Predictive value of early-phase heart rate reduction for subsequent recovery of left ventricular systolic function in heart failure with reduced ejection fraction.

INTRODUCTION: Predictors of heart failure with recovered ejection fraction (HFrecEF) remain to be fully elucidated. This study investigated the impact of heart rate and its change on the recovery of left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF). MATERIAL AND METHODS: From 398 outpatients who had a history of hospitalisation for heart failure, 138 subjects diagnosed as HFrEF (LVEF < 40%) on heart failure hospitalisation were enrolled and longitudinally surveyed. During follow-up periods more than one year, 64 and 46 patients were identified as HFrecEF (improved LVEF to ≥ 40% and its increase of ≥ 10 points) and persistent HFrEF, respectively. RESULTS: In the overall subjects, the reduction of heart rate through the observation periods was closely correlated with the improvement of LVEF (r = -0.508, p < 0.001). Heart rate on hospital admission for heart failure was markedly higher in patients with HFrecEF (112 ± 26 bpm) than in those with persistent HFrEF (90±18 bpm). Whereas heart rate at the first outpatient visit after discharge was already lower in the HFrecEF group (80 ± 13 vs. 85 ± 13 bpm in the persistent HFrEF group). A multivariate logistic regression analysis revealed that the decrease in heart rate from admission to the first visit after discharge was a significant determinant of HFrecEF (p < 0.001), independently of confounding factors such as ischemic heart disease and baseline LVEF and left ventricular dimension. CONCLUSIONS: Our findings suggest that heart rate reduction in the early phase after heart failure onset is a powerful independent predictor of the subsequent recovery of LVEF in HFrEF patients.

Evaluation of novel indices of walking performance taking oxygen desaturation into account during six-minute walk test in cardiovascular disease patients.

In pulmonary disease patients since oxygen desaturation during 6-min walk test (6MWT) affects walk distance (6MWD), some novel indices such as desaturation/distance ratio [DDR, oxygen desaturation area (DAO2)/6MWD] and distance-saturation product [DSP, 6MWD × minimum peripheral oxygen saturation (SpO2)] are evaluated. However, there has been no study examining these indices that consider exercise-induced desaturation (EID) in patients with cardiovascular disease. In 94 cardiovascular disease patients without pulmonary complications, 6MWT and echocardiography were performed at the entry of cardiac rehabilitation. SpO2 was measured during 6MWT using a continuously monitorable pulse oximeter, and DSP and DDR were calculated using minimum SpO2 and DAO2 [sum of (100-SpO2) per second during 6MWT], respectively. EID was defined as SpO2 decrease of ≥ 4% or minimum SpO2 of < 90% during 6MWT. DSP was slightly lower and DDR was markedly higher in patients with EID than in those without. When examining correlations of DSP and DDR with their components, DSP was correlated with 6MWD much closely than minimum SpO2, while DDR was correlated as closely with DAO2 as 6MWD. Furthermore, DAO2, but not minimum SpO2, had a direct correlation with 6MWD. As for associations with cardiac function, DSP was correlated with several cardiac parameters, but DDR was not correlated with any of these parameters. Our findings suggest that oxygen desaturation during 6MWT affects walking distance in cardiovascular disease patients even without pulmonary complications and that DDR is more appropriate than DSP as an index of walking performance that takes EID into consideration, independently of cardiac function.

Impact of diabetes mellitus and triglyceride glucose index on mortality and cardiovascular outcomes in patients with chronic coronary syndrome undergoing coronary computed tomography angiography.

