Diastolic Heart Failure Group Research Articles

Prevalence of respiratory failure and use of mechanical ventilation in heart failure patients undergoing left atrial appendage occlusion device implantation

BackgroundWe sought to evaluate respiratory complications in heart failure patients undergoing left atrial appendage occlusion (LAAO) for stroke prevention in atrial fibrillation. MethodsAdult admissions (>18 years) undergoing LAAO during 2016–2020 were identified from the National Inpatient Sample. Heart failure (HF) was stratified into systolic (SHF) and diastolic heart failure (DHF) and were compared to those without HF. Outcomes of interested included acute respiratory failure, use of non-invasive and invasive mechanical ventilation, and in-hospital mortality. ResultsOf 74,440 admissions for atrial fibrillation undergoing LAAO, SHF and DHF were noted in 8335 (11.2%) and 10,925 (14.7%), respectively. The SHF cohort was predominantly male (78%) whereas DHF cohort were female (53%). Compared to those without HF, presence of SHF (2.3% vs. 0.6%; adjusted odds ratio [OR] 1.61 [95% confidence interval {CI} 1.10–2.36]; p = 0.01) and DHF (2.8% vs. 0.6%; adjusted OR 2.20 [95% CI 1.58–3.06]; p < 0.001) were associated with higher rates of acute respiratory failure. SHF (1.7% vs. 0.6%; adjusted OR 1.70 [95% CI 1.07–2.71]; p = 0.02) group but not DHF (1.2% vs. 0.6%; adjusted OR 1.21 [95% CI 0.78–1.89]; p = 0.39) was associated with higher rates of non-invasive ventilation, whereas the DHF group (0.9% vs. 0.2%; adjusted OR 1.91 [95% CI 1.08–3.34]; p = 0.02) but not SHF (0.8% vs. 0.2%; adjusted OR 1.54 [95% CI 0.83–2.84]; p = 0.17) was associated with higher rates of invasive mechanical ventilation use. In-hospital mortality was comparable between cohorts. ConclusionCompared to those without HF, atrial fibrillation admissions with HF undergoing LAAO had higher rates of acute respiratory failure and mechanical ventilation rates without differences in in-hospital mortality.

Worse In-Hospital Outcomes Among Patients With Heart Failure (HF) and Concomitant Influenza Infection.

A sizable proportion of heart failure (HF) admissions is precipitated by respiratory infections. Influenza has been linked to higher rates of HF hospitalizations and in-hospital morbidity and mortality. We aimto describe the in-hospital outcomes of systolic HF vs. diastolic HF admissions with concomitant influenza infection in US hospitalizations from 2016 to 2017. Materials and Methods:We queried the National Inpatient Sample (NIS) from 2016 to 2017 for discharge diagnosis for SHF and DHF and influenza per ICD-10 CM codes. Using binominal logistic regression analysis and adjusting for demographic and comorbid conditions, we compared the outcomes of SHF vs. DHF admissions with concomitant influenza as an independent risk factor for inpatient mortality, acute respiratory failure, ICU admission,assisted ventilation, as well as length of stay, and total hospital costs. A total of 7,490,596 HF weighted admissions were analyzed, among which 0.9% had concomitant influenza infection. SHF and DHF admissions with influenza had higher mortality, ICU admission, ventilation assistance, and acute respiratory failure when compared to those without influenza. Among influenza admissions, those with SHF had higher mortality (6.6% vs. 5%, adjusted odds ratio - aOR 1.31, p<0.001) compared to DHF. While intensive care unit (ICU) admission(7.8% vs. 5.2%, aOR 1.30, p<0.001) and ventilation assistance rates (22.1% vs. 18.9%, aOR 1.15, p<0.001) were greater among SHF patients with influenza, acute respiratory failure was more common amongst diastolic HF with influenza (46.6% vs. 51.2%, aOR 0.86, p<0.001).Finally, SHF patients with concomitant influenza had higher inpatient costs ($82,788) when compared to diastolic HF patients ($66,373) and a longer in-hospital stay (7.29 days compared to 6.98 days in the diastolic HF group)p <0.001. Concomitant influenza infection in hospitalized patients with HF is associated with higher mortality, ICU admission, and the need for assisted ventilation, especially in those with SHF. A greater emphasis on vaccination against influenza may improve in-patient outcomes among HF patients.

