Abstract
Coronary artery calcium (CAC) is the measure of subclinical coronary artery atherosclerosis most strongly associated with atherosclerotic cardiovascular disease (ASCVD) risk. However, CAC is rarely reported in the inpatient setting to guide chest pain management. We present a case of very high CAC in a 64-year-old woman with hypertension, type 2 diabetes, and hyperlipidemia presenting with dyspnea. Initial electrocardiogram (ECG) demonstrated normal conduction with a heart rate of 76 beats/min, but new T-wave inversions in V1–V4 and a high-sensitivity troponin-I (hsTnI) value of 6 ng/L (normal < 6 ng/L). Repeat ECG in the emergency department showed normal sinus rhythm (heart rate of 80 beats/min); however, it subsequently demonstrated a left bundle branch block (LBBB) with a repeat hsTnI of 7 ng/L. Stress testing with pharmacologic single-photon emission computerized tomography did not show scintigraphic evidence of ischemia but noted extensive CAC and a concern for balanced ischemia. Subsequent coronary computed tomography angiography (CCTA) showed nonobstructive disease and a total Agatston CAC score of 1262. Invasive evaluation with left heart catheterization was deferred given the patient’s unchanged symptoms and CCTA findings. Statin therapy was intensified and aspirin, metoprolol succinate, and antihypertension therapies were continued. Initiation of glucose-lowering therapy and lipoprotein(a) testing was strongly recommended on follow-up. Our case suggests that CAC ⩾ 1000 may be incidentally associated with transient LBBB during the workup of coronary artery disease. Here, we specifically show that functional testing that incorporates measurement of CAC burden can help to improve ASCVD-preventive pharmacotherapy initiation and intensification beyond the identification of obstructive disease alone.
Keywords
Case report
Coronary artery calcium (CAC) is a measure of subclinical atherosclerotic burden that is strongly associated with downstream atherosclerotic cardiovascular disease (ASCVD) risk 1 and can improve treatment allocation for several risk-reduction therapies, including statins,2,3 aspirin, 4 and antihypertensive medications. 5 For example, the number needed to treat with statins to prevent one ASCVD event is approximately twofold higher for statin-eligible individuals with CAC = 0 compared to those with prevalent CAC. 3 In addition, CAC ⩾ 100 can demarcate the threshold where the antithrombotic effects of aspirin outweigh the bleeding risks. 4 Recently, observations from the multiethnic study of atherosclerosis and CAC consortium have shown that primary prevention patients with very high CAC (⩾1000) have a risk for nonfatal stroke, nonfatal myocardial infarction, and ASCVD mortality that is similar to that of a stable, treated secondary prevention population. 6 Thus, there has been growing interest regarding the interplay of coronary stenosis versus plaque burden, as new evidence has suggested that atherosclerotic plaque burden, and not stenosis per se, is the main predictor of ASCVD risk among persons with coronary artery disease. 7
A 64-year-old woman with hypertension, non-insulin-dependent type 2 diabetes, hyperlipidemia, gastroesophageal reflux disease, and osteoarthritis presented to her primary care provider due to several months of dyspnea and fatigue. She initially presented with bilateral knee pain related to her osteoarthritis and subsequently had dyspnea on exertion after climbing just two steps of stairs over the past several months. This dyspnea on exertion was accompanied by episodic, sharp chest pain that radiated to her left arm and neck; it was not associated with activity and improved with massage. On review of systems, she had no recent fevers, nausea, or vomiting, but had a nonproductive cough, dizziness with no loss of consciousness, as well as nightly hot flashes. Demographic history was notable for South Asian ethnicity. Family history was significant for extensive cardiometabolic disease, including premature myocardial infarction in her younger brother (39 years old) and younger sister (30 years old), as well as type 2 diabetes in her mother and father. Electrocardiogram (ECG) performed in the primary care office demonstrated normal conduction with a heart rate of 76 beats/min, but new T-wave inversions in V1–V4 (Figure 1(a)) and a high-sensitivity troponin-I (hsTnI) value of 6 ng/L (normal < 6 ng/L). Due to the recent ECG changes in the setting of dyspnea concerning for an anginal equivalent, the patient was sent directly to the emergency department.
ECG in outpatient office (a) and on hospital admission (b).
Initial findings on presentation showed a blood pressure of 121/54 mmHg, heart rate of 76 beats/min, respiratory rate of 17 breaths/min, and body mass index of 27 kg/m2. ECG in the emergency department showed normal sinus rhythm with a heart of 80 beats/min with a left bundle branch block (LBBB) characterized by a QRS complex duration of 146 ms [Figure 1(b)] and a repeat hsTnI of 7 ng/L. The patient was admitted to the general medicine service and continued her home medication regimen, including 100 mg metoprolol succinate, 100 mg losartan, 80 mg pravastatin, and 81 mg aspirin.
The above presentation was most concerning for an anginal equivalent or transient ischemia due to obstructive coronary artery disease (CAD). Other diagnoses considered included dilated cardiomyopathy secondary to ischemia, inflammatory, or infiltrative causes, aortic valve disease, and electrolyte abnormalities such as hyperkalemia.
