Calcium evaluation using coronary computed tomography in combination with optical coherence tomography.

Optical coherence tomography (OCT) can assess calcium thickness, a key factor for predicting good stent expansion; however, it underestimates coronary calcium severity due to its penetration limitation. This study aimed to evaluate computed tomography (CT) and OCT images to assess calcification. We investigated 25 left anterior descending arteries of 25 patients, using coronary CT and OCT, and assessed their calcification. Of the 25 vessels, 1811 pairs of CT and OCT cross-sectional images were co-registered. Of the 1811 cross-sectional CT images, calcification was not detectable in 256 (14.1%) of the corresponding OCT images due to limited penetration. In the 1555 OCT calcium-detectable images, the maximum calcium thickness was not detectable in 763 (49.1%) images compared to the CT images. In CT images of slices corresponding to undetected calcium in OCT images, the angle, thickness, and maximum density of calcium were significantly smaller compared to slices corresponding to detected calcium in OCT. Calcium with an undetectable maximum thickness in the corresponding OCT image had a significantly greater calcium angle, thickness, and density than calcium with a detectable maximum thickness. There was an excellent correlation between CT and OCT with respect to calcium angle ( R= 0.82, P < 0.001). The calcium thickness on the OCT image had a stronger correlation with the maximum density on the corresponding CT image (R = 0.73, P < 0.001) than with the calcium thickness on the CT image (R = 0.61, P < 0.001). Cross-sectional CT imaging allows for pre-procedural assessment of calcium morphology and severity and could complement the lack of information on calcium severity in OCT-guided percutaneous coronary intervention.

Anti-Kv1.4 Antibody Without Myasthenia Gravis: A Rare Cause of Autoimmune Myocarditis and Myositis.

Anti-Kv1.4 antibody is often detected in thymoma-associated myasthenia gravis patients with anti-acetylcholine receptor antibody. Herein, we describe 2 patients with concurrent myocarditis and myositis. In both cases, anti-Kv1.4 antibody was positive despite the absence of thymoma and anti-acetylcholine receptor antibody, and immunosuppressants eventually resolved their symptoms and cardiac function. (Level of Difficulty: Advanced.).

Mean density of computed tomography for predicting rotational atherectomy during percutaneous coronary intervention.

BACKGROUND: Multi-slice computed tomography (CT) allows noninvasive evaluation of the severity of coronary calcification. However, there has yet to be a definitive parameter based on the cross-sectional CT image for predicting the need for rotational atherectomy (RA). Therefore, we aimed to investigate the mean density of cross-sectional CT images to predict the need for RA during percutaneous coronary intervention (PCI). METHODS: A total of 154 lesions with moderate to severe calcification detected in coronary angiography were identified in 126 patients who underwent coronary CT prior to PCI for stable angina. PCI with RA was performed for 48 lesions, and the remaining 106 were treated without RA. Multi-slice CT was retrospectively evaluated for its ability to predict the use of RA. We chose the most severely calcified cross-sectional image for each lesion. The mean density within the outer vessel contour, calcium arc quadrant of the cross-sectional CT image, calcium length, calcification remodeling index, and per-lesion coronary artery calcium score was studied. RESULTS: Receiver-operator characteristic curve analysis revealed 637 Hounsfield units (HU) (area under the curve â€‹= â€‹0.98, 95% confidence interval: 0.97-1.00, p â€‹< â€‹0.001) as the best mean density cutoff value for predicting RA. Multivariate logistic regression analysis showed that a mean calcium level >637 HU was a strong independent predictor (odds ratio: 32.8, 95% confidence interval: 7.0-153, p â€‹< â€‹0.001) for using RA. CONCLUSIONS: The mean density of the cross-sectional CT image, a simple quantitative parameter, was the strongest predictor of the need for RA during PCI.

Relationship between coronary artery calcium score and bleeding events after percutaneous coronary intervention in chronic coronary syndrome.

