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

2021 ◽  
Vol 8 ◽  
Author(s):  
Giulia Mingrone ◽  
Anna Astarita ◽  
Lorenzo Airale ◽  
Ilaria Maffei ◽  
Marco Cesareo ◽  
...  

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.

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
G Mingrone ◽  
A Astarita ◽  
I Maffei ◽  
M Cesareo ◽  
L Airale ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background Carfilzomib improves the prognosis of multiple myeloma (MM) patients, but significantly increases cardiovascular toxicity. The timing and effect of carfilzomib therapy on left ventricular function is still under investigation. Purpose 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 88 patients with MM performed a baseline cardiovascular evaluation comprehensive of transthoracic echocardiogram (TTE) before the start of Carfilzomib therapy and after about 6 months. All patients were clinically followed-up to early identify the occurrence of CVAEs for the whole therapy duration. Results After Carfilzomib treatment, mean GLS slightly decreased (-22.2% ± 2.6 vs -21.3% ± 2.5; p < 0.001). 58% of patients experienced CVAEs during therapy: 71% of them had uncontrolled hypertension, 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 an increased risk of major CVAEs (OR = 6.2, p = 0.004;  OR = 3.7, p = 0.04, respectively). Carfilzomib led to an increased risk of diastolic dysfunction (5.6% vs 13.4% p = 0.04) and to a rise in E/e’ (8.9 ± 2.7 vs 9.7 ± 3.7; p = 0.006). Conclusions 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.


Author(s):  
Jayanti Venkata Balasubramaniyan ◽  
Ashutosh Prasad Tripathi ◽  
J. S. Satyanarayana Murthy

Background: Mitral annular plane systolic excursion (MAPSE) has been proposed as a parameter for assessing left ventricular function. The assessment of LVF has major diagnostic and prognostic implications in patients with cardiovascular diseases. LVF is measured by Left Ventricular Ejection Fraction, however the accuracy of LVEF estimation by two dimensional echocardiography is limited especially in patients with poor image quality. Mitral annular plane systolic excursion (MAPSE) measurement predicts left ventricular function even in conditions with suboptimal echo window. Objective: To assess the correlation of MAPSE derived LVEF with LVEF measured by Modified Simpson’s method. Methods: This is a cross sectional study which included 279 patients admitted at our tertiary care hospital from December 2019 to March 2020 and the patients were divided in two groups. Group A – Patients with LVEF>= 50% and Group B – Patients with LVEF<50%. All patients underwent 2D echocardiographic examination using Modified Simpsons’ method and MAPSE measurement. The VIVID E9, VIVID T8, VIVID E95 and PHILIPS echocardiography machine was used for the non-invasive measurements. MAPSE was recorded at medial and lateral mitral annuli in the apical four-chamber approach. Results: On analysis, a cut off value for average MAPSE-S (medial mitral annuli) was 8.5 was obtained, denoting preserved LV function with sensitivity of 81.7%, specificity of 84.9%, positive predictive value of 91.6% and negative predictive value of 84.9%. The AUC for MAPSE-S was 0.822. Similarly, the cut off value of average MAPSE-L (lateral mitral annuli) was 7.5 denoting impaired LV functions with an AUC of 0.826, sensitivity of 82.8%, specificity of 72.0%, positive predictive value of 85.6% and negative predictive value of 72.0%. The AUC of 82.6% was observed for MAPSE-L. Conclusion: MAPSE reflects longitudinal myocardial shortening. MAPSE is a rapid and sensitive echocardiographic parameter for assessing normal LV function and global LV systolic dysfunction.


