Predictors of in-hospital mortality in elderly patients with heart failure treated with tolvaptan.

Objectives: We conducted an analysis of first-time tolvaptan users (≥80 years old) to determine the factors associated with the prognosis of elderly patients with heart failure. Methods: We retrospectively analyzed 66 consecutive patients with worsening heart failure (aged ≥80 years) who were admitted to Fujita Health University Bantane Hospital from 2011 to 2016 and treated with tolvaptan. Differences between the in-hospital death and survival groups were evaluated. Multivariate logistic regression analysis was also performed to identify the risk factors for mortality. Results: Sixty-six patients were included, and 26 patients died during the index hospitalization. The patients who died had a significantly higher prevalence of ischemic heart disease; a higher heart rate; higher levels of plasma C-reactive protein, blood urea nitrogen (BUN), and creatinine; a lower serum albumin level; and a lower estimated glomerular filtration rate than surviving patients. The proportion of patients requiring early initiation of tolvaptan treatment (within 3 days of admission) was significantly higher in surviving patients. On the basis of multivariate logistic regression analysis, although a high heart rate and high BUN levels were independent factors for in-hospital prognosis, they were not significantly associated with the early use of tolvaptan (≤3 days vs. ≥4 days; odds ratio=0.39; 95% confidence interval=0.07-2.21; p=0.29). Conclusions: This study revealed that a higher heart rate and higher BUN levels were independent factors for in-hospital prognosis in elderly patients who received tolvaptan and that early tolvaptan use may not always be effective in elderly patients.

A simple proteinuria-based risk score predicts contrast-associated acute kidney injury after percutaneous coronary intervention.

Contrast-associated acute kidney injury (CA-AKI) is a complication of percutaneous coronary intervention (PCI). Because proteinuria is a sentinel marker of renal dysfunction, we assessed its role in predicting CA-AKI in patients undergoing PCI. A total of 1,254 patients undergoing PCI were randomly assigned to a derivation (n = 840) and validation (n = 414) dataset. We identified the independent predictors of CA-AKI where CA-AKI was defined by the new criteria issued in 2020, by a multivariate logistic regression in the derivation dataset. We created a risk score from the remaining predictors. The discrimination and calibration of the risk score in the validation dataset were assessed by the area under the receiver-operating characteristic curves (AUC) and Hosmer-Lemeshow test, respectively. A total of 64 (5.1%) patients developed CA-AKI. The 3 variables of the risk score were emergency procedures, serum creatinine, and proteinuria, which were assigned 1 point each based on the correlation coefficient. The risk score demonstrated a good discriminative power (AUC 0.789, 95% CI 0.766-0.912) and significant calibration. It was strongly associated with the onset of CA-AKI (Cochran-Armitage test, p < 0.0001). Our risk score that included proteinuria was simple to obtain and calculate, and may be useful in assessing the CA-AKI risk before PCI.

Combined Assessment of D-Dimer with the Get with the Guidelines-Heart Failure Risk Score and N-Terminal Pro-B-Type Natriuretic Peptide in Patients with Acute Decompensated Heart Failure with Preserved and Reduced Ejection Fraction.

The prognostic role of D-dimer in different types of heart failure (HF) is poorly understood. We investigated the prognostic value of D-dimer on admission, both independently and in combination with the Get With The Guidelines-Heart Failure (GWTG-HF) risk score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients with preserved left ventricular ejection fraction (LVEF) and acute decompensated HF (HFpEF) or reduced LVEF (HFrEF). Baseline D-dimer levels were measured on admission in 1670 patients (mean age: 75 years) who were hospitalized for worsening HF. Of those patients, 586 (35%) were categorized as HFpEF (LVEF ≥ 50%) and 1084 as HFrEF (LVEF < 50%). During the 12-month follow-up period after admission, 360 patients died. Elevated levels (at least the highest tertile value) of D-dimer, GWTG-HF risk score, and NT-proBNP were all independently associated with mortality in all HFpEF and HFrEF patients (all p < 0.05). Adding D-dimer to a baseline model with a GWTG-HF risk score and NT-proBNP improved the net reclassification and integrated discrimination improvement for mortality greater than the baseline model alone in all populations (all p < 0.001). The number of elevations in D-dimer, GWTG-HF risk score, and NT-proBNP were independently associated with a higher risk of mortality in all study populations (HFpEF and HFrEF patients; all p < 0.001). The combination of D-dimer, which is independently predictive of mortality, with the GWTG-HF risk score and NT-proBNP could improve early prediction of 12-month mortality in patients with acute decompensated HF, regardless of the HF phenotype.

