Effects of catheter-based renal denervation on heart failure with reduced ejection fraction: a meta-analysis of randomized controlled trials.

Despite the major progress in the treatment of heart failure, the burden of heart failure is steadily increasing in the Western world. Heart failure is characterized by increased sympathetic activity, and chronic sympathetic activation is involved in the maintenance of the pathological state. Recent studies have shown that catheter-based renal denervation (RDN) presents a safe and minimally invasive treatment option for uncontrolled hypertension, a condition that is driven by increased sympathetic activity. Although randomized controlled trials (RCTs) have examined the effect of RDN in heart failure patients, results are inconsistent due partly to limited power with small sample sizes. We aimed to conduct a meta-analysis of RCTs on the effect of RDN in heart failure patients with reduced left ventricular (LV) ejection fraction (EF). Electronic search identified 5 RCTs including 177 patients. In the pooled analysis, RDN increased LVEF (weighted mean difference (WMD) [95% CI] = 6.289 [1.883, 10.695]%) and 6-min walk distance (61.063 [24.313, 97.813] m) and decreased B-type natriuretic peptide levels (standardized mean difference [95% CI] = - 1.139 [- 1.824, - 0.454]) compared with control. In contrast, RDN did not significantly change estimated glomerular filtration rate (WMD [95% CI] = 5.969 [- 2.595, 14.533] ml/min/1.73 m2) and systolic (- 1.991 [- 15.639, 11.655] mmHg) or diastolic (- 0.003 [- 10.325, 10.320] mmHg) blood pressure compared with control. Our meta-analysis suggests that RDN may improve LV function and exercise capacity in heart failure patients with reduced EF, providing the rationale to conduct large-scale multicenter trials to confirm the observed potential benefits of RDN.

Effect of renin-angiotensin system inhibition on cardiac structure and function and exercise capacity in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials.

Targeting the renin-angiotensin system (RAS) pathways has been considered a logical intervention for patients with heart failure with preserved ejection fraction (HFpEF), due to its hypothesized link to left ventricular (LV) remodeling. Although the effects of RAS inhibitors including angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and direct renin inhibitors (DRIs) on LV structure and function and exercise capacity in HFpEF patients have been examined in multiple randomized controlled trials (RCTs), results are inconsistent due partly to limited power. We conducted a meta-analysis of RCTs on the effects of RAS inhibitors on LV structure and function as well as exercise capacity in HFpEF patients. The search of electronic databases identified 7 trials including 569 patients; 4 trials were on ACE-Is; 2 on ARBs; and 1 on DRIs. Follow-up duration ranged across trials from 12 to 52 weeks. The pooled analysis showed that RAS inhibitors significantly increased EF compared with control (weighted mean difference [95% CI] = 2.182 [0.462, 3.901] %). In contrast, RAS inhibitors did not significantly change the ratio of peak early to late diastolic mitral inflow velocities (weighted mean difference [95% CI] = 0.046 [- 0.012, 0.105]), early diastolic mitral annular velocity (0.327 [- 0.07, 0.725] cm/s), the ratio of early diastolic mitral inflow to annular velocities (0.291 [- 0.937, 1.518]), LV mass (- 6.254 [- 15.165, 2.656] g), or 6-min walk distance (1.972 [- 14.22, 18.163] m) compared with control. The present meta-analysis suggests that RAS inhibitors may increase LVEF in HFpEF patients.

Effect of beta-blockers on heart failure severity in patients with heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials.

