From Bicuspid to Quadricuspid Aortic Valve: The Clinical Case of a 38-year-old Woman with Chest Pain.

We report a case of a 38-year-old woman with an alleged diagnosis of bicuspid aortic valve disease that was correctly identified as quadricuspid aortic valve (QAV) disease in our cardiology unit. In this case report, we focus on echocardiographic features of this rare congenital valve disease aiming to provide useful tips to achieve correct differential diagnosis according to the updated echocardiographic international guidelines and recommendations, briefly reviewing other QAV cases reported in the current literature as well. In conclusion, we strongly recommend adhering to practical echocardiographic guidelines to reduce interobserver variability, not to miss the diagnosis of rare congenital defects like the one we reported. Copyright:

INTRODUCTION

Quadricuspid aortic valve (QAV) is a rare congenital heart disease, characterized by the presence of four aortic cusps, instead of the usual anatomical three. QAV is found in 28–33 every 10 × 106 individuals according to autoptic examinations and in 590–650 every 10 × 106 individuals undergoing transthoracic echocardiograms showing a female predominance (1:108). Approximately, 16% of all patients with QAV diagnosis require surgical treatment.[1]

Abnormal 4-cusp formation could possibly develop from either aberrant fusion of the aorticopulmonary septum or from abnormal mesenchymal proliferation in the common trunk.[2]

CASE REPORT

A 38-year-old woman was admitted to the emergency room for a clinical picture characterized by the episodes (duration 5–10 min) of atypical chest pain irradiating to the upper left limb. The patient reported previous cocaine and heroin abuse and current smoking of about 20 cigarettes per day. Body mass index of 31 was calculated. The electrocardiogram (ECG) showed normal ECG pattern, and the high-sensitivity troponin I resulted normal on several determinations.

Since 2006, the patient underwent serial echocardiographic examinations that revealed and confirmed alleged bicuspid aortic valve (BAV) with no aortic dilation and mild aortic regurgitation.

In her past clinical history, the patient reported noncomplicated peptic ulcer and chronic gastritis, lymphatic adenopathy of undetermined etiology, and recurrent episodes of anorexia/bulimia and panic attacks, treated with antidepressants – selective serotonin reuptake inhibitor, valproate, and diazepam. She reported two pregnancies: one child was diagnosed with right-sided aortic arch congenital anomaly and cleft palate and the other one was in good health status. Patient's father died from myocardial infarction at the age of 55, and her mother was affected by systemic hypertension.

At admission to our unit, the clinical examination revealed regular heartbeat and 2/6 levine diastolic murmur; blood pressure was 140/80 mmHg and SpO2 was 98% breathing room air. The ECG showed sinus rhythm, and no abnormal findings were detected: the ECG pattern was overall normal and ventricular repolarization was actually within the normal limits; no changes on ECG were detected when compared to previous ones performed in the emergency room.

A transthoracic echocardiography (TTE) was performed: biventricular systolic function was considered normal, ejection fraction was estimated 60%, no wall motion abnormalities were found, and left ventricular dimensions were within the normal limits; according to age and body surface area (LVIDd: 53 mm and LVEDV: 138 ml), the aortic root diameter was within the normal limits (24 mm) and no dilation of ascending aorta or aortic arch was detected; the TTE seemed to reveal an unusual “X-shaped” aortic configuration in a parasternal short-axis (PSAX) view [Figure 1b]. Symmetrical closure of aortic valve cusps was detected in the parasternal long-axis (PLAX) view [Figure 1a]. The ejection fraction was as high as 50%, mild-to-moderate aortic regurgitation was found in PLAX with a vena contracta of 3–4 mm diameter, and an aortic insufficiency pressure half time of 513 ms at continuous Doppler evaluation. The transesophageal echocardiography (TEE) defined the diagnosis showing the picture of an “X-shaped,” QAV (Hurwitz–Robert's “Type A” QAV) with well-balanced, comparable aortic cusp sizes [Figure 2], mild-to-moderate aortic regurgitation was confirmed [Figure 1d], and no doming of the cusps was documented in TEE long-axis view [Figure 1c].[3]

