Use of new and emerging cancer drugs: what the cardiologist needs to know.

The last decade has witnessed a paradigm shift in cancer therapy, from non-specific cytotoxic chemotherapies to agents targeting specific molecular mechanisms. Nonetheless, cardiovascular toxicity of cancer therapies remains an important concern. This is particularly relevant given the significant improvement in survival of solid and haematological cancers achieved in the last decades. Cardio-oncology is a subspecialty of medicine focusing on the identification and prevention of cancer therapy-related cardiovascular toxicity (CTR-CVT). This review will examine the new definition of CTR-CVT and guiding principles for baseline cardiovascular assessment and risk stratification before cancer therapy, providing take-home messages for non-specialized cardiologists.

Effects of Sacubitril/Valsartan on biomarkers of fibrosis and inflammation in patients with heart failure with reduced ejection fraction.

AIMS: To evaluate the circulating levels of remodeling biomarkers procollagen type 1 C-terminal propeptide (PICP), human cartilage glycoprotein-39 (YKL-40), plasma renin activity (PRA), aldosterone (Aldo) as well as clinical and echocardiographic parameters in patients with heart failure with reduced ejection fraction (HFrEF), before and after treatment with Sacubitril/Valsartan (S/V). METHODS AND RESULTS: A total of 26 consecutive patients with HFrEF on stable clinical conditions were studied. Clinical, echocardiographic parameters and circulating biomarkers were measured at baseline, after 30 and 60 days of S/V treatment. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased, from 126 ± 15 to 113 ± 4 mmHg (p < 0.001) and from 77 ± 11 to 72 ± 9 mmHg (p = 0.005), respectively, at the end of study. Concomitantly, left ventricular ejection fraction (LVEF) increased by 22.8% from 29.5 ± 5% to 36.2 ± 5%, (p < 0.001) and indexed left ventricular end-systolic volume (LVESVi) decreased by 12% from 38.6 ± 8.7 ml/m2 to 34.0 ± 10.0 ml/m2. (p = 0.007). Circulating levels of PICP, YKL-40, PRA and Aldo decreased by - 42.2%, - 46.8%, - 79.1% and - 76.7%, respectively (p < 0.001 for all), the decrements being already maximal within 30 days of S/V treatment. No significant changes of plasma electrolytes and creatinine were observed during the study (all p > 0.05). CONCLUSIONS: A decrease of circulating markers of inflammation and fibrosis during chronic treatment with S/V is associated with an improvement of hemodynamic and echographic parameters in patients with HRrEF. These data are compatible with an anti-fibrotic and anti-inflammatory effect of S/V, that may contribute to the beneficial outcomes of the drug in this clinical setting.

Cardiovascular toxicity from therapies for light chain amyloidosis.

Amyloid light-chain (AL) amyloidosis is a hematological disorder characterized by abnormal proliferation of a plasma cell clone producing monoclonal free light chains that misfold and aggregate into insoluble fibrils in various tissues. Cardiac involvement is a common feature leading to restrictive cardiomyopathy and poor prognosis. Current first-line treatments aim at achieving hematological response by targeting the plasma cell clones, and these have been adapted from multiple myeloma therapy. Patients with AL amyloidosis often exhibit multiorgan involvement, making them susceptible to cancer therapy-related cardiovascular toxicity. Managing AL amyloidosis is a complex issue that requires enhanced knowledge of the cardio-oncological implications of hematological treatments. Future research should focus on implementing and validating primary and secondary prevention strategies and understanding the biochemical basis of oncological therapy-related damage to mitigate cardiovascular toxicity.

Clinical management of drug-induced cardiotoxicity in patients with HER-2+ breast cancer: current recommendations and future outlook.

INTRODUCTION: Human epidermal growth factor receptor two (HER2) target therapies have drastically revolutionized the treatment of HER2-positive breast cancer. Starting with trastuzumab, early phase III trials have already highlighted its significant cardiotoxicity, which is also present, albeit to a lesser extent, in the new generation drugs. Also given the growing population of patients with cardiovascular diseases, it is vital to set up proper long-term follow-up to prevent morbidity related to the development of cardiotoxicity. AREAS COVERED: This review discusses the mechanisms of action underlying the cardiotoxicity of HER2 targeted therapies and the main clinical evidence on the toxicity of these drugs. In addition, the patterns of patient assessment prior to the initiation of therapy with HER2 targeted therapies are discussed, as well as the main evidence concerning the follow-up and management of cardiotoxicity. EXPERT OPINION: The mechanisms of cardiotoxicity of new HER2 drugs need further study and, likewise, methods to prevent, monitor and identify HER-2-induced cardiotoxicity need to be implemented. Although some studies highlight the validity of cardiac biomarkers as predictive factors for cardiotoxicity, their actual usefulness and timing is still debated. Further studies are needed to assess the effectiveness of possible pharmacological primary prevention.

Treatment Options in AF Patients with Cancer; Focus on Catheter Ablation.

Longer life expectancy along with advancements in cancer and atrial fibrillation (AF) therapies and treatment strategies have led to an increase in the number of individuals with both diseases. As a result, the complicated management of these patients has become crucial, necessitating individualised treatment that considers the bi-directional relationship between these two diseases. On the one hand, giving appropriate pharmaceutical therapy is exceptionally difficult, considering the recognised thromboembolic risk posed by AF and malignancy, as well as the haemorrhagic risk posed by cancer. The alternative pulmonary vein isolation (PVI) ablation, on the other hand, has been inadequately explored in the cancer patient population; there is yet inadequate data to allow the clinician to unambiguously select patients that can undertake this therapeutic intervention. The goal of this review is to compile the most valuable data and supporting evidence about the characteristics, care, and therapy of cancer patients with AF. Specifically, we will evaluate the pharmaceutical options for a proper anticoagulant therapy, as well as the feasibility and safety of PVI in this population.

Bidirectional Relationship Between Cancer and Heart Failure: Insights on Circulating Biomarkers.

Cancer and heart failure are the two leading causes of death in developed countries. These two apparently distinct clinical entities share similar risk factors, symptoms, and pathophysiological mechanisms (inflammation, metabolic disturbances, neuro-hormonal and immune system activation, and endothelial dysfunction). Beyond the well-known cardiotoxic effects of oncological therapies, cancer and heart failure are thought to be tied by a bidirectional relationship, where one disease favors the other and vice versa. In this context, biomarkers represent a simple, reproducible, sensitive and cost-effective method to explore such relationship. In this review, we recapitulate the evidence on cardiovascular and oncological biomarkers in the field of cardioncology, focusing on their role in treatment-naïve cancer patients. Cardioncological biomarkers are useful tools in risk stratification, early detection of cardiotoxicity, follow-up, and prognostic assessment. Intriguingly, these biomarkers might contribute to better understand the common pathophysiology of cancer and heart failure, thus allowing the implementation of preventive and treatment strategies in cardioncological patients.