Heart Views

: 2021  |  Volume : 22  |  Issue : 1  |  Page : 54--58

Radiation-induced pan-valvular involvement: A rare case report

Hardeep Kaur Grewal1, Shyam Bisht2, Manish Bansal1,  
1 Department of Cardiology, Medanta-The Medicity, Gurgaon, Haryana, India
2 Department of Radiation Oncology, Medanta-The Medicity, Gurgaon, Haryana, India

Correspondence Address:
Dr. Manish Bansal
Medanta-The Medicity, Sector 38, Gurgaon - 122 001, Haryana


Radiotherapy is an important treatment modality for various thoracic malignancies but is associated with long-term risk of radiation-associated valve disease (RAVD). We hereby report a case of a lady who had received radiotherapy 30 years back for carcinoma breast and was now found to be having clinically significant RAVD involving all the four cardiac valves. Simultaneous involvement of all the four valves in RAVD is extremely rare and has not been reported previously.

How to cite this article:
Grewal HK, Bisht S, Bansal M. Radiation-induced pan-valvular involvement: A rare case report.Heart Views 2021;22:54-58

How to cite this URL:
Grewal HK, Bisht S, Bansal M. Radiation-induced pan-valvular involvement: A rare case report. Heart Views [serial online] 2021 [cited 2021 Jun 13 ];22:54-58
Available from: https://www.heartviews.org/text.asp?2021/22/1/54/314402

Full Text


Radiotherapy (RT) is an important treatment modality for various malignancies. However, when used for thoracic malignancies, it is associated with the risk of injury to cardiac tissues. Valvular heart disease is a common form of radiation-induced cardiac injury, which in some patients can lead to significant morbidity and even mortality. Involvement of the various valves has been reported previously and varies with the type and location of malignancy and RT protocol used. However, involvement of all the four valves in the same patient is extremely rare.

We hereby describe a patient who developed pan-valvular involvement secondary to RT which she had received 30 years back for carcinoma breast.

 Case Presentation

A 70-year-old lady, presented to the cardiology outpatient department with complaints of effort dyspnea and palpitations for the past 2 years and pedal edema for the past 6–8 months.

She was a known case of hypertension, and a known case of coronary artery disease for 8 years and had undergone coronary angioplasty with stent implantation to the left anterior descending artery. She also had history of carcinoma left breast which was diagnosed about 30 years back and treated with mastectomy, followed by RT and chemotherapy. There was no recurrence of carcinoma breast, but she had recently developed carcinoma esophagus for which surgical management was planned.

She underwent evaluation for the above complaints. Chest X-ray showed right ventricular enlargement. A transthoracic echocardiogram was performed, which showed evidence of multivalvular heart disease. The anterior mitral leaflet was thickened and calcified with mild mitral regurgitation. The aortic valve was trileaflet with thickened leaflets and calcification of right coronary cusp with no commissural fusion and mild aortic regurgitation [Figure 1]. The aortomitral continuity region was also calcified, and the wall of the aortic root was thickened [Figure 1]. The tricuspid valve leaflets were thickened and densely fibrosed, with rolled out edges and severe low-pressure tricuspid regurgitation due to non-coaptation of the leaflets [Figure 2]. Pulmonary valve leaflets were also thickened with moderate pulmonary regurgitation [Figure 3]. Left and right ventricular systolic function was normal but right ventricle and right atrium were significantly dilated secondary to pulmonary and tricuspid regurgitation. Inferior vena cava was dilated in size with normal inspiratory collapse. There was no pericardial thickening and no pericardial effusion.{Figure 1}{Figure 2}{Figure 3}

Since this patient was seen in the OPD, nothing was done and is being reported mainly as a case of interest.


RT plays an important role in the treatment of various thoracic malignancies and leads to improved outcomes in these patients. However, RT is also associated with several adverse effects. Though the incidence of RT-induced side effects has been declining due to improvement in radiation delivery protocols and technology, a greater number of cancer patients are now presenting with long-term radiation-induced adverse effects due to increased longevity.[1]

One of the long-term toxicities of RT, especially for thoracic malignancies, is radiation-induced heart disease (RIHD) as RT for thoracic malignancies delivers a significant radiation dose to the heart. RIHD comprises of pericardial, myocardial, valvular, conduction system and vascular abnormalities[2] and usually manifests after a latent period of 10–15 years. Long-term follow-up is therefore essential as the incidence of RIHD begins to increase 10 years after initial RT and the disease progresses with time. Concomitant use of cardiotoxic chemotherapeutic agents can further contribute to the development and progression of RIHD. Conventional cardiac risk factors such as hypertension, dyslipidemia, and smoking have also been shown to increase the risk of radiation-induced endothelial damage.[3]

