the efficiency and function of the left ventricle ( lv ) as a pump are represented as systole and diastole .
the systolic function is energy dependent ; the diastolic function is an important part of cardiac output ( as preload ) and also includes active processes such as the suction effect , which is also energy dependent and can be weakened by ischemia .
thus , diastolic dysfunction ( ddf ) is an early marker of ischemia , because it is sensitive to impaired perfusion .
most physicians pay attention to the lv ejection fraction ( ef ) for systolic function in the preoperative echocardiographic evaluation of patients about to undergo surgery ; however , lv ddf is often overlooked in such cardiac risk evaluation .
lv ddf , and even diastolic heart failure ( dhf ) , are usually not significant problems in the daily life of patients who do not suffer from exercise intolerance , dyspnea , or pulmonary edema . however ,
when they reach the ward after an operation , they often end up in the intensive care unit ( icu ) with unstable vital signs in combination with pulmonary edema , which are not responsive to the normal use of intravenous ( iv ) epinephrine or norepinephrine .
this can lead to poor outcomes , caused by lv ddf regardless of lv systolic dysfunction ( sdf ) , with hemodynamic instability developing due to surgery - induced adrenergic stimulation and anesthesia - induced sympathetic attenuation , resulting in a lengthy stay in the icu or even death . in american heart association - american college of cardiology ( aha - acc ) guidelines ,
lv ddf is still underestimated in preoperative risk assessment and few clinical data supporting its importance are available .
in particular , such patients need more appropriate anesthetic management to prevent postoperative complications and to aid in recovery from anesthesia .
because overlooking patients with lv ddf or lv dhf during the perioperative period , regardless of lv systolic function , can be very dangerous and cause poor outcomes , it is important that anesthesiologists are familiar with the pathophysiology , management , and surgical outcomes and are able to notice their phenotypic characteristics , and diagnostic parameters .
regardless of lv systolic function and the patient 's symptoms , ddf indicates impaired filling of the ventricles at low pressure and abnormalities in diastolic distensibility , filling , or relaxation , which are usually associated with hypertension , diabetes , or ischemia .
the diagnosis of ddf can come from cardiac catheterization and doppler patterns of lv diastolic filling .
ddf shows increased lv diastolic pressure ( > 16 mmhg ) with preserved systolic function and lv volume .
ddf itself is a physiological or preclinical state that can be compensated for with an increase in left atrial pressure , so there is essentially an asymptomatic period .
in addition to echocardiographic or angiographic evidence , when accompanied by symptoms and signs that can be confused with chronic obstructive pulmonary disease such as exercise intolerance , exertional dyspnea , and pulmonary edema with normal ef , it could be considered dhf .
dhf is also characterized by a stiff and thickened ventricle , with a small cavity and low cardiac output .
dhf can also show a normal ef ; this is called heart failure with a normal ejection fraction ( hfnef ) or preserved ef ( hfpreef )
in preclinical ddf , hypertension , hyperlipidemia , coronary artery disease , and renal dysfunction are prevalent . in one study ,
the 2-year cumulative probability of developing any symptom was as high as 31% and the probability of cardiac hospitalization was 21% .
asymptomatic ddf is generally common in patients without heart failure , increases with age , and is particularly seen in elderly women with hypertension and hypertrophy of the ventricle .
ddf alone can predict worse outcomes in patients and their prognosis worsens according to its increasing degree .
moreover , more than half of all patients with heart failure have a normal ef . compared to sdf ,
the incidence and prevalence of ddf are increasing , and in geriatric patients in particular , it can cause hospitalization , increasing hospital costs , and even mortality .
a study of two cohorts of patients with decompensated heart failure showed that 35% had preserved lv ef and that they were elderly and mainly women .
phillip et al .   reported that ~60% of elderly patients with normal ef presenting for geriatric cardiac and non - cardiac surgery had lv - filling abnormalities .
moreover , ~15% of these patients had moderate to severe ddf in the absence of symptoms . in patients undergoing high - risk vascular surgery ,
dhf increased proportionally with age , up to 70% in those aged > 70 years .
there are also age - related changes in the cardiovascular system including coronary artery disease , systemic hypertension , and hypertrophic or infiltrative cardiomyopathy .
the effects of these conditions can also increase filling pressure due to abnormalities in relaxation and decreased compliance of the lv .
