scholarly journals N-Terminal Pro-B-Type Natriuretic Peptide after High-Dose Chemotherapy: A Marker Predictive of Cardiac Dysfunction?

2005 ◽  
Vol 51 (8) ◽  
pp. 1405-1410 ◽  
Author(s):  
Maria T Sandri ◽  
Michela Salvatici ◽  
Daniela Cardinale ◽  
Laura Zorzino ◽  
Rita Passerini ◽  
...  

Abstract Background: Chronic cardiac dysfunction may develop after administration of aggressive chemotherapy, sometimes leading to development of congestive heart failure (CHF). Recently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was implicated as a marker of CHF. In this study we evaluated the predictive role of NT-proBNP in patients treated with high-dose chemotherapy (HDC). Methods: NT-proBNP was measured after 62 chemotherapy treatments in 52 patients affected by aggressive malignancies. Blood samples were drawn before the start of HDC, at the end of HDC administration, and 12, 24, 36, and 72 h thereafter. In these patients, echocardiograms were performed regularly during a 1-year follow-up. Results: Seventeen patients (33%) had persistently increased NT-proBNP, 19 patients (36%) had only transient increases (concentrations went back to baseline at 72 h), and 16 (31%) had no increases [mean (SD) values at 72 h, 1163 (936) ng/L vs 185 (101) ng/L vs 39 (19) ng/L, respectively; P <0.0001]. Only patients with persistently increased NT-proBNP had a significant worsening of the left ventricular diastolic indexes from baseline to 12 months [ratio of peak early to peak late flow velocities from 1.42 (0.33) to 0.78 (0.11); P <0.0001; isovolumetric relaxation time from 90 (15) to 141 (26) ms; P <0.0001; E-wave deceleration time from 162 (17) to 224 (32) ms; P = 0.0004] and of the left ventricular ejection fraction [from 62.8 (3.4)% to 45.6 (11.5)%; P <0.0001]. Conclusions: Persistently increased NT-proBNP early after administration of HDC is strongly associated with development of cardiac dysfunction. This finding has important implications for identifying patients at risk of developing chemotherapy-induced cardiotoxicity.

2010 ◽  
Vol 28 (25) ◽  
pp. 3910-3916 ◽  
Author(s):  
Daniela Cardinale ◽  
Alessandro Colombo ◽  
Rosalba Torrisi ◽  
Maria T. Sandri ◽  
Maurizio Civelli ◽  
...  

Purpose Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated. Patients and Methods In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%. Results TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P < .001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P < .001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P < .001) and of lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P < .001). Conclusion TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.


2018 ◽  
Vol 47 (5) ◽  
pp. 361-371 ◽  
Author(s):  
Qing Kuang ◽  
Ning Xue ◽  
Jing Chen ◽  
Ziyan Shen ◽  
Xiaomeng Cui ◽  
...  

Background: Chronic kidney disease (CKD) has been proposed to associate with decreased hydrogen sulfide (H2S) level. Nevertheless, the role of H2S in the pathogenesis of CKD has not been fully investigated. Our study aimed to investigate the plasma level of endogenous H2S in patients with different stages of CKD, and to identify the role of H2S in the progression of CKD and its relationship with cardiovascular diseases. Methods: A total of 157 non-dialysis CKD patients were recruited in our study, with 37 age- and sex-matched healthy individuals as control. Plasma concentration of H2S was measured with spectrophotometry. Sulfhemoglobin, the integration of H2S and hemoglobin, was characterized and measured by dual wavelength spectrophotometry. Serum levels of homocysteine (Hcy), cardiac troponin T (cTnT), and N-terminal pro B type natriuretic peptide were measured using automated analyzers. Conventional transthoracic echocardiography was performed and left ventricular ejection fraction (LVEF) was analyzed as a sensitive parameter of cardiac dysfunction. Results: The plasma H2S level (μmol/L) in CKD patients was significantly lower than those in healthy controls (7.32 ± 4.02 vs. 14.11 ± 5.24 μmol/L, p < 0.01). Plasma H2S level was positively associated with estimated glomerular filtration rate (eGFR; ρ = 0.577, p < 0.01) and negatively associated with plasma indoxyl sulfate concentration (ρ = –0.554, p < 0.01). The mRNA levels of cystathionine β-synthase and cystathionine γ-lyase, 2 catalytic enzymes of H2S formation, were significantly lower in blood mononuclear cells of CKD patients with respect to controls; however, the mRNA level of 3-mercaptopyruvate sulfurtransferase, as another H2S-producing enzyme, was significantly higher in CKD patients. The serum concentration of Hcy, acting as the substrate of H2S synthetase, was higher in the CKD group (p < 0.01). Specifically, the content of serum Hcy in CKD stages 3–5 patients was significantly higher than that in CKD stages 1–2, indicating an increasing trend of serum Hcy with the decline of renal function. Examination of ultrasonic cardiogram revealed a negative ­correlation between plasma H2S level and LVEF (ρ = –0.204, p < 0.05) in CKD patients. The H2S level also correlated negatively with cTnT concentration (ρ = –0.249, p < 0.01). Conclusions: Plasma H2S level decreased with the decline of eGFR, which may contribute to the cardiac dysfunction in CKD ­patients.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Vincenzo Riverso ◽  
Antonio Curcio ◽  
Alessia Tempestini ◽  
Emilia De Luca ◽  
Sabrina La Bella ◽  
...  

