Dose-dense adjuvant Doxorubicin and cyclophosphamide is not associated with frequent short-term changes in left ventricular ejection fraction.
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ABSTRACT: Purpose
Doxorubicin and cyclophosphamide (AC) every 3 weeks has been associated with frequent asymptomatic declines in left ventricular ejection fraction (LVEF). Dose-dense (dd) AC followed by paclitaxel (P) is superior to the same regimen given every third week. Herein, we report the early cardiac safety of three sequential studies of ddAC alone or with bevacizumab (B).Patients and methods
Patients with HER2-positive breast cancer were treated on two trials: ddAC followed by P and trastuzumab (T) and ddAC followed by PT and lapatinib. Patients with HER2-normal breast cancer were treated with B and ddAC followed by B and nanoparticle albumin-bound P. Prospective LVEF measurement by multigated radionuclide angiography scan before and after every 2 week AC for 4 cycles and at month 6 from all three trials were aggregated to determine the early risks of cardiac dysfunction.Results
From January 2005 to May 2008, 245 patients were enrolled. The median age was 47 years (range, 27 to 75 years). Median LVEF pre-ddAC was 68% (range, 52% to 82%). LVEF post-ddAC was available in 241 patients (98%) and the median was unchanged at 68% (range, 47% to 81%). Per protocol no patients were ineligible for subsequent targeted biologic therapy based on LVEF decline post-ddAC. In addition, LVEF was available in 222 patients (92%) at 6 months, at which time the median LVEF was similar at 65% (range, 24% to 80%). Within 6 months of initiating chemotherapy, three patients (1.2%; 95% CI, 0.25% to 3.54%) developed CHF, all of whom received T.Conclusion
Dose-dense AC with or without concurrent bevacizumab is not associated with frequent acute or short-term declines in LVEF.
SUBMITTER: Morris PG
PROVIDER: S-EPMC3664032 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:This study sought to examine the association of a borderline left ventricular ejection fraction (LVEF) of 50% to 55% with cardiovascular morbidity and mortality in a community-based cohort.Guidelines stipulate a LVEF >55% as normal, but the optimal threshold, if any, remains uncertain. The prognosis of a "borderline" LVEF, 50% to 55%, is unknown.This study evaluated Framingham Heart Study participants who underwent echocardiography between 1979 and 2008 (n = 10,270 person-observations, mean age 60 years, 57% women). Using pooled data with up to 12 years of follow-up and multivariable Cox regression, we evaluated the associations of borderline LVEF and continuous LVEF with the risk of developing a composite outcome (heart failure [HF] or death; primary outcome) and incident HF (secondary outcome).During follow-up (median 7.9 years), HF developed in 355 participants, and 1,070 died. Among participants with an LVEF of 50% to 55% (prevalence 3.5%), rates of the composite outcome and HF were 0.24 and 0.13 per 10 years of follow-up, respectively, versus 0.16 and 0.05 in participants having a normal LVEF. In multivariable-adjusted analyses, LVEF of 50% to 55% was associated with increased risk of the composite outcome (hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.05 to 1.80) and HF (HR: 2.15; 95% CI: 1.41 to 3.28). There was a linear inverse relationship of continuous LVEF with the composite outcome (HR per 5 LVEF% decrement: 1.12; 95% CI: 1.07 to 1.16) and HF (HR per 5 LVEF% decrement: 1.23; 95% CI: 1.15 to 1.32).Persons with an LVEF of 50% to 55% in the community have greater risk for morbidity and mortality relative to persons with an LVEF >55%. Additional studies are warranted to elucidate the optimal management of these individuals.
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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:Nonischemic cardiomyopathy is a common cause of left ventricular (LV) dysfunction and myocardial fibrosis. The purpose of this study was to noninvasively evaluate changes in segmental LV extracellular volume (ECV) fraction, LV velocities, myocardial scar, and wall motion in nonischemic cardiomyopathy patients.Cardiac MRI including pre- and postcontrast myocardial T1 mapping and velocity quantification (tissue phase mapping) of the LV (basal, midventricular, and apical short axis) was applied in 31 patients with nonischemic cardiomyopathy (50±18 years). Analysis based on the 16-segment American Heart Association model was used to evaluate the segmental distribution of ECV, peak systolic and diastolic myocardial velocities, scar determined by late gadolinium enhancement, and wall motion abnormalities. LV segments with scar or impaired wall motion were significantly associated with elevated ECV (rs =0.26; P<0.001) and reduced peak systolic radial velocities (r=-0.43; P<0.001). Regional myocardial velocities and ECV were similar for patients with reduced (n=12; ECV=0.28±0.06) and preserved left ventricular ejection fraction (n=19; ECV=0.30±0.09). Patients with preserved left ventricular ejection fraction showed significant relationships between increasing ECV and reduced systolic (r=-0.19; r=-0.30) and diastolic (r=0.34; r=0.26) radial and long-axis peak velocities (P<0.001). Even after excluding myocardial segments with late gadolinium enhancement, significant relationships between ECV and segmental LV velocities were maintained indicating the potential of elevated ECV to identify regional diffuse fibrosis not visible by late gadolinium enhancement, which was associated with impaired regional LV function.Regionally elevated ECV negatively affected myocardial velocities. The association of elevated regional ECV with reduced myocardial velocities independent of left ventricular ejection fraction suggests a structure-function relationship between altered ECV and segmental myocardial function in nonischemic cardiomyopathy.
