Mitral papillary rupture: a rare risk under anthracyclines with preserved LVEF

Anthracycline cardiotoxicity: beyond ejection fraction

While the cardiotoxicity of doxorubicin is classically associated with dose-dependent left ventricular systolic dysfunction, acute structural complications can occur more insidiously. This case report documents an acute mitral papillary muscle rupture in a 78-year-old patient treated for metastatic liposarcoma. Notably, the event occurred despite a preserved left ventricular ejection fraction (LVEF), maintained between 65 and 75% during ultrasound follow-up between 2022 and 2025.

The objective of this presentation is to analyze the etiological mechanism of massive mitral regurgitation (grade 4+) occurring one week after the completion of a liposomal doxorubicin protocol (absolute cumulative dose of 534 mg). The authors explore the hypothesis of a "two-hit model": structural changes induced by chemotherapy may weaken an already vulnerable myocardium. In this specific case, the pre-existing vulnerability is correlated with pulmonary stereotactic body radiation therapy (SBRT) performed 9 months earlier, targeting areas in the immediate vicinity of the diaphragmatic and inferior walls of the heart. This observation suggests that standard onco-cardiological monitoring could benefit from advanced imaging to detect structural risks not correlated solely with LVEF measurement.

Methodology of clinical observation

This case report documents a rare cardiac structural complication in a 78-year-old female patient treated for metastatic liposarcoma. The methodology is based on the retrospective analysis of an acute event occurring in a context of therapeutic multi-exposure.

• Oncological protocol:
  • Radiotherapy: SBRT (Stereotactic Body Radiation Therapy) in 5 fractions administered 9 months before the acute episode, targeting the lower pulmonary lobes near the diaphragmatic and inferior heart walls.
  • Chemotherapy: Administration of liposomal doxorubicin reaching an absolute cumulative dose of 534 mg.
• Follow-up and monitoring:
  • Longitudinal imaging: Follow-up echocardiographies performed between 2022 and 2025, documenting a preserved left ventricular ejection fraction (LVEF) (65–75 %).
  • Acute evaluation: Analysis of cardiac biomarkers (BNP and troponins) and performance of a transoesophageal echocardiography (TOE) one week after the end of anthracycline treatment.
• Diagnostic criteria and intervention:
  • Confirmation by TEE of a rupture of the posteromedial papillary muscle head and chordae, leading to severe mitral regurgitation (4+).
  • Therapeutic management: Comparison of the open surgical strategy versus medical optimization (loop diuretics, lisinopril, metoprolol succinate) and evaluation for transcatheter edge-to-edge repair (TEER).

Clinical presentation and biological profile

A 78-year-old female patient, treated for metastatic liposarcoma, presented with acute dyspnoea one week after completing a cycle of liposomal doxorubicin, reaching an absolute cumulative dose of 534 mg. Despite the acuity of the symptoms, the initial biological assessment revealed a normal BNP level and stable troponins, showing only a minimal and constant ("flat") elevation.

Evaluation of ventricular function and structural imaging

Longitudinal echocardiographic follow-up (2022-2025) confirmed the maintenance of a preserved left ventricular ejection fraction (LVEF), oscillating between 65% and 75%, including during the acute phase. However, transoesophageal echocardiography (TOE) revealed major structural damage, independent of global systolic function.

Ultrasound Parameter	Clinical Observation
Location of the rupture	Head of the posteromedial papillary muscle and associated chordae tendineae
Severity of mitral regurgitation	Grade 4+ (Severe)
Systolic function (LVEF)	65–75 % (Preserved)

History of irradiation and "double impact" model

The analysis of the file revealed a pre-existing structural vulnerability factor: stereotactic body radiation therapy (SBRT) of 5 fractions administered 9 months earlier (September 2024). The treatment fields targeted the lower pulmonary lobes, in the immediate vicinity of the diaphragmatic and inferior walls of the heart, suggesting tissue weakening prior to exposure to anthracyclines.

Therapeutic response and stabilization

Due to the advanced malignant pathology, open-heart surgery was ruled out in favor of medical optimization. The stabilization protocol included:

• Intravenous administration of loop diuretics for the management of acute heart failure.
• Afterload reduction with low-dose lisinopril.
• Introduction of metoprolol succinate.
• Discontinuation of usual amlodipine and hydrochlorothiazide.