The relationship between coronary artery calcium (CAC) and bleeding events after percutaneous coronary intervention (PCI) in patients with chronic coronary syndrome (CCS) is not well established. This study aimed to examine the association between CAC scores and clinical outcomes after PCI in patients with CCS. This retrospective observational study included 295 consecutive patients who underwent multidetector computer tomography and were scheduled for their first elective PCI. Patients were categorized into two groups based on the CAC scores (low: ≤ 400 or high: > 400). The bleeding risk was evaluated using the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. The primary clinical outcome was a major bleeding event within 1 year after PCI, defined as Bleeding Academic Research Consortium (BARC) 3 or 5. The high CAC score group had a higher proportion of patients meeting the ARC-HBR criteria than the low CAC score group (52.7% vs. 31.3%, p < 0.001). Kaplan-Meier survival analysis showed that the incidence of major bleeding events was higher in the high CAC score group as compared to the low CAC score group (p < 0.001). Furthermore, multivariate Cox regression anal ysis revealed that a high CAC score was an independent determinant of major bleeding events during the first year after PCI. A high CAC score is significantly associated with the incidence of major bleeding events after PCI in CCS patients.

Prediction of intracerebral hemorrhage in patients with out-of-hospital cardiac arrest using post-resuscitation electrocardiogram: An observational cohort study.

Aim: We evaluated the characteristics of patients with intracerebral hemorrhage in nontraumatic out-of-hospital cardiac arrests (OHCA) after return of spontaneous circulation (ROSC) to identify patients who required brain computed tomography as the next diagnostic workup. Methods: We conducted a retrospective cohort study on 1303 consecutive patients with nontraumatic OHCA who were admitted to Miyazaki Prefectural Nobeoka Hospital between 2008 and 2020. Among these, 454 patients achieved sustained ROSC. We excluded 126 patients with obvious extracardiac causes. Clinical and demographic characteristics of patients and post-resuscitation 12-lead electrocardiogram were compared. Patients were categorized into the intracerebral hemorrhage (n = 32, 10%) and no intracerebral hemorrhage group (n = 296). All causes of intracerebral hemorrhage were diagnosed based on brain computed tomography images by board-certified radiologists. Results: We included 328 patients (mean age, 74 years; women, 36%) who achieved ROSC. Logistic regression analyses showed that female sex, younger age (<75 years), no shockable rhythm changes, tachycardia (≥100 bpm), lateral ST-segment elevation, and inferior ST-segment depression on post-resuscitation electrocardiogram were independently associated with intracerebral hemorrhage. We developed a new predictive model for intracerebral hemorrhage by considering 1 point for each of the six factors. The odds ratio for intracerebral hemorrhage increased 2.36 for each 1-point increase (P < 0.001). A score ≥ 4 had 43.7% sensitivity, 90.8% specificity, 34.1% positive predictive value, and 93.7% negative predictive value. Conclusion: Our new predictive model might be useful for risk stratification of intracerebral hemorrhage in patients with OHCA who achieved ROSC.

HFA-PEFF scores: prognostic value in heart failure with preserved left ventricular ejection fraction.

BACKGROUND/AIMS: The Heart Failure Association (HFA)-PEFF score is recognized as a simple method to diagnose heart failure (HF) with preserved ejection fraction (HFpEF). This study aimed to evaluate the relationship between HFA-PEFF scores and cardiovascular outcomes in HFpEF patients. METHODS: A total of 502 consecutive HFpEF patients were prospectively observed for up to 1,500 days. Cardiovascular outcomes were compared between two groups of patients, defined by their HFA-PEFF scores: those who scored 2-4 (the intermediate-score group) and those who scored 5-6 group (the high-score group). Overall, 236 cardiovascular events were observed during the follow-up period (median, 1,159 days). RESULTS: Kaplan-Meier analysis showed that there were significant differences in composite cardiovascular events and HF-related events between the intermediate-score group and the high-score group (p = 0.003 and p < 0.001, respectively). Multivariate Cox proportional hazards analysis showed that the HFA-PEFF scores significantly predicted future HF-related events (hazard ratio, 1.66; 95% confidence interval [CI], 1.11 to 2.50; p = 0.014); receiver operating characteristic analysis confirmed this relationship (area under the curve, 0.633; 95% CI, 0.574 to 0.692; p < 0.001). The cutoff HFA-PEFF score for the identification of HF-related events was 4.5. Decision curve analysis revealed that combining the HFA-PEFF score with conventional prognostic factors improved the prediction of HF-related events. CONCLUSION: HFA-PEFF scores may be useful for predicting HF-related events in HFpEF patients.