2011 ◽  
pp. 36-42
Author(s):  
Hung Viet Bui ◽  
Thi Cu Nguyen

Objective: In Vietnam, obesity is increasing particularly in many large cities. Adult cardiovascular diseases are often derived from cardiovascular disorders during the children period. The implementation of early measures to prevent atherosclerosis, such as weight control, better lipid control will reduce the cardiovascular complications, such as hypertension (HTA), coronary heart diseases and some other diseases. Materials and Methods: Overweight - obese children from 5 to 15 years old who visited the Children's Hospital in Can Tho from May 2009 to May 2010. Total number of patients were chosen as 50 children. Method: Descriptive cross-sectional. Children in the study underwent Doppler ultrasound exam to evaluate cardiac morphology and cardiac function. Results: There were increases in left ventricular systolic diameter, left ventricular diastolic diameter, LV mass in overweight-obese children in the study compared with controls at all ages (p <0.05 ). Left ventricular ejection fraction in overweight-obese children in the study was lower than the control group at all ages (p> 0.05). The average rate of left ventricular shortening of overweight-obese children in the study was 34.8 ± 4.5(%). There was no difference in the rate of shortening of the left ventricle in overweight-obese children in the study compared with controls (p>0.05). There was no relationship between variation in morphology and left ventricular function with the degree of overweight-obesity in this study. Conclusion: The study showed that disturbances in morphology and left ventricular function in overweight-obese children but did not find a strong association with the disorder degree of overweight-obesity.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.V Bunting ◽  
S Gill ◽  
A Sitch ◽  
S Mehta ◽  
K O'Connor ◽  
...  

Abstract Introduction Echocardiography is essential for the management of patients with atrial fibrillation (AF), but current methods are time consuming and lack any evidence of reproducibility. Purpose To compare conventional averaging of consecutive beats with an index beat approach, where systolic and diastolic measurements are taken once after two prior beats with a similar RR interval (not more than 60 ms difference). Methods Transthoracic echocardiography was performed using a standardized and blinded protocol in patients enrolled into the RAte control Therapy Evaluation in permanent AF randomised controlled trial (RATE-AF; NCT02391337). AF was confirmed in all patients with a preceding 12-lead ECG. A minimum of 30-beat loops were recorded. Left ventricular function was determined using the recommended averaging of 5 and 10 beats and using the index beat method, with observers blinded to clinical details. Complete loops were used to calculate the within-beat coefficient of variation (CV) and intraclass correlation coefficient (ICC) for Simpson's biplane left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and filling pressure (E/e'). Results 160 patients (median age 75 years (IQR 69–82); 46% female) were included, with median heart rate 100 beats/min (IQR 86–112). For LVEF, the index beat had the lowest CV of 32% compared to 51% for 5 consecutive beats and 53% for 10 consecutive beats (p&lt;0.001). The index beat also had the lowest CV for GLS (26% versus 43% and 42%; p&lt;0.001) and E/e' (25% versus 41% and 41%; p&lt;0.001; see Figure for ICC comparison). Intra-operator reproducibility, assessed by the same operator from two different recordings in 50 patients, was superior for the index beat with GLS bias −0.5 and narrow limits of agreement (−3.6 to 2.6), compared to −1.0 for 10 consecutive beats (−4.0 to 2.0). For inter-operator variability, assessed in 18 random patients, the index beat also showed the smallest bias with narrow confidence intervals (CI). Using a single index beat did not impact on the validity of LVEF, GLS or E/e' measurement when correlated with natriuretic peptides. Index beat analysis substantially shortened analysis time; 35 seconds (95% CI 35 to 39 seconds) for measuring E/e' with the index beat versus 98 seconds (95% CI 92 to 104 seconds) for 10 consecutive beats (see Figure). Conclusion Index beat determination of left ventricular function improves reproducibility, saves time and does not compromise validity compared to conventional quantification in patients with heart failure and AF. After independent validation, the index beat method should be adopted into routine clinical practice. Comparison for measurement of E/e' Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Research UK


2014 ◽  
Vol 1 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Wenjuan Bai ◽  
Hui Li ◽  
Hong Tang ◽  
Qing Zhang ◽  
Ye Zhu ◽  
...  

