Abstract
Unicuspid aortic valve (UAV) is a rare congenital valvular anomaly, often misdiagnosed as the more prevalent bicuspid aortic valve (BAV). The aim of this study was to explore demographic, clinical characteristics, diagnosis, surgical options, short and long term outcomes of young adults with UAV.
A systematic review and meta-analysis of literature were conducted for studies (1971-2024) including patients (≥ 14 years old) with diagnosis of UAV. Among the 2953 studies retrieved, 67 case reports, 6 case series ( n = 130) and 13 retrospective studies ( n = 918), were included in the analysis. Data from retrospective studies were aggregated using a random effects model for estimating the pooled risk ratio and mean difference.
UAV is mostly unicommissural in adults (mean age 36 years old at diagnosis, 76–79 % males). The most common conditions associated in UAV patients were aortic coarctation (from 3.8 to 12 %), ventricular septal defect (3 %) and Turner syndrome (3 %). In general, the diagnosis was performed with TTE and confirmed with TEE (+/- 3D-TEE). The most common types of surgery were AVR. Dilated ascending aorta was described in 44 % and 35 % of retrospective studies and case reports, respectively. Concomitant ascending aorta replacement/repair was reported 38 % and 27 % of retrospective studies and case reports, respectively. Overall survival was reported in 3 studies, ranging from 95 to 98 % at 10 years.
UAV should be considered a separate entity from BAV. Further investigations with regards to the possibility of a familial incidence, associated histopathological changes in the aorta, and ideal follow up and intervention are needed.
Introduction
Unicuspid aortic valve (UAV), a rare congenital cardiac valvular anomaly with an estimated incidence ranging from 0.02 % to 5 % in adults with surgically excised stenotic aortic valves ( Fig. 1 ), is reported as one of the main causes of congenital aortic valve stenosis and regurgitation in infants, children and young adults. UAV is often misdiagnosed as the more prevalent bicuspid aortic valve (BAV), mainly due to the presence of heavy calcification. In this regard, precise information regarding valve morphology is crucial for aortic valve intervention, reconstruction, or replacement.
However, comprehensive data are lacking mostly derived from case reports and small case series. Thus, we sought to perform a systematic review and meta-analysis in order to fully explore demographic, clinical characteristics, diagnosis, surgical options along with short and long term outcomes.
Material and methods
A systematic review and meta-analysis of literature were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) using a prespecified protocol.
Study selection and eligibility criteria
We selected studies including patients (≥ 14 years old) with diagnosis of UAV. The exclusion criteria were: (1) pediatric patients (<14 years old); (2) review/commentary articles without original data and conference abstracts; (3) studies not in English language.
Search strategy and data sources
The following electronic databases were selected: Pubmed, EMBASE/MEDLINE and Scopus databases for relevant articles published between January 1, 1971, and April 30, 2024. The following search filters were applied: document type, language, publication stage. The search was performed in April 2024. The search was conducted independently by a qualified researcher. The search terms used were ‘unicuspid aortic valve’, in conjunction with ‘diagnosis’, ‘pathology’, ‘treatment’, ‘incidence’, and ‘prognosis’. All cases concerning truncal valves were excluded. A manual search of the reference lists of electronically identified studies was performed to identify additional studies.
Data extraction and outcome measures
Data extraction was conducted using piloted forms. Extracted data were compiled and manually checked. The outcomes were demographic features, risk factors, clinical history, clinical characteristics at presentation, diagnostic imaging tests, in-hospital treatments, short and long-term outcomes in UAV patients.
Statistical analysis
Data are represented as mean ± standard deviation or as median (interquartile range, IQR) for continuous variables (on the basis of how they were reported in primary articles) and frequency (percentage) for categorical variables. The handling of data and combining results of the studies was done using proportion and the Random effect model using the Review Manager (RevMan) (2014) Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration and Prometa 3.0 ( https://idostatistics.com/prometa3/ ).
Additionally, data from the case reports were summarized, and descriptive analysis was done using Statistical Package for the Social Sciences (SPSS), version 22. To perform meta-analysis of continuous data and estimate the mean differences, median and IQR (or minimum and maximum value of range) were transformed in mean value and standard deviation, with Cochrane formula or Hozo formula. , Random-effects models were used based on the DerSimonian–Laird method for analyses because allowed a more conservative assessment of the pooled effect size. I 2 was calculated as a measure of variation across studies caused by heterogeneity rather than chance. I 2 values were interpreted as follows: <25 %, 25 %–75 %, and >75 %, representing low, medium, and high heterogeneity, respectively. Publication bias was qualitatively examined using a funnel plot presenting study size against logit event rate (Supplementary Figs. 1–7) and quantitatively with Egger’s test and Begg’s and Mazumdar rank correlation test. ,
Results
A total of 2953 studies were identified after thorough database searching, and 1304 duplicates were removed. Title and abstracts of 1649 studies were screened, and 1561 irrelevant article were excluded. Full-text eligibility of 88 studies was assessed and 3 studies were excluded for definitive reasons (3 pediatric cases [age < 15 years old]). This information was depicted in the PRISMA flow diagram ( Fig. 2 ).