Increased soluble programed cell death-ligand 1 is associated with acute coronary syndrome.

BACKGROUND: Programmed cell death (PD)-1 and its ligand (PD-L1) plays crucial roles in T-cell tolerance as immune checkpoint. Previous studies reported that increased serum levels of soluble PD-L1 (sPD-L1) reflect myocardial and vascular inflammation. However, little is known about the clinical relationship between sPD-L1 and acute coronary syndrome (ACS). We investigated the relation of sPD-L1 and ACS. METHODS: We prospectively measured serum levels of sPD-L1 using a commercially available enzyme-linked immunosorbent assay kit in patients with coronary artery disease (CAD) and continuous non-CAD admitted to Kumamoto University Hospital between December 2017 and June 2019. All malignant diseases, patients who underwent hemodialysis, active collagen diseases, and severe infectious diseases were excluded. RESULTS: Totally, 446 CAD patients [ACS, n = 124; chronic coronary syndrome (CCS), n = 322] and 24 non-CAD patients were analyzed. The levels of sPD-L1 were significantly higher in patients with ACS than those both with non-CAD and CCS {ACS, 188.7 (111.0-260.8) pg/mL, p < 0.001 vs. non-CAD [83.5 (70.8-130.4) pg/mL]; and p = 0.009 vs. CCS [144.2 (94.8-215.5) pg/mL], respectively}. Univariate logistic regression analysis identified that sPD-L1 was significantly associated with ACS [odds ratio (OR): 1.459, 95% confidence interval (CI): 1.198-1.778, p < 0.001]. Multivariable logistic regression analysis with nine significant factors identified from the univariate analysis revealed that sPD-L1 was significantly and independently associated with ACS (OR: 1.561, 95% CI: 1.215-2.006, p < 0.001). CONCLUSIONS: This is the first clinical study to demonstrate the increased level of sPD-L1 in patients with CAD, and the significant association with ACS.

Prognostic significance of liver stiffness assessed by fibrosis-4 index in patients with heart failure.

BACKGROUND: Heart failure (HF)-related congestive hepatopathy is a well-recognized problem in management of HF. The fibrosis-4 (FIB4) index calculated by [age × aspartate aminotransferase (IU/L)/platelet count (109 /L) × square root of alanine aminotransferase (IU/L)] is useful for evaluating liver stiffness. We aimed to investigate the impact of the FIB4 index on prognosis in patients with HF. METHODS AND RESULTS: Consecutive HF patients referred for hospitalization at Kumamoto University Hospital, Japan, were registered between 2006 and 2015. We observed cardiovascular outcomes in each type of HF [HF with reduced left ventricular ejection fraction (LVEF) (HFrEF), HF with mid-range LVEF (HFmrEF) and with preserved LVEF (HFpEF)] according to their FIB4 index; Group 1 (FIB4 index <1.3), Group 2 (FIB4 index: 1.3-2.67), and Group 3 (FIB4 index >2.67). This study enrolled 83 HFrEF patients, 117 HFmrEF patients, and 504 HFpEF patients. In HFpEF patients, the Kaplan-Meier curve revealed that Group 3 had a significantly higher rate of total cardiovascular events compared with the other two groups. By contrast, the occurrences of total cardiovascular events were not different among three groups in HFrEF and HFmrEF patients. Multivariate Cox proportional hazard analysis with significant factors in univariate analysis identified that the FIB4 index as an independent and significant predictor for future total cardiovascular events in HFpEF patients (hazard ratio: 1.09, 95% confidence interval: 1.03-1.15, P = 0.001). CONCLUSIONS: The FIB4 index was a significant predictor for total cardiovascular events in HFpEF.

