Interferon-γ ablation exacerbates myocardial hypertrophy in diastolic heart failure

Diastolic heart failure (HF) accounts for up to 50% of all HF admissions, with hypertension being the major cause of diastolic HF. Hypertension is characterized by left ventricular (LV) hypertrophy (LVH). Proinflammatory cytokines are increased in LVH and hypertension, but it is unknown if they mediate the progression of hypertension-induced diastolic HF. We sought to determine if interferon-γ (IFNγ) plays a role in mediating the transition from hypertension-induced LVH to diastolic HF. Twelve-week old BALB/c (WT) and IFNγ-deficient (IFNγKO) mice underwent either saline ( n = 12) or aldosterone ( n = 16) infusion, uninephrectomy, and fed 1% salt water for 4 wk. Tail-cuff blood pressure, echocardiography, and gene/protein analyses were performed. Isolated adult rat ventricular myocytes were treated with IFNγ (250 U/ml) and/or aldosterone (1 μM). Hypertension was less marked in IFNγKO-aldosterone mice than in WT-aldosterone mice (127 ± 5 vs. 136 ± 4 mmHg; P < 0.01), despite more LVH (LV/body wt ratio: 4.9 ± 0.1 vs. 4.3 ± 0.1 mg/g) and worse diastolic dysfunction (peak early-to-late mitral inflow velocity ratio: 3.1 ± 0.1 vs. 2.8 ± 0.1). LV ejection fraction was no different between IFNγKO-aldosterone vs. WT-aldosterone mice. LV end systolic dimensions were decreased significantly in IFNγKO-aldosterone vs. WT-aldosterone hearts (1.12 ± 0.1 vs. 2.1 ± 0.3 mm). Myocardial fibrosis and collagen expression were increased in both IFNγKO-aldosterone and WT-aldosterone hearts. Myocardial autophagy was greater in IFNγKO-aldosterone than WT-aldosterone mice. Conversely, tumor necrosis factor-α and interleukin-10 expressions were increased only in WT-aldosterone hearts. Recombinant IFNγ attenuated cardiac hypertrophy in vivo and modulated aldosterone-induced hypertrophy and autophagy in cultured cardiomyocytes. Thus IFNγ is a regulator of cardiac hypertrophy in diastolic HF and modulates cardiomyocyte size possibly by regulating autophagy. These findings suggest that IFNγ may mediate adaptive downstream responses and challenge the concept that inflammatory cytokines mediate only adverse effects.

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CXCR4 Cardiac Specific Knockout Mice Develop a Progressive Cardiomyopathy

International Journal of Molecular Sciences ◽

10.3390/ijms20092267 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2267 ◽

Cited By ~ 5

Author(s):

Thomas J. LaRocca ◽

Perry Altman ◽

Andrew A. Jarrah ◽

Ron Gordon ◽

Edward Wang ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Hypertrophy ◽

Cardiac Myocytes ◽

Knockout Mice ◽

Cardiac Dysfunction ◽

Left Ventricular ◽

Subsequent Increase ◽

Transition Electron Microscopy ◽

Cardiac Phenotype

Activation of multiple pathways is associated with cardiac hypertrophy and heart failure. We previously published that CXCR4 negatively regulates β-adrenergic receptor (β-AR) signaling and ultimately limits β-adrenergic diastolic (Ca2+) accumulation in cardiac myocytes. In isolated adult rat cardiac myocytes; CXCL12 treatment prevented isoproterenol-induced hypertrophy and interrupted the calcineurin/NFAT pathway. Moreover; cardiac specific CXCR4 knockout mice show significant hypertrophy and develop cardiac dysfunction in response to chronic catecholamine exposure in an isoproterenol-induced (ISO) heart failure model. We set this study to determine the structural and functional consequences of CXCR4 myocardial knockout in the absence of exogenous stress. Cardiac phenotype and function were examined using (1) gated cardiac magnetic resonance imaging (MRI); (2) terminal cardiac catheterization with in vivo hemodynamics; (3) histological analysis of left ventricular (LV) cardiomyocyte dimension; fibrosis; and; (4) transition electron microscopy at 2-; 6- and 12-months of age to determine the regulatory role of CXCR4 in cardiomyopathy. Cardiomyocyte specific-CXCR4 knockout (CXCR4 cKO) mice demonstrate a progressive cardiac dysfunction leading to cardiac failure by 12-months of age. Histological assessments of CXCR4 cKO at 6-months of age revealed significant tissue fibrosis in knockout mice versus wild-type. The expression of atrial naturietic factor (ANF); a marker of cardiac hypertrophy; was also increased with a subsequent increase in gross heart weights. Furthermore, there were derangements in both the number and the size of the mitochondria within CXCR4 cKO hearts. Moreover, CXCR4 cKO mice were more sensitive to catocholamines, their response to β-AR agonist challenge via acute isoproterenol (ISO) infusion demonstrated a greater increase in ejection fraction, dp/dtmax, and contractility index. Interestingly, prior to ISO infusion, there were significant differences in baseline hemodynamics between the CXCR4 cKO compared to littermate controls. However, upon administering ISO, the CXCR4 cKO responded in a robust manner overcoming the baseline hemodynamic deficits reaching WT values supporting our previous data that CXCR4 negatively regulates β-AR signaling. This further supports that, in the absence of the physiologic negative modulation, there is an overactivation of down-stream pathways, which contribute to the development and progression of contractile dysfunction. Our results demonstrated that CXCR4 plays a non-developmental role in regulating cardiac function and that CXCR4 cKO mice develop a progressive cardiomyopathy leading to clinical heart failure.