Patients with heart failure with preserved ejection fraction (HFpEF) are often elderly and likely to have cardiac comorbidities such as coronary artery disease (CAD) and atrial fibrillation (AF). The primary chronic symptom of HFpEF patients is severe exercise intolerance. The inability to adequately increase heart rate during exercise is commonly present in HFpEF patients and contributes to their exercise intolerance. Although beta-blockers are frequently used for the treatment of myocardial ischemia and tachycardia in HFpEF patients, there is a concern that slowing heart rate by beta-blockers may worsen chronotropic incompetence and further exacerbate their symptoms. Although the effect of beta-blockers on heart failure severity in HFpEF patients has been examined in randomized controlled trials (RCTs), results are inconsistent due partly to limited power. We aimed to conduct a meta-analysis of RCTs on the effect of beta-blockers on heart failure severity in HFpEF patients. The search of electronic databases identified 5 RCTs including 538 patients. In pooled analyses, beta-blockers did not significantly change the New York Heart Association (NYHA) class, exercise capacity expressed as metabolic equivalents, or plasma B-type natriuretic peptide (BNP) levels compared with control but with substantial heterogeneity across trials. In meta-regression analyses, the higher proportion of CAD or AF in the included trials was associated with a decrease in NYHA class and BNP levels and with an increase in exercise capacity. Thus, we found no clear beneficial effect of beta-blockers on heart failure severity in HFpEF patients. However, beta-blockers may be beneficial in HFpEF patients with CAD or AF.

Correlation Between Longitudinal Strain in the Apical Segments of the Left Ventricle at End-Systole Obtained by 2-Dimensional Speckle-Tracking Echocardiography and Left Ventricular Relaxation.

BACKGROUND: It is well acknowledged that left ventricular (LV) contractile performance affects LV relaxation via LV elastic recoil. Accordingly, we aimed to investigate whether global longitudinal strain (GLS), particularly longitudinal strain at LV apical segments at end-systole (ALS), obtained by 2-dimensional speckle-tracking echocardiography could be used to assess LV relaxation.Methods and Results:We enrolled 121 patients with suspected or definite coronary artery disease in whom echocardiography and diagnostic cardiac catheterization were performed on the same day. We obtained conventional echo-Doppler parameters and GLS, as well as ALS prior to catheterization. LV functional parameters were obtained from the LV pressure recorded using a catheter-tipped micromanometer. In all patients, GLS and ALS were significantly correlated with the time constant τ of LV pressure decay during isovolumetric relaxation (r=0.63 [P<0.001] and r=0.66 [P<0.001], respectively). Receiver operating characteristic curve analysis for identifying impaired LV relaxation (τ ≥48 ms) revealed that ALS greater than -22.3% was an optimal cut-off value, with 81.7% sensitivity and 82.4% specificity. Even in patients with preserved LV ejection fraction, the same ALS cut-off value enabled the identification of impaired LV relaxation with 70% sensitivity and 87.5% specificity. CONCLUSIONS: The findings indicate that contractile dysfunction at LV apical segments slows LV relaxation via loss of LV elastic recoil, even in patients with preserved LVEF.

Left ventricular contractile performance and heart failure in patients with left ventricular ejection fraction more than 40.

Heart failure (HF) with mid-range left ventricular ejection fraction (LVEF) (HFmrEF) is considered a new category of HF and LVEF < 50%, which is the upper threshold of LVEF for HFmrEF, is thought to represent a mild decrease in LV contractile performance. We aimed to consider an LVEF threshold value to be taken as a surrogate for impairment of LV contractile performance, resulting in new-onset HF. We enrolled 398 patients with LVEF ≥ 40% that underwent cardiac catheterization. Using the LV pressure recording with a catheter-tipped micromanometer, we calculated the inertia force of late systolic aortic flow (IFLSAF), which was sensitive to the slight impairment in LV contractile performance. We evaluated the utility of the IFLSAF for predicting future cardiovascular death or hospitalization for HF. We performed a receiver operating characteristic (ROC) curve analysis to determine the best LVEF threshold value for distinguishing whether the LV maintained the IFLSAF. A multivariate Cox proportional-hazards model revealed that the loss of IFLSAF was significantly associated with the future adverse events (HR: 7.798, 95%CI 2.174-27.969, p = 0.002). According to the ROC curve analysis, an LVEF ≥ 58% indicated that the LV could maintain the IFLSAF. We concluded that the loss of IFLSAF, which could reflect even slight impairment in LV contractile performance, was a reliable indicator for new-onset HF in patients with LVEF ≥ 40%. LVEF ≥ 58% could be taken as a surrogate for the IFLSAF maintenance; this threshold could be useful for risk stratification of new-onset HF in patients with preserved LVEF.

