Background Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (RCHOP) chemotherapy in non‐Hodgkin's lymphoma (NHL) has risk of cardiotoxicity. Purpose To determine the role of myocardial work and biomarkers in subclinical diagnosis and prediction of cardiotoxicity. Methods The 130 NHL patients (52 ± 9 years, 62% men) scheduled for RCHOP, with LVEF>50%, were evaluated at baseline, after third cycle and chemotherapy completion for 3D LVEF, 2D myocardial deformation (longitudinal, radial, circumferential strain ‐ LS, RS, CS) and myocardial work (global constructive work, waste work, work index and work efficiency ‐ GCW, GWW, GWI, GWE). NT‐pro‐BNP and troponin I were determined. Results After chemotherapy ended, 37 patients (28%) (group I) developed asymptomatic cardiotoxicity (8 mild form, 25 moderate form, 4 severe form); 93 patients (group II) did not. After third cycle, all patients had decreased LS, CS, RS, GCW, GWI, GWE and increased GWW, persistent after chemotherapy completion, with significant changes in group I. After third cycle, GWE and GCW were the best independent predictors for LVEF reduction; GWE decrease with>5% after third cycle predicted cardiotoxicity after chemotherapy completed (91% sensitivity, 94% specificity). Conclusions In NHL, myocardial work can diagnose subclinical cardiotoxicity and predict LVEF decline. These parameters should be used for sensitive evaluation of myocardial function during chemotherapy.
The Coronavirus disease 2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), exhibits a wide spectrum of manifestations, from asymptomatic presentations to acute respiratory failure, myocardial injury, arterial or venous thrombosis, multiorgan failure, and death. Although COVID-19 mainly disrupts the respiratory syndrome, it has been shown to have detrimental impact on cardiac morphology and function, resulting in a broad range of cardiovascular complications and poor outcome, increasing morbidity and mortality of these patients. This review will summarize the knowledge on characterization of myocardial injury in COVID 19, by using cardiac biomarkers, electrocardiographic, and cardiac multi-modality imaging findings for an early and accurate diagnosis, proper management, correct treatment, and follow-up of COVID-19 patients.
Cardiotoxicity is an important side effect of vascular endothelial growth factor (VEGF) inhibitors therapy used in the treatment of various malignancies, leading to increased morbidity and mortality. Arterial hypertension, cardiac ischemia with the acceleration of atherosclerosis, arrhythmias, myocardial dysfunction and thromboembolic disease are the most feared cardiovascular adverse reactions due to VEGF inhibitors. Susceptibility for the occurrence of VEGF inhibitors-induced cardiotoxicity has multifactorial determinants, with a significant inter-individual variation. Baseline cardiovascular risk assessment of the patient, type and stage of cancer, dose and duration of VEGF inhibitors treatment and adjuvant chemotherapy or radiotherapy are the main predictors for cardiotoxicity. The role of the cardio-oncology team becomes essential for achieving maximum therapeutic anti-angiogenic effects with minimum cardiovascular side effects. This review will summarize the incidence, risk factors, mechanisms, management and treatment of VEGF inhibitors-induced cardiovascular toxicity.