Cardiac computed tomography-derived extracellular volume fraction in late anthracycline-induced cardiotoxicity.

Cardiotoxicity in the late phase after anthracycline drugs administration remains to be defined. Of the 44 patients who received anthracycline treatment, 7 were found to have cancer therapeutics-related cardiac dysfunction (CTRCD). The global longitudinal strain determined by echocardiography and myocardial extracellular volume fraction (ECV) determined by cardiac computed tomography (CCT) of the CTRCD(+) group were significantly higher than those of the control group and CTRCD(-) group, whereas there were no significant differences between the control and CTRCD(-) groups. Our findings indicated that CCT may be a tool comparable to echocardiography, indicating the effective evaluation of CTRCD by CCT.

Impact of Reactive Oxidative Metabolites Among New Categories of Nonischemic Heart Failure.

Background We investigated the clinical significance of derivatives of reactive oxygen metabolites (DROMs), a new marker of reactive oxygen species, in patients with nonischemic heart failure (HF) and compared them among new categories of HF. Methods and Results We recruited 201 consecutively hospitalized patients with HF and measured DROM under stable conditions. Then, we divided them according to new categories of HF (HF with reduced ejection fraction [EF], HF with midrangeEF, and HF with preserved EF) without coronary artery disease. In subgroup analysis, we followed EF changes in patients with HF with reduced EF and classified them into HF with recovered EF or nonrecovered EF according to whether EF had improved to >40%. DROMs are significantly and independently associated with HF-related events in patients with NIHF. There were no significant differences in DROM and the probability of HF-related events among HF categories in Kaplan-Meier analysis. However, patients with HF with reduced EF and HF with preserved EF but not HF with midrange EF with HF-related events had higher DROM than those without HF-related events. In subgroup analysis, Kaplan-Meier analysis demonstrated that the probabilities of HF-related events in HF with recovered EF were dramatically decreased. DROM were significantly higher in patients with HF with nonrecovered EF than in HF with recovered EF. In receiver operating characteristic analysis, the cutoff level of DROM for predicting improvements in HF with recovered EF was 347 Carratelli units. Furthermore, the C-statistic value for predicting EF improvement for the DROM levels was 0.703. In multivariable logistic regression analysis, DROM was independently and significantly associated with the prediction of HF with recovered EF. Conclusions DROM measurements can provide important prognostic information for risk stratification in any category of NIHF. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000035827.

Clinical significance of reactive oxidative metabolites in patients with heart failure with reduced left ventricular ejection fraction.

BACKGROUND: We investigated the clinical significance of the derivative of reactive oxygen metabolites (DROM), a new marker of reactive oxygen species (ROS), in patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) (HFrEF). METHODS AND RESULTS: Serum DROM concentrations were measured in 201 consecutive patients with HFrEF (EF < 50%) in stable condition. DROM values were significantly higher in patients with HFrEF than in risk-matched patients without HF (P < 0.01). They also correlated significantly with high-sensitivity C-reactive protein and B-type natriuretic peptide. Kaplan-Meier analysis demonstrated significantly higher probabilities of HF-related events in the high-DROM group than in the low-DROM group (log-rank test, P < 0.01). Multivariable Cox hazard analysis revealed that DROM were independent and significant predictors of cardiovascular events. In a subgroup analysis, DROM levels were also measured at the aortic root and coronary sinus in 49 patients. The transcardiac gradient of DROM values was significantly higher in patients with HFrEF than in patients without HF (P = 0.04), indicating an association between DROM production in the coronary circulation and HFrEF development. Changes in DROM following optimal therapy were significantly associated with LVEF improvement (r = 0.34, P = 0.04). CONCLUSIONS: The higher levels of DROM and their association with cardiovascular events suggest the clinical benefit of DROM measurements in the risk stratification of patients with HFrEF.