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Project description:ImportancePatients categorized as having heart failure (HF) with left ventricular ejection fraction (LVEF) in the midrange between 40% and 50% (HFmrEF) are known to be at increased risk of future events. Although patients can transition into the midrange through either improvement or deterioration in their LVEF, there is limited information available assessing the association of directional change in LVEF with future events. Understanding the association between change in LVEF and the clinical course of patients with HFmrEF would be of value in guiding management strategies.ObjectiveTo determine whether risk of clinical events experienced by patients with HFmrEF varies according to whether LVEF improved or deteriorated into the range of 40% to 50% from previous measurements.Design, setting, and participantsIn this retrospective cohort study, patients were identified from the electronic health records at the UC San Diego Health System who had an LVEF measured between 40% and 50% on transthoracic echocardiography (TTE) performed during the calendar year of 2015 and who also had at least 1 prior TTE for comparison. The clinical course of these patients was then followed from the time of the index TTE through December 2018. Data were analyzed from January to March 2019.Main outcomes and measuresThe composite of all-cause mortality and all-cause hospitalization, the composite of cardiovascular mortality and HF hospitalization, and each of the individual components.ResultsOf the 448 patients who were identified with HFmrEF, 278 (62.1%) were male, and the mean (SD) age was 67.4 (9.7) years. Left ventricular ejection fraction improved from less than 40% in 157 patients (35.0%), deteriorated from greater than 50% in 224 patients (50.0%), and remained between 40% and 50% over time in 67 patients (15.0%). Compared with patients whose LVEF improved from less than 40% to midrange levels, patients whose LVEF deteriorated from greater than 50% had higher risk of all-cause mortality and hospitalization (hazard ratio, 1.34; 95% CI, 1.10-1.82; P = .03) and of cardiovascular mortality and HF hospitalization (hazard ratio, 1.71; 95% CI, 1.08-2.50; P = .02), and these differences persisted after multivariable analysis. Outcomes did not differ significantly between patients whose LVEF improved and those in whom it remained stable.Conclusion and relevanceIn a cohort of patients with HFmrEF from a large academic medical center, the clinical course was strongly influenced by the directional change in LVEF from prior study. Patients whose LVEF deteriorated into midrange levels experienced a significantly higher risk of adverse clinical events than patients whose LVEF had improved. These results suggest that directional change in LVEF from prior measurements should be considered when devising management strategies for patients with HFmrEF.
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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:BACKGROUND AND OBJECTIVES: Little is known about the optimal echocardiographic parameters for risk stratification in stable dialysis patients with preserved left ventricular ejection fraction (LVEF) (ejection fraction ? 50%). Left ventricular (LV) global peak systolic longitudinal strain (GLS) is the ratio of the maximal change in myocardial longitudinal length in systole to the original length and reliably and accurately assesses LV function. During systole, LV myocardium in the longitudinal direction shortens and GLS is represented by a negative value. The more negative value of GLS, the better the LV function is. This study hypothesized that subtle abnormalities of GLS are associated with an adverse prognosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This prospective study collected clinical and echocardiographic data (including GLS) from 88 stable hemodialysis patients (mean age 67.0 ± 11.2 years; 35% men) with preserved LVEF. These patients were enrolled from December 2008 to January 2009 and were followed-up for 25.6 ± 9.9 months. The primary outcome was all-cause mortality. Multivariate Cox regression analysis was used to investigate risk factors for mortality. RESULTS: The mortality group (n=24) had lower albumin levels, less negative GLS, and higher prevalence of coronary artery disease and diabetes mellitus than the survival group. Using a GLS cutoff value of -15%, the less negative GLS group (GLS ?-15%) had a higher mortality rate. Cox regression analyses revealed that lower albumin level (hazard ratio, 0.16; 95% confidence interval, 0.05 to 0.53; P=0.003) and less negative GLS (hazard ratio, 3.57; 95% confidence interval, 1.41 to 9.04; P=0.01) were independent predictors of all-cause mortality. Furthermore, less negative GLS was associated with a higher cardiovascular death rate. CONCLUSIONS: Less negative GLS is predictive of poor prognosis among stable hemodialysis patients with preserved LVEF.
