Effects Of Heart Failure On Cerebral Hemodynamics And Their Correlation To Cognition

BackgroundThe cerebral blood flow is constant in normal subjects under different contexts,which is determined by the cardiac output and the regulatory mechanism.Accumulating studies have shown that patients with severe heart failure have decreased cerebral blood flow and cognitive dysfunction.However,the detailed correlation among cardiac dysfunction,cerebral hemodynamic changes and cognition,remains not fully elucidated,especially when the different degrees of cardiac dysfunction,various causes of heart failure are considered.Theoretically,the brain blood flow will drop when the cardiac output is lower than a threshold,which could also be affected by the brain blood regulatory mechanisms.It is widely accepted that the regulatory mechanism might differ in heart failure patients with different causes,such as dilated cardiomyopathy and coronary artery disease.The study presented here explored the changes of cerebral blood flow dynamics,and cognitive impairment in HF patients with different degrees of cardiacdysfunction due to either dilated cardiomyopathy(DCM)or coronary artery disease(CAD).Objective1.To explore the changes of cerebral blood flow dynamics and cognitive impairment in patients with heart failure(HF)due to either dilated cardiomyopathy or coronary artery disease.And the correlation between heart failure degree and these dynamics would also be explored.2.To explore the putative sensitive parameters for diagnosis of cognitive impairment in DCM and CAD patients.And the differences between the DCM and CAD patients would also be clarified.Materials and methods1.SubjectsHeart failure patients between May 2014 and August 2016 were recruited,including38 DCM(male30,female 8)with averaged age of 52.8(35~80 years old),30 CAD(male22,female 8)with averaged age of 64.5(45~80 years old),and 31 healthy subjects(male24,female 7)with averaged age of 58.2(35~80 years old)as controls.Inclusion criteria of HF patients were as follows:(1)Duration of HF was more than 1 year;(2)Left ventricular ejection fraction(LVEF)by 4D-transthoracic echocardiography was less than 55%;(3)Categorized into NYHA function class II~IV;(4)Unchanged medication regimen within the previous 6 weeks;(5)Clinical stable condition with no clinical evidence of decompensate heart failure,such as hepatomegaly,ascites,edema of lower extremity,pneumonia and pulmonary embolism.Exclusion criteria included:(1)Patients with both dilated cardiomyopathy and coronary heart disease,or severe arrhythmia;(2)severe neck cerebrovascular events,such as carotid arteries plaques,neck cerebrovascular stenosis(>50%)and cerebral ischemic stroke;(3)patients with anxiety and depression;(4)other basic diseases and complications,such as severe liver or renal diseases.All participants signed consent form.2.Measurements and Methods2.1 Physiology measurements :(1)Gender,age,height(cm),weight(kg),blood pressure(mmHg)and heart rate(times/min)measurements: Height and Weight of each subjects measured three times and the averaged values were recorded for BMI calculation.Mean arterial pressure(MAP)=(systolic pressure + 2 × diastolic blood pressure)/ 3.Cardiac function classification was based on the New York Heart Association(NYHA)classification scheme issued in 1928.(2)Basal biochemical indexes including:hemoglobin(g/L),blood hematocrit(%),blood glucose(mmol/L),blood lipid(mmol/L),uric acid(?mmol/L)and creatinine clearance(?mmol/L).(3)Questionnaire:Education history,disease history and treatments(including hypertension,diabetes,and placing cardiac resynchronization therapy(CRT)),smoking,alcohol consumption.(4)Medications: Diuretics,spironolactone,anticoagulant,beta blockers,angiotensin converting enzyme inhibitors(ACEI)or angiotensin receptor blockers(ARBs),nitrates and digoxin.2.2 Ultrasound measurements:Vivid E9 ultrasound instrument from GE Company was used.M5 s and 9L probes were applied for cardiac and neck vascular ultrasound examination respectively.Electrocardiogram(ECG)was recorded simultaneously.(1)Cardiac ultrasound examination: Right ventricular outflow tract diameter(RVOT),pulmonic and aortic diameter(PAd,AOd),Left ventricular end-diastolic and end systolic diameter(LVEDd,LVESd),and left atrium diameter(LAd)as well as the interventricular septum and left ventricular diastolic post wall thickness(IVSTd,LVPWTd)were measured in accordance with the ASE recommendation.Four-dimensional echocardiography from the apical four chamber view beat-to-beat collected left ventricular ejection fraction(4D-EF,%),stroke volume(SV,mL),cardiac output(CO,L/min),left ventricular spherical index(SPI)by a 4V-Full Volume probe,and the heart index(CI,L/min/m2)was calculated.Cardiac index(CI,L/min/m2)was calculated with the formular CI = CO/BSA.(BSA represents body surface area,BSA(m2)=0.0061 × H(cm)+ 0.0124× W(kg)-0.0099.