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Hfnef

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Hfnef

  1. 1. Dr.DurgaPavan HFnEF-CONCEPTS AND MANAGEMENT
  2. 2. Heart failure (HF) can be defined as the inability of the heart to provide sufficient forward output to meet the perfusion and oxygenation requirements of the tissues while maintaining normal filling pressures. There are two major mechanisms by which this can occur: Systolic dysfunction, in which there is impaired cardiac contractile function. Diastolic dysfunction, in which there is abnormal cardiac relaxation, stiffness or filling HFnEF-CONCEPTS AND MANAGEMENT
  3. 3. Nearly half of patients with symptoms of heart failure are found to have a normal left ventricular (LV) ejection fraction. This has variously been labelled as diastolic heart failure, heart failure with preserved LV function or heart failure with a normal ejection fraction (HFNEF).  The preferred term should be HFNEF because accumulative evidence suggests that the physiological abnormalities in these patients are not restricted to diastole only, and systolic function is not entirely ‘‘preserved’’ when measures other than the ejection fraction are used. HFnEF-CONCEPTS AND MANAGEMENT
  4. 4. History Late seventies, the first studies appeared that showed diastolic LV dysfunction to importantly contribute to HF in hypertrophic cardiomyopathy, aortic stenosis, and hypertensive heart disease. First reports on HFPEF date back almost 30 years. Pulmonary congestion was reported in a small group of elderly, mostly female African-American hypertensive patients with supranormal systolic pump function and evidence for diastolic dysfunction. HFnEF-CONCEPTS AND MANAGEMENT
  5. 5. It is now well established that among patients with the clinical syndrome of heart failure (HF), approximately half have preserved systolic function, known most commonly as heart failure with preserved ejection fraction (HFpEF). Although originally considered to be predominantly a syndrome that pathophysiologically involves abnormalities in diastolic function (relaxation and/or stiffness), ongoing investigation suggests that, although diastolic abnormalities may be present in many patients, other aspects of pathophysiology likely also contribute to symptoms HFnEF-CONCEPTS AND MANAGEMENT
  6. 6. Def Current European Society of Cardiology (ESC)/Heart Failure Association (HFA) recommendations require Signs and/or symptoms of heart failure, An ejection fraction above 50% Either direct evidence of diastolic dysfunction or indirect evidence HFnEF-CONCEPTS AND MANAGEMENT
  7. 7. Debates DHF vs HFPEF vs HFNEF (Terminology ) One disease continuum vs. two distinct disease entities HFnEF-CONCEPTS AND MANAGEMENT
  8. 8. Diastolic LV dysfunction was not unique to diastolic HF but also was present in HF with systolic LV dysfunction, the term diastolic HF was largely abandoned and was replaced by the terms HF with preserved LVEF or HFNEF. Preserved LVEF implies knowledge of a pre-existing LVEF, which is usually absent, and the exact range of a normal LVEF is hard to define. HFnEF-CONCEPTS AND MANAGEMENT
  9. 9. HFnEF-CONCEPTS AND MANAGEMENT
  10. 10. Pathophysiology Diastolic LV dysfunction Systolic LV dysfunction Impaired ventricular vascular coupling Abnormal exercise-induced and flow mediated vasodilation, Chronotropic incompetence, Pulmonary arterial hypertension HFnEF-CONCEPTS AND MANAGEMENT
  11. 11. Diastolic LV dysfunction HFnEF-CONCEPTS AND MANAGEMENT
  12. 12. Diastolic Mechanisms Early rapid filling - 70% to 80% of LV filling driven by the LA to LV pressure gradient  Myocardial relaxation,  LV diastolic stiffness,  LV elastic recoil,  LV contractile state,  LA pressures,  Pericardial constraint,  LA stiffness,  Pulmonary vein properties,  Mitral orifice area HFnEF-CONCEPTS AND MANAGEMENT
