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.

838:. 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. 447: 29: 505: 805:

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

242:, 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 1027:

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

802:, 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. 3553:

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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.

273:. 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 559:(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 493:

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).

567:, 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 879:

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

641:, 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 67:– 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 483:

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.

2696: 183:, 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 694:

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

3556:"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" 679:

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.

397:, 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. 393:. 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 1842:"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" 734:

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 (

625:, 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 3504:"Low-sodium dietary approaches to stop hypertension diet reduces blood pressure, arterial stiffness, and oxidative stress in hypertensive heart failure with preserved ejection fraction" 850:

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".

1275:"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" 970:

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.

2461:"Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations" 771:, 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. 4854: 222:

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.

2978:"Effect of endurance training on the determinants of peak exercise oxygen consumption in elderly patients with stable compensated heart failure and preserved ejection fraction" 1043: 609:. 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 3781:

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

1901:"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" 814:

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

113:, which causes a decrease in left ventricular relaxation during diastole, with resultant increased pressure and/or impaired filling. There is an increased risk for 3027:

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).

1955:"Contractility and ventricular systolic stiffening in hypertensive heart disease insights into the pathogenesis of heart failure with preserved ejection fraction" 340:

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

297:, and diastolic dysfunction are characteristic of both processes. It has been suggested that HFpEF merely represents an acceleration of a normal aging process. 863:

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

762:. 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. 1316:"Temporal relationship and prognostic significance of atrial fibrillation in heart failure patients with preserved ejection fraction: a community-based study" 206:

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

76: 433:). While early stage HFrEF is associated with a significant disruption of extracellular matrix proteins initially, as it progresses fibrotic replacement of 3639:"Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS)" 347:

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.

4495: 3595:"Effects of vasodilation in heart failure with preserved or reduced ejection fraction implications of distinct pathophysiologies on response to therapy" 723:. 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. 75:. Approximately half of people with heart failure have preserved ejection fraction, while the other half have a reduction in ejection fraction, called 2652:

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.

4907: 4716: 4553: 3680:"Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction" 3453:"Reversing the Cardiac Effects of Sedentary Aging in Middle Age-A Randomized Controlled Trial: Implications For Heart Failure Prevention" 3072:"Mechanisms of exercise intolerance in heart failure with preserved ejection fraction: the role of abnormal peripheral oxygen extraction" 4721: 4711: 4300: 5018: 4849: 4463: 4080: 3121:"High frequency of diastolic dysfunction in a population-based cohort of elderly women--but poor association with the symptom dyspnea" 876: 289:, or cellular deterioration that occurs as part of normal aging, closely resembles the manifestations of HFpEF. Specifically, loss of 257:, or inadequate oxygenation of the myocardium, is observed in a high proportion of HFpEF patients. This ischemia may be secondary to 4889: 2421: 626: 136:

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

2502:"Left ventricular long axis function in diastolic heart failure is reduced in both diastole and systole: time for a redefinition?" 4884: 1693:

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

4753: 4534: 1059: 266: 215: 4829: 4824: 4748: 3238:"Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis" 1223:"Mechanisms of diastolic dysfunction in heart failure with a preserved ejection fraction: If it's not one thing it's another" 843: 385:

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

5175: 5051: 4980: 4812: 1547:"From Systemic Inflammation to Myocardial Fibrosis: The Heart Failure With Preserved Ejection Fraction Paradigm Revisited" 141: 5170: 4963: 4946: 4879: 4799: 4178: 3172:"Impaired left atrial strain predicts abnormal exercise haemodynamics in heart failure with preserved ejection fraction" 2697:"Right ventricular dysfunction in heart failure with preserved ejection fraction: a systematic review and meta-analysis" 1840:

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

910: 5013: 2796:"Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction" 4458: 2556:"Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction" 934:, can provide a benefit for patients with heart failure regardless of ejection fraction. Additionally, because of the 518: 425:

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

300: 389:(HFrEF). Many patients experience increased thickening of the ventricular wall in comparison to chamber size, termed 758:. Fick may be readily and inexpensively inverted to cardiac output and ejection fraction to mathematically describe 4995: 4483: 4468: 915: 668: 368: 4770: 504: 5073: 4738: 4665: 4392: 695: 363: 5023: 2925:

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

2886:"Systolic and diastolic dyssynchrony in patients with diastolic heart failure and the effect of medical therapy" 5197: 4953: 4743: 4640: 4621: 4451: 4224: 4146: 622: 568: 560: 462: 2094:

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

2226:"Left ventricular systolic performance, function, and contractility in patients with diastolic heart failure" 5273: 5268: 5230: 5204: 5192: 5180: 5165: 4899: 4841: 4645: 4626: 4278: 4218: 4171: 2845:"Diastolic and systolic asynchrony in patients with diastolic heart failure: a common but ignored condition" 991: 827: 659: 294: 258: 149: 99: 72: 421:

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

4819: 4785: 4728: 4706: 4528: 4510: 4446: 4313: 4266: 4194: 3905: 967: 589: 473: 390: 118: 2359:

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).

2267:"Diastolic heart failure can be diagnosed by comprehensive two-dimensional and Doppler echocardiography" 1047: 930:

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

564: 477: 394: 909:) are recommended for appropriately selected patients with symptomatic HFpEF (LVEF >= 45%, elevated 3926:"New Opportunities in Heart Failure with Preserved Ejection Fraction: From Bench to Bedside… and Back" 1453:

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

265:. Ischemia can result in impaired relaxation of the heart; when myocytes fail to relax appropriately, 5079: 4607: 4588: 4488: 4399: 4342: 1063: 807: 674:

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

494: 414: 274: 1736:"Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction" 5084: 4941: 4936: 4859: 4763: 4733: 4692: 4318: 4235: 4135: 2605:"Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study" 847: 799: 700: 137: 114: 3637:, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J, et al. (February 2005). 2927:"The Role of Systemic Microvascular Dysfunction in Heart Failure with Preserved Ejection Fraction" 2135:

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

1785:"Menopause-Related Estrogen Decrease and the Pathogenesis of HFpEF: JACC Review Topic of the Week" 1695:"Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction" 1496:

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).

