Left atrial volume index as a predictor for left atrial appendage thrombus in patients with non-valvular atrial fibrillation receiving appropriate oral anticoagulation therapy: A prospective multi-center study.

OBJECTIVES: We previously reported a higher left atrial volume index (LAVI) was independently associated with left atrial (LA) appendage (LAA) thrombus formation in 737 patients with non-valvular atrial fibrillation (NVAF) receiving appropriate oral anticoagulation therapy. Since our previous study was a retrospective single-center study, we designed and conducted a prospective multi-center study to verify our findings for LAVI as a predictor of LAA thrombus in patients with NVAF receiving appropriate oral anticoagulation therapy. METHODS: This prospective multi-center study comprised 746 consecutive patients with NVAF recruited between December 2021 and March 2023 from eight institutions in Japan, who were receiving appropriate oral anticoagulation therapy, had undergone transthoracic echocardiography and transesophageal echocardiography (TEE). RESULTS: LAA thrombi were observed in 21 patients (2.8%). The prevalence of LAA thrombus formation in patients with paroxysmal AF (PAF) was significantly lower than that in patients with non-PAF (0.7% vs. 4.1%, p = .006). LAA thrombus formation was detected in none (0/171) of the patients with normal size LA (LAVI ≤ 34 mL/m2 ). The prevalence of LAA thrombus formation in patients with mildly dilated LA (LAVI: 34-49.9 mL/m2 ) was 2.1% (6/283), but that in PAF patients was low at 1.0% (1/104). Furthermore, this prevalence in patients with severely dilated LA (LAVI ≥ 50 mL/m2 ) was high at 5.1% (15/292). CONCLUSIONS: The findings of this prospective multi-center study are consistent with those of our previous study. Thus, the need for TEE prior to catheter ablation or electrical cardioversion can be determined by the level of LAVI.

Efficacy of Coronary Sinus Pacing for Cardiogenic Shock Due to Percutaneous Coronary Intervention-induced Sick Sinus Syndrome: Two Case Reports.

We herein report two cases of atrial pacing with coronary sinus (CS) pacing performed to improve hemodynamic instability in cardiogenic shock due to percutaneous coronary intervention (PCI)-induced sick sinus syndrome (SSS). Ventricular pacing alone made it difficult to stabilize hemodynamics due to SSS, which had been caused by the lack of reflow and slow flow of the sinus node artery (SNA) jailed with a stent. Adding atrial pacing with CS pacing may be useful, as in our two cases, where ventricular pacing alone was unable to stabilize hemodynamics.

Unilateral methotrexate-induced lung injury with foreign bodies in the airway: A case report.

A 75-year-old woman who had been taking methotrexate presented to our hospital for fever and dry cough. Chest computed tomography showed ground-glass opacity in the upper lobe of the right lung and foreign bodies in the lower lobe of the right bronchus. During bronchoscopy, foreign bodies were removed from the airway. We found increased levels of lymphocytes and a high CD4/CD8 ratio in the bronchoalveolar lavage fluid. Transbronchial lung biopsy revealed lymphocytic infiltration. Methotrexate was discontinued, and the imaging findings improved. Methotrexate-induced lung injury does occur unilaterally. Foreign bodies in the airway might also trigger unilateral methotrexate-induced lung injury.

Effect of hypertension on the optimal anthracycline cumulative dose for developing left ventricular dysfunction in patients with malignant lymphoma.

The most serious adverse effect of anthracycline chemotherapy is progressive dose-dependent left ventricular (LV) dysfunction, and a total cumulative doxorubicin dose ≥ 240 mg/m2 has been classified as putting patients at high risk for developing cardiac dysfunction. Hypertension is the single most important risk factor for heart failure and chemotherapy-induced LV dysfunction, but the effect of hypertension on the total cumulative doxorubicin dose to prevent the development of LV dysfunction in patients scheduled for anthracycline chemotherapy remains uncertain. The aim of this study was to investigate the effect of hypertension on the optimal total cumulative anthracycline dose to prevent the development of LV dysfunction in patients with malignant lymphoma. We retrospectively studied 92 patients with malignant lymphoma and preserved LV ejection fraction (LVEF) who underwent anthracycline chemotherapy. Echocardiography was performed before and 2 months after anthracycline chemotherapy. LV hypertrophy (LVH) was defined as concentric hypertrophy, and LV dysfunction after chemotherapy as a relative decrease in LVEF ≥ 5%. The cutoff value of the total cumulative doxorubicin dose for the development of LV dysfunction was lower for hypertensive patients (n = 23) than for non-hypertensive patients (n = 69) (259.3 mg/m2 vs. 358.9 mg/m2). Importantly, the cutoff value of the total cumulative doxorubicin dose to prevent the development of LV dysfunction in hypertensive patients with LVH was even lower at 40.1 mg/m2. A lower cumulative anthracycline dose can cause LV dysfunction in hypertensive patients with malignant lymphoma, especially when complicated by LVH. Our findings can thus be expected to have clinical implications for better management of such patients.

