Intermuscular Fat Changes Are Related to Reduced Left Ventricular Ejection Fraction During Cancer Therapy (PREVENT-WF-98213).
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SUBMITTER: Bellissimo MP
PROVIDER: S-EPMC10308035 | biostudies-literature | 2023 Jun
REPOSITORIES: biostudies-literature
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Intermuscular Fat Changes Are Related to Reduced Left Ventricular Ejection Fraction During Cancer Therapy (PREVENT-WF-98213).
Bellissimo Moriah P MP Reding Kerryn W KW O'Connell Nathaniel S NS D'Agostino Ralph B RB Mabudian Leila L Heiston Emily M EM Ladd Amy C AC Weaver Kathryn E KE Lesser Glenn J GJ Fuemmeler Bernard F BF Salloum Fadi N FN Hundley W Gregory WG
JACC. CardioOncology 20230220 3
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Project description:Patients with primary mitral regurgitation (MR) may remain asymptomatic for many years. For unknown reasons, some shift from a compensated to a decompensated state and progress to fatal heart failure. To elucidate the genetic determinants of this process, we recruited 28 patients who underwent mitral valve surgery and stratified them into control, compensated MR, and decompensated MR groups. Tissue biopsies were obtained from the patients' left ventricular (LV) lateral wall for a transcriptome-wide profiling of 64,769 probes to identify differentially expressed genes (DEGs). Using cutoff values at the 1% FDR significance level and sex- and age-adjusted regression models, we identified 12 significant DEGs (CTGF, MAP1B, SERPINE1, MYH9, MICAL2, MYO1D, CRY1, AQP7P3, HTRA1, PRSS23, IGFBP2, and FN1). The most significant gene was CTGF (adjusted R2 = 0.74, p = 1.80 × 10-8). We found that the majority of genes expressed in the more advanced decompensated MR group were pro-fibrotic genes associated with cardiac fibrosis. In particular, six pro-fibrotic genes (CTGF, SERPINE1, MYH9, HTRA1, PRSS23, and FN1) were overexpressed and enriched in pathways involved in ECM (extracellular matrix) protein remodeling. Therapeutic interventions that antagonize these six genes may slow the progression toward decompensated MR.
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Project description:Background Trastuzumab is life-extending therapy for breast cancer patients overexpressing the human epidermal growth factor receptor 2 ( HER 2+), but has known cardiotoxic risk. We sought to determine if trastuzumab can be administered to patients with reduced baseline cardiac function at no higher cardiotoxicity risk than in those with normal cardiac function at baseline. Methods and Results We performed a retrospective study of women treated with trastuzumab for human epidermal growth factor receptor 2 breast cancer at Mayo Clinic Rochester between January 1, 2000 and August 31, 2015 with pre- and on-therapy echocardiograms available for review. A left ventricular ejection fraction (LVEF) <53% was considered abnormal, and a ≥10% decline in LVEF as evidence of cardiotoxicity based on the criteria of the American Society of Echocardiography. A total of 428 women were identified; 408 had a normal cardiac function ( LVEF 63.4±5%) and 20 had an impaired cardiac function ( LVEF 45.4±7%) before trastuzumab. Seven women (35%) with reduced LVEF at baseline had a ≥10% reduction in LVEF , compared with 179 (43.9%) of those with normal LVEF before trastuzumab initiation ( P= NS ). Symptomatic heart failure developed more often in patients with reduced versus normal baseline LVEF (25% versus 4.2%, P<0.05). After adjusting for patient age and breast cancer disease stage, survival rates over 5 years from time of diagnosis were found to be lower for patients with reduced baseline LVEF compared with patients with normal baseline LVEF ( P<0.001); the adjusted proportion of patients surviving at 5 years for those with low LVEF at baseline was 79% and for those with normal LVEF was 93%. Conclusions Women undergoing trastuzumab therapy for breast cancer with impaired baseline cardiac function experience no higher risk of LVEF decline, but more frequently develop symptomatic heart failure. While trastuzumab could be considered, these patients should be co-managed by a cardiologist.
| S-EPMC6201446 | biostudies-literature
Project description:ObjectiveRecent studies have reported suboptimal up-titration of heart failure (HF) therapies in patients with heart failure and a reduced ejection fraction (HFrEF). Here, we report on the achieved doses after nurse-led up-titration, reasons for not achieving the target dose, subsequent changes in left ventricular ejection fraction (LVEF), and mortality.MethodsFrom 2012 to 2018, 378 HFrEF patients with a recent (< 3 months) diagnosis of HF were referred to a specialised HF-nurse led clinic for protocolised up-titration of guideline-directed medical therapy (GDMT). The achieved doses of GDMT at 9 months were recorded, as well as reasons for not achieving the optimal dose in all patients. Echocardiography was performed at baseline and after up-titration in 278 patients.ResultsOf 345 HFrEF patients with a follow-up visit after 9 months, 69% reached ≥ 50% of the recommended dose of renin-angiotensin-system (RAS) inhibitors, 73% reached ≥ 50% of the recommended dose of beta-blockers and 77% reached ≥ 50% of the recommended dose of mineralocorticoid receptor antagonists. The main reasons for not reaching the target dose were hypotension (RAS inhibitors and beta-blockers), bradycardia (beta-blockers) and renal dysfunction (RAS inhibitors). During a median follow-up of 9 months, mean LVEF increased from 27.6% at baseline to 38.8% at follow-up. Each 5% increase in LVEF was associated with an adjusted hazard ratio of 0.84 (0.75-0.94, p = 0.002) for mortality and 0.85 (0.78-0.94, p = 0.001) for the combined endpoint of mortality and/or HF hospitalisation after a mean follow-up of 3.3 years.ConclusionsThis study shows that protocolised up-titration in a nurse-led HF clinic leads to high doses of GDMT and improvement of LVEF in patients with new-onset HFrEF.