| S-EPMC3805079 | biostudies-other
Project description:Patients with heart failure (HF) are typically designated as having reduced or preserved ejection fraction (HFREF, HFPEF) because of the importance of left ventricular ejection fraction (LVEF) on therapeutic decisions and prognosis. Such designations are not necessarily static, yet few data exist to describe the natural history of LVEF over time.We identified 2413 patients from Kaiser Permanente Colorado with a primary discharge diagnosis of HF between January 1, 2001, and December 31, 2008, who had ?2 LVEF measurements separated by ?30 days. We used multi-state Markov modeling to examine transitions among HFREF, HFPEF, and death. We observed a total of 8183 transitions. Women were more likely than men to transition from HFREF to HFPEF (hazard ratio, 1.85; 95% confidence interval, 1.38-2.47). Patients who were adherent to ?-blockers were more likely to transition from HFREF to HFPEF (hazard ratio, 1.53; 95% confidence interval, 1.10-2.13) compared with patients who were nonadherent to ?-blockers, whereas angiotensin-converting enzyme or angiotensin II receptor blocker adherence was not associated with LVEF transitions. Patients who had a previous myocardial infarction were more likely to transition from HFPEF to HFREF (hazard ratio, 1.75; 95% confidence interval, 1.26-2.42).In this cohort of patients with HF, LVEF is a dynamic factor related to sex, coexisting conditions, and drug therapy. These findings have implications for left ventricular systolic function ascertainment in patients with HF and support evidence-based therapy use, especially ?-blockers.
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Project description:Mechanical dyssynchrony has been postulated to play a pathophysiologic role in heart failure with preserved ejection fraction (HFpEF).We quantified left ventricular (LV) systolic dyssynchrony in 130 HFpEF patients with NYHA class II-IV symptoms, ejection fraction (EF) ≥45%, and NT-proBNP levels >400 pg/mL enrolled in the PARAMOUNT trial, and compared them to 40 healthy controls of similar age and gender. Dyssynchrony was assessed by 2D speckle tracking as standard deviation (SD) of time to peak longitudinal systolic strain in 12 ventricular segments and related to measures of systolic and diastolic function. Heart failure with preserved ejection fraction patients (62% women, mean age of 71 ± 9 years, body mass index of 30.2 ± 5.9 kg/m(2), systolic blood pressure 139 ± 15 mmHg) demonstrated significantly greater dyssynchrony than controls (SD of time to peak longitudinal strain; 90.6 ± 50.9 vs. 56.4 ± 33.5 ms, P < 0.001), even in the subset of patients (n = 63) with LVEF ≥55% and narrow QRS (≤100 ms). Among HFpEF patients, dyssynchrony was related to wider QRS interval, higher LV mass, and lower early diastolic tissue Doppler myocardial velocity (E'). Greater dyssynchrony remained significantly associated with worse diastolic function even after restricting the analysis to patients with EF≥55% and adjusting for age, gender, systolic blood pressure, LV mass index, and LVEF.Heart failure with preserved EF is associated with greater mechanical dyssynchrony compared with healthy controls of similar age and gender. Within an HFpEF population, the severity of dyssynchrony is related to the width of QRS complex, LV hypertrophy, and diastolic dysfunction.
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Project description:ObjectivesTo determine clinical and prognostic differences between preserved and deteriorated systolic function (defined as left ventricular (LV) ejection fractions > or = 50% and < 50%, respectively) in patients with heart failure satisfying modified Framingham criteria.Patients and methodsRecords were studied of 1252 patients with congestive heart failure (CHF) (mean (SD) age 69.4 (11.7) years; 485 women, 767 men) who had been admitted to a cardiology service for CHF in the period 1991-2002 and whose LV systolic function had been echocardiographically evaluated within two weeks of admission. Data were collected on the main clinical findings, supplementary examinations, treatment, and duration of hospitalisation. Whether the patient was alive in the spring of 2003 was evaluated by searching the general archives of the hospital and by telephone survey.ResultsLV systolic function was preserved in 39.8% of patients. Age, female to male sex ratio, and prevalence of atrial fibrillation, valve disease, and other non-ischaemic, non-dilated cardiopathies were all significantly greater in the group with preserved systolic function. New York Heart Association functional class IV, third heart sound, jugular vein congestion, cardiomegaly, radiological signs of lung oedema, pathological Q waves, left bundle branch block, sinus rhythm, ischaemic cardiopathy, and dilated cardiomyopathy were all significantly more prevalent in the group with deteriorated systolic function, as was treatment with angiotensin converting enzyme inhibitors and most other antihypertensive drugs on discharge from hospital. There was no significant difference in survival between the groups with preserved and deteriorated systolic function (either survival regardless of age at admission or in subgroups aged < 75 and > or = 75 years at admission). In the whole group, survival rates after one, three, and five years were 84.0%, 66.7%, and 50.9%, respectively.ConclusionIn view of the poor prognosis of patients with CHF with preserved LV systolic function, who are currently treated empirically, it is to be hoped that relevant controlled clinical trials under way will afford information allowing optimisation of their treatment.
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