Virgil Abloh’s Cardiac Angiosarcoma

The fashion world was in shock following the passing of fashion designer Virgil Abloh at the age of 41, after a 2-year private battle with cardiac angiosarcoma, a rare cancer.

Abloh first came to prominence when he was hired by Kanye West to design tour merchandise and album art. In 2013, he founded his own fashion label, Off-White, a line of high-end streetwear. The line became a favorite of celebrities such as Khloé Kardashian, Naomi Campbell, Bella Hadid, and Rihanna, as well as many others.

In 2018, Abloh made history by becoming Louis Vuitton’s first Black artistic director. His line brought in a younger demographic, blurring the lines between high fashion and streetwear and challenging gender norms. Timothée Chalamet wore Abloh’s sparkly “embroidered bib” to the Golden Globes in 2019, and both Michael B. Jordan and Chadwick Boseman wore his clothes on the red carpet.

Cardiac Tumors

Cardiac tumors, whether benign or malignant, are rare. Primary cardiac tumors — i.e., those originating in the heart itself — are even rarer, with an incidence of about 0.001-0.3% in autopsy studies.

Secondary malignancies (metastatic) are much most frequent, with a 20 to 40 times higher incidence than primary tumors. Secondary cardiac tumors may originate from cancer cells disseminated in the bloodstream, direct invasion of adjacent tissues, or spread via the superior or inferior vena cava into the right atrium. The most likely tumors of origin include lung, breast, melanoma, lymphoma, and renal cancers. The pericardium is the most often affected area and can cause a pericardial effusion.

Primary cardiac tumors are categorized as benign or malignant. Nearly 90% of primary cardiac tumors are benign, with myxoma accounting for about 80% of all cardiac tumors. Other benign cardiac tumors include lipomas, papillary fibroelastoma, rhabdomyomas, and fibromas.

Most primary malignant cardiac tumors are sarcomas, and in particular, angiosarcomas. which comprise 25-40% of cardiac sarcomas. Cardiac angiosarcoma occurs more frequently in men within the 3rd and 5th decades of life. Less common malignant cardiac tumors are rhabdomyosarcomas, fibrosarcomas, and leiomyosarcomas.

Angiosarcomas are composed of malignant cells that form vascular channels, and most commonly form in the right atrium. According to StatPearls: Cardiac Cancer:

• Macroscopically, angiosarcomas are typically dark brown or black hemorrhagic masses with infiltrating borders

• Microscopically, angiosarcomas typically infiltrate cardiac muscle without distinct margins; the vascular channels are irregular, anastomosing, and sinusoidal, with pleomorphic lining cells showing frequent mitotic figures

Clinical Manifestations

The clinical manifestations of cardiac tumors often have more to do with their location than their histopathology. Mechanisms that cause symptoms include embolization, obstruction of the circulation through the heart or heart valves, interference with the valves causing regurgitation, and direct invasion of the myocardium or adjacent lung.

Left atria (LA) tumors tend to grow into the atrial lumen, leading to symptoms by obstruction of blood flow or mitral regurgitation. Frequent symptoms include dyspnea, cough, pulmonary edema, paroxysmal nocturnal dyspnea, edema, hemoptysis, and fatigue. LA tumors can also release tumor fragments or thrombi into the general circulation. Benign myxomas are the most common tumors of the LA.

Right atrial (RA) tumors also tend to grow into the lumen of the atrium and cause symptoms similar to those of tricuspid stenosis. A patient may present with right heart failure with fatigue, peripheral edema, hepatomegaly, and ascites. RA tumors can release tumor fragments or thrombi into the pulmonary circulation, mimicking symptoms caused by pulmonary emboli.

Right ventricular (RV) tumors interfere with RV filling or obstruction of RV outflow. This leads to signs and symptoms of right-sided heart failure: fatigue, nausea, hepatomegaly, edema, chest pain, cough, cyanosis, syncope, and even sudden death.

Left ventricular tumors can cause outflow obstruction and systemic embolization, and can also arise in the myocardium, leading to arrhythmias and conduction defects.