The patient has been stabilized under this medical treatment and is currently undergoing evaluation for transcatheter edge-to-edge mitral repair (TEER).

The "double impact" model: a mechanical failure with preserved LVEF

This case study challenges the classic paradigm of anthracycline cardiotoxicity, usually associated with dose-dependent left ventricular systolic dysfunction. In this 78-year-old patient, acute rupture of the posteromedial papillary muscle head occurred despite a maintained ejection fraction (LVEF) between 65 and 75%. This phenomenon suggests a "two-hit model": a structural vulnerability induced by liposomal doxorubicin (cumulative dose of 534 mg) added to pre-existing or latent tissue damage.

The therapeutic history highlights the importance of toxic synergy. Nine months prior to the episode, the patient had received stereotactic body radiation therapy (SBRT) to the lower pulmonary lobes, in close proximity to the diaphragmatic and inferior walls of the heart. The authors hypothesize that structural changes induced by chemotherapy could weaken tissues already compromised by ischemia or radiation, leading to sudden mechanical failure rather than global pump failure.

Clinical limitations and perspectives

Although a direct causal link cannot be formally proven based on a single case, this observation highlights a major diagnostic pitfall: normal BNP levels and near-stable troponins do not exclude a severe mechanical complication. The nine-month delay between radiotherapy and the rupture also underscores the long-term persistence of post-irradiation tissue remodeling risks.

For the clinician, this case suggests that monitoring by standard echocardiography focused on LVEF may prove insufficient. The use of advanced imaging modalities might be necessary for the early detection of subclinical structural alterations in patients receiving high cumulative doses of doxorubicin, particularly in cases with a history of thoracic radiotherapy.

Summary of results

This case reports an acute rupture of the posteromedial papillary muscle head in a 78-year-old patient, occurring one week after a cumulative dose of 534 mg of liposomal doxorubicin. Despite a preserved LVEF (65-75%) and normal BNP, the examination revealed massive mitral regurgitation (4+), illustrating a "double hit" model between chemotherapy cardiotoxicity and stereotactic body radiation therapy for lung cancer undergone 9 months earlier.

In concrete terms, for the practitioner:

• Beyond LVEF: Do not rely exclusively on a normal ejection fraction; acute structural toxicity can occur independently of overall systolic function.
• Anticipating cumulative risks: Systematically integrate the history of thoracic radiotherapy (even if long-standing) into the cardiotoxic risk assessment of anthracyclines, as irradiation can mechanically weaken valvular structures.
• Diagnostic alert threshold: In the event of acute post-chemo dyspnoea with normal biomarkers (BNP), promptly initiate a transoesophageal echocardiography (TOE) to exclude a papillary rupture that transthoracic echocardiography might underestimate.

Une patiente de 78 ans, suivie pour un liposarcome métastatique et présentant plusieurs facteurs de risque cardiovasculaire, a développé une dyspnée aiguë une semaine après la fin de son traitement par doxorubicine liposomale. La dose cumulative absolue administrée était de 534 mg. Neuf mois auparavant, elle avait bénéficié d'une radiothérapie stéréotaxique (SBRT) en 5 fractions pour des nodules pulmonaires inférieurs, ciblant des zones à proximité immédiate des parois diaphragmatique et inférieure du cœur. Le tableau clinique présentait des particularités notables : - Fonction systolique préservée : les échographies de surveillance (2022-2025) montraient une FEVG stable entre 65 et 75 %. - Biomarqueurs atypiques : le BNP était normal et les troponines présentaient une élévation minimale et stable. - Diagnostic échographique : l'échographie transœsophagienne (ETO) a confirmé une rupture aiguë de la tête du muscle papillaire postéromédial et des cordages associés, entraînant une insuffisance mitrale sévère (4+). Face à une pathologie maligne avancée, l'intervention chirurgicale à cœur ouvert a été écartée. La prise en charge s'est concentrée sur l'optimisation médicale (diurétiques de l'anse, lisinopril pour la réduction de la postcharge, métoprolol) et une évaluation pour une réparation transcathéter bord à bord (TEER).

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