General internists of experience suspected variant angina as gastroesophageal reflux diseases in two cases: Heart burn may be related to coronary spasm

Abstract

General physicians of experience suspected variant angina as gastroesophageal reflux disease (GERD) due to heart burn in two patients. Proton pump inhibitors were administered in these patients, although spontaneous ST segment elevations were recognized and total or subtotal coronary spasm was provoked by the pharmacological spasm provocation tests. Under the vasodilators but not proton pump inhibitors, two patients complained of neither heart burn nor chest symptoms. General internists and cardiologists should bear in mind coronary spasm when they suspect GERD due to heart burn. Guidelines for GERD may note the necessity of differential diagnosis of coronary artery spasm as one of etiology of GERD-related chest symptoms.

<Learning objective: We describe two cases of active variant angina suspected as gastroesophageal reflux disease (GERD) initially by experienced general internists. General physicians and cardiologists should discriminate GERD from coronary spastic angina or Prinzmetal variant angina.>

Introduction

Many disorders such as musculoskeletal, gastrointestinal, psychiatric, pulmonary, or mediastinal disease, may lead to non-cardiac chest pain (NCCP) [1]. Among them, gastroenterological expertise is required in the differential diagnosis of NCCP. General internists and cardiologists may suspect gastroesophageal reflux disease (GERD) when patients complain of heart burn after meals. They usually prescribe some proton pump inhibitor (PPIs) or H2 receptor blocker in these patients. Cardiologists may experience some GERD-related chest symptoms in the clinic. Some patients with ischemic heart disease complain of epigastralgia or heart burn without chest pain or chest discomfort. Variant angina is a high disease activity of coronary spasm with transient ST segment elevation during attack [2]. Coronary artery spasm is associated with various cardiac diseases such as sudden cardiac death, acute coronary syndrome, serious fatal arrhythmia, unstable angina, unknown origin heart failure, or other conditions. However, cardiologists or general internists may encounter an irreversible catastrophic cardiac event, when they suspect active variant angina as GERD.

In this report, we report two cases of variant angina that were diagnosed and medicated as GERD initially by general skilled internists due to heart burn.

Case report

Case 1

A 59-year-old man was admitted to our hospital because of heart burn for 5 min after eating a meal. A general internist of experience for more than 36 years in a hospital with more than 500 beds diagnosed him as having GERD due to heart burn regardless of ischemic electrocardiographic (ECG) changes (Fig. 11-1-A). The patient had a history of smoking for more than 39 years and was a current smoker. After he took the medication of PPI (esomeprazole magnesium hydrate 20 mg) for a month, his heart burn improved slightly. The general internist continued the treatment of PPI in this patient. However, he stopped taking the medication of PPI after two months by his own judgment. Five months later, he was again admitted to our hospital due to repetitive heart burn in the early morning every day. He complained of something wrong in his heart but not the gastroesophagus. A cardiologist performed Master double test on suspicion of ischemic heart disease (Fig. 11-1-B). ST segment elevation in V1-4 leads and ST segment depression in inferior leads and V56 leads were observed irrespective of no chest symptoms (Fig. 11-1-C/D/E). The cardiologist diagnosed him as having variant angina which was a condition of unstable angina. After emergency coronary angiography (CAG), he had organic stenosis at proximal left anterior descending (LAD) artery (Fig. 11-2-a). Intracoronary injection of acetylcholine (ACh) 20 μg into the left coronary artery (LCA) disclosed total spasm at segment 6 and focal spasm at distal left circumflex artery (LCX) accompanied with usual heart burn and ST elevation in V1-5 leads (5.0 mm) (Fig. 11-2-c). After the administration of 0.2 mg nitroglycerin into the LCA, total spasm was relieved. We injected the ACh 50/80 μg into the right coronary artery (RCA) and distal RCA showed diffuse spastic change with negative T in inferior leads (Fig. 11-2-d). An intravascular ultrasound showed no plaque rupture or thrombus formation in the LAD. We performed percutaneous coronary intervention for LAD with hybrid sirolimus-eluting stent (Orsiro, BIOTRONIK, Buelach, Switzerland; stent 3.5 × 18 mm) (Fig. 11-2-e/g). Myocardial pharmacologic stress thallium scintigraphy after the percutaneous coronary intervention disclosed partial redistribution in inferior portion and severely decreased washout rate (5.5 ± 5.3%). We administered two calcium channel antagonists (diltiazem R 200 mg/day and nifedipine CR 40 mg/day) and nitrates (isosorbide mononitrate 40 mg/day). He complained of no heart burn or chest symptoms for eight months. We also administered rosuvastatin calcium 5 mg, because he had dyslipidemia [total cholesterol: 238 mg/dl, low-density-lipoprotein (LDL) cholesterol: 158 mg/dl, high-density-lipoprotein (HDL) cholesterol: 59 mg/dl] and no diabetes mellitus (glycohemoglobin: 5.8%).