Aims None of the conventional echocardiographic parameters alone predict increased NTproBNP level and symptoms, making diagnosis of heart failure with preserved ejection fraction (HFpEF) very difficult in some cases, in resting condition. We evaluated LA functions by 2D speckle tracking echocardiography (STE) on top of conventional parameters in HFpEF and preHF patients with diastolic dysfunction (DD), in order to establish the added value of the LA deformation parameters in the diagnosis of HFpEF. Methods We prospectively enrolled 125 patients, 88 with HFpEF (68±9 yrs), and 37 asymptomatic with similar risk factors with DD (preHF) (61±8 yrs). We evaluated them by NTproBNP, conventional DD parameters, and STE. Global longitudinal strain (GS) was added. LA reservoir (R), conduit (C), and pump function (CT) were assessed both by volumetric and STE. 2 reservoir strain (S) derived indices were also measured, stiffness (SI) and distensibility index (DI). Results LA R and CT functions were significantly reduced in HFpEF compared to preHF group (all p<0.001), whereas conduit was similarly in both groups. SI was increased, whereas DI was reduced in HFpEF group (p<0.001). By adding LA strain analysis, from all echocardiographic parameters, SR_CT<-1.66/s and DI<0.57 (AUC = 0.76, p<0.001) demonstrated the highest accuracy to identify HFpEF diagnosis. However, by multivariate logistic regression, the model that best identifies HFpEF included only SR_CT, GS and sPAP (R2 = 0.506, p<0.001). Moreover, SR_CT, DI, and sPAP registered significant correlation with NTproBNP level. Conclusions By adding LA functional analysis, we might improve the HFpEF diagnosis accuracy, compared to present guidelines. LA pump function is the only one able to differentiates preHF from HFpEF patients at rest. A value of SR_CT < -1.66/s outperformed conventional parameters from the scoring system, reservoir strain, and LA overload indices in HFpEF diagnosis. We suggest that LA function by STE could be incorporated in the current protocol for HFpEF diagnosis at rest as a major functional criterion, in order to improve diagnostic algorithm, and also in the follow-up of patients with risk factors and DD, as a prognostic marker. Future studies are needed to validate our findings.
Left ventricular non-compaction (LVNC) with preserved ejection fraction (EF) is still a controverted entity. We aimed to characterize structural and functional changes in LVNC with heart failure with preserved EF (HFpEF). Methods: We enrolled 21 patients with LVNC and HFpEF and 21 HFpEF controls. For all patients, we performed CMR, speckle tracking echocardiography (STE), and biomarker assessment for HFpEF (NT-proBNP), for myocardial fibrosis (Galectin-3), and for endothelial dysfunction [ADAMTS13, von Willebrand factor, and their ratio]. By CMR, we assessed native T1 and extracellular volume (ECV) for each LV level (basal, mid, and apical). By STE, we assessed longitudinal strain (LS), globally and at each LV level, base-to-apex gradient, LS layer by layer, from epicardium to endocardium, and transmural deformation gradient. Results: In the LVNC group, mean NC/C ratio was 2.9 ± 0.4 and the percentage of NC myocardium mass was 24.4 ± 8.7%. LVNC patients, by comparison with controls, had higher apical native T1 (1061 ± 72 vs. 1008 ± 40 ms), diffusely increased ECV (27.2 ± 2.9 vs. 24.4 ± 2.5%), with higher values at the apical level (29.6 ± 3.8 vs. 25.2 ± 2.8%) (all p < 0.01); they had a lower LS only at the apical level (−21.4 ± 4.4 vs. −24.3 ± 3.2%), with decreased base-to-apex gradient (3.8 ± 4.7 vs. 6.9 ± 3.4%) and transmural deformation gradient (3.9 ± 0.8 vs. 4.8 ± 1.0%). LVNC patients had higher NT-proBNP [237 (156–489) vs. 156 (139–257) pg/mL] and Galectin-3 [7.3 (6.0–11.5) vs. 5.6 (4.8–8.3) ng/mL], and lower ADAMTS13 (767.3 ± 335.5 vs. 962.3 ± 253.7 ng/mL) and ADAMTS13/vWF ratio (all p < 0.05). Conclusion: LVNC patients with HFpEF have diffuse fibrosis, which is more extensive at the apical level, explaining the decrease in apical deformation and overexpression of Galectin-3. Lower transmural and base-to-apex deformation gradients underpin the sequence of myocardial maturation failure. Endothelial dysfunction, expressed by the lower ADAMTS13 and ADAMTS13/vWF ratio, may play an important role in the mechanism of HFpEF in patients with LVNC.