The aims of this study were i) to evaluate mitral and aortic annuli excursion, and aortomitral angle (AMA) during the cardiac cycle in healthy adults using two-dimensional speckle tracking echocardiography, ii) to assess two annuli dynamics and coupling behaviors as an integral, and iii) to detect the relation between two annuli and left ventricular ejection fraction (LVEF). A total of 74 healthy adults underwent transthoracic echocardiography. In the parasternal long-axis view, a number of points were extracted, including right coronary aortic annular, aortomitral fibrous junction, and posterior mitral annular points. The annuli excursion and AMA were measured using a speckle tracking-derived software during the cardiac cycle. During the isovolumic contraction and the isovolumic relaxation phase, annuli excursion and AMA remain stable for a short time. During the systole, annuli excursion increased sharply to the maximum, while AMA narrowed quickly to the minimum value. During the diastole, there are three patterns of decrease in annuli excursion and AMA expansion in different phases. The annuli excursion of three points correlates well with the LVEF (right coronary aortic annulus excursion, r=0.71, P<0.05; non-coronary aortic annulus excursion, r=0.70, P<0.05; posterior mitral annulus excursion, r=0.82, P<0.05). Moreover, there are positive correlations between annuli excursion and the variation of AMA (r=0.60, P<0.05). The annuli excursion and AMA have various regular patterns in healthy adults. The interactions of mitral and aortic annuli correlate with the left ventricular function. Our findings may have relevance to the evaluation of left ventricular function and presurgical planning of patients with valvular diseases.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Daniela Ravizzoni Dartora ◽  
Adrien Flahualt ◽  
Carolina Nobre Pontes ◽  
Gabriel Altit ◽  
Alyson Deprez ◽  
...  

Introduction: Preterm (PT) birth is associated with increased risk of cardiovascular diseases (CVD) and heart failure. We previously reported left ventricular (LV) mitochondrial dysfunction in a rat model mimicking the deleterious conditions associated with PT birth. Whether mitochondrial function is altered in humans born PT and associated with LV function changes is unknown. We aimed to determine if serum humanin levels, a mitochondrial-derived peptide with cytoprotective effects, are altered in humans born PT and are associated with impaired myocardial function. Methods: Data were obtained from 55 young adults born PT (<30 weeks of gestational age, GA) compared to 54 full-term (T) controls of the same age. Serum humanin levels were determined by ELISA and LV ejection fraction (LVEF) by echocardiography. Results are shown as median (interquartile range) and comparisons between groups were performed using non-parametric tests. Results: Individuals were evaluated at 23.3 (21.4, 25.3) years, and age and sex distribution were similar between groups. Median GA was 27.5 (26.2, 28.4) weeks in the PT group. Humanin levels (pg/ml) were 132.9 (105.1, 189.3) and 161.1 (123.6, 252) in the PT and the T groups, respectively (p=0.0414). LVEF was within the normal range and similar between groups. Lower LVEF was associated with lower humanin levels (p<0.001), and this association was observed both in the term (p=0.002) and the preterm (p=0.047) groups. Conclusions: Serum humanin levels are lower in adult born PT. Since lower humanin levels are also associated with lower LVEF, our results suggest that mitochondrial alterations could play a role in the long-term adverse cardiovascular consequences of PT birth. Humanin analogs improve LV function in experimental models. Our results pave the way for future studies exploring humanin as a therapeutic avenue for the prevention and treatment of CVD in individuals born PT.


Author(s):  
David Playford ◽  
Geoff Strange ◽  
David S Celermajer ◽  
Geoffrey Evans ◽  
Gregory M Scalia ◽  
...  

Abstract Aims  To examine the characteristics/prognostic impact of diastolic dysfunction (DD) according to 2016 American Society of Echocardiography (ASE) and European Society of Cardiovascular Imaging (ESCVI) guidelines, and individual parameters of DD. Methods and results  Data were derived from a large multicentre mortality-linked echocardiographic registry comprising 436 360 adults with ≥1 diastolic function measurement linked to 100 597 deaths during 2.2 million person-years follow-up. ASE/European Association of Cardiovascular Imaging (EACVI) algorithms could be applied in 392 009 (89.8%) cases; comprising 11.4% of cases with ‘reduced’ left ventricular ejection fraction (LVEF &lt; 50%) and 88.6% with ‘preserved’ LVEF (≥50%). Diastolic function was indeterminate in 21.5% and 62.2% of ‘preserved’ and ‘reduced’ LVEF cases, respectively. Among preserved LVEF cases, the risk of adjusted 5-year cardiovascular-related mortality was elevated in both DD [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.22–1.42; P &lt; 0.001] and indeterminate status cases (OR 1.11, 95% CI 1.04–1.18; P &lt; 0.001) vs. no DD. Among impaired LVEF cases, the equivalent risk of cardiovascular-related mortality was 1.51 (95% CI 1.15–1.98, P &lt; 0.001) for increased filling pressure vs. 1.25 (95% CI 0.96–1.64, P = 0.06) for indeterminate status. Mitral E velocity, septal e’ velocity, E:e’ ratio, and LAVi all correlated with mortality. On adjusted basis, pivot-points of increased risk for cardiovascular-related mortality occurred at 90 cm/s for E wave velocity, 9 cm/s for septal e’ velocity, an E:e’ ratio of 9, and an LAVi of 32 mL/m2. Conclusion  ASE/EACVI-classified DD is correlated with increased mortality. However, many cases remain ‘indeterminate’. Importantly, when analysed individually, mitral E velocity, septal e’ velocity, E:e’ ratio, and LAVi revealed clear pivot-points of increased risk of cardiovascular-related mortality.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tobias Hüppe ◽  
Heinrich Volker Groesdonk ◽  
Thomas Volk ◽  
Stefan Wagenpfeil ◽  
Benedict Wallrich

