Heart failure with preserved ejection fraction

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Michelle M.; Lee, Christopher S.; Link, Mark S.; Milano, Carmelo A.; Nnacheta, Lorraine C.; Sandhu, Alexander T.; Stevenson, Lynne Warner; Vardeny, Orly; Vest, Amanda R.; Yancy, Clyde W.; Beckman, Joshua A.; O'Gara, Patrick T.; Al-Khatib, Sana M.; Armbruster, Anastasia L.; Birtcher, Kim K.; Cigarroa, Joaquin E.; de las Fuentes, Lisa; Deswal, Anita; Dixon, Dave L.; Fleisher, Lee A.; Gentile, Federico; Goldberger, Zachary D.; Gorenek, Bulent; Haynes, Norrisa; Hernandez, Adrian F.; Hlatky, Mark A.; Joglar, José A.; Jones, W. Schuyler; Marine, Joseph E.; Mark, Daniel B.; Mukherjee, Debabrata; Palaniappan, Latha P.; Piano, Mariann R.; Rab, Tanveer; Spatz, Erica S.; Tamis-Holland, Jacqueline E.; Wijeysundera, Duminda N.; Woo, Y. Joseph (May 2022). "2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure".

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is therefore independent of left ventricular systolic function. A leftward shift of the end-diastolic pressure-volume relationship (i.e. decreased left ventricular distensibility) can occur both in those with normal and those with decreased left ventricular systolic function. Likewise, heart failure may occur in those with dilated left ventricular and normal systolic function. This is often seen in valvular heart disease and high-output heart failure. Neither of these situations constitutes a diastolic heart failure.

849:. The benefit patients seem to derive from exercise does not seem to be a direct cardiac effect, but rather is due to changes in peripheral vasculature and skeletal muscle, which show abnormalities in HFpEF patients. A two-year exercise trial on otherwise-healthy middle-aged adults having HFpEF showed improved cardiac function, and regular exercise was recommended to prevent future risk of HFpEF. 458: 40: 516: 816:

Specific aspects of therapeutics should be avoided in HFpEF to prevent the deterioration of the condition. Considerations that are generalizable to heart failure include avoidance of a fast heart rate, elevations in blood pressure, development of ischemia, and atrial fibrillation. Considerations more

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which is significantly associated with increased morbidity and mortality. Left atrial and pulmonary venous pressure increases in HFpEF due to diastolic insufficiency thus increasing pulmonary artery pressure. In patients with advanced HFpEF changes in the pulmonary vasculature may develop, leading to

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Heidenreich, Paul A.; Bozkurt, Biykem; Aguilar, David; Allen, Larry A.; Byun, Joni J.; Colvin, Monica M.; Deswal, Anita; Drazner, Mark H.; Dunlay, Shannon M.; Evers, Linda R.; Fang, James C.; Fedson, Savitri E.; Fonarow, Gregg C.; Hayek, Salim S.; Hernandez, Adrian F.; Khazanie, Prateeti; Kittleson,

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level in the presence of normal ejection fraction to diagnose diastolic heart failure. Concordance of both volumetric and biochemical measurements and markers lends to even stronger terminology regarding scientific/mathematical expression of diastolic heart failure. These are both probably too broad

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at right side) and the blood passes from the atria into the ventricles. First, ventricles are filled by a pressure gradient but near the end, atria contract (atrial kick) and force more blood to pass into ventricles. Atrial contraction is responsible for around 20% of the total filling blood volume.

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play a rather obscure role in HFpEF treatment, though there is suggestion of a beneficial role in patient management. Evidence from a meta-analysis demonstrated significant reductions in all-cause mortality with beta-blocker therapy, though overall effects were driven largely by small, older trials

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function during exercise. This is undertaken because perturbations in diastole are exaggerated during the increased demands of exercise. Exercise requires increased left ventricular filling and subsequent output. Typically the heart responds by increasing heart rate and relaxation time. However, in

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Although the term diastolic heart failure is often used when there are signs and symptoms of heart failure with normal left ventricular systolic function, this is not always appropriate. Diastolic function is determined by the relative end diastolic volume in relation to end diastolic pressure, and

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It may be misguided to classify the volume-overloaded heart as having diastolic dysfunction if it is behaving in a stiff and non-compliant manner. The term diastolic dysfunction should not be applied to the dilated heart. Dilated ("remodeled") hearts have increased volume relative to the amount of

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deposition and infiltration of the myocardium. These influences collectively lead to a decrease in distensibility and elasticity (ability to stretch) of the myocardium. As a consequence, cardiac output becomes diminished. When the left ventricular diastolic pressure is elevated, venous pressure in

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alterations in HFpEF are the predominating factor in impaired cardiac function and subsequent clinical presentation. Diastolic dysfunction is multifaceted, and a given patient may express diverse combinations of the following: incomplete myocardial relaxation, impaired rate of ventricular filling,

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have been demonstrated to show increased diameter without an increase in length; this is consistent with observed concentric ventricular hypertrophy and increased left ventricular mass. HFrEF cardiomyocytes exhibit the opposite morphology; increased length without increased cellular diameter. This

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Though HFpEF is characterized by a normal ejection fraction, this parameter is a rather poor index of the heart's contractile function. Some studies have shown that metrics of load independent contractility (such as left ventricular stiffness) reveal diminished systolic function in HFpEF patients

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The progression of HFpEF and its clinical course is poorly understood in comparison to HFrEF. Despite this, patients with HFrEF and HFpEF appear to have comparable outcomes in terms of hospitalization and mortality. Causes of death in patients vary substantially. However, among patients in more

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are applied to good effect in HFrEF but are largely ineffective at reducing morbidity and mortality in HFpEF. Many of these therapies are effective in reducing the extent of cardiac dilation and increasing ejection fraction in HFrEF patients. It is unsurprising they fail to effect improvement in

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Grade II diastolic dysfunction is called "pseudonormal filling dynamics". This is considered moderate diastolic dysfunction and is associated with elevated left atrial filling pressures. These patients more commonly have symptoms of heart failure, and many have left atrial enlargement due to the

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pre-capillary pulmonary hypertension. Right ventricular dysfunction is also common in HFpEF patients, occurring in 20-35% of patients. This right ventricular dysfunction is more common in patients with more advanced HFpEF as well as those with pulmonary hypertension and lower ejection fractions.

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The presence of either class III and IV diastolic dysfunction is associated with a significantly worse prognosis. These patients will have left atrial enlargement, and many will have a reduced left ventricular ejection fraction that indicates a combination of systolic and diastolic dysfunction.

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There are four basic echocardiographic patterns of diastolic heart failure, which are graded I to IV. Grade III and IV diastolic dysfunction are called "restrictive filling dynamics"; they are both severe forms of diastolic dysfunction, and patients tend to have advanced heart failure symptoms.

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Criteria for diagnosis of diastolic dysfunction or diastolic heart failure remain imprecise. This has made it difficult to conduct valid clinical trials of treatments for diastolic heart failure. The problem is compounded by systolic and diastolic heart failure commonly coexisting when patients

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Diastolic dysfunction must be differentiated from diastolic heart failure. Diastolic dysfunction can be found in elderly and apparently quite healthy patients. If diastolic dysfunction describes an abnormal mechanical property, diastolic heart failure describes a clinical syndrome. Mathematics

253:, as well as a microscopic level. It is thought that increased pressure, in concert with a pro-inflammatory state (insulin resistance, obesity), encourage ventricular stiffening and remodeling that lead to poor cardiac output seen in HFpEF. There changes are a result of left ventricular muscle 1038:

The use of a self-expanding device that attaches to the external surface of the left ventricle has been suggested. When the heart muscle squeezes, energy is loaded into the device, which absorbs the energy and releases it to the left ventricle in the diastolic phase. This helps retain muscle

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conditions or those who are suspected to have HFpEF but lack clear non-invasive findings. Catheterization does represent are more definitive diagnostic assessment as pressure and volume measurements are taken simultaneously and directly. In either technique, the heart is evaluated for left

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No single echocardiographic parameter can confirm a diagnosis of diastolic heart failure. Multiple echocardiographic parameters have been proposed as sufficiently sensitive and specific, including mitral inflow velocity patterns, pulmonary vein flow patterns, E/A reversal, tissue Doppler

813:, coronary artery disease, hypertension, and hyperlipidemia. There are particular factors unique to HFpEF that must be accounted for with therapy. Randomized clinical trials addressing the therapeutic adventure for these conditions in HFpEF have found conflicting or limited evidence. 3564:

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compared to healthy controls, and are corroborated by tissue Doppler findings that reveal changes in longitudinal contraction and motion abnormalities. While these systolic impairments may be minimal at rest, they become more exaggerated with increased demand, as seen in exercise.

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reduction. As patients display normal ejection fraction but reduced cardiac output they are especially sensitive to changes in preloading and may rapidly display signs of output failure. This means administration of diuretics and vasodilators must be monitored carefully.

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a definition for diastolic heart failure, and this group of patients is more precisely described as having heart failure with normal systolic function. Echocardiography can be used to diagnose diastolic dysfunction but is a limited modality unless it is supplemented by

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Solomon SD, Janardhanan R, Verma A, Bourgoun M, Daley WL, Purkayastha D, et al. (June 2007). "Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial".

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may occur, leading to scarring and increased interstitial collagen. Fibrotic changes in HFpEF are more variable. Though there is typically an increased amount of collagen observed in these patients it is usually not dramatically different from healthy individuals.

284:. Ischemia may manifest in distinct ways, either as a result of increasing tissue oxygen demand, or diminished ability of the heart to supply oxygen to the tissue. The former is the result of stress, such as exercise, while the latter is the result of reduced 570:(In atrial fibrillation, this additional 20% filling volume is lost and the patient may experience systolic heart failure symptoms). Complete left ventricular filling is essential to maintain maximum cardiac output. Left ventricular filling is dependent upon 504:

lungs must also become elevated too: left ventricular stiffness makes it more difficult for blood to enter it from the left atrium. As a result, pressure rises in the atrium and is transmitted back to the pulmonary venous system, thereby increasing its

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effect of beta blockers may enable improved filling, reduce myocardial oxygen demand, and lower blood pressure. However, this effect also can contribute to diminished response to exercise demands and can result in an excessive reduction in heart rate.