Background Left ventricular (LV) deformation is dependent on mechanical load and does not reflect directly the myocardial energy consumption. Thus, measurement of global and regional myocardial work might be alternative and complementary methods for the assessment of myocardial function. However, there is no data regarding myocardial work changes during the heart failure continuum, from normal to diastolic dysfunction (DD), and to heart failure with preserved ejection fraction (HFpEF). Methods We assessed 80 subjects by 2D conventional and speckle tracking echocardiography (2DSTE): 25 patients with DD, 30 with HFpEF, and 25 normal, control subjects. We measured NTproBNP, LV ejection fraction (EF), and E/E' ratio. We used a new approach to calculate myocardial work, during mechanical systole and isovolumetric relaxation, by 2DSTE: global constructive work (GCW), as the “positive” work of the heart; global wasted work (GWW), as the “negative” work of the heart; global work efficiency (GWE), as the GCW/(GCW + GWW) in %; and global work index (GWI), as the GCW added to GWW. Similarly, a regional, segmental analysis was performed (18 segments model) (Figure 1). Results GCW increases in patients with DD, probably as a compensatory mechanism to preserve LV function against an increased after load, and decreases back to the normal values in HFpEF, while GWE significantly decreases from normal subjects to patients with DD, and then further in patients with HFpEF (table). Meanwhile, GWW increases from normal subjects to patients with DD, and then further in patients with HFpEF. As expected, GWI does not change significantly. By segmental analysis, first segment affected in terms of myocardial work is basal antero-septal segment, with low WE and higher WW (figure), probably due to the flat shape (based on the Laplace law), with a compensatory increased CW in the apical segments. NTproBNP level and E/E' ratio correlated only with GWW (r=0.4, p=0.013). Comparative global myocardial work Group LVEF (%) E/E' NTproBNP (pg/ml) GWI (mmHg%) GWE (%) GCW (mmHg%) GWW (mmHg%) Controls 58±6 7.3±2.4 – 2102±303 95.5±1.8 2295±279 87.9±39.6 DD 57±8 7.7±2.4 36±25 2296±431 94.8±2.3 2550±463 108±50 HFpEF 63±7 10.3±3.1 349±418 2074±485 93.5±2.5 2300±535 125±51 P (Anova) 0.004 <0.001 <0.001 0.12 0.008 0.05 0.019 Figure 1. Myocardial Work Conclusion Myocardial work efficiency decreases and wasted work increases in parallel with the severity of LV dysfunction. The first myocardial segment affected is basal antero-septal. Therefore, new parameters of myocardial work, derived from 2DSTE, might provide a better assessment of LV function in patients with DD or HFpEF. Acknowledgement/Funding This work was supported by a grant of Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1-TE-2016-0669, within PNCDI III
Funding Acknowledgements Type of funding sources: None. CHOP (cyclophosphamide, doxorubicin, oncovin, prednisone) in non-Hodgkin lymphoma (NHL) is limited by risk of cardiotoxicity. Aim. To define new parameters of LV myocardial work, arterial stiffness, and biomarkers for early diagnosis and prediction of cardiotoxicity. Methods. 91 patients (34 men, 57 ± 11 years), with NHL, with LVEF >50%, scheduled for CHOP, were assessed at baseline, and after 4th and 8th cycle (doxorubicin total dose of 341 ± 52 mg). 3D echo was used for LVEF; 2D STE for longitudinal strain (LS) and myocardial work: global constructive work (GCW) as "the positive" work of the heart; global wasted work (GWW) as "the negative" work of the heart; global work efficiency (GWE) by formula GCW/(GCW + GWW), and global work index (GWI) as sum of GCW and GWW; echo-tracking for pulse wave velocity (PWV) and β index. Troponin I and NTproBNP were measured. Cardiotoxicity was defined as LVEF decrease <50%, with >10% from baseline. Results. After 8th cycle, 17 patients (18%) (group I) developed cardiotoxicity (3D LVEF: 63 ± 3 vs. 48 ± 1, p < 0.0001), whereas 74 patients (group II) did not (3D LVEF: 63 ± 2 vs. 57 ± 3, p < 0.0001). There was a significant reduction of LS, GCW and GWE, with an increase of GWW and arterial stiffness, starting with the 4th