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1.
Mol Pharm ; 18(4): 1593-1603, 2021 04 05.
Article in English | MEDLINE | ID: mdl-33617269

ABSTRACT

Oral delivery of insulin remains a challenge owing to its poor permeability across the small intestine and enzymatic digestion in the gastrointestinal tract. In a previous study, we identified a small intestine-permeable cyclic peptide, C-DNPGNET-C (C-C disulfide bond, cyclic DNP peptide), which facilitated the permeation of macromolecules. Here, we showed that intraintestinal and oral coadministration of insulin with the cyclic DNP derivative significantly reduced blood glucose levels by increasing the portal plasma insulin concentration following permeation across the small intestine of mice. We also found that protecting the cyclic DNP derivative from enzymatic digestion in the small intestine of mice using d-amino acids and by the cyclization of DNP peptide was essential to enhance cyclic DNP derivative-induced insulin absorption across the small intestine. Furthermore, intraintestinal and oral coadministration of insulin hexamer stabilized by zinc ions (Zn-insulin) with cyclic D-DNP derivative was more effective in facilitating insulin absorption and inducing hypoglycemic effects in mice than the coadministration of insulin with the cyclic D-DNP derivative. Moreover, Zn-insulin was more resistant to degradation in the small intestine of mice compared to insulin. Intraintestinal and oral coadministration of Zn-insulin with cyclic DNP derivative also reduced blood glucose levels in a streptozotocin-induced diabetes mellitus mouse model. A single intraintestinal administration of the cyclic D-DNP derivative did not induce any cytotoxicity, either locally in the small intestine or systemically. In summary, we demonstrated that coadministration of Zn-insulin with cyclic D-DNP derivative could enhance oral insulin absorption across the small intestine in mice.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin, Regular, Human/administration & dosage , Peptides, Cyclic/administration & dosage , Zinc/chemistry , Administration, Oral , Animals , Blood Glucose/analysis , Blood Glucose/drug effects , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacokinetics , Insulin, Regular, Human/chemistry , Insulin, Regular, Human/metabolism , Insulin, Regular, Human/pharmacokinetics , Intestinal Absorption , Intestine, Small/metabolism , Male , Mice , Peptides, Cyclic/pharmacokinetics , Permeability , Proteolysis , Streptozocin/administration & dosage , Streptozocin/toxicity
2.
J Card Fail ; 26(1): 43-51, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31487533

ABSTRACT

BACKGROUND: Recent studies have shown that patients with combined pre- and postcapillary pulmonary hypertension (CpcPH) had worse outcomes than those with isolated postcapillary pulmonary hypertension (IpcPH). However, the prognostic factors including right ventricular (RV) function have not been well documented. The aim of this study was to assess the differentiation of PH phenotypes, using echocardiography, and the association between RV longitudinal strain and cardiac events. METHODS AND RESULTS: We prospectively recruited consecutive patients who had undergone right heart catheterization. The primary endpoint was cardiovascular death or readmission due to heart failure. We included 137 patients with Group 2 PH. A RV longitudinal strain of 17% was sensitive (85%) and specific (70%) to determine the CpcPH. During a median period of 31 months, 43 patients experienced the primary endpoint during follow-up. In a multivariate analysis, RV longitudinal strain was associated with the primary endpoint in both CpcPH and IpcPH (HR: 0.84, P = 0.003; HR: 0.86, P = 0.001). CONCLUSIONS: Lower RV longitudinal strain was independently associated with worse outcomes in CpcPH and IpcPH. RV longitudinal strain may play a prognostic role in PH phenotypes.


Subject(s)
Capillaries/diagnostic imaging , Cardiac Catheterization/methods , Hypertension, Pulmonary/diagnostic imaging , Myocardial Contraction/physiology , Ventricular Function, Right/physiology , Adult , Aged , Aged, 80 and over , Capillaries/physiopathology , Cohort Studies , Female , Follow-Up Studies , Humans , Hypertension, Pulmonary/physiopathology , Male , Middle Aged , Prospective Studies
3.
Int Heart J ; 61(4): 787-794, 2020 Jul 30.
Article in English | MEDLINE | ID: mdl-32684602

