Cardioprotection in patients with cancer undergoing chemotherapy: A network meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12008-e12008
Author(s):  
Pragnan Kancharla ◽  
Alexander Ivanov

e12008 Background: Introduction of anthracycline or trastuzumab based regimen for various types of cancer during the past two decades led to substantial improvement in life expectancy, yet resulting in increased prevalence of unintended side effects. Left ventricular systolic dysfunction is a known complication of the currently employed chemotherapy regimens with anthracycline or trastuzumab which not only affects patient’s cardiac outcome but also limits their therapeutic opportunities, especially continuation or reintroduction of chemotherapy treatment. We aimed to perform comprehensive network meta analysis to synthesize data from randomized clinical trials (RCT) comparing all modern regimens to prevent cardiotoxicity in such patients. Methods: We performed a comprehensive search of pubmed, embase, google scholar and TRIP database for all RCT comparing cardioprotective effects of medication in patients with various types of cancer on chemotherapy with either an anthracycline or trastuzumab based regimen from 1997 to 2019. Left ventricular ejection fraction (LVEF) was measured by transthoracic echocardiogram or cardiac magnetic resonance imaging. Patients treated with either Angiotensin Converting Enzyme-Inhibitor(ACE) or Angiotensin receptor blocker(ARB) were combined into one group. Primary outcome was change in LVEF between start and end of the chemotherapy. Network meta-analyses were conducted using consistency and inconsistency models. Results: A total of 16 studies with 1459 patients were included in the analysis where either an Anthracycline or Trastuzumab based chemotherapy regimen was administered. 369 patients received beta blockers(BB), 351 received either an ACE or ARB, 61 received a combination of BB and either an ACE or ARB, 20 received a statin and 657 were given a placebo. The primary cancer was breast cancer in 8 studies, one each of lymphoma, blood cancers and remaining 6 being mixed. Mean age was 48.81 years. Compared to patients on placebo there was a significant cardioprotective effect (smaller reduction in LVEF) noted with ACE/ARB (beta coef 5.2 (1.5-8.9), p<0.01), BB(beta coef 4.62 (0.8-7.8), p<0.02), and spironolactone beta coef 12.9 (1.9-23.4), p<0.03) There was an evidence of inconsistency with all p>0.3, other than in spironolactone arm as there were suggestion of inconsistency with p<0.01 likely due to the presence of single study. Conclusions: BB and ACE/ARB are associated with reduction in cardiotoxicity in patients with cancer undergoing cancer chemotherapy with an anthracycline or trastuzumab based regimen.

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
B Sara ◽  
JJ Monteiro ◽  
P Carvalho ◽  
C Ribeiro Carvalho ◽  
J Chemba ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background Plasma levels and N-terminal pro B-type natriuretic peptide (NT- proBNP), a cardiac neurohormone released in response to increased ventricular stress, represent an important predictor of clinical outcomes and left ventricular (LV) dysfunction; Although, its diagnostic and prognostic role in patients with acute myocarditis is not completely established; Our aim was to evaluate the relationship of BNP levels and LV ejection fraction (LVEF) in patients with myocarditis; Methods Data from patients (pts) discharged with the diagnosis of myocarditis, from 2008 and 2018 were retrospectively analysed. Results 62 pts were included. Mean age was 39.7 17 years and 89% (58 patients) were men. Plasma levels of NT-proBNP measured at admission ranged from 24 to 3110 pg/mL (median 514, IQR 947), and exceeded upper normal levels in 51 pts (82%). This values positively correlated with C- reactive protein (CRP) (p= 0.005, r = 0.36), leucocytes (p = 0.03, r= 0.37) and neutrophil-to-lymphocyte ratio (p= 0.05, r= 0.35), but not with left ventricular ejection fraction (LVEF) (p= 0.829). Higher levels of BNP were associated with higher troponin peak levels but not with increased mortality (p = 0.811), need of inotropic support (p= 0.059) or arrhythmic events (p= 0.130). Inflammatory parameters were significantly increased when BNP&gt; 514 pg/mL vs BNP &lt;514 pg/mL (CRP 7.2 vs 4 mg/dL, p= 0.008). This relationship was maintained at BNP &gt; 900. LVEF was comparable in both groups (p = 0.938); In this population, the magnitude of recovery of the NT- proBNP values (variation between NT-proBNP at admission and discharge) strongly correlated with the magnitude of the inflammatory markers at admission (all p &lt; 0,005) Conclusion In patients with acute myocarditis, there is a significant relationship between NT-proBNP levels and inflammation (as measured by leucocytes, NLR or CRP), but not with LVEF; Despite the limitation of a small sample size, we could hypothesize that NTproBNP in this subset of patients appears to be regulated not only by hemodynamic changes but also by the underlying systemic inflammatory process and, therefore, it interpretation should take that into account;


Author(s):  
N. P. Mitkovskaya ◽  
E. M. Balysh ◽  
T. V. Statkevich ◽  
N. A. Ladygina ◽  
E. B. Petrova ◽  
...  