Diagnosis

Because of the rarity of cardiac angiosarcomas and their generalized and nonspecific symptoms, early diagnosis is unfortunately infrequent. However, echocardiology has become the mainstay for diagnosing cardiac tumors and has dramatically improved the ability to diagnose them.

According to a review by Patel et al., “The rate of ante mortem tissue diagnosis has improved from only four of 41 cases in a 1968 review, to 50% in 1986, 70% in 1992, and 82% in 2000. Transesophageal echocardiography has a 97% sensitivity in detecting cardiac masses.”

Cardiac MRI and CT scans can provide additional important information, such as tumor size, location, and adjacent structures, which can aid in possible surgical resection. Left heart catheterization with coronary angiogram can determine the blood supply of the tumor as well as whether there is tumor invasion of the epicardial blood vessels.

In vivo intracardiac biopsy is a high-risk procedure and is often not necessary. For tumors that look resectable on imaging, the preferred treatment is complete excision, which will provide a biopsy specimen. However, if the tumor appears unresectable or diffuse on imaging and the potential benefit outweighs the potential risk, a percutaneous biopsy may be of value to guide further nonsurgical treatment.

Treatment

The majority of patients with cardiac angiosarcoma have an overall poor prognosis. The locally invasive nature of the disease, along with its tendency to send cancer cells to distant locations through the vascular system, makes treatment especially difficult.

Standard treatment of localized tumors includes surgery and radiation therapy. Studies have shown that those who are able to undergo complete resection of the tumor have an increased survival rate. Despite this, more than 50% of patients develop local or recurrent disease. Chemotherapy with doxorubicin and ifosfamide is often added either as neoadjuvant (pre-surgical) or adjuvant treatment. Unfortunately, doxorubicin can be also be cardiotoxic.

The poor outlook for patients with cardiac angiosarcoma has led researchers to study the genetic aberrations and molecular biology of the tumors. The hope is that it will be possible to uncover novel, tumor-specific drug targets, or find similarities in mechanisms to other tumors for which newer treatments (such as immunotherapy and targeted drug therapy) have shown promise.

A 2020 paper by Urbini et al. reviewed the current literature and noted that molecular aberrations detected in cardiac angiosarcoma often involve KDR and KIT and homozygous deletion of CDKN2A. Not surprisingly, these markers are found in somatic mutations in angiogenic signaling pathways.

In addition, the authors wrote, “Considering the expression of pro-angiogenic growth factors, AS [angiosarcoma] is inherently a target for antiangiogenic agents, thus the evaluation of vascular-targeted agents in these tumors is of particular interest.”

Monoclonal antibodies and tyrosine kinase inhibitors, with antiangiogenic mechanisms of action, such as bevacizumab, sorafenib, and imatinib, have been tested in angiosarcoma alone or in combination with chemotherapy. Unfortunately, the number of cases is still small, and more research is needed.

Finally, a few patients have undergone heart transplantation as part of their treatment for cardiac angiosarcoma. Two reviews of this modality paint a confusing picture. Gowdamarajan and Michler noted that the mean survival of the seven patients found in the literature to date at that time in 2000 who had benign histology was 46 months compared with 12 months for the 21 patients with malignant histology. The authors pointed out, however, that there were also seven patients who had survived for a mean of 27 months without evidence of recurrent disease.

In the second paper, Li et al. reviewed 46 patients with unresectable and non-metastatic primary cardiac sarcomas. The most common histologic type was angiosarcoma, and median survival after heart transplant was 9 months — not much different from the 8 months for patients receiving palliative treatment. Use of neoadjuvant or adjuvant therapy did not improve survival after transplantation.

The authors noted, however, that patients with grade 2 sarcomas survived much longer than those with grade 3 tumors (85 vs 18 months).

There are a few clinical trials for patients with angiosarcoma, but there are currently no active trials solely for cardiac angiosarcomas.

Michele R. Berman, MD, is a pediatrician-turned-medical journalist. She trained at Johns Hopkins, Washington University in St. Louis, and St. Louis Children’s Hospital. Her mission is both journalistic and educational: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.