diastole can be divided into four stages : isovolumetric ventricular relaxation , rapid passive ventricular filling , diastasis , and atrial contraction . these can also be subdivided into early and late phases . in the isovolumetric relaxation period , after mitral valve closure , calcium is sequestered back into the sarcoplasmic reticulum ; this is an active process for the suction effect , which needs adenosine triphosphate ( atp ) . in ddf
, the breakdown of this process causes the ventricle to fail to relax and become stiff / less compliant .
this dysfunction can be caused by impaired lv compliance , a passive process , or by changes in lv active relaxation .
anatomical diastole occurs from aortic valve closing to mitral valve closing , but at the molecular level , relaxation of the lv starts during the early systolic period , because it starts with the dissociation of actin - myosin cross bridges .
because lv segmental and atrio - ventricular synchronization are indispensable in guaranteeing effective relaxation , loss of the atrial kick in atrial fibrillation not only changes lv filling but also slows myocardial relaxation . before doppler - derived variables ,
the gold - standard measurement of lv diastolic function was the invasive measurement of lv pressures using cardiac catheterization .
this can show pressure / volume loops , lv pressure decline , and the time constant of isovolumetric relaxation (  ) .
, lv ddf shows a diastolic loop ( compliance curve ) shifted to the left and upwards . in such cases ,
lv end - diastolic volume is normal but end - diastolic pressure is increased , resulting in pulmonary congestion .
however , sdf causes the end - systolic slope to shift to the right and downwards   ( fig .
1 ) . in active diastole with isovolumetric relaxation , which is energy dependent , abnormalities in relaxation can be caused by myocardial ischemia , hypertension , aortic stenosis , and hypertrophic cardiomyopathy .
in contrast , passive diastole can be impaired by increased stiffness of the lv chamber , caused by an infiltrative disorder ( amyloidosis ) , myocardial fibrosis , and progression from impaired relaxation .
age - related changes in the cardiovascular system can be condensed into a reduction of cardiovascular reserve , which includes increased arterial and myocardial stiffness , impaired -adrenergic responsiveness and lv relaxation , and reduced sinus nodal function and baroreceptor responsiveness .
aging is related to ventricular and arterial stiffness , which increase and exacerbate myocardial oxygen consumption for cardiac output .
apoptotic myocytes are not replaced , but decrease in number with an increased amount of connective tissue matrix .
the afterload causes increased arterial stiffness that affects lv relaxation , resulting in ventricular hypertrophy to preserve systolic function .
age - related arterial stiffening has two important consequences : decreased aortic distensibility and increased pulse wave velocity , which result in higher pulse pressure ( pp ) and prolonged systolic contraction , respectively .
increased pp is an established cardiovascular risk factor   and the early reflected wave , because of prolonged systolic contraction , impinges on early diastole , which can cause greater myocardial stroke work , wall strain , and oxygen consumption such as a mistimed intra - aortic balloon pump . beyond this
, impaired calcium homeostasis and reduced -receptor responsiveness also cause lv ddf . at the cellular level ,
reduced sarcoplasmic / endoplasmic reticulum calcium atpase 2 ( serca2 ) activity and increased phospholamban activity contribute to impaired lv diastolic function .
the signal dampening of -receptors may be due to receptor down - regulation or diminished coupling of -receptors with intracellular adenylate cyclase activity .
consequently , despite increased circulating catecholamines , there is a limited increase in heart rate and contractility in response to endogenous and exogenous catecholamines , so there is impaired baroreflex control of blood pressure ( bp ) .
apoptosis , fibrosis , fatty infiltration , and calcification of pacemaker and his - bundle cells can result in conduction block , sick sinus syndrome , and arterial fibrillation , with loss of the atrial kick for preload in the end - diastole stage .
arrhythmias ( e.g. , atrial fibrillation ) and myocardial ischemia affecting diastolic timing can decompensate pre - existing ddf further .
treatment with  blockers or calcium channel blockers has been recommended to control tachycardia or arrhythmias to improve lv filling .
patients with ddf in the operating room have some common phenotypic characteristics such as being elderly women and having peripheral edema , hypertension , and obesity . they also tend to have limitations in functional capacity caused by reduced chronotropic , vasodilator , and cardiac reserve .
in addition to a functional capacity evaluation , risk factors and phenotypes for heart failure should be checked in the preoperative assessment for ddf because a heart failure history alone is associated with increased morbidity and mortality after non - cardiac surgery   ( table 2 ) .
biomarkers of ddf are important as prognostic parameters in patients with myocardial ischemia , atrial fibrillation , aortic stenosis , and general heart failure .
