Agenesis of the tendinous chords is a rare congenital malformation of the mitral valve, characterized by the complete or partial absence of the tendinous chords, fibrous structures essential for anchoring and the correct movement of the valve leaflets during the cardiac cycle. This condition causes a severe functional impairment of the mitral apparatus, with the valve leaflets unable to coapt properly during ventricular systole. Clinically, it predominantly presents as severe mitral regurgitation, often evident within the first weeks of life. Although it may occur as an isolated anomaly in some cases, agenesis of the tendinous chords is frequently associated with other complex congenital heart diseases, further complicating clinical and surgical management.
The etiology of tendinous chord agenesis lies in an early embryological defect occurring during the formation and differentiation of the mesenchymal tissue of the atrioventricular valvular apparatus, between the 5th and 7th week of gestation. Normally, the tendinous chords derive from the transformation of the mesenchymal tissue of the endocardial cushions into elongated fibrous structures connecting the papillary muscles to the mitral leaflets. An alteration in this differentiation process can lead to a partial or total absence of these structures, resulting in a permanent structural malformation.
The main recognized risk factors include:
No specific environmental or teratogenic factors have been clearly identified in association with this condition, although the role of certain teratogens cannot be entirely excluded.
The pathogenic mechanism underlying tendinous chord agenesis involves a severe functional alteration of the mitral valve. The absence of the chords prevents the stabilization and control of the leaflets during left ventricular systole. Consequently, the valve leaflets become flail and unable to coapt, producing a massive regurgitation of blood from the left ventricle back into the left atrium during ventricular contraction.
The resulting pathophysiology is characterized by a marked volume overload of the left atrium and ventricle. Chronic severe mitral regurgitation leads to early and progressive dilation of the left cardiac chambers, with eccentric ventricular remodeling and significant left atrial enlargement. Initially, the left ventricle can maintain an effective stroke volume due to increased compliance and compensatory eccentric hypertrophy. However, in the short to medium term, this mechanism proves insufficient, rapidly leading to the development of left-sided congestive heart failure, with potential secondary involvement of the right ventricle due to ensuing post-capillary pulmonary hypertension.
The severity of the malformation and its clinical course depend on the presence or absence of associated cardiac anomalies, the extent of chordal absence, and the promptness of diagnosis and corrective intervention. In patients with complete agenesis, the clinical picture tends to be dramatic from the first months of life, making early surgical treatment mandatory to ensure survival and acceptable quality of life.
The clinical manifestations of tendinous chord agenesis are generally early and severe, directly reflecting the severity of mitral regurgitation caused by valve leaflet instability. The clinical picture typically appears within the first months of life, with symptoms dominated by severe mitral insufficiency and the rapid onset of signs and symptoms of left-sided heart failure.
In neonates and infants, the most frequent early signs include:
In older children or patients with less severe partial forms, the clinical course may develop more slowly. In these cases, predominant symptoms include progressive dyspnea, initially on exertion and later at rest, associated with asthenia, fatigue, and limitation of daily activities. Reduced exercise tolerance may be accompanied by the onset of supraventricular arrhythmias, particularly atrial fibrillation or atrial flutter, due to chronic and severe left atrial dilation.
On physical examination, mitral insufficiency typically presents with a loud holosystolic murmur, clearly audible at the cardiac apex with radiation towards the left axillary region. This murmur is often accompanied by a palpable thrill and may vary in intensity depending on the severity and compliance of the involved cardiac chambers. In some cases, an S3 gallop can be appreciated, indicative of left ventricular volume overload.
In patients with advanced disease, signs of congestive heart failure are evident: presence of crackles at the lung bases, hepatomegaly due to systemic venous congestion, peripheral edema (more frequent in adolescent or adult patients with late diagnosis), and jugular venous distension when right ventricular involvement occurs secondary to significant pulmonary hypertension.
The clinical presentation may be influenced by the presence of other associated congenital heart diseases, which can further worsen the clinical picture or, more rarely, partially mask the symptoms of mitral insufficiency. Therefore, a careful and multidisciplinary clinical approach is essential to allow timely diagnosis and appropriate therapeutic management from the earliest manifestations.
The diagnosis of tendinous chord agenesis requires a systematic approach integrating clinical suspicion, cardiac auscultation, and advanced imaging techniques. Diagnostic suspicion typically arises in neonates or infants presenting with early and severe signs of mitral insufficiency, associated with symptoms of congestive heart failure in the absence of signs of rheumatic fever or other acquired diseases. A loud and persistent holosystolic murmur, combined with respiratory distress and growth delay, quickly directs the clinician toward a possible congenital cause of mitral insufficiency.
Initial investigations include:
Definitive diagnostic confirmation relies on transthoracic echocardiography (TTE), the cornerstone exam for structural and functional evaluation of the mitral valve apparatus. Echocardiography clearly demonstrates the complete or partial absence of the fibrous structures that normally connect the mitral leaflets to the papillary muscles. Direct visualization reveals flail mitral valve leaflets without anchoring, characterized by excessive mobility during the cardiac cycle. Color Doppler documents massive mitral regurgitation, often with a wide, centrally directed jet toward the left atrium.