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Despite increasing incidence of HFpEF effective inroads to therapeutics have been largely unsuccessful. Currently, recommendations for treatment are directed at symptom relief and co-morbid conditions. Frequently this involves administration of

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In patients with HFpEF, SGLT2 inhibitors carry a class 2a recommendation according to the 2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure as a potentially beneficial treatment for reducing HF hospitalizations and CV mortality.

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Patients with HFpEF poorly tolerate stress, particularly hemodynamic alterations of ventricular loading or increased diastolic pressures. Often there is a more dramatic elevation in systolic blood pressure in HFpEF than is typical of HFrEF.

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present with many ischemic and nonischemic etiologies of heart failure. Narrowly defined, diastolic failure has often been defined as "heart failure with normal systolic function" (i.e. left ventricular ejection fraction of 60% or more).

578:, mitral valve area, atrio-ventricular gradient, atrial contraction and end-systolic volume. Diastole has four phases: isovolumetric relaxation, rapid filling, diastasis and atrial contraction. All of these phases can be evaluated by 890:

is employed, but does not have a proven benefit in HFpEF patients. Caution is required with use of diuretics or other therapies that can alter loading conditions or blood pressure. It is not recommended that patients be treated with

652:, skeletal muscle metabolism and in fat distribution and character throughout the body. The importance of these changes is demonstrated in that stable, non-decompensated patients seem to benefit from exercise; specifically increased 78:– the percentage of the volume of blood ejected from the left ventricle with each heartbeat divided by the volume of blood when the left ventricle is maximally filled – is normal, defined as greater than 50%; this may be measured by 494:

Diastolic failure is characterized by an elevated diastolic pressure in the left ventricle, despite an essentially normal/physiologic end diastolic volume (EDV). Histological evidence supporting diastolic dysfunction demonstrates

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Until recently, it was generally assumed that the prognosis for individuals with diastolic dysfunction and associated intermittent pulmonary edema was better than those with systolic dysfunction. However, in two studies in the

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Regularly assessment of patients allows determination of progression of the condition, response to interventions, and need for alteration of therapy. Ability to perform daily tasks, hemodynamic status, kidney function,

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Stiffening of the left ventricle contributes to heart failure with preserved ejection fraction, a condition that can be prevented by four exercise sessions/week or more (more than casual exercise) throughout adulthood.

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Class III diastolic dysfunction patients will demonstrate reversal of their diastolic abnormalities on echocardiogram when they perform the Valsalva maneuver. This is referred to as "reversible restrictive diastolic

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Parra-Lucares, Alfredo; Romero-Hernández, Esteban; Villa, Eduardo; Weitz-Muñoz, Sebastián; Vizcarra, Geovana; Reyes, Martín; Vergara, Diego; Bustamante, Sergio; Llancaqueo, Marcelo; Toro, Luis (27 December 2022).

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and exercise tolerance. However, this benefit appears to be derived from changes in muscle and vasculature as opposed to directly on the heart, which displays minimal change in output following exercise training.

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describing the relationship between the ratio of Systole to Diastole in accepted terms of End Systolic Volume to End Diastolic Volume implies many mathematical solutions to forward and backward heart failure.

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Aronow WS, Kronzon I (March 1993). "Effect of enalapril on congestive heart failure treated with diuretics in elderly patients with prior myocardial infarction and normal left ventricular ejection fraction".

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as of 2008. Trials were in progress of the ImCardia (implanted at the level of the pericardium) and the CORolla transapical approach device (CORolla TAA; implanted at the level of the endocardium) as of 2023

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In this condition, called diastolic heart failure, the volume of blood contained in the ventricles during diastole is lower than it should be, and the pressure of the blood within the chambers is elevated.

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Lam, C. S., Donal, E., Kraigher‐Krainer, E., & Vasan, R. S. (2011). Epidemiology and clinical course of heart failure with preserved ejection fraction. European journal of heart failure, 13(1), 18-28.

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Diverse mechanisms contribute to the development of HFpEF, many of which are under-investigated and remain obscure. Despite this, there are clear risk factors that contribute to the development of HFpEF.

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has been hypothesized to contribute to the increase in HFpEF observed amongst post-menopausal women. Animal studies show that even at a young age, a decline in estrogen leads to changes in expression of

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level or heart failure admission within 1 year, eGFR > 30 mL/min/1.73 m2, creatinine < 2.5 ml/dL, potassium < 5.0 mEq/L). Monitoring of serum potassium levels and kidney function, specifically

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HFpEF patients, given their un-dilated phenotype and relative normal ejection fraction. Understanding and targeting mechanisms unique to HFpEF are thus essential to the development of therapeutics.

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measurements, and M-mode echo measurements (i.e. of left atrial size). Algorithms have also been developed which combine multiple echocardiographic parameters to diagnose diastolic heart failure.

2707: 194:, and sedentary lifestyle have been identified as important risk factors for diverse types of heart disease including HFpEF. There is mechanistic and epidemiological evidence for a link between 705:

A patient is said to have diastolic dysfunction if they have signs and symptoms of heart failure but the left ventricular ejection fraction is normal. A second approach is to use an elevated

3567:"2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines" 690:

patients with HFpEF both responses are diminished due to increased ventricular stiffness. Testing during this demanding state may reveal abnormalities that are not as discernible at rest.

408:, characterized by an increase in cardiac chamber size without an accompanying increase in wall thickness. This leads to a corresponding increase in left ventricular end diastolic volume. 404:. This leads to increased left ventricular mass and is typically accompanied by a normal, or slightly reduced, end diastolic filling volume. Conversely, HFrEF is typically associated with 1853:"Cardiac Left Ventricular miRNA-26a Is Downregulated in Ovariectomized Mice, Upregulated upon 17-Beta Estradiol Replacement, and Inversely Correlated with Collagen Type 1 Gene Expression" 745:

Class IV diastolic dysfunction patients will not demonstrate reversibility of their echocardiogram abnormalities, and are therefore said to have "fixed restrictive diastolic dysfunction".

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decreased) distensibility. The term diastolic dysfunction is sometimes erroneously applied in this circumstance, when increased fluid volume retention causes the heart to be over-filled (

636:, is present in up to 58% of HFpEF patients. However, dyssynchrony is also common in HFrEF and its role in HFpEF in particular remains obscure. While therapies for dyssynchrony, such as 3515:"Low-sodium dietary approaches to stop hypertension diet reduces blood pressure, arterial stiffness, and oxidative stress in hypertensive heart failure with preserved ejection fraction" 861:

levels are important parameters. Behavioral management is important in these patients and it is recommended that individuals with HFpEF avoid alcohol, smoking, and high sodium intake.

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In diastolic heart failure, the volume of blood contained in the ventricles during diastole is lower than it should be, and the pressure of the blood within the chambers is elevated.

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Gielen S, Laughlin MH, O'Conner C, Duncker DJ (January–February 2015). "Exercise training in patients with heart disease: review of beneficial effects and clinical recommendations".

1286:"2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines" 981:

but under control to avoid hypotension. ACE inhibitors do not appear to improve morbidity or mortality associated with HFpEF alone. However, they are important in the management of

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Newer echocardiographic techniques such as speckle tracking for strain measurement, particularly for the left atrium, are becoming increasingly utilised for the diagnosis of HFpEF.

2472:"Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations" 782:, which is the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E'). Diastolic dysfunction is assumed when the E/E' ratio exceed 15. 4865: 233:

and thus ventricular stiffening. Cardiac macrophages are thought to play an important role in the development of fibrosis as they are increased in HFpEF and release pro-fibrotic

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In those with HFpEF, the left ventricle of the heart (large chamber on right side of the picture) is stiffened and has impaired relaxation after pumping blood out of the heart.

2989:"Effect of endurance training on the determinants of peak exercise oxygen consumption in elderly patients with stable compensated heart failure and preserved ejection fraction" 1054: 620:. A significant portion (55-77%) of HFpEF patients are unable to increase heart rate to compensate for increased output demand (as in the setting of exercise); this is termed 3792:

Klingbeil AU, Schneider M, Martus P, Messerli FH, Schmieder RE (July 2003). "A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension".

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Grade I diastolic dysfunction, the mildest form, is called an "abnormal relaxation pattern". On the mitral inflow Doppler echocardiogram, there is reversal of the normal

1912:"Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology" 825:

HFrEF and HFpEF represent distinct entities in terms of development and effective therapeutic management. Specifically, cardiac resynchronization, administration of

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Diastolic failure appears when the ventricle cannot be filled properly because it cannot relax because its wall is thick or rigid. This situation presents usually a

124:, which causes a decrease in left ventricular relaxation during diastole, with resultant increased pressure and/or impaired filling. There is an increased risk for 3038:

Erdei T, Aakhus S, Marino P, Paulus WJ, Smiseth OA, Fraser AG (September 2015). "Pathophysiological rationale and diagnostic targets for diastolic stress testing".

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Borlaug BA, Lam CS, Roger VL, Rodeheffer RJ, Redfield MM, et al. (Task Force sullo Scompenso Cardiaco Acuto della Società Europea di Cardiologia) (July 2009).

1966:"Contractility and ventricular systolic stiffening in hypertensive heart disease insights into the pathogenesis of heart failure with preserved ejection fraction" 351:

Any condition or process that leads to stiffening of the left ventricle can lead to diastolic dysfunction. Other causes of left ventricular stiffening include:

308:, and diastolic dysfunction are characteristic of both processes. It has been suggested that HFpEF merely represents an acceleration of a normal aging process. 874:

Management of HFpEF is primarily dependent on the treatment of symptoms and exacerbating conditions. The role of specific treatments for diastolic dysfunction

773:. Decline of ejection fraction paired with decline of E/A ratio seems a stronger argument in support of a mathematical definition of diastolic heart failure. 1327:"Temporal relationship and prognostic significance of atrial fibrillation in heart failure patients with preserved ejection fraction: a community-based study" 217:

activity. As protein kinase G activity diminishes, cardiomyocytes undergo hypertrophic changes. Endothelial cells also are responsible for the production of

87: 444:). While early stage HFrEF is associated with a significant disruption of extracellular matrix proteins initially, as it progresses fibrotic replacement of 3650:"Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS)" 358:

of any cause where the ventricular muscle becomes hypertrophied, and thence stiff, as a result of the increased pressure load placed on it by the stenosis.