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Seipin Deficiency Accelerates Heart Failure Due to Calcium Handling Abnormalities and Endoplasmic Reticulum Stress in Mice

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.644128 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiaoyue Wu ◽

Xuejing Liu ◽

Huan Wang ◽

Zihao Zhou ◽

Chengzhi Yang ◽

...

Keyword(s):

Heart Failure ◽

Endoplasmic Reticulum ◽

Cardiac Hypertrophy ◽

Er Stress ◽

Diastolic Heart Failure ◽

Left Ventricular ◽

Calcium Handling ◽

Related Factors ◽

Current Decay ◽

Protein Levels

Seipin deficiency can induce hypertrophic cardiomyopathy and heart failure, which often leads to death in humans. To explore the effects and the possible mechanisms of Seipin deficiency in myocardial remodeling, Seipin knockout (SKO) mice underwent transverse aortic constriction (TAC) for 12 weeks. We found a more severe left ventricular hypertrophy and diastolic heart failure and increases in inflammatory cell infiltration, collagen deposition, and apoptotic bodies in the SKO group compared to those in the wild type (WT) group after TAC. Electron microscopy also showed a more extensive sarcoplasmic reticulum expansion, deformation of microtubules, and formation of mitochondrial lesions in the cardiomyocytes of SKO mice than in those of WT mice after TAC. Compared with the WT group, the SKO group showed increases in endoplasmic reticulum (ER) stress-, inflammation-, and fibrosis-related gene expression, while calcium ion-related factors, such as Serca2a and Ryr, were decreased in the SKO group after TAC. Increased levels of the ER stress-related protein GRP78 and decreased SERCA2a and P-RYR protein levels were detected in the SKO group compared with the WT group after TAC. Slowing of transient Ca2+ current decay and an increased SR Ca2+ content in myocytes were detected in the cardiomyocytes of SKO mice. Adipose tissue transplantation could not rescue the cardiac hypertrophy after TAC in SKO mice. In conclusion, we found that Seipin deficiency could promote cardiac hypertrophy and diastolic heart failure after TAC in mice. These changes may be related to the impairment of myocardial calcium handling, ER stress, inflammation, and apoptosis.

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Abstract 245: Heart Failure With Preserved Ejection Fraction- a New Animal Model and a Novel Mechanistic Perspective

Circulation Research ◽

10.1161/res.121.suppl_1.245 ◽

2017 ◽

Vol 121 (suppl_1) ◽

Author(s):

Claire L Curl ◽

Vennetia R Danes ◽

James R Bell ◽

Antonia J Raaijmakers ◽

Wendy T Ip ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Diastolic Dysfunction ◽

