Barlow disease

Article written and reviewed by Dr Luca Moretti

Barlow disease represents the most diffuse and anatomically complex phenotype of myxomatous mitral degeneration. The leaflets are bulky, elongated and redundant, multiple segments, often of both leaflets, extend beyond the annular plane, the chordae may be numerous, elongated or ruptured, and the annulus is large, flattened and sometimes disjoined or calcified. It is therefore not simply P2 prolapse, but a disease involving the entire mitral apparatus.

The name derives from the clinical and auscultatory studies of John Barlow, which linked the click, late systolic murmur and valvular origin; today it is used mainly to define a morphologic category of major surgical utility. Diagnosis does not depend on a single measurement or isolated histology, but on the combination of excess tissue, multisegmental involvement, chordal abnormalities and annular dilatation.

Distinguishing Barlow disease from generic myxomatous disease avoids improper synonymy: Barlow disease is a severe clinical-surgical expression of it. The distinction from fibroelastic deficiency is equally practical. The latter often affects an older patient with thin tissue and focal rupture; Barlow disease presents at a younger age, evolves over years and requires a more complex reconstruction.

Anatomic phenotype and mechanics of regurgitation

Excess tissue generally involves the rough zone and body of the leaflets. The posterior leaflet may be tall and bulky, the anterior leaflet broad and flexible. The term bileaflet prolapse does not imply that all segments are equally diseased: an accurate map distinguishes dominant segments, secondary prolapsing segments, deep clefts and commissures.

Primary chordae tend to elongate and some may rupture, whereas secondary chordae may become thickened or retracted and alter leaflet curvature. A flail segment may generate a dominant eccentric jet, but areas of irregular coaptation may produce others: anatomic complexity therefore cannot be inferred simply from the number of visible jets.

The annulus is often markedly dilated and more circular. Posterior expansion increases the area that the leaflets must cover, while flattening alters stress distribution. Systolic contraction may be exaggerated in some phases and reduced in others; characteristic annular curling describes accentuated systolic motion of the posterobasal wall.

Mitral annular disjunction, namely systolic separation between the insertion of the posterior leaflet and ventricular myocardium, is common in Barlow disease, especially inferolaterally. Measurement, however, depends on the phase and imaging plane, and pseudo-disjunction produced by the leaflet must not be mistaken for true anatomic separation. In addition, the presence of MAD does not by itself imply high arrhythmic risk.

Annular calcification may occur despite the relatively young age, sometimes as a deep and irregular band. It increases the risk of injury to the atrioventricular groove, circumflex artery and annular disruption. CT defines distribution and depth when echocardiography suggests complex calcification.

Regurgitation arises from the combination of edges extending beyond the plane, excess height, loss of support and a large annulus. A prolapsing posterior segment directs the jet anteriorly; an anterior segment directs it posteriorly; bileaflet lesions generate central or multiple jets. The Coandă effect can mask a large volume.

The consequences are those of volume overload: atrial and ventricular dilatation, increased pulmonary pressure and atrial fibrillation. Ejection fraction remains elevated for a long time; a value of 60% represents the threshold for dysfunction in severe regurgitation. The long preclinical period may leave the patient adapted and apparently asymptomatic.

The phenotype may involve the tricuspid valve with prolapse or regurgitation. A dilated tricuspid annulus or at least moderate regurgitation should be assessed before surgery. Mitral correction does not guarantee regression of tricuspid disease, especially in atrial fibrillation or pulmonary hypertension.

Carpentier type II motion predominates, but different segments may have opposite mechanisms. A retracted secondary chord can restrict an area adjacent to a prolapsing zone; calcification can fix the base of the posterior leaflet. Repair must therefore restore a continuous line rather than indiscriminately lower every segment.

Excess tissue is simultaneously part of the problem and a resource for repair. It increases leaflet height and the risk of systolic anterior motion, but also provides surface area for broad coaptation if properly redistributed; conversely, excessive resection may leave insufficient tissue and an exclusively chordal strategy may leave the posterior leaflet too tall. The result therefore depends on three-dimensional balancing of the entire apparatus.

Body size affects interpretation of the annulus. A large absolute diameter in a small person has a different meaning from the same value in a tall man; area and diameters should be indexed and correlated with leaflet surface area. No single threshold defines Barlow disease; the combination of redundancy and diffuse involvement does.

