Heart failure with Preserved EF: A Bird Eye View

The concept of ‘‘diastolic’’ heart failure grew out of the observation that many patients who have the symptoms and signs of heart failure had an apparently normal left ventricular (LV) ejection fraction. Thus it was assumed that since systolic function was ‘‘pre- served’’ the problem must lie in diastole, although it is not clear by whom or when this assumption was made. Diastolic heart failure is associated with a lower annual mortality rate of approximately 8% as compared to annual mortality of 19% in heart failure with systolic dysfunction, however, morbidity rate can be substantial. Thus, diastolic heart failure is an important clinical disorder mainly seen in the elderly patients with hypertensive heart disease. Early recognition and appropriate therapy of diastolic dysfunction is advisable to prevent further progression to diastolic heart failure and death. There is no specific therapy to improve LV diastolic function directly. Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts. Nevertheless, there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and ARB as well as nitric oxide donors can be beneficial. Treatment of the underlying disease is currently the most important therapeutic approach.Keywords: diastolic heart failure; doppler echocardiography; treatment.

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Link between diabetes and diastolic dysfunction and the diagnostic role of echocardiography

Orvosi Hetilap ◽

10.1556/oh.2009.28738 ◽

2009 ◽

Vol 150 (45) ◽

pp. 2060-2067 ◽

Cited By ~ 1

Author(s):

András Nagy ◽

Zsuzsanna Cserép

Keyword(s):

Heart Failure ◽

Diastolic Dysfunction ◽

Systolic Function ◽

Diastolic Heart Failure ◽

Systolic Dysfunction ◽

Mitral Annulus ◽

Left Ventricular ◽

Diabetic Patients ◽

Doppler Study

Diabetes mellitus, a disease that has been reaching epidemic proportions, is an important risk factor to the development of cardiovascular complication. The left ventricular diastolic dysfunction represents the earliest pre-clinical manifestation of diabetic cardiomyopathy, preceding systolic dysfunction and being able to evolve to symptomatic heart failure. In early stages, these changes appear reversible with tight metabolic control, but as pathologic processes become organized, the changes are irreversible and contribute to an excess risk of heart failure among diabetic patients. Doppler echocardiography provides reliable data in the stages of diastolic function, as well as for systolic function. Combination of pulsed tissue Doppler study of mitral annulus with transmitral inflow may be clinically valuable for obtaining information about left ventricular filling pressure and unmasking Doppler inflow pseudonormal pattern, a hinge point for the progression toward advanced heart failure. Subsequently we give an overview about diabetes and its complications, their clinical relevance and the role of echocardiography in detection of diastolic heart failure in diabetes.

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Peripartum Cardiomyopathy Presenting with Predominant Left Ventricular Diastolic Dysfunction: Efficacy of Bromocriptine

Case Reports in Medicine ◽

10.1155/2012/476903 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 10

Author(s):

Piercarlo Ballo ◽

Irene Betti ◽

Giuseppe Mangialavori ◽

Leandro Chiodi ◽

Gherardo Rapisardi ◽

...

Keyword(s):

Heart Failure ◽

Diastolic Dysfunction ◽

Diastolic Function ◽

Systolic Function ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Peripartum Cardiomyopathy ◽

Lv Function ◽

Lv Diastolic Dysfunction ◽

Lv Diastolic Function

Management of patients with peripartum cardiomyopathy (PPCM) is still a major clinical problem, as only half of them or slightly more show complete recovery of left ventricular (LV) function despite conventional evidence-based treatment for heart failure. Recent observations suggested that bromocriptine might favor recovery of LV systolic function in patients with PPCM. However, no evidence exists regarding its effect on LV diastolic dysfunction, which is commonly observed in these patients. Tissue Doppler (TD) is an echocardiographic technique that provides unique information on LV diastolic performance. We report the case of a 37-year-old white woman with heart failure (NYHA class II), moderate LV systolic dysfunction (ejection fraction 35%), and severe LV diastolic dysfunction secondary to PPCM, who showed no improvement after 2 weeks of treatment with ramipril, bisoprolol, and furosemide. At 6-week followup after addition of bromocriptine, despite persistence of LV systolic dysfunction, normalization of LV diastolic function was shown by TD, together with improvement in functional status (NYHA I). At 18-month followup, the improvement in LV diastolic function was maintained, and normalization of systolic function was observed. This paper might support the clinical utility of bromocriptine in patients with PPCM by suggesting a potential benefit on LV diastolic dysfunction.