The aim of the study was to investigate the features of clinically suspected myocarditis complicated by the left ventricular systolic dysfunction development. 93 patients with clinically suspected myocarditis were examined. The average age was 36.63 ± 1.15 years. In 43.01 % of patients the disease was accompanied by a decrease in left ventricular systolic function. In the group of patients with left ventricular systolic dysfunction in comparison with those with preserved left ventricular ejection fraction, a significantly lower proportion of men (75 % versus 81 %, respectively, χ2 = 9.3, p < 0,01) and a higher average group age (40.7 ± 1.87 versus 33.6 ± 1.3 years, respectively, p <  0,01) were revealed. The course of the disease in patients with left ventricular systolic dysfunction was characterized by a more frequent development of rhythm disturbances (65 % versus 43.3 %, respectively, χ2  = 4.3, p  < 0,05) and a higher heart rate at admission (94.5 (75‒100) and 85 (70‒89) beats per minute, respectively, p = 0.006). The structural and functional state of the heart according to echocardiography in patients with a reduced left ventricular ejection fraction versus comparison group was characterized by larger heart chambers sizes, more pronounced violations of local left ventricular contractility, more frequent involvement of the right ventricle in the pathological process (56.3  % versus 22.2  %, respectively, χ2   =  6.4, p  < 0,05). The relationships between the left ventricular ejection fraction Весці Нацыянальнай акадэміі навук Беларусі. Серыя медыцынскіх навук. 2020. Т. 17, № 4. C. 452–460 453 and the patient’s age (r = ‒0.36), the value of the heart rate at admission (r = ‒0.32), the severity of heart failure at admission, the degree of impaired local contractility of the left ventricle, the degree of right ventricular function (TAPSE, r  =  0.58), the severity of myocardial fibrosis according to cardiovascular magnetic resonance imaging (r = ‒0.32) were revealed.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Thomsen ◽  
S Pedersen ◽  
P K Jacobsen ◽  
H V Huikuri ◽  
P E Bloch Thomsen ◽  
...  

Abstract Introduction The CARISMA trial was the first study to use continuous monitoring for documentation of long-term arrhythmias in post-infarction patients with left ventricular dysfunction. During the study duration (2000–2005), primary PCI (pPCI) as treatment of acute myocardial infarction was introduced approximately midway (2002) on the enrolling centres. Purpose The aim of this study was to describe the influence of mode of revascularization after myocardial infarction (AMI) on long-term risk of risk of new onset atrial fibrillation, ventricular tachyarrhythmias and brady arrhythmias. Methods The study is a sub-study on the CARISMA study population that consisted of patients with AMI and left ventricular ejection fraction ≤40%, which received an implantable loop recorder and was followed for 2 years. After exclusion of 15 patients who refused device implantation and 26 with pre-existing arrhythmias, 268 of the 312 patients were included. Choice of revascularization was made by the treating team independently of the trial and was retrospectively divided into primary percutaneous intervention (pPCI), subacute PCI (24 hours to 2 weeks after AMI), primary thrombolysis or no revascularization. Endpoints were new-onset of arrhythmias and major cardiovascular events (MACE). The Kaplan-Meier (figure 1) and Mantel-Byar methods were used for time to first event risk analysis. Results A total of 77 patients received no revascularization, whereas 49 received thrombolysis only and 142 received PCI. At two-years follow up patients treated with any PCI had a significant lower risk (0.40, n=63) of any arrhythmia compared to patients treated with trombolysis (0.60, n=30) or no revascularization (0.68, n=16) (p<0.001, unadjusted) (figure 1). Risk of MACE was significant higher in patients with any arrhythmia (0.25, n=76) compared to no arrhythmia (0.11, n=93) at two years follow-up (p=0.004, unadjusted). Figure 1 Conclusion(s) The long-term risk of new onset arrhythmias after AMI was significantly lower in patients treated with any PCI compared to patients not revascularized or treated with thrombolysis. Risk of MACE was significantly higher in patients with new onset arrhythmias compared to patients with no arrhythmias.


Circulation ◽  
2020 ◽  
Vol 141 (17) ◽  
pp. 1371-1383 ◽  
Author(s):  
Peter Marstrand ◽  
Larry Han ◽  
Sharlene M. Day ◽  
Iacopo Olivotto ◽  
Euan A. Ashley ◽  
...  