Heart Failure and Aortic Stiffening in Patients with Preserved Ejection Fraction

Objective: This study aimed to explore a possible relationship between aortic stiffness parameters and diastolic function in patients with asymptomatic or symptomatic diastolic dysfunction, and subsequently, the effect of aortic stiffness parameters on the progression from asymptomatic diastolic dysfunction to clinical diastolic heart failure.&#x0D; Methods: Seventy-five subjects were enrolled in the study of whom 20 had diastolic heart failure with the left ventricle ejection fraction (LVEF) &gt;50%, 20 had asymptomatic diastolic dysfunction with LVEF&gt;50%, 16 had hypertension with normal diastolic function, and 19 were normotensive healthy subjects. Ascending aorta recordings for measuring aortic strain and distensibility as markers of aortic stiffness were obtained from a spot nearly 3 cm above the aortic valve using 2-D echocardiography under M-mode. Doppler echocardiography and 2-D echocardiographic measurements were used to determine diastolic function. &#x0D; Results: While no statistically significant difference in aortic strain or distensibility values was observed between the asymptomatic group and the diastolic heart failure group; however, E/E’ values were higher in the heart failure group [12.1 (10.0-17.1) vs. 10.0 (6.2-22.5)] (p=0.014). Aortic strain and distensibility values significantly decreased as E/E’ values increased (r = −0.416; p &lt; 0.001 and r = −0.576; p &lt; 0.001, respectively) for pooled data from all groups.&#x0D; Conclusion: Although aortic stiffness parameters did not have a direct effect on the progression from asymptomatic diastolic dysfunction to diastolic heart failure, echocardiographic monitoring of these parameters may be beneficial in identifying patients who would progress to clinical heart failure from diastolic dysfunction.

Diagnostic and prognostic value of autoantibodies against β1-adrenoreceptors in patients with heart failure following acute myocardial infarction: A 5-year prospective study.

A number of studies have suggested that autoantibodies against β1-adrenoreceptors (β1R-AAbs) have an important role in pathophysiological processes of heart failure. The aim of the present study was to determine whether β1R-AAbs are implicated in cardiac dysfunction following acute myocardial infarction (AMI) and their association with prognosis. A total of 33 cases with systolic heart failure (SHF), 49 with diastolic heart failure (DHF) and 44 with normal heart function following AMI were recruited. β1R-AAbs were detected by ELISA and major adverse cardiac events (MACEs) were recorded during the 5-year follow-up. The positive rate of β1R-AAbs in the SHF group (45.5%) was significantly higher compared with that in the DHF (22.4%; P<0.05) and normal (15.9%; P<0.05) groups. The area under the receiver operating characteristics curve for the diagnosis of SHF was 0.630 (95% CI: 0.514–0.747, P=0.026). During a median follow-up period of 51.0±15.4 months, the positive rate of β1R-AAbs in the MACEs group was significantly higher compared with that in the non-MACEs group (P<0.05). Multivariate logistic regression analysis indicated that the left ventricular ejection fraction and diabetes were independent predictors of 5-year MACEs following AMI, whereas β1R-AAbs were not. Kaplan-Meier analysis revealed that the cumulative MACEs-free survival rate was the lowest in the SHF group, followed by the DHF and normal groups (P<0.05). Therefore, β1R-AAbs were indicated to be of value for early diagnosis of SHF after AMI but not as independent predictors for the prognosis of patients with AMI.