cardiac catheterization can show increased ventricular diastolic pressure ( > 16 mmhg ) with preserved systolic function and normal ventricular volumes in ddf . beyond the analysis of pressure / volume curves from cardiac catheterization , echocardiographic assessment of diastolic function
becomes very important in perioperative risk stratification , surgical care , and anesthetic management of patients undergoing operations .
however , before considering echocardiographic findings , the different application of variables in transthoracic echocardiography ( tte ) and transesophageal echocardiography ( tee ) in the outpatient clinic from intraoperative tee should be acknowledged because of differences in the postures of patients and their ventilation status , as well as the effects of anesthetic drugs .
the classification and assessment of ddf comes from the initial , transmitral flow ( tmf ) examination with a pulsed - wave doppler ( pwd)-based evaluation of la and lv filling and its abnormalities , according to current guidelines .
however , because of the known limitations of the rigid application of conventional doppler indices , the most recent guidelines no longer recommend determining e and a waves on tmf with pwd as the initial step in the decision for grading ddf with normal lv ef .
new guidelines based on tte have been simplified and focus on the increase in left atrial pressure ( lap ) rather than grading diastolic dysfunction . in patients with normal lv ef
, more than half of the following should be positive to determine the presence of ddf : average e / e > 14 , lateral e < 10 cm / s , tricuspid regurgitation ( tr ) velocity > 2.8 m / s , and la volume index > 34 ml / m . in patients with depressed lv ef and with normal lv ef but myocardial disease ,
the mitral inflow ratio and the criteria above are used for evaluating lap and grading ddf ( table 3 ) .
some doppler variables are valuable for the assessment of myocardial diastolic function including tmf with pwd ( e / a wave , deceleration time [ dt ] , a duration ) , pulmonary venous inflow with pwd ( s / d , atrial reversal [ ar ] ) , tissue doppler image ( tdi ) with pwd ( e/a wave ) , and transmitral color m - mode ( tmf propagation velocity [ vp ] ) , usually on midesophageal ( me ) four - chamber and me long - axis views .
conventionally , the lv filling pattern of tmf ( e and a wave , e / a ratio ) and dt are most commonly used in echocardiographic examinations regarding ddf , but these , along with pulmonary venous flow patterns , are dependent on preload variation and heart rate and rhythm disturbances . in this regard
, the patient 's preload can be reduced using nitroglycerin ( ntg ) or with the use of the valsalva maneuver in an awake state ( or reverse trendelenburg position or a prolonged lung recruit maneuver in a patient under general anesthesia ) potentially unmasking an e , a pattern and impaired relaxation to discriminate normal from a pseudo - normal state .
in contrast , tissue doppler imaging of the mitral annulus is considered a more sensitive tool in the assessment of ddf , in which measurements of e indicate the myocardial velocity , and not blood flow velocity .
e may be influenced by preload variation in the normal heart , but becomes preload - independent in a heart with ddf .
the abnormal range of e values is also influenced by age : an e < 10 cm / s in those < 50 years and e < 8 in those > 50 .
the value of e is higher at the lateral annulus than the septal annulus , because the motion of the lateral annulus is freer than that of the septal annulus due to the surrounding structures .
it is convenient to use the lateral e in intraoperative tee and the septal e in tte .
measurements of e represent the early diastolic active relaxation phase , but do not represent lv compliance for which the e / e ratio ( the ratio of the transmitral e wave velocity to the mitral annular velocity ) normalizes early transmitral lv filling to mitral annular motion .
this is used to estimate mean left atrial pressure , with values > 15 representing elevated filling pressures and < 8 reflecting normal filling pressures . with a ratio between 8 and 15 ,
this measurement has been considered accurate and relatively independent of lv systolic function , rhythm abnormalities , lv hypertrophy , and functional mitral regurgitation .
the prediction of lv filling pressure using doppler modalities is important in patients with ddf .
elevated lv filling pressures may be the most important factor in poor outcomes , rather than merely the presence of delayed relaxation .