Impact of heart failure severity on bone mineral density among older patients with heart failure.

The study aimed to identify factors related to bone mineral density (BMD) among older patients with heart failure (HF). A total of 70 consecutive patients with HF aged 65 years or older who were admitted to an acute hospital due to worsening condition were enrolled before discharge. BMD of the femoral neck was evaluated using the DEXA method. Physical function, as well as echocardiographic and laboratory findings including biomarker of HF severity were collected. Bivariate and multiple regression analyses were employed to determine the association between BMD and the clinical variables. Bivariate analysis determined that age, grip strength, walking speed, serum albumin, and N-terminal pro B-type natriuretic peptide (NT-proBNP) were significantly correlated with BMD (P < 0.01), whereas other clinical parameters were not. The multiple regression analysis identified NT-proBNP as an independent related factor for BMD after adjusting with confounding clinical variables. NT-proBNP was independently related to BMD among older patients with HF. Our results suggest the inclusion of bone fracture prevention strategies in disease management programs, especially for older patients with HF.

Circulating miR-489 as a potential new biomarker for idiopathic dilated cardiomyopathy.

OBJECTIVES: MicroRNAs (miRNA) are functional RNAs that have emerged as pivotal gene expression regulators in cardiac disease. Although several cardiomyocyte miRNAs have been reported to play roles in heart failure progression among patients with idiopathic dilated cardiomyopathy (DCM), the role of circulating miRNAs has not yet been well-examined. METHODS: After total RNA extraction from the peripheral blood samples of three control participants and six patients with DCM, miRNA profiling was performed using miRNA arrays. Based on the results of this initial screening, real-time polymerase chain reaction (RT-PCR) was used to perform a quantitative analysis of blood samples from a larger number of matched patients (DCM, n=20; controls, n=5). Finally, the correlations between specific miRNA expression levels and hemodynamic parameters were analyzed. RESULTS: A primary screening of 2,565 miRNAs resulted in the identification of nine miRNA candidates. Quantitative RT-PCR results revealed significantly increased miR-489 expression levels in the DCM group. Moreover, there was a significant positive correlation between miR-489 expression level and left ventricular ejection fraction. CONCLUSIONS: Our results suggest that circulating miR-489 could be a potential noninvasive diagnostic biomarker for DCM. Additionally, the quantification of circulating miR-489 may have value as a potential prognostic marker for patients with DCM.

Impact of physical function on indeterminable anaerobic threshold in patients with heart failure.

BACKGROUND: Anaerobic threshold (AT) during cardiopulmonary exercise testing (CPET) is not always determinable in patients with heart failure (HF). However, little is known about the clinical features of patients with HF who have indeterminable AT. Therefore, the present study aimed to clarify the clinical features of such patients. METHODS: A total of 70 patients with HF (58 males; age: 68±12 years) who underwent CPET during hospitalization were divided into two groups: determinable AT (n=50) and indeterminable AT (n=20). Physical function, echocardiographic results, and laboratory findings were subsequently determined. RESULTS: Univariate analyses showed that the indeterminable AT group had significantly higher age and left ventricular ejection fraction, and significantly lower body mass index, calf circumference, handgrip strength, walking speed, serum hemoglobin, and serum albumin than the determinable AT group. Multiple logistic regression analysis identified handgrip strength and walking speed as independent predictive factors for indeterminable AT. Receiver-operating characteristic analyses revealed that handgrip strength of 21.2 kg and walking speed of 0.97 m/s were optimal cutoff values for differentiating patients who were likely to experience indeterminable AT. CONCLUSIONS: The present study identified handgrip strength and walking speed as powerful predictors for indeterminable AT with HF.

Effect of cardiac rehabilitation on circulating microRNA expression in heart failure: a preliminary study.