Ventricular Myocytes ◽

Interventricular Septum ◽

Premature Mortality ◽

Left Ventricular ◽

Preserved Ejection Fraction ◽

Reduced Ejection Fraction

Diagnosis of heart failure with preserved ejection fraction (HFpEF) is becoming the prevalent form of disease type. Established treatments for heart failure with reduced ejection fraction (HFrEF) have proven minimally effective for HFpEF. This may reflect differences in underlying cardiomyocyte pathophysiology. In HFrEF cardiomyocyte phenotype is characterized by impaired contractile response and diminished systolic Ca 2+ levels. Studies of intact HFpEF-derived cardiomyocytes are lacking. Progress in understanding the etiology of HFpEF has been impeded by limited availability of appropriate pre-clinical models. Our goal was to validate and characterize a new rodent model of HFpEF, the ‘Hypertrophic Heart Rat’ (HHR), undertaking longitudinal investigations to delineate the associated cardiac and cardiomyocyte pathophysiology. The selectively inbred HHR strain exhibits adult cardiac enlargement (without hypertension) and premature mortality (40% at age 50 weeks) compared to the control ‘Normal Heart Rat’ (NHR). Echo analyses established that cardiac hypertrophy was characterized in vivo by maintained systolic parameters (i.e. ejection fraction at 85-90% control) with marked diastolic dysfunction (i.e. increased E/E’). Diastolic dysfunction was detectable in young adult HHR, as an early disease marker. Histological examination identified regions of focal reparative fibrosis in HHR hearts, most prominent in the transverse midwall area of the left ventricle adjacent to the interventricular septum. Evaluation of cardiomyocyte function using left ventricular myocytes isolated from hearts of 30 week (prefailing ) HHR revealed a hypercontractile phenotype with high Ca 2+ operational levels and arrhythmogenic vulnerability. HHR cardiomyocytes exhibited dramatically increased L-type Ca 2+ channel current density (almost 2-fold), and molecular analyses identified hyperphosphorylation of key sarcoplasmic reticulum Ca 2+ regulatory proteins, without change in total phospho-titin. These findings strongly support the contention that HFpEF and HFrEF can have different underlying cardiomyocyte phenotypes. New directions for HFpEF therapies are indicated, and the HHR provides a new model for preclinical HFpEF investigations.

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MCU Overexpression Rescues Inotropy and Reverses Heart Failure by Reducing SR Ca 2+ Leak

Circulation Research ◽

10.1161/circresaha.120.318562 ◽

2021 ◽

Author(s):

Ting Liu ◽

Ni Yang ◽

Agnieszka Sidor ◽

Brian O'Rourke

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Cardiac Function ◽

Ventricular Myocytes ◽

Interstitial Fibrosis ◽

Left Ventricular ◽

Viral Gene ◽

Adrenergic Stimulation ◽

Guinea Pig Model

Rationale: In heart failure (HF), impaired sarcoplasmic reticulum (SR) Ca 2+ release and cytosolic Na + overload depress mitochondrial Ca 2+ (mCa 2+ ) signaling, resulting in a diminished ability to maintain matrix NAD(P)H redox potential, leading to increased oxidative stress when workload increases. Enhancing mCa 2+ can reverse this defect but could potentially increase the likelihood of mitochondrial Ca 2+ overload. Objective: To determine if moderate mitochondrial Ca 2+ uniporter (MCU) overexpression has beneficial or detrimental effects on the development of HF and incident arrythmias in a guinea pig model (ACi) of HF and sudden cardiac death. Methods and Results: In vivo viral gene transfer was used to increase MCU levels by ~30% in ACi hearts. Left ventricular myocytes from hearts with MCU overexpression (ACi+MCU) displayed enhanced mCa 2+ uptake, decreased oxidative stress, and increased β‐adrenergic- and frequency-dependent augmentation of Ca 2+ transients and contractions, compared to myocytes from ACi hearts. MCU overexpression decreased SR Ca 2+ leak in the ACi group and mitigated the elevated ryanodine receptor disulfide crosslinks in HF. β‐adrenergic responses were blunted in isolated perfused ACi hearts and these deficiencies were normalized in ACI+MCU hearts. To examine the in vivo effects of MCU overexpression, ACi hearts were transduced with the MCU virus 2 3w after aortic constriction, at the onset of cardiac decompensation. Two weeks later, cardiac function worsened in the untreated ACi group (fractional shortening: 39{plus minus}1% at 2w and 32{plus minus}1% at 4w), whereas MCU overexpression significantly improved cardiac function (36{plus minus}1% at 2w and 42{plus minus}2% at 4w). MCU overexpression in the decompensating ACi heart also attenuated pulmonary edema and interstitial fibrosis and prevented triggered arrhythmias. Conclusions: Moderate MCU overexpression in failing hearts enhances contractility and responses to β-adrenergic stimulation in isolated myocytes and perfused hearts by inhibiting mitochondrial oxidative stress-induced SR Ca 2+ leak. MCU overexpression also reversed HF and inhibited ectopic ventricular arrhythmias.