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Evaluation of Diastolic Dysfunction Using Cardiac Magnetic Resonance Imaging

European Cardiology Review ◽

10.15420/ecr.2010.6.1.21 ◽

2010 ◽

Vol 6 (1) ◽

pp. 21 ◽

Cited By ~ 2

Author(s):

Tarun Pandey ◽

Kedar Jambhekar ◽

◽

Keyword(s):

Heart Failure ◽

Cardiac Magnetic Resonance ◽

Magnetic Resonance ◽

Diastolic Dysfunction ◽

Systolic Function ◽

Diastolic Heart Failure ◽

Pulmonary Veins ◽

Left Ventricular ◽

Function Evaluation ◽

Lv Function

Left ventricular (LV) diastolic dysfunction and diastolic heart failure (DHF) account for approximately 40–50% of all patients with congestive heart failure (CHF). Diastolic dysfunction can be evaluated directly by invasive cardiac catheterisation techniques or non-invasively by transthoracic echocardiography (TTE) or cardiac magnetic resonance (CMR) imaging. Due to its high spatial and temporal resolution, CMR is the accepted gold standard for evaluating ventricular systolic function. Using the cine-phase contrast technique, CMR can interrogate inflow through the mitral valve and pulmonary veins towards evaluation of diastolic dysfunction and has shown good correlation with TTE. Additionally, CMR can evaluate direct myocardial diastolic parameters that have no echo correlate, such as diastolic torsion rate. As CMR has the ability to characterise a range of diastolic impairments, it will likely become an important diagnostic test in the future, capable of comprehensive LV function evaluation. In this article, we focus on LV diastology, and review CMR methodology and parameters for the diagnosis of diastolic dysfunction.

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Inhibition of late Na+ current, a novel target to improve diastolic function and electrical abnormalities in Dahl salt-sensitive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00863.2015 ◽

2016 ◽

Vol 310 (10) ◽

pp. H1313-H1320 ◽

Cited By ~ 1

Author(s):

Liguo Chi ◽

Luiz Belardinelli ◽

Aliya Zeng ◽

Ryoko Hirakawa ◽

Sridharan Rajamani ◽

...

Keyword(s):