OBJECTIVES: There are benefits of exercise-based cardiac rehabilitation (CR) in patients with heart failure (HF), but their underlying molecular mechanisms remain elusive. The effect of CR on the expression profile of circulating microRNAs (miRNAs), which are short noncoding RNAs that regulate posttranscriptional expression of target genes, is unknown. If miRNAs respond to changes following CR for HF, then serum profiling of miRNAs may reveal cardioprotective mechanisms of CR. METHODS: This study enrolled three hospitalized patients with progressed systolic HF and three normal volunteer controls. In patients, CR was initiated after improvement of HF, which included 2 weeks of bicycle ergometer and resistance exercises. Genome-wide expression profiling of circulating miRNAs was performed using microarrays for the patients (mean±SD age, 60.0±12.2 years) and controls (58.7±0.58 years). Circulating miRNA expression profiles were compared between patients with HF before and after CR and the controls. RESULTS: Expression levels of two miRNAs were significantly different in patients before CR compared with controls and patients after CR. The expression of hsa-miR-125b-1-3p was significantly downregulated and that of hsa-miR-1290 was significantly upregulated in patients before CR. CONCLUSIONS: When performing CR, expression of certain circulating miRNAs in patients with HF is restored to nonpathological levels. The benefits of CR for HF may result from regulation of miRNAs through multiple effects of gene expression.

On-site assessment of computed tomography-derived fractional flow reserve in comparison with myocardial perfusion imaging and invasive fractional flow reserve.

Myocardial perfusion imaging (MPI) using Single Photon Emission Computed Tomography has been established as a standard noninvasive tool for risk stratification of coronary artery disease (CAD). We evaluated the diagnostic performance of on-site workstation-based computed tomography-derived fractional flow reserve (CT-FFR) in comparison with MPI using invasive fractional flow reserve (invasive FFR) as a gold standard. We enrolled 97 patients with suspected CAD. Diagnostic performance of CT angiography (CTA), and CT-FFR was compared in 105 lesions of 97 patients. Invasive FFR ≤ 0.8 was detected in 38 (36%) lesions. Diagnostic performance of CT-FFR was improved compared with CTA (AUC 0.83 vs. 0.60, p < 0.0001). The lesions with both CTA and MPI findings (n = 47), invasive FFR ≤ 0.8 was detected in 19 (40.4) lesions. CT-FFR (AUC 0.81, 95% CI 0.72-0.94) significantly improved diagnostic performance compared with CTA-50% (AUC 0.59, p = 0.00019) and MPI (AUC 0.64, p = 0.0082). In lesions with ≥ 50% on CTA (n = 42), diagnostic accuracy of CT-FFR (AUC 0.81) was significantly superior to MPI (AUC 0.64, p = 0.0239). In conclusions, CT-FFR improved diagnostic accuracy to detect invasive FFR ≤ 0.8 compared with luminal stenosis on CTA and ischemia on MPI. Patients with ≥ 50% stenosis on CTA would be the candidates for CT-FFR.

Urinary Liver-Type Fatty-Acid-Binding Protein Predicts Long-Term Adverse Outcomes in Medical Cardiac Intensive Care Units.

We prospectively investigated the prognostic value of urinary liver-type fatty-acid-binding protein (L-FABP) levels on hospital admission, both independently and in combination with serum creatinine-defined acute kidney injury (AKI), to predict long-term adverse outcomes in 1119 heterogeneous patients (mean age; 68 years) treated at medical (non-surgical) cardiac intensive care units (CICUs). Patients with stage 5 chronic kidney disease were excluded from the study. Of these patients, 47% had acute coronary syndrome and 38% had acute decompensated heart failure. The creatinine-defined AKI was diagnosed according to the "Kidney Disease: Improving Global Outcomes" criteria. The primary endpoint was a composite of all-cause death or progression to end-stage kidney disease, indicating the initiation of maintenance dialysis therapy or kidney transplantation. Creatinine-defined AKI occurred in 207 patients, with 44 patients having stage 2 or 3 disease. During a mean follow-up period of 41 months after enrollment, the primary endpoint occurred in 242 patients. Multivariate Cox regression analyses revealed L-FABP levels as independent predictors of the primary endpoint (p < 0.001). Adding L-FABP to a baseline model with established risk factors further enhanced reclassification and discrimination beyond that of the baseline model alone, for primary-endpoint prediction (both; p < 0.01). On Kaplan-Meier analyses, increased L-FABP (≥4th quintile value of 9.0 ng/mL) on admission or presence of creatinine-defined AKI, correlated with an increased risk of the primary endpoint (p < 0.001). Thus, urinary L-FABP levels on admission are potent and independent predictors of long-term adverse outcomes, and they might improve the long-term risk stratification of patients admitted at medical CICUs, when used in combination with creatinine-defined AKI.

The difference in determinant factor of six-minute walking distance between sarcopenic and non-sarcopenic elderly patients with heart failure.