  13. 13. Diastasis LA and LV pressures are usually almost equal. It contributes < 5% of the LV filling, Its duration shortens with tachycardia HFnEF-CONCEPTS AND MANAGEMENT
  14. 14. Atrial systole - 15% to 25% of LV diastolic filling without raising the mean LA pressure.  depends on  PR interval,  Atrial inotropic state,  Atrial preload,  Atrial afterload,  Autonomic tone,  Heart rate. HFnEF-CONCEPTS AND MANAGEMENT
  15. 15. Although diastolic function is complex, the most important components are LV relaxation and LV diastolic stiffness. HFnEF-CONCEPTS AND MANAGEMENT
  16. 16. Left Ventricular Relaxation Active, energy-dependent process Begins during the ejection phase of systole , continues through isovolumic relaxation and the rapid filling phase HFnEF-CONCEPTS AND MANAGEMENT
  17. 17. HFnEF-CONCEPTS AND MANAGEMENT
  18. 18. Left Ventricular Relaxation and stiffness Diastolic dysfunction is caused by one or more of the following structural abnormalities: Hypertrophy Fibrosis Infiltrative diseases Pericardial constriction Myocardial edema HFnEF-CONCEPTS AND MANAGEMENT
  19. 19. Left Ventricular Relaxation and stiffness Functional cellular abnormalities  which is reversible and transient . Causes of impaired myocyte relaxation include: Ischemia and/or hypoxia Cellular calcium overload and/or ATP depletion Certain cardiovascular drugs, eg, digitalis The hypertrophy process itself which alters the contractile and metabolic phenotype HFnEF-CONCEPTS AND MANAGEMENT
  20. 20. Cellular mechanisms of LV relaxation and stiffness Role of calcium For complete myocyte relaxation to occur, the cytosol must be largely cleared of calcium so that calcium dissociates from troponin C, and all tension-generating actin-myosin bonds must be lysed. Increased intracellular calcium can directly impair diastolic relaxation by persistent activation of the actin- myosin cross-bridge interaction if calcium is not adequately cleared from the cytosol. HFnEF-CONCEPTS AND MANAGEMENT
  21. 21. HFnEF-CONCEPTS AND MANAGEMENT
  22. 22. Role of titin Giant elastic protein expressed in cardiomyocytes in two main isoforms, N2B (stiffer spring) and N2BA (more compliant spring). Titin functions as a bidirectional spring responsible for early diastolic LV recoil and late diastolic resistance to stretch. Titin is compressed when the myocyte shortens during systole. At the beginning of cell relaxation, when the actin-myosin crossbridges detach and active shortening tension begins to dissipate, the compressed titin forcefully expands and generates an intracellular "restoring force" that relengthens the sarcomere and myocyte HFnEF-CONCEPTS AND MANAGEMENT
  23. 23. Isoform expression of titin differs in patients with SHF and DHF: in patients with SHF, titin isoform expression shifts towards the more compliant isoform, whereas in patients with DHF the shift is towards the less compliant isoform. Isoform shifting may have an impact on diastolic function. shift to a larger isoform would predict a substantial decrease in passive myocardial stiffness. HFnEF-CONCEPTS AND MANAGEMENT
  24. 24. N2BA:N2B - HFREF N2BA:N2B - HFNEF HFnEF-CONCEPTS AND MANAGEMENT
  25. 25. Systolic dysfunction Ejection fraction is an index of global haemodynamic pump performance, insensitive to disturbances of ventricular muscle function. A preserved ejection fraction often merely indicates that the radial (or circumferential) fibres of the ventricle have compensated for dysfunction of the longitudinal fibres. Impaired longitudinal fibre function may be the single or most marked sign of cardiac dysfunction in HFpEF. HFnEF-CONCEPTS AND MANAGEMENT
  26. 26. Patients with HFNEF have concentric LV remodeling with high LV mass/volume ratio in contrast to patients with HFREF, who have eccentric LV remodeling with low LV mass/volume ratio. Signal transduction cascades driving myocardial remodeling differ in HFNEF and HFREF HFnEF-CONCEPTS AND MANAGEMENT