Presentation, progression and arrhythmic risk

The patient may remain asymptomatic for years despite an obvious murmur. Dyspnea, reduced performance, palpitations and fatigue tend to appear as regurgitation increases or the chambers lose reserve; on auscultation the click may be multiple and the murmur long, while a large flail leaflet often makes it holosystolic. These findings help identify the phenotype but do not quantify severity by themselves.

Progression occurs through increasing redundancy, chordal elongation and rupture, and annular dilatation. An additional rupture may produce sudden worsening on a chronic substrate. An already enlarged atrium attenuates fulminant pulmonary edema but favors atrial fibrillation and loss of functional capacity.

Compared with fibroelastic deficiency, Barlow disease tends to present at a younger age and with a longer history. This generalization should not be used as an absolute criterion: older adults may have Barlow disease and younger people may have focal lesions. Imaging and surgical inspection take precedence over age.

Atrial arrhythmias result from dilatation, fibrosis and pressure. Atrial fibrillation modifies the surgical indication and may be treated with concomitant ablation and appendage management. Rhythm success declines with a very large atrium and long duration, so waiting for advanced symptoms reduces options.

Barlow disease is overrepresented in arrhythmic mitral valve prolapse. Redundant bileaflet leaflets, disjunction, curling and traction on the papillary muscles may contribute to premature ventricular complexes and inferolateral fibrosis. The risk of sudden death remains low in absolute terms and is not defined by the name Barlow disease alone.

Unexplained syncope, inferior T-wave inversion, multifocal premature ventricular complexes, rapid nonsustained tachycardia and late enhancement related to the apparatus warrant intensified monitoring. Every patient should undergo ECG and symptom assessment; Holter monitoring, extended recordings and magnetic resonance imaging are selected according to the profile.

Surgery may reduce regurgitation and traction, but its antiarrhythmic effect is variable. An established scar may continue to generate events, and recent studies show persistent risk associated with true disjunction after repair. Arrhythmic follow-up should not be discontinued solely because the valve repair is successful.

Endocarditis, acute mitral regurgitation due to rupture, heart failure, pulmonary hypertension and ventricular dysfunction are the other complications. Antibiotic prophylaxis is not indicated for an uncomplicated native valve; oral hygiene and prompt evaluation of fever are fundamental.

Functional assessment should not depend on spontaneous reporting. Young patients may gradually reduce activity and deny symptoms; history obtained with family members, exercise testing and oxygen consumption can reveal decline. An abnormal blood pressure response, marked increase in regurgitation or exercise pulmonary pressure contribute to decision-making without constituting an absolute indication by themselves.

BNP may be low in the compensated phase and rises with wall stress and atrial fibrillation. Its trend has complementary value. A persistent increase in a patient with severe regurgitation should prompt reassessment of symptoms and function; it does not measure myxomatous activity or the probability of chordal rupture.

Family history seeks mitral interventions, aortopathies and sudden death. In early-onset disease or a family with multiple affected members, counseling and echocardiographic screening are reasonable. In most cases, Barlow disease remains genetically complex, and a negative panel does not make it acquired.

Echocardiographic mapping and preoperative planning

Transthoracic echocardiography confirms prolapse in the long-axis view, quantifies regurgitation and measures its consequences. Each segment is examined in multiple views. Carpentier terminology describes excessive motion as type II, but does not replace etiology: Barlow disease combines multisegmental type II motion with annular dilatation and, sometimes, local restriction.

Jet direction helps guide the anatomic search but does not complete it. An anterior jet often suggests involvement of P2 or P3, a posterior jet of A2 or A3, and a central jet a bileaflet lesion, but multiple jets can merge and wall-hugging jets may appear less extensive. Quantification should therefore integrate three-dimensional vena contracta, EROA, regurgitant volume, pulmonary venous flow and chamber remodeling.

Three-dimensional transesophageal echocardiography provides the surgical view from the atrium, with the aortic valve at 12 o’clock and the appendage to the left. It defines the width and height of prolapse, flail segments, clefts, commissures, posterior leaflet length and calcifications. An incomplete map can leave a residual jet after correction of the most obvious segment.