BACKGROUND: The purpose of this study was to identify the factors determining exercise capacity in elderly patients with heart failure (HF) with and without sarcopenia. METHODS: We studied 186 consecutive patients with HF who met the criteria of being >60 years, with no physical disability. During hospitalization, we measured the 6-min walking distance (6MWD) and other physical functional parameters and evaluated echocardiographic and laboratory measurements indicating the severity of HF. First, we divided patients into two groups (the sarcopenia group and the nonsarcopenia group) according to the presence of sarcopenia defined as fulfilling more than or equal to two criteria-body mass index <18.5, walking speed <0.8m/s, and grip strength <26kg in males, or <18kg in females. Then the association between the 6MWD and the clinical variables mentioned above was analyzed by univariate and multiple logistic regression analyses. RESULTS: The sarcopenia group comprised 77 patients (41.2%). In univariate analysis, age, grip strength, walking speed, and knee extensor muscle strength were significantly correlated with the 6MWD (p<0.05), whereas other clinical parameters were not. In multivariate analysis, walking speed was selected as an independent factor determining the 6MWD in both groups; however, knee extensor muscle strength was selected as an independent factor determining the 6MWD only in the sarcopenia group. CONCLUSION: We demonstrated that knee extensor muscle strength was an independent factor determining exercise capacity-especially in elderly patients with HF with sarcopenia, and provided useful information in terms of exercise prescription.

Predictive impact of early mobilization on rehospitalization for elderly Japanese heart failure patients.

The aim of this study was to determine whether early mobilization was associated with rehospitalization among elderly heart failure patients. We measured the time from admission to mobilization and other clinical characteristics for 190 heart failure patients (mean age, 80.7 years). The primary outcome was heart failure rehospitalization. Kaplan-Meier survival curves were plotted and the hazard ratios for rehospitalization were determined using Cox proportional hazards regression models. During a median follow-up period of 750 days, 58 patients underwent rehospitalization. The time from admission to mobilization was significantly longer for these patients than for those who were not rehospitalized. Univariate and multivariate Cox proportional hazards analyses showed that the time from admission to mobilization was an independent predictor of rehospitalization, and receiver-operating characteristic analysis determined an optimal cutoff value of 3 days for differentiating the patients more likely to experience a subsequent cardiac event (sensitivity, 76%; specificity, 69%; area under the curve, 0.667). Kaplan-Meier survival curve analysis showed a significantly lower event rate in the ≤ 3-day group (p = 0.001, log-rank test). In conclusion, the time from admission to mobilization may be one of the strongest predictors of rehospitalization in elderly heart failure patients. Early mobilization within 3 days may be an initial target for the acute phase treatment of heart failure.

Serum microRNA-126 and -223 as new-generation biomarkers for sarcoidosis in patients with heart failure.

BACKGROUND: Although cardiac sarcoidosis is associated with poor prognosis, diagnosis of the disease is challenging and the sensitivity and specificity of diagnostic modalities are limited. This study was performed to evaluate the potential of serum microRNAs (miRNAs) as diagnostic biomarkers for cardiac sarcoidosis. METHODS: We performed genome-wide expression profiling for 2565 miRNAs (Human-miRNA ver.21) using peripheral blood samples from 5 patients with cardiac sarcoidosis (61±9 years) and 3 healthy controls (54±7 years). From this screening study, we selected 12 miRNAs that were significantly related to cardiac sarcoidosis. Next, we performed real-time polymerase chain reaction (PCR) on blood samples from 15 new patients with cardiac sarcoidosis and 4 healthy controls to quantify the expression of these 12 miRNAs. RESULTS: In the screening study, 12 miRNAs were differentially expressed (p<0.01) in all 5 patients with cardiac sarcoidosis, showing greater fold-change values (>4 or <0.25) compared with the expression in the 3 healthy controls. Analysis of the real-time PCR for blood samples from the other 15 patients and 4 controls using Mann-Whitney U tests revealed that the expression of miR-126 and miR-223 was significantly higher in the patients than in the healthy individuals. However, there were no differences in the expressions of miRNA-126 and miR-223 between patients with only cardiac lesions and those with extra-cardiac lesions. CONCLUSIONS: Our results demonstrate the potential of serum miR-126 and miR-223 as new-generation biomarkers for the differential diagnosis of cardiac sarcoidosis in patients with heart failure.

Antihypertensive efficacy and safety of the angiotensin receptor blocker azilsartan in elderly patients with hypertension.