ABSTRACT

Advanced age, obesity, and muscle weakness are independent factors in the onset of deep vein thrombosis (DVT). Recently, an association between sarcopenia and DVT has been reported. We hypothesized that sarcopenia related factors, observed by ultrasonography, are associated with the regression effect on the thrombus following anticoagulation therapy. The present study focused on gastrocnemius muscle (GCM) thickness and the GCM's internal echogenic brightness. We examined the association with DVT regression following direct oral anticoagulants (DOACs) treatment.The prospective cohort study period was between October 2017 and August 2018. We enrolled 46 patients diagnosed with DVT by ultrasonography, who were aged >60 years old and treated with DOACs. Sarcopenia was evaluated using the Asian Working Group for Sarcopenia flowchart. The average DOACs treatment period was 94 days, and 29 patients exhibited thrombus regression. On univariate logistic regression analysis, sarcopenia, average GCM diameter index, and gastrocnemius integrated backscatter index were significantly associated with thrombus regression. In a multivariate model, only the average GCM diameter index correlated with thrombus regression.The average GCM diameter index is associated with DVT regression treated with DOACs. Considering the GCM diameter during DVT treatment can be a marker to make a decision for the treatment of DVT.


Subject(s)
Factor Xa Inhibitors/therapeutic use , Muscle, Skeletal/diagnostic imaging , Sarcopenia/diagnostic imaging , Venous Thrombosis/drug therapy , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Ultrasonography , Venous Thrombosis/diagnostic imaging
4.
Circ J ; 83(12): 2512-2519, 2019 11 25.
Article in English | MEDLINE | ID: mdl-31611537

ABSTRACT

BACKGROUND: Whether preoperative echocardiography improves postoperative outcomes is not well established, so we examined the value of echocardiographic assessment on the onset of postoperative heart failure (HF), and determining which patients benefitted most from undergoing echocardiography prior to major elective non-cardiac surgery.Methods and Results:We identified all patients aged 50 years and older who had major elective non-cardiac surgery, and excluded patients with previously identified severe cardiovascular disease. The primary endpoint was the onset of HF during hospitalization. A total of 806 patients were included in the analysis. During hospitalization, 49 patients (6%) reached the primary endpoint. Within the matched cohort, preoperative echocardiography was associated with a statistically significant decrease in postoperative HF (hazard ratio: 0.46, P=0.01). In subgroup analyses, age, sex, body surface area, hypertension, diabetes mellitus, prior HF, surgical type, chronic kidney disease, pulmonary disease, and malignancy influenced the association of echocardiography with postoperative HF. CONCLUSIONS: The use of echocardiography in elderly patients with certain risk factors was associated with improved postoperative outcomes. The basis for this finding remains to be determined; particularly whether echocardiography is simply a marker of a population with better outcomes or whether it leads to better management that improves outcomes.


Subject(s)
Echocardiography , Heart Failure/prevention & control , Preoperative Care , Surgical Procedures, Operative/adverse effects , Aged , Female , Heart Failure/diagnostic imaging , Heart Failure/epidemiology , Heart Failure/physiopathology , Humans , Incidence , Japan/epidemiology , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
5.
Circ J ; 82(8): 2103-2110, 2018 07 25.
Article in English | MEDLINE | ID: mdl-29709994

ABSTRACT

BACKGROUND: High prevalence of frailty and of diastolic dysfunction (DD) in heart failure and high mortality in frail adults have been noted. We characterized frailty by quantifying differences on echocardiography, and assessed the added prognostic utility of frailty and DD grade in an elderly population. METHODS AND RESULTS: One hundred and ninety-one patients ≥65 years who had at least 1 cardiovascular risk factor were prospectively recruited for clinically indicated echocardiography at the present institute. Weight loss, exhaustion, and deficits in physical activity, gait speed, and handgrip strength were used to categorize patients as frail (≥3 features), intermediately frail (1 or 2 features), or non-frail (0 features). DD grade ≥2 was defined as severe. Frailty was associated with larger left atrial volume, smaller stroke volume, and worse DD grade after adjustment for age. In a period of 14 months, 29 patients (15%) had cardiovascular events. The addition of frailty score and severe DD significantly improved the prognostic power of a model containing male gender (model 1, male gender, χ2=6.4; model 2, model 1 plus frailty score, χ2=16.7, P=0.004; model 3, model 2 plus severe DD, χ2=25.5, P=0.015). CONCLUSIONS: Both frailty and DD grade were significantly associated with future cardiovascular events in an elderly population with preserved ejection fraction and ≥1 risk factor of cardiovascular disease.


