Abstract
Left ventricular outflow tract obstruction (LVOTO) complicated with unstable angina (uAP) has not been described widely, but patients with these two conditions have several problems. Differentiation of the two conditions is also often difficult because the chest symptoms are similar. Moreover, nitrates are commonly used for ischemic heart disease, but have the effect of worsening LVOTO. We experienced three cases of dynamic LVOTO with a sigmoid-shaped septum, and without typical hypertrophic obstructive cardiomyopathy, that were complicated with uAP. In all cases, LVOTO was improved after initial percutaneous coronary intervention (PCI) for the left anterior descending artery lesion. Next, a dobutamine stress test was performed and LVOTO was provoked again in two cases, but not in a case with small acute myocardial infarction of the basal septum during PCI. All cases remained asymptomatic with beta-blocker therapy. Therefore, PCI and beta-blocker administration for LVOTO with uAP resulted in favorable clinical courses in all three cases. These outcomes suggest that revascularization including PCI should have priority in the therapeutic strategy for a case of acute coronary syndrome with LVOTO.
Keywords: Percutaneous coronary intervention, Septal branch, Dobutamine, Sigmoid-shaped septum
Introduction
Dynamic left ventricular outflow tract (LVOT) obstruction (LVOTO) is usually complicated with hypertrophic cardiomyopathy (HCM) or severe left ventricular hypertrophy (LVH). In contrast, LVOTO rarely occurs in cases with sigmoid-shaped septum (SS), and without LVH, which are a normal part of the aging process [1]. The main symptoms of ischemic heart disease (IHD) and LVOTO are similar (chest pain and dyspnea on effort) and differential diagnosis is difficult based on these symptoms. Although we have described cases of LVOTO complicated with anteroseptal acute myocardial infarction (AMI) [2], and it is not uncommon for patients with hypertrophic obstructive cardiomyopathy (HOCM) to have coronary lesions, there are few reports of patients with LVOTO complicated with unstable angina (uAP).
Therapy for LVOTO complicated with IHD has several difficulties, including that nitrates that are commonly used for IHD will worsen LVOTO. Here, we describe three cases of dynamic LVOTO with a SS, without typical HOCM, and complicated with uAP. These cases were first treated with PCI for uAP, followed by beta-blockers for LVOTO.
Case 1
The patient was a 78-year-old female with dyspnea and chest pain on effort for one month. She was undergoing treatment for hypertension (HT) and taking cilostazol for transient ischemic attacks. A grade 2/6 ejection systolic murmur (ESM) was detected at cardiac-apex. An electrocardiogram (ECG) revealed sinus rhythm (85 bpm) and complete right bundle branch block (Fig. 1A1). Transthoracic echocardiography (TTE) showed normal left ventricular (LV) wall motion, mild concentric LVH [interventricular septum (IVS) wall thickness of 13 mm and posterior wall (PW) thickness of 11 mm], systolic anterior movement of the mitral valve (SAM), and basal IVS bulging into the LVOT with an aortoseptal-angle of 104° (Fig. 1B1). Peak Doppler velocity at LVOT was 3.42 m/s, corresponding to a peak gradient of 47 mmHg (Fig. 1B2). Coronary angiography (CAG) revealed severe diffuse stenosis at proximal to middle portion of the left anterior descending artery (LAD) and stenosis at proximal right coronary artery (RCA) (Fig. 1C).
Fig. 1.
Case 1. (A) Electrocardiogram. Heart rate (HR) was 85 bpm at sinus rhythm and complete right bundle branch block was found at admission (A1). HR was 70 bpm at sinus rhythm and ST elevation in the V2 lead was present after percutaneous coronary intervention (PCI) (A2). (B) Transthoracic echocardiography on admission. A parasternal long-axis view showed normal left ventricular wall motion, mild concentric left ventricular hypertrophy, systolic anterior movement of the mitral valve, and the basal intraventricular septum bulging into the left ventricular outflow tract (LVOT) with an aortoseptal angle of 104° (B1). A continuous wave Doppler recording with the sample volume positioned at the LVOT gave a peak Doppler velocity of 3.42 m/s, corresponding to a peak gradient of 47 mmHg across the LVOT (B2). (C) Findings in coronary angiography (CAG) in the right anterior oblique cranial view before (left) and after (right) PCI. CAG before PCI showed severe diffuse stenosis at the proximal to middle portion of the left anterior descending artery (LAD) (left). After rotational ablation of the LAD lesion, three everolimus-eluting stents (black bars) were implanted while crossing over several septal branches (right). There was slightly delayed flow in some of the septal branches.