2776: 2719: 2669: 2634: 2585: 2533: 2482: 2417: 2411: 2392: 2313: 2307: 2288: 2247: 2206: 2168: 2117: 2076: 2019: 1984: 1932: 1881: 1863: 1822: 1814: 1765: 1716: 1666: 1625: 1576: 1527: 1470: 1435: 1394: 1345: 1296: 1252: 1203: 1162: 1113: 743: 629:

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

426: 386: 64: 41: 2747:"Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction" 5220: 5112: 5005: 4701: 4037: 3996: 3955: 3937: 3870: 3826: 3790: 3740: 3691: 3650: 3606: 3593:

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

3567: 3525: 3515: 3474: 3466: 3425: 3388: 3347: 3306: 3298: 3285:

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

3257: 3249: 3193: 3183: 3142: 3132: 3091: 3083: 3036: 2999: 2989: 2948: 2938: 2897: 2856: 2815: 2807: 2766: 2758: 2745:

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

2711: 2661: 2624: 2616: 2575: 2567: 2523: 2513: 2472: 2382: 2372: 2278: 2237: 2198: 2158: 2148: 2107: 2066: 2058: 2011: 1974: 1966: 1922: 1912: 1871: 1853: 1804: 1796: 1755: 1747: 1706: 1656: 1615: 1607: 1566: 1558: 1517: 1509: 1462: 1425: 1384: 1376: 1335: 1327: 1286: 1242: 1234: 1193: 1152: 1144: 1103: 835: 795: 655: 638: 637:

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

262: 219: 203: 68: 3287:"Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction" 1363:

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

1273:

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

359:

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

5242: 4634: 4615: 4602: 4409: 4288: 3170:

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

555: 498: 450: 344: 290: 3236:

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

3087: 2189:

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

1876: 1841: 1611: 1238: 5235: 5143: 5041: 5033: 4931: 4441: 4434: 4421: 3985:"Outcome of heart failure with preserved ejection fraction in a population-based study" 3960: 3925: 3634: 3530: 3520: 3503: 3479: 3452: 3311: 3286: 3262: 3237: 3147: 3120: 3096: 3071: 3004: 2977: 2953: 2926: 2820: 2795: 2771: 2746: 2629: 2604: 2580: 2555: 2528: 2501: 2477: 2460: 2387: 2360: 2242: 2225: 2153: 2136: 2071: 2046: 1979: 1954: 1760: 1735: 1620: 1595: 1571: 1546: 1522: 1497: 1414:"Insulin-resistant cardiomyopathy clinical evidence, mechanisms, and treatment options" 1389: 1364: 1340: 1315: 1247: 1222: 1157: 1132: 1051: 902: 881: 755: 688: 466: 434: 406: 311:

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

226:, such as IL-10. Further investigation of the role of inflammation in HFpEF is needed. 110: 87: 4140: 4075:. Principles and clinical practice (2nd ed.). Lippincott Williams & Wilkins. 3830: 3794: 3696: 3679: 3470: 2976:

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

2361:"Impact of lifelong exercise "dose" on left ventricular compliance and distensibility" 2112: 2095: 1596:"Zooming in on the Microvasculature in Heart Failure With Preserved Ejection Fraction" 1331: 1198: 1181: 875:

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

5262: 5225: 5136: 4271: 3890: 3744: 1365:"The Association of Obesity and Cardiometabolic Traits With Incident HFpEF and HFrEF" 819: 602: 550:. When this pressure falls below the atrial pressure, atrio-ventricular valves open ( 304: 239: 60: 3846: 3393: 3376: 3215: 3056: 2731: 2031: 1092:"Trends in prevalence and outcome of heart failure with preserved ejection fraction" 546:

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

5157: 5131: 4975: 4923: 4596: 4572: 4542: 4519: 4388: 4378: 3983:

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

3874: 3713: 2681: 971: 935: 926: 815: 742:

Imaged volumetric definition of systolic heart performance is commonly accepted as

610: 551: 195: 172: 83: 2603:

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

2096:"Myocardial structure and function differ in systolic and diastolic heart failure" 1562: 1482: 1182:"Heart failure with preserved ejection fraction: is this diastolic heart failure?" 4163: 4151: 3942: 3571: 3253: 3040: 371:, which includes Amyloidosis (most common restrictive), Sarcoidosis and fibrosis. 5092: 4990: 4780: 4697: 4679: 4505: 4478: 4429: 4370: 1007: 939: 751: 663: 485: 430: 243: 199: 191: 3655: 3638: 3611: 3594: 3429: 3352: 3335: 3302: 2994: 2902: 2885: 2861: 2844: 2762: 2620: 2571: 2377: 2283: 2266: 1970: 1917: 1900: 1800: 1751: 1711: 1694: 1661: 1644: 1430: 1413: 1380: 1291: 1274: 405:

Cellular changes generally underlie alterations in cardiac structure. In HFpEF

5120: 4670: 2665: 2062: 2015: 1090:

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

906: 606: 446: 308: 286: 211: 207: 3951: 3579: 1867: 1818: 1809: 1466: 4042: 4025: 3137: 2811: 2413:

An Introduction to Human Disease: Pathology and Pathophysiology Correlations

1784: 995: 959: 931: 831: 720: 457: 324: 235: 234:

Conditions, such as hypertension, that encourage increased left ventricular

145: 4051: 4010: 3969: 3882: 3838: 3802: 3705: 3664: 3620: 3539: 3437: 3402: 3361: 3320: 3271: 3207: 3156: 3105: 3048: 3013: 2962: 2911: 2870: 2829: 2780: 2723: 2673: 2638: 2589: 2537: 2518: 2486: 2396: 2292: 2251: 2210: 2172: 2121: 2080: 2023: 2002:

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

1988: 1936: 1885: 1826: 1769: 1720: 1670: 1629: 1580: 1531: 1474: 1439: 1398: 1349: 1300: 1256: 1207: 1166: 1117: 246:

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

4026:"How do patients with heart failure with preserved ejection fraction die?" 3752: 3488: 1148: 5046: 4203: 4001: 3984: 2943: 2202: 1858: 1513: 1108: 1091: 963: 784: 759: 675: 541: 489: 422: 418: 350: 329: 320: 254: 223: 106: 91: 4123: 3377:"Management of heart failure with preserved ejection fraction: a review" 3198: 2843:

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

1927: 966:, and many others, may be of benefit due to their effect on preventing 885: 826:

Randomized studies on HFpEF patients have shown that exercise improves

642: 270: 176: 95: 3188: 3171: 2500:

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

2163: 667:

ventricular diastolic function. Important parameters include, rate of

469:

demands, increased diastolic left heart or pulmonary venous pressure.

5126: 5106: 4261: 4094:(10 (International edition) ed.). McGraw-Hill. pp. 658–60. 3231: 3229: 3227: 3225: 2715: 994:

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

410:

too is consistent with eccentric hypertrophy seen in this condition.

190:

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

28: 453:, depicting the cardiac cycle. Two complete cycles are illustrated. 2884:

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

1314:

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

788: 787:

to relieve complications associated with volume overload, such as

503: 445: 214:

into the tissue beneath the endothelium that subsequently release

153: 3336:"Heart failure: what does ejection fraction have to do with it?" 704: 4167: 1783:

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

1645:"Heart failure with normal left ventricular ejection fraction" 1029: 621:

Non-simultaneous contraction of the left and right ventricle,

2554:

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

662:

are invasive procedures and thus reserved for patients with

2342: 2340: 2338: 2336: 1054:, was the predominant cause in population-based studies. 938:

perturbation and diminished LV filling seen in HFpEF the

2184: 2182: 974:, a significant player in the pathophysiology of HFpEF. 671:

relaxation, rate of ventricular filling, and stiffness.