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Heart Failure with Preserved Ejection Fraction – A Review

US Cardiology Review ◽

10.15420/usc.2012.9.2.90 ◽

2012 ◽

Vol 9 (1) ◽

pp. 90-95 ◽

Cited By ~ 1

Author(s):

Otto A Smiseth ◽

Anders Opdahl ◽

Espen Boe ◽

Helge Skulstad

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Diastolic Heart Failure ◽

The Elderly ◽

Left Ventricular ◽

Filling Pressure ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Reduced Ejection Fraction ◽

Objective Evidence

Heart failure with preserved left ventricular ejection fraction (HF-PEF), sometimes named diastolic heart failure, is a common condition most frequently seen in the elderly and is associated with arterial hypertension and left ventricular (LV) hypertrophy. Symptoms are attributed to a stiff left ventricle with compensatory elevation of filling pressure and reduced ability to increase stroke volume by the Frank-Starling mechanism. LV interaction with stiff arteries aggravates these problems. Prognosis is almost as severe as for heart failure with reduced ejection fraction (HF-REF), in part reflecting co-morbidities. Before the diagnosis of HF-PEF is made, non-cardiac etiologies must be excluded. Due to the non-specific nature of heart failure symptoms, it is essential to search for objective evidence of diastolic dysfunction which, in the absence of invasive data, is done by echocardiography and demonstration of signs of elevated LV filling pressure, impaired LV relaxation, or increased LV diastolic stiffness. Antihypertensive treatment can effectively prevent HF-PEF. Treatment of HF-PEF is symptomatic, with similar drugs as in HF-REF.

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The Pattern of Ventricular Remodeling Influences the Level of Oxidative Stress in Heart Failure Patients

Revista de Chimie ◽

10.37358/rc.17.7.5705 ◽

2017 ◽

Vol 68 (7) ◽

pp. 1506-1511

Author(s):

Cerasela Mihaela Goidescu ◽

Anca Daniela Farcas ◽

Florin Petru Anton ◽

Luminita Animarie Vida Simiti

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Ventricular Remodeling ◽

Clinical Laboratory ◽

Left Ventricular ◽

Control Group ◽

Reactive Protein ◽

Lv Mass ◽

Few Data

Oxidative stress (OS) is increased in chronic diseases, including cardiovascular (CV), but there are few data on its effects on the heart and vessels. The isoprostanes (IsoP) are bioactive compounds, with 8-iso-PGF25a being the most representative in vivo marker of OS. They correlate with the severity of heart failure (HF), but because data regarding OS levels in different types of HF are scarce, our study was aimed to evaluate it by assessing the urinary levels of 8-iso-PGF2aand its correlations with various biomarkers and parameters. Our prospective study included 53 consecutive patients with HF secondary to ischemic heart disease or dilative cardiomyopathy, divided according to the type of HF (acute, chronic decompensated or chronic compensated HF). The control group included 13 hypertensive patients, effectively treated. They underwent clinical, laboratory - serum NT-proBNP, creatinine, uric acid, lipids, C reactive protein (CRP) and urinary 8-iso-PGF2a and echocardiographic assessment. HF patients, regardless the type of HF, had higher 8-iso-PGF2a than controls (267.32pg/�mol vs. 19.82pg/�mol, p[0.001). The IsoP level was directly correlated with ejection fraction (EF) (r=-0.31, p=0.01) and NT-proBNP level (r=0.29, p=0.019). The relative wall thickness (RWT) was negatively correlated with IsoP (r=-0.55, p[0.001). Also 8-iso-PGF25a was higher by 213.59pg/�mol in the eccentric left ventricular (LV) hypertrophy subgroup comparing with the concentric subgroup (p=0.014), and the subgroups with severe mitral regurgitation (MR) and moderate/severe pulmonary hypertension (PAH) had the highest 8-iso-PGF2a levels. Male sex, severe MR, moderate/severe PAH, high LV mass and low RWT values were predictive for high OS level in HF patients.Eccentric cardiac remodeling, MR severity and PAH severity are independent predictors of OS in HF patients.

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Cardiac mitofusin-1 is declined in non-responding patients with idiopathic dilated cardiomyopathy

European Heart Journal ◽

10.1093/ehjci/ehaa946.3601 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

Y Hsiao ◽

I Shimizu ◽

T Wakasugi ◽

S Jiao ◽

T Watanabe ◽

...

