Michael Peyrol

Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor–Related Cardiotoxicity

Immune checkpoint inhibitors (ICIs) represent a major advance in the treatment of cancer. Although clinical trials reported a low incidence of immune-related cardiovascular adverse events,1 the number of published life-threatening cases of cardiotoxicity is increasing.2 In this descriptive observational analysis, we aimed to describe the clinical manifestations, management, and outcomes of patients who developed ICI-related cardiotoxicity. The medical records of patients with a clinical suspicion of ICI-related cardiotoxicity were reviewed from the databases of 2 cardio-oncology units between March 2015 and April 2017. The patients are managed according to similar protocols. Because no specific follow-up had previously been established for patients receiving ICIs during the study period, the oncologists referred patients receiving ICIs only on the basis of their clinical suspicion of cardiovascular events. These patients had a standardized evaluation including clinical consultation, ECG, transthoracic echocardiography, and measurement of brain natriuretic peptide and troponin I serum levels. The management of cardiotoxicity was left to the physician’s discretion. The study was approved by our institutional review board, and informed consent has been obtained from the subjects. To create a pooled analysis, we also searched PubMed for English articles reporting cases of ICI-related cardiotoxicity until April 2017. We selected …

Reduction of procedure duration and radiation exposure with a dedicated inner lumen mapping catheter during pulmonary vein cryoablation.

The Achieve catheter (AC; Medtronic‐CryoCath, Pointe‐Claire, Canada) is a circular mapping catheter introduced through the lumen of the cryoballoon (CB) catheter which is safe and effective to both navigate the CB to the pulmonary veins (PV) and allow PV potential recording during PV cryoablation. The aim of this study was to evaluate the impact of the use of the AC on procedural outcomes.

Management and research in cancer treatment-related cardiovascular toxicity: Challenges and perspectives

Cardiovascular toxicity is a potentially serious complication that can result from the use of various cancer therapies and can impact the short- and long-term prognosis of treated patients as well as cancer survivors. In addition to their potential acute cardiovascular adverse events, new treatments can lead to late toxicity even after their completion because patients who survive longer generally have an increased exposure to the cancer therapies combined to standard cardiovascular risk factors. These complications expose the patient to the risk of cardiovascular morbi-mortality, which makes managing cardiovascular toxicity a significant challenge. Cardio-oncology programs offer the opportunity to improve cardiovascular monitoring, safety, and management through a better understanding of the pathogenesis of toxicity and interdisciplinary collaborations. In this review, we address new challenges, perspectives, and research priorities in cancer therapy-related cardiovascular toxicity to identify strategies that could improve the overall prognosis and survival of cancer patients. We also focus our discussion on the contribution of cardio-oncology in each step of the development and use of cancer therapies.

A randomized trial of platelet reactivity monitoring-adjusted clopidogrel therapy versus prasugrel therapy to reduce high on-treatment platelet reactivity

BACKGROUND Peri-procedural platelet reactivity (PR) inhibition is critical in patients undergoing percutaneous coronary intervention (PCI). High on-treatment PR (HTPR) was associated with recurrent ischemic events in acute coronary syndrome (ACS) patients undergoing PCI. We aimed to compare a strategy of clopidogrel loading dose-adjustment (CDA) according to PR monitoring with standard prasugrel therapy to reduce the rate of patients exhibiting HTPR. METHODS We enrolled 177 ACS patients in a prospective multicentre randomized trial comparing CDA according to PR monitoring and prasugrel therapy. The VASP index was used to measure PR and a VASP ≥ 50% defined HTPR. The primary endpoint of the study was the rate of HTPR on discharge. RESULTS Baseline characteristics of the CDA group (n = 88) and of the prasugrel group (n = 89) were similar. CDA significantly reduced PR and the rate of HTPR compared to a single LD of clopidogrel (30.9 ± 13.9%; p < 0.0001 and 43 to 2.3%; p < 0.001, respectively). Following CDA the rate of patients with HTPR was significantly lower in the CDA group compared to the prasugrel group on discharge (2.3 vs 15.7%; p = 0.005). In addition fewer patients in the CDA group had a VASP < 16% on discharge (14.7 vs 50.5%; p <0.0001). CONCLUSION In the present study, PR monitoring was superior to standard prasugrel therapy to reduce the rate of HTPR in ACS patients. In addition such strategy reduced the number of patients with very low PR.

Practices in management of cancer treatment-related cardiovascular toxicity: A cardio-oncology survey

BACKGROUND Cardiovascular toxicity has become a challenging issue during cancer therapy. Nonetheless, there is a lack of consensual guidelines for their management. We aimed to determine the current practices of oncologists regarding cardiovascular toxicity related to anthracyclines, trastuzumab and angiogenic inhibitors and to gather their opinions on the development of cardio-oncology programs. METHODS A cross-sectional declarative study was submitted to French oncologists in the form of an individual, structured questionnaire. RESULTS A total of 303 oncologists responded to the survey. Ninety-nine percent of oncologists prescribed cardiotoxic therapies, including anthracyclines (83%), trastuzumab (51%) and other angiogenic inhibitors (64%). The method adopted for managing cardiovascular toxicity was based on guidelines from expert oncology societies for only 35% of oncologists. None was aware of recommendations from expert cardiology societies. Prescription of pre-, peri- and post-therapy cardiovascular assessment was inconsistent and significantly less frequent for all classes of angiogenic inhibitors than for anthracyclines and trastuzumab (P<0.0001). Relative to pre-therapy assessment, post-therapy assessment was prescribed significantly less often for all cancer therapies (P<0.0001). Attitudes regarding the onset of left ventricular dysfunction were much more inconsistent when angiogenic inhibitors were involved. Additionally, the management of hypertension and QT prolongation was also inconsistent. Finally, 88% of oncologists supported projects of cardio-oncology programs development. CONCLUSIONS Practices of oncologists are disparate in the field of cardiovascular toxicity. This finding underlines the complexity of managing many different situations and the need for distribution of formal guidelines from oncology and cardiology expert societies. The development of personalized cardio-oncology programs seems essential.