(H: Height,W: Weight)(2)Vascular ultrasound examination: All subjects underwent two-dimensional and Doppler echocardiography examination.After aninitial 10 min of rest with the subjects in a supine position,a 9L linear array transducer was used to image the ICA 1~2cm distal to the carotid bifurcation and C4~C5 segment of the VA to measure the diameter and hemodynamic parameters of bilateral ICA and VA,respectively.CBF volume determined as the sum of the flow volume of bilateral internal carotid artery(ICA)and vertebral artery(VA)measured by extracranial ultrasound.Resistance index(RI),a parameter of cerebrovascular resistance derived automatically from the Doppler spectrum,was calculated as follows:(peak systolic velocity-end diastolic velocity)/peak systolic velocity for both ICA and VA.Mean resistance index(M-RI)of the cerebral blood flow was calculated(Supplementary Figure 2).2.3 Cognitive function assessment: The mini-mental state examination(MMSE)evaluated cognitive function respectively from five aspects including direction,memory,attention,calculation,delayed memory and language ability.The test process lasts for5~10 minutes.MMSE reference and instruction manual stated that the higher scores were,the better cognitive function reflected.MMSE score > 27 represents normal,21~26 was mild,10~20 was moderate,< 10 was severe;According to the criteria of culture,the illiteracy below 17 points,primary school less than 20 points,high school less than 24,were divided into dementia.The standardized questionnaire and language were needed.MMSE test was done in each patient with a good emotion and concentration in a quiet environment.2.4 Statistics Analysis: All values were expressed as mean + standard deviation(continuous variables)or as counts and percentages(categorical variables).Continuous variables were compared using unpaired Student's t tests,and categorical variables were compared using the analysis of variance(ANOVA)test of deviation or using ?2statistics from a significant linearity of the correlation between 4D-EF and M-RI as well as MMSE.Count data relationship between groups using Pearson correlation analysis.A p value less than 0.05 was considered to indicate statistical significance,and all statistical analyses were performed using the SPSS software for windows,version 21.0.Results1.The comparison of the parameters between DCM group and normal control group:Compared with control group,the left heart was significantly enlarged with relatively normal ventricular wall thickness in DCM patients.In addition,4D-EF was remarkably reduced and SPI was increased(P < 0.01)in DCM patients.NYHA II and III patients did not shown decrease in CBF,while class IV patients had decreased CBF.M-RI was significantly lower in DCM patients(P < 0.05).4D-EF strongly correlated with M-RI as well as MMSE score(P < 0.01),but not with CBF.Compared with normal control group,the heart rate in DCM group was significantly faster.2.The comparison of the parameters between CAD group and normal control group:Compared with control group,the left heart was significantly enlarged with relatively normal ventricular wall thickness and SPI in the CAD patients.In addition,4D-EF was remarkably reduced(P < 0.01)in CAD patients,while no significant decrease of CBF or M-RI was found in CAD patients(P > 0.05).4D-EF strongly correlated with MMSE score(P < 0.01),but not with CBF.Compared with normal control group,the heart rate in CAD group was significantly faster.3.The comparison of the parameters between DCM group and CAD group: When the age,sex,BMI and 4D-derived systolic function parameters matched,the DCM group showed significantly lower of M-RI compared to the CAD group.CBF gradually decreased in DCM group with the increased grades of NYHA function.MMSE significantly decreased both in DCM and CAD patients with increased NYHA function grades.SPI was significantly enlarged in DCM group with the LV more sphere-like shape.The heart rate in both groups was significantly faster.Conclusion1.Patients with NYHA II or III could have decreased cognition capacity,even when there was no significant decrease of blood flow volume in both DCM and CAD patients in this study.The cognition decrease was correlated with the 4D-EF.2.Since their cognition decreases when the blood flow volume remains normal in this study,suggesting that blood flow volume is not a good marker for early detection ofthe cognition defect in heart failure patients.3.Heart rate increase is the main mechanism for compensation of the blood flow volume.In addition,cerebrovascular resistance decrease is the additional mechanism for blood flow maintenance in DCM patients,rather than CAD patients.4.4D-EF is a good marker for predicting cognition defect in both DCM and CAD patients.Cerebrovascular resistance decrease could reflect the cognition defect in DCM patients,while have no diagnostic value in CAD patients.