Abstract Aims Complications of acute myocardial infarction (MI) can be life-threatening leading to sudden cardiac death. While guidelines recommend prompt revascularization and prolonged intensive care hospitalization, predictors of major adverse cardiovascular outcomes are yet poorly understood. The role of implantable cardioverter-defibrillators, even in cases of non-sustained arrhythmias is still debated. To date, it is unknown how to follow-up patients with mild cardiac dysfunction after MI. Implantable cardiac monitors (ICMs) can be helpful for stratifying patients in the early discharge period, and remote monitoring might speed up arrhythmia recognition and treatment. We investigated the role of remote monitoring of ICMs to detect arrhythmic events in post-MI patients without overt cardiac dysfunction. Methods and results We enrolled 13 patients (9 males; 69.8 years) after either ST-segment (N = 7) or non-ST-segment elevation (N = 6) MI with a left ventricular ejection fraction (LVEF) &gt;35%, admitted to our coronary care unit for urgent revascularization between September 2019 and September 2021. Twelve patients underwent percutaneous myocardial revascularization, whereas one was treated with medical therapy only. All patients received an ICM during hospitalization according to echo and EKG parameters. We considered LVEF ≤ 40% as sole risk factor or LVEF between 40% and 50% in addition to either PQ length prolongation, or QRS widening, or pathologic heart rate variability, or non-sustained ventricular tachycardia/paroxysmal advanced second degree atrioventricular block. Patients with multiple revascularization procedures and several hospital admissions were excluded. Implanted ICM were frequently monitored both remotely and in-office when required. During follow-up, brady- and tachy-arrhythmias were recorded in four patients (30.8%). The remote monitoring of the ICM documented new-onset atrial fibrillation, high-degree atrioventricular block, severe bradycardia, and sustained ventricular tachycardia. Three patients required hospitalization and upgrade of the implanted device with pacemakers and cardioverter/defibrillator. For arrhythmic risk stratification, patients were divided into two subgroups; group A included patients with LVEF 40% associated with heart rate &gt; 60 b.p.m., PQ length &gt;160 ms and QRS width &gt;86 ms (N = 4); group B included patients with EF 41%/50%, PQ length &lt;159 and QRS width &lt;85 ms (N = 10). First group experienced more advanced rhythm disorders than group B (P &lt; 0.05). Device implantation was significantly higher in group A (P &lt; 0.05%). Conclusions OFF-label implementation of ICMs coupled with remote device monitoring may be effective for early detection of serious adverse cardiac rhythm alterations in patients after MI and LVEF higher than 35%. Further monitoring is ongoing for assessing the occurrence of multiple arrhythmias or their increased occurrence.


2003 ◽  
Vol 49 (2) ◽  
pp. 248-252 ◽  
Author(s):  
Maria Teresa Sandri ◽  
Daniela Cardinale ◽  
Laura Zorzino ◽  
Rita Passerini ◽  
Paola Lentati ◽  
...  