Annular diameters and area, saddle height, leaflet surface area and gaps are measured. Disjunction is sought at end systole along the inferolateral wall. A very tall posterior leaflet predisposes to systolic anterior motion after repair, especially with a small ventricle, prominent septum and unfavorable leaflet ratio.

Magnetic resonance imaging is useful when echocardiographic regurgitant volume is discordant and for chamber volumes and fibrosis. Exercise or cardiopulmonary testing can unmask symptoms, increased pressure and reduced reserve. Coronary angiography or coronary CT follows age and risk; CT also defines calcification and its relationship to the circumflex artery.

Preoperative assessment does not end with the valve. Left and right ventricular function, atrium, pulmonary pressure, tricuspid valve, coronary arteries, aorta and frailty determine technique and risk. In younger patients, family history and aortopathy are considered; in patients with arrhythmias, postoperative monitoring is planned.

The distance between the annulus and circumflex artery varies along P1-P3 and is relevant to annuloplasty sutures, especially with left coronary dominance. CT or coronary angiography can clarify the course in complex cases. Intraoperative circumflex injury causes posterolateral ischemia and new regurgitation and requires immediate recognition.

Assessment of SAM risk includes the aorto-mitral angle, coaptation-septum distance, posterior leaflet height, anterior leaflet length, septal thickness and ventricular dimensions. No single parameter is sufficient, but the combination guides ring selection and technique. Simulation and three-dimensional printing are promising, not necessary in routine practice.

If deep calcification is present, CT can help anticipate whether to decalcify and reconstruct, leave the calcium undisturbed, or replace the valve. The risk of embolization and rupture should be discussed. A planned strategy is safer than an unexpected finding after atriotomy.

Repairability should be judged by the center that will perform the operation. A valve deemed “unrepairable” in a low-volume setting may be reconstructed at a referral center. Because early surgery in an asymptomatic patient presupposes a very high probability of repair and minimal mortality, program volume is part of the indication.

Principles and techniques of surgical repair

The goal is to obtain a long coaptation surface below the annular plane, without stenosis, residual regurgitation or systolic anterior motion, while preserving mobility and ventricular geometry. There is no single technique for Barlow disease. The strategy is adapted to the map and verified with a saline test and transesophageal echocardiography.

Complete annuloplasty always stabilizes the annulus. A ring that is too small increases the gradient and risk of SAM; one that is too large leaves insufficient coaptation. Sizing considers anterior leaflet surface area, intertrigonal distance, posterior leaflet height and overall geometry, not merely a sizer.

Quadrangular or triangular resection removes posterior leaflet tissue and may be combined with sliding plasty to reduce height. It is effective in highly redundant segments, but extensive resections reduce surface area and place tension on the annulus. “Respect” strategies use ePTFE neochordae to return the edge to the correct level while preserving tissue.

Neochordae may be implanted individually, as loops or in preformed configurations. Length is calibrated against normal segments or coaptation; a chord that is too short restricts, one that is too long leaves prolapse. For anterior involvement, neochordae or chordal transfer are primary tools. Barlow disease often requires combinations on both leaflets.

Commissuroplasty, limited edge-to-edge suturing, cleft closure and transfers complete the repair. Physiologic indentations should not all be closed, because excessive closure causes narrowing. Calcification requires cautious debridement, patch reconstruction or strategies that avoid the groove; replacement is preferable to a fragile repair.

SAM results from anterior displacement of coaptation and interaction with the outflow tract. Prevention includes reducing posterior leaflet height, selecting an appropriate ring, correcting anterior excess and maintaining posterior coaptation. If it appears after bypass, hypovolemia and hypercontractility are corrected; persistent structural SAM requires revision.

The sternotomy, mini-thoracotomy, endoscopic or robotic approach does not by itself determine quality. Minimally invasive techniques may offer faster recovery, but require the same completeness and have a learning curve. In Barlow disease, the priority is repair durability, not incision size.

Intraoperative echocardiography ideally accepts no or trace regurgitation, a low gradient, long coaptation and absence of SAM. More than mild regurgitation or a new eccentric jet should not be casually attributed to loading conditions. Immediate revision is often preferable to early recurrence.

Before final assessment, pressure and volume should approach physiologic conditions. An empty ventricle under catecholamines accentuates SAM; very low pressure hides residual regurgitation. Testing with controlled loading and reduction of inotropic support distinguishes a transient problem from geometry that requires revision.

