typically made with a combination of patient history, cardiac biomarkers, and electrocardiography (ECG), but additional modalities, such as transthoracic echocardiography (TTE), are utilized when necessary.³

Despite several competing criteria, the diagnosis of HF is based on patient history and physical examination and can further be stratified by measuring the patient’s ejection fraction (EF), typically by echocardiography.⁴ The 2022 AHA/ACC/HFSA guidelines define HF with preserved EF (HFpEF) as EF greater than 50%, and HF with mildly reduced or reduced EF (HFmrEF, HFrEF) as EF less than 50%.⁵

Although CAD and HF are separate entities, HF is a common sequalae of CAD due to the myocardial dysfunction caused by ischemic insult, and both CAD and HF are known causes of myocardial wall motion abnormalities (WMA) on TTE. TTE is supportive of CAD when a pattern of regional wall motion abnormalities (RWMA) is identified, which correlates to a coronary artery’s myocardial distribution without another explanation. It is well established that global hypokinesis may also be observed in the systolic dysfunction of HF. We additionally hypothesized that global hypokinesis, instead of RWMA, may be observed in multivessel CAD, which could logically impact all myocardial segments directly. Despite the association between CAD and HF and each entity’s ability to cause WMA on TTE, few investigations have studied the relationship between CAD, HF, and WMA on TTE.

To investigate the relationship between CAD, HF, and WMA on TTE, we first evaluated the association between global hypokinesis on TTE and HF (at many EF levels) and multivessel CAD. We then evaluated how HF status, EF, and global hypokinesis affect the ability of RWMA on TTE to detect significant CAD. We hypothesized that there would be a positive correlation between multivessel CAD and global hypokinesis on TTE, and a diagnosis of HF would enhance this positive correlation.

Study design and patient selection. All patients were admitted to Baylor Scott & White (BS&W) in Temple, Texas, or seen as outpatients by the BS&W Cardiology group between January 1, 2019, and December 31, 2022. The inclusion criteria in this retrospective study were (1) at least 18 years of age, (2) resting TTE performed within 30 days prior to or after cardiac catheterization, and (3) cardiac catheterization performed within the time period. Exclusion criteria included patients who did not receive a coronary angiogram during their catheterization or had a prior history of CAD, cardiac catheterization, CT angiography, or coronary artery bypass graft (CABG). 

Records of patients who met criteria were pulled from the EPIC electronic medical record by the Research Data Core at our hospital. A comprehensive electronic medical record review of the included participants was conducted to collect each patient’s age, sex, race, ethnicity, body mass index (BMI), and past medical history at the time of the angiography. Past medical history collected is shown in Table 1. All medical history items were collected by a standardized keyword search pattern and ICD-10 (International Classification of Disease-10) code in the EPIC electronic medical record.

This study was reviewed and approved by the Baylor Scott & White Institutional Review Board (IRB), and informed consent was waived by the IRB as this was a retrospective review. This study complied with all institutional and federal guidelines for ethical research.

Transthoracic echocardiography. TTE protocol included conventional 2-dimensional planes, color and spectral Doppler, and M-mode. TTE reports were reviewed for indication for TTE by ICD-10 code, use of ultrasound enhancing agent (UEA), ejection fraction (EF), and the presence of any valvular abnormalities, systolic dysfunction, diastolic dysfunction, technical difficulties, global hypokinesis, or RWMA. RWMA was defined as 1 or more hypokinetic, akinetic, dyskinetic, or aneurysmal segments of any of the 17 myocardial segments outlined in the American Heart Association guidelines as assessed by 2 different cardiologists.⁶ Global hypokinesis was not considered to be positive for RWMA unless there were discrete, superimposed akinetic segments identified. 

Coronary angiography. Coronary angiography reports were reviewed for the diagnostic angiogram findings detailing stenosis of any observed vessel. Significant CAD was defined as at least 70% vessel occlusion of 1 or more of the major coronary arteries and/or their major branches as diagnosed and confirmed by 2 independent cardiologists.  

Data analysis. Descriptive statistics were presented using frequencies and percentages as well as means and standard deviations. Associations between 2 categorical variables were assessed using chi-square and Fisher's exact tests, when applicable. Cochran-Armitage trend tests were used to test for trends in ordinal variables between binary variables. Breslow-Day Tarone (BDT) tests were used to assess homogeneity in the relationship between 2 categorical variables over the strata of a third categorical variable. Alternatively, BDT tests were used for assessing a modifying/confounding relationship between 3 categorical variables.

Heart failure definition. We defined heart failure according to past medical history and TTE findings, both listed in Table 1. Specifically, we defined heart failure as a patient with either a history of heart failure listed in the medical record or with systolic dysfunction (< 50% EF) on TTE (Table 2).