584:

Pulmonary hypertension and right ventricular dysfunction

355:

Age – elderly patients mainly if they have hypertension.

194:

of the heart. Specifically, by reducing availability of

124:

There is controversy regarding the relationship between

3764: 3762: 2459:

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

2224:

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

109:

function: there is an increase in the stiffness of the

2045:

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

1948: 1946: 1046:(NYHA classes II-IV), cardiovascular death, including 765:

Another parameter to assess diastolic function is the

303:, resulting from accumulation of aggregated wild-type 2265:

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

476:. In contrast, systolic heart failure has usually an 261:, or a result of the previously described changes in 4113: 2312:. Lippincott Williams & Wilkins. pp. 420–. 2137:"Cardiomyocyte stiffness in diastolic heart failure" 5213: 5156: 5065: 5032: 5004: 4962: 4921: 4898: 4872: 4840: 4798: 4779: 4678: 4664: 4564: 4518: 4504: 4420: 4369: 4362: 4299: 4254: 4211: 4202: 4117: 1498:"Cardiac macrophages promote diastolic dysfunction" 40: 21: 513:diastolic pressure, and therefore have increased ( 1594:Mohammed SF, Majure DT, Redfield MM (July 2016). 238:can lead to structural changes in the heart on a 2416:. Jones & Bartlett Publishers. p. 323. 1133:"Heart Failure with Preserved Ejection Fraction" 3906:"Israel's CorAssist keeps a weak heart pumping" 2549: 2547: 3725: 3723: 1085: 1083: 1081: 1079: 1028:elasticity. This had not been approved by the 950:Angiotensin converting enzyme (ACE) inhibitors 53:Heart failure with preserved ejection fraction 4179: 3599:Journal of the American College of Cardiology 3291:Journal of the American College of Cardiology 2982:Journal of the American College of Cardiology 2890:Journal of the American College of Cardiology 2849:Journal of the American College of Cardiology 2751:Journal of the American College of Cardiology 2609:Journal of the American College of Cardiology 2365:Journal of the American College of Cardiology 2271:Journal of the American College of Cardiology 1959:Journal of the American College of Cardiology 1789:Journal of the American College of Cardiology 1649:Journal of the American College of Cardiology 1418:Journal of the American College of Cardiology 1279:Journal of the American College of Cardiology 1186:Journal of the American College of Cardiology 897:Mineralocorticoid receptor antagonists (MRAs) 8: 77:heart failure with reduced ejection fraction 1846:International Journal of Molecular Sciences 1268: 1266: 4795: 4675: 4515: 4496:Arrhythmogenic right ventricular dysplasia 4366: 4208: 4186: 4172: 4164: 4114: 2446: 998:has the benefit lowering the heart rate). 508:End Diastolic Pressure Volume Relationship 148:, exercise intolerance, fatigue, elevated 27: 18: 4041: 4000: 3959: 3941: 3695: 3654: 3610: 3529: 3519: 3478: 3392: 3351: 3310: 3261: 3197: 3187: 3146: 3136: 3095: 3003: 2993: 2952: 2942: 2901: 2860: 2819: 2770: 2628: 2579: 2527: 2517: 2476: 2386: 2376: 2282: 2241: 2162: 2152: 2111: 2070: 1978: 1926: 1916: 1875: 1857: 1808: 1759: 1710: 1660: 1619: 1570: 1521: 1429: 1388: 1339: 1290: 1246: 1197: 1156: 1107: 956:angiotensin converting enzyme inhibitors 820:angiotensin converting enzyme inhibitors 746:. Volumetric definition of the heart in 3375:Nanayakkara S, Kaye DM (October 2015). 1412:Witteles RM, Fowler MB (January 2008). 1075: 978:Angiotensin II receptor blockers (ARBs) 806:specific to HFpEF include avoidance of 4230:Spontaneous coronary artery dissection 3904:Kloosterman, Karin (27 October 2008). 3451:Howden EJ, Sarma S, Levine BD (2018). 2047:"The pathogenesis of cardiac fibrosis" 1221:LeWinter MM, Meyer M (November 2013). 3768: 2346: 727:elevated pressures in the left heart. 7: 4554:Nonbacterial thrombotic endocarditis 2051:Cellular and Molecular Life Sciences 1502:The Journal of Experimental Medicine 3989:The New England Journal of Medicine 3418:Progress in Cardiovascular Diseases 3088:10.1161/circheartfailure.114.001825 2309:Textbook of cardiovascular medicine 2191:The New England Journal of Medicine 1612:10.1161/CIRCHEARTFAILURE.116.003272 1239:10.1161/CIRCHEARTFAILURE.113.000825 1137:The New England Journal of Medicine 1096:The New England Journal of Medicine 828:left ventricular diastolic function 105:HFpEF is characterized by abnormal 4850:Accelerated idioventricular rhythm 3733:The American Journal of Cardiology 3521:10.1161/hypertensionaha.112.202705 2478:10.1161/01.cir.0000048123.22359.a0 2243:10.1161/01.cir.0000164273.57823.26 2154:10.1161/01.cir.0000155257.33485.6d 834:, and is associated with improved 654:HFpEF is typically diagnosed with 14: 4030:European Journal of Heart Failure 3697:10.1161/CIRCULATIONAHA.106.632745 3471:10.1161/CIRCULATIONAHA.117.030617 3176:European Journal of Heart Failure 2800:European Journal of Heart Failure 2704:European Journal of Heart Failure 2113:10.1161/circulationaha.105.587519 1643:Maeder MT, Kaye DM (March 2009). 