Characteristics of non-valvular atrial fibrillation with left atrial appendage thrombus who are undergoing appropriate oral anticoagulation therapy.

We investigated the characteristics of patients with non-valvular atrial fibrillation (NVAF) and left atrial (LA) appendage (LAA) thrombus who had been given appropriate oral anticoagulation therapy. We studied 737 NVAF patients who were scheduled for catheter ablation or electrical cardioversion. All patients received appropriate oral anticoagulation therapy for at least 3 weeks prior to echocardiography in accordance with the guidelines. Whether LAA thrombus was present or absent on transesophageal echocardiography (TEE) was determined by at least three senior echocardiologists. LAA thrombi were observed in 22 patients (3.0%). Multivariate logistic regression analysis showed that LAA flow and LA volume index were both independent predictors of LAA thrombus formation; however, LAA flow (≤ 18 cm/s) was indicated as a more powerful predictor. Moreover, the prevalence of LAA thrombus formation in patients with NVAF without LA enlargement (LA volume index ≤ 34 mL/m2) was extremely rare (0.4%). LAA thrombus formation in patients with a mildly dilated LA volume index of 34-49.9 mL/m2 and paroxysmal AF was also extremely rare (0.0%). LAA flow is strongly associated with LAA thrombus formation, even in NVAF patients treated with appropriate oral anticoagulation therapy. Augmented oral anticoagulation therapy or transcatheter or surgical LAA closure should be considered for such patients, especially for those with an LAA flow < 18 cm/s. Furthermore, TEE for evaluating LAA thrombus before catheter ablation or electrical cardioversion may be unnecessary for NVAF patients who are undergoing appropriate oral anticoagulation therapy, depending on LA size.

Association of left ventricular longitudinal myocardial function with subclinical right ventricular dysfunction in type 2 diabetes mellitus.

BACKGROUND: Left ventricular (LV) involvement in diabetic cardiomyopathy has been reported; however, only limited data exist on right ventricular (RV) involvement. Therefore, our purpose was to investigate RV systolic dysfunction and its association with LV longitudinal myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM) and preserved LV ejection fraction (LVEF). METHODS: We studied 177 T2DM patients with preserved LVEF and 79 age-, sex-, and LVEF-matched healthy volunteers. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), and RV systolic function was assessed as RV free-wall strain, and predefined cutoff values for subclinical dysfunction were set at GLS < 18% and RV free-wall strain < 20%, respectively. RESULTS: RV free-wall strain in T2DM patients was significantly lower than that in normal controls (19.3% ± 4.8% vs. 24.4% ± 5.1%; P < 0.0001). RV free-wall strain in T2DM patients and LV longitudinal dysfunction was similar compared to that in T2DM patients without (19.0 ± 4.5% vs. 19.6 ± 5.0%, P = 0.40). Furthermore, multivariate logistic regression analyses showed that GLS was independently associated with RV systolic dysfunction as well as mitral inflow E and mitral e' annular velocities ratio (odds ratio, 1.16; 95% confidence interval: 1.03-1.31; P < 0.05). Sequential logistic models evaluating the association of RV systolic dysfunction in T2DM patients showed an improvement in clinical variables (χ2 = 6.2) with the addition of conventional echocardiographic parameters (χ2 = 13.4, P < 0.001) and a further improvement with the addition of GLS (χ2 = 20.8, P < 0.001). CONCLUSION: RV subclinical systolic dysfunction was observed in T2DM patients with preserved LVEF and was associated with LV longitudinal myocardial dysfunction. Our findings may provide additional findings for the management of T2DM patients.