Background: There is limited knowledge regarding whether an elevated triglyceride glucose (TyG) index can serve as a prognostic marker for mortality and cardiovascular outcomes, independent of diabetes mellitus (DM) and plaque burden, in patients with chronic coronary syndrome (CCS). Methods: Patients with CCS (n = 684) were categorized into subgroups based on the presence of DM, and patients without DM were further divided into two groups based on presence or absence of an elevation of TyG index >8.8. Coronary plaque burden was evaluated using coronary computed tomography angiography. Major cardiovascular adverse event (MACE) was defined as a composite event of nonfatal myocardial infarction, unstable angina or unplanned coronary revascularization, stroke, non-cardiovascular mortality and cardiovascular mortality. Results: Patients without DM exhibited significantly greater plaque and epicardial adipose tissue volumes than those with DM. Multivariable Cox proportional hazards models demonstrated that DM and an elevated TyG index >8.8 were independently associated with the risk of MACE after adjusting for age, sex, and plaque volume. Patients with DM (hazard ratio, 3.74; 95% confidence interval, 1.97-7.08; p < 0.001) and patients without DM with an elevated TyG index (hazard ratio, 1.99; 95% confidence interval, 1.01-3.91; p = 0.045) had an increased risk of MACE. Conclusion: This study indicates that DM and an elevated TyG index are predictors of MACE, independent of plaque volume, in patients with CCS.

Thoracic Aortic Plaque Burden and Prediction of Cardiovascular Events in Patients Undergoing 320-row Multidetector CT Coronary Angiography.

AIM: Wide volume scan (WVS) coronary computed tomography angiography (CCTA) enables aortic arch visualization. This study assessed whether the thoracic aortic plaque burden (TAPB) score can predict major cardiovascular adverse events (MACE) in addition to and independently of other obstructive coronary artery disease (CAD) attributes. METHODS: This study included patients with suspected CAD who underwent CCTA (n=455). CCTA-WVS was used to assess CAD and the prognostic capacity of TAPB scores. Data analysis included the coronary artery calcification score (CACS), CAD status and extent, and TAPB score, calculated as the sum of plaque thickness and plaque angle at five thoracic aortic segments. The primary endpoint was MACE defined as a composite event comprised of ischemic stroke, acute coronary syndrome, and cardiovascular death. RESULTS: During a mean follow-up period of 2.8±0.9 years, 40 of 455 (8.8%) patients experienced MACE. In the Cox proportional hazards model adjusted for clinical risks (Suita cardiovascular disease risk score), we identified TAPB score (T3) as a predictor of MACE independent of CACS ＞400 (hazards ratio [HR], 2.91; 95% confidence interval [CI], 1.26-6.72; p=0.012) or obstructive CAD (HR, 2.83; 95% CI, 1.30-6.18; p=0.009). The area under the curve for predicting MACE improved from 0.75 to 0.795 (p value=0.008) when TAPB score was added to CACS ＞400 and obstructive CAD. CONCLUSIONS: We found that comprehensive non-invasive evaluation of TAPB and CAD has prognostic value in MACE risk stratification for suspected CAD patients undergoing CCTA.

The E/e' ratio on echocardiography as an independent predictor of the improvement of left ventricular contraction in patients with heart failure with reduced ejection fraction.

OBJECTIVE: Clinical feature of heart failure with improved ejection fraction (HFimpEF) remains to be fully elucidated. The present study investigated the association of clinical and echocardiographic parameters with the subsequent improvement of left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF). METHODS: From outpatients with a history of hospitalized for heart failure, 128 subjects diagnosed as HFrEF (LVEF <40%) on heart failure hospitalization were enrolled and longitudinally surveyed. During follow-up periods more than 1 year, 58 and 42 patients were identified as HFimpEF (improved LVEF to ≥40% and its increase of ≥10 points) and persistent HFrEF, respectively. RESULTS: There was no difference in age or sex between the two groups with HFimpEF and persistent HFrEF. The rate of ischemic heart disease was lower and that of tachyarrhythmia was higher in the HFimpEF group than in the persistent HFrEF group. At baseline (i.e., on heart failure hospitalization), LVEF did not differ between the two groups, but left ventricular systolic and diastolic diameters were already smaller and the ratio of early diastolic transmitral velocity to early diastolic tissue velocity (E/e') was lower in the HFimpEF group. A multiple logistic regression analysis revealed that lower baseline E/e' was a significant determinant of HFimpEF, independently of confounding factors such as ischemic heart disease, tachyarrhythmia, and baseline left ventricular dimension. CONCLUSION: Our findings indicate that the lower ratio of E/e' in the acute phase of heart failure onset is an independent predictor of the subsequent improvement of LVEF in HFrEF patients.