Heart Failure ◽

Diastolic Dysfunction ◽

Chronic Treatment ◽

Systolic Function ◽

Diastolic Heart Failure ◽

Mitral Annulus ◽

Left Ventricular ◽

Mitral Annulus Velocity ◽

Lv Mass ◽

Lv Systolic Function

Late Na+ current ( INaL) is enhanced in myocytes of animals with chronic heart failure and patients with hypertrophic cardiomyopathy. To define the role of INaL in diastolic heart failure, the effects of GS-458967 (GS-967), a potent INaL inhibitor on mechanical and electrical abnormalities, were determined in an animal model of diastolic dysfunction. Dahl salt-sensitive (DSS) rats fed a high-salt (HS) diet for 8 wk, compared with a normal salt (NS) diet, had increased left ventricular (LV) mass (1,257 ± 96 vs. 891 ± 34 mg) and diastolic dysfunction [isovolumic relaxation time (IVRT): 26.8 ± 0.5 vs. 18.9 ± 0.2 ms; early transmitral flow velocity/early mitral annulus velocity (E/E') ratio: 25.5 ± 1.9 vs. 14.9 ± 0.9]. INaL in LV myocytes from HS rats was significantly increased to 0.41 ± 0.02 from 0.14 ± 0.02 pA/pF in NS rats. The action potential duration (APD) was prolonged to 136 ± 12 from 68 ± 9 ms in NS rats. QTc intervals were longer in HS vs. NS rats (267 ± 8 vs. 212 ± 2 ms). Acute and chronic treatment with GS-967 decreased the enhanced INaL to 0.24 ± 0.01 and 0.17 ± 0.02 pA/pF, respectively, vs. 0.41 ± 0.02 pA/pF in the HS group. Chronic treatment with GS-967 dose-dependently reduced LV mass, the increases in E/E' ratio, and the prolongation of IVRT by 27, 27, and 20%, respectively, at the 1.0 mg·kg−1·day−1 dose without affecting blood pressure or LV systolic function. The prolonged APDs in myocytes and QTc of HS rats were significantly reduced with GS-967 treatment. These results indicate that INaL is a significant contributor to the LV diastolic dysfunction, hypertrophy, and repolarization abnormalities and thus, inhibition of this current is a promising therapeutic target for diastolic heart failure.

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Modifications of Titin Contribute to the Progression of Cardiomyopathy and Represent a Therapeutic Target for Treatment of Heart Failure

Journal of Clinical Medicine ◽

10.3390/jcm9092770 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2770 ◽

Cited By ~ 1

Author(s):

Charles Tharp ◽

Luisa Mestroni ◽

Matthew Taylor

Keyword(s):

Heart Failure ◽

Dilated Cardiomyopathy ◽

Diastolic Dysfunction ◽

Therapeutic Target ◽

Systolic Function ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Post Translational Modifications ◽

Left Ventricular Dilation ◽

Molecular Springs

Titin is the largest human protein and an essential component of the cardiac sarcomere. With multiple immunoglobulin(Ig)-like domains that serve as molecular springs, titin contributes significantly to the passive tension, systolic function, and diastolic function of the heart. Mutations leading to early termination of titin are the most common genetic cause of dilated cardiomyopathy. Modifications of titin, which change protein length, and relative stiffness affect resting tension of the ventricle and are associated with acquired forms of heart failure. Transcriptional and post-translational changes that increase titin’s length and extensibility, making the sarcomere longer and softer, are associated with systolic dysfunction and left ventricular dilation. Modifications of titin that decrease its length and extensibility, making the sarcomere shorter and stiffer, are associated with diastolic dysfunction in animal models. There has been significant progress in understanding the mechanisms by which titin is modified. As molecular pathways that modify titin’s mechanical properties are elucidated, they represent therapeutic targets for treatment of both systolic and diastolic dysfunction. In this article, we review titin’s contribution to normal cardiac physiology, the pathophysiology of titin truncation variations leading to dilated cardiomyopathy, and transcriptional and post-translational modifications of titin. Emphasis is on how modification of titin can be utilized as a therapeutic target for treatment of heart failure.

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Diastolic Dysfunction- Anaesthesiologist’s Dilemma!

Journal of Anaesthesia and Critical Care Reports ◽

10.13107/jaccr.2021.v07i01.164 ◽

2021 ◽

Vol 7 (1) ◽

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Left Ventricle ◽

Diastolic Dysfunction ◽

Independent Predictor ◽

Left Ventricular Systolic Dysfunction ◽

Systolic Function ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Ventricular Compliance