Evaluation of oxidant status in both systolic and diastolic heart failure

Objective: Oxidative stress status in subgroup of heart failure (HF) syndrome still remains unknown. We aimed to study Total Antioxidant Status (TAS), Total Oxidant Status (TOS) and Oxidative Stress Index (OSI) in both systolic and diastolic HF, and also in both ischemic and non-ischemic HF. Materials and Methods: Consecutive 123 chronic HF patients were included in this cross-sectional study. Group 1 consisted of 73 systolic HF patients (50 ischemic patients and 23 non-ischemic patients) and group 2 consisted of 50 diastolic HF patients. As a control group (group 3), 37 healthy subjects were included. Echocardiographic evaluation was performed and TAS, TOS and OSI were studied in all patients. Results: The highest TAS value (1.10±0.24) was found in Group 1, but the lowest in Group 2 (0.90±0.14). Diastolic HF group had the highest TOS value (37.2±10.41) while systolic HF group (32.9±7.26) and control group (26.19±8.00) followed it. OSI was found the highest in diastolic HF group (4.37±1.24) and the lowest in systolic HF group (2.24±0.80). TOS and OSI were similar between ischemic and non-ischemic subgroups of systolic HF but TAS was statistically higher in non-ischemic (p:0.0005). Conclusions: We found higher oxidative stress in HF patients, predominantly in diastolic HF patients. The difference between diastolic and systolic HF with regard to oxidative and antioxidative status seems to come from distinct drugs usage between the groups, which have potential effects on oxidative and antioxidative parameters. To reduce, at least, oxidative stress in diastolic HF patients, medical therapy is needed.

Contractile Function of Isolated Hearts With Preserved and Reduced Ejection Fraction In Vivo.

The aim of the study was comparison of contractile function of isolated hearts of rats with doxorubicin-induced myocardial injury which were tentatively divided according to the level of ejection fraction determined by echocardiography in vivo. After 4 weeks of doxorubicin administration (2 mg/kg subcutaneously once a week) about half of animals had normal (86±1%) and the other half reduced (61±4%) ejection fraction. The first group was defined as diastolic heart failure (DHF) and the other as systolic (SHF). The maximal pressure developed by the isolated heart in isovolumic mode was reduced in DHF by 13%, and in SHF by 34%. The relaxation index in both groups was lowed by 22-24%. Both groups were characterized by a decline in the ability to raise developed pressure while increasing coronary perfusion pressure, as well as by the loss of the ability of coronary vessels to maintain a stable flow rate while increasing perfusion pressure. The hearts of control animals were able to raise the cardiac work index (the product of developed pressure and heart rate) during prolonged high frequency (7-9 Hz) stimulation, while the two groups treated with doxorubicin reduced the level of this index. The content of basic energy metabolites (ATP, phosphocreatine, creatine) in both groups was reduced by 20-38%. The results showed that the hearts in DHF and SHF groups showed approximately the same level of reduction of the contractile function and energy metabolism, and hence their difference in vivo was probably due to varying degrees of mobilization of compensatory mechanisms.

ASSESSMENT THE DIFFERENT ROTATION OF ENDOCARDIUM AND EPICARDIUM IN DHF PATIENTS USING TWO-DIMENSIONAL SPECKLE TRACKING IMAGING

ObjectivesTo observe the rotation of endocardium and epicardium by two-dimensional speckle tracking imaging (2D-STI), and to evaluate its performance in diastolic heart failure (DHF) patients with a normal left ventricular...

Relationship between red cell distribution width and echocardiographic parameters in patients with diastolic heart failure

Red cell distribution width (RDW) was found to be a prognostic marker in heart failure patients. The aim of the study was to investigate the relationship between RDW and echocardiographic parameters in diastolic heart failure (DHF). Seventy-one consecutive DHF patients (26 men) and 50 controls (21 men) were included in the study. All of the study population underwent echocardiographic evaluation, and blood samples were obtained. RDW and N-terminal pro-B-type natriuretic peptide (NT-proBNP) values were significantly higher, whereas there was an increasing trend for high-sensitivity C-reactive protein levels in DHF patients than those in controls (p<0.001, p<0.001, and p=0.064, respectively). All of the echocardiographic parameters evaluating diastolic function were more deteriorated in the DHF group. Patients who had an RDW value greater than the cutoff point also had higher NT-proBNP levels, an elevated ratio of mitral peak velocity of early diastolic filling to early diastolic mitral annular velocity, and increased estimated pulmonary capillary wedge pressures by tissue Doppler parameters, but lower creatinine clearance (p<0.05 for all). According to the cutoff values calculated using receiver operating characteristic analysis, RDW>13.6% and NT-proBNP>125pg/mL have high diagnostic accuracy for predicting DHF. RDW values were increased in the DHF population. Our results suggest that the high RDW levels in patients with DHF may be related to increased neurohormonal activity, impaired renal functions, and elevated filling pressure, but not to increased inflammation.

