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Vascular Dysfunction Predicts Future Deterioration of Left Ventricular Ejection Fraction in Patients with Heart Failure with Mildly Reduced Ejection Fraction.

ABSTRACT: 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.

SUBMITTER: Kishimoto S

PROVIDER: S-EPMC8704434 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Vascular Dysfunction Predicts Future Deterioration of Left Ventricular Ejection Fraction in Patients with Heart Failure with Mildly Reduced Ejection Fraction.

Kishimoto Shinji S Maruhashi Tatsuya T Kajikawa Masato M Harada Takahiro T Yamaji Takayuki T Han Yiming Y Mizobuchi Aya A Hashimoto Yu Y Yoshimura Kenichi K Nakano Yukiko Y Chayama Kazuaki K Goto Chikara C Yusoff Farina Mohamad FM Nakashima Ayumu A Higashi Yukihito Y

Journal of clinical medicine 20211220 24

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 deterio ...[more]

PMID: 34945276

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Project description:AimsHeart failure with mildly reduced ejection fraction (HFmrEF) is associated with a favourable prognosis compared with heart failure (HF) with reduced ejection fraction (EF). We assessed whether left ventricular ejection fraction (LVEF) trajectory can be used to identify groups of patients with HFmrEF who have different clinical outcomes in a large retrospective study of patients with serial imaging.Methods and resultsPatients with HF and ≥2 echocardiograms performed ≥6 months apart were included if the LVEF measured 40-49% on the second study. Patients were classified as HFmrEF-Increasing if LVEF had increased ≥10% (n = 450), HFmrEF-Decreasing if LVEF had decreased ≥10% (n = 512), or HFmrEF-Stable if they did not meet other criteria (n = 389). The primary outcome was all-cause mortality or cardiovascular hospitalization after the second echocardiogram. Associations with time to first event were assessed with multivariable Cox analyses adjusted for age, co-morbidities, and medications. In total, 1351 patients with HFmrEF (median age 74, 64.2% male) were included with 28.8% exhibiting stable LVEF. During median follow-up of 15.3 months, the composite outcome occurred in 811 patients. During follow-up, patients with HFmrEF-Increasing were less likely to experience the primary outcome [adjusted hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.60-0.88, P < 0.001] compared with HFmrEF-Stable. Patients with HFmrEF-Decreasing were more likely to experience the composite outcome in unadjusted analyses (unadjusted HR 1.19, 95% CI 1.01-1.40, P = 0.040) but not adjusted analyses (adjusted HR 1.16, 95% CI 0.98-1.37, P = 0.092). Associations with death or HF hospitalizations were similar (HFmrEF-Increasing: adjusted HR 0.72, 95% CI 0.59-0.88, P = 0.005; HFmrEF-Decreasing: adjusted HR 1.20, 95% CI 1.01-1.44, P = 0.044). Patients with HFmrEF-Decreasing had a similar risk of the composite outcome as patients with HF with reduced EF (adjusted HR 1.03, 95% CI 0.89-1.20, P = 0.670). Patients with HFmrEF-Increasing were less likely to experience the composite outcome compared with patients with HF with preserved EF (adjusted HR 0.73, 95% CI 0.62-0.87, P < 0.001).ConclusionsAmongst patients with HFmrEF, those exhibiting positive LVEF trajectory were less likely to experience adverse outcomes after correcting for important confounders including medical therapy. Categorizing HFmrEF patients based on LVEF trajectory provides meaningful clinical information and may assist clinicians with management decisions.

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.

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.

Dataset Information

Vascular Dysfunction Predicts Future Deterioration of Left Ventricular Ejection Fraction in Patients with Heart Failure with Mildly Reduced Ejection Fraction.

Publications

Vascular Dysfunction Predicts Future Deterioration of Left Ventricular Ejection Fraction in Patients with Heart Failure with Mildly Reduced Ejection Fraction.

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