Background: The term “end stage” has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (LVSD), defined as occurring when left ventricular ejection fraction is <50%. The prognosis of HCM-LVSD has reportedly been poor, but because of its relative rarity, the natural history remains incompletely characterized. Methods: Data from 11 high-volume HCM specialty centers making up the international SHaRe Registry (Sarcomeric Human Cardiomyopathy Registry) were used to describe the natural history of patients with HCM-LVSD. Cox proportional hazards models were used to identify predictors of prognosis and incident development. Results: From a cohort of 6793 patients with HCM, 553 (8%) met the criteria for HCM-LVSD. Overall, 75% of patients with HCM-LVSD experienced clinically relevant events, and 35% met the composite outcome (all-cause death [n=128], cardiac transplantation [n=55], or left ventricular assist device implantation [n=9]). After recognition of HCM-LVSD, the median time to composite outcome was 8.4 years. However, there was substantial individual variation in natural history. Significant predictors of the composite outcome included the presence of multiple pathogenic/likely pathogenic sarcomeric variants (hazard ratio [HR], 5.6 [95% CI, 2.3–13.5]), atrial fibrillation (HR, 2.6 [95% CI, 1.7–3.5]), and left ventricular ejection fraction <35% (HR, 2.0 [95% CI, 1.3–2.8]). The incidence of new HCM-LVSD was ≈7.5% over 15 years. Significant predictors of developing incident HCM-LVSD included greater left ventricular cavity size (HR, 1.1 [95% CI, 1.0–1.3] and wall thickness (HR, 1.3 [95% CI, 1.1–1.4]), left ventricular ejection fraction of 50% to 60% (HR, 1.8 [95% CI, 1.2, 2.8]–2.8 [95% CI, 1.8–4.2]) at baseline evaluation, the presence of late gadolinium enhancement on cardiac magnetic resonance imaging (HR, 2.3 [95% CI, 1.0–4.9]), and the presence of a pathogenic/likely pathogenic sarcomeric variant, particularly in thin filament genes (HR, 1.5 [95% CI, 1.0–2.1] and 2.5 [95% CI, 1.2–5.1], respectively). Conclusions: HCM-LVSD affects ≈8% of patients with HCM. Although the natural history of HCM-LVSD was variable, 75% of patients experienced adverse events, including 35% experiencing a death equivalent an estimated median time of 8.4 years after developing systolic dysfunction. In addition to clinical features, genetic substrate appears to play a role in both prognosis (multiple sarcomeric variants) and the risk for incident development of HCM-LVSD (thin filament variants).


Author(s):  
Alexandre Mebazaa ◽  
Mervyn Singer

Organ congestion upstream of the dysfunctional left and/or right ventricle, with preserved stroke volume, is the most frequkeywordent feature of myocardial failure.Clinical manifestations do not necessarily correlate with the degree of left ventricular systolic dysfunction (i.e. left ventricular ejection fraction).Systolic and/or diastolic dysfunction may be present, with systolic dysfunction usually predominating.Pulmonary oedema is related to left ventricular diastolic dysfunction. Compensatory mechanisms (within the heart and/or periphery) may prove paradoxically disadvantageous on ventricular stroke work and stroke volume.


Heart ◽  
2019 ◽  
Vol 105 (18) ◽  
pp. 1408-1413 ◽  
Author(s):  
Andrea K Y Lee ◽  
Jason Andrade ◽  
Nathaniel M Hawkins ◽  
George Alexander ◽  
Matthew T Bennett ◽  
...  

ObjectiveThe natural history of frequent premature ventricular complexes (PVCs) in association with preserved left ventricular ejection fraction (LVEF) is uncertain. The optimal management of this population is thus undefined. We studied the outcomes of untreated patients with frequent PVCs and preserved LVEF.MethodsThis cohort study prospectively evaluated consecutive patients from 2012 to 2017, with asymptomatic or minimally symptomatic frequent idiopathic PVCs (≥5% PVCs in 24 hours; normal LVEF; no cause identified on comprehensive evaluation). No suppressive therapy (ablation or antiarrhythmic drugs) were used and patients were followed with serial ambulatory ECG monitoring and echocardiography. The primary arrhythmic outcome was reduction in PVC burden to <1% on serial ambulatory monitoring. The primary echocardiographic outcome was a reduction of LVEF to <50%.ResultsOne hundred patients met inclusion criteria (mean age 51.8 years, 57% female) with a median PVC burden of 18.4%. Reduction to <1% PVCs occurred in 44 of 100 patients (44.0%) at a median of 15.4 months (range 2.6 to 64.3). Recurrence was uncommon (4/44, 9.1%). Four patients (4.3%) with a persistently elevated PVC burden developed left ventricular dysfunction (LVEF <50%) during the follow-up period at a range of 53–71 months. The initial PVC burden did not predict subsequent resolution (HR 1.00(0.97, 1.03); p=0.86).ConclusionsA strategy of active surveillance is appropriate for the majority of patients with frequent idiopathic PVCs in association with preserved LVEF, owing to the low risk of developing left ventricular systolic dysfunction and the high rate of spontaneous resolution.