  27. 27. ventriculo-vascular coupling Ventricular and vascular stiffening increase with ageing, hypertension, and diabetes, and are abnormally elevated in patients with HFpEF Combined ventricular-arterial stiffening leads to greater blood pressure lability, by creating a ‘high gain’ system— with amplified blood pressure changes for any alteration in preload or afterload Patients with HFpEF display attenuated exercise-mediated reductions in mean vascular resistance and arterial elastance, coupled with abnormalities in endothelial function and dynamic ventricular –arterial coupling HFnEF-CONCEPTS AND MANAGEMENT
  28. 28. HFnEF-CONCEPTS AND MANAGEMENT
  29. 29. Chronotropic incompetence Chronotropic response during submaximal and peak workload is impaired in HFpEF. Autonomic dysfunction Baroreflex sensitivity is reduced HFnEF-CONCEPTS AND MANAGEMENT
  30. 30. cardiovascular reserve dysfunction HFnEF-CONCEPTS AND MANAGEMENT
  31. 31. Pulmonary HTN Both pre & post-capillary components HFnEF-CONCEPTS AND MANAGEMENT
  32. 32. HFpEF may be conceived as a fundamental disorder of cardiovascular reserve function— Diastolic, Systolic, Chronotropic, Vascular. HFnEF-CONCEPTS AND MANAGEMENT
  33. 33. Exaggerated hypertensive ageing Many of the abnormalities are noted with normal ageing and are simply more markedly abnormal in HFpEF HFnEF-CONCEPTS AND MANAGEMENT
  34. 34. Diagnosis Signs and/or symptoms of HF, Evidence of normal systolic LV function, Evidence of diastolic LV dysfunction or of surrogate markers of diastolic LV dysfunction such as LV hypertrophy, LA enlargement, plasma levels of natriuretic peptides (NP) HFnEF-CONCEPTS AND MANAGEMENT
  35. 35. C/F Framingham criteria HFnEF-CONCEPTS AND MANAGEMENT 2 major criteriA OR 1 major criteriA plus 2 minor criteria
  36. 36. Diagnostic value of symptoms and signs HFnEF-CONCEPTS AND MANAGEMENT Brunner-La Rocca [41] and Schweiz Me Forum2007;7(Suppl. 39):3–14 S
  37. 37. EVALUATION OF DIASTOLIC FUNCTION HFnEF-CONCEPTS AND MANAGEMENT
  38. 38. DD INDICES MITRAL B BUMP IVRT MITRAL INFLOW – E, A MITRAL ANNULAR VELOCITIES- Mitral inflow propagation velocity -VP Pulmonary Venous Doppler Flow into LA –  SYSTOLIC (S), DIASTOLIC (D) , ATRIAL REVERSAL (Ar), HFnEF-CONCEPTS AND MANAGEMENT
  39. 39. Two-Dimensional Echocardiography The combination of  Thickened left ventricular walls,  Left atrial dilation,  Absence of mitral valve disease Strong evidence of diastolic dysfunction and elevated left ventricular diastolic pressure. HFnEF-CONCEPTS AND MANAGEMENT
  40. 40. The normal rate of mitral valve closure after atrial systole is smooth and of brief duration. Pts with increased LVEDP  Onset of closure is premature  Notch in between A and C  Prolonged AC wave with a B bump Sign is low sensitivity but high specificity for LVEDP(LAP) > 20 mmhg Mitral B – bump HFnEF-CONCEPTS AND MANAGEMENT
  41. 41. M-Mode Echocardiography HFnEF-CONCEPTS AND MANAGEMENT
  42. 42. Mitral inflow patterns Pulmonary vein flow Doppler Evaluation of Diastolic Function HFnEF-CONCEPTS AND MANAGEMENT
  43. 43. Transmitral Doppler Inflow E velocity, A velocity, E/A deceleration time (DT) IVRT. HFnEF-CONCEPTS AND MANAGEMENT
  44. 44. E -PEAK EARLY FILLING VELOCITY A – PEAK FILLING VELOCITY DURING ATRIAL SYS E/A –LA-LV GRADIENT IN EARLY AND LATE DIASTOLE. DT –TIME INTERVAL FROM EARLY PEAK INFLOW (E) TO CESSATION OF RAPID FILLING PHASE.  A WAVE DURATION- ALONG WITH Pva REFLECTS LV FILLING PRESSURES HFnEF-CONCEPTS AND MANAGEMENT
  45. 45. A=83CM/S E/A=1.4E=123cm/s HFnEF-CONCEPTS AND MANAGEMENT
  46. 46. 1. E -PEAK EARLY FILLING VELOCITY 2. A – PEAK FILLING VELOCITY DURING ATRIAL SYS 3.E/A –LA-LV GRADIENT IN EARLY AND LATE DIASTOLE. 4.DT –TIME INTERVALFROM EARLY PEAK INFLOW (E) TO CESSATION OF RAPID FILLING PHASE. DT=148ms HFnEF-CONCEPTS AND MANAGEMENT