Effects of exercise training on cardiac function, exercise capacity, and quality of life in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials.

Left ventricular (LV) diastolic dysfunction is associated with the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and contributes importantly to exercise intolerance that results in a reduced quality of life (QOL) in HFpEF patients. Although the effects of exercise training on LV diastolic function, exercise capacity, or QOL in HFpEF patients have been examined in randomized clinical trials (RCTs), results are inconsistent due partly to limited power with small sample sizes. We aimed to conduct a meta-analysis of RCTs examining the effects of exercise training on LV diastolic function and exercise capacity as well as QOL in HFpEF patients. The search of electronic databases identified 8 RCTs with 436 patients. The duration of exercise training ranged from 12 to 24 weeks. In the pooled analysis, exercise training improved peak exercise oxygen uptake (weighted mean difference [95% CI], 1.660 [0.973, 2.348] ml/min/kg), 6-min walk distance (33.883 [12.384 55.381] m), and Minnesota Living With Heart Failure Questionnaire total score (9.059 [3.083, 15.035] point) compared with control. In contrast, exercise training did not significantly change early diastolic mitral annular velocity (weighted mean difference [95% CI], 0.317 [- 0.952, 1.587] cm/s), the ratio of early diastolic mitral inflow to annular velocities (- 1.203 [- 4.065, 1.658]), or LV ejection fraction (0.850 [- 0.128, 1.828] %) compared with control. In conclusion, the present meta-analysis suggests that exercise training improves exercise capacity and QOL without significant change in LV systolic or diastolic function in HFpEF patients.

The effect of influenza vaccination on mortality and hospitalization in patients with heart failure: a systematic review and meta-analysis.

Influenza infection is associated with increased risk for mortality and hospitalization in heart failure patients. Although there are no published randomized controlled trials examining the effect of influenza vaccination on clinical outcomes in heart failure patients, the effect has been examined in observational cohort studies. Nevertheless, results are inconsistent due partly to limited power with small sample sizes and use of different definitions of outcomes. We therefore aimed to conduct a systematic review and meta-analysis of the effect of influenza vaccination on mortality and hospitalization in heart failure patients. The search of electronic databases identified 6 observational cohort studies with 22,486 patients examining the effect of influenza vaccination on mortality and hospitalization in heart failure patients. Pooled analysis of confounder-adjusted hazard ratio showed that influenza vaccination was associated with reduced risk of mortality during 1-year follow-up (risk ratio [95% CI] = 0.76 [0.63-0.92], Pfix < 0.01) and during long-term (up to 4 years) follow-up (0.80 [0.71-0.90], Pfix < 0.001). Furthermore, influenza vaccination was associated with reduced risk of mortality during influenza season (risk ratio [95% CI] = 0.52 [0.39-0.69], Prandom < 0.001) and during non-influenza season (0.79 [0.69-0.90], Pfix < 0.001). Only a few studies reported the effect of influenza vaccination on hospitalization, which did not permit us to perform pooled analysis. In conclusion, our meta-analysis showed that influenza vaccination was associated with reduced risk of mortality in heart failure patients. Large-scale and adequately powered randomized controlled trials should be planned to confirm our observed potential survival benefit of influenza vaccination in these patients.

Effects of mineralocorticoid receptor antagonists on left ventricular diastolic function, exercise capacity, and quality of life in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials.

