Patients with Very High Risk of Cardiovascular Adverse Events during Carfilzomib Therapy: Prevention and Management of Events in a Single Center Experience.

Carfilzomib (CFZ) improves the prognosis of multiple myeloma (MM) patients but has shown cardiovascular toxicity. The risk stratification of cardiovascular adverse events (CVAEs) now seems well established, while little is known about the course and management of patients with a high-cardiovascular-risk profile or experiencing CVAEs during therapy. Therefore, we aimed to describe our experience in decision making to support health professionals in selecting the best management strategies to prevent and treat CVAEs. A total of 194 patients with indication to CFZ underwent baseline evaluation of CVAEs risk and were prospectively followed. We propose a novel approach, which includes advanced cardiac imaging testing for patients at high baseline CV risk to rule out clinical conditions that could contraindicate starting CFZ. After baseline evaluation, 19 (9.8%) patients were found at high risk of CVAEs: 13 (6.7%) patients underwent advanced cardiac testing and 3 (1.5%) could not receive CFZ due to CV contraindications. A total of 178 (91.7%) patients started CFZ: 82 (46%) experienced arterial-hypertension-related events and 37 (20.8%) major CVAEs; 19 (10.7%) patients had to discontinue or modify the CFZ dosing regimen. Along with baseline risk stratification, subsequent cardiovascular clinical events and diagnostic follow-up both provided critical data to help identify conditions that could contraindicate the anticancer therapy.

Carfilzomib-Based Regimen and Cardiotoxicity in Multiple Myeloma: Incidence of Cardiovascular Events and Organ Damage in Carfilzomib-Dexamethasone versus Carfilzomib-Lenalidomide-Dexamethasone. A Real-Life Prospective Study.

Carfilzomib-mediated cardiotoxicity in multiple myeloma (MM) is a well-established adverse effect, however limited data are available on the comparison of cardiovascular complications in patients treated with Carfilzomib-dexamethasone (target dose of K 56 mg/m2) versus Carfilzomib-lenalidomide-dexamethasone (target dose of K 27 mg/m2) beyond controlled trials. A total of 109 patients were enrolled, 47 (43%) received Kd and 62 (57%) KRd. They then underwent a baseline and follow-up evaluation including trans-thoracic echocardiography and arterial stiffness estimation. All types of cardiovascular and hypertensive events occurred more frequently in the Kd group compared with the KRd (59% vs. 40% and 55% vs. 35.5% patients, respectively, p ≤ 0.05), with higher incidence of hypertensive. The time of onset of any type of CVAE, and of major and hypertensive events was shorter in the Kd regimen (p ≤ 0.05). At follow-up, Kd patients more frequently developed signs of cardiac (decline of global longitudinal strain) and vascular organ damage (rise of pulse wave velocity), as compared with KRd. Despite the older age, longer history of MM and longer period of pre-treatment of Kd patients, these factors did not increase the probability of incidence for all types of cardiovascular events at multivariate analysis (p > 0.05). In conclusion, the Kd regimen showed greater cardiovascular toxicity and earlier onset of events with respect to KRd. Thus, a closer and thorough follow-up should be considered.

A structured physical activity program in an adolescent population with overweight or obesity: a prospective interventional study.