Vagal Reactions during Cryoballoon-Based Pulmonary Vein Isolation: A Clue for Autonomic Nervous System Modulation?

Although paroxysmal atrial fibrillation (AF) is known to be initiated by rapid firing of pulmonary veins (PV) and non-PV triggers, the crucial role of cardiac autonomic nervous system (ANS) in the initiation and maintenance of AF has long been appreciated in both experimental and clinical studies. The cardiac intrinsic ANS is composed of ganglionated plexi (GPs), located close to the left atrium-pulmonary vein junctions and a vast network of interconnecting neurons. Ablation strategies aiming for complete PV isolation (PVI) remain the cornerstone of AF ablation procedures. However, several observational studies and few randomized studies have suggested that GP ablation, as an adjunctive strategy, might achieve better clinical outcomes in patients undergoing radiofrequency-based PVI for both paroxysmal and nonparoxysmal AF. In these patients, vagal reactions (VR) such as vagally mediated bradycardia or asystole are thought to reflect intrinsic cardiac ANS modulation and/or denervation. Vagal reactions occurring during cryoballoon- (CB-) based PVI have been previously reported; however, little is known on resulting ANS modulation and/or prevalence and significance of vagal reactions during PVI with the CB technique. We conducted a review of prevalence, putative mechanisms, and significance of VR during CB-based PVI.

Clinical Impact of Genetically Determined Platelet Reactivity

Dual antiplatelet therapy with aspirin and clopidogrel dramatically reduced the rate of major adverse cardiac events following percutaneous coronary intervention. Clopidogrel is a prodrug which requires a two-step hepatic biotransformation thanks to the cytochrome P450 (CYP450) enzyme system. Genetic polymorphism of CYP450 system (e.g., CYP2C19*2) responsible for altered clopidogrel metabolism is a major cause of high on-treatment platelet reactivity (HTPR), which translates into thrombotic events in stented patients. Studies demonstrated that HTPR could be overcome in poor metabolizers thanks to increased loading doses or maintenance doses of clopidogrel or with the use of more potent antiplatelet agents such as prasugrel. Other genetic polymorphisms have also been correlated with HTPR: ABCB1, ATP2B2, and TIAM2. Large-scale randomized trials with clinical endpoints remain necessary to determine the optimal antiplatelet therapy in patients carrying genetic polymorphism associated with HTPR and thrombotic events.

Commotio cordis as a result of neutralization shot with the Flash Ball™ less- lethal weapon

Commotio cordis (CC) is a well-known cause of sudden cardiac death mainly reported in young patients who are accidentally struck in the left precordium. Clinical spectrumof CC iswide but eventsmainly occurred during sports. We report the first case of a patient who suffered CC related cardiac arrest after being shot with the Flash-BallTM less-lethal weapon. During an intervention by a police patrol, officers encountered a man described as threatening and aggressive. Neutralization shot was attempted with the Flash-BallTM handgun to the required distance of 7 m according to the police officer. The man was struck over the left precordium by a rubber bullet, and collapsed to the ground within few seconds. A mobile intensive care unit was dispatched to the scene. Ten minutes after the call, the medical team arrived on field and found a pulse less 43 year-old man with asystole as initial cardiac rhythm. After 12 min of resuscitation, a return of spontaneous circulation occurred. However, the patient was unstable, with mean arterial pressure of 40 mm Hg. At this time, inotropic support was undertaken with adrenaline and dobutamine. Physical examination found a large contusion mark on the left precordium. Cardiac auscultation was normal. Twelve lead ECG showed sinus bradycardia with premature ventricular complex (Fig. 1). Pre-admission transthoracic echocardiography found global severe left ventricular hypokinesia and absence of pericardial or pleural effusion (Fig. 2). The patient was

Massively Calcified Left Ventricular Endomyocardial Fibrosis Occurring in a Caucasian Patient

A man, living in France, complained about dyspnea and weakness for the last year. At admission, the electrocardiogram showed atrial fibrillation. Transthoracic echocardiographyandcardiacmagnetic resonance imaging revealed a rare case of massively calcified left ventricular endomyocardial fibrosis (EMF), resulting in an obliteration of the apex (Fig. 1A and B). Despite the severity of the calcification intruding the fibrosis, h

Clinical presentation of inappropriate sinus tachycardia and differential diagnosis

Inappropriate sinus tachycardia (IST) is a syndrome characterized by a sinus tachycardia not related to a medical condition, to a physiological response, or to medication or drugs and associated with symptoms, often invalidating and altering the quality of life of affected patients. It occurs predominantly in adolescents and young adults, and in the female sex. The diagnosis requires a complete work-up in order to exclude other causes of sinus tachycardia and one or several additional tests: 24-h ECG ambulatory recordings, echocardiogram, exercise testing, and autonomous nervous system assessment. It should be differentiated from the postural orthostatic tachycardia syndrome, with which it shares a number of symptoms, and other supraventricular tachycardias originating in the high right atrium. An electrophysiological study should be considered in selected cases in order to differentiate IST from other supraventricular tachycardias. The mechanism is still unclear, and possible etiologies may include intrinsic abnormality of the sinus node, autonomic dysfunction, hypersensitivity of the sinus node to catecholamines, blunted vagal system, or a combination of the above. The authors emphasize the wide spectrum of clinical presentations and the need to better define the IST and the criteria required to ascertain its diagnosis.