Left ventricular (LV) diastolic dysfunction is associated with the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and contributes importantly to exercise intolerance that results in a reduced quality of life (QOL) in HFpEF patients. Experimental studies have shown that aldosterone plays a role in the genesis of myocardial hypertrophy and fibrosis, thereby enhancing LV diastolic dysfunction, and that aldosterone antagonists (mineralocorticoid receptor antagonists [MRAs]) prevents myocardial hypertrophy and fibrosis. Although the effects of MRAs on LV diastolic function, exercise capacity, and QOL in HFpEF patients have been examined in randomized clinical trials (RCTs), results are inconsistent due partly to limited power with small sample sizes. We aimed to conduct a meta-analysis of RCTs on the effects of MRAs on LV diastolic function, exercise capacity, and QOL in HFpEF patients. The search of electronic databases identified 6 studies including 755 HFpEF patients. In the pooled analysis, MRAs increased early diastolic mitral annular velocity (weighted mean difference [95% CI] = 0.455 [0.232-0.679] cm/s; Pfix < 0.001) and decreased the ratio of early diastolic mitral inflow to annular velocities (- 1.474 [- 2.073 to - 0.875]; Pfix < 0.001) compared with control. There was no significant difference in change of peak exercise oxygen uptake, 6-minute walking distance, or QOL questionnaire scores between MRA and control group. In conclusion, our meta-analysis showed that MRAs improved LV diastolic function in HFpEF patients. However, the observed improvement in LV diastolic function with the use of MRAs did not translate into improved exercise capacity or QOL in these patients.

Left Ventricular Mass Influences Relationship Between Filling Pressure and Early-Diastolic Ratio of Inflow Velocity to Mitral Annular Velocity (E/e').

BACKGROUND: Early-diastolic mitral annular velocity (e') and the ratio of early-diastolic left ventricular (LV) inflow velocity (E) to e' (E/e') have been widely used as indexes of LV relaxation and filling pressure, respectively. However, many recent studies have demonstrated that they are not reliable in various clinical settings. We thus investigated the factors influencing these echocardiographic parameters in a multicenter study.Methods and Results:The study group comprised 69 patients, referred for cardiac catheterization, and enrolled in 5 university hospitals. Time constant (τ) and LV mean diastolic pressure (LVMDP) were measured using a micromanometer-tipped catheter. Although e' only weakly correlated with τ (r=-0.35, P<0.01), E/e' modestly correlated with LVMDP (r=0.48, P<0.001). Multivariable analysis revealed that hypertension (ß=-0.33, P<0.01) and LV ejection fraction (LVEF) (ß=0.44, P<0.001) were the independent determinants of e', and LV mass index (LVMI) (ß=0.37, P<0.001) and LVMDP (ß=0.47, P<0.001) were those of E/e'. Additionally, E/e' significantly correlated with LVMDP in patients with normal LVMI (r=0.74, P<0.001) but not in those with increased LVMI. CONCLUSIONS: The coincidence of hypertension and LVEF affected the relationship between LV relaxation and e', whereas LVMI altered the relationship between LV filling pressure and E/e'. Thus, clinical conditions associated with an increase in LVMI, such as LV hypertrophy and LV dilatation, should be considered when estimating the filling pressure from E/e'.

Compensatory Increase in Heart Rate Is Responsible for Exercise Tolerance among Male Patients with Permanent Atrial Fibrillation.

Atrial fibrillation (AF) is an exacerbating factor for exercise tolerance due to the loss of atrial kick. However, many patients with permanent AF, which lasts for at least a year without interruption, and preserved left ventricular ejection fraction (LVEF ≥ 50%) are asymptomatic and have good exercise tolerance. In such cases, the possible mechanism that compensates for the decrease in cardiac output accompanying the loss of atrial kick is a sufficient increase in heart rate (HR) during exercise. We investigated the relationship between exercise tolerance and peak HR during exercise using cardiopulmonary exercise testing in 242 male patients with preserved LVEF, 214 with sinus rhythm (SR) and 28 with permanent AF. Peak HR was significantly higher in the AF group than the SR group (148.9 ± 41.9 vs. 132.0 ± 22.0 beats/min, p = 0.001). However, oxygen uptake at peak exercise did not differ between the AF and SR groups (19.4 ± 5.7 vs. 21.6 ± 6.0 mL/kg/min, p = 0.17). In multiple regression analysis, peak HR (ß, 0.091; p < 0.001) and the interaction term constructed by peak HR and presence of permanent AF (ß, 0.05; p = 0.04) were selected as determinants for peak VO2; however, presence of permanent AF was not selected (ß, -0.38; p = 0.31). Therefore, the impact of peak HR on exercise tolerance differed between the AF and SR groups, suggesting that a sufficient increase in HR during exercise is an important factor to preserve exercise tolerance among patients with AF.