Obesity is a significant health problem, with increasing involvement of young population worldwide. The aim of this study was to evaluate the effects of 2 different types of physical exercise (resistance vs. combined aerobic-resistance) on cardiovascular and anthropometric profile of a sample of sedentary adolescents with overweight and obesity. After undergoing clinical, cardiovascular and anthropometric-metabolic evaluation (T0), subjects with overweight and obesity were randomized to a 6-month resistance or combined aerobic-resistance training program. Clinical, cardiovascular and anthropometric-metabolic evaluations were repeated after 6 months of training (T1) and after 3 months of detraining (T2). Thirty adolescents with overweight/obesity were enrolled and 20 subjects completed training program. A significant improvement in body composition was detected after 6 months, with a reduction of body mass index (32.1 [30.5 to 34.4] vs. 31.1 [29.6 to 33.4] kg/m2, p = 0.02) and adipose tissue (45.5 [41.1 to 49.7] vs. 41.6 [37.0 to 49.2] kg, p < 0.01). A reduction in diastolic blood pressure (75.5 ± 8.9 vs. 68.2 ± 6.4 mm Hg, p = 0.02) and pulse wave velocity (5.7 [5.1 to 5.9] vs. 5.2 [4.7 to 5.7] m/s, p = 0.04) was also observed. Persistence of the effect on the most important parameters was observed also after detraining period. In conclusion, regular physical exercise induces positive metabolic and cardiovascular effects, persisting even after brief discontinuation. Novelty: Physical exercise induces positive effect on cardiovascular risk profile. Positive effects persist also after brief discontinuation. Physical exercise reduces early signs of autonomic disfunction.

Effects of Carfilzomib Therapy on Left Ventricular Function in Multiple Myeloma Patients.

Background: Carfilzomib improves the prognosis of multiple myeloma (MM) patients but significantly increases cardiovascular toxicity. The timing and effect of Carfilzomib therapy on the left ventricular function is still under investigation. We sought to assess the echocardiographic systo-diastolic changes, including global longitudinal strain (GLS), in patients treated with Carfilzomib and to identify predictors of increased risk of cardiovascular adverse events (CVAEs) during therapy. Methods: Eighty-eight patients with MM performed a baseline cardiovascular evaluation comprehensive of transthoracic echocardiogram (TTE) before the start of Carfilzomib therapy and after 6 months. All patients were clinically followed up to early identify the occurrence of CVAEs during the whole therapy duration. Results: After Carfilzomib treatment, mean GLS slightly decreased (-22.2% ± 2.6 vs. -21.3% ± 2.5; p < 0.001). Fifty-eight percent of patients experienced CVAEs during therapy: 71% of them had uncontrolled hypertension, and 29% had major CVAEs or CV events not related to arterial hypertension. GLS variation during therapy was not related to an increased risk of CVAEs; however, patients with baseline GLS ≥ -21% and/or left ventricular ejection fraction (LVEF) ≤ 60% had a greater risk of major CVAEs (OR = 6.2, p = 0.004; OR = 3.7, p = 0.04, respectively). Carfilzomib led to a higher risk of diastolic dysfunction (5.6 vs. 13.4%, p = 0.04) and to a rise in E/e' ratio (8.9 ± 2.7 vs. 9.7 ± 3.7; p = 0.006). Conclusion: Carfilzomib leads to early LV function impairment early demonstrated by GLS changes and diastolic dysfunction. Baseline echocardiographic parameters, especially GLS and LVEF, might improve cardiovascular risk stratification before treatment.

Multiple Myeloma Patients Undergoing Carfilzomib: Development and Validation of a Risk Score for Cardiovascular Adverse Events Prediction.

Cardiovascular adverse events (CVAEs) are linked to Carfilzomib (CFZ) therapy in multiple myeloma (MM); however, no validated protocols on cardiovascular risk assessment are available. In this prospective study, the effectiveness of the European Myeloma Network protocol (EMN) in cardiovascular risk assessment was investigated, identifying major predictors of CVAEs. From January 2015 to March 2020, 116 MM patients who had indication for CFZ therapy underwent a baseline evaluation (including blood pressure measurements, echocardiography and arterial stiffness estimation) and were prospectively followed. The median age was 64.53 ± 8.42 years old, 56% male. Five baseline independent predictors of CVAEs were identified: office systolic blood pressure, 24-h blood pressure variability, left ventricular hypertrophy, pulse wave velocity value and global longitudinal strain. The resulting 'CVAEs risk score' distinguished a low- and a high-risk group, obtaining a negative predicting value for the high-risk group of 90%. 52 patients (44.9%) experienced one or more CVAEs: 17 (14.7%) had major and 45 (38.7%) had hypertension-related events. In conclusion, CVAEs are frequent and a specific management protocol is crucial. The EMN protocol and the risk score proved to be useful to estimate the baseline risk for CVAEs during CFZ therapy, allowing the identification of higher-risk patients.