Differences in Sarcoplasmic Reticulum Ca(superscript 2+) Leak Characteristics between Systolic and Diastolic Heart Failure Rabbit Models

Diastolic heart failure (DHF) and systolic heart failure (SHF) are two clinical subsets of chronic heart failure (CHF). Sarcoplasmic reticulum (SR) Ca²⁺ leak has been measured in SHF and might contribute to contractile dysfunction and arrhythmogenesis. However, no study has investigated a similar phenomenon in DHF. Thus, we established DHF and SHF rabbit models and compared the differences in Ca²⁺ leak between these models. New Zealand white rabbits were randomly divided into three groups (n = 8 in each group): sham operation (SO) group, DHF group and SHF group. Cardiac functions were determined by echocardiography and hemodynamic assays. The SR Ca²⁺ leak was measured with a calcium-imaging device and the expression and activities of related proteins were evaluated with Western blots and autophosphorylation. In the DHF group, there was significantly increased ventricular wall thickness and stiffness, reduced diastolic function, and total amount of FK506 binding protein 12.6 (FKBP12.6), increased expression and activity of protein kinase A (PKA) and phosphorylation site (P2809) in the ryanodine receptor (RyR2), but no prominent Ca²⁺ leak. In the SHF group, there was significantly increased ventricular cavity size, reduced systolic function, increased SR Ca²⁺ leak, reduced total amount of FKBP12.6 and FKBP12.6-RyR2 association, increased expression and activity of PKA and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and their RyR2 phosphorylation sites with unchanged P2030. Our results suggest that a prominent SR Ca²⁺ leak was not observed in the DHF model, which may provide a new idea for the reasons in preserved systolic function, and CaMKII possibly plays a more important role in SR Ca²⁺ leak.

Evaluation of left ventricular twist in rabbit model with heart failure by speckle tracking imaging

Objective To assess left ventricular twist and untwist in rabbit models with diastolic heart failure(DHF) and systolic heart failure(SHF) by speckle tracking imaging(STI).Methods Thirtythree male New Zealand rabbits were divided into three groups:one group was used to establish DHF model by suprarenal abdominal aortic constriction(n = 12) and the other was used to establish SHF model by abdominal aortic constriction subdiaphragmly above celiac artery origin(n = 11),another was control group established by sham operation(n = 10).After two weeks,left ventricular twist-related parameters were measured.by STE.Finallly,left ventricular catheterization and myocardial pathological examination were performed.Results Compared with control group,peak twist angle (Ptw) and peak twisting velocity(PTV)remained unchanged in DHF group (P ＞ 0.05) and decreased in SHF group (P ＜ 0.05).Isovolumic untwisting rate (IUR) decreased,untwisting half-time(UHT) was prolonged,time to peak twist (tPtw) and peak untwisting velocity (tPUTV) were delayed in SHF and DHF groups.In additon,Peak untwisting velocity(PUTV) decreased in SHF group,but increased in DHF group (P ＜0.05).Ptw correlated correlated positively with LVEF,+ dp/dtmax significantly in both groups (DHF group:r = 0.897,P =0.002; r = 0.719,P = 0.044;SHF group:r = 0.727,P = 0.041; r = 0.780,P = 0.022).A significantly positive correlation was observed between PUTV and - dp/dtmax Tau,LVEDP(r = 0.801,P = 0.017; r =0.814,P = 0.014; r = 0.875,P = 0.004) in SHF group.Conclusions STI is useful in evaluating left ventricular twist and untwist in rabbit model of DHF and SHF. Key words: Echocardiography; Heart failure,congestive; Torsion; Speckle tracking imaging