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Project description:Aims The latest guidelines recommended to assess the trajectory of left ventricular ejection fraction (LVEF) in patients with heart failure (HF). However, there is limited data on the trajectory of LVEF in real-world settings. In this study, we investigated the frequency and prognostic implications of changes in LVEF trajectory. Methods Patients were divided into intensified LVEF, static LVEF, and worsening LVEF groups based on the transitions of HF types from baseline to follow-up. The intensified and worsening LVEF groups were further subdivided into mild (≤10% absolute changes of LVEF) and significant (>10% absolute changes of LVEF) increase or decrease groups according to the magnitude of change. The incidences and associations of changes in LVEF with patient outcomes were analyzed. Results Among the 2,429 patients in the study cohort, 38.3% of HF with reduced ejection fraction (HFrEF) and 37.6% of HF with mildly reduced ejection fraction (HFmrEF) showed an improvement in their LVEF. In contrast, a decline in LVEF was observed in 19.3% of HF patients with preserved ejection fraction (HFpEF) and 34.9% of those with HFmrEF. Cox regression analysis showed that the intensified LVEF group was associated with a lower risk of composite endpoints, while the worsening LVEF group yielded opposite findings. Subgroup analysis revealed that compared to those with mild changes in LVEF, baseline HFrEF patients with significant increase showed a lower risk of composite outcome, while baseline HFpEF patients were the opposite. Conclusions The trajectories of LVEF changes are strongly correlated with outcomes in patients with HF who had prior history of HF admission. The most significant prognostic implications observed in patients with significant LVEF changes. Trajectory LVEF and type of HF changes are useful tools recommended for prognostication.
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Project description:The purpose of this study was to evaluate whether heart failure with mildly reduced ejection fraction (HFmrEF) is associated with vascular dysfunction and whether vascular function predicts future deterioration of LVEF in patients with HFmrEF. We evaluated endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID) in 69 patients with HFmrEF and 426 patients without HF and evaluated the future deterioration of LVEF, defined as a decrease in LVEF to <40%, in 39 patients with HFmrEF for up to 3 years. Both FMD and NID were significantly lower in patients with HFmrEF than in patients without HF. We categorized patients into two groups based on low tertiles of NID: a low group (NID of <7.0%) and an intermediate and high group (NID of ≥7.0%). There were significant differences between the Kaplan-Meier curves for the deterioration of LVEF in the two groups (p < 0.01). Multivariate Cox proportional hazard analysis revealed that NID of <7.0% was an independent predictor of future deterioration of LVEF in patients with HFmrEF. Both endothelial function and vascular smooth muscle function are impaired in patients with HFmrEF compared with those in patients without HF. In addition, low NID of <7.0% predicts future deterioration of LVEF.
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Project description:Aims: Evidence-based guidelines for heart failure management depend mainly on current left ventricular ejection fraction (LVEF). However, fewer studies have examined the impact of prior LVEF. Patients may enter the heart failure with midrange ejection fraction (HFmrEF) category when heart failure with preserved ejection fraction (HFpEF) deteriorates or heart failure with reduced ejection fraction (HFrEF) improves. In this study, we examined the association between change in LVEF and adverse outcomes. Methods: HFmrEF patients with at least two or more echocardiograms 3 months apart at the First Affiliated Hospital of Dalian Medical University between September 1, 2015 and November 30, 2019 were identified. According to the prior LVEF, the subjects were divided into improved group (prior LVEF < 40%), stable group (prior LVEF between 40 and 50%), and deteriorated group (prior LVEF ≥ 50%). The primary outcomes were cardiovascular death, all-cause mortality, hospitalization for worsening heart failure, and composite event of all-cause mortality or all-cause hospitalization. Results: A total of 1,168 HFmrEF patients (67.04% male, mean age 63.60 ± 12.18 years) were included. The percentages of improved, stable, and deteriorated group were 310 (26.54%), 334 (28.60%), and 524 (44.86%), respectively. After a period of follow-up, 208 patients (17.81%) died and 500 patients met the composite endpoint. The rates of all-cause mortality were 35 (11.29%), 55 (16.47%), and 118 (22.52%), and the composite outcome was 102 (32.90%), 145 (43.41%), and 253 (48.28%) for the improved, stable, and deteriorated groups, respectively. Cox regression analysis showed that the deterioration group had higher risk of cardiovascular death (HR: 1.707, 95% CI: 1.064-2.739, P = 0.027), all-cause death (HR 1.948, 95% CI 1.335-2.840, P = 0.001), and composite outcome (HR 1.379, 95% CI 1.096-1.736, P = 0.006) compared to the improvement group. The association still remained significant after fully adjusted for both all-cause mortality (HR = 1.899, 95% CI 1.247-2.893, P = 0.003) and composite outcome (HR: 1.324, 95% CI: 1.020-1.718, P = 0.035). Conclusion: HFmrEF patients are heterogeneous with three different subsets identified, each with different outcomes. Strategies for managing HFmrEF should include previously measured LVEF to allow stratification based on direction changes in LVEF to better optimize treatment.