1332:10.1161/CIRCULATIONAHA.113.001475 918:, during treatment is necessary. 3783:The American Journal of Medicine 3334:Iwano H, Little WC (July 2013). 4535:Subacute bacterial endocarditis 3394:10.1016/j.clinthera.2015.08.005 1545:Paulus WJ, Zile MR (May 2021). 1060:New England Journal of Medicine 601:Cardiac output is dependent on 332:related genes in the heart. 216:transforming growth factor beta 82:Risk factors for HFpEF include 3875:10.1016/j.cardfail.2022.02.010 882:phosphodiesterase-5-inhibitors 381:Gross structural abnormalities 1: 5052:Pulseless electrical activity 4981:Multifocal atrial tachycardia 4855:Catecholaminergic polymorphic 4090:Fuster V, O'Rouke RA (2001). 4024:Chan MM, Lam CS (June 2013). 3831:10.1016/s0140-6736(07)60980-5 3795:10.1016/s0002-9343(03)00158-x 1563:10.1161/CIRCRESAHA.121.318159 1199:10.1016/S0735-1097(03)00186-4 1131:Redfield MM (November 2016). 877:angiotensin receptor blockers 3943:10.3390/biomedicines11010070 3745:10.1016/0002-9149(93)90520-m 3572:10.1161/CIR.0000000000001063 3254:10.1136/heartjnl-2017-311652 3041:10.1136/heartjnl-2014-307040 2306:Topol EJ, Califf RM (2007). 990:There is some evidence that 588:Most HFpEF patients exhibit 142:paroxysmal nocturnal dyspnea 519:high output cardiac failure 301:Senile systemic amyloidosis 5292: 4996:Wandering atrial pacemaker 4543:non-infective endocarditis 4484:Endocardial fibroelastosis 3863:Journal of Cardiac Failure 3612:10.1016/j.jacc.2011.09.062 3430:10.1016/j.pcad.2014.10.001 3353:10.1016/j.jjcc.2013.02.017 3303:10.1016/j.jacc.2014.08.036 3076:Circulation: Heart Failure 2995:10.1016/j.jacc.2012.02.055 2903:10.1016/j.jacc.2006.10.023 2862:10.1016/j.jacc.2006.10.022 2763:10.1016/j.jacc.2010.03.077 2621:10.1016/j.jacc.2008.11.051 2378:10.1016/j.jacc.2014.03.062 2284:10.1016/j.jacc.2005.09.032 1971:10.1016/j.jacc.2009.05.013 1801:10.1016/j.jacc.2019.12.049 1752:10.1016/j.jchf.2013.11.004 1662:10.1016/j.jacc.2008.12.007 1600:Circulation: Heart Failure 1455:Nature Reviews. Cardiology 1431:10.1016/j.jacc.2007.10.021 1381:10.1016/j.jchf.2018.05.018 1292:10.1016/j.jacc.2013.05.019 1227:Circulation: Heart Failure 916:glomerular filtration rate 539: 369:Restrictive cardiomyopathy 5074:hexaxial reference system 5019:Jervell and Lange-Nielsen 4549:Libman–Sacks endocarditis 2666:10.1007/s10741-015-9523-6 2063:10.1007/s00018-013-1349-6 2016:10.1007/s10741-012-9365-4 954:Likewise, treatment with 836:aerobic exercise capacity 791:and high blood pressure. 575:Non-diastolic dysfunction 488:, increased interstitial 364:Constrictive pericarditis 35: 26: 4954:Ventricular fibrillation 4225:Coronary artery aneurysm 3656:10.1093/eurheartj/ehi115 2572:10.1093/eurheartj/ehw241 1918:10.1093/eurheartj/ehi044 1712:10.1093/eurheartj/ehv338 1467:10.1038/nrcardio.2018.19 992:calcium channel blockers 986:Calcium channel blockers 569:Doppler echocardiography 463:Frank-Starling mechanism 323:levels that occurs with 5231:Diastolic heart failure 5205:Athletic heart syndrome 5166:Ventricular hypertrophy 4900:Pre-excitation syndrome 4754:Left posterior fascicle 4279:Acute coronary syndrome 4219:Coronary artery disease 3138:10.1186/1471-2318-11-71 750:was first described by 486:ventricular hypertrophy 259:coronary artery disease 150:jugular venous pressure 126:diastolic heart failure 100:obstructive sleep apnea 73:cardiac catheterization 4749:Left anterior fascicle 4529:infective endocarditis 4314:Hibernating myocardium 4195:Cardiovascular disease 4069:Estafanous FG (2001). 3643:European Heart Journal 2560:European Heart Journal 2519:10.1136/heart.87.2.121 1699:European Heart Journal 1044:advanced heart failure 968:ventricular remodeling 689:Chagasic heart disease 639:microvascular function 633:Systemic abnormalities 590:pulmonary hypertension 561:ventricular relaxation 509: 474:concentric hypertrophy 454: 401:Cellular abnormalities 391:concentric hypertrophy 119:pulmonary hypertension 4913:Wolff–Parkinson–White 4873:Premature contraction 4771:Adams–Stokes syndrome 4474:Loeffler endocarditis 4284:Myocardial infarction 4043:10.1093/eurjhf/hft062 3381:Clinical Therapeutics 3340:Journal of Cardiology 2812:10.1093/eurjhf/hft026 2654:Heart Failure Reviews 2004:Heart Failure Reviews 1149:10.1056/NEJMcp1511175 854:Pharmacologic therapy 658:. Techniques such as 507: 478:eccentric hypertrophy 449: 442:Diastolic dysfunction 395:eccentric hypertrophy 22:Diastolic dysfunction 5080:Right axis deviation 5042:Sudden cardiac death 4400:Pericardial effusion 4343:Ventricular aneurysm 4002:10.1056/NEJMoa051530 2944:10.3390/biom12020278 2203:10.1056/nejmcp022709 1859:10.3390/ijms25105153 1551:Circulation Research 1514:10.1084/jem.20171274 1180:Zile MR (May 2003). 