Figure 1

(a) Transthoracic echocardiography parasternal long-axis diastolic view: White arrows: symmetrical closure of the aortic cusps; (b) parasternal short-axis systolic and diastolic view; (c) transesophageal echocardiography 126° long-axis view, systolic: *Aortic root and valve, no doming of the cusps; (d) transesophageal echocardiography 126° long-axis view, diastolic: head arrow: mild-to-moderate aortic regurgitation with aliasing intraaortic signal due to flow turbulence. Transthoracic echocardiography was performed using Philips CX50 Cart ultrasound system supplied by common phased array sector probe

Figure 2

Transesophageal echocardiography 33° short-axis view, diastolic: “X-shaped” aortic valve with well-balanced aortic cusp sizes. Transesophageal echocardiography was performed using Philips IE33 ultrasound system with the use of dedicated multiplanar probe. Pictures and clips were then stored and analyzed offline through the use of SuitEstensa software, release 2.0, by Esaote Group

The patient underwent submaximal, fatigue limited, ergometer stress test that revealed no angina-like symptoms neither ECG alterations. High-sensitivity troponin I remained within the normal range limits on several determinations during the hospital stay.

As isolated systolic hypertension was diagnosed during hospitalization, a mild dosage of angiotensin-converting enzyme inhibitor was prescribed.

Considering the current clinical condition not suitable for any surgical or invasive treatment, the patient was selected for medical treatment only and regular clinical and echocardiographic follow-up.

After 3 days, the patient was discharged home with a schedule of clinical follow-up. Indications to quit smoking and reduce body weight were given. After 21 days, during the first scheduled consultation, the patient reported the absence of further episodes of chest pain. She reported good compliance with the pharmacological treatment, maintaining acceptable blood pressure values at self-check measurement at home.

DISCUSSION

We managed the case of a 38-year-old woman with nontreated systemic hypertension, admitted to the emergency room complaining of episodic, nonfatigue-related chest pain; QAV diagnosis was suspected through TTE and confirmed by TEE. Antihypertensive therapy was administered with acceptable blood pressure result.

Types A, B, and C in Hurwitz/Roberts classification account for more than 85% of the cases of QAV; type D variant is very rare. In our patient, we identified a Type A QAV with well-balanced, comparable aortic cusp sizes.[3]

Controversies remain about the role of genetics in the etiology of QAV. Although basically considered as pure congenital anomaly, case reports consider the involvement of genes encoding 21-hydroxylase, CYP21A2, tenascin-X, TNXB, and correlations with connective tissue genetic anomalies such as Ehlers–Danlos syndrome.[45]

Symptoms of chest pain reported by our patient remain unclear: after hospitalization and administration of antihypertensive drug, she declared regression of the symptom: possible extracardiac etiology of the symptom with coincidental diagnosis of QAV has to be considered as the patient suffered from chronic gastritis; if myocardial shear stress related to nontreated hypertension in concomitant QAV could be involved remains unclear.

This clinical case implies interesting considerations regarding technical echocardiographic examination. The strict adherence to standardized echocardiographic examination technique, extensively recommended by the international guidelines allowed us to identify the QAV.[6] The initial suspicion of QAV was triggered by the identification of perfectly symmetrical, central aortic regurgitation in TTE in PLAX view. BAV is often associated with asymmetric image of leaflets coaptation at the level of the tips in PLAX view with sometimes slight concurrent systolic doming of the leaflets, with prominent convexity toward inner lumen of the aorta: this echographic feature was not present in our case; moreover, the regurgitant jet was not eccentric but central mild-to-moderate despite the turbulent and eccentric regurgitation that can be related to BAV diagnosis.[7] In TTE PSAX view, the suspicion was further supported by the presence of clear evidence of four swinging leaflets with no evidence of bicuspid coaptation, evidence of “X-shaped” aortic sign during closure of the cusps, and “squared-shaped” sign during systolic phase should trigger QAV suspicion. These features could not support the hypothesis of the presence of “raphe in BAV;” nevertheless, the patient was “labeled” with “BAV” diagnosis in many previous serial echocardiograms. The case report brings back into vogue the debate regarding the “inter-observer variability” in echocardiography and stresses the need for the standardization of technique and high-quality training of the operator to reduce the probability of incorrect diagnosis.