Comparison of electron microscopic findings and clinical presentation in three patients with mitochondrial cardiomyopathy caused by the mitochondrial DNA mutation m.3243A > G.

Mitochondrial cardiomyopathy can be described as a condition characterized by abnormal heart-muscle structure and/or function, secondary to mutations in nuclear or mitochondrial DNA. Its severity can range from subclinical to critical conditions. We presented three cases of mitochondrial cardiomyopathy with m.3243A > G mutation and compared the clinical manifestations with the histological findings for each of these cases. All cases showed cardiac hypertrophy, juvenile-onset diabetes mellitus, and hearing loss. Case 1 (43-year-old male) showed less cardiac involvement and shorter duration of mitochondrial disease-related symptoms than case 2 (67-year-old female) and case 3 (51-year-old male), who showed the most advanced cardiac condition and longest duration from the manifestation of heart failure. The histological findings revealed that cardiomyocytes from case 1 showed no hypertrophy and mitochondrial degeneration in electron microscopy. Alternatively, cases 2 and 3 showed hypertrophy in their cardiomyocytes, and mitochondrial degeneration (e.g. onion-like lesions, swollen cristae, and lamellar bodies) was most apparent in case 3. These results suggested that mitochondrial degeneration, as evaluated by electron microscopy, might be correlated with impaired heart function in patients with mitochondrial cardiomyopathy.

Elevated C-reactive protein is significantly associated with left ventricular dysfunction in patients with aortic regurgitation and concomitant collagen disease.

BACKGROUND: Collagen disease is an important cause of aortic regurgitation (AR). Although aortic valve surgery is recommended for patients with AR and depressed left ventricular (LV) function, there have been few reports about risk factors for LV dysfunction in patients with AR concomitant with collagen disease. METHODS AND RESULTS: We conducted this study at Kumamoto University Hospital in Japan. A total of 41 patients who had moderate to severe AR and concomitant collagen disease between January 2014 and December 2019 were enrolled. With regard to baseline characteristics, there were no significant differences in the type of collagen disease or El Khoury class between patients with preserved LV function and those with reduced LV function. B-type natriuretic peptide (375.2 [257.9-3852.6]pg/ml vs. 64.0 [33.3-133.6]pg/ml, p < 0.01), C-reactive protein (CRP) levels (2.00 [1.24-9.14]mg/dl vs. 0.19 [0.06-0.52]mg/dl, p < 0.01) and neutrophil-to-lymphocyte ratio (7.94 [3.30-9.98] vs. 3.94 [1.83-5.58], p < 0.05) were significantly higher, and hemoglobin level (10.7 ± 1.6 g/dl vs. 12.2 ± 1.8 g/dl, p < 0.05) was significantly lower in patients with reduced LV function than in those with preserved LV function. There were no significant differences in any variables associated with severity and features of AR. Multivariable logistic regression analysis showed that high CRP levels (≥1.0 mg/dl) were independently and significantly associated with LV dysfunction in patients with AR and collagen disease, even after adjusting for the severity of AR (odds ratio: 95.7; 95% confidence interval: 4.6-1990.4, p < 0.01). CONCLUSIONS: Uncontrolled inflammation, represented as high CRP levels, is an important marker for LV dysfunction in patients with AR and collagen disease.

The controlling nutritional status score predicts outcomes of cardiovascular events in patients with heart failure with preserved ejection fraction.