1109:10.1056/nejmoa052256 1064:systolic dysfunction 1052:sudden cardiac death 627:biventricular pacing 495:hydrostatic pressure 267:myosin cross bridges 5085:Left axis deviation 4942:Atrial fibrillation 4937:Ventricular flutter 4860:Torsades de pointes 4734:Bundle branch block 4693:Sick sinus syndrome 4479:Cardiac amyloidosis 4464:Tachycardia-induced 4319:Myocardial stunning 4267:Prinzmetal's angina 4236:Coronary thrombosis 3825:(9579): 2079–2087. 2410:Crowley LV (2013). 1740:JACC. Heart Failure 1369:JACC. Heart Failure 867:is as yet unclear. 848:natriuretic peptide 846:balance, and serum 800:atrial fibrillation 423:fibrillar collagens 295:vascular compliance 115:atrial fibrillation 5188:Atrial enlargement 4986:Pacemaker syndrome 4908:Lown–Ganong–Levine 4830:Junctional ectopic 4825:AV nodal reentrant 4331:Myocardial rupture 4241:Coronary vasospasm 4072:Cardiac anesthesia 2349:, pp. 658–60. 1008:low blood pressure 510: 455: 427:metalloproteinases 309:degenerative aging 185:insulin resistance 181:metabolic syndrome 132:Signs and symptoms 5256: 5255: 5248:Obstructive shock 5152: 5151: 5099:Short QT syndrome 5066:Other / ungrouped 5057:Sinoatrial arrest 4972:Ectopic pacemaker 4868: 4867: 4688:Sinus bradycardia 4660: 4659: 4656: 4655: 4405:Cardiac tamponade 4358: 4357: 4348:Dressler syndrome 4246:Myocardial bridge 4161: 4160: 4101:978-0-07-116296-8 4092:Hurst's The Heart 3690:(20): 2138–2147. 3465:(15): 1549–1560. 3387:(10): 2186–2198. 3297:(21): 2281–2293. 3189:10.1002/ejhf.1399 3035:(17): 1355–1360. 2710:(12): 1472–1487. 2615:(13): 1119–1126. 2566:(43): 3293–3302. 2371:(12): 1257–1266. 2319:978-0-7817-7012-5 2236:(18): 2306–2312. 2197:(11): 1097–1105. 2106:(16): 1966–1973. 1810:20.500.11815/3349 1705:(38): 2585–2594. 1557:(10): 1451–1467. 1285:(16): e147–e239. 1143:(19): 1868–1877. 744:ejection fraction 554:at left side and 387:ejection fraction 210:, which recruits 202:and regulator of 65:ejection fraction 50: 49: 16:Medical condition 5281: 5221:Cardiac fibrosis 5113:T wave alternans 5006:Long QT syndrome 4800:Supraventricular 4796: 4729:Intraventricular 4676: 4516: 4367: 4212:Coronary disease 4209: 4188: 4181: 4174: 4165: 4115: 4105: 4086: 4056: 4055: 4045: 4021: 4015: 4014: 4004: 3980: 3974: 3973: 3963: 3945: 3920: 3914: 3913: 3901: 3895: 3894: 3857: 3851: 3850: 3813: 3807: 3806: 3778: 3772: 3766: 3757: 3756: 3727: 3718: 3717: 3699: 3675: 3669: 3668: 3658: 3631: 3625: 3624: 3614: 3590: 3584: 3583: 3550: 3544: 3543: 3533: 3523: 3514:(5): 1200–1206. 3499: 3493: 3492: 3482: 3448: 3442: 3441: 3413: 3407: 3406: 3396: 3372: 3366: 3365: 3355: 3331: 3325: 3324: 3314: 3282: 3276: 3275: 3265: 3233: 3220: 3219: 3201: 3191: 3167: 3161: 3160: 3150: 3140: 3116: 3110: 3109: 3099: 3067: 3061: 3060: 3024: 3018: 3017: 3007: 2997: 2973: 2967: 2966: 2956: 2946: 2922: 2916: 2915: 2905: 2881: 2875: 2874: 2864: 2840: 2834: 2833: 2823: 2791: 2785: 2784: 2774: 2742: 2736: 2735: 2716:10.1002/ejhf.630 2701: 2692: 2686: 2685: 2649: 2643: 2642: 2632: 2600: 2594: 2593: 2583: 2551: 2542: 2541: 2531: 2521: 2497: 2491: 2490: 2480: 2456: 2450: 2444: 2438: 2437: 2432: 2430: 2407: 2401: 2400: 2390: 2380: 2356: 2350: 2344: 2331: 2330: 2328: 2326: 2303: 2297: 2296: 2286: 2262: 2256: 2255: 2245: 2221: 2215: 2214: 2186: 2177: 2176: 2166: 2156: 2132: 2126: 2125: 2115: 2091: 2085: 2084: 2074: 2042: 2036: 2035: 1999: 1993: 1992: 1982: 1950: 1941: 1940: 1930: 1920: 1896: 1890: 1889: 1879: 1861: 1837: 1831: 1830: 1812: 1795:(9): 1074–1082. 1780: 1774: 1773: 1763: 1731: 1725: 1724: 1714: 1690: 1684: 1681: 1675: 1674: 1664: 1640: 1634: 1633: 1623: 1591: 1585: 1584: 1574: 1542: 1536: 1535: 1525: 1493: 1487: 1486: 1450: 1444: 1443: 1433: 1409: 1403: 1402: 1392: 1360: 1354: 1353: 1343: 1311: 1305: 1304: 1294: 1270: 1261: 1260: 1250: 1233:(6): 1112–1115. 1218: 1212: 1211: 1201: 1192:(9): 1519–1522. 1177: 1171: 1170: 1160: 1128: 1122: 1121: 1111: 1087: 1014:SGLT2 Inhibitors 832:ability to relax 796:standard of care 770: 769: 656:echocardiography 263:microvasculature 204:protein kinase G 69:echocardiography 31: 19: 5291: 5290: 5284: 5283: 5282: 5280: 5279: 5278: 5259: 5258: 5257: 5252: 5243:Rheumatic fever 5209: 5148: 5061: 5028: 5000: 4958: 4917: 4894: 4864: 4836: 4783: 4775: 4669: 4652: 4560: 4509: 4500: 4416: 4410:Hemopericardium 4354: 4295: 4289:Unstable angina 4262:Angina pectoris 4255:Active ischemia 4250: 4198: 4192: 4162: 4157: 4156: 4126: 4112: 4102: 4089: 4083: 4068: 4065: 4060: 4059: 4023: 4022: 4018: 3982: 3981: 3977: 3922: 3921: 3917: 3903: 3902: 3898: 3859: 3858: 3854: 3815: 3814: 3810: 3780: 3779: 3775: 3767: 3760: 3729: 3728: 3721: 3677: 3676: 3672: 3633: 3632: 3628: 3592: 3591: 3587: 3552: 3551: 3547: 3501: 3500: 3496: 3450: 3449: 3445: 3415: 3414: 3410: 3374: 3373: 3369: 3333: 3332: 3328: 3284: 3283: 3279: 3235: 3234: 3223: 3169: 3168: 3164: 3118: 3117: 3113: 3069: 3068: 3064: 3026: 3025: 3021: 2975: 2974: 2970: 2924: 2923: 2919: 2883: 2882: 2878: 2842: 2841: 2837: 2793: 2792: 2788: 2757:(11): 845–854. 