Easy-to-use preload stress echocardiography by using combined dynamic postural stress can identify high-risk patients with heart failure with reduced ejection fraction.

AIMS: Haemodynamic assessment during stress testing is not commonly performed in patients with heart failure with reduced ejection fraction (HFrEF) because of its invasiveness, lower feasibility, and safety concerns. This study aimed to assess the haemodynamic characteristics of patients with HFrEF in response to non-invasive preload stress during dynamic postural alterations achieved by combining both semi-sitting position and passive leg-lifting and to evaluate whether combined postural stress could be used for risk stratification in these patients. METHODS AND RESULTS: For this study, 101 patients with HFrEF and 35 age-matched and sex-matched healthy controls were prospectively recruited. After all standard echocardiographic measurements were obtained in the left decubitus position, all subjects underwent postural stress testing, which consisted of changing from semi-sitting position to passive leg-lifting. During a median follow-up period of 12.2 months, 21 (21%) patients developed adverse cardiovascular events. In patients without adverse cardiovascular events, the stroke volume index (SVi) significantly changed from 28 ± 8 to 35 ± 10 mL/m2 (P < 0.001) during combined postural stress. By contrast, ΔSVi during combined dynamic postural stress was significantly smaller in patients with cardiovascular events than in those without events (ΔSVi 3.4 ± 4.0 vs. 6.4 ± 3.8 mL/m2 , P = 0.002), which indicated severely diseased heart operated on a relatively flat portion of the Frank-Starling curve. In a multivariate Cox proportional hazard analysis, ΔSVi (hazard ratio 0.81, P = 0.02) was an independent predictor of future adverse cardiovascular events. CONCLUSIONS: The combined assessment of dynamic postural stress is a non-invasive, simple, quick, and easy-to-use clinical tool for assessing preload reserve and risk stratification in HFrEF patients.

Preoperative coupling between right ventricle and pulmonary vasculature is an important determinant of residual symptoms after the closure of atrial septal defect.

PURPOSES: The closure of atrial septal defect (ASD) is associated with a significant reduction in right ventricular (RV) overload and an improvement in functional capacity in most adults with ASD. However, a subset of patients remains symptomatic even after closure due to therapeutic delay. To date, no clinically robust preoperative predictor of postoperative residual symptoms has been clearly identified. METHODS: In this study, 120 adult patients with ASD and 39 controls were investigated. As an index of RV myocardial deformation, RV global longitudinal strain (RV-GLS) was evaluated. The degree of coupling between RV and pulmonary artery (PA) was quantified by the tricuspid annular plane systolic excursion (TAPSE) divided by the PA systolic pressure (PASP). RESULTS: Compared to controls, baseline RV-GLS was significantly greater (- 27 ± 7 vs. - 23 ± 5%, P = 0.02) and TAPSE/PASP ratio was severely impaired (0.8 ± 0.3 vs. 2.1 ± 1.6 mm/mmHg, P < 0.01) in ASD patients. At 6 months after closure, 15 patients (12.5%) remained symptomatic. In patients without residual symptoms, TAPSE/PASP ratio significantly improved from 0.9 ± 0.3 to 1.0 ± 0.6 mm/mmHg (P = 0.02), and RV-GLS normalized (from - 28 ± 11 to - 24 ± 7%, P < 0.01) after closure. However, RV-GLS and TAPSE/PASP ratio showed no significant change in ASD patients with residual symptoms. On multivariate analysis, preoperative TAPSE/PASP ratio (odds ratio [OR] 0.034, 95% confidence interval [CI] 0.000-0.604, P = 0.03) and pulmonary vascular resistance index ([PVRI], OR 1.011, 95% CI 1.000-1.021, P < 0.05) were associated with the postoperative symptomatic status. CONCLUSION: In terms of integrated assessment of the RV-PA unit, preoperative TAPSE/PASP ratio and PVRI were important determinants of residual symptoms after ASD closure.

"Accelerated aging" of the heart as heart failure with preserved ejection fraction-analysis using leg-positive pressure stress echocardiography.

