Mean Left Ventricular Ejection Fraction Change Research Articles

Prophylaxis to Prevent Cardiotoxicity in Patients Receiving Anthracycline for Breast Cancer: A Combined Bayesian and Frequentist Network Meta-Analysis of Randomised Controlled Trials

The benefits in survivorship gained with anthracycline (ANT)-based chemotherapies for breast cancer are unfortunately mitigated for some patients by irreversible cardiotoxicity. Randomised controlled trials (RCTs) have explored multiple cardioprotection options, however, it remains unclear which drug is most effective in preserving left ventricular ejection fraction (LVEF). This study aimed to perform a systematic review and network meta-analysis, using Bayesian and frequentist approaches, of RCTs evaluating cardioprotective agents. Two authors searched four databases (CENTRAL, Cochrane Reviews, MEDLINE, SCOPUS), to find RCTs evaluating cardioprotective agents. Trial populations were limited to patients with breast cancer without prior ANT exposure. The primary outcome was mean LVEF change pre and post ANT dosing. Our primary analysis utilised a Bayesian approach, while our sensitivity analysis used frequentist methodology (Prospero registration number CRD42020199580). From 4,007 search results, we identified 12 RCTs, with their various trial arms considered separately-nine beta-blocker (BB), two angiotensin-converting enzyme inhibitor /angiotensin receptor blockers [(AA)+BB=AABB], one AA, one spironolactone, one statin-evaluating 1,126 patients (age 50.5 years). Bayesian network meta-analysis showed no difference in LVEF preservation between AA (1.3%, 95% credible interval [-0.20, 2.9]), BB (0.77, [-0.21, 1.8]), AABB (0.84 [-1.1, 2.8]), spironolactone (0.72, [-2.3, 3.7]) or statin (0.60, [-2.4, 3.6]) when compared against placebo. However, the frequentist analysis showed benefits from using AA (mean difference, 1.32% [0.32, 2.33]) and BB (mean difference, 0.76% [0.12, 1.4]). There is insufficient evidence to support prophylactic cardioprotection to prevent EF reduction. However, frequentist analysis suggested that AA or BBs provide cardioprotection. Thus, for those already on other anti-hypertensives, switching to AA or BBs could be considered.

Efficacy of sacubitril-valsartan and SGLT2 inhibitors in heart failure with reduced ejection fraction: A systematic review and meta-analysis.

Sacubitril-valsartan (SV) monotherapy has been shown to help patients with Heart failure with reduced ejection fraction (HFrEF), but whether adding a sodium-glucose cotransporter-2 inhibitor (SGLT2i) improves treatment results even more is unknown. The goal of this study was to look at the efficacy of SV with additional SGLT2i in HFrEF patients. For this study, several databases, such as PubMed, EMBASE, Web of Science, and the Cochrane Library, were searched. A coherent search approach was used for data extraction. Review Manager 5.2 and MedCalc were used for conducting the meta-analysis and bias analysis. A meta-regression study correlates patient mean age with primary and secondary outcomes. Seven trials totaling 16 100 patients were included in this meta-analysis. All-cause mortality, cardiovascular mortality, and improvement in mean left ventricular ejection fraction (LVEF) were the study's major objectives, while hospitalization for heart failure (HF) was calculated to be its secondary outcome. Our analysis showed that HFrEF patients receiving the combination of SV and SGLT2i had better treatment outcomes than the standard SV monotherapy, with risk ratios of 0.76 (0.65-0.88) for all-cause mortality, 0.65 (0.49-0.86) for cardiovascular mortality, 1.41 (-0.59 to 3.42) for change in mean LVEF, and 0.80 (0.64-1.01) for hospitalization for HF. According to the regression analysis, older HFrEF patients have higher rates of hospitalization, cardiovascular disease, and overall death. The combination of SV and SGLT2i may have a greater cardiovascular protective effect and minimize the risk of death or hospitalization due to heart failure in HFrEF.

Statin Use Can Attenuate the Decline in Left Ventricular Ejection Fraction and the Incidence of Cardiomyopathy in Cardiotoxic Chemotherapy Recipients: A Systematic Review and Meta-Analysis.