2744: 2743: 2739: 2699: 2694: 2693: 2689: 2651: 2650: 2646: 2602: 2601: 2597: 2553: 2552: 2545: 2499: 2498: 2494: 2458: 2457: 2453: 2447:Estafanous 2001 2445: 2441: 2428: 2426: 2424: 2409: 2408: 2404: 2358: 2357: 2353: 2345: 2334: 2324: 2322: 2320: 2305: 2304: 2300: 2264: 2263: 2259: 2223: 2222: 2218: 2188: 2187: 2180: 2134: 2133: 2129: 2093: 2092: 2088: 2044: 2043: 2039: 2001: 2000: 1996: 1952: 1951: 1944: 1898: 1897: 1893: 1839: 1838: 1834: 1782: 1781: 1777: 1733: 1732: 1728: 1692: 1691: 1687: 1682: 1678: 1655:(11): 905–918. 1642: 1641: 1637: 1593: 1592: 1588: 1544: 1543: 1539: 1495: 1494: 1490: 1452: 1451: 1447: 1411: 1410: 1406: 1362: 1361: 1357: 1326:(10): 1085–93. 1313: 1312: 1308: 1272: 1271: 1264: 1220: 1219: 1215: 1179: 1178: 1174: 1130: 1129: 1125: 1089: 1088: 1077: 1072: 1039: 1025: 1016: 1004: 988: 980: 952: 924: 899: 894: 873: 861: 856: 780: 767: 766: 660:catheterization 652: 635: 619: 599: 586: 577: 556:tricuspid valve 544: 538: 499:pulmonary edema 465:with increased 451:Wiggers diagram 444: 413:Changes in the 403: 383: 378: 376:Pathophysiology 345:Aortic stenosis 338: 319:The decline in 317: 307:as part of the 291:cardiac reserve 283: 252: 232: 198:, an important 166: 134: 59:) is a form of 17: 12: 11: 5: 5289: 5288: 5285: 5277: 5276: 5274:Cardiomyopathy 5271: 5269:Heart diseases 5261: 5260: 5254: 5253: 5251: 5250: 5245: 5240: 5239: 5238: 5236:Cardiac asthma 5233: 5223: 5217: 5215: 5211: 5210: 5208: 5207: 5202: 5201: 5200: 5195: 5185: 5184: 5183: 5178: 5173: 5162: 5160: 5154: 5153: 5150: 5149: 5147: 5146: 5144:Strain pattern 5141: 5140: 5139: 5134: 5129: 5117: 5116: 5115: 5103: 5102: 5101: 5089: 5088: 5087: 5082: 5069: 5067: 5063: 5062: 5060: 5059: 5054: 5049: 5044: 5038: 5036: 5034:Cardiac arrest 5030: 5029: 5027: 5026: 5021: 5016: 5014:Andersen–Tawil 5010: 5008: 5002: 5001: 4999: 4998: 4993: 4988: 4983: 4978: 4968: 4966: 4960: 4959: 4957: 4956: 4951: 4950: 4949: 4939: 4934: 4932:Atrial flutter 4928: 4926: 4919: 4918: 4916: 4915: 4910: 4904: 4902: 4896: 4895: 4893: 4892: 4887: 4882: 4876: 4874: 4870: 4869: 4866: 4865: 4863: 4862: 4857: 4852: 4846: 4844: 4838: 4837: 4835: 4834: 4833: 4832: 4827: 4817: 4816: 4815: 4804: 4802: 4793: 4777: 4776: 4774: 4773: 4768: 4767: 4766: 4761: 4756: 4751: 4746: 4741: 4731: 4726: 4725: 4724: 4719: 4714: 4704: 4695: 4690: 4684: 4682: 4673: 4662: 4661: 4658: 4657: 4654: 4653: 4651: 4650: 4649: 4648: 4643: 4631: 4630: 4629: 4624: 4612: 4611: 4610: 4605: 4593: 4592: 4591: 4586: 4581: 4568: 4566: 4562: 4561: 4559: 4558: 4557: 4556: 4551: 4539: 4538: 4537: 4524: 4522: 4513: 4502: 4501: 4499: 4498: 4493: 4492: 4491: 4486: 4481: 4476: 4471: 4466: 4461: 4456: 4455: 4454: 4442:Cardiomyopathy 4439: 4438: 4437: 4435:Chagas disease 4426: 4424: 4418: 4417: 4415: 4414: 4413: 4412: 4407: 4397: 4396: 4395: 4386: 4375: 4373: 4364: 4360: 4359: 4356: 4355: 4353: 4352: 4351: 4350: 4345: 4335: 4334: 4333: 4323: 4322: 4321: 4316: 4305: 4303: 4297: 4296: 4294: 4293: 4292: 4291: 4286: 4276: 4275: 4274: 4269: 4258: 4256: 4252: 4251: 4249: 4248: 4243: 4238: 4233: 4227: 4222: 4215: 4213: 4206: 4200: 4199: 4193: 4191: 4190: 4183: 4176: 4168: 4159: 4158: 4155: 4154: 4143: 4127: 4122: 4121: 4119: 4118:Classification 4111: 4110:External links 4108: 4107: 4106: 4100: 4087: 4082:978-0781721950 4081: 4064: 4061: 4058: 4057: 4016: 3975: 3915: 3896: 3869:(5): e1–e167. 3852: 3808: 3773: 3771:, p. 709. 3758: 3739:(7): 602–604. 3719: 3670: 3649:(3): 215–225. 3626: 3605:(5): 442–451. 3585: 3545: 3494: 3443: 3424:(4): 347–355. 3408: 3367: 3326: 3277: 3248:(5): 407–415. 3221: 3182:(4): 495–505. 3162: 3125:BMC Geriatrics 3111: 3082:(2): 286–294. 3062: 3019: 2988:(2): 120–128. 2968: 2917: 2876: 2835: 2806:(7): 776–785. 2786: 2737: 2687: 2644: 2595: 2543: 2512:(2): 121–125. 2492: 2471:(5): 714–720. 2451: 2449:, p. 562. 2439: 2422: 2402: 2351: 2332: 2318: 2298: 2277:(3): 500–506. 2257: 2216: 2178: 2147:(6): 774–781. 2127: 2086: 2057:(4): 549–574. 2037: 1994: 1965:(5): 410–418. 1942: 1911:(4): 384–416. 1891: 1832: 1775: 1746:(2): 113–122. 1726: 1685: 1676: 1635: 1586: 1537: 1508:(2): 423–440. 1488: 1461:(4): 196–197. 1445: 1404: 1375:(8): 701–709. 1355: 1306: 1262: 1213: 1172: 1123: 1102:(3): 251–259. 