Cardiac Effects of BRAF and MEK Inhibitors: Mechanisms and Clinical Management.

PURPOSE OF REVIEW: The identification of BRAF mutation prompted the development of new class of targeted therapy for treating melanoma: BRAF inhibitors and MEK inhibitors. Cardiovascular events have been reported with these treatments and could counterbalance their long-term maintenance. RECENT FINDINGS: LVEF decrease due to BRAF and MEK inhibitors appears fairly common (10%) but usually not severe, without impact on patient outcomes. To date, no treatment options have been tested to prevent or to treat a decrease of LVEF associated with BRAF and MEK inhibitors. QTc prolongation was observed in 3% and arterial hypertension in 20% during treatment but only one-third of cases required a therapeutic change. BRAF and MEK inhibitors have revolutionized the management and the prognosis of melanoma patients. Cardio-oncology units may be useful for a better care of potential cardiac toxicity and particularly to inappropriately avoid discontinuing BRAF and MEK inhibitors.

In situ kinetics studies of Zn-Al LDH intercalation with corrosion related species.

Kinetic parameters for three anion exchange reactions - Zn-LDH-NO3→ Zn-LDH-Cl, Zn-LDH-NO3→ Zn-LDH-SO4 and Zn-LDH-NO3→ Zn-LDH-VOx- were obtained by in situ synchrotron study. The first and the second ones are two-stage reactions; the first stage is characterized by the two-dimensional diffusion-controlled reaction following deceleratory nucleation and the second stage is a one-dimensional diffusion-controlled reaction also with a decelerator nucleation effect. In the case of exchange NO3-→ Cl- host anions are completely released, while in the case of NO3-→ SO42- the reaction ends without complete release of nitrate anions. The exchange of Zn-LDH-NO3→ Zn-LDH-VOx is a one-stage reaction and goes much slower than the previous two cases. The latter is characterized by a one stage two-dimensional reaction with an instantaneous nucleation. As a result, at the end of this process there are two crystalline phases with different polyvanadate species, presumably V4O124- and V2O74-, nitrate anions were not completely released. The rate of replacing NO3- anions by guest ones can be represented as Cl- > SO42- > VOxy-.

[Myocarditis: Uncommon but severe toxicity of immune checkpoint inhibitors]. / La myocardite : une toxicité rare mais grave sous immunothérapie.

Traditional cancer therapies, such as treatment with anthracyclines and chest radiation, are known to induce cardiovascular complications. Currently, the increase of cancer therapies will involve new mechanisms such as cancer immunotherapies, also called immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors). These treatments have shown long-term remissions in subgroup of cancers, including melanomas, non-small-cell lung cancer, urothelial carcinoma, renal cell carcinoma, squamous cell carcinoma of the head and neck and colorectal cancer. Although these treatments will change the natural course of these cancers, they may sometimes induce cardiovascular complications, which has been reported as about 1 % in the literature. Currently, the physicians must keep in mind one uncommon but severe cardiac complication: auto-immune myocarditis. The clinical presentation may include various symptoms like chest pain, heart failure or rhythm disorders. In this situation, a baseline cardiologic check-up before starting cancer immunotherapy may be very helpful. Cardiac biomarkers (troponin and brain natriuretic peptide) and 12-lead resting electrocardiogram must be promptly performed when myocarditis is suspected. A cardiologist's opinion must be requested in emergency to discuss both a transthoracic echocardiography and the appropriate treatment (stopping immunotherapy, adding immunosuppressive treatment such as corticoids) and the monitoring in an intensive care unit. Cardiac MRI and endomyocardial biopsies may help to approach the final diagnosis. In this situation, other cancer therapies may be discussed.

Pulseless electrical activity after myocardial infarction: not always a left ventricular free wall rupture.

Pulseless electrical activity (PEA) after acute myocardial infarction is classically caused by ventricular free wall rupture. We report the case of a 76-year-old woman who presented a cardiac arrest with PEA 5 days after an embolic acute myocardial infarction. Transthoracic echocardiogram showed a massive mitral regurgitation due to posterior papillary muscle rupture. This case demonstrates that other causes potentially treatable than cardiac tamponade must be sought in patients with PEA after myocardial infarction.