The aging process is a significant risk factor for heart failure. The incidence of heart failure with preserved ejection fraction (HFpEF) dramatically increases with age. Although HFpEF occurs along a continuum of aging of the cardiovascular system, the pathophysiology that differentiates overt HFpEF from physiological aging is not fully understood. A total of 102 subjects were prospectively recruited: 25 patients with HFpEF and 77 healthy controls. Controls were stratified into three age-groups: young (n = 27, 20-40 years), middle aged (n = 25, 40-65 years), and elderly (n = 25, > 65 years). All participants underwent preload stress echocardiography using a leg-positive pressure (LPP) maneuver. With an increase in age, progressive concentric left ventricular (LV) remodeling was observed in healthy controls, resulting in the hemodynamic consequences of an age-dependent increase in the E/e' ratio (ANOVA, P < 0.001). During LPP stress, the E/e' ratio significantly increased in the middle-aged and elderly groups (from 8 ± 2 to 9 ± 3, from 10 ± 2 to 12 ± 3, P < 0.05, respectively), and this was more pronounced in patients with HFpEF (from 16 ± 5 to 17 ± 7, P < 0.05). Forward stroke volume (SV) significantly increased in each healthy group during LPP stress (all P < 0.001) but failed to increase in the HFpEF group (from 43 ± 13 to 44 ± 14 mL/m2, P = 0.65). In a multivariate analysis, LV mass index (odds ratio [OR] 1.051, P < 0.05), E/e' ratio (OR 1.480; P < 0.05), and change in SV (OR 0.780; P < 0.05) were independent parameters that differentiated HFpEF from physiological aging. Structural remodeling and impaired preload reserve may both be critical features that characterize the pathophysiology of HFpEF.

Effect of heart rate on left ventricular longitudinal myocardial function in type 2 diabetes mellitus.

BACKGROUND: Left ventricular (LV) longitudinal myocardial dysfunction is considered a marker of preclinical LV dysfunction in patients with type 2 diabetes mellitus (T2DM). High heart rate (HR) is associated with cardiovascular outcomes, but the effect of HR on LV longitudinal myocardial function in T2DM patients is uncertain. METHODS: We studied 192 T2DM patients with preserved LV ejection fraction (LVEF), and 81 age-, sex-, and LVEF-matched healthy volunteers. HR was measured as the average HR during echocardiography, and high HR was defined as resting HR ≥ 70 beats/minute. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS). The predefined cutoff for subclinical LV dysfunction was set at GLS < 18%. RESULTS: GLS in T2DM patients with high HR was significantly lower than that in T2DM patients with low HR (16.3% ± 4.2% vs. 17.8% ± 2.8%; P = 0.03), whereas GLS in normal subjects with high and low HR was similar (20.3 ± 1.7% vs. 20.3 ± 2.0%; P = 0.99). Multivariable logistic regression analysis showed that high HR (odds ratio: 1.04; 95% confidence interval: 1.01-1.07; P = 0.01) was independently associated with GLS < 18% in T2DM patients as well as HbA1c, T2DM duration, LVEF, body mass index, and mitral inflow E and mitral e' annular velocity ratio. One sequential logistic model evaluating the associations between GLS < 18% and clinical variables in T2DM patients showed an improvement with the addition of LVEF and E/e' (P < 0.001) and a further improvement with the addition of high HR (P < 0.001). CONCLUSION: Compared with normal subjects, resting HR was associated with LV longitudinal myocardial function in asymptomatic T2DM patients with preserved LVEF. Our findings provide new insights on the management of T2DM patients.

Impact of hypertension on left ventricular function in patients after anthracycline chemotherapy for malignant lymphoma.

BACKGROUND: Hypertension is considered an important risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) as well as heart failure. However, the impact of hypertension and left ventricular (LV) hypertrophy (LVH), which is associated with hypertension, on LV function in patients treated with anthracycline chemotherapy for malignant lymphoma remains uncertain. METHOD: We studied 92 patients with malignant lymphoma and with preserved LV ejection fraction (LVEF). Echocardiography was performed before and two-month after anthracycline chemotherapy. CTRCD was defined as the presence of an absolute decrease in LVEF ≥10% to a final value <53%. LVH was defined as concentric hypertrophy, which was determined as relative wall thickness ≥ 0.42 and LV mass index >95 g/m2 for females and > 115 g/m2 for males. RESULTS: Relative decrease in LVEF after anthracycline chemotherapy in patients with hypertension (n = 23) was significantly higher than that in patients without hypertension (n = 69) (-5.8% [-9.4, -1.3]) vs. (-1.1% [-4.1, 2.5]); P = .005). Moreover, the prevalence of CTRCD in patients with hypertension tended to be higher than in those without hypertension (17% vs. 5%, p = .09). A sequential logistic model for predicting CTRCD, based on baseline clinical variables including major clinical risk factors, was improved by the addition of the complication of hypertension (P = .049), and further improved by the addition of the presence of LVH (P = .023). CONCLUSIONS: Hypertension, especially when complicated by LVH, was found to be associated with LV dysfunction after anthracycline chemotherapy in patients with malignant lymphoma and preserved LVEF. Watchful observation or early therapeutic intervention may thus be needed for such patients by the addition of the presence of LVH.