A total of 1048 UAV patients were reported in the literature from 86 articles (67 case reports, 6 case series [130 patients] (Supplementary Tables 1–3) and 13 retrospective studies [918 patients]), being included in the present review ( Fig. 2 ).
Qualitative analysis of the retrospective studies
In 6/13 studies, the diagnosis of UAV was performed with transthoracic echocardiography (TTE) and/or transesophageal echocardiography (TEE) , , whereas in 6/13 studies with surgical inspection and/or pathological analysis of the valve. , , , Abels and Slotad et al did not reported this data. Six studies reported patients comorbidities. , , Abeln et al. and Ewen et al. reported a rate of 22 % ( n = 57) and 47 % ( n = 29) of arterial hypertension. Infective endocarditis at diagnosis was reported in 2/12 studies (25, 42) in 3.2 % ( n = 1) and 0.7 % ( n = 1), respectively. Noly et al. described repaired aortic coarctation in 12 % ( n = 5) and a Shone syndrome in 2.3 % ( n = 1).
Symptoms at diagnosis were described in 4/13 studies and the dyspnea on exertion was the most common.
The morphology of the UAV was described in 10/13 studies as unicommissural UAV. Only Igarashi et al. described in 0.7 % ( n = 1) of patients acommissural UAV.
The most common types of surgery were aortic valve replacement (AVR), , , bicuspidization repair , , , , and Ross intervention. , , , In Novaro et al. and Butany et al AVR was performed in 81 % ( n = 17) and 87 % ( n = 34) of patients, respectively; in three studies AVR was performed in 100 % of patients enrolled ( n = 31, n = 46 and n = 149, respectively). , , Only Slotad et al. specified the type of valve implanted (65 % mechanical vs 12 % bioprosthesis). Bicuspidization was performed in 64 % ( n = 167) and 19 % ( n = 8) of patients by Abeln et al and Noly et al whereas in three studies was performed in 100 % of patients enrolled ( n = 25, n = 137 and n = 17, respectively). , ,
In five studies, Ross procedure was performed in 35 % ( n = 91) and 13 % ( n = 5), 81 % ( n = 34) 9.5 % ( n = 2) and 5 % ( n = 4). , , , , Tricuspidization repair using autologous pericardium was described only in one study performed in 100 % of patients ( n = 9).
In-hospital complications were reported in 2 studies: Abeln et al. reported 1.9 % ( n = 5) of perioperative bleeding, 0.7 % ( n = 2) of re-operation for dehiscence and 0.38 % ( n = 1) of early death. Slotad et al. reported 12 % ( n = 9) AV block requiring pacemaker implantation and 2.6 % ( n = 2) ischemic stroke and transient ischemic attack. Igarashi et al. reported 1.4 % ( n = 2) of early deaths, for sepsis and cerebral hemorrhage. 5/13 studies did not report information about in-hospital outcomes. The time of follow-up was reported in 7/13 studies, ranging from 22 days to 17 years. Aortic valve re-intervention was described in 18 % ( n = 47), 12 % ( n = 3), 34 % ( n = 47), 2 % ( n = 3) and in 19.7 % ( n = 14) in 5/13 studies. , , , ,
Overall survival was reported in 4 studies, , , ranging from 95 to 98 % at 10 years.
Tables 1–3 summarized the characteristics of included retrospective studies.