OBJECTIVES: The number of elderly patients with hypertension has been steadily increasing. However, there are limited data on the safety and efficacy of the new angiotensin type 1 receptor blocker (ARB) azilsartan in elderly patients with hypertension. We investigated the clinical efficacy and safety of azilsartan in this population. METHODS: The study population comprised 56 ambulatory patients with essential hypertension. We evaluated the reduction in blood pressure and safety after 12 weeks of treatment with azilsartan in 29 hypertensive patients ≥65 years of age (aged group) in comparison with the findings in 27 patients <65 years of age (non-aged group). RESULTS: Systolic blood pressure in the aged group declined significantly from 155 ± 18 mmHg at baseline to 138 ± 11 mmHg after 12 weeks of treatment with azilsartan, and that in the non-aged group also declined significantly from 152 ± 20 mmHg at baseline to 142 ± 13 mmHg after 12 weeks of treatment with azilsartan. There were no significant differences in the magnitude of change in blood pressures from pre-treatment to post-treatment with azilsartan between the non-aged and aged groups. There were no changes in clinical laboratory findings, including serum levels of creatinine, potassium, lipids, and other metabolic variables, after 12 weeks of treatment with azilsartan in both groups. CONCLUSIONS: Our findings suggest that azilsartan is effective in lowering blood pressure in elderly patients and may be safe. Therefore, azilsartan could be a valuable option for treating hypertension in elderly and non-elderly patients.

Brain natriuretic peptide as a potential novel marker of salt-sensitivity in chronic kidney disease patients without cardiac dysfunction.

Although the renin-angiotensin system (RAS) is counter-balanced by a salt-sensitive mechanism in the hypertensive state, both are reported to be up-regulated in chronic kidney disease (CKD) patients. We conducted this study to evaluate the associations among the RAS, renal function, hypertension, and atherosclerosis, as well as to identify markers for salt-sensitivity. A total of 213 pre-dialysis CKD patients with preserved cardiac function (EF >50 %) were enrolled. Their renal and cardiac biochemical markers and plasma renin activity (PRA) were measured, and echocardiography and carotid artery ultrasound were performed. Their salt intake was estimated by the NaCl excretion from a 24-h collected urine sample. The PRA was higher in patients with hypertension (p = 0.018), and had a significant negative correlation with the eGFR (r = -0.23, p = 0.0067). Importantly, the PRA had a strong negative correlation with the brain natriuretic peptide (BNP) level (r = -0.28, p = 0.017) regardless of whether the patients were being treated with RAS inhibitors. The BNP level was related to the renal functions (eGFR: p = 0.001, ACR: p = 0.009). There was a significant positive correlation between the BNP level and carotid intima-media thickness (p < 0.001). A multivariate analysis revealed that older age and an excess of NaCl excretion were independent predictors of BNP elevation (p = 0.02 and 0.003, respectively). Our analysis revealed details of the counterbalance between BNP and PRA, as well as identifying that excess salt intake is a predictor of BNP elevation. These results indicate that the BNP could be a possible valuable marker for salt sensitivity, and that high salt sensitivity could facilitate atherosclerosis in CKD patients.

Prescription patterns of oral anticoagulants for patients with non-valvular atrial fibrillation: experience at a Japanese single institution.

New oral anticoagulants (NOACs) are now clinically available. However, few studies have demonstrated which patients with non-valvular atrial fibrillation (NVAF) actually receive NOACs in a clinical setting. We analyzed 182 NVAF patients who received oral anticoagulants. Clinical backgrounds and the risk of stroke, systemic embolism, and bleeding associated with oral anticoagulants were investigated. Seventy-three (40 %) patients were treated with NOACs and 109 (60 %) patients were treated with warfarin. A significantly lower mean number of bleeding risk factors was observed among the patients treated with NOACs than among those treated with warfarin (P = 0.010). Of the bleeding risk factors, NOACs were significantly less frequently prescribed in patients with a bleeding history and elderly subjects (>65 years) than in those who received warfarin (P < 0.001 and P = 0.029). A multivariate logistic regression analysis revealed that CHF and bleeding history were independently and significantly associated with the administration of NOACs (P = 0.047 and P = 0.003). The rate of a history of intracranial hemorrhage was comparable between the patients treated with NOACs and those treated with warfarin (P = 1.000). Significantly lower rates of a history of gastrointestinal and other minor bleeding were observed in the patients who received NOACs versus those who received warfarin (P = 0.001 and P = 0.026). NOACs were less frequently prescribed in patients with a history of bleeding, especially those with a history of gastrointestinal bleeding in a clinical setting.