Extent of coronary atherosclerosis is associated with deterioration of left ventricular global longitudinal strain in patients with preserved ejection fraction undergoing coronary computed tomography angiography.

Background: This study aimed to investigate the association between the extent and severity of coronary atherosclerosis, epicardial adipose tissue (EAT) accumulation, and left ventricular (LV) global longitudinal strain (GLS) in patients with preserved LV ejection fraction (LVEF) and without LV regional wall motion abnormalities. Methods: This study included 169 preserved LVEF patients without LV wall motion abnormalities who underwent coronary computed tomography (CT) angiography for the assessment of suspected coronary artery disease (CAD). The segment stenosis score (SSS) and segment involvement score (SIS) were calculated to evaluate CAD extent. The EAT volume was defined as CT attenuation values ranging from -250 to -30 HU within the pericardial sac. LVGLS was measured using echocardiography to assess subclinical LV dysfunction. Results: All patients had preserved LVEF of ≥50%, and the mean LVGLS was -18.7% (-20.5% to -16.9%). Mean SSS and SIS were 2.0 (0-5) and 4.0 (0-36), respectively, while mean EAT volume was 116.1 mL (22.9-282.5 mL). Multivariate analysis using linear regression model demonstrated that LVEF (ß, -17.0; 95% CI, -20.9 - -13.1), LV mass index (ß, 0.03; 95% CI, 0.01-0.06), and EAT volume (ß, 0.010; 95% CI, 0.0020-0.0195) were independently associated with LVGLS; however, obstructive CAD was not. The multivariate models demonstrated that SSS (Î, 0.12; 95% CI, 0.05-0.18) and SIS (Î, 0.27; 95% CI, 0.10-0.44) were correlated with deterioration of LVGLS, independent of other parameters. Conclusion: This study demonstrates that EAT volume and CAD extent are associated with the deterioration of LVGLS in this population.

Renoprotective effect of chronic treatment with sodium-glucose cotransporter 2 inhibitors and its associated factors in Japanese patients with chronic heart failure and diabetes.

Background: Recent clinical trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on renal function in heart failure patients. This study confirmed the renoprotective effect of treatment with SGLT2 inhibitors in Japanese patients with chronic heart failure and diabetes and further investigated what cardiac/hemodynamic and noncardiac factors are involved in its effect. Methods: Eligible 50 outpatients with chronic heart failure and type-2 diabetes mellitus chronically taking SGLT2 inhibitors were enrolled. Annual changing rates of estimated glomerular filtration rate (eGFR) were compered before and after treatment with SGLT2 inhibitors and the associations of the change in eGFR slope after SGLT2 inhibitor administration with changes in various clinical and echocardiographic parameters were evaluated. Results: The mean follow-up periods before and after SGLT2 inhibitor administration were 2.6 and 1.9 years, respectively. Changing rates of eGFR per year were significantly improved after treatment with SGLT2 inhibitors (-5.78 ± 7.67 to -0.43 ± 10.81 mL/min/1.73 m2/year, p = 0.006). The daily doses of loop diuretics were not altered after SGLT2 inhibitor administration. Neither decreased body weight nor increased hematocrit was associated with the change in eGFR slope before and after SGLT2 inhibitor administration. While, the decrease in inferior vena cava diameter and the increase in its respiratory collapsibility were significantly correlated with the improvement of eGFR decline slope after SGLT2 inhibitor administration. Conclusions: Our findings indicated that chronic treatment with SGLT2 inhibitors ameliorated annual decline in eGFR in Japanese patients with chronic heart failure, suggesting the possibility that the improvement of venous congestion was involved in its renoprotective effect.

Aortic arch plaque morphology in patients with coronary artery disease undergoing coronary computed tomography angiography with wide-volume scan.