Demographics. In this cohort, 754 patients met the inclusion criteria. The mean age among all patients was 61.6 ± 13.3 years; 60% were male. The mean BMI was 30.4 ± 7.1 kg/m². Eighty-one percent of the patients were white (613), 13% were black (96), and 3% were other races; 14% were Hispanic or Latino of any race (103). Of the 754 included patients, 453 had CAD, 337 had RWMA, 272 were found to have both CAD and RWMA, 170 had global hypokinesis, 115 had triple-vessel CAD, and 84 had chronic HF. Of the 84 patients with a history of chronic HF, 33 had HFpEF, 18 had HFrEF or HFmrEF, 24 had combined HF (diagnosis of both HFrEF/HFmrEF and HFpEF by chart review), and 9 had unspecified chronic HF. Additional patient characteristics were shown in Table 1.  

Global hypokinesis and ejection fraction. Patients with global hypokinesis had significantly lower EF compared with patients without global hypokinesis (Figure 1A). A Cochran-Armitage test used to assess this trend yielded P < .001. This trend persisted in patients who received their TTE for HF (Figure 1B) and other indications (Figure 1C).

Global hypokinesis and triple-vessel CAD

In all patients, 22 of 170 (13%) with global hypokinesis on TTE had triple-vessel CAD, compared with 93 of 584 patients (16%) without global hypokinesis (P = .341, Table 3A, Figure 2A).

In patients with a diagnosis of heart failure as described in Table 2, 22 of 165 (13%) with global hypokinesis had triple-vessel CAD, compared with 47 of 208 (23%) without global hypokinesis (P = .022, Table 3B, Figure 2B). The odds ratio for this group showed a correlation between triple-vessel CAD and a lack of global hypokinesis on TTE (OR 0.53, 95% CI, 0.30; 0.92). In patients without a diagnosis of heart failure, there were not enough patients with global hypokinesis to obtain useful statistics; however, 46 of 376 (12%) without global hypokinesis had triple-vessel CAD. A test of homogeny did not suggest a significant modifying effect of HF diagnosis on the relationship between triple-vessel CAD and global hypokinesis (P = .54).

In patients who received their TTE for a HF indication, 7 of 91 (8%) with global hypokinesis had triple-vessel CAD, compared with 6 of 25 patients (24%) without global hypokinesis (P = .036, Table 3C, Figure 2C). The odds ratio for this group showed a correlation between triple-vessel CAD and a lack of global hypokinesis on TTE (OR 0.27, 95% CI, 0.08; 0.90). In patients who received their TTE for other indications, 15 of 81 (19%) with global hypokinesis had triple-vessel CAD, compared with 87 of 559 (16%) without global hypokinesis (P = .50, Table 3B, Figure 2B). The odds ratio for this group showed no correlation (OR 1.23, 95% CI, 0.67; 2.26). A test of homogeny suggested a significant modifying effect of TTE indication for HF on the relationship between triple-vessel CAD and global hypokinesis (P = .022).

Impact of heart function on resting TTE detection of CAD in adults

In patients with an EF less than 35%, sensitivity and specificity of RWMA on TTE for detection of CAD were 70.2% and 68.4%, respectively. In patients with an EF of 35% to 50%, sensitivity and specificity were 89.2% and 59.6%, respectively. In patients with a normal EF (> 50%), sensitivity and specificity were 43.7% and 89.8%, respectively (Table 4A, Figure 3). The BDT P-value across groups was P = .26.

In patients with heart failure, sensitivity was 45.8% when the patient had global hypokinesis and 89.2% when the patient did not have global hypokinesis. In these same heart failure patients, the specificity was 75.5% when the patient had global hypokinesis, and 54.0% when the patient did not have global hypokinesis. In comparison, the sensitivity was 44.0% and the specificity was 89.4% in patients without heart failure (Table 4B). The BDT P-value was 0.72 across groups.

Global hypokinesis was associated with a lower EF in all patients receiving TTE, regardless of whether they received the TTE for HF or not (Figure 1). While there was a clear association between low EF and global hypokinesis, not all patients with a low EF were noted to have global hypokinesis on the ECG report.

We hypothesized that triple-vessel disease would positively correlate with global hypokinesis due to the nature of triple-vessel disease affecting cardiac muscle throughout the heart, as noted in literature that identifies the coronary distributions in the 17-segment model.⁶ A 1985 paper by Medina et al found that diffuse LV hypokinesis on TTE does not exclude CAD but does not predict CAD with the same accuracy as RWMA.⁷ More recently, and in contrast to our hypothesis, Kim et al found that among patients with LV dysfunction and global hypokinesis relatively few have CAD,⁸ and Chandra et al found that only 36% of cases of global hypokinesis are due to ischemia.⁹Empirically, we found no correlation between global hypokinesis and triple-vessel disease (Table 3, Figure 2). In fact, we found an apparent inverse correlation between global hypokinesis and triple-vessel disease in patients diagnosed with heart failure (Table 3B); however, a broader test of homogeny did not indicate a significant modifying effect by heart failure diagnosis in this relationship. We additionally found an inverse correlation between global hypokinesis and triple-vessel disease in patients who received their TTE for heart failure (Table 3C), and a broader test of homogeny indicated a significant modifying effect by heart failure TTE indication in this relationship (P = .022).