Left ventricular systolic dysfunction is well recognized and ably managed by anesthesiologists. Left ventricular diastolic function needs to be reckoned as well, every single time anaesthesia is planned in a patient with cardiac disease. This article emphasizes why one should take cognizance of diastolic dysfunction during perioperative anaesthesia management. Diastolic dysfunction(DD) is the inefficiency of the left ventricle to allow filling at lower atrial pressures.[1] In other words, it is the abnormal relaxation during diastole along with the reduction in left ventricular compliance which culminates into higher filling pressures of the left ventricle.[2] It is associated with comorbid conditions such as hypertension, diabetes and atrial fibrillation. Oftentimes it is asymptomatic at rest but can manifest in stress-induced circumstances such as acute severe hypertension, tachycardia, overzealous fluid administration or arrhythmias especially atrial fibrillation.[3] Various reciprocal changes occur over time within the systolic function due to long-standing diastolic dysfunction. Also, mild to moderate diastolic dysfunction forms an independent predictor for the risk of mortality in addition to the established risk of hypertension, diabetes, coronary artery disease and advanced age.[4] It is also an independent predictor of major adverse cardiac events (MACE). (5) Most of the patients in whom anaesthesia is given for various surgical procedures have comorbidities like hypertension, diabetes, dyslipidemia, atrial fibrillation and ischemic heart disease which endure high risk for DD. They may have associated heart failure with preserved ejection fraction (HFpEF).DD can contribute to postoperative heart failure [6] and is associated with various complications in the postoperative period.[2] The act of administration of anaesthesia, mechanical ventilation and intraoperative events like tachycardia, hypertension, inordinate fluid therapy along with the overall surgic

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Diastolic dysfunction types in the prediction of viable myocardium functional recovery

Vojnosanitetski pregled ◽

10.2298/vsp0802113m ◽

2008 ◽

Vol 65 (2) ◽

pp. 113-118

Author(s):

Radomir Matunovic ◽

Zdravko Mijailovic ◽

Dragan Tavciovski ◽

Zoran Cosic ◽

Zoran Stajic

Keyword(s):

Heart Failure ◽

Diastolic Dysfunction ◽

Systolic Function ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Diastolic Filling ◽

Surgical Revascularization ◽

Medication Therapy ◽

Group I ◽

Number Of Patients

Background/Aim. It is well known that patients with coronary artery disease and viable tissue as a guarantee of contractile recovery (CR), despite of decreasing ejection fraction (EF) and systolic dysfunction, could have benefit from surgical revascularization. Therefore, relationship between diastolic filling type and early postoperative recovery and complications need to be established. The aim of this study was to investigate the relation between different left ventricular (LV) diastolic filling types and CR in patients after surgical revascularization with differently preserved systolic function. Methods. We investigated 60 patients. All of them had CR estimated by stress echocardiography regardless the extent of recovery of the heart systolic function. Echocardiographic evidence of diastolic dysfunction was estimated by Doppler examination of transmitral diastolic flow. According to the derived different diastolic filling types the patients were divided into three groups: I ? patients with disorder of LV relaxation, II ? with pseudovascularisation, and III ? with restrictive filling type, and according to the value of systolic function into two subgroups: 1) relatively recovered systolic function ? EF > 40% and 2) pronounced LV dysfunction ? EF < 40%. Echocardiographic evaluation was performed before and two week after surgical revascularization. In the preoperative period the medication therapy was optimized. We estimated CR by echocardiografic paremeters but also by detection of cardiovascular events. Results. After CABG the mean value of WMSI LV tended to decrease in any groups: in the group I (n = 12) from 1.64?0.22 to 1.34?0.22; in the group II (n = 22) from 1.85?0.16 to 1.53?0.42, and in the group III (n = 26) from 1.92?0.29 to 1.81?0.52. The lowest improvement of systolic function according to EF value expressed by the number of patients was found in the group of patients with restrictive LV filling type (12; 53.8%) as contrasting to the group with pseudonormalisation (15; 78.9%). In the group of patients with restrictive diastolic filling type also was recorded the highest number of lethal outcomes (6; 23.1%), as well as cardiovascular complications (10; 38.5%). Conclusions. Restrictive LV diastolic filling type was the marker of poor prognosis in the patients with clinical heart failure undergoing surgical revascularization. The patients with heart failure and preserved systolic function were associated with similar prognosis.

