Vascular Dysfunction Predicts Future Deterioration of Left Ventricular Ejection Fraction in Patients with Heart Failure with Mildly Reduced Ejection Fraction.
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SUBMITTER: Kishimoto S
PROVIDER: S-EPMC8704434 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Patients with recovery of left ventricular ejection fraction (LVEF) remain at risk for future deterioration of LVEF. However, there are no tools to risk stratify these patients. We hypothesized that global longitudinal strain (GLS) could predict sustained recovery within this population.We retrospectively identified 96 patients with a reduced LVEF <50% (screening echocardiogram), whose LVEF had increased by at least 10% and normalized (>50%) on evidence-based medical therapies (baseline echocardiogram). We examined absolute GLS on the baseline echocardiogram in relation to changes in LVEF on a follow-up echocardiogram. Patients with recovered LVEF had a wide range of GLS. The GLS on the baseline study correlated with the LVEF at the time of follow-up (r=0.33; P<0.001). The likelihood of having an LVEF >50% on follow-up increased by 24% for each point increase in absolute GLS on the baseline study (odds ratio, 1.24; P=0.001). An abnormal GLS (?16%) at baseline had a sensitivity of 88%, a specificity of 46%, and an accuracy of 0.67 (P<0.001) as a predictor of a decrease in LVEF >5% during follow-up. A normal GLS (>16%) on the baseline study had a sensitivity of 47%, a specificity of 83%, and an accuracy of 0.65 (P=0.002) for predicting a stable LVEF (-5% to 5%) on follow-up.In patients with a recovered LVEF, an abnormal GLS predicts the likelihood of having a decreased LVEF during follow-up, whereas a normal GLS predicts the likelihood of stable LVEF during recovery.
| S-EPMC5505492 | biostudies-literature
Project description:Left ventricular remodeling, as commonly measured by left ventricular ejection fraction (LVEF), is associated with clinical outcomes. Although change in LVEF over time should reflect response to therapy and clinical course, serial measurement of LVEF is inconsistently performed in observational settings, and the incremental prognostic value of change in LVEF has not been well characterized.The ?-Blocker Evaluation of Survival Trial measured LVEF by radionuclide ventriculography at baseline and at 3 and 12 months after randomization. We built a series of multivariable models with 16 clinical parameters plus change in LVEF for predicting 4 major clinical end points, including the trial's primary end point of all-cause mortality. Among 2484 patients with at least 1 follow-up LVEF, change in LVEF was the second most significant predictor (behind baseline creatinine) of all-cause mortality (adjusted hazard ratio for improvement in LVEF by ?5 U responder versus nonresponder [95% confidence intervals] for all-cause mortality=0.62 [0.52-0.73]). Other end points, including heart failure hospitalization or the composite of all-cause mortality and heart failure hospitalization, yielded similar results. LVEF change ?5 U was associated with a modest increase in discrimination when added to traditional predictors and was predictive of outcomes in both the bucindolol and placebo treatment groups. LVEF change as a predictor of outcomes was affected by sex and race, with evidence that LVEF improvement is associated with less survival benefit in African Americans and women.Serial evaluation for LVEF change predicts both survival and heart failure hospitalization and provides a dynamic/real-time measure of prognosis in heart failure with reduced LVEF.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000560.
| S-EPMC5082710 | biostudies-literature
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.