BACKGROUND: Wide-volume scanning with 320-row multidetector computed tomography coronary angiography (CTCA-WVS) enables the assessment of the aortic arch plaque (AAP) morphology and coronary arteries without requiring additional contrast volume. This study aimed to investigate the prevalence of AAPs and their association with coronary artery disease (CAD) and major adverse cardiovascular events (MACEs) in patients who underwent CTCA-WVS. METHODS: This study included 204 patients without known CAD (mean age, 65 years; 53% men) who underwent CTCA-WVS. We evaluated the presence of aortic plaques in the ascending aorta, aortic arch, and thoracic descending aorta using CTCA-WVS. Large aortic plaques were defined as plaques of at least 4 mm in thickness. A complex aortic plaque was defined as a plaque with ulceration or protrusion. MACEs were defined as composite events of cardiovascular (CV) death, nonfatal myocardial infarction, and ischemic stroke. RESULTS: AAPs and large/complex AAPs were identified in 51% ( n = 105) and 18% ( n = 36) of the study patients, respectively. The prevalence of AAPs with large/complex morphology increased with CAD severity (2.1% in no CAD, 12% in nonobstructive CAD, and 39% in obstructive CAD). The univariate Cox hazard model demonstrated that the predictors associated with MACEs were diabetes, obstructive CAD, and large/complex AAPs. Independent factors associated with large/complex AAPs were male sex [odds ratio (OR), 2.90; P = 0.025], stroke history (OR, 3.48; P = 0.026), obstructive CAD (OR, 3.35; P = 0.011), and thoracic aortic calcification (OR, 1.77; P = 0.005). CONCLUSION: CTCA-WVS provides a comprehensive assessment of coronary atherosclerosis and thoracic aortic plaques in patients with CAD, which may improve the stratification of patients at risk for CV events.

Determinants of Non-calcified Low-Attenuation Coronary Plaque Burden in Patients Without Known Coronary Artery Disease: A Coronary CT Angiography Study.

Background: Although epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD), it is unclear whether EAT volume (EAV) can be used to diagnose high-risk coronary plaque burden associated with coronary events. This study aimed to investigate (1) the prognostic impact of low-attenuation non-calcified coronary plaque (LAP) burden on patient level analysis, and (2) the association of EAV with LAP volume in patients without known CAD undergoing coronary computed tomography angiography (CCTA). Materials and Methods: This retrospective study consisted of 376 patients (male, 57%; mean age, 65.2 ± 13 years) without known CAD undergoing CCTA. Percent LAP volume (%LAP, <30 HU) was calculated as the LAP volume divided by the vessel volume. EAT was defined as adipose tissue with a CT attenuation value ranging from -250 to -30 HU within the pericardial sac. The primary endpoint was a composite event of death, non-fatal myocardial infarction, and unstable angina and worsening symptoms requiring unplanned coronary revascularization >3 months after CCTA. The determinants of %LAP (Q4) were analyzed using a multivariable logistic regression model. Results: During the follow-up period (mean, 2.2 ± 0.9 years), the primary endpoint was observed in 17 patients (4.5%). The independent predictors of the primary endpoint were %LAP (Q4) (hazard ratio [HR], 3.05; 95% confidence interval [CI], 1.09-8.54; p = 0.033] in the Cox proportional hazard model adjusted by CAD-RADS category. Cox proportional hazard ratio analysis demonstrated that %LAP (Q4) was a predictor of the primary endpoint, independnet of CAD severity, Suita score, EAV, or CACS. The independent determinants of %LAP (Q4) were CACS ≥218.3 (p < 0.0001) and EAV ≥125.3 ml (p < 0.0001). The addition of EAV to CACS significantly improved the area under the curve (AUC) to identify %LAP (Q4) than CACS alone (AUC, EAV + CACS vs. CACS alone: 0.728 vs. 0.637; p = 0.013). Conclusions: CCTA-based assessment of EAV, CACS, and LAP could help improve personalized cardiac risk management by administering patient-suited therapy.

Achilles tendon thickness is associated with coronary lesion severity in acute coronary syndrome patients without familial hypercholesterolemia.