Keyword(s):

Electron Microscopy ◽

Heart Failure ◽

Ventricular Myocytes ◽

Severe Heart Failure ◽

Left Ventricular ◽

Neonatal Rat ◽

Heart Failure Patients ◽

Underlying Mechanisms ◽

Neonatal Rat Ventricular Myocytes ◽

Mitofusin 1

Abstract Background/Introduction Mitochondria are dynamic regulators of cellular metabolism and homeostasis. The dysfunction of mitochondria has long been considered a major contributor to aging and age-related diseases. The prognosis of severe heart failure is still unacceptably poor and it is urgent to establish new therapies for this critical condition. Some patients with heart failure do not respond to established multidisciplinary treatment and they are classified as “non-responders”. The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Purpose Studies indicate mitochondrial dysfunction has causal roles for metabolic remodeling in the failing heart, but underlying mechanisms remain to be explored. This study tried to elucidate the role of Mitofusin-1 in a failing heart. Methods We examined twenty-two heart failure patients who underwent endomyocardial biopsy of intraventricular septum. Patients were classified as non-responders when their left-ventricular (LV) ejection fraction did not show more than 10% improvement at remote phase after biopsy. Fourteen patients were classified as responders, and eight as non-responders. Electron microscopy, quantitative PCR, and immunofluorescence studies were performed to explore the biological processes or molecules involved in failure to respond. In addition to studies with cardiac tissue specific knockout mice, we also conducted functional in-vitro studies with neonatal rat ventricular myocytes. Results Twenty-two patients with IDCM who underwent endomyocardial biopsy were enrolled in this study, including 14 responders and 8 non-responders. Transmission electron microscopy (EM) showed a significant reduction in mitochondrial size in cardiomyocytes of non-responders compared to responders. Quantitative PCR revealed that transcript of mitochondrial fusion protein, Mitofusin-1, was significantly reduced in non-responders. Studies with neonatal rat ventricular myocytes (NRVMs) indicated that the beta-1 adrenergic receptor-mediated signaling pathway negatively regulates Mitofusin-1 expression. Suppression of Mitofusin-1 resulted in a significant reduction in mitochondrial respiration of NRVMs. We generated left ventricular pressure overload model with thoracic aortic constriction (TAC) in cardiac specific Mitofusin-1 knockout model (c-Mfn1 KO). Systolic function was reduced in c-Mfn1 KO mice, and EM study showed an increase in dysfunctional mitochondria in the KO group subjected to TAC. Conclusions Mitofusin-1 becomes a biomarker for non-responders with heart failure. In addition, our results suggest that therapies targeting mitochondrial dynamics and homeostasis would become next generation therapy for severe heart failure patients. Funding Acknowledgement Type of funding source: None

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Inhibition of the canonical Wnt signaling pathway by a β-catenin/CBP inhibitor prevents heart failure by ameliorating cardiac hypertrophy and fibrosis

Scientific Reports ◽

10.1038/s41598-021-94169-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Thanachai Methatham ◽

Shota Tomida ◽

Natsuka Kimura ◽

Yasushi Imai ◽

Kenichi Aizawa

Keyword(s):

Heart Failure ◽

Cardiac Hypertrophy ◽

Signaling Pathway ◽

Wnt Signaling Pathway ◽

Left Ventricular ◽

Cardiac Wall ◽

Macrophage Marker ◽

Glycolysis Pathway ◽

Canonical Wnt ◽

Macrophage Accumulation

AbstractIn heart failure (HF) caused by hypertension, the myocyte size increases, and the cardiac wall thickens. A low-molecular-weight compound called ICG001 impedes β-catenin-mediated gene transcription, thereby protecting both the heart and kidney. However, the HF-preventive mechanisms of ICG001 remain unclear. Hence, we investigated how ICG001 can prevent cardiac hypertrophy and fibrosis induced by transverse aortic constriction (TAC). Four weeks after TAC, ICG001 attenuated cardiac hypertrophy and fibrosis in the left ventricular wall. The TAC mice treated with ICG001 showed a decrease in the following: mRNA expression of brain natriuretic peptide (Bnp), Klf5, fibronectin, β-MHC, and β-catenin, number of cells expressing the macrophage marker CD68 shown in immunohistochemistry, and macrophage accumulation shown in flow cytometry. Moreover, ICG001 may mediate the substrates in the glycolysis pathway and the distinct alteration of oxidative stress during cardiac hypertrophy and HF. In conclusion, ICG001 is a potential drug that may prevent cardiac hypertrophy and fibrosis by regulating KLF5, immune activation, and the Wnt/β-catenin signaling pathway and inhibiting the inflammatory response involving macrophages.