Subject(s)
Frail Elderly , Frailty/mortality , Heart Failure, Diastolic/epidemiology , Aged , Aged, 80 and over , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/etiology , Female , Frailty/diagnosis , Heart Failure, Diastolic/diagnosis , Humans , Male , Prevalence , Prognosis , Risk Factors
6.
Echocardiography ; 35(10): 1587-1595, 2018 10.
Article in English | MEDLINE | ID: mdl-30005132

ABSTRACT

AIM: To improve the prognosis of patients with heart failure, risk stratification in their early stage is important. We assessed whether the change in transmitral flow (TMF) velocity pattern during preload augmentation can predict future hemodynamic worsening in early-stage heart failure patients with impaired relaxation TMF pattern. METHODS: We designed a prospective cohort study that included 155 consecutive patients with impaired relaxation (IR) pattern at rest. Preload stress echocardiography was achieved using leg-positive pressure (LPP), and changes in TMF pattern during the LPP was observed during baseline echocardiographic examination. The patients whose TMF pattern developed to pseudonormal (PN) pattern throughout the study period were classified into the change to PN group, and patients whose TMF pattern stayed in IR pattern were classified into the stay in IR group. RESULTS: The median follow-up period was 17 months. The average age was 68 ± 11 years old, and 97 patients (63%) were male. Among 155 patients, 27 were classified into the change to PN group. A Cox proportional hazard analysis confirmed that the change in the peak atrial systolic TMF velocity during the LPP (ΔA, hazard ratio = 0.58 per 1SD; 95% CI = 0.39-0.88, P = 0.010) was the powerful independent predictor of change into PN pattern. Kaplan-Meier analysis revealed that the patients with ΔA ≤ -7 cm/s had more likely to develop into PN pattern than patients with ΔA > -7 cm/s (P = 0.001). CONCLUSIONS: Evaluation of a response in TMF during the LPP might provide an incremental diagnostic value to detect future overt heart failure in patients with early-stage heart failure.


Subject(s)
Disease Progression , Echocardiography, Stress/methods , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Hemodynamics/physiology , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies
7.
Cardiovasc Ultrasound ; 13: 34, 2015 Jul 25.
Article in English | MEDLINE | ID: mdl-26209244

ABSTRACT

BACKGROUND: The association of the tissue characteristics of carotid plaques with coronary artery disease has attracted interest. The present study compared the tissue characteristics of carotid plaques in patients with acute coronary syndrome (ACS) with those in patients with stable angina pectoris (SAP) using the iPlaque system, which is based on ultrasound integrated backscatter. METHODS AND RESULTS: Carotid ultrasound examinations were performed in 26 patients with ACS, and 38 age- and gender-matched patients with SAP. Neither plaque area nor maximal intima-media thickness differed significantly between the two groups. However, the average integrated backscatter value within the plaque was greater in the ACS patients than in the SAP patients. iPlaque analysis revealed that the percentage blue area (lipid pool) was greater in the ACS patients than in the SAP patients (43.4 ± 11.2 vs 18.3 ± 10.3%, p < 0.0001), and that the percentage green area (fibrosis) was lower in the ACS than in the SAP patients (7.5 ± 7.5% vs 20.7 ± 11.7%, p < 0.0001). CONCLUSIONS: The lipid component of carotid plaques is greater in ACS patients than in SAP patients. Our iPlaque system provides a useful and feasible method for the tissue characterization of carotid plaques in the clinical setting.


Subject(s)
Acute Coronary Syndrome/diagnostic imaging , Angina, Stable/diagnostic imaging , Carotid Artery Diseases/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Ultrasonography/methods , Acute Coronary Syndrome/complications , Aged , Algorithms , Angina, Stable/complications , Carotid Artery Diseases/complications , Female , Humans , Male , Reproducibility of Results , Sensitivity and Specificity , Software , Systems Integration
9.
J Am Soc Echocardiogr ; 34(9): 966-975.e2, 2021 09.
Article in English | MEDLINE | ID: mdl-33852960