| First author, Year | Study design, Region | N | Age (years) | Sex, male N | Other conditions | Symptoms | UAV diagnosis (first modality) | Other Imaging modalities |
|---|---|---|---|---|---|---|---|---|
| Abeln, 2023 | Retrospective Germany | 258 | 18-54 35 (9.3) * | 193 | AH ( n = 51) | – | – | – |
| Butany, 2009 | Retrospective Canada | 39 | 38 (18-64) ⁎⁎ | 36 | – | Dyspnea, palpitations | TTE, pathological analysis | – |
| Collins, 2008 | Retrospective Canada | 31 | 41.6 (14.3) * | 26 | IE ( n = 1) | – | Surgery + pathological analysis | TTE,TEE |
| Ewen, 2019 | Retrospective Germany | 69 | 29.0 (13.0) * | 61 | CAD ( n = 1); AH ( n = 29) | – | TTE, TEE | – |
| Franciulli, 2014 | Retrospective Italy | 25 | 38 (12) | 23 | Valvuloplasty in the childhood ( n = 1). | – | TEE | TTE |
| Igarashi, 2019 | Retrospective Germany | 137 | 26 [3-64] ⁎⁎ | 108 | IE ( n = 1) | – | TTE,TEE | – |
| Kawase, 2012 | Retrospective Japan | 9 | 48.9 (19.9) * | 8 | – | – | 3D-TEE | – |
| Kolesar, 2017 | Retrospective Slovakia | 17 | 23(5) * | 9 | Dyspnea, Angina pectoris | Surgery | ||
| Noly, 2016 | Retrospective Canada | 42 | 33.9 (1.7) * | 33 | Valvuloplasty in the childhood ( n = 9); Repaired aortic coarctation ( n = 5); Shone syndrome ( n = 2); WPW ( n = 2) . | Dyspnea ( n = 23); Angina pectoris ( n = 1); Syncope ( n = 5) | Surgery | TTE, TEE BAV on TTE ( n = 33) |
| Novaro, 2003 | Retrospective USA | 21 | 34 (10) * | 14 | – | Dyspnea ( n = 11) | TTE/TEE | – |
| Roberts, 2005 | Retrospective USA | 46 | 51(14) * | 34 | – | – | Pathological analysis | TTE,TEE Angiography |
| Slotad, 2019 | Retrospective USA | 75 | 37 (12) | 48 | PFO ( n = 4), Aortic coarctation ( n = 2), HCM ( n = 1); AD ( n = 1). Family history of congenital aortic valve disease ( n = 7). | Pathological analysis (71 after surgery, 4 at autopsy) | ||
| Zhu, 2016 | Retrospective USA | 149 | 43.8 (11.7) | 52 | – | – | Surgery | TTE, TEE, CT |
| First Author, | N | Ejection Fraction ( %) | LV diameters (mm) | Aortic Stenosis | Aortic Regurgitation | AVA (cm 2 ) | Aorta |
|---|---|---|---|---|---|---|---|
| Abeln, 2023 | 258 | – | – | Isolated AS ( n = 45) MG: 20 (12) * mmHg in the repair group and 39 (22) * mmHg in the Ross group. | Isolated AR ( n = 104) AS+AR ( n = 103) | – | AA (>43 mm) ( n = 51) |
| Butany, 2009 | 39 | – | – | – | AS+AR ( n = 18) | 0.8 * | AA 40-55 mm ( n = 39) |
| Collins, 2008 | 31 | – | – | Grade 3 ( n = 18) | Grade 3 ( n = 6) AS+AR ( n = 6) | – | – |
| Ewen, 2019 | 69 | 58 (13) * | EDD 30 (7) * ESD 20.4 (4.9) * | – | – | – | Dilated aorta (>40 mm) ( n = 30) |
| Franciulli, 2014 | 25 | 59 (5) * | EDD 59 (16) * ESD 43 (6) | Grade 3 ( n = 1) MG 11.5 (10) * mmHg | Grade 3 ( n = 24) | – | AA 51(4) * mm |
| Igarashi, 2019 | 137 | <50 ( n = 18) | Dilated LV ( n = 46) | Grade 2 ( n = 25) Grade 2-3 ( n = 14) Grade 3 ( n = 30) | Grade 2 ( n = 29) Grade 2-3 ( n = 73) Grade 3 ( n = 20) | – | Dilated annulus ( n = 49) Dilated SV ( n = 20) Dilated AA ( n = 49) |
| Kawase, 2012 | 9 | – | – | Grade 3 ( n = 8) MG 92.0 (31.2) * | Grade 3 ( n = 4) Grade 2 ( n = 3) | 1.05 (0.58) * | – |
| Kolesar, 2017 | 17 | 56 (8) * | EDD 49 (7.1) * | MG 36 (13) mmHg | – | 0.8 (0.1) * | AA 41(7) * mm |
| Noly, 2016 | 42 | 61(6) * | EDD 53 (12) * | Isolated AS ( n = 9) AS+AR ( n = 29) PG 80.9 (29) * mmHg MG 50.6 (20) * mmHg | Isolated AR ( n = 5) Grade 1 ( n = 17) Grade 2 ( n = 19) Grade 3 ( n = 5) | 1.1 (0.49) * | Dilated annulus ( n = 31) Dilated AA ( n = 6) AA+SV dilated ( n = 2) SV dilated ( n = 1) Annulus 25.8 (3.4) * mm SV 32.1 (5) * mm AA 36 (5) * mm |
| Novaro, 2003 | 21 | 58.0 (8) * | EDD 47 (6) | PG 90 (28) * mmHg MG 54 (17) * mmHg | Grade 3 ( n = 4) | 0.7 (0.2) * | AA 3.9 (0.6) * mm |
| Roberts, 2005 | 46 | – | – | – | – | – | – |
| Slotad, 2019 | 58 | AS (any degree) ( n = 58) Mixed AR/AS ( n = 54) AS (pure) 4 ( n = 7) | AR (any degree) ( n = 54) | SV or AA dilated ( n = 57) | |||
| Zhu, 2016 | 149 | 55 (0.8) * | – | Grade 1 ( n = 18) Grade 2 ( n = 28) Grade 3 ( n = 80) | Grade 1 ( n = 40) Grade 2 ( n = 27) Grade 3 ( n = 61) | 0.9 (0.44) * | AA 43.3 (7.4) * mm |
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