  47. 47. HFnEF-CONCEPTS AND MANAGEMENT
  48. 48. Limitations :  A large number of factors can affect the transmitral flow including age, heart rate, heart rhythm, loading conditions, LV systolic function, atrial function, and mitral valve disease.  TM flow cannot be used in isolation to assess diastolic function. HFnEF-CONCEPTS AND MANAGEMENT
  49. 49. Valsalva Maneuver Valsalva maneuver decreases preload during the strain phase, pseudonormal mitral inflow changes to a pattern of impaired relaxation. Mitral E velocity decreases with a prolongation of DT, whereas the A velocity is unchanged or increases, such that the E/A ratio decreases. A decrease of 50% in the E/A ratio is highly specific for increased LV filling pressures. HFnEF-CONCEPTS AND MANAGEMENT
  50. 50. IVRT Normal – 70-90 ms. HFnEF-CONCEPTS AND MANAGEMENT
  51. 51.  IVRT  lengthens - impaired LV relaxation  shortens - LV compliance is decreased and LV filling pressures increase. IVRT varies with HR, preload and ventricular fn. HFnEF-CONCEPTS AND MANAGEMENT
  52. 52. Pulmonary Venous Doppler Flow  right upper pul vein  > 0.5 cm into the pul vein  End-expiration  Sweep speed of 50 to 100 mm/s  Average of 3 values HFnEF-CONCEPTS AND MANAGEMENT
  53. 53. Measurements of pulmonary venous waveforms include Peak systolic (S) velocity- S1,S2 in bradycardia Peak anterograde diastolic (D) velocity, The S/D ratio – stages of diastolic dysfunction. Systolic filling fraction (S TVI/[S TVI + D TVI]) Peak Ar velocity late diastole , Duration of the Ar increases with increasing filling pressures (Ar – A ) most sensitive and earliest indicator elevated LV filling pressures. = LVEDP HFnEF-CONCEPTS AND MANAGEMENT
  54. 54. HFnEF-CONCEPTS AND MANAGEMENT
  55. 55. S wave -54.3 cm/sec
  56. 56. D = 74.2cm/sec S/D<1 HFnEF-CONCEPTS AND MANAGEMENT
  57. 57. Ar vel = 36cm/s HFnEF-CONCEPTS AND MANAGEMENT
  58. 58. Ar=130ms Ar-A=130-106=24ms HFnEF-CONCEPTS AND MANAGEMENT
  59. 59. Normal values-  Peak S wave velocity: 60 ± 15 cm/sec.  Peak D wave velocity: 40 ± 15 cm/sec.  Peak S / Peak D ratio: 1.3 – 1.5 ( ± 0.3).  Systolic fraction= 60 – 68 ±10%  Peak Ar wave velocity: -32 ± 10 cm/sec.  Ar duration: 137 ± 31 msec.  Ar – A : < 30 msec HFnEF-CONCEPTS AND MANAGEMENT
  60. 60.  An Ar velocity >35 cm/sec & a difference in duration ( Ar – A ) >30 msec, is higly predictive of a LVEDP > 15 mm Hg.  Major limitation is difficult to obtain and influence by rhythm distrubances HFnEF-CONCEPTS AND MANAGEMENT
  61. 61. Color M-Mode Vp - the slope of the first aliasing velocity during early filling, measured from the MV plane to 4 cm into the LV or the slope of the transition from no color to color. mitral inflow propagation velocity
  62. 62.  Normal Values: Vp>5O cm/s(< 45 is abnormal in adults)  PCWP = [5.27 x E/Vp] + 4.6 (in mmHg)  (5.27X 123/33.5)+4.6 = 23.5  E/Vp > 2.5 to predict PCWP >15 mm Hg.  E/Vp ratio for the prediction of LV filling pressures in patients with normal Efs should be cautious . (Vp may be normal in pts with normal EF) HFnEF-CONCEPTS AND MANAGEMENT
  63. 63. AFFECTED BY-  LV GEOMETRY  CHAMBER VOL  REGIONAL DYSSYNCHRONY  SYS FUNCTION NEVER IN ISLOATION HFnEF-CONCEPTS AND MANAGEMENT
  64. 64. Tissue Doppler Imaging (e’) •Apical 4 chamber view •Positioned at or 1 cm within the septal and lateral insertion sites of the mitral leaflets •Sweep speed of 50 to 100 mm/s •end-expiration •average of 3 •For mean take both medial and lateral annulus sites HFnEF-CONCEPTS AND MANAGEMENT
  65. 65. systolic (S), early diastolic(Ea, Em, E’, e’, and late diastolic velocities(Aa,Am, A’, or a’). e’/a’ , E/e’ , TE-e’ . e' is determined by LV relaxation, preload (minimally) a’ is determined by LA systolic function and LvEDP HFnEF-CONCEPTS AND MANAGEMENT