The patient was diagnosed with uAP complicated with LVOTO from TTE and CAG findings. Immediately, cilostazol administration was terminated and atenolol was started at 25 mg/day. Thereafter, PCI was performed for LAD and RCA lesions. First, stenting for RCA proximal lesion was conducted successfully, and then PCI for LAD lesion was performed. After rotational ablation of the LAD lesion, three everolimus-eluting stents (EES) were implanted while crossing over several septal branches (SBs) (Fig. 1C). There was slightly delayed flow in some SBs, but the patient had no chest pain. ECG showed ST elevation in V2 lead after successful completion of PCI (Fig. 1A2).
The peak serum creatine kinase (CK) level was 655IU/L in the hospital course. Chest symptoms improved after PCI, and ESM was not detected the next day. 2D TTE findings were unchanged after PCI. A Doppler study revealed a peak LVOT pressure gradient (PG) of 4 mmHg. An exercise stress test and dobutamine administration under beta-blocker withdrawal did not provoke LVOTO without chest symptoms (the peak provoked LVOT-PG was 13 mmHg with treadmill exercise stress of Bruce 6′25’’ and 17 mmHg with 20 µg/kg/min dobutamine infusion). Atenolol was continued without symptoms.
Case 2
The patient was a 65-year-old female with shortness of breath for three months and chest pain occurring daily for one month. She was undergoing treatment for HT and hyperlipidemia. A grade 2/6 ESM was detected. An ECG revealed sinus rhythm (65 bpm) and terminal T wave inversion in V3–5 leads (Fig. 21-A1). TTE showed normal LV wall motion, SAM, mild mitral regurgitation (MR), and basal IVS bulging into the LVOT (aortoseptal-angle: 84°) (Fig. 21-B1). The peak Doppler velocity at LVOT was 3.35 m/s (PG: 45 mmHg) (Fig. 21-B2). LVH was not evident (IVS: 10 mm, PW: 11 mm). CAG revealed severe stenosis in middle LAD (Fig. 21-C). The diagnosis was uAP complicated with LVOTO.
Fig. 2.
2-1. Case 2. (A) Electrocardiogram (ECG). Heart rate (HR) was 65 bpm at sinus rhythm and terminal T wave inversion in V3–5 leads was detected upon admission (A1). HR was 60 bpm at sinus rhythm and no significant ST-T change was evident after percutaneous coronary intervention (PCI) (A2). (B) Transthoracic echocardiography (TTE) on admission. A parasternal long-axis view showed normal left ventricular wall motion, systolic anterior movement of the mitral valve, mild mitral regurgitation (MR), and the basal intraventricular septum bulging into left ventricular outflow tract (LVOT) with an aortoseptal angle of 84° (white arrowhead) (B1). A continuous wave Doppler recording with the sample volume positioned at the LVOT showed a peak Doppler velocity of 3.35 m/s, corresponding to a peak gradient (PG) of 45 mmHg across the LVOT (B2). Although a Doppler study of TTE revealed a peak PG across the LVOT of 14 mmHg, dobutamine (15 µg/kg/min) provoked LVOT obstruction (PG: 153 mmHg) (B3). (C) Findings in left coronary angiography (CAG) in the right anterior oblique (RAO) cranial view before (left) and after (right) PCI. CAG before PCI revealed severe stenosis in the middle portion of the left anterior descending artery (LAD) (left). PCI for the LAD lesion was performed and an everolimus-eluting stent was implanted crossing over the major septal branch (right). The flow of the major septal branch jailed by the stent was maintained.