4506: 3606:"Effects of vasodilation in heart failure with preserved or reduced ejection fraction implications of distinct pathophysiologies on response to therapy" 734:. This pattern may develop normally with age in some patients, and many grade I patients will not have any clinical signs or symptoms of heart failure. 86:. Approximately half of people with heart failure have preserved ejection fraction, while the other half have a reduction in ejection fraction, called 2663:

Dixon DD, Trivedi A, Shah SJ (May 2016). "Combined post- and pre-capillary pulmonary hypertension in heart failure with preserved ejection fraction".

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incompetence. Combined with the characteristic deficit in stroke volume observed in HFpEF patients, many individuals display poor exercise tolerance.

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increased left atrial pressure in filling, increased passive stiffness and decreased distensibility of the ventricle, limited ability to exploit the

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Beta-blockers are the first-line therapy: they lower the heart rate and thus give more time for ventricles to fill. They may also improve survival.

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ARB treatment results in an improvement in diastolic dysfunction and hypertension that is comparable to other anti-hypertensive medication.

4918: 4727: 4564: 3691:"Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction" 3464:"Reversing the Cardiac Effects of Sedentary Aging in Middle Age-A Randomized Controlled Trial: Implications For Heart Failure Prevention" 3083:"Mechanisms of exercise intolerance in heart failure with preserved ejection fraction: the role of abnormal peripheral oxygen extraction" 4732: 4722: 4311: 5029: 4860: 4474: 4091: 3132:"High frequency of diastolic dysfunction in a population-based cohort of elderly women--but poor association with the symptom dyspnea" 887: 300:, or cellular deterioration that occurs as part of normal aging, closely resembles the manifestations of HFpEF. Specifically, loss of 268:, or inadequate oxygenation of the myocardium, is observed in a high proportion of HFpEF patients. This ischemia may be secondary to 4900: 2432: 637: 147:

Clinical manifestations of HFpEF are similar to those observed in HFrEF and include shortness of breath including exercise induced

2513:"Left ventricular long axis function in diastolic heart failure is reduced in both diastole and systole: time for a redefinition?" 4895: 1704:

González-López E, Gallego-Delgado M, Guzzo-Merello G, de Haro-Del Moral FJ, Cobo-Marcos M, Robles C, et al. (October 2015).

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remain intact and generate tension throughout diastole and thus increase stress on the heart. This is termed partial persistent

4764: 4545: 1070: 277: 226: 4840: 4835: 4759: 3249:"Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis" 1234:"Mechanisms of diastolic dysfunction in heart failure with a preserved ejection fraction: If it's not one thing it's another" 854: 396:

Structural changes that occur with HFpEF are often radically different from those associated with heart failure with reduced

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Diuretics can be useful if significant congestion develops, but patients must be monitored because they frequently develop

5186: 5062: 4991: 4823: 1558:"From Systemic Inflammation to Myocardial Fibrosis: The Heart Failure With Preserved Ejection Fraction Paradigm Revisited" 152: 5181: 4974: 4957: 4890: 4810: 4189: 3183:"Impaired left atrial strain predicts abnormal exercise haemodynamics in heart failure with preserved ejection fraction" 2708:"Right ventricular dysfunction in heart failure with preserved ejection fraction: a systematic review and meta-analysis" 1851:

Assayag, Elishai; Gurt, Irina; Cohen-Kfir, Einav; Stokar, Joshua; Zwas, Donna R.; Dresner-Pollak, Rivka (January 2024).

921: 5024: 2807:"Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction" 4469: 2567:"Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction" 945:, can provide a benefit for patients with heart failure regardless of ejection fraction. Additionally, because of the 529: 436:

through increased deposition as well as inhibition of enzymes that break down extracellular matrix components (matrix

311: 400:(HFrEF). Many patients experience increased thickening of the ventricular wall in comparison to chamber size, termed 769:. Fick may be readily and inexpensively inverted to cardiac output and ejection fraction to mathematically describe 5006: 4494: 4479: 926: 679: 379: 4781: 515: 5084: 4749: 4676: 4403: 706: 374: 5034: 2936:

Weerts J, Mourmans SG, Barandiarán Aizpurua A, Schroen BL, Knackstedt C, Eringa E, et al. (February 2022).

2897:"Systolic and diastolic dyssynchrony in patients with diastolic heart failure and the effect of medical therapy" 5208: 4964: 4754: 4651: 4632: 4462: 4235: 4157: 633: 579: 571: 473: 2105:

van Heerebeek L, Borbély A, Niessen HW, Bronzwaer JG, van der Velden J, Stienen GJ, et al. (April 2006).

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in 2006, evidence was presented to suggest that the prognosis in diastolic dysfunction is the same as that in

2237:"Left ventricular systolic performance, function, and contractility in patients with diastolic heart failure" 5284: 5279: 5241: 5215: 5203: 5191: 5176: 4910: 4852: 4656: 4637: 4289: 4229: 4182: 2856:"Diastolic and systolic asynchrony in patients with diastolic heart failure: a common but ignored condition" 1002: 838: 670: 305: 269: 160: 110: 83: 432:

contribute to the development and progression of HFrEF. This regulation is dynamic and involves changes in

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Bhella PS, Hastings JL, Fujimoto N, Shibata S, Carrick-Ranson G, Palmer MD, et al. (26 March 2014).

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environment are of significant importance in heart disease. Particularly, regulation of genes that alter

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Dhakal BP, Malhotra R, Murphy RM, Pappagianopoulos PP, Baggish AL, Weiner RB, et al. (March 2015).

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Gorter TM, Hoendermis ES, van Veldhuisen DJ, Voors AA, Lam CS, Geelhoed B, et al. (December 2016).

2278:"Diastolic heart failure can be diagnosed by comprehensive two-dimensional and Doppler echocardiography" 1058: 941:

of patients post-myocardial infarction. Some evidence suggests that vasodilating beta blockers, such as

575: 488: 405: 920:) are recommended for appropriately selected patients with symptomatic HFpEF (LVEF >= 45%, elevated 3937:"New Opportunities in Heart Failure with Preserved Ejection Fraction: From Bench to Bedside… and Back" 1464:

Lim GB (April 2018). "Heart failure: Macrophages promote cardiac fibrosis and diastolic dysfunction".

276:. Ischemia can result in impaired relaxation of the heart; when myocytes fail to relax appropriately, 5090: 4618: 4599: 4499: 4410: 4353: 1074: 818: 685:

Frequently patients are subjected to stress echocardiography, which involves the above assessment of

505: 425: 285: 1747:"Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction" 5095: 4952: 4947: 4870: 4774: 4744: 4703: 4329: 4246: 4146: 2616:"Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study" 858: 810: 711: 148: 125: 3648:, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J, et al. (February 2005). 2938:"The Role of Systemic Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction" 2146:

Borbély A, van der Velden J, Papp Z, Bronzwaer JG, Edes I, Stienen GJ, Paulus WJ (February 2005).

1796:"Menopause-Related Estrogen Decrease and the Pathogenesis of HFpEF: JACC Review Topic of the Week" 1706:"Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction" 1507:

Hulsmans M, Sager HB, Roh JD, Valero-Muñoz M, Houstis NE, Iwamoto Y, et al. (February 2018).

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Commonly encountered conditions that must be treated for and have independent recommendations for

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may represent an optimal academic model of diastolic heart failure that spares systolic function.

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Hummel SL, Seymour EM, Brook RD, Kolias TJ, Sheth SS, Rosenblum HR, et al. (November 2012).

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Nieminen MS, Böhm M, Cowie MR, Drexler H, Filippatos GS, Jondeau G, et al. (February 2005).

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imaging is an earlier mathematical attempt to distinguish systolic from diastolic heart failure.

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Germing A, Gotzmann M, Schikowski T, Vierkötter A, Ranft U, Krämer U, Mügge A (November 2011).

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Mohammed SF, Mirzoyev SA, Edwards WD, Dogan A, Grogan DR, Dunlay SM, et al. (April 2014).

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Borlaug BA, Melenovsky V, Russell SD, Kessler K, Pacak K, Becker LC, Kass DA (November 2006).

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Abudiab MM, Redfield MM, Melenovsky V, Olson TP, Kass DA, Johnson BD, Borlaug BA (July 2013).

2787: 2730: 2680: 2645: 2596: 2544: 2493: 2428: 2422: 2403: 2324: 2318: 2299: 2258: 2217: 2179: 2128: 2087: 2030: 1995: 1943: 1892: 1874: 1833: 1825: 1776: 1727: 1677: 1636: 1587: 1538: 1481: 1446: 1405: 1356: 1307: 1263: 1214: 1173: 1124: 754: 640:

provide benefits to HFrEF patients, no benefit is appreciable in HFpEF patients at this time.

437: 397: 75: 52: 2758:"Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction" 5231: 5123: 5016: 4712: 4048: 4007: 3966: 3948: 3881: 3837: 3801: 3751: 3702: 3661: 3617: 3604:

Schwartzenberg S, Redfield MM, From AM, Sorajja P, Nishimura RA, Borlaug BA (January 2012).

3578: 3536: 3526: 3485: 3477: 3436: 3399: 3358: 3317: 3309: 3296:

Mentz RJ, Kelly JP, von Lueder TG, Voors AA, Lam CS, Cowie MR, et al. (December 2014).

3268: 3260: 3204: 3194: 3153: 3143: 3102: 3094: 3047: 3010: 3000: 2959: 2949: 2908: 2867: 2826: 2818: 2777: 2769: 2756:

Borlaug BA, Olson TP, Lam CS, Flood KS, Lerman A, Johnson BD, Redfield MM (September 2010).