There is insufficient evidence about the cardioprotective effects of statins against chemotherapy-induced cardiomyopathy. The MEDLINE and EMBASE databases were searched from inception to March 2021 for studies that reported the mean left ventricular ejection fraction (LVEF) before and after chemotherapy and the incidence of chemotherapy-induced cardiotoxicity in patients who received concurrent statin therapy and those who received chemotherapy alone. A random effects meta-analysis was performed to obtain the pooled weighted mean difference (WMD) and the 95% confidence interval (CI) for the mean final LVEF and the mean LVEF change, and the pooled odds ratio (OR) and the 95% CI of the incidence of chemotherapy-induced cardiomyopathy. Seven studies with 3042 patients were included in this meta-analysis (statin group: 1382 patients received concurrent statin with chemotherapy; control group: 1660 patients received chemotherapy alone). Patients in the control group had a more significant decline in LVEF (WMD = −6.08%, 95% CI: −8.55 to −3.61, p < 0.001) compared to those in the statin group. Additionally, the statin group had a significantly lower incidence of chemotherapy-induced cardiomyopathy compared to the control group (OR = 0.41, 95% CI = 0.28–0.60, p < 0.001). Consequently, our study showed a significant reduction in the incidence of chemotherapy-induced cardiomyopathy and the degree of LVEF decline in patients in the statin group compared to those in the control group.

Impact of Beta Blockers on Left Ventricular Reverse Remodeling Following Primary Coronary Intervention for ST-elevation Myocardial Infarction

Background. Benefits of beta-adrenergic receptor blockers (BB) following ST-elevation myocardial infarction (STEMI) are based on data before primary percutaneous coronary intervention (PCI) became the therapeutic first choice. This study examined the relationship between BB dose and magnitude of left ventricular ejection fraction (LVEF) improvement in STEMI following primary PCI. Methods and Findings. A total of 235 STEMI patients following primary PCI who underwent echocardiography during the acute phase and over 6 months from onset were studied retrospectively. Serial LVEFs were assessed for three groups: no BB (n=33), carvedilol (n=163), and bisoprolol (n=42). Left ventricular reverse remodeling (RR) was defined as LVEF improvement ≥10%. All patients received fixed doses of BB and renin-angiotensin system inhibitor during observation. The median interval between echocardiographs was 526 days. The mean LVEF change was +2.6% (acute: 53.9±9.9%, chronic: 56.4±10.6%). Carvedilol and bisoprolol groups showed LVEF improvement, but none was seen in the no BB group (+3.7±6.5%, +3.8±6.9%, -4.2±5.0%, P<0.0001, respectively). The LVEF improvement effect was BB dose dependent. Therapy with BBs had a high rate of RR (no BB 0%, carvedilol 19.4%, bisoprolol 16.7%, P=0.0225, respectively). Multivariate analysis showed the following predictors of RR: baseline LVEF <50% and regular dose of BB, ≥10 mg of carvedilol or ≥1.25 mg of bisoprolol (Odds ratio 2.35, 95% Confidence Interval [CI] 1.12-5.02, P=0.0242; Odds ratio 4.45, 95% CI 2.06-10.27, P=0.0001). Conclusions. Immediate BB administration following primary PCI for STEMI provided a dose-dependent LVEF improvement. A LVEF <50% and regular dose of BB are predictors of RR.

Abstract 18942: Is Bilirubin Protective Against Anthracycline-induced Cardiomyopathy?

Introduction: Reductions in left ventricular ejection fraction (LVEF) may occur after the administration of anthracycline-based chemotherapeutic regimens. Oxidative stress at the myocellular level has been implicated in these reductions, and as a consequence, we hypothesized that bilirubin, an effective endogenous anti-oxidant, would ameliorate some of the reductions in LVEF associated with anthracyline administration. Methods: From 1/1/2002 to 12/31/2012, we identified 751 consecutive individuals who were treated with anthracyclines at Wake Forest Baptist Medical Center, received serial LVEF measures, and exhibited basal serum bilirubin levels &lt; 2mg/dl prior to their treatment for cancer. The correlation between pre-chemotherapy bilirubin levels and serial pre- to post-chemotherapy changes in LVEF was analyzed using linear regression models. For dose response analysis, the participants were divided into 3 groups based on their bilirubin levels. ANOVA was used to test for the difference in the mean LVEF change across groups. Tukey’s Studentized Range test was used in pairwise comparisons. Chi-square test was used for categorical variables. Results: There were 65 (35%), 86 (30%) and 68 (24%) participants whose LVEF decreased by more than 15% in Group 1 (bilirubin ≤0.5mg/dl), Group2 (bilirubin 0.6 - 0.8mg/dl) and Group 3 (bilirubin 0.9 - 1.9mg/dl) respectively (Table 1). On pairwise comparison, there was a significant decrease in LVEF between Group 1 and Group 3 (2.9, 95% CI: 0.15 - 5.7). After adjusting for age, BMI, race, CAD/MI, diabetes, hematocrit and medications; increased bilirubin and reduced BMI were associated with LVEF preservation (p = 0.028 and 0.033 respectively). Conclusions: In patients treated with anthracyclines, bilirubin level was negatively correlated with reduction in LVEF. These results have potential therapeutic implications for preserving left ventricular function in patients treated with anthracyclines.