BACKGROUND: Thickening of Achilles tendon (≥9 mm on radiography) is one of the diagnostic criteria for familial hypercholesterolemia (FH). Since FH is associated with premature coronary artery disease (CAD) including acute coronary syndrome (ACS), measurement of Achilles tendon thickness (ATT) is important for early diagnosis of FH. However, clinical significance of mild thickening of Achilles tendon in non-FH patients with CAD is unclear. The present study investigated the association of ATT with coronary lesion severity in early-onset ACS without clinically diagnosed FH. METHODS: From outpatients who had a history of ACS under 60 years old, 76 clinically non-FH subjects (71 men and 5 women; mean age at the onset of ACS, 50.5 years) with maximum ATT of <9 mm were enrolled in this study. The severity of coronary lesions was assessed by SYNTAX score derived from coronary angiography at the onset of ACS. RESULTS: ATT levels were not significantly different among patients with ST-elevation myocardial infarction (STEMI, n=47), non-STEMI (n=12), and unstable angina (n=17). Whereas, both average and maximum ATT were significantly larger in patients with multivessel lesions (n=25) than in those with single-vessel disease (n=51). Furthermore, SYNTAX score was positively correlated with average ATT (r=0.368, p=0.0011) and maximum ATT (r=0.388, p=0.0005). As for the relation to clinical parameters, maximum ATT had positive correlations with body mass index and C-reactive protein. A multiple regression analysis revealed that average and maximum ATT were significantly associated with SYNTAX score, independently of various confounding factors. CONCLUSIONS: Our findings demonstrated that ATT, even though its level was <9 mm, was associated with coronary lesion severity in clinically non-FH patients with early-onset ACS. Apart from diagnosing FH, ATT may be a predictor of the progression of CAD.

Long-term administration of tolvaptan ameliorates annual decline in estimated glomerular filtration rate in outpatients with chronic heart failure.

Protective effects of tolvaptan against worsening renal function in acute heart failure have been shown. However, long-term effects of its agent on renal function remain to be elucidated. The present study investigated retrospectively whether long-term treatment with tolvaptan exerts renoprotective effects in patients with chronic heart failure, by comparing serial changes in estimated glomerular filtration rate (eGFR) for years before and after tolvaptan administration. From 63 outpatients with chronic heart failure taking diuretics including tolvaptan, 34 patients whose eGFR levels were continuously measured for more than 6 months both before and after administration of tolvaptan (average dose, 7.8 mg/day at the end of the follow-up period) were selected as eligible for the present analyses. All eGFR values were separately plotted before and after the initiation of treatment with tolvaptan (except hospitalization periods) along the time course axis and the slope of the linear regression curve was calculated as an annual change in eGFR. The mean follow-up periods before and after tolvaptan administration were 1197 and 784 days (3.3 and 2.1 years), respectively. Changing rates of eGFR per year were significantly ameliorated after treatment with tolvaptan (mean ± SD, - 8.02 ± 9.35 to - 1.62 ± 5.09 mL/min/1.73m2 /year, P = 0.001). In echocardiographic parameters, inferior vena cava (IVC) diameter significantly decreased after tolvaptan administration, and the decrease in IVC diameter was correlated with the improvement of eGFR decline slope after administration of tolvaptan (P = 0.0075). This longitudinal observational study indicated that long-term treatment with tolvaptan ameliorated annual decline in eGFR in outpatients with chronic heart failure. Our findings suggest that tolvaptan has a protective effect against chronically worsening renal function in heart failure patients.

Usefulness of pre- and post-stent optical frequency domain imaging findings in the prediction of periprocedural cardiac troponin elevation in patients with coronary artery disease.