2722: 2672: 2635: 2627: 2586: 2578: 2534: 2524: 2483: 2393: 2383: 2289: 2248: 2209: 2169: 2159: 2118: 2077: 2069: 2022: 1985: 1977: 1933: 1923: 1882: 1864: 1815: 1807: 1766: 1758: 1717: 1667: 1626: 1618: 1577: 1569: 1528: 1520: 1473: 1436: 1395: 1387: 1346: 1338: 1297: 1253: 1245: 1204: 1163: 1155: 1114: 846: 806: 666: 649: 648:

Patients with HFpEF, in addition to cardiac abnormalities, display changes in (endothelial)

273: 230: 214: 79: 3298:"Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction" 1374:

Savji N, Meijers WC, Bartz TM, Bhambhani V, Cushman M, Nayor M, et al. (August 2018).

1284:

Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. (October 2013).

370:

Causes of isolated right ventricular diastolic failure are uncommon. These causes include:

5253: 4645: 4626: 4613: 4420: 4299: 3181:

Telles F, Nanayakkara S, Evans S, Patel HC, Mariani JA, Vizi D, et al. (April 2019).

566: 509: 461: 355: 301: 3247:

Zheng SL, Chan FT, Nabeebaccus AA, Shah AM, McDonagh T, Okonko DO, Ayis S (March 2018).

3098: 2200:

Aurigemma GP, Gaasch WH (September 2004). "Clinical practice. Diastolic heart failure".

1887: 1852: 1622: 1249: 5246: 5154: 5052: 5044: 4942: 4452: 4445: 4432: 3996:"Outcome of heart failure with preserved ejection fraction in a population-based study" 3971: 3936: 3645: 3541: 3531: 3514: 3490: 3463: 3322: 3297: 3273: 3248: 3158: 3131: 3107: 3082: 3015: 2988: 2964: 2937: 2831: 2806: 2782: 2757: 2640: 2615: 2591: 2566: 2539: 2512: 2488: 2471: 2398: 2371: 2253: 2236: 2164: 2147: 2082: 2057: 1990: 1965: 1771: 1746: 1631: 1606: 1582: 1557: 1533: 1508: 1425:"Insulin-resistant cardiomyopathy clinical evidence, mechanisms, and treatment options" 1400: 1375: 1351: 1326: 1258: 1233: 1168: 1143: 1062: 913: 892: 766: 699: 477: 445: 417: 322:

process, is emerging as an important and underdiagnosed contributor to HFpEF with age.

237:, such as IL-10. Further investigation of the role of inflammation in HFpEF is needed. 121: 98: 4151: 4086:. Principles and clinical practice (2nd ed.). Lippincott Williams & Wilkins. 3841: 3805: 3707: 3690: 3481: 2987:

Haykowsky MJ, Brubaker PH, Stewart KP, Morgan TM, Eggebeen J, Kitzman DW (July 2012).

2372:"Impact of lifelong exercise "dose" on left ventricular compliance and distensibility" 2123: 2106: 1607:"Zooming in on the Microvasculature in Heart Failure With Preserved Ejection Fraction" 1342: 1209: 1192: 886:

Currently treatment with ACE inhibitors, calcium channel blockers, beta blockers, and

5273: 5236: 5147: 4282: 3901: 3755: 1376:"The Association of Obesity and Cardiometabolic Traits With Incident HFpEF and HFrEF" 830: 613: 561:. When this pressure falls below the atrial pressure, atrio-ventricular valves open ( 315: 250: 71: 17: 3857: 3404: 3387: 3226: 3067: 2742: 2042: 1103:"Trends in prevalence and outcome of heart failure with preserved ejection fraction" 557:

During diastole, the ventricular pressure falls from the peak reached at the end of

5168: 5142: 4986: 4934: 4607: 4583: 4553: 4530: 4399: 4389: 3994:

Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A, Gong Y, Liu PP (July 2006).

3885: 3724: 2692: 982: 946: 937: 826: 753:

Imaged volumetric definition of systolic heart performance is commonly accepted as

621: 562: 206: 183: 94: 2614:

Lam CS, Roger VL, Rodeheffer RJ, Borlaug BA, Enders FT, Redfield MM (March 2009).

2107:"Myocardial structure and function differ in systolic and diastolic heart failure" 1573: 1493: 1193:"Heart failure with preserved ejection fraction: is this diastolic heart failure?" 4174: 4162: 3953: 3582: 3264: 3051: 382:, which includes Amyloidosis (most common restrictive), Sarcoidosis and fibrosis. 5103: 5001: 4791: 4708: 4690: 4516: 4489: 4440: 4381: 1018: 950: 762: 674: 496: 441: 254: 210: 202: 3666: 3649: 3622: 3605: 3440: 3363: 3346: 3313: 3005: 2913: 2896: 2872: 2855: 2773: 2631: 2582: 2388: 2294: 2277: 1981: 1928: 1911: 1811: 1762: 1722: 1705: 1672: 1655: 1441: 1424: 1391: 1302: 1285: 416:

Cellular changes generally underlie alterations in cardiac structure. In HFpEF

5131: 4681: 2676: 2073: 2026: 1101:

Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM (July 2006).

917: 617: 457: 319: 297: 222: 218: 3962: 3590: 1878: 1829: 1820: 1477: 4053: 4036: 3148: 2822: 2424:

An Introduction to Human Disease: Pathology and Pathophysiology Correlations

1795: 1006: 970: 942: 842: 731: 468: 335: 246: 245:

Conditions, such as hypertension, that encourage increased left ventricular

156: 4062: 4021: 3980: 3893: 3849: 3813: 3716: 3675: 3631: 3550: 3448: 3413: 3372: 3331: 3282: 3218: 3167: 3116: 3059: 3024: 2973: 2922: 2881: 2840: 2791: 2734: 2684: 2649: 2600: 2548: 2529: 2497: 2407: 2303: 2262: 2221: 2183: 2132: 2091: 2034: 2013:

Segura AM, Frazier OH, Buja LM (March 2014). "Fibrosis and heart failure".

1999: 1947: 1896: 1837: 1780: 1731: 1681: 1640: 1591: 1542: 1485: 1450: 1409: 1360: 1311: 1267: 1218: 1177: 1128: 257:

caused by the high pressure, leading to the left ventricle becoming stiff.

4037:"How do patients with heart failure with preserved ejection fraction die?" 3763: 3499: 1159: 5057: 4214: 4012: 3995: 2954: 2213: 1869: 1524: 1119: 1102: 974: 795: 770: 686: 552: 500: 433: 429: 361: 340: 331: 265: 234: 117: 102: 4134: 3388:"Management of heart failure with preserved ejection fraction: a review" 3209: 2854:

Yu CM, Zhang Q, Yip GW, Lee PW, Kum LC, Lam YY, Fung JW (January 2007).

1938: 977:, and many others, may be of benefit due to their effect on preventing 896: 837:

Randomized studies on HFpEF patients have shown that exercise improves

653: 281: 187: 106: 3199: 3182: 2511:

Yip G, Wang M, Zhang Y, Fung JW, Ho PY, Sanderson JE (February 2002).

2174: 678:

ventricular diastolic function. Important parameters include, rate of

480:

demands, increased diastolic left heart or pulmonary venous pressure.

5137: 5117: 4272: 4105:(10 (International edition) ed.). McGraw-Hill. pp. 658–60. 3242: 3240: 3238: 3236: 2726: 1005:

may be of benefit in reducing ventricular stiffness. In some cases, (

421:

too is consistent with eccentric hypertrophy seen in this condition.

201:

This pro-inflammatory state may also induce changes in the vascular

39: 464:, depicting the cardiac cycle. Two complete cycles are illustrated. 2895:

Wang J, Kurrelmeyer KM, Torre-Amione G, Nagueh SF (January 2007).

1325:

Zakeri R, Chamberlain AM, Roger VL, Redfield MM (September 2013).

799: 798:

to relieve complications associated with volume overload, such as

514: 456: 225:

into the tissue beneath the endothelium that subsequently release

164: 3347:"Heart failure: what does ejection fraction have to do with it?" 715: 4178: 1794:

Sabbatini, Andrea Rodrigues; Kararigas, Georgios (2020-03-10).

1656:"Heart failure with normal left ventricular ejection fraction" 1040: 632:

Non-simultaneous contraction of the left and right ventricle,

2565:

Borlaug BA, Kane GC, Melenovsky V, Olson TP (November 2016).

673:

are invasive procedures and thus reserved for patients with

2353: 2351: 2349: 2347: 1065:, was the predominant cause in population-based studies. 949:

perturbation and diminished LV filling seen in HFpEF the

2195: 2193: 985:, a significant player in the pathophysiology of HFpEF. 682:

relaxation, rate of ventricular filling, and stiffness.

595:

Pulmonary hypertension and right ventricular dysfunction

366:

Age – elderly patients mainly if they have hypertension.

205:

of the heart. Specifically, by reducing availability of

135:

There is controversy regarding the relationship between

3775: 3773: 2470:

Kawaguchi M, Hay I, Fetics B, Kass DA (February 2003).

2235:

Baicu CF, Zile MR, Aurigemma GP, Gaasch WH (May 2005).

120:

function: there is an increase in the stiffness of the

2056:

Kong P, Christia P, Frangogiannis NG (February 2014).

1959: 1957: 1057:(NYHA classes II-IV), cardiovascular death, including 776:

Another parameter to assess diastolic function is the

314:, resulting from accumulation of aggregated wild-type 2276:

Oh JK, Hatle L, Tajik AJ, Little WC (February 2006).