Evaluation of Short-Term Use of N-Acetylcysteine as a Strategy for Prevention of Anthracycline-Induced Cardiomyopathy: EPOCH Trial - A Prospective Randomized Study

Background and ObjectivesWe investigate to determine whether N-acetylcysteine (NAC) can prevent anthracycline-induced cardiotoxicity.Subjects and MethodsA total of 103 patients were enrolled in this prospective randomized open label controlled trial. They are patients first diagnosed with breast cancer or lymphoma, who require chemotherapy, including anthracycline like adriamycine or epirubicine. Patients were randomized to the NAC group {n=50; 1200 mg orally every 8 hours starting before and ending after the intravenous infusion of anthracycline in all chemotherapy cycles (3-6)} or the control group (n=53). Primary outcome was the decrease in left ventricular ejection fraction (LVEF) absolutely ≥10% from the baseline and concomitantly <50% at 6-month. Composite of all-cause death, heart failure and readmission were compared.ResultsThe primary outcome was not significantly different in the NAC and control groups {3/47 (6.4%) vs. 1/52 (1.9%), p=0.343}. The mean LVEF significantly decreased in both the NAC (from 64.5 to 60.8%, p=0.001) and control groups (from 64.1 to 61.3%, p<0.001) after the completion of whole chemotherapy. The mean LVEF change did not differ between the two groups (-3.64% in NAC vs. -2.78% in control group, p=0.502). Left ventricular (LV) end systolic dimension increased with higher trend in NAC by 3.08±4.56 mm as compared with 1.47±1.83 mm in the control group (p=0.064). LV end diastolic dimension did not change in each group and change does not differ in both. Peak E, A and E/A ratio change and cardiac enzymes were comparable in two groups. Cumulative 12-month event rate was 6% and 3.8% in the NAC group and the control group, respectively, with no difference (p=0.672).ConclusionWe cannot prove that NAC prevents anthracycline-induced cardiomyopathy.

P2-18-05: Cardiotoxicity Risks of Adjuvant Trastuzumab in Asian Breast Cancer Patients.

Abstract Background: Adjuvant trastuzumab (T)-based chemotherapy reduces relapse and improves overall survival in early breast cancer. However, T-associated cardiotoxicity potentially limits its use. Our study aims to report the incidence, severity and reversibility of cardiotoxicity amongst Asian breast cancer patients. Methods: This is a retrospective review of patients who have received adjuvant T from June 2005 to March 2011 at our centre. CT was defined as a drop in left ventricular ejection fraction (LVEF) to less than 50% and / or reduction of ≥ 10% of baseline. Cardiovascular (CVS) risk factors were defined as having at least one of the following factors: family or previous history of CAD, hypertension, diabetes mellitus, hyperlipidemia and smoking. One-way repeated measures ANOVA was used to evaluate the mean LVEF change and Chi-square test to evaluate the association of demographics and CT. Results: A total of 314 female patients were reviewed. CT was reported in 124 (39.5%), of whom 96 had asymptomatic decline in LVEF and 28 were symptomatic. T was withheld (n=53) due to asymptomatic decline in LVEF (n=40), symptomatic heart failure (n=3) and both (n=10). Forty-three patients with resolution of CHF (n=11) or LVEF recovery (n=32) were rechallenged. Cardiotoxicity recurred in 14 - asymptomatic decline in LVEF (n=10), recurrent CHF (n=1) and both (n=3). Overall, there were no cardiac-related deaths. Factors that predicted for CT included low normal pre-trastuzumab LVEF (&amp;lt;60%) (p=0.01), prior anthracyclines (p=0.011), decline in LVEF pre-anthracycline and before T (p=0.022) and BMI ≥ 23kg/m2 (p=0.018). Three-monthly LVEF showed statistically significant decline against baseline over the time points (p=0.005). As expected, the decline in LVEF demonstrated significant interaction with CT groups and non CT group (p&amp;lt;0.001). Conclusions: A higher incidence of CT (39.5%) was observed among Asian breast cancer patients compared to previously reported in Caucasians (24%). Although 77.4% of patients presented with asymptomatic decline in LVEF, approximately one-third of patients experienced recurrent CT upon rechallenge. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-05.