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Chronic receptor-mediated activation of Gi/o proteins alters basal t-tubular and sarcolemmal L-type Ca2+ channel activity through phosphatases in heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00589.2011 ◽

2012 ◽

Vol 302 (8) ◽

pp. H1645-H1654 ◽

Cited By ~ 10

Author(s):

Toshihide Kashihara ◽

Tsutomu Nakada ◽

Hisashi Shimojo ◽

Miwa Horiuchi-Hirose ◽

Simmon Gomi ◽

...

Keyword(s):

Heart Failure ◽

Current Density ◽

Ventricular Myocytes ◽

Heterotrimeric G Proteins ◽

Channel Activity ◽

Open Probability ◽

Current Densities ◽

Fractional Shortening ◽

Pp2a Inhibitor

L-type Ca2+ channels (LTCCs) play an essential role in the excitation-contraction coupling of ventricular myocytes. We previously found that t-tubular (TT) LTCC current density was halved by the activation of protein phosphatase (PP)1 and/or PP2A, whereas surface sarcolemmal (SS) LTCC current density was increased by the inhibition of PP1 and/or PP2A activity in failing ventricular myocytes of mice chronically treated with isoproterenol (ISO mice). In the present study, we examined the possible involvement of inhibitory heterotrimeric G proteins (Gi/o) in these abnormalities by chronically administrating pertussis toxin (PTX) to ISO mice (ISO + PTX mice). Compared with ISO mice, ISO + PTX mice exhibited significantly higher fractional shortening of the left ventricle. The expression level of Gαi2 proteins was not altered by the treatment of mice with ISO and/or PTX. ISO + PTX myocytes had normal TT and SS LTCC current densities because they had higher and lower availability and/or open probability of TT and SS LTCCs than ISO myocytes, respectively. A selective PKA inhibitor, H-89, did not affect LTCC current densities in ISO + PTX myocytes. A selective PP2A inhibitor, fostriecin, did not affect SS or TT current density in control or ISO + PTX myocytes but significantly increased TT but not SS LTCC current density in ISO myocytes. These results indicate that chronic receptor-mediated activation of Gi/o in vivo decreases basal TT LTCC activity by activating PP2A and increases basal SS LTCC activity by inhibiting PP1 without modulating PKA in heart failure.

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Abstract 18599: Clinical Assessment of Hemodynamic Profiles Predict Readmission and Mortality in Diastolic Heart Failure Patients

Circulation ◽

10.1161/circ.132.suppl_3.18599 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Mohammed Siddiqui ◽

Salpy V Pamboukian ◽

Jose A Tallaj ◽

Michael Falola ◽

Sula Mazimba

Keyword(s):

Heart Failure ◽

Clinical Assessment ◽

Diastolic Heart Failure ◽

Clinical Care ◽

Systolic Heart Failure ◽

Health Care Expenditures ◽

Left Ventricular ◽

Readmission Rates ◽

Heart Failure Patients ◽

Increased Risk

Background: Reducing 30 day readmission rates for patients with heart failure (HF) has been a recent focus of lowering health care expenditures. Hemodynamic profiles (HP) have been associated with clinical outcomes in chronic systolic HF. The relationship of HP to outcomes in acute decompensated diastolic HF (DHF) has not been defined. Methods: This case-control study of 1892 DHF patients discharged alive from an academic hospital between 2002-2012 with left ventricular function greater or equal to 45% were categorized into 4 groups: Profile A, no evidence of congestion and hypoperfusion (dry-warm); Profile B, congestion with adequate perfusion (wet-warm); Profile C, congestion with hypoperfusion (wet-cold); and Profile L, hypoperfusion without congestion (dry-cold). All cause readmissions at 30 days and 1 year and mortality at 30 days and 1 year were examined. Statistical analysis using multivariable Cox Proportional hazard model was performed adjusting for demographic, clinical, care and hospital characteristics. Results: Of the 1892 patients, 1196 (63%) were females; mean age was 68 (±14) years. There were 724(38%), 1000 (53%), 88(5%) and 80 (4%) patients in the hemodynamic profiles A, B, C and L respectively. Profiles B and C were associated with an increased risk for 30-day all-cause HF readmission compared to profiles A and L: Hazard ratio (HR) [1.38 (95% C.I 1.17-1.61)], [1.39 (95% C.I 1.18-1.62)] for B and C profiles respectively. Profiles C and L were associated with increased mortality at 1 year: HR [1.46 (95% CI 1.06-1.89)] and [1.31 (95% CI 1.01-1.64)] for A and L profiles respectively (Table). Conclusions: Clinical assessment of HP can help identify DHF patients at increased risk of readmission and mortality, similar to systolic heart failure patients.

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