  66. 66. e’ The velocity of mitral annular movement during early diastole, designated as e or E velocity.′ ′ correlates well with invasive measures of the time constant of myocardial relaxation tau . In healthy young individuals, septal e is >10 cm/s′ and lateral e >15 cm/s at rest.′ HFnEF-CONCEPTS AND MANAGEMENT
  67. 67. E/e’ , Normal-5-10 cm/sec Predicts lv filling pressure- LAP - PCWP HFnEF-CONCEPTS AND MANAGEMENT
  68. 68. E/e’ Limitations Different cardiac cycles Age,preload,sys function Prosthetic valves Annular rings ---- DECREASE e’ Annular calcification Severe primary MR – increase e’ so, IVRT/E-e’ used HFnEF-CONCEPTS AND MANAGEMENT
  69. 69. IVRT/Te −E′ The ratio of IVRT/Te−E′ was inversely related to mean wedge pressure (and LA pressure) in patients with high filling pressures. The concept was evaluated in patients with mitral disease and atrial fibrillation. The major limitation to this method is the need to measure 3 time intervals from different cardiac cycles. IVRT/TE-e’ <2 indicates increased LAP. HFnEF-CONCEPTS AND MANAGEMENT
  70. 70. QRS TO e’ 458msHFnEF-CONCEPTS AND MANAGEMENT T e’-E = 21
  71. 71. E/e’ > 158 –15< 8 LVEDP > 12 LVEDPN Normal LV F Mitral valve diease IVRT/ TE-e’ < 2 YesNo TISSUE DOPPLER ANNULAR DIASTOLIC VELOCITIES HFnEF-CONCEPTS AND MANAGEMENT
  72. 72. HFnEF-CONCEPTS AND MANAGEMENT
  73. 73. QRS TO E 479msHFnEF-CONCEPTS AND MANAGEMENT
  74. 74. Stages of DHF HFnEF-CONCEPTS AND MANAGEMENT
  75. 75. HFnEF-CONCEPTS AND MANAGEMENT
  76. 76. Diastolic Stress Test E/e ´ ratio remains unchanged or is reduced-NORMAL E/e´ratio increases - impaired myocardial relaxation Exercise is usually performed using a supine bicycle protocol, HFnEF-CONCEPTS AND MANAGEMENT
  77. 77. In patients with diastolic heart failure, LA pressure is increased, leading to an increase in mitral E velocity, whereas annular e velocity remains reduced given the′ limited preload effect on e .′ On the other hand, in the absence of cardiac disease, e′ increases to a similar extent to the increase in mitral E velocity, and the normal E/e ratio essentially is′ unchanged with exercise. HFnEF-CONCEPTS AND MANAGEMENT
  78. 78. Twisting and untwisting  Twisting and untwisting of the LV are important aspects of cardiac mechanics and function.  The apical portion of the LV normally twists counterclockwise and the basal segment twists clockwise during systole, storing potential energy.  The LV untwists immediately after systolic contraction, contributing to generating an intraventricular pressure gradient.  LV torsion is the summation of the apical and the basal twisting.  measure twist using TDI and STE from short-axis images of the LV  These studies showed that torsion and circumferential strain are normal in patients with diastolic heart failure whereas longitudinal and radial deformation are reduced. HFnEF-CONCEPTS AND MANAGEMENT
  79. 79. MRI Acquire images in any selected plane or along any selected axis. This makes CMR the gold standard for LV volume, LA volume, and LV mass measurements. MR can provide a whole range of LV filling parameters which are identical or nearly identical to those obtained with echocardiography. CMR constitutes not only a valid alternative to echocardiography but could also be the first-choice technique if small changes in LA or LV volumes and in LV mass are expected. Several morphological and functional parameters such as tissue characterization or LV diastolic untwisting can only be assessed by CMR HFnEF-CONCEPTS AND MANAGEMENT
  80. 80. NP NPs may be much less useful in this condition: Increased wall stress is the stimulus for NP production and release from the cardiomyocyte, but, according to La-Place’s law, wall stress may be normal in a non-dilated, hypertrophied ventricle. Under these circumstances, NPs may mainly originate from the atria, explaining the common finding of only marginally elevated BNP or NT-proBNP levels despite highly symptomatic patients. NPs rise sharply once atrial fibrillation occurs, further underpinning the poor diagnostic value of these markers. HFnEF-CONCEPTS AND MANAGEMENT