Clinical Characteristics and Long-Term Outcomes of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) has various morphological and clinical features. A decade has passed since the previous survey of the epidemiological and clinical characteristics of Japanese HCM patients. The Aichi Hypertrophic Cardiomyopathy (AHC) Registry is based on a prospective multicenter observational study of HCM patients. The clinical characteristics of 42 ambulant HCM patients followed up for up to 5 years were investigated. The primary endpoint was major adverse cardiac events (MACE), defined as death, non-fatal stroke, admission due to congestive heart failure (CHF), or episodes of sustained ventricular tachycardia/fibrillation. The MACE-free survival during the 5-year follow-up period was 76% according to Kaplan-Meier analysis. HCM-related death occurred in 3 (7%) patients and SCD occurred in 2 (5%) patients. Additionally, 3 (7%) patients were admitted to the hospital due to CHF. Meanwhile, sustained VT was detected in one (2%) of the patients who received ICD implantation and subsequently terminated with antitachycardia pacing using an ICD. The patients with HCM exhibiting left ventricular outflow obstruction (HOCM) had a slightly lower MACE-free survival rate than those with neither HOCM nor dilated-HCM (dHCM) (71% versus 81%, log-rank P = 0.581). Furthermore, the patients with dHCM demonstrated a significantly lower MACE-free survival rate than those with neither HOCM nor dHCM (33% versus 81%, log-rank P = 0.029). In the AHC Registry targeting current Japanese HCM patients, we demonstrated that many HCM patients continue to suffer from MACE despite the development of various treatments for HCM.

Takotsubo cardiomyopathy with involvement of delayed-onset rhabdomyolysis and acute kidney injury after rosuvastatin treatment.

Takotsubo cardiomyopathy is a disorder characterized by left ventricular apical ballooning with preceding emotional and/or physical stressors. This condition is also an important differential diagnosis of acute coronary syndrome. We herein describe a case of Takotsubo cardiomyopathy, a significant clinical phenomenon, triggered by delayed-onset rhabdomyolysis following the administration of long-term statin treatment, without any preceding stressors or changes in the patient's medical condition, in association with complaints of non-specific muscle-related symptoms. Although an electrocardiogram showed remarkable ST-segment elevation, a careful reading of the electrocardiogram findings revealed the features of Takotsubo cardiomyopathy. Withdrawing the statin therapy improved the patient's cardiac function.

Role of the left atrial function on the pseudonormalization of the transmitral flow velocity pattern evaluated by two-dimensional tissue tracking technique.

BACKGROUND: Mechanisms of the pseudonormalization (PN) of the transmitral flow (TMF) velocity pattern have been mainly attributed to left ventricular diastolic function. PURPOSE: To assess the influence of left atrial (LA) function on the PN with two-dimensional tissue tracking technique. METHODS: The subjects consisted of 21 healthy volunteers and 70 patients with various cardiac diseases. Images of one cardiac cycle in the apical four-chamber view were stored by the HIVISION 900 (Hitachi Medico, Chiba, Japan). The LA volume (LAV) loop was created using two-dimensional tissue tracking technique and LAV index (LAVI) at a given cardiac phase was calculated. A preload of 90mmHg was applied using a customized lower body positive pressure (LBPP) system. Patients were divided into the PN group (n=18) with their early diastolic TMF velocity (E) increased and late diastolic TMF velocity (A) decreased, and the non-(N)-PN group (n=52) with both E and A wave velocities increased by LBPP. RESULTS: (1) During LBPP, the LAVImax in both the groups increased significantly. (2) In the N-PN group, the LAVIpass (p<0.001), LAVIact (p<0.01), and LAVItotal (p<0.0001) increased significantly. The dV/dts (p<0.0001) and dV/dtE (p<0.0001) increased significantly with an increase in the dV/dtA. On the other hand, there was no change in those parameters except LAVIpass (p<0.05) and dV/dtE (p<0.05) significantly increased in the PN group. (3) As a result, the LAVImin was significantly greater in the PN group than in the N-PN group (p<0.0001) during LBPP. The ratio of E velocity to early diastolic mitral annular velocity (E/E') during LBPP was significantly greater in the PN group than in the N-PN group (p<0.0001). CONCLUSIONS: The lack of an increase in active LA emptying volume in response to an increase of preload leads to elevated LA pressure and the pseudonormalization of the TMF velocity pattern in patients with various cardiac diseases.