Association between clinical risk factors and left ventricular function in patients with breast cancer following chemotherapy.

The sequential or concurrent use of two different types of agents such as anthracyclines and trastuzumab may increase myocardial injury and cancer therapeutics-related cardiac dysfunction (CTRCD), which is often the result of the combined detrimental effect of the two therapies for breast cancer patients. However, the association between clinical risk factors and left ventricular (LV) function in such patients is currently unclear. We studied 86 breast cancer patients with preserved LV ejection fraction (LVEF) and treated with anthracyclines, trastuzumab, or both. Echocardiography was performed before and 16 days after chemotherapy. In accordance with the current position paper, clinical risk factors for CTRCD were defined as: cumulative dose of doxorubicin > 240 mg/m2, age > 65-year-old, body mass index > 30 kg/m2, previous radiation therapy, B-type natriuretic peptide > 100 pg/mL, previous history of cardiovascular disease, atrial fibrillation, hypertension, diabetes, and smoking. The relative decrease in LVEF after chemotherapy for patients with more than four risk factors was significantly greater than that for patients without (- 9.3 ± 10.8% vs. - 2.2 ± 10.2%; p = 0.02). However, this finding did not apply to patients with more than one, two or three risk factors. Patients with more than four risk factors also tended to show a higher prevalence of CTRCD than those without (14.3% vs. 2.8%; p = 0.12). Moreover, the relative decrease in LVEF became greater as the number of risk factors increased. This study found multiple risk factors were associated with LV dysfunction following chemotherapy. Our findings can thus be expected to have clinical implications for better management of patients with breast cancer referred for chemotherapy.

Mitral Ebstein's Anomaly Modified with a Scarred Rhabdomyoma in Tuberous Sclerosis: An Extremely Rare Cause of Mitral Insufficiency.

We present an extremely rare case of mitral Ebstein's anomaly that resulted in severe mitral regurgitation (MR). A 41-year-old woman with a history of tuberous sclerosis underwent surgery. Preoperatively, it was assumed that MR had occurred due to leaflet tethering related to left ventricular posterior wall motion asynergy due to a scarred rhabdomyoma. However, surgical inspection revealed a dysplastic posterior leaflet adhering to the ventricular wall, which was completely covered by the endocardium. Both congenital mitral Ebstein's anomaly and acquired wall motion abnormality due to a scarred rhabdomyoma may have contributed to the development of severe MR in this case.

Noninvasive Leg-Positive Pressure Stress Echocardiography Reveals Preload Reserve in Adult Patients after Complete Repair of Tetralogy of Fallot.

BACKGROUND: Long-term sequelae such as right ventricular dysfunction and reduced hemodynamic reserve are the main determinants of cardiovascular outcomes after repair of tetralogy of Fallot (TOF). Echocardiographic parameters at rest offer only partial information on impaired hemodynamics in these patients, and data during stress testing are lacking. The leg-positive pressure (LPP) maneuver has recently been reported to be able to apply acute preload stress. The aim of this study was to test the hypothesis that preload reserve is impaired and ventricular interaction is exacerbated in patients with TOF. METHODS: In this prospective cross-sectional study, we recruited 44 consecutive patients with TOF and 30 normal control subjects. Echocardiography was performed both at rest and during LPP stress, and preload reserve was defined as the change between baseline stroke volume (SV) and that obtained during LPP stress. The eccentricity index was calculated as the ratio of the left ventricular anteroposterior to septal-lateral dimensions to quantify ventricular interaction. RESULTS: LPP stress significantly increased SV from 73 ± 14 to 83 ± 16 mL (P < .01) in control subjects, while the increase in SV was significantly blunted (from 75 ± 19 to 79 ± 18 mL; P < .01 for interaction) in patients with TOF. The eccentricity index significantly changed during LPP stress in patients with TOF only from 1.07 ± 0.13 to 1.13 ± 0.14 (P < .01 for interaction). Patients with TOF were subdivided into two subgroups on the basis of the median value of increased response in SV (22 with sufficient and 22 with insufficient preload reserve). Multivariate analysis identified significant pulmonary regurgitation as the only independent determinant factor for insufficient preload reserve (odds ratio, 4.57; 95% CI, 1.048-19.90; P = .04). CONCLUSIONS: In patients after repair of TOF, ventricular interaction was exacerbated and preload reserve was impaired, especially in patients with significant pulmonary regurgitation. LPP stress testing may direct tailored treatment approaches, risk stratification, and clinical decision-making, such as more aggressive pharmacologic therapy, meticulous outpatient follow-up, or earlier reintervention.