Effect of renin-angiotensin system inhibitors on mortality in heart failure with preserved ejection fraction: a meta-analysis of observational cohort and randomized controlled studies.

Despite the high mortality rate, there is no therapy to improve survival in heart failure with preserved ejection fraction (HFpEF). Large randomized controlled trials (RCTs) did not show clear mortality benefit of renin-angiotensin system (RAS) inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) in HFpEF. However, because of the strict enrollment criteria, the patients who participated in these trials might represent a selected group of patients that is poorly representative of patients treated in routine clinical practice. In contrast, clinical characteristics of real-world patients are similar to those of patients enrolled in observational cohort studies (OCSs). Although many OCSs have examined the prognostic effect of RAS inhibitors in HFpEF, the results are inconsistent due to limited power with small sample sizes and/or inadequate adjustment for known prognostic factors. We aimed to conduct a meta-analysis of OCSs with and those without propensity score (PS) analysis and RCTs on the effect of RAS inhibitors on mortality in HFpEF patients. The search of electronic databases identified 4 OCSs with PS analysis (10,164 patients), 8 OCSs without PS analysis (16,393 patients), and 3 RCTs (8001 patients). Use of RAS inhibitors was associated with reduced mortality in the pooled analysis of OCSs with PS analysis (RR [95% CI] = 0.90 [0.81-1.00]) and in that of OCSs without PS analysis (0.81 [0.68-0.96]) but not in that of RCTs (0.99 [0.87-1.12]). In conclusion, the present meta-analysis suggests the potential mortality benefit of RAS inhibitors in HFpEF, emphasizing the importance of conducting new well-designed RCTs.

Effects of catheter-based renal denervation on heart failure with reduced ejection fraction: a systematic review and meta-analysis.

Despite the recent advances in the management of heart failure, the mortality of heart failure patients remains high. It is of urgent need to develop new therapy for heart failure. Heart failure is characterized by increased sympathetic activity, and chronic sympathetic activation is involved in the maintenance of the pathological state. Catheter-based renal denervation (RDN) has emerged as an invasive but safe approach that can reduce sympathetic activation. Studies have reported inconsistent results regarding the effect of RDN in heart failure patients due to limited power with small sample sizes. We aimed to conduct a meta-analysis of the effect of RDN on heart failure patients with reduced left ventricular (LV) ejection fraction (EF). An electronic search for studies examining the effect of RDN on LV function in heart failure patients with reduced EF was conducted. Two controlled (80 patients) and 2 uncontrolled studies (21 patients) were included in this meta-analysis. In the pooled analysis, 6 months after RDN, there was a greater increase in EF (weighted mean difference [95% CI] = 8.63 [6.02, 11.24] %) and a greater decrease in LV end-diastolic diameter (-0.58 [-0.83, -0.34] cm) in RDN group than in control group. No serious adverse events such as acute renal artery stenosis and dissection occurred. Our meta-analysis of feasibility studies suggests that RDN may improve LV function in heart failure patients with reduced EF, providing the rationale to conduct next phase trials to confirm the observed potential benefits of RDN.

Left Ventricular Global Strain for Estimating Relaxation and Filling Pressure　- A Multicenter Study.