Decreased intralymphocytic magnesium content is associated with diastolic heart dysfunction in patients with essential hypertension

Diastolic heart failure (DHF) is a clinical syndrome characterized by the symptoms and signs of heart failure, preserved ejection fraction (EF) and abnormal diastolic function [1]. Hypertension is the most common risk factor and the principal precursor for DHF [2]. Hypertension-induced left ventricular (LV) hypertrophy that includes myocardial hypertrophy and abnormal accumulation of fibrillar collagen causes a decreased compliance and LV diastolic dysfunction. It is estimated that 20–60% of patients with heart failure have preserved EF [3,4]. Unfortunately, in contrast to the situation of heart failure with low EF, the mortality and morbidity of DHF have not been significantly decreased in the past decades [5,6]. Magnesium is the second most abundant intracellular cation. As a cofactor formany enzymes,magnesiumplays a role in various biological functions including energy metabolism and muscle contraction [7]. It is known that activation of the rennin–angiotensin–aldosterone system and the use of diuretics in patients with essential hypertension or cardiac failure may deplete serum potassium and affect intracellular magnesium homeostasis [8,9]. We have shown the importance of maintaining magnesium homeostasis in reducing arrhythmia and myocardial hypertrophy in patients with heart failure or hypertension [10,11]. However, the role of magnesium homeostasis in diastolic heart dysfunction is not known yet. Thus, we designed this study to address this issue. Since myocardium of patients is usually not easily accessible, we measured intralymphocytic magnesium content to reflect the magnesium content in myocardial cells. This was a single center prospective study that conformed to the ethical principles outlined in the Declaration of Helsinki. The study protocol was approved by the ethics committee of the First Affiliated Hospital of the SunYat-SenUniversity (Guangzhou, China). Consecutive 206 essential hypertension patients with diastolic heart dysfunction documented by Doppler echocardiography from November 2007 to October 2009 were enrolled. Patients with diastolic heart dysfunction and clinical signs and symptoms of heart failure as described in the European Society of Cardiology Guidelines published in 2008 [12] were attributed to DHF group (group A). Those free of signs and symptoms of

Relationship of arterial stiffness and early mild diastolic heart failure in general middle and aged population

The brachial-ankle pulse wave velocity (baPWV) has been recognized as a marker that reflects arterial stiffness. We conducted an investigation to evaluate whether baPWV is independently associated with early mild diastolic heart failure (DHF) in a general middle and aged population. From 1 July 2009 until 31 August 2009, we investigated 2095 subjects for the relevant factors of heart failure in the Lujiazui Community, Shanghai. The baPWV, echocardiography, and blood sampling were performed in the morning after a 12 h overnight fast. A total of 1929 subjects had the complete data, including questionnaire, age, gender, baPWV, brain natriuretic peptide, and E/A ratio. Early mild DHF was defined as a left ventricular ejection fraction >50%, E/A ratio <0.8, and E/E' ≤ 8; finally, 482 subjects with early mild DHF and 1282 subjects with non-DHF entered into analysis. Among 1764 subjects, 31.6% of the subjects were male (average age was 58.0 ± 12.3), 35.8% of the subjects had hypertension, the average body mass index (BMI) was 24.2 ± 3.3 kg/m(2), baPWV was 1513.0 (1329.1, 1763.5) cm/s, and the baPWV was significantly correlated with the E/A ratio (r = -0.39, P < 0.01). There was a difference of the baPWV [1456.0 (1295.3, 1698.3) vs. 1670.5 (1465.6, 1910.8) cm/s] between the non-DHF group and the early mild DHF group (P < 0.01). Multiple logistic-regression analyses demonstrated that age, male gender, BMI, baPWV, posterior left ventricular wall thickness (PVWT), interventricular septal thickness (IVST), E/E' ratio, left ventricular mass index (LVMI), systolic blood pressure (≥140 mmHg), and diastolic blood pressure (≥90 mmHg) were independently correlated with early mild DHF. The increased arterial stiffness is associated with early mild DHF in a general middle and aged population independently of age, male gender, BMI, PVWT, IVST, E/E' ratio, LVMI, and high blood pressure. The non-invasive techniques described may allow serial measurements to be made over time to monitor baPWV changes in arteries provided the introduction of anti-arteriosclerosis therapy.