ABSTRACT

BACKGROUND: Heart failure with recovered ejection fraction (HFrecEF) has been reported in several previous studies to have a better prognosis than heart failure with reduced ejection fraction (HFrEF). However, the factors associated with HFrecEF have not been identified. The aim of this study was to test the hypothesis that left atrial (LA) strain could help identify patients with recovered ejection fraction (EF) among those with heart failure (HF) with low EF on admission. METHODS: One hundred consecutive patients hospitalized for the first time for new-onset HF were enrolled. Patients were clinically diagnosed with HFrEF on admission (left ventricular EF < 40%) and received optimal treatment for HF. Twenty-eight patients improved to HFrecEF during 6 months of follow-up. RESULTS: Regarding clinical background, there were significantly more women and a lower rate of atrial fibrillation in the HFrecEF group than in the HFrEF group. In a multivariate logistic regression analysis, LA strain was an independent predictor of HFrecEF, even after adjustment for gender and left ventricular EF (odds ratio: 4.06; 95% CI: 2.04-8.07; P < .001). A cutoff value of 10.8% for LA strain showed high sensitivity (96%) and specificity (82%) in identifying HFrecEF in patients with HF presenting with low EF on admission. During a follow-up period of 24 ± 13 months, 31 patients (31%) had cardiovascular death or readmission for HF. Patients with reduced LA strain (<10.8%) had significantly shorter event-free survival than those with preserved LA strain (P = .02). CONCLUSIONS: LA strain is a useful indicator for predicting HFrecEF and should be considered as a routine measurement in patients with HFrEF on admission.


Subject(s)
Heart Failure , Ventricular Dysfunction, Left , Female , Heart Atria/diagnostic imaging , Heart Failure/diagnosis , Humans , Prognosis , Stroke Volume , Ventricular Function, Left
10.
Front Cardiovasc Med ; 7: 607825, 2020.
Article in English | MEDLINE | ID: mdl-33521062

ABSTRACT

Background: It is known that epicardial adipose tissue (EAT) volume is linked to cardiac dysfunction. However, it is unclear whether EAT volume (EATV) is closely linked to abnormal LV strain. We examined the relationship between EATV and global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in patients with preserved LV function. Methods: Notably, 180 consecutive subjects (68 ± 12 years; 53% men) underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into coronary artery disease (CAD) (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. GLS, GCS, and GRS were evaluated by 2-dimensional speckle tracking in patients with preserved left ventricular (LV) ejection fraction (LVEF) ≥50%. Results: First, GLS, but not GRS and GCS, was lower in the high EATV group though the LVEF was comparable to the low EATV group. Frequency of GLS ≤18 was higher in the high EATV group. Second, multiple regression model showed that EATV, age, male sex, and CAD, were determinants of GLS. Third, the cutoff points of EATV were comparable (~116-117 mL) in both groups. The cutoff of EATV ≥116 showed a significant correlation with GLS ≤18 in overall subjects. Conclusions: Increasing EATV was independently associated with global longitudinal strain despite the preserved LVEF and lacking obstructive CAD. Our findings suggest an additional role of EAT on myocardial systolic function by impaired LV longitudinal strain.

11.
Eur Heart J Cardiovasc Imaging ; 21(7): 796-804, 2020 07 01.
Article in English | MEDLINE | ID: mdl-31566217

ABSTRACT

AIMS: Risk assessment of developing cardiac involvement in systemic sarcoidosis can be challenging because of limited data. Recently, attention has been given to left ventricular and right ventricular (LV and RV) involvement in cardiac sarcoidosis (CS) and its prevalence, relevance, and prognostic value. The aim of this study was to assess the role of biventricular strain to predict prognosis in confirmed sarcoidosis patients. METHODS AND RESULTS: LV and RV longitudinal strains (LSs) were evaluated by 2D speckle tracking in 139 consecutive confirmed sarcoidosis patients without other pre-existing structural heart diseases, and 52 age- and gender-matched control subjects. The primary endpoint was CS-related events (cardiac death or development of cardiac involvement). Sarcoidosis without cardiac involvement had significantly lower LV and RV free wall LS compared with control subjects. Basal LS had a higher area under the curve for differentiation of sarcoidosis in patients without cardiac involvement compared to control (cut-off value: -18% with 89% sensitivity and 69% specificity). During a median period of 50 months, the occurrence of CS-related events was observed in 20 patients. In a multivariate analysis, basal LV LS and RV free wall LS were associated with the events [hazard ratio (HR) 0.72, P < 0.001 and HR: 0.83, P = 0.006, respectively]. Patients with impaired biventricular function had significantly shorter event-free survival than those with preserved biventricular function (P < 0.001). CONCLUSION: Deterioration of biventricular strain was associated with CS-related events. This information might be useful for clinical evaluation and follow-up in sarcoidosis.