Hypertensive emergencies and urgencies in emergency departments: a systematic review and meta-analysis.

OBJECTIVES: The prevalence of hypertensive emergencies and urgencies and of acute hypertension-mediated organ damage (aHMOD) in emergency departments is unknown. Moreover, the predictive value of symptoms, blood pressure (BP) levels and cardiovascular risk factors to suspect the presence of aHMOD is still unclear. The aim of this study was to investigate the prevalence of hypertensive emergencies and hypertensive urgencies in emergency departments and of the relative frequency of subtypes of aHMOD, as well as to assess the clinical variables associated with aHMOD. METHODS: We conducted a systematic literature search on PubMed, OVID, and Web of Science from their inception to 22 August 2019. Two independent investigators extracted study-level data for a random-effects meta-analysis. RESULTS: Eight studies were analysed, including 1970 hypertensive emergencies and 4983 hypertensive urgencies. The prevalence of hypertensive emergencies and hypertensive urgencies was 0.3 and 0.9%, respectively [odds ratio for hypertensive urgencies vs. hypertensive emergencies 2.5 (1.4-4.3)]. Pulmonary oedema/heart failure was the most frequent subtype of aHMOD (32%), followed by ischemic stroke (29%), acute coronary syndrome (18%), haemorrhagic stroke (11%), acute aortic syndrome (2%) and hypertensive encephalopathy (2%). No clinically meaningful difference was found for BP levels at presentations. Hypertensive urgency patients were younger than hypertensive emergency patients by 5.4 years and more often complained of nonspecific symptoms and/or headache, whereas specific symptoms were more frequent among hypertensive emergency patients. CONCLUSION: Hypertensive emergencies and hypertensive urgencies are a frequent cause of access to emergency departments, with hypertensive urgencies being significantly more common. BP levels alone do not reliably predict the presence of aHMOD, which should be suspected according to the presenting signs and symptoms.

Cardiovascular Organ Damage and Blood Pressure Levels Predict Adverse Events in Multiple Myeloma Patients Undergoing Carfilzomib Therapy.

Carfilzomib is a second-generation proteasome inhibitor approved for the treatment of multiple myeloma (MM). It seems to determine cardiovascular toxicity, primarily arterial hypertension. No predictive factors for cardiovascular adverse events (CVAEs) are known in patients affected by multiple myeloma treated with carfilzomib. We evaluated the role of cardiovascular organ damage parameters to predict CVAEs in MM patients taking carfilzomib. Seventy patients affected by MM were prospectively enrolled. A comprehensive cardiovascular evaluation was performed before carfilzomib therapy; they underwent a transthoracic echocardiogram and the assessment of carotid-femoral pulse wave velocity. All the patients were followed up (FU) to determine the incidence of CVAEs. The mean age was 60.3 ± 8.2, and 51% were male. The median FU was 9.3 (4.3; 20.4) months. A proportion of 33% experienced CVAEs, 91% of them had uncontrolled hypertension, 4.5% acute coronary syndrome, and 4.5% cardiac arrhythmias. Subjects with CVAEs after carfilzomib treatment had significantly higher blood pressure values, left ventricular mass (98 ± 23 vs. 85 ± 17 g/m2, p = 0.01), and pulse wave velocity (8.5 ± 1.7 vs. 7.5 ± 1.6 m/s, p = 0.02) at baseline evaluation compared to the others. Furthermore, baseline uncontrolled blood pressure, left ventricular hypertrophy, and pulse wave velocity ≥ 9 m/s were able to identify patients at higher risk of developing CVAEs during FU. These preliminary findings indicate that blood pressure control, left ventricular mass, and pulse wave velocity may predict CVAEs in MM patients treated with carfilzomib.