There are many potential explanations for this lack of correlation and/or apparent inverse correlation between global hypokinesis and triple-vessel disease. First, the strong association between heart failure and global hypokinesis would likely overshadow any other variable affecting global hypokinesis. Perhaps a study isolating only non-HF patients in much larger numbers than our study would address this potential confounding variable; as we see in Table 3B, there are very few patients who have global hypokinesis on TTE but no HF diagnosis. WMA, especially global hypokinesis, may also be attributed to other etiologies such as left bundle branch blocks, premature ventricular contractions, pre-excitation, congenital abnormalities, infection, toxins (alcohol, drug-abuse, etc), or an infiltrative process (amyloidosis).^10-15 These etiologies were not consistently evaluated among the patients studied, and this may influence how the TTE was interpreted. Just as correcting for HF may isolate the relationship between triple-vessel CAD and global hypokinesis, correcting for these many etiologies may further isolate this relationship.

Although the subendocardial layer contributes disproportionally greater systolic deformation compared with other layers and is often the first layer subjected to ischemia and infarct, subendocardial injury is not unique to ischemic heart disease and lacks specificity for a vascular insult. In fact, ischemic pattern injury by cardiac MRI is not uncommon in dilated cardiomyopathies without CAD,¹⁶ and patients with both ischemic and nonischemic cardiomyopathy may have mid-wall injury pattern on cardiac MRI.¹⁷ Finally, it is not uncommon for ischemic and nonischemic cardiomyopathy to overlap,¹⁸ which further complicates any relationship between global hypokinesis and triple-vessel disease.    

We found that the sensitivity and specificity of RWMA on TTE for diagnosis of CAD were not modified by EF, heart failure status, or global hypokinesis on TTE. However, trends still existed in this data. Specifically, the sensitivity of RWMA for CAD diagnosis appeared to be lower in patients without heart failure (Table 4), and the specificity appears to be higher in these same patients. This observation held true whether measuring by EF greater than 50% (Table 4A) or our broader definition of heart failure diagnosis (Table 4B). Interestingly, among heart failure patients, the patients with global hypokinesis had a sensitivity and specificity profile similar to those without heart failure, while those with heart failure but no global hypokinesis had a high sensitivity and low specificity for this test (Table 4B).

Though a broader test of homogeny showed no significant modifying effect of EF on these diagnostic measures (Table 4), these results could still be used to inform clinical decision-making. Based on these sensitivity results, one could be more inclined to rule out CAD or ACS based on negative TTE in a patient with heart failure but no global hypokinesis.  Similarly, based on these specificity results, one could be more inclined to pursue further diagnostic testing based on positive TTE results in a patient with normal EF and/or no heart failure diagnosis, but less so in a patient with heart failure and/or a reduced EF. Cardiac CT can also play a role in diagnosis of these borderline cases by helping to avoid angiography in patients with low pretest probability of CAD or ACS.

Limitations. This study was chiefly limited by its retrospective nature. Many confounding variables in this study could have accounted for the patients noted to have global hypokinesis on imaging. This would include non-ischemic causes of global hypokinesis including, but not limited to, infection, toxins (alcohol, drug-abuse, etc), or an infiltrative process (amyloidosis). There was no further data stratification to evaluate for these other etiologies of global hypokinesis. However, it is important to note that, given the clinically significant CAD observed in many of the patients in this study, non-ischemic workup is often felt not to be indicated. A second limitation is the lack of context, both clinical context and context of further imaging data. Hypokinesis on TTE is typically assessed in clinical context and with appreciation of left ventricular (LV) size, thickness, global function, segmental strain distribution, and other parameters; our analysis is isolated from these additional factors. Other institutional and design limitations include technician error when performing TTE, suboptimal windows for adequate evaluation of LV function, the single-institution design of the study, and reader variability among the interpreting physicians of each TTE.

There was a positive association between global hypokinesis and HF but no positive correlation, and a potential inverse correlation, between global hypokinesis and triple-vessel CAD. Further study with a larger patient population and controlling for more confounding variables is required to explore the etiology of this potential inverse correlation. In addition, the sensitivity and specificity results for RWMA on CAD, stratified by HF status and global hypokinesis, can be used to inform diagnostic choices in patients with borderline ECG and troponin findings. Ongoing study is necessary to further specify which populations may be candidates for non-invasive imaging prior to invasive angiography.

Jess Hatfield, MD¹;Michael D. Woods, BS¹; Kendall Hammonds, MPH²; Laith Wahab, DO³; Vinh Nguyen, MD⁴; Ossama Abou Hassan, MD⁴; Javed Butler, MD⁴; Robert J. Widmer, MD PhD^1,4 

From the ¹Texas A&M College of Medicine, Bryan, Texas, USA; ²Biostatistics Core, Baylor Scott & White, Temple, Texas, USA; ³Department of Internal Medicine, Baylor Scott & White, Temple, Texas, USA; ⁴Department of Cardiology, Baylor Scott & White, Temple, Texas, USA 

Disclosures: The authors report no financial relationships or conflicts of interest regarding the content herein.

Address for correspondence: Robert J. Widmer, MD, PhD, 2401 S 31st St, Temple 76508, TX, USA. Email: Robert.Widmer@bswhealth.org; X: @DrArgyle