Subject(s)
Sarcoidosis , Heart Ventricles , Humans , Prognosis , Proportional Hazards Models , Risk Assessment , Sarcoidosis/diagnostic imaging
12.
Int J Cardiovasc Imaging ; 35(4): 633-643, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30470971

ABSTRACT

Middle-aged marathon runners have an increased risk of developing atrial fibrillation (AF). A previous study described that repetitive marathon running was associated with left atrial (LA) dysfunction. However, whether this change is common in marathon runners and which runners are at risk of LA dysfunction remain unknown. The purpose of this study was to determine which factors could predict LA dysfunction. We prospectively examined 12 healthy amateur volunteers (9 males, 31 ± 8 years old) who participated in a full marathon. All echocardiographic measurements and speckle-tracking echocardiography were performed before and after the marathon. The endpoint was defined as reduced LA reservoir strain 1 day after the marathon (non-responder group). Seven participants were in the non-responder group. Age (35 ± 9 vs. 26 ± 2 years, p = 0.020), augmentation index (76 ± 12 vs. 55 ± 8, p = 0.002), and diastolic blood pressures (83 ± 11 vs. 70 ± 7 mmHg, p = 0.021) in the non-responder group were significantly higher compared with the responder group. In multivariate linear regression analysis, only the augmentation index was an independent predictor of reduced LA reservoir function after the marathon (ß = - 0.646, p = 0.023). The augmentation index was a predictive marker for reduction in LA reservoir function after a marathon in healthy amateur volunteers.


Subject(s)
Atrial Function, Left , Atrial Remodeling , Physical Endurance , Running , Adaptation, Physiological , Adult , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/etiology , Atrial Fibrillation/physiopathology , Echocardiography, Doppler , Female , Healthy Volunteers , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Time Factors , Young Adult
13.
J Am Soc Echocardiogr ; 32(10): 1286-1297.e2, 2019 10.
Article in English | MEDLINE | ID: mdl-31378421

ABSTRACT

BACKGROUND: Evaluation of diastolic dysfunction is crucial in determining elevated left atrial pressure. However, a validation of the long-term prognostic value of the newly proposed algorithm updated in 2016 has not been performed. The aim of the present study was to investigate the relative value of the updated 2016 diastolic dysfunction grading system for the incidence of readmission in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). METHODS: Two hundred thirty-two patients hospitalized with HF were retrospectively evaluated. Subjects were divided into two subgroups: those with HFrEF (n = 127) and those with HFpEF (n = 105). Readmission risk scores were calculated using the Yale Center for Outcomes Research and Evaluation HF, LACE index, and HOSPITAL scores. The primary end point was readmission following HF and cardiac death. RESULTS: Over a period of 24 months, 86 patients were either readmitted or died. Multivariate Cox analysis was performed on both the HFrEF and HFpEF groups. In the HFrEF group, both the 2009 and 2016 algorithms had superior incremental value for the association of the primary end point to several readmission risk scores. In the HFpEF group, only the 2016 algorithm led to significant improvement in association with the primary end point. The 2016 algorithm had incremental value over several readmission risk scores alone. CONCLUSIONS: The recommendations of the 2016 algorithm can be useful for readmission and cardiac mortality risk assessment in patients with HFrEF and HFpEF. The use of echocardiography to estimate elevated left atrial pressure appears to identify a higher risk group and may allow a more tailored approach to therapy.