Associations between functional tricuspid regurgitation and long-term outcomes for patients with pulmonary hypertension.

Functional tricuspid regurgitation (FTR) is associated with prognosis for various heart diseases, but its association with pulmonary hypertension (PH) remains unclear. We studied 111 PH patients. Mid-term follow-up echocardiography was performed 7.1 ± 4.1 months after PH-specific therapy. The severity of FTR was graded as none or trace, mild, moderate, or severe, while more than moderate TR was defined as significant. Moreover, mid-term improvement in FTR after therapy was defined as an improvement in severity of FTR by a grade of 1 or more. Long-term follow-up to determine the primary endpoint of death or hospitalization for heart failure lasted 39 ± 14 months. Mid-term improvement in FTR after PH-specific treatment was observed in 25 patients (23%), and the primary end points occurred in 27 patients (24%) during the long-term follow-up. The Kaplan-Meier curve indicated that the non-FTR group showed more favorable long-term outcomes than the FTR group (log-rank P = 0.008). It further indicated that patients with mid-term improvement in FTR also had more favorable long-term outcomes than those without such improvement (log-rank P = 0.03). When divided into four sub-groups based on combined assessment of baseline FTR and mid-term improvement in FTR, long-term outcomes for patients without mid-term improvement in their baseline FTR were worse than for the other sub-groups (log-rank P = 0.02). Multiple regression analysis showed that a relative change in tricuspid annular diameter at the mid-term follow-up after PH-specific therapy was the only independent determinant parameters for mid-term improvement in FTR. FTR appears to be a valuable factor for predicting long-term outcomes for PH patients, and combined assessment of baseline FTR and mid-term improvement in FTR after PH-specific therapy may have clinical implications for better management of such patients.

Effects of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension on remodeling in right-sided heart.

Remodeling in the right-sided heart plays an important role in the management of pulmonary hypertension (PH) patients. However, the effect of balloon pulmonary angioplasty (BPA) on right ventricular (RV) and right atrial (RA) morphology of patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains uncertain. This study involved 45 CTEPH patients who underwent BPA with mean pulmonary artery pressure (mPAP) of 37.0 mmHg (all ≥ 25 mmHg). All patients underwent echocardiography and right-heart catheterization at baseline and 3 months after BPA. RV and RA remodeling was assessed as RV and the RA area, and RV systolic function was calculated by averaging peak speckle-tracking longitudinal strain of the RV free-wall (RV free-wall strain). Significant reverse remodeling in the right-sided heart was observed after BPA, resulting in improvement of mPAP and pulmonary vascular resistance (RV area: from 15.0 ± 5.3 to 9.6 ± 3.0 cm2, p < 0.0001; RA area: from 17.3 ± 6.6 to 13.4 ± 3.8 cm2, p = 0.0002; RV free-wall strain: from 15.9 ± 5.6 to 21.2 ± 4.9%, p < 0.0001). Furthermore, multiple regression analysis showed that the baseline RV area was an independent predictor of post-BPA normalization of RV systolic function defined as RV free-wall strain ≥ 20% (odds ratio = 1.16, p = 0.0305). Interestingly, significant RV reverse remodeling was also observed after additional BPA even in 18 CTEPH patients with residual pulmonary arterial stenosis, whose mPAP was normalized after BPA (RV area: from 11.5 ± 3.8 to 9.2 ± 3.8 cm2, p = 0.0045; RV free-wall strain: from 17.2 ± 4.8 to 22.8 ± 7.4%, p = 0.0216). Significant reverse remodeling in the right-sided heart, as well as hemodynamic improvement, was observed in CTEPH patients after BPA.

