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Prognostic importance of left ventricular mechanical dyssynchrony in heart failure with preserved ejection fraction.

ABSTRACT: Left ventricular mechanical dyssynchrony has been described in heart failure with preserved ejection fraction (HFpEF), but its prognostic significance is not known.Of 3445 patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, dyssynchrony analysis was performed on 424 patients (12%) by multiple speckle tracking echocardiography strain-based criteria. The primary dyssynchrony analysis was the standard deviation of the time to peak longitudinal strain (SD T2P LS). Cox proportional hazards models assessed the association of dyssynchrony with the composite outcome of cardiovascular death or heart failure hospitalization. Mean age was 70?±?10?years, LVEF was 60?±?8%, and QRS duration was 101?±?27?ms. Worse dyssynchrony, reflected in SD T2P LS, was associated with wider QRS, prior myocardial infarction, larger LV volume and mass, and worse systolic (lower LVEF and global longitudinal strain) and diastolic (lower e' and higher E/e') function. During a median follow-up of 2.6 (interquartile range 1.5-3.8) years, 107 patients experienced the composite outcome. Worse dyssynchrony was associated with the composite outcome in unadjusted analysis [hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01-1.07; P = 0.021, per 10?ms increase], but not after adjusting for clinical characteristics, or after further adjustment for LVEF, AF, NYHA class, stroke, heart rate, creatinine, haematocrit, and QRS duration (HR 1.03, 95% CI 0.99-1.06; P = 0.16, per 10?ms increase).Worse LV mechanical dyssynchrony, assessed by speckle tracking echocardiography, is not an independent predictor of adverse outcomes in HFpEF, suggesting that mechanical dyssynchrony is unlikely to be an important mechanism underlying this syndrome. These findings warrant validation in an independent study specifically designed to assess the prognostic utility of mechanical dyssynchrony in HFpEF.NCT00094302.

SUBMITTER: Biering-Sorensen T

PROVIDER: S-EPMC5544562 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Prognostic importance of left ventricular mechanical dyssynchrony in heart failure with preserved ejection fraction.

Biering-Sørensen Tor T Shah Sanjiv J SJ Anand Inder I Sweitzer Nancy N Claggett Brian B Liu Li L Pitt Bertram B Pfeffer Marc A MA Solomon Scott D SD Shah Amil M AM

European journal of heart failure 20170321 8

<h4>Aims</h4>Left ventricular mechanical dyssynchrony has been described in heart failure with preserved ejection fraction (HFpEF), but its prognostic significance is not known.<h4>Methods and results</h4>Of 3445 patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, dyssynchrony analysis was performed on 424 patients (12%) by multiple speckle tracking echocardiography strain-based criteria. The primary dyssynchron ...[more]

PMID: 28322009

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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.

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).

Project description:Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome associated with multiple pathophysiologic abnormalities, including left ventricular (LV) diastolic dysfunction, longitudinal LV systolic dysfunction, abnormal ventricular-arterial coupling, pulmonary hypertension, and right ventricular (RV) remodeling/dysfunction. However, the relative prognostic significance of each of these pathophysiologic abnormalities in HFpEF is unknown.We prospectively studied 419 patients with HFpEF using echocardiography and sphygmomanometry to assess HFpEF pathophysiologic markers. Cox proportional hazards analyses were used to determine the associations between pathophysiologic markers and outcomes. Mean age was 65±12 years; 62% were women; 39% were black; comorbidities were common; and study participants met published criteria for HFpEF. RV abnormalities were frequent: 28% had abnormal tricuspid annular plane systolic excursion, 15% had reduced RV fractional area change, and 34% had RV hypertrophy. During a median follow-up time of 18 months, 102 (24%) were hospitalized for HF and 175 (42%) experienced the composite end point of cardiovascular hospitalization or death. Decreased LV compliance, measured as reduced LV end-diastolic volume at an idealized LV end-diastolic pressure of 20 mm Hg (EDV20), and RV remodeling, as indicated by increased RV wall thickness, were the 2 pathophysiologic markers most predictive of worse outcomes: adjusted hazard ratio per 1 SD decrease in EDV20=1.39 (95% confidence interval [CI], 1.10-1.75; P=0.006), and hazard ratio per 1 SD increase in RV wall thickness=1.37 (95% CI, 1.16-1.61; P<0.001). These associations persisted after additional adjustment for markers of HF severity. By contrast, markers of LV relaxation, longitudinal LV systolic dysfunction, and ventricular-arterial coupling were not significantly associated with adverse outcomes.In patients with HFpEF, reduced LV compliance and RV remodeling are the strongest pathophysiologic predictors of adverse outcomes.

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Prognostic importance of left ventricular mechanical dyssynchrony in heart failure with preserved ejection fraction.

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Prognostic importance of left ventricular mechanical dyssynchrony in heart failure with preserved ejection fraction.

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