after cardiac surgery , it can also predict a prolonged icu / hospital stay and mortality independently of systolic function . when evaluating diastolic function with echocardiographic tools , measurements should be performed multiple times , considering multiple doppler variables ( table 4 ) . according to these echocardiographic variables , based on tee , it might be suggested that predictors for increased perioperative cardiovascular risk would include e / a of 12 , dt of 150200 ms , e < 8 cm / s , e / e > 15 , vp < 40 cm / s , an enlarged la , and lv hypertrophy in tte . in fact , tdi is of limited use in analyzing regional wall motion abnormalities ; however , there are some recent advances in color tdi , such as strain , strain rate , speckle tracking , and velocity vector imaging   that may allow a better appreciation of lv filling dynamics and a more accurate classification of diastolic function . brain natriuretic peptide ( bnp ) and n - terminal probnp ( nt probnp )
are recognized as specific markers of heart failure ( hf ) with acute dyspnea   and are elevated in both hfpreef and hf with reduced hf ( hfref ) .
these markers tend to be higher in hfref than hfpreef , but do not distinguish hfpreef from hfref effectively . suggested levels for a diagnosis of acute hf are bnp > 100 pg / ml or nt probnp > 300 pg / ml , which are independent predictors of adverse cardiovascular events in hfpreef .
other reasons for elevated bnp factors include renal failure and pulmonary hypertension , caused by lung disease , and obesity , which decrease bnp levels .
as mentioned above , it is important not to overlook patients with asymptomatic lv ddf in the preoperative evaluations , and risk factors for heart failure should also be considered .
although not specific to geriatric patients , the latest acc / aha guidelines   should be used for the perioperative care of cardiac patients undergoing general surgery , and if needed , preoperative cardiovascular risk factors should be evaluated and treated by cardiologists . in ischemic heart disease - related procedures ,
bare - metal stenting can be performed with dual anti - platelet therapy for 46 weeks .
statins should not be discontinued before surgery . because the renin - angiotensin - aldosterone system plays an important role in the development of dhf and particularly in myocardial remodeling and fluid retention , angiotensin - converting enzyme inhibitors , angiotensin receptor antagonists , and aldosterone antagonists
as aforementioned mentioned , drugs for the treatment of pre - existing heart failure , arrhythmias , hypertension , and ischemic heart diseases ( e.g. , diuretics , -blockers , calcium channel blockers , antiplatelet agents ) should be maintained during the perioperative period .
the principles of anesthetic management for patients with ddf must be addressed on a case - by - case basis .
in addition to standard monitoring tools , monitoring the volume status in these patients is important , because they are very sensitive to volume changes due to surgical bleeding and sympathetic tone changes due to anesthesia in the perioperative period .
thus , instituting an arterial cannula is necessary for invasive arterial monitoring , indirect assessments of preload by stroke volume variance , and frequent blood sampling ; the timing of each should be based on experience and local practice . in major or vascular surgery , central venous catheterization , pulmonary artery catheterization , and/or tee may be needed , which can contribute to evaluating intravascular volume during anesthesia . during anesthesia ,
patients with ddf or dhf are commonly elderly and may have hemodynamic instability because of general and regional anesthesia disturbing the baseline sympathetic tone , thereby leaving the patient with a higher resting sympathetic tone and altered -receptor sensitivity .
in addition , the frequent use of diuretics due to pre - existing diseases , a reduction in the thirst response in the elderly , and age - related renal function changes can aggravate the reduction of preload , increasing the sensitivity to volume status .
moreover , direct effects of anesthetics on cardiac inotropy and lusitropy as well as arterial and venous vasodilation can not be ignored with regard to unstable hemodynamics either .
the choice of regional versus general anesthesia is still debated and there are no definitive recommendations either way .
however , epidural anesthesia is preferable to spinal anesthesia because of slower hemodynamic changes from the slow onset time and the smooth removal of sympathetic tone .
in addition , for general anesthesia , iv induction and maintenance with balanced anesthesia of volatile agents and opioids are recommended .
sevoflurane during spontaneous ventilation preserves diastolic relaxation better than propofol , but there are no differences between them regarding diastolic function during positive pressure ventilation through balanced anesthesia .
the common volatile agents ( sevoflurane , desflurane , isoflurane ) , iv anesthetics ( propofol , midazolam ) , and opioids ( morphine , remifentanil ) have no significant effects on diastolic performance in healthy people , unlike some animal models
. however , in high - risk dhf patients , anesthesiologists should avoid acute changes in hemodynamic load conditions , heart rate , and myocardial oxygen balance . to achieve this , a 3050% reduced dose of induction agents should be used , followed by waiting for their delayed effects due to the reduced cardiac reserve and slower circulation time , as well as titrating the anesthetics .
intraoperative bp control is important , in that systolic bp must be within 1020% of the baseline value and pp should be kept below the diastolic bp .