Abstract Background Transthoracic echocardiography is the primary imaging modality for diagnosing cardiac conditions but medical education in this field is limited. We tested the hypothesis that a structured theoretical and supervised practical course of training in focused echocardiography in last year medical students results in a more accurate assessment and more precise calculation of left ventricular ejection fraction after ten patient examinations. Methods After a theoretical introduction course 25 last year medical students performed ten transthoracic echocardiographic examination blocks in postsurgical patients. Left ventricular function was evaluated both with an eye-balling method and with the calculated ejection fraction using diameter and area of left ventricles. Each examination block was controlled by a certified and blinded tutor. Bias and precision of measurements were assessed with Bland and Altman method. Results Using the eye-balling method students agreed with the tutor’s findings both at the beginning (88%) but more at the end of the course (95.7%). The variation between student and tutor for calculation of area, diameter and ejection fraction, respectively, was significantly lower in examination block 10 than in examination block 1 (each p < 0.001). Students underestimated both the length and the area of the left ventricle at the outset, as complete imaging of the left heart in the ultrasound sector was initially unsuccessful. Conclusions A structured theoretical and practical transthoracic echocardiography course of training for last year medical students provides a clear and measurable learning experience in assessing and measuring left ventricular function. At least 14 examination blocks are necessary to achieve 90% agreement of correct determination of the ejection fraction.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Lars R Herda ◽  
Christiane Trimpert ◽  
Astrid Hummel ◽  
Ute Nauke ◽  
Pfeiffersche Stiftungen ◽  
...  

Recent data indicate that cardiac antibodies play an active role in the pathogenesis of dilated cardiomyopathy (DCM), and may contribute to cardiac dysfunction of DCM patients. Previous studies have suggested that immunoadsorption with subsequent IgG substitution (IA/IgG) improves left ventricular function in DCM. The potential influence of this immunomodulatory therapy on cardiopulmonary exercise remains to be elucidated. 60 patients with DCM ( n = 60, NYHA II-IV, left ventricular ejection fraction ≤ 45%) underwent either IA/IgG ( n = 30), or were followed up without IA ( n = 30). IA/IgG was performed in one course of five consecutive days. After three months we compared echocardiographic assessment of left ventricular function and spiroergometric exercise parameters in both groups. Left ventricular ejection fraction (LVEF) improved significantly in the IA/IgG group from 33.0 ± 1.2% to 40.1 ± 1.5% (p < 0.001 vs. control, p < 0.001 vs. baseline). In the control group, spiroergometric exercise parameters did not change during follow-up. In contrast, patients receiving IA/IgG improved significantly in the following parameters: peak oxygen uptake (peak VO 2 ; 17.3 ± 0.9 ml/min/kg to 21.8 ± 1.0 ml/min/kg; p < 0.01 vs. control, p < 0.01 vs. baseline), oxygen pulse (10.7 ± 0.7 ml/bpm to 13.6 ± 0.7 ml/bpm; p < 0.05 vs. control, p < 0.01 vs. baseline), and anaerobic threshold (VO 2 AT; 10.3 ± 0.5 ml/min/kg to 13.2 ± 0.5 ml/min/kg; p < 0.001 vs. control, p < 0.001 vs. baseline). The ventilatory response to exercise (V E /VCO 2 slope) decreased after IA/IgG therapy from 32.3 ± 1.5 to 28.7 ± 0.9 (p = 0.18 vs. controls, p = 0.02 vs. baseline), whereas there was no significant change in the control group after 3 months. IA/IgG therapy in DCM patients may induce improvement in echocardiographic and cardiopulmonary exercise parameters.


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