BACKGROUND: Speckle-tracking echocardiography (STE)-derived parameters may have better correlation with left ventricular (LV) relaxation and filling pressure than tissue Doppler-derived parameters. However, it has not been elucidated which parameter - strain or strain rate - and which direction of myocardial deformation - longitudinal or circumferential - is the most useful marker of LV relaxation and filling pressure. METHODS AND RESULTS: We conducted a prospective multicenter study and compared the correlation of tissue Doppler- and STE-derived parameters with the time constant of LV pressure decay (τ) and LV mean diastolic pressure (MDP) in 77 patients. The correlation of early-diastolic mitral annular velocity (e´) with τ was weak (r=-0.32, P<0.01), and that of peak longitudinal strain (LS) was the strongest (r=-0.45, P<0.001) among the STE-derived parameters. There was a modest correlation between LVMDP and the ratio of early-diastolic inflow velocity (E) to e´ (E/e´) (r=0.50, P<0.001). In contrast, the ratio of E to LS (E/LS) correlated strongly with LVMDP (r=0.70, P<0.001). The correlation of E/LS with LVMDP was significantly better than that for E/e´ (P<0.01). Receiver-operating characteristic analysis showed that E/LS had the largest area under the curve for distinguishing elevated LVMDP (E/LS 0.86, E/e´ 0.74, E/A 0.67). CONCLUSIONS: STE-derived longitudinal parameters correlated well with LV relaxation and filling pressure. In particular, E/LS could be more accurate than E/e´ for estimating LV filling pressure. (Circ J 2016; 80: 1163-1170).

Patients with left ventricular ejection fraction greater than 58 % have fewer incidences of future acute decompensated heart failure admission and all-cause mortality.

Based on our previous observation, inertia stress (IS) of late systolic aortic flow was often observed in left ventricles with relatively higher left ventricular (LV) ejection fraction (EF). Most left ventricles with relatively lower LVEF did not have IS. Accordingly, lack of IS may correlate with LV diastolic dysfunction through the loss of LV elastic recoil and may contribute to the pathogenesis of heart failure (HF) and reduced survival. We enrolled 144 consecutive patients that underwent cardiac catheterization for the diagnosis of coronary artery disease. Left ventricular ejection fraction (LVEF) was obtained from left ventriculography. The IS was calculated from the LV pressure (P)-dP/dt relation. The study endpoint of this retrospective outcome-observational study was combined subsequent acute decompensated heart failure (ADHF) and all-cause mortality. During the follow-up period (median 6.1 years), seven unscheduled hospitalizations for ADHF and nine all-cause deaths were observed. The event-free survival rate was significantly higher among patients with IS than among patients without IS (log-rank, p = 0.001). On a multivariate Cox regression analysis, lack of IS was a prime predictor of the endpoint during follow-up (hazard ratio: 6.98; 95 % confidence interval: 1.48-33.03; p = 0.01). An LVEF ≥ 58 % was a surrogate indicator for the presence of IS, and patients with LVEF ≥ 58 % had fewer incidences of the endpoint than patients with LVEF < 58 %. In conclusion, lack of IS or LVEF < 58 % should be a predictor of future ADHF and all-cause mortality.

Vascular Physiology according to Clinical Scenario in Patients with Acute Heart Failure: Evaluation using the Cardio-Ankle Vascular Index.

Increased aortic stiffness may be an important cause of acute heart failure (AHF). Clinical scenario (CS), which classifies the pathophysiology of AHF based on the initial systolic blood pressure (sBP), was proposed to provide the most appropriate therapy for AHF patients. In CS, elevated aortic stiffness, vascular failure, has been considered as a feature of patients categorized as CS1 (sBP > 140 mmHg at initial presentation). However, whether elevated aortic stiffness, vascular failure, is present in such patients has not been fully elucidated. Therefore, we assessed aortic stiffness in AHF patients using the cardio-ankle vascular index (CAVI), which is considered to be independent of instantaneous blood pressure. Sixty-four consecutive AHF patients (mean age, 70.6 ± 12.8 years; 39 men) were classified with CS, based on their initial sBP: CS1: sBP > 140 mmHg (n = 29); CS2: sBP 100-140 mmHg (n = 22); and CS3: sBP < 100 mmHg (n = 13). There were significant group differences in CAVI (CS1 vs. CS2 vs. CS3: 9.7 ± 1.4 vs. 8.4 ± 1.7 vs. 8.3 ± 1.7, p = 0.006, analysis of variance). CAVI was significantly higher in CS1 than in CS2 (p = 0.02) and CS3 (p = 0.04). CAVI did not significantly correlate with sBP at the time of measurement of CAVI (r = 0.24 and p = 0.06). Aortic stiffness assessed using blood pressure-independent methodology apparently increased in CS1 AHF patients. We conclude that vascular failure is a feature of CS1 AHF initiation.