1074: 1073: 1071: 1068: 1038: 1035: 1024: 1021: 1015: 1012: 1003: 1000: 987: 984: 979: 976: 951: 948: 923: 920: 903:spironolactone 898: 895: 893: 890: 872: 869: 860: 857: 855: 852: 830:, the heart's 779: 776: 756:cardiac output 736: 735: 732: 728: 724: 701:stress imaging 651: 648: 634: 631: 618: 615: 598: 595: 585: 582: 576: 573: 540:Main article: 537: 534: 497:and promoting 443: 440: 407:cardiomyocytes 402: 399: 382: 379: 377: 374: 373: 372: 366: 357: 356: 353: 348: 337: 334: 316: 313: 282: 279: 251: 248: 231: 228: 218:, encouraging 165: 162: 133: 130: 111:left ventricle 88:hyperlipidemia 48: 47: 44: 38: 37: 33: 32: 24: 23: 15: 13: 10: 9: 6: 4: 3: 2: 5287: 5286: 5275: 5272: 5270: 5267: 5266: 5264: 5249: 5246: 5244: 5241: 5237: 5234: 5232: 5229: 5228: 5227: 5226:Heart failure 5224: 5222: 5219: 5218: 5216: 5212: 5206: 5203: 5199: 5196: 5194: 5191: 5190: 5189: 5186: 5182: 5179: 5177: 5174: 5172: 5169: 5168: 5167: 5164: 5163: 5161: 5159: 5155: 5145: 5142: 5138: 5137:ST depression 5135: 5133: 5130: 5128: 5125: 5124: 5123: 5122: 5118: 5114: 5111: 5110: 5109: 5108: 5104: 5100: 5097: 5096: 5095: 5094: 5090: 5086: 5083: 5081: 5078: 5077: 5076: 5075: 5071: 5070: 5068: 5064: 5058: 5055: 5053: 5050: 5048: 5045: 5043: 5040: 5039: 5037: 5035: 5031: 5025: 5022: 5020: 5017: 5015: 5012: 5011: 5009: 5007: 5003: 4997: 4994: 4992: 4989: 4987: 4984: 4982: 4979: 4977: 4973: 4970: 4969: 4967: 4965: 4961: 4955: 4952: 4948: 4945: 4944: 4943: 4940: 4938: 4935: 4933: 4930: 4929: 4927: 4925: 4920: 4914: 4911: 4909: 4906: 4905: 4903: 4901: 4897: 4891: 4888: 4886: 4883: 4881: 4878: 4877: 4875: 4871: 4861: 4858: 4856: 4853: 4851: 4848: 4847: 4845: 4843: 4839: 4831: 4828: 4826: 4823: 4822: 4821: 4818: 4814: 4811: 4810: 4809: 4806: 4805: 4803: 4801: 4797: 4794: 4791: 4787: 4782: 4778: 4772: 4769: 4765: 4764:Trifascicular 4762: 4760: 4757: 4755: 4752: 4750: 4747: 4745: 4742: 4740: 4737: 4736: 4735: 4732: 4730: 4727: 4723: 4720: 4718: 4715: 4713: 4710: 4709: 4708: 4705: 4703: 4699: 4696: 4694: 4691: 4689: 4686: 4685: 4683: 4681: 4677: 4674: 4672: 4667: 4663: 4647: 4646:regurgitation 4644: 4642: 4639: 4638: 4637: 4636: 4632: 4628: 4627:regurgitation 4625: 4623: 4620: 4619: 4618: 4617: 4613: 4609: 4608:regurgitation 4606: 4604: 4601: 4600: 4599: 4598: 4594: 4590: 4589:regurgitation 4587: 4585: 4582: 4580: 4577: 4576: 4575: 4574: 4570: 4569: 4567: 4563: 4555: 4552: 4550: 4547: 4546: 4545: 4544: 4540: 4536: 4533: 4532: 4531: 4530: 4526: 4525: 4523: 4521: 4517: 4514: 4512: 4507: 4503: 4497: 4494: 4490: 4487: 4485: 4482: 4480: 4477: 4475: 4472: 4470: 4467: 4465: 4462: 4460: 4457: 4453: 4450: 4449: 4448: 4445: 4444: 4443: 4440: 4436: 4433: 4432: 4431: 4428: 4427: 4425: 4423: 4419: 4411: 4408: 4406: 4403: 4402: 4401: 4398: 4394: 4390: 4387: 4385: 4382: 4381: 4380: 4377: 4376: 4374: 4372: 4368: 4365: 4361: 4349: 4346: 4344: 4341: 4340: 4339: 4336: 4332: 4329: 4328: 4327: 4324: 4320: 4317: 4315: 4312: 4311: 4310: 4307: 4306: 4304: 4302: 4298: 4290: 4287: 4285: 4282: 4281: 4280: 4277: 4273: 4272:Stable angina 4270: 4268: 4265: 4264: 4263: 4260: 4259: 4257: 4253: 4247: 4244: 4242: 4239: 4237: 4234: 4231: 4228: 4226: 4223: 4220: 4217: 4216: 4214: 4210: 4207: 4205: 4201: 4196: 4189: 4184: 4182: 4177: 4175: 4170: 4169: 4166: 4153: 4149: 4148: 4144: 4142: 4138: 4137: 4133: 4129: 4128: 4125: 4120: 4116: 4109: 4103: 4097: 4093: 4088: 4084: 4078: 4074: 4073: 4067: 4066: 4062: 4053: 4049: 4044: 4039: 4036:(6): 604–13. 4035: 4031: 4027: 4020: 4017: 4012: 4008: 4003: 3998: 3994: 3990: 3986: 3979: 3976: 3971: 3967: 3962: 3957: 3953: 3949: 3944: 3939: 3935: 3931: 3927: 3919: 3916: 3911: 3907: 3900: 3897: 3892: 3888: 3884: 3880: 3876: 3872: 3868: 3864: 3856: 3853: 3848: 3844: 3840: 3836: 3832: 3828: 3824: 3820: 3812: 3809: 3804: 3800: 3796: 3792: 3788: 3784: 3777: 3774: 3770: 3765: 3763: 3759: 3754: 3750: 3746: 3742: 3738: 3734: 3726: 3724: 3720: 3715: 3711: 3707: 3703: 3698: 3693: 3689: 3685: 3681: 3674: 3671: 3666: 3662: 3657: 3652: 3648: 3644: 3640: 3636: 3630: 3627: 3622: 3618: 3613: 3608: 3604: 3600: 3596: 3589: 3586: 3581: 3577: 3573: 3569: 3565: 3561: 3557: 3549: 3546: 3541: 3537: 3532: 3527: 3522: 3517: 3513: 3509: 3505: 3498: 3495: 3490: 3486: 3481: 3476: 3472: 3468: 3464: 3460: 3459: 3454: 3447: 3444: 3439: 3435: 3431: 3427: 3423: 3419: 3412: 3409: 3404: 3400: 3395: 3390: 3386: 3382: 3378: 3371: 3368: 3363: 3359: 3354: 3349: 3345: 3341: 3337: 3330: 3327: 3322: 3318: 3313: 3308: 3304: 3300: 3296: 3292: 3288: 3281: 3278: 3273: 3269: 3264: 3259: 3255: 3251: 3247: 3243: 3239: 3232: 3230: 3228: 3226: 3222: 3217: 3213: 3209: 3205: 3200: 3195: 3190: 3185: 3181: 3177: 3173: 3166: 3163: 3158: 3154: 3149: 3144: 3139: 3134: 3130: 3126: 3122: 3115: 3112: 3107: 3103: 3098: 3093: 3089: 3085: 3081: 3077: 3073: 3066: 3063: 3058: 3054: 3050: 3046: 3042: 3038: 3034: 3030: 3023: 3020: 3015: 3011: 3006: 3001: 2996: 2991: 2987: 2983: 2979: 2972: 2969: 2964: 2960: 2955: 2950: 2945: 2940: 2936: 2932: 2928: 2921: 2918: 2913: 2909: 2904: 2899: 2895: 2891: 2887: 2880: 2877: 2872: 2868: 2863: 2858: 2855:(1): 97–105. 2854: 2850: 2846: 2839: 2836: 2831: 2827: 2822: 2817: 2813: 2809: 2805: 2801: 2797: 2790: 2787: 2782: 2778: 2773: 2768: 2764: 2760: 2756: 2752: 2748: 2741: 2738: 2733: 2729: 2725: 2721: 2717: 2713: 2709: 2705: 2698: 2691: 2688: 2683: 2679: 2675: 2671: 2667: 2663: 2660:(3): 285–97. 