487:. In contrast, systolic heart failure has usually an 272:, or a result of the previously described changes in 4124: 2323:. Lippincott Williams & Wilkins. pp. 420–. 2148:"Cardiomyocyte stiffness in diastolic heart failure" 5224: 5167: 5076: 5043: 5015: 4973: 4932: 4909: 4883: 4851: 4809: 4790: 4689: 4675: 4575: 4529: 4515: 4431: 4380: 4373: 4310: 4265: 4222: 4213: 4128: 1509:"Cardiac macrophages promote diastolic dysfunction" 51: 32: 524:diastolic pressure, and therefore have increased ( 1605:Mohammed SF, Majure DT, Redfield MM (July 2016). 249:can lead to structural changes in the heart on a 2427:. Jones & Bartlett Publishers. p. 323. 1144:"Heart Failure with Preserved Ejection Fraction" 3917:"Israel's CorAssist keeps a weak heart pumping" 2560: 2558: 3736: 3734: 1096: 1094: 1092: 1090: 1039:elasticity. This had not been approved by the 961:Angiotensin converting enzyme (ACE) inhibitors 64:Heart failure with preserved ejection fraction 4190: 3610:Journal of the American College of Cardiology 3302:Journal of the American College of Cardiology 2993:Journal of the American College of Cardiology 2901:Journal of the American College of Cardiology 2860:Journal of the American College of Cardiology 2762:Journal of the American College of Cardiology 2620:Journal of the American College of Cardiology 2376:Journal of the American College of Cardiology 2282:Journal of the American College of Cardiology 1970:Journal of the American College of Cardiology 1800:Journal of the American College of Cardiology 1660:Journal of the American College of Cardiology 1429:Journal of the American College of Cardiology 1290:Journal of the American College of Cardiology 1197:Journal of the American College of Cardiology 908:Mineralocorticoid receptor antagonists (MRAs) 8: 88:heart failure with reduced ejection fraction 1857:International Journal of Molecular Sciences 1279: 1277: 4806: 4686: 4526: 4507:Arrhythmogenic right ventricular dysplasia 4377: 4219: 4197: 4183: 4175: 4125: 2457: 1009:has the benefit lowering the heart rate). 519:End Diastolic Pressure Volume Relationship 159:, exercise intolerance, fatigue, elevated 38: 29: 4052: 4011: 3970: 3952: 3706: 3665: 3621: 3540: 3530: 3489: 3403: 3362: 3321: 3272: 3208: 3198: 3157: 3147: 3106: 3014: 3004: 2963: 2953: 2912: 2871: 2830: 2781: 2639: 2590: 2538: 2528: 2487: 2397: 2387: 2293: 2252: 2173: 2163: 2122: 2081: 1989: 1937: 1927: 1886: 1868: 1819: 1770: 1721: 1671: 1630: 1581: 1532: 1440: 1399: 1350: 1301: 1257: 1208: 1167: 1118: 967:angiotensin converting enzyme inhibitors 831:angiotensin converting enzyme inhibitors 757:. Volumetric definition of the heart in 3386:Nanayakkara S, Kaye DM (October 2015). 1423:Witteles RM, Fowler MB (January 2008). 1086: 989:Angiotensin II receptor blockers (ARBs) 817:specific to HFpEF include avoidance of 4241:Spontaneous coronary artery dissection 3915:Kloosterman, Karin (27 October 2008). 3462:Howden EJ, Sarma S, Levine BD (2018). 2058:"The pathogenesis of cardiac fibrosis" 1232:LeWinter MM, Meyer M (November 2013). 3779: 2357: 738:elevated pressures in the left heart. 7: 4565:Nonbacterial thrombotic endocarditis 2062:Cellular and Molecular Life Sciences 1513:The Journal of Experimental Medicine 4000:The New England Journal of Medicine 3429:Progress in Cardiovascular Diseases 3099:10.1161/circheartfailure.114.001825 2320:Textbook of cardiovascular medicine 2202:The New England Journal of Medicine 1623:10.1161/CIRCHEARTFAILURE.116.003272 1250:10.1161/CIRCHEARTFAILURE.113.000825 1148:The New England Journal of Medicine 1107:The New England Journal of Medicine 839:left ventricular diastolic function 116:HFpEF is characterized by abnormal 4861:Accelerated idioventricular rhythm 3744:The American Journal of Cardiology 3532:10.1161/hypertensionaha.112.202705 2489:10.1161/01.cir.0000048123.22359.a0 2254:10.1161/01.cir.0000164273.57823.26 2165:10.1161/01.cir.0000155257.33485.6d 845:, and is associated with improved 665:HFpEF is typically diagnosed with 25: 4041:European Journal of Heart Failure 3708:10.1161/CIRCULATIONAHA.106.632745 3482:10.1161/CIRCULATIONAHA.117.030617 3187:European Journal of Heart Failure 2811:European Journal of Heart Failure 2715:European Journal of Heart Failure 2124:10.1161/circulationaha.105.587519 1654:Maeder MT, Kaye DM (March 2009). 1343:10.1161/CIRCULATIONAHA.113.001475 929:, during treatment is necessary. 3794:The American Journal of Medicine 3345:Iwano H, Little WC (July 2013). 4546:Subacute bacterial endocarditis 3405:10.1016/j.clinthera.2015.08.005 1556:Paulus WJ, Zile MR (May 2021). 1071:New England Journal of Medicine 612:Cardiac output is dependent on 343:related genes in the heart. 227:transforming growth factor beta 93:Risk factors for HFpEF include 3886:10.1016/j.cardfail.2022.02.010 893:phosphodiesterase-5-inhibitors 392:Gross structural abnormalities 1: 5063:Pulseless electrical activity 4992:Multifocal atrial tachycardia 4866:Catecholaminergic polymorphic 4101:Fuster V, O'Rouke RA (2001). 4035:Chan MM, Lam CS (June 2013). 3842:10.1016/s0140-6736(07)60980-5 3806:10.1016/s0002-9343(03)00158-x 1574:10.1161/CIRCRESAHA.121.318159 1210:10.1016/S0735-1097(03)00186-4 1142:Redfield MM (November 2016). 888:angiotensin receptor blockers 3954:10.3390/biomedicines11010070 3756:10.1016/0002-9149(93)90520-m 3583:10.1161/CIR.0000000000001063 3265:10.1136/heartjnl-2017-311652 3052:10.1136/heartjnl-2014-307040 2317:Topol EJ, Califf RM (2007). 1001:There is some evidence that 599:Most HFpEF patients exhibit 153:paroxysmal nocturnal dyspnea 530:high output cardiac failure 312:Senile systemic amyloidosis 5301: 5007:Wandering atrial pacemaker 4554:non-infective endocarditis 4495:Endocardial fibroelastosis 3874:Journal of Cardiac Failure 3623:10.1016/j.jacc.2011.09.062 3441:10.1016/j.pcad.2014.10.001 3364:10.1016/j.jjcc.2013.02.017 3314:10.1016/j.jacc.2014.08.036 3087:Circulation: Heart Failure 3006:10.1016/j.jacc.2012.02.055 2914:10.1016/j.jacc.2006.10.023 2873:10.1016/j.jacc.2006.10.022 2774:10.1016/j.jacc.2010.03.077 2632:10.1016/j.jacc.2008.11.051 2389:10.1016/j.jacc.2014.03.062 2295:10.1016/j.jacc.2005.09.032 1982:10.1016/j.jacc.2009.05.013 1812:10.1016/j.jacc.2019.12.049 1763:10.1016/j.jchf.2013.11.004 1673:10.1016/j.jacc.2008.12.007 1611:Circulation: Heart Failure 1466:Nature Reviews. Cardiology 1442:10.1016/j.jacc.2007.10.021 1392:10.1016/j.jchf.2018.05.018 1303:10.1016/j.jacc.2013.05.019 1238:Circulation: Heart Failure 927:glomerular filtration rate 550: 380:Restrictive cardiomyopathy 5085:hexaxial reference system 5030:Jervell and Lange-Nielsen 4560:Libman–Sacks endocarditis 2677:10.1007/s10741-015-9523-6 2074:10.1007/s00018-013-1349-6 2027:10.1007/s10741-012-9365-4 965:Likewise, treatment with 847:aerobic exercise capacity 802:and high blood pressure. 