Left ventricular global systolic dysfunction has a significant role in the development of diastolic heart failure in patients with systemic hypertension

Regional left ventricular (LV) systolic dysfunction has been identified in diastolic heart failure (DHF). However, the relationship between regional or global LV systolic function and heart failure symptoms in DHF has not been evaluated in detail. The present study evaluates such relationships in patients with systemic hypertension (HT) and DHF. We assessed LV systolic and diastolic function in 220 consecutive patients with systemic HT and in 30 normal individuals (Control) using Doppler echocardiography. Patients with HT were assigned to groups with DHF, asymptomatic diastolic dysfunction (ADD) and no diastolic dysfunction (Simple HT). Ejection fraction in DHF was significantly decreased (63±8%) compared with the Control, Simple HT and ADD groups (67±5, 66±7 and 68±8%, respectively). Isovolumetric contraction time in DHF (70±30 msec) was significantly increased compared with those in the ADD, Simple HT and Control groups (31±17, 31±15 and 30±19 msec, respectively). Mitral annular systolic velocities were significantly decreased in the DHF and ADD groups (6.4±1.5 and 7.2±1.3 cm sec⁻¹, respectively) compared with those in the Simple HT and Control groups (8.5±1.8 and 8.4±3.0 cm sec⁻¹, respectively), and in the DHF group compared with the ADD group. LV global systolic dysfunction has a significant role in the development of heart failure symptoms associated with DHF in patients with systemic HT.

Enhancement of the endothelial NO synthase attenuates experimental diastolic heart failure

Diastolic heart failure is a rising problem with a high incidence and similar mortality and morbidity compared to patients with systolic heart failure. Nevertheless, the underlying pathophysiology is still debated. We investigated the effect of pharmacological enhancement of endothelial nitric oxide synthase (eNOS) on experimental diastolic heart failure (DHF). DHF was induced in 60 DAHL salt-sensitive rats by salt diet in 8-week-old animals. 30 were treated with the eNOS enhancer AVE3085 (DHFeNOS) and 30 with placebo (DHF). Rats with normal salt intake served as controls. Diastolic dysfunction with increased diastolic stiffness constant and increased left ventricular (LV) pressure was analyzed by invasive pressure-volume loop measurements in the DHF group compared to controls. Cardiac hypertrophy as indicated by LV mass measurements by echocardiography, and increased cardiac collagen content as measured by immunohistochemistry were associated with an increased activation state of calcineurin, AKT, ERK(1/2), but not JNK and p38 kinases. Titin isoforms were not altered in this model of DHF. Treatment with AVE3085 significantly increased eNOS mRNA and protein levels in the cardiac tissue and decreases NAD(P)H oxidase subunits p22phox and gp91phox. Diastolic dysfunction was attenuated and cardiac hypertrophy and fibrosis were improved in comparison with untreated DHF animals. This was associated with a normalized activation state of calcineurin, AKT and ERK(1/2). Therefore, we suggest that targeting the NO system might yield a future therapeutic aim for the treatment of DHF.