Fig. 1.

Electrocardiographic findings on first admission and during Master double test (1-1) and coronary angiography during spasm provocation test and after the percutaneous coronary intervention (1-2).

1-1. (A) ST segment elevation in V1-3 leads and ST segment depression in V56 leads were observed on first admission. (B) negative T was observed in V2-5 leads before Master double test. (C) no ischemic change was found just after the Master double test. (D) ST elevation in V1-4 leads and ST depression in inferior leads and V56 leads was recognized after two-minute test. (E) negative T was observed in V2-5 leads after five-minute test.

1-2. (a/b) Organic stenosis was found at proximal LAD but no stenosis was observed in the RCA or LCX on control CAG. (c/d) Total spasm at proximal LAD and focal spasm at mid LCX was documented after the intracoronary injection of 20 μg ACh into the LCA, while diffuse distal spasm was provoked in the RCA after the injection of ACh 80 μg. (e/f) Significant stenosis was recognized at proximal LAD, whereas no stenosis was found on RCA or LCX after the administration of nitrate. (g/h) No stenosis was found at proximal LAD after PCI.

Case 2

A skilled medical practitioner in a general practice for more than 40 years treated a 65-year-old man for hypertension and diabetes mellitus. The patient took amlodipine 5 mg, valsartan 80 mg, and DPP-4 inhibitor (anagliptin 200 mg/day). He had a history of smoking for 50 years and was a current smoker. Approximately one month previously, he complained of heart burn at early morning (4:00 am or 5:00 am) or at evening after the meal (7:00 pm or 8:00 pm). Duration of heart burn varied from a few minutes to 10 min. The medical practitioner prescribed the PPI (esomeprazole magnesium hydrate 20 mg) to suspected GERD because of no ischemic ECG change. However, he still complained of heart burn irrespective of having PPI for a month. He requested the medical practitioner to investigate the heart disease with 24-h Holter monitoring after an internet search about his conditions. The medical practitioner referred him to our hospital by ambulance because of ST segment elevation on 24-h Holter monitoring (Fig. 2A/B/C). At the emergency room, he again complained of usual heart burn with ST elevation in inferior leads (Fig. 2D/E). After the sublingual use of nitroglycerine, his heart burn disappeared within a few minutes. We diagnosed him as having variant angina. We also performed CAG the next day. He had mild atherosclerosis and ecstatic portion but no significant stenosis (Fig. 3a/d). We performed the intracoronary injection of ACh 20/50 μg into the LCA but we could not obtain the positive provoked spasm, whereas intracoronary injection of ACh 100/200 μg into the LCA documented the focal spasm at mid LAD with usual heart burn and ST segment depression in anterior leads [V2-6 (J), 1.5 mm] (Fig. 3b). Intracoronary administration of ACh 50/80 μg disclosed distal diffuse spasm accompanied with usual heart burn and ST segment elevation in V12 leads (Fig. 3e). After the spontaneous relief of distal RCA spasm, we administered ergonovine 40 μg into the RCA. We observed the subtotal spasm at proximal RCA accompanied with usual heart burn and ST segment depression in inferior leads (Fig. 3f). We diagnosed him as having multi-vessel spasm without significant organic stenosis (Fig. 3c/g). Partial redistribution in inferior portion and decreased washout rate (14.7 ± 5.3%) was observed on myocardial pharmacologic stress thallium scintigraphy. Under the medication of diltiazem R 200 mg twice a day, isosorbide mononitrate 20 mg before sleep, isosorbide mononitrate tape 40 mg once a day, he never complained of heart burn all day. Because total cholesterol and LDL-cholesterlol was 178 mg/dl or 144 g/dl, we administered rosuvastatin 2.5 mg before discharge. Glycohemoglobin was 6.6%.

Fig. 2.