586:Non-diastolic dysfunction 499:, increased interstitial 375:Constrictive pericarditis 46: 37: 4965:Ventricular fibrillation 4236:Coronary artery aneurysm 3667:10.1093/eurheartj/ehi115 2583:10.1093/eurheartj/ehw241 1929:10.1093/eurheartj/ehi044 1723:10.1093/eurheartj/ehv338 1478:10.1038/nrcardio.2018.19 1003:calcium channel blockers 997:Calcium channel blockers 580:Doppler echocardiography 474:Frank-Starling mechanism 334:levels that occurs with 5242:Diastolic heart failure 5216:Athletic heart syndrome 5177:Ventricular hypertrophy 4911:Pre-excitation syndrome 4765:Left posterior fascicle 4290:Acute coronary syndrome 4230:Coronary artery disease 3149:10.1186/1471-2318-11-71 761:was first described by 497:ventricular hypertrophy 270:coronary artery disease 161:jugular venous pressure 137:diastolic heart failure 111:obstructive sleep apnea 84:cardiac catheterization 4760:Left anterior fascicle 4540:infective endocarditis 4325:Hibernating myocardium 4206:Cardiovascular disease 4080:Estafanous FG (2001). 3654:European Heart Journal 2571:European Heart Journal 2530:10.1136/heart.87.2.121 1710:European Heart Journal 1055:advanced heart failure 979:ventricular remodeling 700:Chagasic heart disease 650:microvascular function 644:Systemic abnormalities 601:pulmonary hypertension 572:ventricular relaxation 520: 485:concentric hypertrophy 465: 412:Cellular abnormalities 402:concentric hypertrophy 130:pulmonary hypertension 4924:Wolff–Parkinson–White 4884:Premature contraction 4782:Adams–Stokes syndrome 4485:Loeffler endocarditis 4295:Myocardial infarction 4054:10.1093/eurjhf/hft062 3392:Clinical Therapeutics 3351:Journal of Cardiology 2823:10.1093/eurjhf/hft026 2665:Heart Failure Reviews 2015:Heart Failure Reviews 1160:10.1056/NEJMcp1511175 865:Pharmacologic therapy 669:. Techniques such as 518: 489:eccentric hypertrophy 460: 453:Diastolic dysfunction 406:eccentric hypertrophy 33:Diastolic dysfunction 18:Diastolic Dysfunction 5091:Right axis deviation 5053:Sudden cardiac death 4411:Pericardial effusion 4354:Ventricular aneurysm 4013:10.1056/NEJMoa051530 2955:10.3390/biom12020278 2214:10.1056/nejmcp022709 1870:10.3390/ijms25105153 1562:Circulation Research 1525:10.1084/jem.20171274 1191:Zile MR (May 2003). 1120:10.1056/nejmoa052256 1075:systolic dysfunction 1063:sudden cardiac death 638:biventricular pacing 506:hydrostatic pressure 278:myosin cross bridges 5096:Left axis deviation 4953:Atrial fibrillation 4948:Ventricular flutter 4871:Torsades de pointes 4745:Bundle branch block 4704:Sick sinus syndrome 4490:Cardiac amyloidosis 4475:Tachycardia-induced 4330:Myocardial stunning 4278:Prinzmetal's angina 4247:Coronary thrombosis 3836:(9579): 2079–2087. 2421:Crowley LV (2013). 1751:JACC. Heart Failure 1380:JACC. Heart Failure 878:is as yet unclear. 859:natriuretic peptide 857:balance, and serum 811:atrial fibrillation 434:fibrillar collagens 306:vascular compliance 126:atrial fibrillation 5199:Atrial enlargement 4997:Pacemaker syndrome 4919:Lown–Ganong–Levine 4841:Junctional ectopic 4836:AV nodal reentrant 4342:Myocardial rupture 4252:Coronary vasospasm 4083:Cardiac anesthesia 2360:, pp. 658–60. 1019:low blood pressure 521: 466: 438:metalloproteinases 320:degenerative aging 196:insulin resistance 192:metabolic syndrome 143:Signs and symptoms 5267: 5266: 5259:Obstructive shock 5163: 5162: 5110:Short QT syndrome 5077:Other / ungrouped 5068:Sinoatrial arrest 4983:Ectopic pacemaker 4879: 4878: 4699:Sinus bradycardia 4671: 4670: 4667: 4666: 4416:Cardiac tamponade 4369: 4368: 4359:Dressler syndrome 4257:Myocardial bridge 4172: 4171: 4112:978-0-07-116296-8 4103:Hurst's The Heart 3701:(20): 2138–2147. 3476:(15): 1549–1560. 3398:(10): 2186–2198. 3308:(21): 2281–2293. 3200:10.1002/ejhf.1399 3046:(17): 1355–1360. 2721:(12): 1472–1487. 2626:(13): 1119–1126. 2577:(43): 3293–3302. 2382:(12): 1257–1266. 2330:978-0-7817-7012-5 2247:(18): 2306–2312. 2208:(11): 1097–1105. 2117:(16): 1966–1973. 1821:20.500.11815/3349 1716:(38): 2585–2594. 1568:(10): 1451–1467. 1296:(16): e147–e239. 1154:(19): 1868–1877. 755:ejection fraction 565:at left side and 398:ejection fraction 221:, which recruits 213:and regulator of 76:ejection fraction 61: 60: 27:Medical condition 16:(Redirected from 5292: 5232:Cardiac fibrosis 5124:T wave alternans 5017:Long QT syndrome 4811:Supraventricular 4807: 4740:Intraventricular 4687: 4527: 4378: 4223:Coronary disease 4220: 4199: 4192: 4185: 4176: 4126: 4116: 4097: 4067: 4066: 4056: 4032: 4026: 4025: 4015: 3991: 3985: 3984: 3974: 3956: 3931: 3925: 3924: 3912: 3906: 3905: 3868: 3862: 3861: 3824: 3818: 3817: 3789: 3783: 3777: 3768: 3767: 3738: 3729: 3728: 3710: 3686: 3680: 3679: 3669: 3642: 3636: 3635: 3625: 3601: 3595: 3594: 3561: 3555: 3554: 3544: 3534: 3525:(5): 1200–1206. 3510: 3504: 3503: 3493: 3459: 3453: 3452: 3424: 3418: 3417: 3407: 3383: 3377: 3376: 3366: 3342: 3336: 3335: 3325: 3293: 3287: 3286: 3276: 3244: 3231: 3230: 3212: 3202: 3178: 3172: 3171: 3161: 3151: 3127: 3121: 3120: 3110: 3078: 3072: 3071: 3035: 3029: 3028: 3018: 3008: 2984: 2978: 2977: 2967: 2957: 2933: 2927: 2926: 2916: 2892: 2886: 2885: 2875: 2851: 2845: 2844: 2834: 2802: 2796: 2795: 2785: 2753: 2747: 2746: 2727:10.1002/ejhf.630 2712: 2703: 2697: 2696: 2660: 2654: 2653: 2643: 2611: 2605: 2604: 2594: 2562: 2553: 2552: 2542: 2532: 2508: 2502: 2501: 2491: 2467: 2461: 2455: 2449: 2448: 2443: 2441: 2418: 2412: 2411: 2401: 2391: 2367: 2361: 2355: 2342: 2341: 2339: 2337: 2314: 2308: 2307: 2297: 2273: 2267: 2266: 2256: 2232: 2226: 2225: 2197: 2188: 2187: 2177: 2167: 2143: 2137: 2136: 2126: 2102: 2096: 2095: 2085: 2053: 2047: 2046: 2010: 2004: 2003: 1993: 1961: 1952: 1951: 1941: 1931: 1907: 1901: 1900: 1890: 1872: 1848: 1842: 1841: 1823: 1806:(9): 1074–1082. 1791: 1785: 1784: 1774: 1742: 1736: 1735: 1725: 1701: 1695: 1692: 1686: 1685: 1675: 1651: 1645: 1644: 1634: 1602: 1596: 1595: 1585: 1553: 1547: 1546: 1536: 1504: 1498: 1497: 1461: 1455: 1454: 1444: 1420: 1414: 1413: 1403: 1371: 1365: 1364: 1354: 1322: 1316: 1315: 1305: 1281: 1272: 1271: 1261: 1244:(6): 1112–1115. 1229: 1223: 1222: 1212: 1203:(9): 1519–1522. 1188: 1182: 1181: 1171: 1139: 1133: 1132: 1122: 1098: 1025:SGLT2 Inhibitors 843:ability to relax 807:standard of care 781: 780: 667:echocardiography 274:microvasculature 215:protein kinase G 80:echocardiography 42: 30: 21: 5300: 5299: 5295: 5294: 5293: 5291: 5290: 5289: 5270: 5269: 5268: 5263: 5254:Rheumatic fever 5220: 5159: 5072: 5039: 5011: 4969: 4928: 4905: 4875: 4847: 4794: 4786: 4680: 4663: 4571: 4520: 4511: 4427: 4421:Hemopericardium 4365: 4306: 4300:Unstable angina 4273:Angina pectoris 4266:Active ischemia 4261: 4209: 4203: 4173: 4168: 4167: 4137: 4123: 4113: 4100: 4094: 4079: 4076: 4071: 4070: 4034: 4033: 4029: 3993: 3992: 3988: 3933: 3932: 3928: 3914: 3913: 3909: 3870: 3869: 3865: 3826: 3825: 3821: 3791: 3790: 3786: 3778: 3771: 3740: 3739: 3732: 3688: 3687: 3683: 3644: 3643: 3639: 3603: 3602: 3598: 3563: 3562: 3558: 3512: 3511: 3507: 3461: 3460: 3456: 3426: 3425: 3421: 3385: 3384: 3380: 3344: 3343: 3339: 3295: 3294: 3290: 3246: 3245: 3234: 3180: 3179: 3175: 3129: 3128: 3124: 3080: 3079: 3075: 3037: 3036: 3032: 2986: 2985: 2981: 2935: 2934: 2930: 2894: 2893: 2889: 2853: 2852: 2848: 2804: 2803: 2799: 2768:(11): 845–854. 