| S-EPMC8271074 | biostudies-literature
Project description:AIMS:Neuregulin1-? (NRG1-?) is released from microvascular endothelial cells in response to inflammation with compensatory cardioprotective effects. Circulating NRG1-? is elevated in heart failure (HF) with reduced ejection fraction (HFrEF) but not studied in HF with preserved EF (HFpEF). METHODS AND RESULTS:Circulating NRG1-? was quantified in 86 stable patients with HFpEF (EF ?45% and N-terminal pro-brain natriuretic peptide >300 ng/L), in 86 patients with HFrEF prior to and after left ventricular assist device (LVAD) and/or heart transplantation (HTx) and in 21 healthy controls. Association between NRG1-? and the composite outcome of all-cause mortality/HF hospitalization in HFpEF and all-cause mortality/HTx/LVAD implantation in HFrEF with and without ischaemia assessed as macrovascular coronary artery disease was assessed. In HFpEF, median (25th-75th percentile) NRG1-? was 6.5 (2.1-11.3) ng/mL; in HFrEF, 3.6 (2.1-7.6) ng/mL (P = 0.035); after LVAD, 1.7 (0.9-3.6) ng/mL; after HTx 2.1 (1.4-3.6) ng/mL (overall P < 0.001); and in controls, 29.0 (23.1-34.3) ng/mL (P = 0.001). In HFrEF, higher NRG1-? was associated with worse outcomes (hazard ratio per log increase 1.45, 95% confidence interval 1.04-2.03, P = 0.029), regardless of ischaemia. In HFpEF, the association of NRG1-? with outcomes was modified by ischaemia (log-rank P = 0.020; Pinteraction = 0.553) such that only in ischaemic patients, higher NRG1-? was related to worse outcomes. In contrast, in patients without ischaemia, higher NRG1-? trended towards better outcomes (hazard ratio 0.71, 95% confidence interval 0.48-1.05, P = 0.085). CONCLUSIONS:Neuregulin1-? was reduced in HFpEF and further reduced in HFrEF. The opposing relationships of NRG1-? with outcomes in non-ischaemic HFpEF compared with HFrEF and ischaemic HFpEF may indicate compensatory increases of cardioprotective NRG1-? from microvascular endothelial dysfunction in the former (non-ischaemic HFpEF), but this compensatory mechanism is overwhelmed by the presence of ischaemia in the latter (HFrEF and ischaemic HFpEF).
| S-EPMC7160501 | biostudies-literature
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.
| S-EPMC8364975 | biostudies-literature
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.
| S-EPMC6107690 | biostudies-literature
Project description:BackgroundDecompensated heart failure may present with severe hypertension in patients with preserved (PreEF) or reduced left ventricular (LV) ejection fraction (RedEF) and is clinically indistinguishable. Previously, we demonstrated that arterial pressure elevation increases LV filling pressures in a canine model of chronic LV dysfunction with PreEF or RedEF. It is not clear whether any differences in hemodynamics, LV volume or performance, or diastolic function can be demonstrated between canines with PreEF or RedEF in response to arterial pressure elevation. We hypothesized that the LV systolic, diastolic, and hemodynamic response to pressure loading would be similar in RedEF or PreEF.MethodsWe studied 25 dogs with chronic LV dysfunction due to coronary microsphere embolization with RedEF (35 +/- 4%) and 20 dogs with PreEF (50 +/- 3%). Arterial pressure was increased with methoxamine infusion and hemodynamics and echo-Doppler parameters of LV size, function, transaortic and transmitral pulsed Doppler prior to and with methoxamine infusion was obtained.ResultsThough LV filling pressures were similar at baseline, LV size was larger (p < 0.01) and ejection fraction lower in dogs with RedEF (p < 0.001). With methoxamine, there were similar increases in LV size, LV pressures, and index of myocardial performance with the ejection fraction reduced similarly. Diastolic parameters demonstrated similar tau increases, E/A reduction, and diastolic filling shortening in RedEF and PreEF dogs. A similar extent of isovolumic contraction and relaxation times and index of myocardial performance prolongation occurred with pressure loading.ConclusionPressure loading in a canine model of LV dysfunction with PreEF and RedEF resulted in similar degrees of LV dilatation, increased filling pressures, and increased index of myocardial performance.
