Rare manifestation of paclitaxel-induced cardiotoxicity: A case of restrictive cardiomyopathy in an elderly breast cancer patient.

Introduction
Paclitaxel is a natural chemotherapeutic agent frequently used to treat a variety of solid tumors, including breast, ovarian, and lung cancers, as well as Kaposi’s sarcoma. Although commonly associated with side effects such as hypersensitivity reactions, bone marrow suppression, and peripheral neuropathy, it can also lead to rare but potentially life-threatening cardiovascular complications. Among these, paclitaxel-induced restrictive cardiomyopathy is extremely rare and may mimic heart failure with preserved ejection fraction, especially in elderly patients with underlying comorbidities. Cardiotoxicity, in general, represents one of the most serious complications of chemotherapy and contributes significantly to both morbidity and mortality.[12]

Case Report

Patient information
A 78-year-old female with a history of type 2 diabetes, hypertension, hypothyroidism, and dyslipidemia presented with a right breast lump. Investigations confirmed Grade III-invasive ductal carcinoma, estrogen receptor/progesterone receptor positive, HER2 negative, Ki67-15%.
Positron emission tomography-computed tomography showed a spiculated lesion in the right breast with axillary lymphadenopathy. Right modified radical mastectomy was performed. Histopathology revealed multifocal involvement, pT3N3aM0, lymphovascular invasion, and extra nodal extension. She was planned for upfront surgery followed by adjuvant chemotherapy with Paclitaxel, followed by radiotherapy.
Adjuvant chemotherapy was initiated with weekly paclitaxel (120 mg intravenous) in 250 mL 5% Dextrose over 90 min. The first eight doses were well tolerated. After the ninth dose, the patient presented with complaints of breathing difficulty with PND and generalized tenderness for 3 days. No history of chest pain, palpitation, swelling in feet, recent fever, and cough. On physical examination, blood pressure: 140/90, pulse rate: 92 bpm, respiratory rate: 24 cpm, SpO2: 92% RA. Cardiovascular examination was unremarkable, but examination of the lungs revealed bilateral basal crackles.

Investigation
A 12-lead electrocardiogram performed revealed atrial fibrillation (AF) accompanied by premature ventricular complexes and nonspecific ST segment abnormalities, as illustrated in Figure 1. The two-dimensional echocardiogram revealed that the patient was in AF during the study, with bi-atrial enlargement, no regional wall motion abnormalities, and preserved Left ventricular ejection fraction (LVEF 53%). Severe mitral regurgitation (MR), moderate-to-severe tricuspid regurgitation (TR), and severe Pulmonary arterial systolic pressure (PASP 70 mmHg) were present. The inferior vena cava was dilated and collapsed <50%, and there was no evidence of clot, effusion, or vegetation, as shown in Figure 2a. Laboratory result revealed N-terminal pro-B-type natriuretic peptide was 5466 pg/mL.
Cardiac magnetic resonance imaging (MRI) showed increased left ventricular end-diastolic volume and left ventricular end-systolic volume with LVEF of 51%. No LV hypertrophy was seen. Global hypokinesia with intraventricular dyssynchrony. Normal indexed right ventricular end-diastolic volume and right ventricular end-systolic volume with right ventricular ejection fraction of 57%. There was no RV hypertrophy. Biatrial dilatation with moderate MR and TR as shown in Figure 2b. On delayed enhancement imaging, a patchy area of mid-myocardial enhancement is seen in the basal/mid-lateral wall. There was no myocardial edema on STRI images, no LV thrombus, no abnormal thickening of the pericardium, but a raised T1 of 1044 ms was noted. Cardiac magnetic resonance (CMR) features suggested of restrictive cardiomyopathy. Temporal correlation with chemotherapy was suggested to assess for etiology, and no convincing infiltrative process was demonstrated.

Intervention
Relevant investigations were done, and the patient was diagnosed with restrictive cardiomyopathy mimicking acute decompensated heart failure. She was treated with diuretics, anticoagulants, beta blockers, and other supported medications. She improved symptomatically with the above line of management. Medical oncology consultations were given, chemoport was flushed, and paclitaxel was discontinued.

Discussion
Paclitaxel-related cardiotoxicity is uncommon, and the pathway leading to restrictive cardiomyopathy remains poorly defined. Paclitaxel’s microtubule-stabilizing action may disrupt normal calcium handling, promote oxidative injury, and impair mitochondrial function, contributing to myocardial damage.[1] In addition, the solvent Cremophor EL used in some formulations can intensify cardiac stress through immune-mediated or vasospastic mechanisms.[3] These processes may explain the diastolic impairment, atrial remodeling, and AF documented in our patient.
Paclitaxel is extensively used in the management of breast, ovarian, and other solid tumors, and its adverse effects typically involve myelosuppression, neuropathy, and infusion-related reactions.[1] Cardiovascular complications such as arrhythmias, conduction disturbances, and ischemia have been described but occur infrequently and often present acutely during treatment.[2] Structural cardiomyopathy, particularly a restrictive phenotype, is extremely rare. In this case, an elderly woman with multiple cardiac risk factors developed progressive breathlessness and orthopnea after several weekly doses of paclitaxel. Echocardiography demonstrated preserved systolic function with bi-atrial enlargement and features suggestive of restrictive physiology. Cardiac MRI further supported chemotherapy-induced myocardial injury, showing mid-myocardial delayed enhancement and elevated native T1 values, consistent with diffuse fibrosis and absent hypertrophy or infiltrative pathology. These findings collectively point toward paclitaxel-associated restrictive cardiomyopathy.[45]
This case emphasizes the need for heightened awareness of rare cardiac toxicities in older patients with comorbidities undergoing taxane therapy. Early, multimodal cardiac evaluation, including echocardiography, cardiac biomarkers, and advanced imaging such as CMR, may facilitate timely detection of evolving myocardial injury.[45] Discontinuation of paclitaxel and initiation of standard heart failure management led to clinical improvement in our patient. Strengthening collaboration between oncology and cardiology teams is essential to ensure early recognition and intervention, ultimately improving outcomes in patients who may be vulnerable to such uncommon but clinically important adverse effects.

Conclusion
Paclitaxel-induced restrictive cardiomyopathy is an exceptionally rare adverse effect but carries significant clinical implications, particularly in elderly patients with cardiovascular risk factors. Early recognition through appropriate cardiac evaluation and prompt discontinuation of the drug can help prevent progression to irreversible myocardial damage. This case emphasizes the need for heightened vigilance and multidisciplinary collaboration to ensure timely detection and safer use of taxane-based chemotherapy.

Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Conflicts of interest
There are no conflicts of interest.