BACKGROUNDS: The relationship between cardiovascular outcomes and the Controlling Nutritional Status (CONUT) score in heart failure (HF) with preserved ejection fraction (HFpEF) patients is unknown. This study aimed to evaluate the relationship between the score and cardiovascular outcomes in HFpEF patients. METHODS AND RESULTS: A total of 506 consecutive HFpEF patients were prospectively observed for up to 1500 days or until the occurrence of cardiovascular events. The mean age was 71.6 ± 9.4 years. Cardiovascular outcomes were compared between the CONUT score 0-1 group with a normal nutritional state (normal group), the CONUT score 2-4 group with a light degree of undernutrition (light group), and the CONUT score 5-8 group with a moderate degree of undernutrition (moderate group). In this study, there were no patients who scored 9-12, which was defined as a severe state of undernutrition. Overall, 238 cardiovascular events were observed during the follow-up period (median: 1159 days). Kaplan-Meier analysis showed that the moderate group was at higher risk of composite cardiovascular events than the normal group (P < 0.001) and the light group (P = 0.031). The analysis also showed that the light group was at higher risk of composite cardiovascular events than the normal group (P = 0.038). Multivariable Cox proportional hazards analysis with the significant factors from the univariate analysis showed that the CONUT score (hazard ratio: 1.12, 95% confidence interval: 1.03-1.21, P = 0.005) significantly predicted future cardiovascular events. CONCLUSION: Nutritional screening using the CONUT score may be useful for predicting cardiovascular events in HFpEF patients.

Clinical significance of diastolic late mitral annular velocity in heart failure with preserved ejection fraction.

OBJECTIVES: Because diastolic late mitral annular velocity (a') obtained by transthoracic-echocardiography (TTE) represents left atrial (LA) function, we investigated the clinical significance of a' in heart failure (HF) with a preserved left ventricular (LV) ejection fraction (HFpEF). METHODS: We enrolled 448 consecutive HFpEF patients (sinus rhythm: 66.3%, atrial fibrillation [AF] rhythm: 33.7%) and performed TTE under stable conditions after optimal therapy. In patients with sinus rhythm, a' values were measured at septal mitral annuli. RESULTS: A' had weak but significant negative correlations with the natural-logarithm-B-type natriuretic peptide (Ln-BNP), LA diameter, LV mass index and tricuspid regurgitation pressure gradient. Receiver operating characteristic (ROC) curve analysis showed that the best cut-off value of a' and systolic mitral annular velocity (s') for the prediction of HF-related events were 7.45 cm/s and 6.5 cm/s with areas under the curve (AUC) of 0.841 and 0.682, respectively. The AUC of ROC analysis for the logistic regression model of a' plus s' was improved to 0.97. In Kaplan-Meier analysis, HFpEF patients with low-a' (<7.45 cm/s) had a significantly higher risk of total cardiovascular and HF-related events (both p < .01 by log-rank test) than those with high-a' (≥ 7.45 cm/s) and were prognostically equivalent to those with AF. Multivariate Cox proportional hazard analysis identified low-a' as an independent predictor of both total cardiovascular (hazard ratio [HR]: 0.823, 95% confidence interval [CI]: 0.714-0.949, p = .007) and HF-related events (HR: 0.551, 95% CI: 0.422-0.720, p < .001). CONCLUSION: A' value measurement is a non-invasive and useful method for risk stratification in HFpEF.

Temporal Change in Longitudinal Strain After Domino Liver Transplantation With Liver Grafts Explanted From Patients With Hereditary Amyloidogenic Transthyretin Amyloidosis.

Background: Using transthoracic echocardiography, including 2D speckle tracking imaging (STI), this study examined cardiac function after domino liver transplantation (DLT) with liver grafts explanted from patients with hereditary amyloidogenic transthyretin amyloidosis. Methods and Results: In all, 14 patients who underwent DLT at Kumamoto University Hospital and for whom 2D STI information was available were enrolled in the study; time-dependent echocardiographic changes were evaluated in 7. Although left ventricular (LV) systolic and diastolic function did not differ between the pre- and post-DLT periods (mean [±SD] 5.4±1.0 years after DLT), there were significant (P<0.05 for all) increases in the post- vs. pre-DLT period in basal longitudinal strain (LS; -13.4±2.3 vs. -19.3±4.4), relative apical LS index (=apical LS/[basal LS+mid LS]; 0.75±0.20 vs. 0.58±0.08), and LV ejection fraction/global LS (3.91±0.58 vs. 3.06±0.44). Age at the time of DLT was significantly higher in the group with impaired (>-14%) than preserved basal LS (57.2±3.5 vs. 39.6±16.0 years; P<0.05). When control subjects (n=14) were added to the enrolled DLT recipients, multivariable logistic regression analysis revealed that a history of DLT was significantly associated with impaired basal LS (>-14%; odds ratio 28.39, 95% confidence interval 1.89-427.45, P<0.05). Conclusions: LV systolic and diastolic function was preserved in the long term after DLT. However, 2D STI revealed subtle cardiac dysfunction in DLT recipients, which may be an early manifestation of cardiac amyloidosis.