Fig. 2-2 Case 3. (A) ECG. HR was 85 bpm at sinus rhythm and T wave inversion in V1–6, I, II, aVL leads and ST depression in V4–6, I, II, aVF leads were detected on admission (A1). HR was 110 bpm at sinus rhythm and additional significant ST-T change was not evident after PCI (A2). (B) TTE on admission. A parasternal long-axis view showed normal LV wall motion, mild concentric left ventricular hypertrophy, a sigmoid-shaped septum (aortoseptal angle 82°, white arrowhead), systolic anterior movement of the mitral valve, and a mild level of MR (B1). The peak Doppler velocity across the LVOT was 3.53 m/s, corresponding to a PG of 50 mmHg (B2). Although a Doppler TTE study revealed a peak PG across the LVOT of 24 mmHg, dobutamine (5 µg/kg/min) provoked LVOT obstruction (PG: 141 mmHg) (B3). (C) Findings in left CAG in the RAO cranial view before (left) and after (right) PCI. CAG before PCI revealed a diffuse severe stenotic lesion in the middle LAD (left). PCI for the LAD lesion was performed and two sirolimus-eluting stents were implanted in the diffuse stenotic lesion of the LAD, jailing the major septal branch (right). The flow of the major septal branch jailed by the stent was maintained.
A few days later, PCI for LAD lesion was performed. An EES was implanted for stenotic LAD lesion crossing over major-SB (Fig. 21-C), and flow of major-SB was maintained. After PCI, no significant ST-T change was evident (Fig. 21-A2), serum CK was not elevated, chest pain and ESM disappeared. A Doppler TTE study revealed a peak LVOT-PG of 14 mmHg, but dobutamine (15 µg/kg/min) provoked LVOTO without chest symptoms under beta-blocker withdrawal (PG 153 mmHg) (Fig. 21-B3). These findings suggest latent LVOTO. Atenolol (50 mg/day) was continued with no symptoms.
Case 3
The patient was a 66-year-old female who had suffered from progressive chest pain on effort for two months. She was undergoing treatment for HT, dyslipidemia, and diabetes mellitus. A grade 2/6 ESM was detected by chest auscultation. An ECG showed sinus rhythm (85 beats/min), T wave inversion in V1–6, I, II, aVL leads, and ST depression in V4–6, I, II, aVF leads (Fig. 22-A1). TTE revealed normal LV wall motion, mild concentric LVH (IVS: 12 mm, PW: 12 mm), SS (aortoseptal angle of 82°), SAM, and mild MR (Fig. 22-B1). The peak LVOT Doppler velocity was 3.53 m/s (PG: 50 mmHg) (Fig. 3B2). CAG revealed a diffuse severe stenotic lesion in middle LAD (Fig. 22-C). The diagnosis was uAP complicated with LVOTO.
Nitrates were not administered because of the risk of worsenning LVOTO. PCI for LAD lesion was performed after a few days. Two sirolimus-eluting stents were implanted in diffuse stenotic lesion of LAD, jailing major-SB (Fig. 22-C). Flow in the jailed major-SB was maintained. After PCI, there was no additional significant ST-T change (Fig. 22-A2), serum CK was not elevated, and chest pain and ESM resolved. A Doppler TTE study revealed a peak LVOT-PG of 24 mmHg, but dobutamine (5 µg/kg/min) provoked LVOTO without chest symptoms under beta-blocker withdrawal (LVOT-PG: 141 mmHg) (Fig. 22-B3). These findings suggest latent LVOTO. Atenolol was started at 50 mg/day with no symptoms.
Discussion
Almost 20% of patients with HOCM have coexistent coronary atherosclerosis [3], and some cases of HOCM have LAD lesions that require revascularization [4]. There are several reports of HOCM patients complicated with coronary lesions of LAD who were treated with PCI and percutaneous transluminal septal myocardial ablation (PTSMA) [4], [5], [6] or surgical myectomy and CABG [7]. However, there are few reports of patients with LVOTO due to HOCM complicated with uAP, and cases of LVOTO due to SS, rather than typical HOCM, complicated with uAP have not been reported previously.
