Takotsubo Cardiomyopathy as Epiphenomenon of Cardiotoxicity in Patients With Cancer: A Meta-summary of Case Reports

Abstract

Many antitumoral drugs have been linked to takotsubo cardiomyopathy, with no clear pathogenetic mechanisms. Data about this condition are lacking in literature. The aim of this metasummary is to summarize the characteristics of patients with antitumoral drug-induced takotsubo cardiomyopathy, described in case reports available in literature. We searched for published case reports in PubMed, Google Scholar, EMBASE, and Scopus from 2009 about stress cardiomyopathy and antiblastic drugs. We selected 41 case reports. All cases underwent chemotherapy/immunotherapy for different types of cancer. The median age was 58 years, and 61% of them were women. The most common comorbidities were hypertension (12.2%) and dyslipidemia (4.9%), but most of the population had no cardiological clinical history. Takotsubo cardiomyopathy is associated to the 5-fluorouracil (36.5%), capecitabine (9.7%), trastuzumab (9.7%), and immune check point inhibitor (9.7%) treatment. The median time of onset was 2 days (1-150). Cardiogenic shock was the first manifestation in 11 patients (26.8%). Left ventricle ejection fraction recovery was showed in 33 patients (89%) with mean ejection fraction 57.7 6 7%, after a median of 30-day (4-300) follow-up. Patients with cancer experienced takotsubo cardiomyopathy within few days from the beginning of therapy, and the most of them normalized the heart function in few weeks. Cardiogenic shock showed high prevalence in this setting of patients. Larger studies are needed to better understand the pathological mechanisms of antiblastic drug-induced stress cardiomyopathy, to find risk factors associated and preventive strategies for limit this type of cardiotoxicities.

Genetic and Epigenetic Factors of Takotsubo Syndrome: A Systematic Review

“…Drugs, such as dopamine, dobutamine, epinephrine, norepinephrine, and anesthesia drugs, can also represent TTS triggers, evocating a TTS like disorder [5]. Likewise, it has been reported that chemotherapeutical drugs can determine TTS onset in cancer patients, as an epiphenomenon of induced cardiotoxicity [6]. Such conditions have been defined as TTS phenocopies [5], different to the classical TTS phenotypes.…”

Cancer and Takotsubo syndrome: from rarity to clinical practice

“…Among them, 5‐fluorouracil capecitabine, anthracyclines, trastuzumab, and immune checkpoint inhibitors, either alone or in combination with and without concurrent radiotherapy, have been mostly associated with TTS. 2 , 15 , 16 Among cancer patients exposed to these therapies, those with additional risk factors are more prone to develop TTS. Javaid et al .…”

“…and previous investigators have identified a series of risk factors including female sex, age older than 45 years, and cardiovascular and non‐cardiovascular comorbidities, such as hypertension, dyslipidaemia, anaemia, lung and neurologic disease. 6 , 14 , 15 , 17 …”

“… 15 The typical clinical presentation of TTS is that of chest pain or dyspnea during or after treatment, but in 26.8% of patients, cardiogenic shock may be the first manifestation being potentially lethal. 15 , 18 Other complications include respiratory failure, pulmonary edema, arrhythmias, and cardiac thrombus or even cardiac arrest. 13 Although TTS is usually a benign, self‐restricted syndrome, its prognostic effect in oncological patients is questionable.…”

“…Among them, 5-fluorouracil capecitabine, anthracyclines, trastuzumab, and immune checkpoint inhibitors, either alone or in combination with and without concurrent radiotherapy, have been mostly associated with TTS. 2,15,16 Among cancer patients exposed to these therapies, those with additional risk factors are more prone to develop TTS. Javaid et al and previous investigators have identified a series of risk factors including female sex, age older than 45 years, and cardiovascular and non-cardiovascular comorbidities, such as hypertension, dyslipidaemia, anaemia, lung and neurologic disease.…”