Clinical significance of serum magnesium levels in patients with heart failure with preserved ejection fraction.

Although serum magnesium (Mg) levels are closely associated with the prognosis of heart failure (HF) patients, the clinical significance of sMg levels on the cardiovascular outcomes of HF with preserved ejection fraction (HFpEF) patients is not fully understood. This study was a retrospective, single-center, observational study. We enrolled 452 consecutive HFpEF patients admitted to Kumamoto University Hospital. We defined lower sMg as <2.0 mg/dl (=0.8 mmol/L) based on recent clinical evidence and compared their clinical characteristics and prognosis. There were no significant differences between groups in the use of all medications (loop diuretics, mineralocorticoid receptor antagonists, renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, beta blockers, statins, and Mg preparations). The lower sMg group showed a significantly higher prevalence of diabetes mellitus (DM), uric acid levels, and BNP levels compared with the higher sMg group. Kaplan-Meier curve revealed a significantly higher probability of HF-related events in the lower sMg group compared with the higher sMg group (log-rank test, P = .012). Multivariate Cox-proportional-hazard analysis revealed that the lower sMg group had significantly and independently higher probabilities of HF-related events compared with the higher sMg group (hazard ratio = 2.37, 95% confidence intervals = 1.27-4.41, P = .007). We reclassified the risk of HF-related events after adding the lower sMg to the other prognostic factors (age, previous hospitalization for HF, DM, Ln-BNP); the continuous net reclassification improvement was 29.0% (P = .041). sMg levels might provide important prognostic information in regard to HFpEF.

Prognostic significance of polyvascular disease in heart failure with preserved left ventricular ejection fraction.

The prognostic significance of systemic atherothrombosis in heart failure (HF) with preserved ejection fraction (HFpEF) remains unclear. This study aimed to investigate the relation between the presence of polyvascular disease (PVD) and cardiovascular outcomes in HFpEF patients.A total of 510 consecutive HFpEF patients were prospectively observed for up to 1500 days or until occurrence of cardiovascular events. PVD was defined as ≥2 coexistence of coronary artery disease, peripheral arterial disease, and cerebrovascular disease.Overall, 124 cardiovascular events were observed during follow-up (median: 1430 days). Kaplan-Meier curve showed HFpEF with PVD (n = 84) experienced more cardiovascular events than did those without PVD patients (44.0% vs 20.4%, log-rank: P < .001). Multivariable Cox proportional hazards analysis with significant factors from univariate analysis showed the presence of PVD (hazard ratio [HR]: 2.875, 95% [CI]: 1.894-4.365, P < .001), previous HF hospitalization (HR: 1.578, 95% CI: 1.031-2.414, P = .036), hemoglobin (HR: 0.889, 95% CI: 0.805-0.983, P = .021), serum sodium (HR: 0.946, 95% CI 0.896-1.000, P = .048), ln-BNP (per 1.0, HR: 1.255, 95% CI: 1.055-1.494, P = .010), and E/e' (HR: 1.047, 95% CI: 1.020-1.075, P < .001) significantly predicted future cardiovascular events. Multivariable Cox hazard analysis with 4 established factors (age, BNP, diabetes mellitus, and previous HF hospitalization) from the I-PRESERVE (Irbesartan in HFpEF) study showed PVD was independently associated with cardiovascular events in HFpEF patients (HR: 2.562, 95% CI: 1.715-3.827, P < .001).The presence of PVD is significantly associated with cardiovascular events in HFpEF, suggesting the importance of screening PVD in HFpEF.