| S-EPMC2626582 | biostudies-literature
Project description:AimsTwo key echocardiographic parameters that are currently used to diagnose heart failure (HF) with preserved ejection fraction (HFpEF) are left atrial volume index (LAVi) and left ventricular mass index (LVMi). We investigated whether patients' characteristics, biomarkers, and co-morbidities are associated with these parameters and whether the relationships differ between patients with HFpEF or HF with reduced ejection fraction (HFrEF).MethodsWe consecutively enrolled 831 outpatients with typical signs and symptoms of HF and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels and categorized patients based upon left ventricular ejection fraction (LVEF): LVEF < 40% (HFrEF), LVEF between 40% and 50% (HF with mid-range ejection fraction), and LVEF ≥ 50% (HFpEF). The study includes consecutively enrolled HF patients from an HF outpatient clinic at a tertiary medical centre in the Netherlands. All patients underwent baseline characterization, laboratory measurements, and echocardiography.ResultsFour hundred sixty-nine patients had HFrEF, 189 HF with mid-range ejection fraction, and 173 HFpEF. The patients with HFrEF were rather male [HFrEF: 323 (69%); HFpEF: 80 (46%); P < 0.001], and the age was comparable (HFrEF 67 ± 13; HFpEF 70 ± 14; P = 0.069). In HFpEF, more patients had hypertension [190 (40.5%); 114 (65.9%); P < 0.001], higher body mass indices (27 ± 8; 30 ± 7; P < 0.001), and atrial fibrillation [194 (41.4); 86 (49.7); P = 0.029]. The correlation analyses showed that in HFrEF patients, LAVi was significantly associated with age (β 0.293; P < 0.001), male gender (β 0.104; P = 0.042), body mass index (β -0160; P = 0.002), diastolic blood pressure (β -0.136; P < 0.001), New York Heart Association (β 0.174; P = 0.001), atrial fibrillation (β 0.381; P < 0.001), galectin 3 (β 0.230; P < 0.001), NT-proBNP (β 0.183; P < 0.001), estimated glomerular filtration rate (β -0.205; P < 0.001), LVEF (β -0.173; P = 0.001), and LVMi (β 0.337; P < 0.001). In HFpEF patients, only age (β 0.326; P < 0.001), atrial fibrillation (β 0.386; P < 0.001), NT-proBNP (β 0.176; P = 0.036), and LVMi (β 0.213; P = 0.013) were associated with LAVi.ConclusionsAlthough LVMi and LAVi are hallmark parameters to diagnose HFpEF, they only correlate with a few characteristics of HF and mainly with atrial fibrillation. In contrast, in HFrEF patients, LAVi relates strongly to several other HF parameters. These findings underscore the complexity in visualizing the pathophysiology of HFpEF and question the relation between cardiac structural remodeling and the impact of co-morbidities.
| S-EPMC8318400 | biostudies-literature
Project description:BackgroundExercise capacity is a powerful predictor of all-cause mortality. The duration of exercise with treadmill stress testing is an important prognostic marker in both healthy subjects and patients with cardiovascular disease. Left ventricular (LV) structure is known to adapt to sustained changes in level of physical activity.HypothesisPoor exercise capacity in patients with a preserved LV ejection fraction (LVEF) should be reflected in smaller LV dimensions, and a normal exercise capacity should be associated with larger LV dimensions, irrespective of comorbidities.MethodsThis hypothesis was first tested in a cross-sectional analysis of 201 patients with normal chamber dimensions and preserved LVEF who underwent a clinically indicated treadmill stress echocardiogram using the Bruce protocol (derivation cohort). The best LV dimensional predictor of exercise capacity was then tested in 1285 patients who had a Bruce-protocol treadmill exercise stress test and a separate transthoracic echocardiogram (validation cohort).ResultsIn the derivation cohort, there was a strong positive relationship between exercise duration and LV end-diastolic volume deciles (r 2 = 0.85; P < 0.001). Regression analyses of several LV dimensional parameters revealed that the body surface area-based LV end-diastolic volume index was best suited to predict exercise capacity (P < 0.0001). In a large validation cohort, LV end-diastolic volume was confirmed to predict exercise capacity (P < 0.0001).ConclusionsAmong patients referred for outpatient stress echocardiography who have a preserved LVEF and no evidence of myocardial ischemia, we found a strong positive association between LV volume and exercise capacity.
| S-EPMC6489861 | biostudies-literature