Relationship between effective arterial elastance, total vascular resistance, and augmentation index at the ascending aorta and left ventricular diastolic function in older women.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is frequently observed in older women. Increased arterial stiffness in this population may be a cause of HFpEF. METHODS AND RESULTS: In 75 patients who underwent cardiac catheterization and who had no significant coronary artery stenosis or left ventricular (LV) wall motion abnormalities, the LV relaxation time constant (Tp) was calculated. The LVEF was obtained from left ventriculography, and plasma brain natriuretic peptide (BNP) level was measured. From the pressure waveforms at the ascending aorta, the augmentation index (AIx) was calculated. Effective arterial elastance (Ea) and total vascular resistance (TVR) were also determined. No significant differences were found between genders for age, heart rate, central blood pressure, or LVEF. Ea, TVR, AIx, and BNP level were significantly greater in women than in men, but only AIx was significantly correlated with Tp (r=0.25, P=0.04) and BNP level (r=0.33, P=0.005). CONCLUSIONS: The arterial system is stiffer in women than in men of the same age. Among the parameters of arterial stiffness, only AIx is related to abnormal LV relaxation and increased BNP level. Elevated AIx is a factor that causes LV diastolic dysfunction and may be associated with the development of HFpEF in this gender.

Clinical significance of abnormal relaxation pattern of the transmitral flow velocity waveform in older patients with preserved left ventricular ejection fraction.

BACKGROUND: The pathophysiology of abnormal relaxation pattern in the transmitral flow (TMF) velocity waveform has not been fully elucidated. METHODS AND RESULTS: A total of 173 patients who underwent comprehensive Doppler echocardiography and diagnostic cardiac catheterization for coronary artery disease were enrolled in the study. Peak early and late diastolic TMF velocities (E and A, respectively) were measured. Minimum left ventricular (LV) pressure; LV pre-A wave pressure (surrogate of mean left atrial [LA] pressure); time constant (τ) of LV pressure decay; and LV ejection fraction (LVEF) were calculated. Patients with E/A ratio <1.0 and LVEF ≥ 50% were enrolled. Patients with τ ≥ 48 ms and those with τ <48 ms were compared. The 2 groups had no significant differences in E or E/A. Minimum LV pressure (6.9 ± 2.2 mmHg vs. 3.6 ± 2.9 mmHg, P<0.0001) and LV pre-A wave pressure (9.5 ± 2.4 mmHg vs. 6.1 ± 3.0 mmHg, P<0.0001) were significantly higher in patients with τ ≥ 48 ms compared to those with τ <48 ms, but the difference between the LV pre-A and minimum LV pressures was similar between the groups (2.6 ± 1.4 mmHg vs. 2.5 ± 1.5 mmHg, P=0.89). CONCLUSIONS: Proportional elevations in minimum LV and pre-A pressures, due to deteriorated LV relaxation, resulted in no changes in the pressure gradient between the LA and LV in early diastole, E, or E/A.

Plasma N-terminal pro-brain natriuretic peptide levels identifying left ventricular diastolic dysfunction in patients with preserved ejection fraction.