Preservation of the subvalvular apparatus maintains annulo-ventricular continuity. If repair is unreliable and replacement is performed, preserving compatible chordae and leaflets protects function while avoiding interference with the prosthesis. Conversion to replacement is not a failure if it prevents a fragile result, but preoperative prediction should minimize improvised decisions.

Concomitant surgery for atrial fibrillation and the appendage is individualized according to duration, atrial size and age. Tricuspid repair is considered for severe regurgitation or a dilated annulus. Treating these components during the first operation may avoid a later high-risk procedure.

Indications, outcomes and long-term follow-up

Indications are those for severe primary regurgitation: symptoms, ejection fraction no greater than 60%, end-systolic diameter at least 40 mm and other markers of decompensation. New atrial fibrillation and pulmonary hypertension support intervention before advanced damage. In an asymptomatic patient, early repair requires an expert center, very low risk and a predictably durable result.

Series from referral centers show repair rates above 95% and low mortality, including with minimally invasive and robotic approaches. These results do not eliminate the greater complexity: Barlow disease requires more neochordae, commissural techniques and operative time than a focal lesion. The patient should know the team’s specific experience.

At ten years, freedom from reintervention is generally high, but freedom from moderate regurgitation may be lower and depends on definition, technique and era. The Flameng series showed excellent survival and freedom from reintervention, but greater echocardiographic recurrence in Barlow disease than in fibroelastic deficiency. Reintervention alone underestimates subclinical failure.

Causes of early recurrence include an unrecognized lesion, incorrect chordal length, dehiscence and SAM. Late recurrences result from progression of untreated segments, chordal degeneration, dilatation or endocarditis. An overly focal strategy in a diffuse disease may correct the current jet without stabilizing the substrate.

Outcomes should be reported with independent echocardiography and complete follow-up. Freedom from reintervention may appear excellent even if older patients live with recurrent regurgitation; for Barlow disease, survival, at least moderate regurgitation, gradient, quality of life and arrhythmias are important. Comparisons among techniques are affected by selection and learning curves.

Stable mild residual regurgitation is not equivalent to failure, but an eccentric jet at the site of an uncorrected lesion deserves attention. Serial progression and remodeling determine whether to observe or reintervene. After previous repair, repeat TEER or surgery is selected by considering the ring, gradients, age and feasibility of a second reconstruction.

Initial antithrombotic therapy after repair varies with guidelines, rhythm and local practice; its duration should be stated explicitly. Atrial fibrillation requires anticoagulation according to risk even if ablation has been performed, until the specialist pathway demonstrates conditions for modification. The ring alone does not justify permanent anticoagulation.

TEER may be offered to symptomatic patients with high surgical risk and suitable anatomy. In Barlow disease, a wide gap, multiple segments, clefts and a large annulus may require multiple devices and leave residual regurgitation. The clip does not correct the annulus or disjunction; in a young repairable patient it is not equivalent to surgical reconstruction.

After repair, baseline echocardiography is performed, followed by regular assessments of regurgitation, gradient, volumes, function, pressure and the tricuspid valve. A new murmur, fever, dyspnea or palpitations prompts earlier examination. Arrhythmic surveillance continues in patients with syncope, tachycardia, fibrosis or disjunction, even if the jet has been eliminated.

Anticoagulation and medications follow rhythm, function, technique and protocols; native valve repair does not automatically require permanent anticoagulation. Antibiotic prophylaxis depends on recommendations for prosthetic material and procedures, while oral hygiene remains essential. Rehabilitation and return to sport are graded according to function and arrhythmias.

Pregnancy in the presence of Barlow disease without severe regurgitation is often tolerated, but preconception assessment is required when dilatation, arrhythmias or syndromic aortopathy are present. Reduced vascular resistance may lessen the jet during pregnancy; increased volume and heart rate can nevertheless unmask symptoms. Repair, if already indicated, is preferably performed before pregnancy.

Barlow disease is a test of the quality of a mitral program: it requires segmental diagnosis, appropriate timing and the ability to combine techniques without stenosis or SAM. The best outcome is not merely avoiding replacement, but restoring a valve with physiologic coaptation, low tension and stability that can be verified over the years.