Myofilament Dysfunction in a Guinea-pig model of Diastolic Heart Failure

Diastolic heart failure (DHF) is characterized as heart failure with preserved systolic function; the mechanisms underlying this syndrome are incompletely understood. Accordingly, we studied myofilament function in an experimental model of DHF. DHF was induced by chronic Angiotensin II infusion via surgically implanted infusion pumps (400ng/kg/min)/saline pumps (0.9%) in female Dunkin Hartley Guinea pigs (400g). Following eight weeks of treatment, LV samples were snap frozen in liquid N2. Skinned myocyte fragments were prepared by mechanical dissociation and subsequently glued to a force transducer and motor attached to micropipettes that were positioned on the stage of an inverted microscope. Preliminary data indicate that myocyte myofilament function is depressed in the DHF group in terms of maximum Ca2+ saturated force development (15.8±0.9 vs. 28.1±0.9 mN/mm2) and cooperativity (Hill coefficient; 2.8±0.1 vs. 3.4±0.6), but not Ca2+ sensitivity (EC50; 2.21±0.06 vs. 2.23±0.13 μM). In addition, 2-D DIGE gel analysis revealed shifts in the phosphorylation profiles of the contractile proteins MyBP-C and Troponin I. We conclude that myofilament dysfunction underlies, in part, the decreased pump function that is seen in this guinea-pig experimental model of DHF and that this phenomenon may be caused by maladaptive contractile protein phosphorylation.

Elevation of the ratio of transmitral E velocity to early diastolic mitral annular velocity continues even after recovery from acute stage in patients with diastolic heart failure

Clinical features of diastolic heart failure (DHF) have not been well characterized, leading to an inaccuracy in the diagnosis of DHF. Recently, the ratio of transmitral E velocity to early diastolic mitral annular velocity (E/E') has been shown to be useful to assess LV filling pressure. We tested the hypothesis that persistent elevation of E/E' ratio is one of the characteristics of patients with DHF. Candidates of this study were 89 patients who presented to the emergency department because of acute pulmonary congestion. Those with an ejection fraction of >45% on admission comprised the DHF group (n=18). A control group consisted of consecutive 30 hypertensive patients with an ejection fraction of >45%. Doppler echocardiographic data were obtained with plasma BNP measure in the chronic stage >6 months after the emergent admission. The E/E' ratio was higher in the DHF group than in the control group (16.7±2.8 vs. 9.4±3.3, p<0.01). BNP level was also elevated in the DHF group. A persistent elevation of E/E' ratio may be an indicator of patients with or at risk of DHF among subjects with preserved systolic function independent of LV hypertrophy.

Exaggerated Hypertensive Response to Exercise in Patients with Diastolic Heart Failure

Systolic load elevation during exercise prolongs left ventricular (LV) relaxation, compromises filling, and raises end-diastolic pressure, leading to reduced exercise tolerance. The aim of this study was to test the hypothesis that the hypertensive response to exercise is exaggerated in patients with diastolic heart failure (DHF). Echocardiograms and treadmill testing were performed in patients with DHF (n=20) and age-matched hypertension with LV hypertrophy (HTN; n=20). The Minnesota Living with Heart Failure Questionnaire was used to estimate quality of life (QOL). There were no differences in resting blood pressure or echocardiographic parameters between the groups. The maximum exercise time was significantly shorter in the DHF group than in the HTN group (6.0+/-3.0 vs. 12.5+/-2.5 min), and the peak systolic blood pressure during exercise was significantly higher in the DHF group (212+/-18 vs. 189+/-16 mmHg, p<0.05). After 4 weeks of treatment with candesartan, an angiotensin II receptor blocker (8 mg/d), peak systolic blood pressure during exercise decreased to 191+/-13 mmHg, maximum exercise time increased (10.4+/-3.0 min; p<0.05), and QOL improved in patients with DHF, while there was no change in patients with HTN, despite the similar resting blood pressure. In patients with DHF, systolic blood pressure markedly increased during exercise, and this was accompanied by impaired exercise tolerance and a decreased QOL, both of which were partly suppressed by blocking angiotensin II.