Cardiotoxicity risks of adjuvant trastuzumab in Asian breast cancer patients

561 Background: Adjuvant trastuzumab (T)-based chemotherapy has been shown to reduce relapse and improve survival in breast cancer patients but has been associated with increased risks of cardiotoxicity. Our study aims to define the incidence and severity of cardiotoxicity amongst Asian breast cancer patients. Methods: This is a retrospective review of patients who have received adjuvant T from June 2005 to 2007. Cardiotoxicity was defined as a drop in left ventricular ejection fraction (LVEF) to less than 50% and/or reduction of &gt; 10% of baseline. Cardiovascular (CVS) risk factors were defined as having a family history or presence of CAD, hypertension, diabetes mellitus, hyperlipidemia and smoking. We used pair sampled t-test to evaluate the mean LVEF change and Chi-square test to evaluate the association of cardiotoxicity and demographics. Results: There were 179 female patients. Cardiotoxicity was reported in 70 (39.1%), of whom 59 had asymptomatic decline in LVEF and 11 experienced CHF. Mean LVEF, comparing various time points (3, 6, 9 and 12 months) against baseline showed statistically significant decline (p&lt;0.05). T was withheld (n=33) due to asymptomatic decline in LVEF (n=24), symptomatic heart failure (n=4) and both (n=5). Twenty-one with resolution of CHF (n=7) or LVEF recovery (n=14) were rechallenged. Cardiotoxicity recurred in 9 - asymptomatic decline in LVEF (n=8) and recurrent CHF (n=1). There were no cardiac-related deaths. Neither patient demographics nor CVS risk factors predicted for cardiotoxicity. Conclusions: This is one of the largest series reported in Asians receiving T. As previously reported, T-induced cardiotoxicity resulted in mostly asymptomatic reversible decline in LVEF. Our incidence of cardiotoxicity appeared higher (39.1%) in Asians and more importantly, almost half of the patients experienced cardiotoxicity upon rechallenge. It would be prudent to explore whether there is any difference in susceptibility to T-induced cardiotoxicity between the different races. [Table: see text] No significant financial relationships to disclose.

Preserved Left Ventricular Ejection Fraction Following Atrioventricular Junction Ablation and Pacing for Atrial Fibrillation

Right ventricular apical (RVA) pacing creates ventricular dyssynchrony and may compromise left ventricular ejection fraction (LVEF). The impact of RVA pacing in patients who have undergone atrioventricular junction (AVJ) ablation for atrial fibrillation (AF) is unclear. We sought to determine whether RVA pacing after AVJ ablation for patients with AF compromises LVEF in the short- or long-term. We studied 286 patients with AF who underwent AVJ ablation and RVA pacing at our institution between 1990 and 2002. Patients were stratified into a short-term follow-up group (LVEF reassessed by echocardiography within a year after AVJ ablation, n = 134) and a long-term group (LVEF reassessed after a year, n = 152). Among all 286 patients (mean follow-up 20 months), we observed no change in mean LVEF after AVJ ablation and RVA pacing (48% before vs. 48% after, P = 0.42). Short-term follow-up patients had a statistically significant improvement in mean LVEF (46% before vs. 49% after, P = 0.03), whereas there was no statistically significant change in mean LVEF in long-term follow-up patients (49% before vs. 48% after, P = 0.37). Only 9% of short-term patients, 15% of long-term patients, and 1% of patients with baseline LVEF <or= 40% experienced >or=10% absolute decrease in LVEF. Baseline LVEF > 40% was a multivariate predictor of LVEF decline. RVA pacing after AVJ ablation does not compromise LVEF in the short- or long-term for the vast majority of patients. Better predictors are needed to help us select patients for biventricular pacing after AVJ ablation.

Assessment of pulmonary thromboendarterectomy by tomographic electrocardiogram-gated equilibrium radionuclide angiocardiography compared with electron beam computed tomography

Successful thromboendarterectomy for chronic thromboembolic pulmonary hypertension promptly improves right ventricular (RV) function by decreasing RV volume and increasing ejection fraction (EF). Single photon emission computed tomography (SPECT) equilibrium radionuclide angiocardiography (ERNA) has been validated as a measure of RV and left ventricular (LV) volume and EF. Nine patients with chronic thromboembolic pulmonary hypertension underwent electron beam computed tomography (EBCT) and SPECT ERNA cardiac studies before and after thromboendarterectomy. EBCT and SPECT ERNA measures of RV and LV volume and EF were compared. Before thromboendarterectomy, EBCT and SPECT ERNA RV and LV volumes and RV EF were similar. LV EF was within the normal range with both methods but was slightly greater (P = .004) when measured by EBCT (mean +/- SD, 0.61 +/- 0.08) compared with SPECT ERNA (0.54 +/- 0.10). Thromboendarterectomy measured by EBCT and SPECT ERNA produced marked similar and significant decreases in RV end-systolic (-72 +/- 59 mL vs -58 +/- 25 mL) and end-diastolic (-75 +/- 85 mL vs -76 +/- 32 mL) volumes and similar slight increases in RV EF (0.12 +/- 0.07 vs 0.05 +/- 0.06). Slight decreases in mean LV end-systolic (-19 +/- 23 mL vs -5 +/- 13 mL, P = .05) and end-diastolic (-32 +/- 53 mL vs -9 +/- 31 mL, P = .21) volumes occurred, with little change in mean LV EF (0.05 +/- 0.07 vs 0.00 +/- 0.10). SPECT ERNA is an accurate method for measuring RV and LV volume and EF before and after thromboendarterectomy.