Subject(s)
Echocardiography , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology , Aged , Algorithms , Diastole , Female , Hospitalization , Humans , Japan , Male , Prognosis , Retrospective Studies , Risk Assessment , Stroke Volume
14.
Int J Cardiovasc Imaging ; 34(2): 321-328, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28808846

ABSTRACT

The purpose of this study was to evaluate the relationship between age and frequency of left atrial appendage (LAA) morphology in patients with atrial fibrillation (AF) compared with sinus rhythm (SR). We enrolled 145 AF patients, and 199 SR patients for the control group without any cardiovascular disease. LAA volume index (LAAVi) and morphology were assessed by electrocardiogram-gated computed tomography angiography. LAA morphology was classified into "chicken wing" or "non-chicken wing" according to the previously described classification. There was no significant trend in frequency of non-chicken wing morphology among ages in the SR group (p = 0.36 for trend), whereas the frequency was negatively related to age in the AF group (p = 0.002 for trend). In multivariable logistic regression, age > 65 (odds ratio [OR] 0.42, p = 0.002) and duration of AF (OR 0.53, p = 0.010) and LAAVi (OR 0.62, p = 0.017) were independent factors of non-chicken wing LAA morphology in the AF group. LAA morphology is affected by age, especially in patients with AF. When we utilize non-chicken wing LAA morphology as a stroke risk factor in patients with AF, we should pay attention to their age.


Subject(s)
Atrial Appendage/diagnostic imaging , Atrial Fibrillation/diagnostic imaging , Computed Tomography Angiography , Coronary Angiography/methods , Multidetector Computed Tomography , Adult , Age Factors , Aged , Aged, 80 and over , Aging , Atrial Appendage/physiopathology , Atrial Fibrillation/complications , Atrial Fibrillation/physiopathology , Cardiac-Gated Imaging Techniques , Cross-Sectional Studies , Electrocardiography , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Predictive Value of Tests , Retrospective Studies , Risk Factors , Stroke/etiology
15.
Can J Cardiol ; 34(10): 1307-1315, 2018 10.
Article in English | MEDLINE | ID: mdl-30146462

ABSTRACT

BACKGROUND: It has been recognized that a comprehensive cardiac rehabilitation (CR) program improves mortality in patients with chronic heart failure. On the other hand, the magnitude of the improvement in exercise capacity after CR differs among individuals. The aim of this study was to assess the echocardiographic determinants of responders to CR using preload stress echocardiography. METHODS: We prospectively enrolled 58 chronic heart failure patients with reduced left ventricular ejection fraction (aged 62 ± 11 years; 69% male; left ventricular ejection fraction 43% ± 7%) who had received optimized medical treatment in a CR program for 5 months. We performed preload echocardiographic studies using leg positive pressure (LPP) to assess the echocardiographic parameters during preload augmentation. We defined 41 patients as a development cohort to assess the predictive value of echocardiographic variables. Next, we validated results in the remaining 17 patients as a validation cohort. RESULTS: In the development cohort, significant improvement in peak oxygen uptake (VO2) (>10%) after CR was observed in 58% patients. In a multivariable logistic regression model, the significant predictor of improvement in exercise capacity was right ventricular (RV) strain during LPP (odds ratio: 3.96 per 1 standard deviation; P = 0.01). An RV strain value of -16% during LPP had a good sensitivity of 0.79 and a specificity of 0.71 to identify patients with improvement in peak VO2. In the validation cohort, an optimal cutoff value of RV strain value was the same (area under the curve: 0.77, sensitivity: 0.78, specificity: 0.65). CONCLUSIONS: RV strain during LPP may be an echocardiographic parameter for assessing beneficial effects of CR.


Subject(s)
Cardiac Rehabilitation/methods , Exercise Therapy/methods , Heart Failure, Systolic/physiopathology , Heart Ventricles/diagnostic imaging , Stroke Volume/physiology , Ventricular Function, Right/physiology , Echocardiography, Doppler , Echocardiography, Stress , Female , Follow-Up Studies , Heart Failure, Systolic/diagnosis , Heart Failure, Systolic/rehabilitation , Heart Ventricles/physiopathology , Humans , Male , Middle Aged , Prognosis , Prospective Studies
16.
J Cardiol ; 71(3): 305-309, 2018 03.
Article in English | MEDLINE | ID: mdl-29100817