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 282-282 ◽  
Author(s):  
L. Militello ◽  
P. Carli ◽  
S. Spazzapan ◽  
C. Lestuzzi ◽  
G. Miolo ◽  
...  

282 Background: T is a mainstay in adjuvant therapy for HER2+ breast cancer (BC) patients (pts). Safety and efficacy of T in elderly patients are largely unknown. In HERA trial, NSABP B-31, NCCTG N9831 only 16% of pts were older than 60 years. Risk factors for T related cardiotoxicity are age (>50 y/o), hypertension, baseline LVEF (left ventricular ejection fraction <55%), previous antracycline therapy and BMI. Methods: Charts of pts >65 y/o with early HER2+ BC treated with T as adjuvant or neoadjuvant therapy at our institution were retrospectively reviewed. Primary endpoint was the evaluation of T cardiac toxicity and safety. Results: 22 elderly out of 172 pts (12%) were identified: 19 pts were treated only with surgery and adjuvant chemotherapy with concomitant or sequential T, 3 more pts also received neoadjuvant chemotherapy concomitant with T. According to Balducci’s criteria, fit, vulnerable and frail pts were 20, 2, 0 respectively. Median age was 69 y/o (range 65-76). Hormonal status was negative in 10/22 (45%). 21/22 were histologic grade 3. Median follow-up was 33 months. Baseline comorbidities were the following: hypertension (G2-3) in 17 pts, diabetes mellitus in 1, supra/infraventricular arrhythmia (G1-2) in 3 and 1 pts. Antracyclines were administered in 16 pts (liposomal-doxorubicin in 5 pts), a sequential taxane-regimen was used in 3 more pts. Neoadjuvant weekly Paclitaxel and concomitant T was used in 3 pts. Median basal LVEF was 65% (range 59-74%). 2 pts developed an asymptomatic 10% LVEF drop from baseline (left ventricular systolic dysfunction G1) during T treatment. Known cardiac risk factors were hypertension in 1 pt and previous antracycline based chemotherapy in both. They recovered within 9 months. One minor adverse event was atrial fibrillation (G2) during T treatment. Conclusions: T was well tolerated in elderly pts. More data are needed in order to understand the correlations between T related toxicity and cardiovascular risk factors. Long term safety of T treatment should verify the reversibility of cardiac T related toxicity on elderly pts.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
I Chung

Abstract Funding Acknowledgements Type of funding sources: None. Background Background: In 1982, Goldberger described an electrocardiographic triad (SV1 or SV2 +RV5 or RV6 ≥3.5mV, total QRS amplitude in limb leads ≤0.8mV, and R/S ratio &lt; 1 in lead V4) that was 70% sensitive and &gt;90% specific for detecting severe left ventricular (LV) dysfunction. The pathophysiology of this highly specific ECG triad probably relates to a number of mechanical and vectorial factors associated with congestive heart failure of a variety of etiologies. Left ventricular enlargement causes increased precordial voltage. The horizontal plane vector shifts posteriorly, orthogonal to the frontal plane, causing poor R wave progression and low limb lead voltage. Finally, increased extracellular fluid may preferentially attenuates QRS voltage in the limb leads. Objective To test the sensitivity of this triad in patients with non-ischaemic cardiomyopathy and severe left ventricular systolic dysfunction Methods Methods: 386 patients mean age 62.45 ± 13.96 years, male 72%, NYHA II-IV, with non-ischaemic cardiomyopathy, 70 had bundle branch block (18%) and mean left ventricular ejection fraction(EF) 22.57 ± 8.62%. 76% hypertension, 39% diabetes mellitus, 32% atrial fibrillation. The electrocardiographic triad was sought in the ECG recorded at time of the echocardiographic study. The mean LV end-diastolic diameter was 5.81 ± 1.53 cm. Result Results: 56% patients had SV1 or SV2 +RV5 or RV6 ≥3.5mV, 85% patients had R/S ratio &lt; 1 in lead V4, 19% had total QRS amplitude in limb leads ≤0.8mV. 50% patients had SV1 or SV2 +RV5 or RV6 ≥3.5mV and R/S ratio &lt; 1 in lead V4. Only 6% patients fulfilled the triad. Conclusions Conclusion: Goldberger"s triad is an insensitive marker for severe LV dysfunction. Using SV1 or SV2 +RV5 or RV6 ≥3.5mV and R/S ratio &lt; 1 in lead V4 had a sensitivity of 50%. 85% patients had R/S ratio &lt; 1 in lead V4. R/S ratio &lt; 1 in lead V4 is a simple way to select dilated LV.


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