Cholesterol crystals (CCs) are frequently found in high-risk plaques, such as thin-capped fibroatheromas. The purpose of this study was to investigate the associations of CCs, plaque morphologies, and post-stent optical frequency domain imaging (OFDI) findings with periprocedural cardiac troponin (cTn) elevation in patients treated with percutaneous coronary intervention (PCI). This study consists of 119 patients with stable coronary artery disease (CAD) with normal cTn levels who underwent OFDI-guided PCI. Periprocedural cTn elevation was defined as an elevation of cTn ≥ × 5 times the upper reference limit after PCI. Pre- and post-stent OFDI findings, including fibrous cap thickness (FCT), presence of CCs, and parameters for lipid and calcification were analyzed. A total of 37 (31%) patients were classified into the periprocedural cTn elevation group. Compared with lesions without CCs, lesions exhibiting CCs had thinner FCT, larger lipid arc, and longer lipid length, and were more likely to have irregular protrusion and in-stent thrombus (all p < 0.05). For pre-stent OFDI features, FCT < 82 µm [odds ratio (OR) 4.11; p = 0.003] and CCs (OR 3.23; p = 0.017) were associated with periprocedural cTn elevation. For post-stent OFDI features, in-stent dissection (OR 3.08; p = 0.035) and in-stent thrombus (OR 7.98; p = 0.002) were independent predictors of cTn elevation. The combination of CCs and FCT < 82 µm showed increased risk of periprocedural cTn elevation (OR 7.22; p = 0.002). OFDI-guided PCI provides unique insight into the mechanism for periprocedural cTn elevation in CAD patients.

Ankle-brachial index, arterial stiffness, and biomarkers in the prediction of mortality and outcomes in patients with end-stage kidney disease.

BACKGROUND: Although ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are significant predictors of major adverse cardiovascular event (MACE), their prognostic value in association with biomarkers has not been fully evaluated in patients with end-stage kidney disease (ESKD). HYPOTHESIS: We hypothesized that ABI/baPWV would provide better prognostic value independent of biomarkers in ESKD patients. METHODS: This study included 104 ESKD patients treated with maintenance hemodialysis who underwent ABI and baPWV examinations and laboratory tests, including brain-natriuretic peptide, high-sensitive cardiac troponin T (hs-cTnT), and high-sensitive C-reactive protein (hs-CRP). MACE was defined as a composite event of all-cause death, acute coronary syndrome, and stroke. RESULTS: During a mean follow-up of 3.6 ± 1.7 years, a total of 51 MACE were observed. The independent factors associated with MACE were age >75 years (adjusted hazard ratio [HR], 2.15; P < .05), abnormal ABI (adjusted HR, 2.01; P < .05), left ventricular ejection fraction (LVEF) <50% (adjusted HR, 3.33; P < .001), the upper tertile of hs-cTnT (adjusted HR, 2.77; P < .05), and hs-CRP (HR, 1.96; P < .05). However, baPWV did not remain as an independent predictor of MACE in the entire cohort and also in patients without abnormal ABI. The combination of predictors improves the predictive value of MACE, providing increased HR with 4.00 for abnormal ABI + hs-CRP, 4.42 for abnormal ABI + hs-cTnT, and 7.04 for abnormal ABI + LVEF <50% (all P < .001). CONCLUSION: Abnormal ABI is a robust predictor of MACE independent of biomarkers and their combination provides better risk stratification compared with a single predictor in ESKD patients.

Prognostic significance of renal dysfunction and its change pattern on outcomes in patients with acute coronary syndrome treated with emergent percutaneous coronary intervention.

Renal dysfunction and its change pattern are associated with short- and long-term mortality. However, it remains to be investigated whether or not worsening renal function (WRF) defined by baseline renal function identified from different time points would provide prognostic implication on outcomes in acute coronary syndrome (ACS) patients. This study consists of 334 ACS patients (mean age 68 ± 11 years, 75% male) treated with emergent percutaneous coronary intervention (PCI). Estimated glomerular filtration rate (eGFR) was evaluated on baseline, during hospitalization, at discharge, and at 3-month follow-up. WRF was defined as a relative decrease of eGFR > 20% at 3 months using baseline eGFR identified from different time points. The primary end point was a composite event of major cardiovascular events (MACE), including all-cause death, ACS, and heart failure hospitalization. The associations of chronic kidney disease (CKD), acute kidney injury (AKI), and WRF with MACE were evaluated. During a mean follow-up of 3.3 ± 1.7 years, a total of 64 MACE were observed. Multivariable analysis revealed that CKD (hazard ratio 2.16; p = 0.018) and AKI (hazard ratio 1.95; p = 0.030) were independent predictors of MACE, but WRF did not remain as an independent predictor of MACE (p = 0.208). The highest risk was observed in AKI patients with CKD when stratified by the presence or absence of CKD and AKI. In ACS patients treated with emergent PCI, this study demonstrated that CKD and AKI were independent predictors of MACE, while there was no independent relationship between WRF and MACE.