  81. 81. Cardiac catheterization Simultaneous right & left heart catheterization can be useful in total hemodynamic assessment including elevated LV pressures & CO. Coronary angiography will help us to diagnose significant CAD. HFnEF-CONCEPTS AND MANAGEMENT
  82. 82. HFnEF-CONCEPTS AND MANAGEMENT
  83. 83. HFnEF-CONCEPTS AND MANAGEMENT
  84. 84. Diagnostic guidelines HFnEF-CONCEPTS AND MANAGEMENT
  85. 85. When comparing these 4 sets of diagnostic guidelines, it becomes evident that the mere presence of signs or symptoms of HF and a normal LVEF never sufficed to firmly establish the diagnosis of HFNEF, which always required additional evidence of diastolic LV dysfunction, LA size, or LV mass. HFnEF-CONCEPTS AND MANAGEMENT
  86. 86. HFnEF-CONCEPTS AND MANAGEMENT
  87. 87. Natural History Mortality - Allcause mortality for HFnlEF is similar to that of HF with a reduced EF. HF patients with normal EF more often died of noncardiovascular causes, whereas deaths due to coronary disease were less frequent. HFnEF-CONCEPTS AND MANAGEMENT
  88. 88. Framingham Heart Study, for patients with HFNEF the annual mortality was 8.7% compared with 3% in matched controls and for SHF was 18.9% compared with a 4.1% in age- and sexmatched controls over 6.2 years. HFnEF-CONCEPTS AND MANAGEMENT
  89. 89. Management Two objectives Treat the presenting syndrome of HF—  Relieve resting or exercise-associated venous congestion and  Eliminate precipitating factors. Reverse the factors responsible for diastolic dysfunction or other perturbations that lead to HFnlEF HFnEF-CONCEPTS AND MANAGEMENT
  90. 90. HFnEF-CONCEPTS AND MANAGEMENT
  91. 91. Age ≥60 years Current HF symptoms LVEF ≥0.45 NYHA Class III/IV • Echo (LVH, LAE) • ECG (LVH, LBBB) • CXR congestion I-PRESERVE NYHA class II - IV • CHF hosp. ≤6 months Key Exclusions: SBP >160 mm Hg; prior EF <40%; ACS or stroke ≤ 3m, hypertrophic or restrictive CM, pericardial or valvular disease, significant pulmonary disease, creatinine >2.5, Hb <11 HFnEF-CONCEPTS AND MANAGEMENT
  92. 92. Months from Randomization CumulativeIncidenceof PrimaryEvents(%) 40 - 0 - 10 - 20 - 30 - 0 6 12 18 24 36 4230 48 6054 2067 1929 1812 1730 1640 1513 12911569 1088 497816 2061 1921 1808 1715 1618 1466 12461539 1051 446776 No. at Risk Irbesartan Placebo HR (95% CI) = 0.95 (0.86-1.05) Log-rank p=0.35 Placebo Irbesartan HFnEF-CONCEPTS AND MANAGEMENT
  93. 93. Hong Kong Diastolic Heart Failure study  Diuretics, Diuretics + Irbesartan, or Diuretics + Ramipril were used. At the end of one year Irbesartan & Ramipril groups were better than diuretics alone in reducing BNP & improving LV systolic & diastolic function. Although quality of life & SBP & DBP were similar in all 3 groups HFnEF-CONCEPTS AND MANAGEMENT
  94. 94. HFnEF-CONCEPTS AND MANAGEMENT
  95. 95. HFnEF-CONCEPTS AND MANAGEMENT
  96. 96. HFnEF-CONCEPTS AND MANAGEMENT
  97. 97. HFnEF-CONCEPTS AND MANAGEMENT
  98. 98. HFnEF-CONCEPTS AND MANAGEMENT
  99. 99. HFnEF-CONCEPTS AND MANAGEMENT
  100. 100. Diuretics Mainstay of symptomatic treatment. Loop diuretics are preferred as they are more potent compared with thiazides. Diuretics should be initiated at lower doses and gradually up-titrated to maintenance doses. However, patients with HFNEF are typically very sensitive to relatively small changes in blood volume and care must be taken to avoid hypotension. HFnEF-CONCEPTS AND MANAGEMENT
  101. 101. Statins Possible Mechanisms • Beneficial effects of statins in patients with coronary artery disease, diabetes and impaired renal function which are common in patients with diastolic HF. • Beneficial effects on LV hypertrophy and fibrosis. • Mild antihypertensive effect of statins. • Beneficial effect on endothelial function and regression of aortic atherosclerosis. • Protective effect on LV remodeling. • Antiinflammatory and antioxidant effects. HFnEF-CONCEPTS AND MANAGEMENT