BACKGROUND: Diagnosis of left ventricular (LV) diastolic dysfunction by blood testing is expedient in the clinical setting. METHODS AND RESULTS: In 98 patients with LV ejection fraction ≥50% who underwent cardiac catheterization for evaluation of coronary artery disease, LV pressure (LVP) was measured using a catheter-tipped micromanometer. A time constant, τ, of LV relaxation was computed from LVP decay; the inertia force (IF) of late systolic aortic flow, a surrogate index of LV elastic recoil, was also computed from the LVP-dP/dt relation (phase loop). Patients were classified into 2 groups: those with impaired LV relaxation (τ ≥48 ms) and those with preserved LV relaxation (τ <48 ms). Patients were also classified into another 2 groups: those with IF (≥0.5 mmHg) and those without (<0.5 mmHg). Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥56.5 pg/ml had a sensitivity of 100%, specificity of 52.5%, and negative predictive value of 100% for identifying impaired LV relaxation. NT-proBNP ≥244.5 pg/ml had a sensitivity of 62.5% and specificity of 93.9% for detecting lack of IF. CONCLUSIONS: NT-proBNP level <56.5 pg/ml could be used as a value to sensitively identify patients with preserved LV systolic and diastolic function among those with coronary artery disease. NT-proBNP level ≥244.5 pg/ml is able to specifically detect a lack of IF and has potential for specifically diagnosing LV isolated diastolic dysfunction.

Early detection and progression of sepsis-related myocardial calcification with subsequent left ventricular systolic dysfunction: a case report.

Sepsis-related myocardial calcification (SRMC) is a life-threatening complication. However, it is a rare entity and its clinical course is not well-understood. A 54-year-old man after bone graft surgery presented with septic shock due to surgical site infection. The initial computed tomography (CT) showed no deposit of calcium in the left ventricle (LV), and echocardiography demonstrated preserved left ventricular ejection fraction (LVEF) of 61%. On the 10th day of admission, CT detected new-onset LV myocardial calcification with preserved LVEF of 60% in echocardiography. On the 63rd day, follow-up CT revealed an increased density of the calcified lesion in the LV, and echocardiography showed a significantly reduced LVEF of 30%. This case report clarified a clinical course of SRMC that the calcium deposit began early after the onset of sepsis and LV systolic function declined subsequently along with the progression of the LV calcification. A serial assessment of CT and echocardiography from the initial stage in sepsis could be helpful for early detection and appropriate management of SRMC patients. Learning objective:Sepsis-related myocardial calcification (SRMC) is under-diagnosed in daily clinical practice because most cases progress silently. By serially assessing computed tomography and echocardiography in patients with sepsis from the initial stage, we can detect SRMC early and follow a change in the calcium in the left ventricle (LV) and LV function.>.

Clinical impact of the pathological quantification of myocardial fibrosis and infiltrating T lymphocytes using an endomyocardial biopsy in patients with hypertrophic cardiomyopathy.

BACKGROUND: The impact of quantitative pathological findings derived from endomyocardial biopsies (EMB) on clinical prognosis in patients with hypertrophic cardiomyopathy (HCM) remains unclear. METHODS: We retrospectively studied 55 consecutive HCM patients who underwent EMB. We quantified the collagen area fraction (CAF), the cardiomyocyte diameter, the nuclear area and circularity, and the number of myocardial infiltrating CD3+ cells using EMB samples by image analyzing software. The primary clinical endpoint was defined as a composite including cardiovascular death, admission due to heart failure and ventricular arrhythmia. RESULTS: During the median follow-up of 37.2 months, the primary endpoint was found in 12 patients. No significant difference in the risk score of 5-year sudden cardiac death was observed between the event-occurrence group and the event-free group. In the multivariable Cox proportional-hazard analysis, CAF [hazard ratio (HR) per 10% increase: 1.555, 95% CI: 1.014-2.367, p = 0.044] and the number of infiltrating CD3+ cells (HR per 10% increase: 1.231, 95% CI: 1.011-1.453, p = 0.041) were the independent predictors of the primary endpoint, while the myocardial diameter and the nuclear irregularity had no significant prognostic impact. Kaplan-Meier survival curves demonstrated that patients with both higher CAF and higher number of CD3+ cells had the worst prognosis (log-rank, P < 0.001). CONCLUSIONS: The higher CAF and the higher number of infiltrating CD3+ cells quantified using EMB samples were the independent predictors of poor clinical outcomes in patients with HCM. Cardiomyocyte diameter and nuclear irregularity did not significantly impact the clinical prognosis.