Optimal Cut-Off of Tricuspid Regurgitation Velocity According to the New Definition of Pulmonary Hypertension　- Its Use in Predicting Pulmonary Hypertension.

Background: The 6th World Symposium on Pulmonary Hypertension proposed that precapillary pulmonary hypertension (PH) be defined as mean pulmonary arterial pressure (mPAP) >20 mmHg instead of mPAP ≥25 mmHg. Peak tricuspid regurgitation velocity (TRV) >3.4 m/s is widely used to predict PH, but it is unclear whether this value remains reliable for the new definition of PH. Methods and Results: We found that the optimal cut-off value of peak TRV for 511 PH patients was >2.8 m/s, with a sensitivity of 89.5%, specificity of 73.4%, and area under the curve of 0.89 (P<0.001). Conclusions: Based on the new definition of PH, TRV >2.8 m/s can be considered to indicate a high probability of PH.

Association of body fat mass with left ventricular longitudinal myocardial systolic function in type 2 diabetes mellitus.

BACKGROUND: Left ventricular (LV) longitudinal myocardial systolic dysfunction (LVSD) has been identified in type 2 diabetes mellitus (T2DM) patients, and it should be considered the first marker of a preclinical form of DM-related cardiac dysfunction. Overweight has been postulated to contribute to the development of LVSD in T2DM patients, but the impact of amount of body fat mass on LVSD in T2DM patients remains uncertain. METHODS: We studied 71 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) (all ≥55%) without coronary artery disease. LVSD for T2DM patients with preserved LVEF was identified as global longitudinal strain (GLS) <18%. Body fat mass was measured with a commercially available body composition analyzer (In Body S-10, Biospace, Tokyo, Japan), and corrected by body surface area (BFI: body fat index). RESULTS: Univariate logistic regression analysis revealed that body weight, body mass index (BMI), and BFI were all associated with LVSD, whereas multivariate logistic regression analysis showed BFI was the only variable independently associated with LVSD (OR 1.147; 95% CI 1.001-1.314; p = 0.027). For sequential logistic regression models to predict LVSD, clinical variables including age, DM duration, and HbA1c tended to be improved by addition of BMI, but without statistical significance (p = 0.09), while it was significantly improved by addition of BFI (p = 0.047). CONCLUSIONS: Using BFI for the control of body compression by means of a bioelectrical impedance assay is simple and easy-to-use, and this may have clinical implications for better management of T2DM patients with preserved LVEF to prevent future development of DM-related cardiac dysfunction.

Association of glycemic variability with left ventricular diastolic function in type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major cause of heart failure (HF) with preserved ejection fraction (HFpEF), usually presenting as left ventricular (LV) diastolic dysfunction. Thus, LV diastolic function should be considered a crucial marker of a preclinical form of DM-related cardiac dysfunction. However, the impact of glycemic variability (GV) on LV diastolic function in such patients remains unclear. METHODS: We studied 100 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) without coronary artery disease (age: 60 ± 14 years, female: 45%). GV was evaluated as standard deviation of blood glucose level using continuous glucose monitoring system for at least 72 consecutive hours. LV diastolic function was defined as mitral inflow E and mitral e' annular velocities (E/e'), and > 14 was determined as abnormal. RESULTS: E/e' in patients with high GV (≥ 35.9 mg/dL) was significantly higher than that in patients with low GV (11.3 ± 3.9 vs. 9.8 ± 2.8, p = 0.03) despite similar age, gender-distribution, and hemoglobin A1c (HbA1c). Multivariate logistic regression analysis showed that GV ≥ 35.9 mg/dL (odds ratio: 3.67; 95% confidence interval: 1.02-13.22; p < 0.05) was an independently associated factor, as was age, of E/e' > 14. In sequential logistic models for the associations of LV diastolic dysfunction, one model based on clinical variables including age, gender and hypertension was not improved by addition of HbA1c (p = 0.67) but was improved by addition of high GV (p = 0.04). CONCLUSION: Since HFpEF is a syndrome caused by diverse agents, reducing GV may represent a potential new therapeutic strategy for the prevention of the development of HFpEF in T2DM patients.