The TEE was necessary in this case and defined the diagnosis: whenever suspicion is high or any critical doubt about the diagnosis occurs if TTE is not diriment, TEE is a safe and suitable examination when performed by expert operators following international recommendations and guidelines to achieve the best echographic performance; in this case, we performed a complete, standardized TEE examination searching for any possible associated congenital and morphological disorder that was finally excluded. The TEE made the diagnosis clear after many years of serial, misdiagnosed TTE examinations; the examination was well tolerated by the patient, was not time-consuming, and was carried out with no complications for the patient. Clearly, we underline and stress the importance of proper, accurate training of sonographers and cardiologists in echographic field, and we strongly recommend to adhere to international guidelines and apply a well-defined, commonly shared, and standardized protocol; this is essential not to miss important echocardiographic features that can make the difference in an accurate diagnosis in the end.

QAV is commonly diagnosed as an isolated congenital anomaly; rarely, other congenital heart defects can be associated in 18%–32% of the patients.[1] Moreover, considering that coronary artery and coronary ostium anomalies are the most frequent associated disorders with QAV, taking in consideration the atypical recurrent chest pain referred by the patients, we focused on the detection of possible anomalies in origin of coronary ostia confirming that there was no coronary anomaly in coronary origin.[1] Finally, considering that Tsang et al. observed that aortic dilation was present in 29% studied patients, including aortic root dilation in 36%, tubular ascending aorta dilation in 36%, and both aortic root and tubular ascending aorta dilation in 29%, we evaluated aortic diameters in our patients that resulted within the normal limits.[1] Finally, we need to mention a case report that could be partially related to our case; Henley and Kumar in fact reported a case of a young cocaine abuser woman that was initially diagnosed with suspicious QAV; further tests then clarified that in this specific case, it was not a diagnosis of real congenital QAV rather than a rare complication of cocaine abuse implying aortic dissection: on direct inspection during cardiopulmonary bypass, the aortic valve was confirmed to be trileaflet and intact with a circumferential intimal flap above the sinuses of the Valsalva, consistent with a focal chronic aortic dissection due to chronic cocaine abuse; the echocardiographic findings were then consistent in “false” misleading image of QAV.[8] In our patient, although she was previously cocaine abuser, we confirmed that there were neither aortic miointimal flaps nor dissections and we definitely confirmed the true nature of congenital QAV defect.

There are no specific guidelines leading the optimal follow-up and treatment of this rare congenital disease. It is remarkable to notice that despite structurally abnormal valve and presence or not of dilation of the ascending aorta, the patient with the diagnosis of true QAV is apparently less prone to aortic dissection when compared to patients affected by BAV: the latter is in fact associated with an 8-fold increase in the age-adjusted risk of aortic dissection compared with that of the general population and in QAV patients.[1] Although classical, surgical aortic valve replacement or repair was safely and successfully achieved in a small number of patients affected by complicated QAV, there are recent case reports that also prove safe use of transcatheter aortic valve implantation in selected patients.[9]

CONCLUSIONS

QAV is a rare congenital heart disease. The outcomes of the disease, whether surgically or interventionally treated or not, are apparently good despite the small number of patients reviewed in literature. All efforts have to be made to increase the accuracy and standardization in echocardiographic techniques in order not to miss the rare diagnosis as QAV as well.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.