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

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

I.S.Mu.L.T. Achilles Tendon Ruptures Guidelines

This work provides easily accessible guidelines for the diagnosis, treatment and rehabilitation of Achilles tendon ruptures. These guidelines could be considered as recommendations for good clinical practice developed through a process of systematic review of the literature and expert opinion, to improve the quality of care for the individual patient and rationalize the use of resources. This work is divided into two sessions: 1) questions about hot topics; 2) answers to the questions following Evidence Based Medicine principles. Despite the frequency of the pathology andthe high level of satisfaction achieved in treatment of Achilles tendon ruptures, a global consensus is lacking. In fact, there is not a uniform treatment and rehabilitation protocol used for Achilles tendon ruptures

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

Cardiotossicità da trastuzumab in pazienti con eteroplasia mammaria HER2+: un approccio traslazionale

Il cancro alla mammella è un’entità epidemiologica di rilievo, essendo il tumore più diagnosticato tra le donne e la seconda causa di mortalità per cancro. Circa il 15-20% delle eteroplasie mammarie è positivo per l’amplificazione del gene del recettore 2 del fattore di crescita epidermico umano (HER2). Nonostante le terapie a bersaglio molecolare dirette contro HER2 abbiano rappresentato una rivoluzione nel trattamento di questa neoplasia, queste rimangono gravate dal possibile sviluppo di cardiotossicità, che si manifesta principalmente come comparsa e progressione di disfunzione ventricolare sinistra. In questo studio prospettico osservazionale traslazionale, nel braccio clinico, è stato valutato l’impatto cardiovascolare della somministrazione sequenziale di antracicline e Trastuzumab, la principale terapia a bersaglio molecolare dirette contro HER2, in una popolazione di 25 donne a rischio intermedio di cardiotossicità affette da carcinoma mammario HER2+; il protocollo di studio ha previsto la misurazione dei biomarcatori cardiaci (troponina cardiaca [cTn] I e T, Il peptide natriuretico cerebrale [BNP] e il frammento inattivo amino-terminale del propeptide natriuretico di tipo B [NT-pro-BNP]) e dei principali parametri ecocardiografici standard, inclusi quelli derivanti dall’utilizzo dell’ecocardiografia 2D-speckle tracking (2D-STE). Il monitoraggio delle pazienti, che si è articolato in cinque tempi (tempo-t zero, mese 1, mese 3, mese 6 e mese 12), ha evidenziato rialzo della troponina oltre il 99°percentile nel 64% dei pazienti, prevalentemente al mese 3, accompagnato da una concorde lieve riduzione dello strain globale longitudinale (GLS). Come da raccomandazioni, è stata introdotta e titolata terapia cardioattiva (Ace inibitore/sartano e/o beta-bloccante) in presenza di rileivo di alterazione silente. La normalizzazione del biomarcatore è avvenuta entro il mese 6 per tutte le pazienti con rialzo del biomarcatore. Non è stata riscontrato alcun evento cardiovascolare rilevante e in nessuna delle pazienti si è resa necessaria l’interruzione del trattamento oncologico. Nel braccio preclinico è stato valutato l’effetto della somministrazione di trastuzumab in un gruppo di topi wild type (WT), affiancato da un gruppo di controllo a cui è stata somministrata salina. I topi sono stati sottoposti a valutazione elettrocardiografica ed ecocardiografica e una parte di essa è stata sacrificata per condurre l’analisi istologica del tessuto miocardico. I dati preliminari hanno mostrato un aumento del QTc e JTc nei topi trattati con trastuzumab; la volumetria e diametria ventricolare non hanno subito variazioni significative, così come l’analisi istologica, che non ha mostrato significative alterazioni morfologiche e strutturali dei miocardiociti. Nel nostro studio la somministrazione del trastuzumab non ha determinato l’insorgenza di eventi cardiovascolari rilevanti; mostrando un alto profilo di tollerabilità e sicurezza CV. Più della metà delle pazienti, come testimoniato dal rialzo della troponina e dalla concorde deflessione del GLS, ha sviluppato cardiotossicità sub clinica. Il rialzo del biomarcatore, avvenuto al mese 3, è da imputare ai primi quattro cicli di antracicline precendenti alla somministrazione del trastuzumab, così come il calo del GLS. La successiva somministrazione del trastuzumab non ha portato a un significativo aggravamento della cardiotossicità. In uno schema di somministrazione di trastuzumab consequenziale alle antracicline la valutazione periodica dei biomarcatori cardiaci può essere una strategia di monitoraggio utile per l’instaurazione precoce di un regime terapeutico cardioprotettivo

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

MRI of popliteo-meniscal fasciculi of the knee: a pictorial review

The popliteomeniscal fascicules (PMFs) provide the attachment of the lateral meniscus to the popliteus musculotendinous region, forming the floor and the roof the popliteal hiatus. In the second half of 1900's, some anatomic studies claim the important function of the PMF as stabilizers of the lateral meniscus; these anatomical structures work in conjunction with the popliteus musculotendinous unit to prevent excessive lateral meniscal movement and possible meniscus subluxation. A correct diagnosis of the PMFs pathology is crucial to establish the suitable surgical treatment for each patient. MRI is a well-established imaging technique in the musculoskeletal system and the frequency of recognition of normal PMF in the normal knees is high in almost all MRI studies. At day, the gold standard for diagnosis is the arthroscopic evaluation that allows the direct visualization of the popliteo-meniscal ligaments at popliteal hiatus and evaluation of lateral meniscal movements. For this reason if unstable condition of meniscus was suspected, arthroscopic observation with probing into the popliteo-meniscal fascicle area is essential for the identification of the fascicle tears. Despite many treatments have being proposed in literature since now there is high recurrence of knee locking after repair and it is fundamental to develop new surgical techniques in order to achieve better outcome

Management and treatment of cardiotoxicity due to anticancer drugs: 10 questions and answers

: Since the introduction of anthracyclines into clinical practice in the 1960s, chemotherapy has always been associated with cardiotoxicity. Patients on cardiotoxic drugs can develop a wide range of cardiovascular diseases, including left ventricular (LV) systolic dysfunction and heart failure (HF), arrhythmias, hypertension, and coronary artery disease (CAD). The rising number of cancer patients, population ageing, and the frequent overlap of cardiovascular and oncological diseases have highlighted the importance of close collaboration between cardiologists and oncologists. As a result, in 1995, cardiologists at the IEO (European Institute of Oncology) coined the term cardioncology, a new discipline focused on the dynamics of cardiovascular disease in cancer patients. Given the complex scenario characterized by a constant dialogue between the oncological condition and cardiovascular comorbidity, it is essential for the clinician to get the knowledge to properly fulfill the needs of the oncological patient under cardiotoxic treatment. Through the answer to 10 questions, we aim to describe the complex issue of cardiotoxicity by addressing the main critical points and current evidence related to the assessment, management, treatment, and surveillance of cancer patients under chemotherapy