Myocardial Systolic and Diastolic Performance Derived by 2-Dimensional Speckle Tracking Echocardiography in Heart Failure With Normal Left Ventricular Ejection Fraction

Morris, Daniel A.; Boldt, Leif‐Hendrik; Eichstädt, H.; Özcelik, Cemil; Haverkamp, Wilhelm

doi:10.1161/circheartfailure.112.966564

Cited by 79 publications

(69 citation statements)

References 41 publications

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“…Although it did not prevent the reduced longitudinal systolic strain commonly observed in HFpEF patients,40, 41, 42 which is known to correlate with higher LV filling pressures, lower cardiac output, and worse New York Heart Association functional class,40 treatment with saxagliptin attenuated or prevented alterations to LV systolic function at the whole heart and cellular level observed in the HF group. Attenuation of the heightened contractile state often seen under resting conditions in HFpEF may be due to the preservation or improvement of normal LV diastolic cellular mechanics, myocardial collagen deposition, mitochondrial function, and cardiomyocyte diastolic function in HF‐SAX animals despite an increase in the EDPVR.…”

Section: Discussionmentioning

confidence: 83%

Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic‐Banded Mini‐Swine

Hiemstra

Lee

Chakir

et al. 2016

JAHA

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BackgroundCyclic guanosine monophosphate‐protein kinase G‐phosphodiesterase 5 signaling may be disturbed in heart failure (HF) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was to manipulate cyclic guanosine monophosphate signaling using the dipeptidyl‐peptidase 4 inhibitor saxagliptin and phosphodiesterase 5 inhibitor tadalafil. We hypothesized that preservation of cyclic guanosine monophosphate cGMP signaling would attenuate pathological cardiac remodeling and improve left ventricular (LV) function.Methods and ResultsWe assessed LV hypertrophy and function at the organ and cellular level in aortic‐banded pigs. Concentric hypertrophy was equal in all groups, but LV collagen deposition was increased in only HF animals. Prevention of fibrotic remodeling by saxagliptin and tadalafil was correlated with neuropeptide Y plasma levels. Saxagliptin better preserved integrated LV systolic and diastolic function by maintaining normal LV chamber volumes and contractility (end‐systolic pressure‐volume relationship, preload recruitable SW) while preventing changes to early/late diastolic longitudinal strain rate. Function was similar to the HF group in tadalafil‐treated animals including increased LV contractility, reduced chamber volume, and decreased longitudinal, circumferential, and radial mechanics. Saxagliptin and tadalafil prevented a negative cardiomyocyte shortening‐frequency relationship observed in HF animals. Saxagliptin increased phosphodiesterase 5 activity while tadalafil increased cyclic guanosine monophosphate levels; however, neither drug increased downstream PKG activity. Early mitochondrial dysfunction, evident as decreased calcium‐retention capacity and Complex II‐dependent respiratory control, was present in both HF and tadalafil‐treated animals.ConclusionsBoth saxagliptin and tadalafil prevented increased LV collagen deposition in a manner related to the attenuation of increased plasma neuropeptide Y levels. Saxagliptin appears superior for treating heart failure with preserved ejection fraction, considering its comprehensive effects on integrated LV systolic and diastolic function.

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Section: Discussionmentioning

confidence: 83%

Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic‐Banded Mini‐Swine

Hiemstra

Lee

Chakir

et al. 2016

JAHA

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“…While several studies have explored the prevalence of LV systolic dysfunction in HFpEF, most have been limited in their ability to evaluate strain as a discriminating feature of HFpEF due to differences in age and comorbidity status in the control group. 17,19,40 To our knowledge, this study is the largest to compare well-phenotyped elderly HFpEF patients with elderly persons in the community matched for key demographic feature and for comorbidities. LS, in addition to E/e’ ratio and LV mass index, were significantly lower in the HFpEF patients while e’ velocity was not.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with HFpEF, measures of systolic function are frequently abnormal when assessed by mitral annular systolic excursion 11,12 and velocity 12,13,14,15 , midwall fractional shortening 14,16 , and longitudinal strain. 17,18,19 Strain imaging in particular allows for quantitative assessment of myocardial deformation, 20 appears to be a less load-dependent index of systolic function than LVEF, 21 and is associated with clinical outcomes in HFrEF and LV dysfunction post-myocardial infarction. 22,23,24,25 Limited data are available regarding both the prognostic relevance of systolic dysfunction in HFpEF beyond clinical and conventional echocardiographic predictors, and the impact of treatment with an aldosterone antagonist on LV deformation.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Importance of Impaired Systolic Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone

et al. 2015

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Background Impairment in left ventricular (LV) systolic function has been described in heart failure with preserved ejection fraction (HFpEF), but its prognostic relevance is not known. We determined whether LV longitudinal strain (LS) is predictive of cardiovascular (CV) outcomes in HFpEF beyond clinical and conventional echocardiographic measures. Methods and Results LS was assessed by 2D speckle-tracking echocardiography at baseline in 447 HFpEF patients enrolled in the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. At a median follow-up of 2.6 (IQR 1.5–3.9) years, 115 patients experienced the primary composite outcome of CV death, HF hospitalization, or aborted cardiac arrest. Impaired LS, defined as an absolute LS<15.8%, was present in 52% of patients and was predictive of the composite outcome (adjusted HR 2.14, 95% CI 1.26–3.66; p=0.005), CV death alone (adjusted HR 3.20, 95% CI 1.44–7.12; p=0.004), and HF hospitalization alone (adjusted HR 2.23, 95% CI 1.16–4.28; p=0.016) after adjusting for clinical and conventional echocardiographic variables. LS was the strongest echocardiographic predictor of the composite outcome. Exploratory analysis in a subset of 131 patients with follow-up LS assessed after 12–18 months demonstrated a trend towards improvement in LS associated with spironolactone in patients enrolled in the Americas but not in Russia or Georgia. Conclusions Impaired LV systolic function is a powerful predictor of HF hospitalization, CV death, or aborted cardiac arrest in HFpEF, independent of clinical predictors. Impaired LS represents a novel imaging biomarker to identify HFpEF patients at particularly high risk for CV morbidity and mortality. Clinical Trial Registration Information Clinicaltrials.gov. Identifier NCT00094302.

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“…While there were no differences between these groups in LV mass, these data suggest those patients with elevated BNP but without CKD may represent an elderly population with a lower burden of chronic hypertensive and renal disease, yet have elevated wall stress due to mildly impaired systolic function in addition to diastolic dysfunction[15]. Although speculative, another possible explanation for their markedly elevated BNP in the absence of CKD is reduced activity of neutral endopeptidase, as seen in patients with aging[16].…”

Section: Discussionmentioning

confidence: 88%

Marked elevation of B-type natriuretic peptide in patients with heart failure and preserved ejection fraction

et al. 2014

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Marked elevations of B-type natriuretic peptide (BNP) are not generally seen in patients with heart failure and preserved ejection fraction (HFpEF). The objective of this study was to examine the clinical and laboratory characteristics of a large cohort of patients with HFpEF and markedly elevated BNP. A retrospective examination of 421 inpatients at a university hospital admitted with a diagnosis of HFpEF was performed. Clinical and echocardiographic data in 4 groups of patients with levels of BNP ≤ 100 pg/mL, 100–400 pg/mL, 400–1,000 pg/mL and > 1,000 pg/mL were compared. Patients with HFpEF and BNP > 1,000 pg/mL (28% of the population) were characterized by impaired renal function and greater use of anti-hypertensive medications. A subset of these patients with BNP > 1,000 pg/mL had normal renal function (21%) and were significantly older, more frequently female, and tended to have lower ejection fractions. Conversely, patients with HFpEF and BNP ≤ 100 pg/mL were younger and had preserved renal function. BNP was inversely related to the likelihood of subsequent admission for heart failure, but not to myocardial infarction or death. In conclusion: BNP > 1,000 pg/mL is seen in almost 1/3 of patients hospitalized with HFpEF. This elevation of BNP often reflects impaired renal function, but can also be seen in patients with preserved renal function but relatively impaired systolic function.

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Myocardial Systolic and Diastolic Performance Derived by 2-Dimensional Speckle Tracking Echocardiography in Heart Failure With Normal Left Ventricular Ejection Fraction

Cited by 79 publications

References 41 publications

Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic‐Banded Mini‐Swine

Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic‐Banded Mini‐Swine

Prognostic Importance of Impaired Systolic Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone

Marked elevation of B-type natriuretic peptide in patients with heart failure and preserved ejection fraction

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