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Central and obstructive apneas prevalence in heart failure with reduced, mid-range and preserved ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.1170 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Borrelli ◽

P Sciarrone ◽

F Gentile ◽

N Ghionzoli ◽

G Mirizzi ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Left Ventricular Systolic Dysfunction ◽

Systolic Function ◽

Systolic Dysfunction ◽

Cardiopulmonary Exercise Testing ◽

Left Ventricular ◽

Apnea Hypopnea Index ◽

Preserved Ejection Fraction ◽

2D Echocardiography

Abstract Background Central apneas (CA) and obstructive apneas (OA) are highly prevalent in heart failure (HF) both with reduced and preserved systolic function. However, a comprehensive evaluation of apnea prevalence across HF according to ejection fraction (i.e HF with patients with reduced, mid-range and preserved ejection fraction- HFrEf, HFmrEF and HFpEF, respectively) throughout the 24 hours has never been done before. Materials and methods 700 HF patients were prospectively enrolled and then divided according to left ventricular EF (408 HFrEF, 117 HFmrEF, 175 HFpEF). All patients underwent a thorough evaluation including: 2D echocardiography; 24-h Holter-ECG monitoring; cardiopulmonary exercise testing; neuro-hormonal assessment and 24-h cardiorespiratory monitoring. Results In the whole population, prevalence of normal breathing (NB), CA and OA at daytime was 40%, 51%, and 9%, respectively, while at nighttime 15%, 55%, and 30%, respectively. When stratified according to left ventricular EF, CA prevalence decreased from HFrEF to HFmrEF and HFpEF: (daytime CA: 57% vs. 43% vs. 42%, respectively, p=0.001; nighttime CA: 66% vs. 48% vs. 34%, respectively, p<0.0001), while OA prevalence increased (daytime OA: 5% vs. 8% vs. 18%, respectively, p<0.0001; nighttime OA: 20 vs. 29 vs. 53%, respectively, p<0.0001). When assessing moderte-severe apneas, defined with an apnea/hypopnea index >15 events/hour, prevalence of CA was again higher in HFrEF than HFmrEF and HFpEF both at daytime (daytime moderate-severe CA: 28% vs. 19% and 23%, respectively, p<0.05) and at nighttime (nighttime moderate-severe CA: 50% vs. 39% and 28%, respectively, p<0.05). Conversely, moderate-severe OA decreased from HFrEF to HFmrEF to HFpEF both at daytime (daytime moderate-severe OA: 1% vs. 3% and 8%, respectively, p<0.05) and nighttime (noghttime moderate-severe OA: 10% vs. 11% and 30%, respectively, p<0.05). Conclusions Daytime and nighttime apneas, both central and obstructive in nature, are highly prevalent in HF regardless of EF. Across the whole spectrum of HF, CA prevalence increases and OA decreases as left ventricular systolic dysfunction progresses, both during daytime and nighttime. Funding Acknowledgement Type of funding source: None

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Long-term levosimendan treatment improves systolic function and myocardial relaxation in mice with cardiomyocyte-specific disruption of the Serca2 gene

Journal of Applied Physiology ◽

10.1152/japplphysiol.01044.2012 ◽

2013 ◽

Vol 115 (10) ◽

pp. 1572-1580 ◽

Cited By ~ 7

Author(s):

Vigdis Hillestad ◽

Frank Kramer ◽

Stefan Golz ◽

Andreas Knorr ◽

Kristin B. Andersson ◽

...

Keyword(s):