2659: 2655: 2648: 2645: 2640: 2636: 2631: 2626: 2622: 2618: 2614: 2610: 2606: 2599: 2596: 2591: 2587: 2582: 2577: 2573: 2569: 2565: 2561: 2557: 2550: 2548: 2544: 2539: 2535: 2530: 2525: 2520: 2515: 2511: 2507: 2503: 2496: 2493: 2488: 2484: 2479: 2474: 2470: 2466: 2462: 2455: 2452: 2448: 2443: 2440: 2436: 2425: 2423:9781449632403 2419: 2415: 2414: 2406: 2403: 2398: 2394: 2389: 2384: 2379: 2374: 2370: 2366: 2362: 2355: 2352: 2348: 2343: 2341: 2339: 2337: 2333: 2321: 2315: 2311: 2310: 2302: 2299: 2294: 2290: 2285: 2280: 2276: 2272: 2268: 2261: 2258: 2253: 2249: 2244: 2239: 2235: 2231: 2227: 2220: 2217: 2212: 2208: 2204: 2200: 2196: 2192: 2185: 2183: 2179: 2174: 2170: 2165: 2160: 2155: 2150: 2146: 2142: 2138: 2131: 2128: 2123: 2119: 2114: 2109: 2105: 2101: 2097: 2090: 2087: 2082: 2078: 2073: 2068: 2064: 2060: 2056: 2052: 2048: 2041: 2038: 2033: 2029: 2025: 2021: 2017: 2013: 2010:(2): 173–85. 2009: 2005: 1998: 1995: 1990: 1986: 1981: 1976: 1972: 1968: 1964: 1960: 1956: 1949: 1947: 1943: 1938: 1934: 1929: 1924: 1919: 1914: 1910: 1906: 1902: 1895: 1892: 1887: 1883: 1878: 1873: 1869: 1865: 1860: 1855: 1851: 1847: 1843: 1836: 1833: 1828: 1824: 1820: 1816: 1811: 1806: 1802: 1798: 1794: 1790: 1786: 1779: 1776: 1771: 1767: 1762: 1757: 1753: 1749: 1745: 1741: 1737: 1730: 1727: 1722: 1718: 1713: 1708: 1704: 1700: 1696: 1689: 1686: 1680: 1677: 1672: 1668: 1663: 1658: 1654: 1650: 1646: 1639: 1636: 1631: 1627: 1622: 1617: 1613: 1609: 1605: 1601: 1597: 1590: 1587: 1582: 1578: 1573: 1568: 1564: 1560: 1556: 1552: 1548: 1541: 1538: 1533: 1529: 1524: 1519: 1515: 1511: 1507: 1503: 1499: 1492: 1489: 1484: 1480: 1476: 1472: 1468: 1464: 1460: 1456: 1449: 1446: 1441: 1437: 1432: 1427: 1424:(2): 93–102. 1423: 1419: 1415: 1408: 1405: 1400: 1396: 1391: 1386: 1382: 1378: 1374: 1370: 1366: 1359: 1356: 1351: 1347: 1342: 1337: 1333: 1329: 1325: 1321: 1317: 1310: 1307: 1302: 1298: 1293: 1288: 1284: 1280: 1276: 1269: 1267: 1263: 1258: 1254: 1249: 1244: 1240: 1236: 1232: 1228: 1224: 1217: 1214: 1209: 1205: 1200: 1195: 1191: 1187: 1183: 1176: 1173: 1168: 1164: 1159: 1154: 1150: 1146: 1142: 1138: 1134: 1127: 1124: 1119: 1115: 1110: 1105: 1101: 1097: 1093: 1086: 1084: 1082: 1080: 1076: 1069: 1067: 1065: 1061: 1055: 1053: 1049: 1048:heart attacks 1045: 1036: 1034: 1031: 1022: 1020: 1013: 1011: 1009: 1001: 999: 997: 993: 985: 983: 977: 975: 973: 969: 965: 961: 957: 949: 947: 944: 941: 937: 933: 928: 927:Beta blockers 922:Beta blockers 921: 919: 917: 912: 908: 904: 896: 891: 889: 887: 883: 878: 870: 868: 866: 858: 853: 851: 849: 845: 839: 837: 833: 829: 824: 821: 817: 816:beta blockers 812: 809: 803: 801: 797: 792: 790: 786: 777: 775: 772: 763: 761: 757: 753: 749: 745: 740: 733: 731:dysfunction". 729: 725: 722: 718: 717: 716: 712: 708: 706: 702: 697: 692: 690: 684: 680: 677: 672: 670: 665: 661: 657: 649: 647: 644: 640: 632: 630: 628: 624: 616: 614: 612: 608: 604: 603:stroke volume 596: 594: 591: 583: 581: 574: 572: 570: 566: 562: 557: 553: 549: 543: 535: 533: 530: 526: 522: 520: 516: 506: 502: 500: 496: 491: 487: 481: 479: 475: 470: 468: 464: 459: 452: 448: 441: 439: 436: 432: 428: 424: 420: 416: 415:extracellular 411: 408: 400: 398: 396: 392: 388: 380: 375: 370: 367: 365: 362: 361: 360: 354: 352: 349: 346: 343: 342: 341: 335: 333: 331: 326: 322: 314: 312: 310: 306: 305:transthyretin 302: 298: 296: 293:, diminished 292: 288: 280: 278: 276: 272: 268: 264: 260: 256: 249: 247: 245: 241: 237: 229: 227: 225: 221: 217: 213: 209: 205: 201: 197: 193: 188: 186: 182: 178: 174: 170: 163: 161: 157: 155: 151: 147: 143: 139: 131: 129: 127: 122: 120: 116: 112: 108: 103: 101: 97: 93: 89: 85: 80: 78: 74: 70: 66: 63:in which the 62: 61:heart failure 58: 54: 45: 43: 39: 34: 30: 25: 20: 5158:Cardiomegaly 5132:ST elevation 5119: 5105: 5091: 5072: 4976:Ectopic beat 4924:fibrillation 4759:Bifascicular 4633: 4614: 4595: 4571: 4541: 4527: 4520:Endocarditis 4459:Hypertrophic 4393:Constrictive 4379:Pericarditis 4337: 4325: 4308: 4145: 4130: 4091: 4071: 4063:Bibliography 4033: 4029: 4019: 3995:(3): 260–9. 3992: 3988: 3978: 3933: 3930:Biomedicines 3929: 3918: 3909: 3899: 3866: 3862: 3855: 3822: 3818: 3811: 3786: 3782: 3776: 3736: 3732: 3687: 3683: 3673: 3646: 3642: 3629: 3602: 3598: 3588: 3563: 3559: 3548: 3511: 3508:Hypertension 3507: 3497: 3462: 3456: 3446: 3421: 3417: 3411: 3384: 3380: 3370: 3343: 3339: 3329: 3294: 3290: 3280: 3245: 3241: 3199:11343/285286 3179: 3175: 3165: 3128: 3124: 3114: 3079: 3075: 3065: 3032: 3028: 3022: 2985: 2981: 2971: 2934: 2931:Biomolecules 2930: 2920: 2896:(1): 88–96. 2893: 2889: 2879: 2852: 2848: 2838: 2803: 2799: 2789: 2754: 2750: 2740: 2707: 2703: 2690: 2657: 2653: 2647: 2612: 2608: 2598: 2563: 2559: 2509: 2505: 2495: 2468: 2464: 2454: 2442: 2434: 2427:. 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