Long-term Inhibition of Rho-kinase Ameliorates Diastolic Heart Failure in Hypertensive Rats

Diastolic heart failure (DHF) is a major cardiovascular disorder with poor prognosis; however, its molecular mechanism still remains to be fully elucidated. We have previously demonstrated the important roles of Rho-kinase pathway in the molecular mechanisms of cardiovascular fibrosis/hypertrophy and oxidative stress, but not examined in the development of heart failure. Therefore, we examined in this study whether Rho-kinase pathway is also involved in the pathogenesis of DHF in Dahl salt-sensitive rats, an established animal model of DHF. They were maintained with or without fasudil, a Rho-kinase inhibitor (30 or 100 mg/kg/day, PO) for 10 weeks. Untreated DHF group exhibited overt heart failure associated with diastolic dysfunction but with preserved systolic function, characterized by increased myocardial stiffness, cardiomyocyte hypertrophy, and enhanced cardiac fibrosis and superoxide production. Fasudil treatment significantly ameliorated those DHF-related myocardial changes. Western blot analysis showed that cardiac Rho-kinase activity was significantly increased in the untreated DHF group and was dose-dependently inhibited by fasudil. Importantly, there was a significant correlation between the extent of myocardial stiffness and that of cardiac Rho-kinase activity. These results indicate that Rho-kinase pathway plays an important role in the pathogenesis of DHF and thus could be an important therapeutic target for the disorder.

Subclinical Left Ventricular Longitudinal Systolic Dysfunction in Hypertension With No Evidence of Heart Failure

The prevalence of subclinical left ventricular (LV) systolic dysfunction in asymptomatic hypertensive patients was determined using tissue Doppler imaging (TDI). TDI-derived mitral annular velocities were acquired in 35 control subjects, 92 asymptomatic hypertensive patients with no heart failure (HHD), and 15 patients with diastolic heart failure (DHF). No significant intergroup differences in LV ejection fraction were noted. Peak systolic annular velocity was significantly reduced in the DHF group compared with the control and HHD group. Using peak systolic velocity <6.1 cm/s as a cut-off value for abnormal velocity, 10% of HHD patients and 53% of DHF showed impaired LV longitudinal systolic velocity. Peak early diastolic annular velocities were significantly reduced in both the HHD and DHF groups compared with the control group. With multivariable regression analysis, peak early and late diastolic annular velocities, female gender and deceleration time of the E wave velocity were selected as independent predictors for peak systolic annular velocities. Systolic long-axis LV function was impaired in 10% of asymptomatic hypertensive patients. Its reduction was closely correlated with impaired diastolic function. Assessment of LV longitudinal function by TDI plays an important role in identifying diastolic dysfunction and subclinical LV systolic dysfunction in asymptomatic hypertensive patients.

Preserved left ventricular twist and circumferential deformation, but depressed longitudinal and radial deformation in patients with diastolic heart failure

To examine myocardial deformation and rotation in patients with heart failure, and elucidate the underlying mechanisms that account for normal ejection fraction (EF) in patients with diastolic heart failure (DHF). Fifty consecutive patients presenting with congestive heart failure (age: 58 +/- 16 years) underwent simultaneous right heart catheterization and transthoracic echocardiography. Left ventricular (LV) volumes, mass, EF, meridional, and circumferential wall stress were measured in addition to haemodynamic measurements. 2-D speckle tracking was applied to measure longitudinal, radial, and circumferential strain and twist. Twist was reduced only in patients with systolic heart failure (SHF: 5 +/- 2 degrees, DHF: 13 +/- 6 degrees, control: 14 +/- 5 degrees, P < 0.001). Circumferential strain was not different between DHF (-15 +/- 5%) and control groups (-20 +/- 3%, P > 0.05), though it was significantly lower in patients with SHF (-7 +/- 3%, P < 0.05). Importantly, longitudinal (DHF:-12%, SHF: -4%, control: -19%, P < 0.001) and radial (DHF: 28 +/- 9%, SHF: 14 +/- 8%, control: 47 +/- 7%, P < 0.001) strains were significantly lower in both heart failure groups than in controls, and were depressed to a larger extent in SHF patients than in those with DHF (both P < 0.05). LV longitudinal and radial strains are reduced, but circumferential deformation and twist are normal in DHF patients. On the other hand, in patients with SHF, longitudinal, radial, and circumferential deformation, and twist are all reduced. Multivariable regression analysis suggests that preserved LV twist and circumferential strain may contribute to normal EF in patients with DHF.