ABSTRACT

BACKGROUND: It is well known that warfarin inhibits the synthesis of vitamin K-dependent anticoagulants, including thrombin, protein C and S, and factor Xa, leading, paradoxically, to an initial hypercoagulable state. Edoxaban, a direct inhibitor of activated factor X is widely used for the treatment of acute venous thromboembolism (VTE). However, the effect of edoxaban on circulating coagulation factors, in patients with acute VTE, remains unknown. METHODS AND RESULTS: We enrolled 57 patients with acute VTE with/without pulmonary embolism treated with edoxaban (n=37) or warfarin (n=20) in a clinical setting. Before treatment and 2 weeks after treatment, we evaluated thrombotic burden using ultrasound or computed tomography angiography. We also evaluated thrombin generation, represented by prothrombin fragment F1+2; thrombus degradation, represented by D-dimer; and levels of anticoagulants, including protein C, protein S, and antithrombin III. Both edoxaban and warfarin treatment improved thrombotic burden and decreased prothrombin fragment F1+2, and D-dimer. Edoxaban treatment preserved protein C and protein S levels. In contrast, warfarin decreased protein C and protein S levels. Neither treatment affected antithrombin III. CONCLUSIONS: Edoxaban improves VTE while preserving protein C and protein S levels, thereby indicating that edoxaban improves thrombotic burden while maintaining levels of anticoagulants.


Subject(s)
Anticoagulants/pharmacology , Protein C/drug effects , Protein S/drug effects , Pyridines/pharmacology , Thiazoles/pharmacology , Venous Thromboembolism/drug therapy , Acute Disease , Aged , Antithrombin III/drug effects , Female , Humans , Male , Middle Aged , Pulmonary Embolism/drug therapy , Treatment Outcome , Venous Thromboembolism/blood , Warfarin/pharmacology
17.
Circ Cardiovasc Imaging ; 10(10)2017 10.
Article in English | MEDLINE | ID: mdl-29021259

ABSTRACT

BACKGROUND: The projected aortic valve area (AVAproj) at a normal transvalvular flow rate using dobutamine is helpful to determine the actual severity of aortic stenosis (AS) and to predict risk of adverse events in low-gradient AS cases with unclear surgical indication. Our study aimed to identify the independent and incremental value of preload stress echocardiography-derived AVAproj to predict outcomes in patients with preserved ejection fraction and low-gradient AS. METHODS AND RESULTS: We prospectively performed echocardiographic studies in 79 patients with low-gradient AS (age, 77±7 years; 30% men) with preload stress echocardiography using leg positive pressure. AVAproj was calculated using AVA and transvalvular flow rate at baseline and during leg positive pressure. The primary end point was the decision for aortic valve surgery or cardiac death. During a median period of 19 months, 23 patients had the decision for aortic valve surgery, and none died during follow-up. In a stepwise multivariable analysis, indexed AVAproj (AVAiproj; hazard ratio, 2.00 per 0.1 cm2/m2 decrease; 95% confidence interval, 1.36-2.96; P<0.001) was associated with the primary end point. Using a receiver operating characteristic curve analysis, the best cutoff value of AVAiproj for predicting cardiac events was <0.72 cm2/m2. By incorporating AVAiproj into AVAi at baseline, continuous net reclassification index for cardiac events was 0.48 (P=0.04). CONCLUSIONS: In patients with low-gradient AS, indexed AVAproj derived from preload stress echocardiography can be useful to predict risk of adverse events. The present article should be considered as a proof of concept study, and we think that larger multicenter studies are warranted.


Subject(s)
Aortic Valve Stenosis/diagnostic imaging , Aortic Valve/diagnostic imaging , Echocardiography, Stress , Stroke Volume , Ventricular Function, Left , Aged , Aged, 80 and over , Aortic Valve/physiopathology , Aortic Valve/surgery , Aortic Valve Stenosis/physiopathology , Aortic Valve Stenosis/surgery , Area Under Curve , Disease Progression , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Models, Cardiovascular , Predictive Value of Tests , Prospective Studies , ROC Curve , Severity of Illness Index , Time Factors
18.
JACC Cardiovasc Imaging ; 10(2): 118-126, 2017 02.
Article in English | MEDLINE | ID: mdl-27665160