Abstract Background: Increased cardiac troponin I (cTnI) in patients treated with high-dose chemotherapy (HDCT) for aggressive malignancy has been proposed as an early marker of late HDCT-induced cardiac dysfunction. We investigated whether cTnI measured by the Stratus CS (Dade Behring) would allow detection of minimal cTnI increases in patients treated with HDCT. Methods: Plasma cTnI concentrations were determined in 179 consecutive patients before HDCT, at the end of the treatment, and after 12, 24, 36, and 72 h. Cardiac function was explored by echocardiography, and left ventricular ejection fraction (LVEF) was recorded during follow-up. The greatest variation in LVEF from the baseline value was used as a measure of cardiac damage. Results: In 99 healthy volunteers, the 99th percentile was at 0.07 μg/L. On the basis of ROC curve analysis (area under the curve, 0.89), a cutoff of 0.08 μg/L was chosen (sensitivity, 82%; specificity, 77%). cTnI ≥0.08 μg/L occurred in 57 patients (32%) with echocardiographic monitoring revealing a mean decrease in LVEF of 18%. In comparison, the group of cTnI-negative patients had a mean decrease in LVEF of 2.5% (P &lt;0.001). Conclusions: Plasma cTnI, as measured with the Stratus CS, can detect minor myocardial injury in patients treated with HDCT.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Esther Una Cidon ◽  
Tamas Hickish ◽  
Pilar Alonso

Trastuzumab, a humanized monoclonal antibody against the extracellular domain of human epidermal growth factor receptor 2 (HER-2) prolongs disease-free survival (DFS) and overall survival (OS) in patients with early-stage breast cancer. Although it is generally well tolerated, it has been associated with cardiotoxicity, mainly a reduction of left-ventricular ejection fraction (LVEF), especially if the patient has received anthracyclines.It is generally known that a drop in LVEF has limited diagnostic ability. Therefore, the identification of serum biomarkers of cardiotoxicity, able to detect damage at an earlier phase, has become ideal. Troponins (conventional and high sensitive), natriuretic peptides, reactive C protein (CRP), myeloperoxidase (MPO), etc are different molecular markers which have been assessed to check their role in the detection of treatment induced cardiotoxicity (CTIC) with controversial results.OBJECTIVEThis systematic review will synthesize available evidence assessing the role of different serum biomarkers in early prediction of cardiotoxicity in breast cancer patients treated with adjuvant trastuzumab.METHODS/DESIGNSystematic review conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Distinct scientific databases such as Google Scholar, Pubmed, EBSCOhost, and PsycINFO were searched to aid in the investigation of the research problem.Randomized clinical trials (RCT) and observational studies of patients with early breast cancer receiving adjuvant trastuzumab were eligible for inclusion. Two investigators have independently evaluated those studies and used standardized data extraction templates to collect data on the study and patients’ characteristics.RESULTS 11 articles were selected, one RCT and ten observational studies. The most studied biomarker was N-terminal-pro-brain natriuretic peptide (NT-proBNP) followed by troponins. Findings showed that NT-proBNP was not predictive of CTIC while conflictive results were seen with troponins.One study showed a predictive role of high sensitive (hs) CRP and another found a relationship with the levels of MPO.CONCLUSIONBiomarkers offer a unique potential to improve the effectiveness and safety of trastuzumab through timely detection of CTIC and prompt initiation of appropriate treatment. Troponins I and T have shown a predictive role in early detection of CTIC but further research would be needed to enable more insight and improve the overall patient outcome.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B.M.L Rocha ◽  
G.J Lopes Da Cunha ◽  
P.M.D Lopes ◽  
P.N Freitas ◽  
F Gama ◽  
...  