an increased pp increases ventricular wall stress , alters ventricular contraction time , and impairs early diastolic filling , increasing the cardiac workload .
the  rule of 70s  is useful for controlling bp : age > 70 , diastolic bp > 70 , hr = 70 , and pp < 70 . given the effects on cardiac work by controlling pp , the combined use of low - dose ntg ( 0.54 g / kg / min ) and phenylephrine titration ( from 0.25 g / kg / min ) is applicable and helpful , but either agent alone can worsen hemodynamics .
this protocol preserves vascular distensibility , and prevents reductions in preload and coronary perfusion pressure , thereby maintaining stroke volume with minimal cardiac work . in the postoperative period in patients with known ddf , hypoxemia and/or atrial fibrillation
are the most common complications , because restored vascular sympathetic tone due to emergence and resolution from general or regional anesthesia causes a volume shift to central blood volume .
the subsequent volume overload can result in pulmonary edema and/or atrial fibrillation due to decompensation . because these events can happen acutely in a patient with an initially stable appearance , continued and careful monitoring are essential .
maintenance of ntg at a low dose ( 25 g / min ) is also useful for the pulmonary vasculature , and it is important to avoid the risk factors that predispose patients to hf ( table 5 ) . among these factors , a hypertensive crisis can be managed with sound anesthetic practices , planning for appropriate postoperative analgesia , preventing shivering by control of body temperature during the operation , and using iv calcium channel blockers ( nicardipine , diltiazem ) and high doses of iv ntg .
specific drugs with positive lusitropic effects are often invaluable in circulatory failure related to ddf and include phosphodiesterase iii inhibitors ( milrinone ) and calcium channel sensitizers ( levosimendan ) , both of which are inodilators .
milrinone has inotropic , vasodilatory , and lusitropic ( particularly in a heart failure state ) effects with minimal chronotropy , by increasing calcium ion uptake in the sarcoplasmic reticulum
. it can be used at a bolus dose of 50 g / kg over 10 min and an infusion of 0.3750.75 g / kg / min .
levosimendan sensitizes the contractile elements to calcium and has positive inotropic effects , modulating the interaction between troponin and calcium
. it also has vasodilatory effects by opening atp - sensitive potassium channels and improving both systolic and diastolic functions .
ddf of the lv and dhf with preserved ef are not rare pathologies , but are frequently underestimated . in the preoperative evaluation of asymptomatic patients undergoing high - risk surgery , echocardiographic assessment of lv diastolic function should be included in cardiovascular assessments , as should consideration of the risk factors for dhf
. early detection of and not overlooking preclinical lv diastolic dysfunction can be useful for the choice of appropriate surgery , appropriate bp control , timely monitoring tools , and proper volume management to maintain normovolemia on a case - by - case basis .
although anesthesiologists may not appreciate the stages of ddf , those who are involved in the perioperative care of these patients with cardiovascular disorders need to be able to manage them appropriately . because there is not yet an evidence - based treatment of choice regarding acute decompensated dhf , its management should focus on resolving known precipitating factors such as myocardial ischemia , hypertensive crisis , arrhythmias , and pulmonary congestion .
 anesthesiologists frequently see asymptomatic patients with diastolic dysfunction or heart failure for various surgeries . 
 these patients typically show normal systolic function but abnormal diastolic parameters in their preoperative echocardiographic evaluations . 
 the symptoms that are sometimes seen are similar to those of chronic obstructive pulmonary disease . 
 patients with diastolic dysfunction , and even with diastolic heart failure , have the potential to develop a hypertensive crisis or pulmonary congestion . 
 thus , in addition to conventional perioperative risk quantification , it may be important to consider the results of diastolic assessment for predicting the postoperative outcome and making better decisions . 
 if anesthesiologists see female patients older than 70 years of age who have hypertension , diabetes , chronic renal disease , recent weight gain , or exercise intolerance , they should focus on the patient 's diastologic echocardiography indicators such as left atrial enlargement or left ventricular hypertrophy . 
 in addition , there is a need for perioperative strategies to mitigate diastolic dysfunction - related morbidity . 
 specifically , hypertension should be controlled , keeping pulse pressure below diastolic blood pressure , maintaining a sinus rhythm and normovolemia , and avoiding tachycardia and myocardial ischemia . 
 there is no need to classify these diastolic dysfunction , but it is important to manage this condition to avoid worsening outcomes . 
Introduction
Definitions
Epidemiology
Pathophysiology
Perioperative Clinical Assessment
Perioperative Management
Conclusions