One of the common manifestations of RIHD is valvular involvement. In one postmortem series, 81% of the patients showed evidence of RAVD.[4] However, most of the patients with RAVD are asymptomatic and only a few develop clinically significant dysfunction of the valves.[4] The progression from asymptomatic thickening of the valves to symptomatic valvular dysfunction is generally very slow and difficult to predict. Wethal et al.[5] reported that 37% of the patients with no significant regurgitation 10 years after RT developed moderate regurgitation after a further 12–14 years. Additionally, 39% of the patients with no aortic stenosis 10 years after RT developed varying degrees of aortic stenosis after a further 12–14 years. Cutter et al.[6] also reported that valvular dysfunction progressed over time in 56% of their cohort with RAVD.

The exact mechanism of RAVD is unknown but is probably due to phenotypic change in the valvular interstitial cells from a myofibroblast to an osteoblast-like cell. The valve leaflets become thickened, retracted and fibrotic with focal dystrophic calcification.[7],[8] Both stenotic and regurgitant lesions have been described in RAVD, with valvular regurgitation being more common. The aortic and mitral valves are affected more commonly than the tricuspid and pulmonic valves.[4],[9],[10] Pulmonary valve is the least commonly involved. In patients >20 years post irradiation, Heidenreich et al.[11] found moderate or severe aortic, mitral, tricuspid, and pulmonary regurgitation in 15%, 4.1%, 4.1%, and 0% of the patients, respectively. Aortic stenosis was reported in 16% of the patients who were irradiated >20 years back compared with <0.5% of the age- and sex-matched controls. The incidence of thickening and calcification of the aortomitral curtain also progresses with age[11] and is an independent predictor of the long-term risk of death in patients with RAVD.[12]

Echocardiographic characteristics of RAVD[13],[14],[15],[16] include fibrosis and calcification of the aortic cusps, aortic annulus, aortic root, aortic-mitral intervalvular fibrosa, mitral valve annulus, and the mid and basal portions of the mitral valve leaflets. Valve tips and commissures are typically spared in RAVD.[14]

Diagnosis of RAVD is often challenging and is usually a diagnosis of exclusion. A detailed history and clinical examination are of utmost importance for diagnosis. Common causes should be ruled out before considering the diagnosis of RAVD. Various other manifestations of RIHD should also be looked for when considering the diagnosis of RAVD.

In patients who develop significant valvular dysfunction requiring intervention, valve replacement is generally preferred over valve repair because of high failure rates secondary to ongoing RT-induced valvular changes after repair.[17] These patients are also at higher risk for perioperative and post-surgical long-term morbidity and death in comparison to general population, and the risk is even higher with repeat cardiac surgery. Bioprosthetic valves are usually not preferred as they may deteriorate over time. Transcatheter aortic valve replacement has been successful in RAVD and may become the preferred method of aortic valve replacement in the future.[18]

In our patient, not only aortic and mitral valves were involved but there was tricuspid and pulmonary valve involvement also, with significant regurgitation. This case is possibly the first case showing quadrivalvular involvement secondary to RT.

Various possible etiologies were considered for this valvular disease. Rheumatic heart disease (RHD) seemed unlikely as there was no commissural fusion and no thickening of the subvalvular apparatus. Moreover, the posterior mitral leaflet was not involved which was very unusual for rheumatic mitral valve disease in which posterior mitral leaflet is invariably affected and is restricted in motion or fixed. Also, RHD predominantly involves the tips of the valve leaflets, whereas in her case, only the basal and mid portions of the anterior mitral leaflet were involved.

Age-related degenerative valvular heart disease also seemed less likely as there was no evidence of annular calcification. Moreover, in age-related valvular degeneration, pulmonary and tricuspid valve involvement is not seen.

Based on these exclusions and considering the characteristic echocardiographic findings and history of RT in the past, we made a diagnosis of radiation-induced valvular heart disease (RAVD) involving all four valves in this patient.


For clinicians caring for patients who have previously received RT, it is important to be aware of radiation-induced heart disease (RIHD) and its various manifestations. Valvular dysfunction is a common manifestation of RIHD.

However, as majority of these patients are asymptomatic, regular screening and follow-up are required to look for any development and progression of valvular dysfunction. Typical echocardiographic features with the background of previous RT help in reaching the diagnosis of RAVD.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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