Associations of sensitive cardiac troponin-I with left ventricular morphology, function and prognosis in end-stage renal disease patients with preserved ejection fraction.

Sensitive cardiac troponin I (cTnI) predicts all-cause and cardiovascular mortality in various clinical settings. However, its clinical significance in hemodialysis (HD) patients with preserved left ventricular ejection fraction (LVEF) has not been fully elucidated. This study investigated the association of cTnI with LV morphology and function, and its long-term outcome in HD patients with preserved LVEF. This prospective study consists of 96 HD patients with preserved LVEF (69 ± 8 years and 63% male) who underwent two-dimensional echocardiographic examination and biomarker tests including cTnI, brain natriuretic peptide, and high-sensitive C-reactive protein. The primary endpoint was all-cause death and secondary endpoint was cardiovascular death. Factors independently associated with cTnI were systolic blood pressure (ß = - 0.239, p = 0.011), heart rate (ß = 0.216, p = 0.021), LV mass index (ß = 0.231, p = 0.020), and E to e' ratio (ß = 0.237, p = 0.016). During a mean follow-up of 3.6 years, primary and secondary endpoints were observed in 23 (24%) and 18 (19%) patients, respectively. In the multivariate Cox proportional hazard analysis, the upper cTnI tertile has significantly increased risk of all-cause mortality [hazard ratio (HR), 2.69; 95% confidence interval (CI), 1.139-6.386; p = 0.024] and that of cardiovascular death (HR, 4.56; 95% CI 2.021-16.968; p = 0.006) independent of echocardiographic measures and other serum biomarkers. In HD patients with preserved LVEF, serum cTnI levels were significantly associated with diastolic function and risk of mortality independent of echocardiographic variables and other biomarkers.

Adding thiazide to a renin-angiotensin blocker improves left ventricular relaxation and improves heart failure in patients with hypertension.

Hypertension is associated with an increased risk of diastolic dysfunction. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) have failed to show improvement in clinical outcomes for patients with diastolic dysfunction. In this study, we investigated the effect of changing an ACEi or ARB to a combination of losartan and hydrochlorothiazide (HCTZ) on left ventricular (LV) preload and relaxation in patients with hypertension and diastolic dysfunction. We enrolled 371 hypertensive patients with diastolic dysfunction who had not achieved their treatment goals with an ACEi or ARB. We switched the ACEi or ARB to losartan/HCTZ and followed the patients for 24 weeks. The primary end points were changes in septal mitral annular velocity during diastole (e') and in the ratio of mitral inflow velocity to e' velocity (E/e' ratio) from baseline to the end of follow-up. Mean systolic and diastolic blood pressures (BP) decreased by 22 and 11 mm Hg, respectively, after changing from an ACEi or ARB to losartan/HCTZ. The e' velocity increased, and the E/e' ratio and brain natriuretic peptide level decreased significantly. High-sensitivity C-reactive protein also decreased significantly (0.50 vs. 0.29 mg dl(-1), P<0.0001). There were only slight or no changes in glucose levels, homeostasis model assessment insulin resistance (HOMA-R), uric acid and electrolytes after the drug change. Changing from an ACEi or ARB to losartan/HCTZ is associated with a reduction in BP, improvement in LV relaxation, improvement in heart failure state and attenuation of systemic inflammation with few adverse effects in patients with hypertension and diastolic dysfunction.