H2FPEF Score as a Prognostic Value in HFpEF Patients.

BACKGROUND: The H2FPEF score is recognized as a simple method to diagnose heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). We investigated the value of the H2FPEF score in predicting subsequent cardiovascular events in HFpEF patients. METHODS: This study was a retrospective, single-center, observational study. We calculated the H2FPEF scores for 404 consecutive HFpEF patients. Subjects were subdivided into low- (0-3), intermediate- (4-6), and high-score (7-9) groups and followed for 50 months. The primary and secondary endpoints were composite cardiovascular/cerebrovascular events (cardiovascular death, nonfatal myocardial infarction, unstable angina pectoris, hospitalization for HF decompensation, and nonfatal stroke) occurrence and HF-related events (hospitalization for HF decompensation) occurrence at 50 months, respectively. RESULTS: Kaplan-Meier analyses demonstrated a significantly higher incidence of cardiovascular/cerebrovascular events among those with a higher H2FPEF score (log-rank test, P = 0.005). The HF-related event rate was higher in proportion to the H2FPEF score (log-rank test, P < 0.001). Multivariate Cox hazard analyses identified the H2FPEF score (per 1 point) as an independent predictor of cardiovascular and HF-related events (hazard ratio [HR], 1.179; 95% confidence interval [CI], 1.066-1.305; P = 0.001 and HR, 1.288; 95% CI, 1.134-1.463; P = 0.001, respectively). Receiver operating characteristic analysis showed that the H2FPEF significantly predicted cardiovascular events (area under the curve [AUC], 0.626; 95% CI, 0.557-0.693; P < 0.001) and HF-related events (AUC, 0.680; 95% CI, 0.600-0.759; P < 0.001). The cutoff H2FPEF score was 5.5 for the identification of cardiovascular and HF-related events. CONCLUSION: The H2FPEF score might be a potentially useful marker for the prediction of cardiovascular and HF-related events in HFpEF patients. CLINICAL TRAILS REGISTRATION: Trail Number UMIN000029600.

Clinical Significance of Brachial-Ankle Pulse Wave Velocity in Patients With Heart Failure With Reduced Left Ventricular Ejection Fraction.

BACKGROUND: Although pulse wave velocity (PWV) is recognized to be a risk predictor for various cardiovascular diseases, the association of brachial-ankle PWV (baPWV) with cardiovascular outcomes in heart failure (HF) with reduced ejection fraction (HFrEF) patients remains uncertain. METHODS: We measured ankle-brachial pressure index (ABI) and baPWV values at stable condition after optimal therapy for HF in 201 consecutive HFrEF patients admitted to Kumamoto University Hospital from 2007 to 2015 who were enrolled and followed until the occurrence of cardiovascular events. We defined peripheral artery disease (PAD) as ABI value ≤ 0.9. RESULTS: Kaplan-Meier analysis revealed that HFrEF patients with peripheral artery disease PAD had a significant higher risk of total cardiovascular and HF-related events than those without PAD (P = 0.03 and P = 0.01, respectively). Next, we divided HFrEF patients without PAD into 3 groups according to baPWV values. In the Kaplan-Meier analysis, total cardiovascular and HF-related events in the highest baPWV group (1,800 cm/second ≤ baPWV) had a significantly higher frequency than those in the mid-level baPWV group (1,400 cm/second ≤ baPWV < 1,800 cm/second) (P = 0.007 and P = 0.004, respectively). The hazard ratio between HFrEF patients in the mid-level baPWV group and those with other baPWV groups was compared after adjustment for other cofounders. The probabilities of HF-related events were significantly higher in the lowest and highest baPWV group. CONCLUSION: Identifying complications of PAD and measuring baPWV values in HFrEF patients were useful for predicting their prognosis.Trial Registration: UMIN000034358.