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Project description:Background Intracoronary physiologic indexes such as coronary flow reserve (CFR) and left ventricular ejection fraction (LVEF) have been regarded as prognostic indicators in patients with coronary artery disease. The current study evaluated the association between intracoronary physiologic indexes and LVEF and their differential prognostic implications in patients with coronary artery disease. Methods and Results A total of 1889 patients with 2492 vessels with available CFR and LVEF were selected from an international multicenter prospective registry. Baseline physiologic indexes were measured by thermodilution or Doppler methods and LVEF was recorded at the index procedure. The primary outcome was target vessel failure, which was a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization over 5 years of follow-up. Patients with reduced LVEF <50% (162 patients [8.6%], 202 vessels [8.1%]) showed a similar degree of epicardial coronary artery disease but lower CFR values than those with preserved LVEF (2.4±1.2 versus 2.7±1.2, P<0.001), mainly driven by the increased resting coronary flow. Conversely, hyperemic coronary flow, fractional flow reserve, and the degree of microvascular dysfunction were similar between the 2 groups. Reduced CFR (≤2.0) was seen in 613 patients (32.5%) with 771 vessels (30.9%). Reduced CFR was an independent predictor for target vessel failure (hazard ratio, 2.081 [95% CI, 1.385-3.126], P<0.001), regardless of LVEF. Conclusions CFR was lower in patients with reduced LVEF because of increased resting coronary flow. Patients with reduced CFR showed a significantly higher risk of target vessel failure than did those with preserved CFR, regardless of LVEF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04485234.
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Project description:Moderate aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF) constitute a clinical entity that has been proposed as a therapeutic target for transcatheter aortic valve replacement (TAVR). It is defined by a mean trans-aortic gradient between 20 and 40 mmHg and an aortic valve area between 1.0 and 1.5 cm2 in patients with LVEF < 50%. Retrospective data suggests a prevalence of 0.8% among patients referred for echocardiographic assessment. These patients are younger and show a higher frequency of previous myocardial infarction than those with severe AS randomized to TAVR in recent trials. In two retrospective studies including patients with moderate AS and reduced LVEF, a one-year mortality rate of 9 and 32% was reported, the latter in patients treated with medical therapy only during follow-up. Echocardiographic diagnosis of moderate AS poses challenges as current guidelines are directed to determine severe AS, and different presentations of moderate and mild AS have been generally neglected. Thus, the nomenclature would need to be revised and a description of possible scenarios is provided in this review. Dobutamine stress echocardiography and computed tomography are promising complementary tools. Likewise, a standardized clinical pathway is needed, in which a high level of suspicion and a low threshold for referral to a heart valve center is warranted. The Transcatheter Aortic Valve Replacement to UNload the Left ventricle in patients with Advanced heart failure (TAVR UNLOAD) trial (NCT02661451) is exploring whether TAVR would improve outcomes in patients receiving optimal heart failure therapy.
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Project description:Clinical studies on heart failure with mildly reduced left ventricular ejection fraction (HFmrEF) have gradually increased. However, studies on the prognostic differences between men and women among patients with HFmrEF are few, and no evidence on sex differences in such patients exists. Therefore, we retrospectively assessed the data of patients with HFmrEF using propensity score-matched analysis (PSMA). A total of 1691 patients with HFmrEF were enrolled in the Outcome of Discharged HFmrEF Patients study (OUDI-HF study), which included 1095 men and 596 women. After propensity score matching, we compared the difference in cardiovascular (CV) events (cardiovascular death or heart failure readmission) and all-cause mortality at 90 days and 1 year after discharge between men and women using Kaplan-Meier analysis and Cox regression. After PSMA, men with HFmrEF were 2.2 times more likely to die at 90 days than women with HFmrEF [hazard ratio (HR) 1.88; 95% confidence interval (95% CI) 1.03-3.46; P = 0.041]. However, there was no difference in the 90-day CV events (HR 0.96; 95% CI 0.75-1.22; P = 0.718). Similarly, there was no difference in all-cause mortality (HR 1.16; 95% CI 0.81-1.65; P = 0.417) and CV events (HR 0.98; 95% CI 0.83-1.16; P = 0.817) between men and women after 1 year. Among the patients with HFmrEF, men had a higher 90-day risk of all-cause mortality than women after hospital discharge, and this risk disappeared after 1 year.Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT05240118 (ESC Heart Failure. (2022). doi: https://doi.org/10.1002/ehf2.14044 ).
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