Electrocardiographic (ECG) findings during 24-h Holter monitoring and at emergency admission. (A) Control ECG during 24-h Holter monitoring. (B) ST elevation and monofocal premature ventricular complex was observed at 15:15 h when he complained of usual heart burn. (C) ST elevation was recognized after the meal at 20:48 h when he had heart burn. (D) no ST-T change was observed at emergency admission. (E) ST elevation in inferior leads was found when he complained of usual heart burn.

Fig. 3.

Coronary angiography during spasm provocation test. (a) No stenosis was found at control CAG in the LCA. (b) Intracoronary injection of ACh 200 μg provoked focal spasm at mid LAD accompanied with usual heart burn and ischemic ECG changes. (c) No significant stenosis was observed in the LCA after the administration of nitrate. (d) Just mild stenosis was found at proximal RCA on control CAG. (e) Intracoronary injection of ACh 80 μg into the RCA provoked focal spasm at segment 4 accompanied with usual chest symptoms and no ischemic ECG change. (f) Intracoronary administration of 40 μg ergonovine into the RCA documented subtotal spasm at proximal RCA with usual heart burn and ST elevation in inferior leads. (g) No significant stenosis was found in the RCA after the administration of nitrate.

CAG, coronary angiography; ECG, electrocardiography; LCA, left coronary artery; LAD, left anterior descending artery; RCA, right coronary artery; ACh, acetylcholine.

Discussion

In this case report, two skilled general internists suspected variant angina as GERD initially possibly due to chief complaints of heart burn but not chest pain. They administered PPIs in these two patients on first admission. Fortunately, these two patients were diagnosed as having variant angina without the occurrence of serious irreversible cardiac events. General physicians do not perform the routine esophago-gastroscopy in these suspected GERD patients. In the real world, general physicians or internists may prescribe PPIs or H2 receptor blockers without esophago-gastroscopy when they suspect patients of having GERD. After the administration of PPIs or H2 receptor blockers, general physicians or internists may have a potential proof of diagnosis for GERD when the heart burn improved or disappeared. If general physicians or internists performed esophago-gastroscopy in these patients, they might have a correct diagnosis of coronary spastic angina more early.

Recommendation for general internists and for cardiologists

The cardiologists administer calcium channel antagonists in patients with coronary spastic angina. However, calcium channel antagonists aggravate the symptoms of GERD. In patients with resistant coronary artery spasm, cardiologists may add another calcium channel antagonist when they cannot obtain an improvement in chest symptoms. Gastroenterologists would recommend the esophago-gastroscopy in these patients with resistant coronary spasm. Cardiologists would administer some PPIs or H2 receptor blockers in these patients with refractory coronary spastic angina. In contrast, the cardiologists recommend that general internists or physicians should employ the use of nitroglycerine in patients with resistant GERD when they still complain of heart burn or regurgitation irrespective of the medication of PPIs or H2 receptor blockers. If the administration of nitroglycerine was effective to suppress heart burn, general internists should differentiate coronary spasm in patient with GERD. Furthermore, general internists would perform esophago-gastroscopy in patient with suspected resistant GERD. If they could not obtain the findings of GERD on esophago-gastroscopy, they may diagnose heart disease as a cause of heart burn. General physicians also should perform the examination of 24-h Holter monitoring to clarify the ischemic ECG changes during heart burn in these patients with resistant GERD.

Necessity of differential diagnosis of coronary spasm for GERD

GERD is a global disease and its prevalence is increasing. Compared with North America or Northern Europe, incidence of GERD symptoms in Eastern Asia is low [3]. Guidelines for GERD all over the world did not have the item of coronary spasm as a differential diagnosis for GERD [4], [5], [6]. There was no racial difference about coronary spasm according to the report of Ong et al. and ours [7], [8]. Recently, Teragawa et al. reported that medical history of GERD was frequently observed in approximately one-fifth of patients with coronary spastic angina [9]. Furthermore, GERD is associated with an increased risk of developing coronary heart disease [10]. The cardiologists and gastroenterologists should cooperate about the diagnosis and medication of GERD-related symptoms. The cardiologists hope that guidelines for GERD all over the world should note the differential diagnosis of coronary spastic angina/Prinzmetal variant angina as one of etiology of GERD-related chest symptoms.

Funding

None.

Conflict of interest

The authors declare that they have no conflicts of interest.