Gene Expression ◽

Heart Failure ◽

Cardiac Function ◽

Diastolic Dysfunction ◽

Systolic Function ◽

Cytosolic Calcium ◽

Left Ventricular ◽

Pressure Measurements ◽

Human Heart Failure

In human heart failure (HF), reduced cardiac function has, at least partly, been ascribed to altered calcium homeostasis in cardiomyocytes. The effects of the calcium sensitizer levosimendan on diastolic dysfunction caused by reduced removal of calcium from cytosol in early diastole are not well known. In this study, we investigated the effect of long-term levosimendan treatment in a murine model of HF where the sarco(endo)plasmatic reticulum ATPase ( Serca) gene is specifically disrupted in the cardiomyocytes, leading to reduced removal of cytosolic calcium. After induction of Serca2 gene disruption, these mice develop marked diastolic dysfunction as well as impaired contractility. SERCA2 knockout (SERCA2KO) mice were treated with levosimendan or vehicle from the time of KO induction. At the 7-wk end point, cardiac function was assessed by echocardiography and pressure measurements. Vehicle-treated SERCA2KO mice showed significantly diminished left-ventricular (LV) contractility, as shown by decreased ejection fraction, stroke volume, and cardiac output. LV pressure measurements revealed a marked increase in the time constant (τ) of isovolumetric pressure decay, showing impaired relaxation. Levosimendan treatment significantly improved all three systolic parameters. Moreover, a significant reduction in τ toward normalization indicated improved relaxation. Gene-expression analysis, however, revealed an increase in genes related to production of the ECM in animals treated with levosimendan. In conclusion, long-term levosimendan treatment improves both contractility and relaxation in a heart-failure model with marked diastolic dysfunction due to reduced calcium transients. However, altered gene expression related to fibrosis was observed.

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Abstract 16485: The Nitroxyl Donor 1-Nitrosocyclohexyl Acetate Limits Cardiac Superoxide Upregulation and Diastolic Dysfunction in a Mouse Model of Diabetic Cardiomyopathy

Circulation ◽

10.1161/circ.130.suppl_2.16485 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Rebecca H Ritchie ◽

Nga Cao ◽

Yung George Wong ◽

Sarah Rosli ◽

Helen Kiriazis ◽

...

Keyword(s):

Heart Failure ◽

Mouse Model ◽

Diastolic Dysfunction ◽

Diabetic Cardiomyopathy ◽

Ex Vivo ◽

Systolic Function ◽

Left Ventricular ◽

Cardiomyocyte Hypertrophy ◽

Lv Diastolic Dysfunction ◽

The Impact

Nitroxyl (HNO), a redox congener of NO•, is a novel regulator of cardiovascular function combining vasodilator and positive inotropic properties. Our previous studies have demonstrated these properties occur concomitantly in the intact heart; HNO moreover also exhibits antihypertrophic and superoxide-suppressing actions. HNO donors may thus offer favorable actions in heart failure. The impact of chronic HNO donor administration has however yet to be reported in this context. We tested the hypothesis that the HNO donor 1-nitrosocyclohexyl acetate (1-NCA) limits cardiomyocyte hypertrophy and left ventricular (LV) diastolic dysfunction in a mouse model of diabetic cardiomyopathy in vivo. Male 6 week-old FVB/N mice received either streptozotocin (55 mg/kg/day i.p. for 5 days, n=17), to induce type 1 diabetes, or citrate vehicle (n=16). After 4 weeks of hyperglycemia, mice were allocated to 1-NCA therapy (83mg/kg/day i.p.) or vehicle, and followed for a further 4 weeks. As shown in the table, blood glucose was unaffected by 1-NCA. LV diastolic dysfunction was evident in diabetic mice, measured as echocardiography-derived A wave velocity, deceleration time and E:A ratio; LV systolic function was preserved. Diabetes-induced diastolic dysfunction was accompanied by increased LV cardiomyocyte size, hypertrophic and pro-fibrotic gene expression, and upregulation of LV superoxide. These characteristics of diabetic cardiomyopathy were largely prevented by 1-NCA treatment. Selectivity of 1-NCA as a donor of HNO versus NO• was demonstrated by the sensitivity of the coronary vasodilation response of 1-NCA to the HNO scavenger L-cysteine (4mM), but not to the NO• scavenger hydroxocobalamin (50μM), in the normal rat heart ex vivo (n=3-7). Collectively, our studies provide the first evidence that HNO donors may represent a promising new strategy for the treatment of diabetic cardiomyopathy, and implies their therapeutic efficacy in settings of chronic heart failure.

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