The features of these three cases are described in Table 1. All were diagnosed with uAP based on clinical symptoms and ECG and CAG findings. The culprit lesions were in LAD (Cases 2 and 3) and included LAD (Case 1). Acute coronary syndrome including uAP required immediate treatment. Since these cases were complicated with LVOTO, they could not be treated with nitrates since these worsen LVOTO. Moreover, a dobutamine provocation test, which is often used to evaluate latent LVOTO [8], has a risk for uAP. Therefore, the therapeutic strategies in the three cases were coronary revascularization with PCI followed by evaluation and treatment of LVOTO.
Table 1.
The features of 3 cases.
| Case | 1 | 2 | 3 |
| IHD | Unstable angina | Unstable angina | Unstable angina |
| LVOT PG | 47 mmHg | 45 mmHg | 50 mmHg |
| PCI target | LAD, RCA | LAD | LAD |
| Septal branch flow | Partly worsened | Maintained | Maintained |
| ST elevation in V2 | + | – | – |
| CK increased | + (655 IU/L) | – | – |
| Post-PCI LVOT PG | 4 mmHg | 14 mmHg | 24 mmHg |
| Provoked LVOT PG | 17 mmHg (DOB 20 µg/kg/min) | 153 mmHg (DOB 10 µg/kg/min) | 141 mmHg (DOB 5 µg/kg/min) |
IHD, ischemic heart disease; LVOT, left ventricular outflow tract; PG, pressure gradient;.
PCI, percutaneous coronary intervention; LAD, left anterior descending artery;.
RCA, right coronary artery; CK, creatine kinase; DOB, dobutamine.
PCI was performed as soon as possible after diagnosis of uAP in all three cases, using drug-eluting stents for jailing some SBs. After PCI, chest symptoms improved in all cases and LVOT-PG decreased. The mechanism of reduction of PG after PCI is uncertain, but septal ischemia due to LAD stenting may be a reason for improvement of LVOTO after PCI. Interruption of blood flow to first major-SB with balloon occlusion has been found to reduce the LVOT-PG in patients with HOCM [9]. Moreover, ischemia of LAD itself can be a LVOTO mechanism [2].
After PCI and improvement of LVOTO, a dobutamine provocation test was performed in all three cases without risk for uAP. In Cases 2 and 3, a LVOT-PG of >100 mmHg was provoked by dobutamine infusion, which showed that these cases had latent LVOTO. Therefore, beta-blockers were administered in both cases, since the efficacy of beta-blockers for LVOTO with SS has been shown [1,10]. In contrast, dobutamine infusion did not provoke LVOTO in Case 1. In this case, SB flow partially worsened after LAD stenting, ECG after PCI indicated ST elevation in V2 lead, and CK increased to 655 IU/L after PCI. These data suggest minor AMI in the basal septum with PCI in this case. A case report showed that reduced LVOT-PG by creation of artificial septal myocardial infarction by implantation of covered stent in LAD with jailing of major-SB, instead of PTSMA [5]. Dynamic LVOTO in Case 1 unexpectedly improved after PCI for LAD lesion and this effect might be related to septal ischemia induced by jailing some SBs. Since permanent septal necrosis may not have been achieved, beta-blockers were continued in Case 1. All cases remained asymptomatic for at least 4 years with beta-blocker therapy.
The three cases of dynamic LVOTO with SS and without typical HOCM that were complicated with uAP were initially treated with PCI for uAP and then with a beta-blocker for LVOTO. All had favorable clinical courses. This suggests that revascularization including PCI should have priority in therapy for acute coronary syndrome with LVOTO.
Compliance with ethical standards
Conflict of interest: The authors declare that they have no conflict of interest of this study.
Research in human participants: The study complied strictly with human rights guidelines.
Informed consent: This study was approved by the ethics committee of Niigata City General Hospital.
Declarations of Competing Interest
None.
Footnotes
Learning objective
Therapy for left ventricular outflow tract obstruction (LVOTO) complicated with ischemic heart disease (IHD) is difficult because these conditions have similar symptons, and because nitrates that are commonly used for IHD will worsen LVOTO. In such cases that also have LVOTO due to a sigmoid-shaped septum, rather than hypertrophic obstructive cardiomyopathy, treatment with percutaneous coronary intervention for unstable angina followed by beta-blockers for LVOTO is likely to be effective.
Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.jccase.2021.01.013.
Appendix. Supplementary materials
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