2755: 2754: 2750: 2710: 2705: 2704: 2700: 2662: 2661: 2657: 2613: 2612: 2608: 2564: 2563: 2556: 2510: 2509: 2505: 2469: 2468: 2464: 2458:Estafanous 2001 2456: 2452: 2439: 2437: 2435: 2420: 2419: 2415: 2369: 2368: 2364: 2356: 2345: 2335: 2333: 2331: 2316: 2315: 2311: 2275: 2274: 2270: 2234: 2233: 2229: 2199: 2198: 2191: 2145: 2144: 2140: 2104: 2103: 2099: 2055: 2054: 2050: 2012: 2011: 2007: 1963: 1962: 1955: 1909: 1908: 1904: 1850: 1849: 1845: 1793: 1792: 1788: 1744: 1743: 1739: 1703: 1702: 1698: 1693: 1689: 1666:(11): 905–918. 1653: 1652: 1648: 1604: 1603: 1599: 1555: 1554: 1550: 1506: 1505: 1501: 1463: 1462: 1458: 1422: 1421: 1417: 1373: 1372: 1368: 1337:(10): 1085–93. 1324: 1323: 1319: 1283: 1282: 1275: 1231: 1230: 1226: 1190: 1189: 1185: 1141: 1140: 1136: 1100: 1099: 1088: 1083: 1050: 1036: 1027: 1015: 999: 991: 963: 935: 910: 905: 884: 872: 867: 791: 778: 777: 671:catheterization 663: 646: 630: 610: 597: 588: 567:tricuspid valve 555: 549: 510:pulmonary edema 476:with increased 462:Wiggers diagram 455: 424:Changes in the 414: 394: 389: 387:Pathophysiology 356:Aortic stenosis 349: 330:The decline in 328: 318:as part of the 302:cardiac reserve 294: 263: 243: 209:, an important 177: 145: 70:) is a form of 28: 23: 22: 15: 12: 11: 5: 5298: 5296: 5288: 5287: 5285:Cardiomyopathy 5282: 5280:Heart diseases 5272: 5271: 5265: 5264: 5262: 5261: 5256: 5251: 5250: 5249: 5247:Cardiac asthma 5244: 5234: 5228: 5226: 5222: 5221: 5219: 5218: 5213: 5212: 5211: 5206: 5196: 5195: 5194: 5189: 5184: 5173: 5171: 5165: 5164: 5161: 5160: 5158: 5157: 5155:Strain pattern 5152: 5151: 5150: 5145: 5140: 5128: 5127: 5126: 5114: 5113: 5112: 5100: 5099: 5098: 5093: 5080: 5078: 5074: 5073: 5071: 5070: 5065: 5060: 5055: 5049: 5047: 5045:Cardiac arrest 5041: 5040: 5038: 5037: 5032: 5027: 5025:Andersen–Tawil 5021: 5019: 5013: 5012: 5010: 5009: 5004: 4999: 4994: 4989: 4979: 4977: 4971: 4970: 4968: 4967: 4962: 4961: 4960: 4950: 4945: 4943:Atrial flutter 4939: 4937: 4930: 4929: 4927: 4926: 4921: 4915: 4913: 4907: 4906: 4904: 4903: 4898: 4893: 4887: 4885: 4881: 4880: 4877: 4876: 4874: 4873: 4868: 4863: 4857: 4855: 4849: 4848: 4846: 4845: 4844: 4843: 4838: 4828: 4827: 4826: 4815: 4813: 4804: 4788: 4787: 4785: 4784: 4779: 4778: 4777: 4772: 4767: 4762: 4757: 4752: 4742: 4737: 4736: 4735: 4730: 4725: 4715: 4706: 4701: 4695: 4693: 4684: 4673: 4672: 4669: 4668: 4665: 4664: 4662: 4661: 4660: 4659: 4654: 4642: 4641: 4640: 4635: 4623: 4622: 4621: 4616: 4604: 4603: 4602: 4597: 4592: 4579: 4577: 4573: 4572: 4570: 4569: 4568: 4567: 4562: 4550: 4549: 4548: 4535: 4533: 4524: 4513: 4512: 4510: 4509: 4504: 4503: 4502: 4497: 4492: 4487: 4482: 4477: 4472: 4467: 4466: 4465: 4453:Cardiomyopathy 4450: 4449: 4448: 4446:Chagas disease 4437: 4435: 4429: 4428: 4426: 4425: 4424: 4423: 4418: 4408: 4407: 4406: 4397: 4386: 4384: 4375: 4371: 4370: 4367: 4366: 4364: 4363: 4362: 4361: 4356: 4346: 4345: 4344: 4334: 4333: 4332: 4327: 4316: 4314: 4308: 4307: 4305: 4304: 4303: 4302: 4297: 4287: 4286: 4285: 4280: 4269: 4267: 4263: 4262: 4260: 4259: 4254: 4249: 4244: 4238: 4233: 4226: 4224: 4217: 4211: 4210: 4204: 4202: 4201: 4194: 4187: 4179: 4170: 4169: 4166: 4165: 4154: 4138: 4133: 4132: 4130: 4129:Classification 4122: 4121:External links 4119: 4118: 4117: 4111: 4098: 4093:978-0781721950 4092: 4075: 4072: 4069: 4068: 4027: 3986: 3926: 3907: 3880:(5): e1–e167. 3863: 3819: 3784: 3782:, p. 709. 3769: 3750:(7): 602–604. 3730: 3681: 3660:(3): 215–225. 3637: 3616:(5): 442–451. 3596: 3556: 3505: 3454: 3435:(4): 347–355. 3419: 3378: 3337: 3288: 3259:(5): 407–415. 3232: 3193:(4): 495–505. 3173: 3136:BMC Geriatrics 3122: 3093:(2): 286–294. 3073: 3030: 2999:(2): 120–128. 2979: 2928: 2887: 2846: 2817:(7): 776–785. 2797: 2748: 2698: 2655: 2606: 2554: 2523:(2): 121–125. 2503: 2482:(5): 714–720. 2462: 2460:, p. 562. 2450: 2433: 2413: 2362: 2343: 2329: 2309: 2288:(3): 500–506. 2268: 2227: 2189: 2158:(6): 774–781. 2138: 2097: 2068:(4): 549–574. 2048: 2005: 1976:(5): 410–418. 1953: 1922:(4): 384–416. 1902: 1843: 1786: 1757:(2): 113–122. 1737: 1696: 1687: 1646: 1597: 1548: 1519:(2): 423–440. 1499: 1472:(4): 196–197. 1456: 1415: 1386:(8): 701–709. 1366: 1317: 1273: 1224: 1183: 1134: 1113:(3): 251–259. 1085: 1084: 1082: 1079: 1049: 1046: 1035: 1032: 1026: 1023: 1014: 1011: 998: 995: 990: 987: 962: 959: 934: 931: 914:spironolactone 909: 906: 904: 901: 883: 880: 871: 868: 866: 863: 841:, the heart's 790: 787: 767:cardiac output 747: 746: 743: 739: 735: 712:stress imaging 662: 659: 645: 642: 629: 626: 609: 606: 596: 593: 587: 584: 551:Main article: 548: 545: 508:and promoting 454: 451: 418:cardiomyocytes 413: 410: 393: 390: 388: 385: 384: 383: 377: 368: 367: 364: 359: 348: 345: 327: 324: 293: 290: 262: 259: 242: 239: 229:, encouraging 176: 173: 144: 141: 122:left ventricle 99:hyperlipidemia 59: 58: 55: 49: 48: 44: 43: 35: 34: 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 5297: 5286: 5283: 5281: 5278: 5277: 5275: 5260: 5257: 5255: 5252: 5248: 5245: 5243: 5240: 5239: 5238: 5237:Heart failure 5235: 5233: 5230: 5229: 5227: 5223: 5217: 5214: 5210: 5207: 5205: 5202: 5201: 5200: 5197: 5193: 5190: 5188: 5185: 5183: 5180: 5179: 5178: 5175: 5174: 5172: 5170: 5166: 5156: 5153: 5149: 5148:ST depression 5146: 5144: 5141: 5139: 5136: 5135: 5134: 5133: 5129: 5125: 5122: 5121: 5120: 5119: 5115: 5111: 5108: 5107: 5106: 5105: 5101: 5097: 5094: 5092: 5089: 5088: 5087: 5086: 5082: 5081: 5079: 5075: 5069: 5066: 5064: 5061: 5059: 5056: 5054: 5051: 5050: 5048: 5046: 5042: 5036: 5033: 5031: 5028: 5026: 5023: 5022: 5020: 5018: 5014: 5008: 5005: 5003: 5000: 4998: 4995: 4993: 4990: 4988: 4984: 4981: 4980: 4978: 4976: 4972: 4966: 4963: 4959: 4956: 4955: 4954: 4951: 4949: 4946: 4944: 4941: 4940: 4938: 4936: 4931: 4925: 4922: 4920: 4917: 4916: 4914: 4912: 4908: 4902: 4899: 4897: 4894: 4892: 4889: 4888: 4886: 4882: 4872: 4869: 4867: 4864: 4862: 4859: 4858: 4856: 4854: 4850: 4842: 4839: 4837: 4834: 4833: 4832: 4829: 4825: 4822: 4821: 4820: 4817: 4816: 4814: 4812: 4808: 4805: 4802: 4798: 4793: 4789: 4783: 4780: 4776: 4775:Trifascicular 4773: 4771: 4768: 4766: 4763: 4761: 4758: 4756: 4753: 4751: 4748: 4747: 4746: 4743: 4741: 4738: 4734: 4731: 4729: 4726: 4724: 4721: 4720: 4719: 4716: 4714: 4710: 4707: 4705: 4702: 4700: 4697: 4696: 4694: 4692: 4688: 4685: 4683: 4678: 4674: 4658: 4657:regurgitation 4655: 4653: 4650: 4649: 4648: 4647: 4643: 4639: 4638:regurgitation 4636: 4634: 4631: 4630: 4629: 4628: 4624: 4620: 4619:regurgitation 4617: 4615: 4612: 4611: 4610: 4609: 4605: 4601: 4600:regurgitation 4598: 4596: 4593: 4591: 4588: 4587: 4586: 4585: 4581: 4580: 4578: 4574: 4566: 4563: 4561: 4558: 4557: 4556: 4555: 4551: 4547: 4544: 4543: 4542: 4541: 4537: 4536: 4534: 4532: 4528: 4525: 4523: 4518: 4514: 4508: 4505: 4501: 4498: 4496: 4493: 4491: 4488: 4486: 4483: 4481: 4478: 4476: 4473: 4471: 4468: 4464: 4461: 4460: 4459: 4456: 4455: 4454: 4451: 4447: 4444: 4443: 4442: 4439: 4438: 4436: 4434: 4430: 4422: 4419: 4417: 4414: 4413: 4412: 4409: 4405: 4401: 4398: 4396: 4393: 4392: 4391: 4388: 4387: 4385: 4383: 4379: 4376: 4372: 4360: 4357: 4355: 4352: 4351: 4350: 4347: 4343: 4340: 4339: 4338: 4335: 4331: 4328: 4326: 4323: 4322: 4321: 4318: 4317: 4315: 4313: 4309: 4301: 4298: 4296: 4293: 4292: 4291: 4288: 4284: 4283:Stable angina 4281: 4279: 4276: 4275: 4274: 4271: 4270: 4268: 4264: 4258: 4255: 4253: 4250: 4248: 4245: 4242: 4239: 4237: 4234: 4231: 4228: 4227: 4225: 4221: 4218: 4216: 4212: 4207: 4200: 4195: 4193: 4188: 4186: 4181: 4180: 4177: 4164: 4160: 4159: 4155: 4153: 4149: 4148: 4144: 4140: 4139: 4136: 4131: 4127: 4120: 4114: 4108: 4104: 4099: 4095: 4089: 4085: 4084: 4078: 4077: 4073: 4064: 4060: 4055: 4050: 4047:(6): 604–13. 