Abstract Background Cardiopulmonary exercise testing (CPET) is recommended in the evaluation of selected patients with Heart Failure (HF). Notwithstanding, its prognostic significance has mainly been ascertained in those with left ventricular ejection fraction (LVEF) &lt;40% (i.e., HFrEF). The main goal of our study was to assess the role of CPET in risk stratification of HF with mid-range (40–49%) LVEF (i.e., HFmrEF) compared to HFrEF. Methods We conducted a single-center retrospective study of consecutive patients with HF and LVEF &lt;50% who underwent CPET from 2003–2018. The primary composite endpoint of death, heart transplant or HF hospitalization was assessed. Results Overall, 404 HF patients (mean age 57±11 years, 78.2% male, 55.4% ischemic HF) were included, of whom 321 (79.5%) had HFrEF and 83 (20.5%) HFmrEF. Compared to the former, those with HFmrEF had a significantly higher mean peak oxygen uptake (pVO2) (20.2±6.1 vs 16.1±5.0 mL/kg/min; p&lt;0.001), lower median minute ventilation/carbon dioxide production (VE/VCO2) [35.0 (IQR: 29.1–41.2) vs 39.0 (IQR: 32.0–47.0); p=0.002) and fewer patients with exercise oscillatory ventilation (EOV) (22.0 vs 46.3%; p&lt;0.001). Over a median follow-up of 28.7 (IQR: 13.0–92.3) months, 117 (28.9%) patients died, 53 (13.1%) underwent heart transplantation, and 134 (33.2%) had at least one HF hospitalization. In both HFmrEF and HFrEF, pVO2 &lt;12 mL/kg/min, VE/VCO2 &gt;35 and EOV identified patients at higher risk for events (all p&lt;0.05). In Cox regression multivariate analysis, pVO2 was predictive of the primary endpoint in both HFmrEF and HFrEF (HR per +1 mL/kg/min: 0.81; CI: 0.72–0.92; p=0.001; and HR per +1 mL/kg/min: 0.92; CI: 0.87–0.97; p=0.004), as was EOV (HR: 4.79; CI: 1.41–16.39; p=0.012; and HR: 2.15; CI: 1.51–3.07; p&lt;0.001). VE/VCO2, on the other hand, was predictive of events in HFrEF but not in HFmrEF (HR per unit: 1.03; CI: 1.02–1.05; p&lt;0.001; and HR per unit: 0.99; CI: 0.95–1.03; p=0.512, respectively). ROC curve analysis demonstrated that a pVO2 &gt;16.7 and &gt;15.8 mL/kg/min more accurately identified patients at lower risk for the primary endpoint (NPV: 91.2 and 60.5% for HFmrEF and HFrEF, respectively; both p&lt;0.001). Conclusions CPET is a useful tool in HFmrEF. Both pVO2 and EOV independently predicted the primary endpoint in HFmrEF and HFrEF, contrasting with VE/VCO2, which remained predictive only in latter group. Our findings strengthen the prognostic role of CPET in HF with either reduced or mid-range LVEF. Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Ahmed Ayuna ◽  
Nik Abidin

Abstract Background Anthracycline-induced cardiotoxicity has been classified based on its onset into acute, early, and late. It may have a significant burden on the quality and quantity of life of those exposed to this class of medication. Currently, there are several ongoing debates on the role of different measures in the primary prevention of cardiotoxicity in cancer survivors. Our article aims to focus on the role of neurohormonal blockers in the primary prevention of anthracycline-induced cardiotoxicity, whether it is acute, early, or late onset. Main body of the abstract PubMed and Google Scholar database were searched for the relevant articles; we reviewed and appraised 15 RCTs, and we found that angiotensin-converting enzyme inhibitors (ACEI) and B-blockers were the most commonly used agents. Angiotensin II receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRAs) were used in a few other trials. The follow-up period was on the range of 1–156 weeks (mode 26 weeks). Left ventricular ejection fraction (LVEF), left ventricular diameters, and diastolic function were assessed by either echocardiogram or occasionally by cardiac magnetic resonance imaging (MRI). The occurrence of myocardial injury was assessed by troponin I. It was obvious that neurohormonal blockers reduced the occurrence of LVEF and myocardial injury in 14/15 RCTs. Short conclusion Beta-blockers, especially carvedilol and ACEI, especially enalapril, should be considered for the primary prevention of acute- and early-onset cardiotoxicity. ARB and MRA are suitable alternatives when patients are intolerant to ACE-I and B-blockers. We recommend further studies to explore and establish the role of neurohormonal blockers in the primary prevention of the acute-, early-, and late-onset cardiotoxicity.


2007 ◽  
Vol 25 (25) ◽  
pp. 3859-3865 ◽  
Author(s):  
Thomas M. Suter ◽  
Marion Procter ◽  
Dirk J. van Veldhuisen ◽  
Michael Muscholl ◽  
Jonas Bergh ◽  
...  

Purpose The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2–positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF ≥ 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. Results Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m2 v 257 mg/m2) or epirubicin (480 mg/m2 v 422 mg/m2) and had a lower screening LVEF and a higher body mass index. Conclusion Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.


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