ABSTRACT

OBJECTIVES: This study sought to assess the time course of presumptive tachycardia-induced cardiomyopathy and the predictors of left ventricular (LV) functional recovery in such patients. BACKGROUND: Tachycardia-induced cardiomyopathy is a potentially reversible cardiomyopathy with effective treatment of the tachyarrhythmia. However, cases without improvement of LV systolic function were found occasionally. The diagnosis of tachycardia-induced cardiomyopathy can be challenging, and the role of echocardiographic imaging in the prediction of LV functional recovery is limited. METHODS: LV segmental longitudinal strains (LS) were evaluated by 2-dimensional speckle tracking in 71 consecutive patients (65 ± 16 years; 61% men) with tachyarrhythmia and reduced left ventricular ejection fraction (LVEF) without any other known cardiovascular disease, and 30 age and sex-matched control subjects. Relative apical LS ratio (RALSR) was defined using the equation: average apical LS / (average basal LS + average mid LS) as a marker of strain distribution. RESULTS: Compared with control subjects, patients with tachyarrhythmia had significantly lower global LS. Improvement in LVEF within 6 months after treatment of index arrhythmia was observed in 41 patients, and LVEF did not improve in 30 patients. In univariate analysis, lower LVEF at baseline (hazard ratio: 0.59 per 1 SD; p = 0.04) and higher RALSR (hazard ratio: 11.2 per 1 SD; p < 0.001) were associated with no recovery in LVEF during follow-up. In a multivariate logistic regression model, the significant predictor of LV systolic functional recovery was RALSR (hazard ratio: 22.9 per 1 SD; p = 0.001). A RALSR of 0.61 was sensitive (71%) and specific (90%) in differentiating LV systolic functional recovery (area under the curve: 0.88). CONCLUSIONS: The RALSR was associated with LV systolic functional recovery. This information might be useful for clinical evaluation and follow-up in patients with reduced LVEF.


Subject(s)
Arrhythmias, Cardiac/therapy , Cardiomyopathies/diagnostic imaging , Echocardiography , Myocardial Contraction , Stroke Volume , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Function, Left , Aged , Aged, 80 and over , Area Under Curve , Arrhythmias, Cardiac/complications , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/physiopathology , Biomechanical Phenomena , Cardiomyopathies/etiology , Cardiomyopathies/physiopathology , Case-Control Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , ROC Curve , Recovery of Function , Reproducibility of Results , Stress, Mechanical , Treatment Outcome , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology
20.
Am J Cardiol ; 117(2): 226-32, 2016 Jan 15.
Article in English | MEDLINE | ID: mdl-26651451

ABSTRACT

Echocardiography now plays a central guiding role in the management of patients with atrial fibrillation (AF). However, the current guidelines mention little about the presence AF during the assessment of echocardiographic variables in the clinical setting. AF itself may impact on tricuspid annular plane systolic excursion (TAPSE) as a right ventricular systolic function compared with sinus rhythm (SR). The aim of this study was to compare and assess the echocardiographic parameters including TAPSE in patients with AF and SR. From January 1, 2013, to September 30, 2014, patients with AF without any cardiovascular disease were retrospectively evaluated using echocardiography. Age-, gender-, and left ventricular ejection fraction-matched patients with SR were selected from our database on the basis of a comprehensive history, physical examination, and echocardiographic findings. During the study period, we identified 239 patients with AF (74 ± 9 years; 65% men) and without any cardiac disease who underwent echocardiography. We also included 281 patients in the SR group (74 ± 8 years; 67% men). In all study subjects, TAPSE in AF was smaller than in SR regardless of age (17 ± 3 vs 20 ± 3 mm, p <0.001). In the stepwise multiple regression model, TAPSE was strongly associated with the presence of AF (standardized ß = -0.362, p <0.001) and stroke volume index (standardized ß = 0.173, p <0.001) after adjustment for age, gender, heart rate, left ventricular ejection fraction, and tricuspid regurgitant grade. In conclusions, patients with AF had lower TAPSE than those with SR regardless of age. When we assess TAPSE in the clinical setting, we must pay attention to the presence of AF.


Subject(s)
Atrial Fibrillation/physiopathology , Echocardiography/methods , Heart Rate/physiology , Stroke Volume , Tricuspid Valve Insufficiency/physiopathology , Tricuspid Valve/diagnostic imaging , Ventricular Function, Right/physiology , Aged , Atrial Fibrillation/complications , Atrial Fibrillation/diagnostic imaging , Female , Humans , Male , Prognosis , Retrospective Studies , Systole , Tricuspid Valve Insufficiency/complications , Tricuspid Valve Insufficiency/diagnostic imaging , Ventricular Function, Left
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