4046: 4042: 4038: 4031: 4028: 4023: 4019: 4014: 4009: 4005: 4001: 3997: 3990: 3987: 3982: 3978: 3973: 3968: 3964: 3960: 3955: 3950: 3946: 3942: 3938: 3930: 3927: 3922: 3918: 3911: 3908: 3903: 3899: 3895: 3891: 3887: 3883: 3879: 3875: 3867: 3864: 3859: 3855: 3851: 3847: 3843: 3839: 3835: 3831: 3823: 3820: 3815: 3811: 3807: 3803: 3799: 3795: 3788: 3785: 3781: 3776: 3774: 3770: 3765: 3761: 3757: 3753: 3749: 3745: 3737: 3735: 3731: 3726: 3722: 3718: 3714: 3709: 3704: 3700: 3696: 3692: 3685: 3682: 3677: 3673: 3668: 3663: 3659: 3655: 3651: 3647: 3641: 3638: 3633: 3629: 3624: 3619: 3615: 3611: 3607: 3600: 3597: 3592: 3588: 3584: 3580: 3576: 3572: 3568: 3560: 3557: 3552: 3548: 3543: 3538: 3533: 3528: 3524: 3520: 3516: 3509: 3506: 3501: 3497: 3492: 3487: 3483: 3479: 3475: 3471: 3470: 3465: 3458: 3455: 3450: 3446: 3442: 3438: 3434: 3430: 3423: 3420: 3415: 3411: 3406: 3401: 3397: 3393: 3389: 3382: 3379: 3374: 3370: 3365: 3360: 3356: 3352: 3348: 3341: 3338: 3333: 3329: 3324: 3319: 3315: 3311: 3307: 3303: 3299: 3292: 3289: 3284: 3280: 3275: 3270: 3266: 3262: 3258: 3254: 3250: 3243: 3241: 3239: 3237: 3233: 3228: 3224: 3220: 3216: 3211: 3206: 3201: 3196: 3192: 3188: 3184: 3177: 3174: 3169: 3165: 3160: 3155: 3150: 3145: 3141: 3137: 3133: 3126: 3123: 3118: 3114: 3109: 3104: 3100: 3096: 3092: 3088: 3084: 3077: 3074: 3069: 3065: 3061: 3057: 3053: 3049: 3045: 3041: 3034: 3031: 3026: 3022: 3017: 3012: 3007: 3002: 2998: 2994: 2990: 2983: 2980: 2975: 2971: 2966: 2961: 2956: 2951: 2947: 2943: 2939: 2932: 2929: 2924: 2920: 2915: 2910: 2906: 2902: 2898: 2891: 2888: 2883: 2879: 2874: 2869: 2866:(1): 97–105. 2865: 2861: 2857: 2850: 2847: 2842: 2838: 2833: 2828: 2824: 2820: 2816: 2812: 2808: 2801: 2798: 2793: 2789: 2784: 2779: 2775: 2771: 2767: 2763: 2759: 2752: 2749: 2744: 2740: 2736: 2732: 2728: 2724: 2720: 2716: 2709: 2702: 2699: 2694: 2690: 2686: 2682: 2678: 2674: 2671:(3): 285–97. 2670: 2666: 2659: 2656: 2651: 2647: 2642: 2637: 2633: 2629: 2625: 2621: 2617: 2610: 2607: 2602: 2598: 2593: 2588: 2584: 2580: 2576: 2572: 2568: 2561: 2559: 2555: 2550: 2546: 2541: 2536: 2531: 2526: 2522: 2518: 2514: 2507: 2504: 2499: 2495: 2490: 2485: 2481: 2477: 2473: 2466: 2463: 2459: 2454: 2451: 2447: 2436: 2434:9781449632403 2430: 2426: 2425: 2417: 2414: 2409: 2405: 2400: 2395: 2390: 2385: 2381: 2377: 2373: 2366: 2363: 2359: 2354: 2352: 2350: 2348: 2344: 2332: 2326: 2322: 2321: 2313: 2310: 2305: 2301: 2296: 2291: 2287: 2283: 2279: 2272: 2269: 2264: 2260: 2255: 2250: 2246: 2242: 2238: 2231: 2228: 2223: 2219: 2215: 2211: 2207: 2203: 2196: 2194: 2190: 2185: 2181: 2176: 2171: 2166: 2161: 2157: 2153: 2149: 2142: 2139: 2134: 2130: 2125: 2120: 2116: 2112: 2108: 2101: 2098: 2093: 2089: 2084: 2079: 2075: 2071: 2067: 2063: 2059: 2052: 2049: 2044: 2040: 2036: 2032: 2028: 2024: 2021:(2): 173–85. 2020: 2016: 2009: 2006: 2001: 1997: 1992: 1987: 1983: 1979: 1975: 1971: 1967: 1960: 1958: 1954: 1949: 1945: 1940: 1935: 1930: 1925: 1921: 1917: 1913: 1906: 1903: 1898: 1894: 1889: 1884: 1880: 1876: 1871: 1866: 1862: 1858: 1854: 1847: 1844: 1839: 1835: 1831: 1827: 1822: 1817: 1813: 1809: 1805: 1801: 1797: 1790: 1787: 1782: 1778: 1773: 1768: 1764: 1760: 1756: 1752: 1748: 1741: 1738: 1733: 1729: 1724: 1719: 1715: 1711: 1707: 1700: 1697: 1691: 1688: 1683: 1679: 1674: 1669: 1665: 1661: 1657: 1650: 1647: 1642: 1638: 1633: 1628: 1624: 1620: 1616: 1612: 1608: 1601: 1598: 1593: 1589: 1584: 1579: 1575: 1571: 1567: 1563: 1559: 1552: 1549: 1544: 1540: 1535: 1530: 1526: 1522: 1518: 1514: 1510: 1503: 1500: 1495: 1491: 1487: 1483: 1479: 1475: 1471: 1467: 1460: 1457: 1452: 1448: 1443: 1438: 1435:(2): 93–102. 1434: 1430: 1426: 1419: 1416: 1411: 1407: 1402: 1397: 1393: 1389: 1385: 1381: 1377: 1370: 1367: 1362: 1358: 1353: 1348: 1344: 1340: 1336: 1332: 1328: 1321: 1318: 1313: 1309: 1304: 1299: 1295: 1291: 1287: 1280: 1278: 1274: 1269: 1265: 1260: 1255: 1251: 1247: 1243: 1239: 1235: 1228: 1225: 1220: 1216: 1211: 1206: 1202: 1198: 1194: 1187: 1184: 1179: 1175: 1170: 1165: 1161: 1157: 1153: 1149: 1145: 1138: 1135: 1130: 1126: 1121: 1116: 1112: 1108: 1104: 1097: 1095: 1093: 1091: 1087: 1080: 1078: 1076: 1072: 1066: 1064: 1060: 1059:heart attacks 1056: 1047: 1045: 1042: 1033: 1031: 1024: 1022: 1020: 1012: 1010: 1008: 1004: 996: 994: 988: 986: 984: 980: 976: 972: 968: 960: 958: 955: 952: 948: 944: 939: 938:Beta blockers 933:Beta blockers 932: 930: 928: 923: 919: 915: 907: 902: 900: 898: 894: 889: 881: 879: 877: 869: 864: 862: 860: 856: 850: 848: 844: 840: 835: 832: 828: 827:beta blockers 823: 820: 814: 812: 808: 803: 801: 797: 788: 786: 783: 774: 772: 768: 764: 760: 756: 751: 744: 742:dysfunction". 740: 736: 733: 729: 728: 727: 723: 719: 717: 713: 708: 703: 701: 695: 691: 688: 683: 681: 676: 672: 668: 660: 658: 655: 651: 643: 641: 639: 635: 627: 625: 623: 619: 615: 614:stroke volume 607: 605: 602: 594: 592: 585: 583: 581: 577: 573: 568: 564: 560: 554: 546: 544: 541: 537: 533: 531: 527: 517: 513: 511: 507: 502: 498: 492: 490: 486: 481: 479: 475: 470: 463: 459: 452: 450: 447: 443: 439: 435: 431: 427: 426:extracellular 422: 419: 411: 409: 407: 403: 399: 391: 386: 381: 378: 376: 373: 372: 371: 365: 363: 360: 357: 354: 353: 352: 346: 344: 342: 337: 333: 325: 323: 321: 317: 316:transthyretin 313: 309: 307: 304:, diminished 303: 299: 291: 289: 287: 283: 279: 275: 271: 267: 260: 258: 256: 252: 248: 240: 238: 236: 232: 228: 224: 220: 216: 212: 208: 204: 199: 197: 193: 189: 185: 181: 174: 172: 168: 166: 162: 158: 154: 150: 142: 140: 138: 133: 131: 127: 123: 119: 114: 112: 108: 104: 100: 96: 91: 89: 85: 81: 77: 74:in which the 73: 72:heart failure 69: 65: 56: 54: 50: 45: 41: 36: 31: 19: 5169:Cardiomegaly 5143:ST elevation 5130: 5116: 5102: 5083: 4987:Ectopic beat 4935:fibrillation 4770:Bifascicular 4644: 4625: 4606: 4582: 4552: 4538: 4531:Endocarditis 4470:Hypertrophic 4404:Constrictive 4390:Pericarditis 4348: 4336: 4319: 4156: 4141: 4102: 4082: 4074:Bibliography 4044: 4040: 4030: 4006:(3): 260–9. 4003: 3999: 3989: 3944: 3941:Biomedicines 3940: 3929: 3920: 3910: 3877: 3873: 3866: 3833: 3829: 3822: 3797: 3793: 3787: 3747: 3743: 3698: 3694: 3684: 3657: 3653: 3640: 3613: 3609: 3599: 3574: 3570: 3559: 3522: 3519:Hypertension 3518: 3508: 3473: 3467: 3457: 3432: 3428: 3422: 3395: 3391: 3381: 3354: 3350: 3340: 3305: 3301: 3291: 3256: 3252: 3210:11343/285286 3190: 3186: 3176: 3139: 3135: 3125: 3090: 3086: 3076: 3043: 3039: 3033: 2996: 2992: 2982: 2945: 2942:Biomolecules 2941: 2931: 2907:(1): 88–96. 2904: 2900: 2890: 2863: 2859: 2849: 2814: 2810: 2800: 2765: 2761: 2751: 2718: 2714: 2701: 2668: 2664: 2658: 2623: 2619: 2609: 2574: 2570: 2520: 2516: 2506: 2479: 2475: 2465: 2453: 2445: 2438:. 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