Initial hsTnI was 7 ng/L and was stable when it was repeated after a new LBBB was noted on ECG in the emergency department. Lipid panel showed a normal total cholesterol of 138 mg/dL (normal <200 mg/dL) and normal low-density lipoprotein cholesterol of 54 mg/dL (normal <70 mg/dL), but a low high-density lipoprotein cholesterol of 41 mg/dL (normal 50–100 mg/dL) and moderately high triglycerides of 217 mg/dL (normal <150 mg/dL). Blood glucose level was 208 mg/dL with a glycated hemoglobin value of 7.3%. Electrolytes were within normal limits. Pharmacologic single-photon emission computerized tomography with regadenoson (Lexiscan) and tetrofosmin intravenous infusion did not show scintigraphic evidence of ischemia. Diffuse CAC noted on attenuation correction CT raised concern for balanced ischemia, and the patient subsequently underwent a coronary computed tomography angiogram (CCTA). This revealed atherosclerotic plaque with mild stenosis (25–49%) in left main (LM), left anterior descending (LAD), left circumflex (LCx), and right coronary arteries (RCA). The total Agatston CAC score was 1262, distributed as LM 200, LAD 166, LCx 553, and RCA 342 (Figure 2). The patient also underwent transthoracic echocardiogram, which revealed a left ventricular ejection fraction of 65–70% with normal left ventricular (LV) systolic function. There were no regional wall motion or valvular abnormalities. There was evidence of grade II LV diastolic dysfunction as measured by E/A ratio of 1.1, average E/e′ of 16.4, left arial maximum volume index of 18.9 mL/m2, and a maximum tricuspid regurgitation velocity of 2.5 m/s.
Coronary computed tomography angiography obtained during hospital admission.
Invasive evaluation with left heart catheterization was deferred given the patient’s unchanged symptoms and CCTA findings. Instead, the decision was made to intensify statin therapy by switching from 80 mg pravastatin to 80 mg atorvastatin daily. The patient was continued on 81 mg aspirin, 100 mg metoprolol succinate, 100 mg losartan, and 10 mg amlodipine. Initiation of glucose-lowering therapy was strongly recommended on primary care and cardiology follow-up. In addition, given the very high CAC burden and family history of CAD, outpatient lipoprotein(a) testing was also scheduled. For lifestyle, she was encouraged to adhere to a low sodium diet and to prioritize glycemic control. ECG on discharge showed resolution of the LBBB and precordial T-wave inversions with a heart rate of 73 beats/min (Figure 3). Intensification of metoprolol and the addition of a long-acting nitrate were to be considered as an outpatient if her anginal symptoms persisted. A post-hospital follow-up appointment was made for her as an outpatient in cardiology clinic and with her primary care provider to continue medical management of stable CAD and further optimize her ASCVD risk profile.
ECG on hospital discharge.
Discussion
This case highlights the presence of a new and transient LBBB, an ischemia equivalent, associated with a very high CAC burden. Among individuals with a high pretest probability CAD, stress testing that does not incorporate measurement of subclinical atherosclerosis during the workup of stable angina may miss prognostically significant CAC, which could lead to missed opportunities for ASCVD risk reduction. However, the specificity of CCTA for diagnosing obstructive CAD may decline across higher CAC scores, 8 therefore our case also demonstrates the challenges in preventive cardiology management for those with CAC ⩾ 1000. While there is no universally accepted Agatston score cut-off value, primary prevention patients with high CAC burden have annualized ASCVD event rates equivalent to that of secondary prevention patients with stable and treated CAD beginning at an Agatston CAC score of 781 (95% confidence interval: 418–1467). 9 Thus, the true risk of our current patient was certainly higher than anticipated on admission, and likely similar to an individual who has already experienced an ASCVD event.
The mechanisms of LBBB associated with very high burden of CAC heart disease are less clear. The left bundle branch receives nearly all its blood supply from the LM coronary artery, and it is possible that extensive atherosclerosis could temporarily disrupt perfusion to the conducting system in the absence of critical stenosis due to microvascular ischemia or endothelial dysfunction. However, it is also possible that CCTA underestimated the degree of stenosis due to very high CAC burden and that T-wave inversions in this patient represent cardiac memory-associated LBBB. Other causes of LBBB to consider would be functional, as a result of a rate-dependent bundle branch block due to a long R-R interval after a short cycle, or structural heart disease. In particular, indolent degenerative disease of the conducting system due to hypertension or CAD may lead to the formation of LBBB.
CAC ⩾ 1000 may be incidentally associated with transient LBBB among patients during the workup of CAD. Among such patients presenting with chest pain found to have very high CAC burden, nuclear medicine stress testing may possibly underestimate ASCVD risk, whereas CCTA may be the preferred imaging modality to quantify subclinical atherosclerosis burden and guide intensification of preventive pharmacotherapies.