Transesophageal echocardiography (TEE) is indicated in cases where detailed definition of valve morphology is required to precisely plan surgical intervention. TEE provides high-resolution visualization of the mitral structures, clarifying the anatomical relationship of the leaflets to the papillary muscles and identifying any associated ventricular septal defects or abnormalities of the subvalvular apparatus.
In particularly complex cases or in the presence of concomitant cardiac anomalies, three-dimensional (3D) echocardiography represents a valuable diagnostic support. This technique allows detailed spatial reconstruction of the mitral valve, facilitating precise identification of the absence of tendinous chords and characterization of mitral regurgitation.
Cardiac magnetic resonance imaging (CMR) may be selectively used to accurately assess ventricular volumes, left ventricular function, and to quantify mitral regurgitation volume, especially in anticipation of corrective surgery.
The differential diagnosis should consider other forms of congenital mitral insufficiency, such as congenital leaflet clefts, congenital mitral valve prolapse with myxomatous dysplasia, Ebstein anomaly of the mitral valve (extremely rare), and acquired lesions like traumatic or infective endocarditis-related ruptures. Differentiation is generally straightforward due to the precise morphological definition achievable with advanced echocardiographic techniques.
Timely diagnosis is crucial to establish effective therapeutic management, minimizing the risk of irreversible heart failure and optimizing long-term surgical outcomes.
The treatment of tendinous chord agenesis is exclusively surgical and represents an absolute priority in patients with severe mitral insufficiency, regardless of age. Due to the severity and rapid onset of cardiac complications, corrective surgery must be performed early, often within the first months or years of life, to prevent irreversible cardiac deterioration and ensure the best possible clinical outcome.
The surgical indications are clear and well-defined, including:
Mitral valve repair is always the primary goal of surgery. The procedure consists of restoring the functional anatomy of the mitral valve by reconstructing the missing tendinous chords using artificial chords made of synthetic material (generally polytetrafluoroethylene, Gore-Tex®) or harvested from autologous pericardial tissue. This reconstruction aims to stabilize the valve leaflets, restoring proper coaptation during systole. Often, to further improve the outcome, valve annuloplasty with a prosthetic ring is added to optimize valve geometry and prevent secondary dilation of the mitral annulus.
In rare cases, when the mitral valve is severely dysplastic or adequate repair is not feasible, mitral valve replacement is performed. Although effective in correcting mitral insufficiency, this procedure entails more complex long-term management, especially in children, due to the need for chronic anticoagulation and the risk of future surgical revisions related to body growth.
The postoperative prognosis is generally favorable in patients treated early and with optimal repair techniques. Long-term survival exceeds 90% in cases managed at specialized centers, with good quality of life and significant regression of symptoms and volume overload of the left cardiac chambers. Patients undergoing effective valve repair show normalization of left ventricular function and a marked reduction in the risk of late complications such as arrhythmias or chronic heart failure.
Clinical and echocardiographic follow-up is essential to monitor valve function, assess the stability of implanted artificial chords, and prevent possible recurrence of mitral insufficiency. In children, body growth is a critical factor: often, subsequent adaptation of the valvular apparatus is necessary during adolescent development. Periodic surveillance enables timely intervention if loss of initial repair effectiveness occurs.
The main positive prognostic factors include the promptness of surgical intervention, the ability to perform a durable mitral valve repair, the absence of complex associated cardiac pathologies, and optimal multidisciplinary postoperative management.
Complications of tendinous chord agenesis may arise both in the natural course of untreated disease and as undesired outcomes of corrective surgery. Their incidence and severity are closely related to the timeliness of diagnosis, the severity of the initial clinical presentation, and the technical quality of the surgical repair performed.
Without treatment, the main and inevitable complication is the rapid progression of congestive heart failure. Chronic volume overload of the left cardiac chambers induces increasingly marked atrial and ventricular dilation, with progressive worsening of left ventricular function and development of refractory heart failure. Associated with this deterioration is the frequent onset of post-capillary pulmonary hypertension, initially reversible but which can become chronic over time, causing irreversible pulmonary vascular damage.
Left atrial dilation also represents an important anatomical substrate for the development of supraventricular arrhythmias, particularly atrial fibrillation and atrial flutter. These arrhythmias can further complicate the clinical picture with thromboembolic events, requiring dedicated pharmacological or interventional management.
Surgical complications are generally rare in specialized centers but may include:
In very rare cases, thromboembolic complications may occur, particularly in patients with persistent atrial fibrillation or significant residual atrial dilation, thus requiring careful management of postoperative anticoagulant or antiplatelet therapy.
In the long term, a peculiar problem in the pediatric population is the need for reoperation related to somatic growth. As cardiac dimensions and body size increase, implanted artificial chords may lose their optimal tension, requiring further surgical adjustment to maintain satisfactory mitral valve function.
The best strategy to minimize complications consists of early diagnosis of the malformation, careful surgical planning, and strict clinical and echocardiographic follow-up. When these conditions are met, the incidence of severe complications is extremely low, ensuring a favorable prognosis and good long-term quality of life.