cycle; changes in group I were higher than in group II (p < 0.001) (table). Univariate analysis showed significant correlation between reduction of 3D LVEF and decrease of LS, GCW, GWE (r = 0.65; r = 0.74; r = 0.54), and increase of GWW, PWV, β index, and troponin level after 4th cycle (r=-0.44; r=-0.38; r=-0.39; r=-0.35; all p < 0.05). Reduction of GCW after the 4th cycle was the best independent predictor of decrease of 3D LVEF after the 8th cycle (R2 = 0.48, p = 0.001). By ROC analysis, decrease of GCW by more than 29% after the 4th cycle predicted development of cardiotoxicity after the 8th cycle of CHOP (Sb 82%, Sp 81%). Conclusion. Assessment of myocardial work, combined with arterial stiffness and biomarkers, are able to detect early chemotherapy-induced cardiotoxicity and to predict further decline of LVEF in non-Hodgkin lymphoma. Myocardial work and cardiotoxicity CHOP Group I Group II LS(-%) Baseline 4th cycle 8th cycle 22 ± 2 17 ± 1† 13 ± 2† 22 ± 2 19 ± 2† 17 ± 2±† GCW (mmHg%) Baseline 4th cycle 8th cycle 2256 ± 123 1902 ± 133† 1633 ± 167† 2278 ± 168 2104 ± 111† 1937 ± 102† GWW (mmHg%) Baseline 4th cycle 8th cycle 84 ± 4 124 ± 18† 198 ± 24† 85 ± 11 94 ± 21† 113 ± 19† GWE (%) Baseline 4th cycle 8th cycle 98 ± 1 92 ± 2† 86 ± 2† 98 ± 1 95 ± 2 94 ± 1† GWI (mmHg%) Baseline 4th cycle 8th cycle 1982 ± 155 1888 ± 136† 1723 ± 172† 2003 ± 189 1945 ± 111 1873†±102† GCW = global constructive work; GWE = global work efficiency; GWI = global work index; GWW = global waste work; LS = longitudinal strain; † p < 0.001
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 2 National Grants of the Romanian Ministry of Research and Innovation - UEFISCDI: "Heart Preserved" and "PRO HEART 3D. Background The so-called left ventricle non-compaction (LVNC), better described as excessive trabeculation, is a highly debated myocardial phenotype. One of the main debates is whether excessive trabeculation is a remodeling feature due to volume load and LV dilation, or is the primary cause of LV dysfunction with LV dilation in the advanced stages. Purpose We aim to evaluate the relationship of LV trabeculations with LV volumes and systolic function in patients with LVNC. Methods 50 patients with suspected LVNC were evaluated by cardiac magnetic resonance (CMR), transthoracic echocardiography (TTE), and N-terminal prohormone of brain natriuretic peptide (NTproBNP). To avoid over-diagnosis of LVNC, we analyzed 27 patients confirmed by CMR, with a positive Jacquier criterion [the percentage of non-compact myocardium mass (NCCM) >20%], excluding those having only a positive Petersen criterion. By CMR, we measured left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), and left ventricular ejection fraction (LVEF). By TTE, we measured global longitudinal strain (GLS), and we performed myocardial work analysis (MWA), as a less afterload-dependent parameter than GLS, measuring global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Results Clinical and biological characteristics, CMR, GLS, and MWA results are detailed in Table 1. Mean percentage of NCMM was 29.45±10.3%. 89% of patients had HF, with LVEF ranging from 17% to 73%. There was no correlation between percentage of NCMM and LVEDVi. Instead, percentage of NCMM correlated positively with LVESVi (R=0.389, p = 0.045) and negatively with LVEF (R=-0.507, p = 0.007) (Figure 1). There was also no correlation between percentage of NCMM and GLS. Percentage of NCMM correlated negatively with GWE (R=-0.539, p = 0.004) (Figure 1), but not with GWI (p = 0.161), GCW (p = 0.249), or GWW (p = 0.060). By linear regression, per 10% increase in NCMM, LVEF decrease by 8.3% and GWE decrease by 4.2%. Percentage of NCCM had a trend to correlate positively with logNTproBNP (R=0.321, p = 0.103). Conclusions Our results suggest that excessive trabeculation in patients with LVNC is not a marker of chronic preload. LVNC seems to be a distinct cardiomyopathy, with a spectrum of systolic impairment proportional to the degree of hypertrabeculation. MWA is a promising tool to evaluate the functional implication of LV trabeculations.
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