  102. 102. Recently CORONA trial reported neutral outcome of statin therapy in the HFrEF patients of the. HFnEF-CONCEPTS AND MANAGEMENT
  103. 103. Spirinolactone  TOPCAT  Aldosterone in Diastolic HF (ALDO-DHF) the role of spironolactone versus placebo is being studied to elucidate if an anti-fibrotic intervention strategy is adequate to improve the outcome in HFNEF. Long-term aldosterone receptor blockade with spironolactone improved diastolic function but did not affect clinical symptoms or exercise capacity. HFnEF-CONCEPTS AND MANAGEMENT
  104. 104. Decompensation Triggers Uncontrolled hypertension Increased salt and water intake and/or retention Tachyarrhythmias Ischemia Chronic kidney disease Anemia Chronic lung disease Infection HFnEF-CONCEPTS AND MANAGEMENT
  105. 105. ACC/AHA Heart Failure Guidelines HFNEF Recommendation Class Control systolic and diastolic hypertension I Ventricular rate control in patients with atrial fibrillation I Diuretics to control congestion and edema I Coronary revascularization is reasonable in patients with symptomatic coronary artery disease IIa Restoration and maintenance of sinus rhythm in patients with atrial fibrillation might be useful to improve symptoms IIb Beta-blocking agents, ACE inhibitors, AT II receptor blockers, or calcium antagonists might be effective to minimize symptoms IIb The use of digitalis is not established IIb Hunt et al. ACC/AHA Practice Guidelines JACC 2005;46:1-82HFnEF-CONCEPTS AND MANAGEMENT
  106. 106. HFSA Guidelines HFnEF-CONCEPTS AND MANAGEMENT
  107. 107. Novel therapies Novel strategies should try to interfere with HFNEF- specific myocardial signal transduction pathways, which account for Prominent cardiomyocyte hypertrophy, Down-regulation of MMPs, Up-regulation of TIMPs, Hypophosphorylation of stiff titin isoforms, Substrate shifts from glucose to free fatty acids. HFnEF-CONCEPTS AND MANAGEMENT
  108. 108. Novel therapies Cyclic GMP Modulator Reduce ventricular –vascular stiffening, Antagonize maladaptive chamber remodelling, Improve endothelial function, Reduce pulmonary vascular resistance, Enhance renal responsiveness to NP. HFnEF-CONCEPTS AND MANAGEMENT
  109. 109. Sildenafil  Patients with HFPEF, phosphodiesterase-5 inhibition with administration of sildenafil for 24 weeks, compared with placebo, did not result in significant improvement in exercise capacity or clinical status. HFnEF-CONCEPTS AND MANAGEMENT
  110. 110. Rho-kinase inhibitors such as fasudil and Y-27632 have vasorelaxation properties and have demonstrated the ability to blunt progression of hypertrophic remodelling in animal models of HF. Alagebrium chloride (ALT-711) is a novel compound that breaks glucose cross-links and improves ventricular and arterial compliance in animals. Acute modification of titin PKG phosphorylation sites may dynamically modulate titin stiffness. The anti-anginal drug ranolazine blocks inward sodium Current, thereby reducing intracellular calcium, and it has also been suggested as a potential treatment for HFpEF,although human HFpEF data are currently unavailable. HFnEF-CONCEPTS AND MANAGEMENT
  111. 111. HFNEF syndrome is a heterogenous entity with high prevalence and mortality rates almost as high as that of systolic HF. It is a relatively common cause of HF in the elderly and has a variety of causes and pathophysiological mechanisms. Despite improvements in its understanding, many questions remain and, as yet, there are no treatments of any proven benefit. Ongoing trials are underway. HFnEF-CONCEPTS AND MANAGEMENT

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