Impact of the Barthel Index Score and Prognosis on Patients Undergoing Transcatheter Aortic Valve Replacement and Surgical Aortic Valve Replacement.

BACKGROUND: Few studies have compared the Barthel Index (BI) score and postoperative outcomes of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). We aimed to examine the relationship between the BI score and postoperative outcomes in patients who underwent TAVR and SAVR.Methods and Results: The study included patients who underwent SAVR between January 2014 and December 2022 (n=293) and patients who underwent TAVR between January 2016 and December 2022 (n=312). We examined the risk factors for long-term mortality in the 2 groups. The mean (±SD) preoperative BI score was 88.7±18.0 in the TAVR group and 95.8±12.3 in the SAVR group. The home discharge rate was significantly lower in the SAVR than TAVR group. The BI score at discharge was significantly higher in the SAVR than in TAVR group (86.2 vs. 80.2; P<0.001). Significant risk factors for long-term mortality in the TAVR group were sex (P<0.001) and preoperative hemoglobin level (P=0.008), whereas those in the SAVR group were preoperative albumin level (P=0.04) and postoperative BI score (P=0.02). The cut-off point of the postoperative BI score determined by receiver operating characteristic curve analysis was 60.0. CONCLUSIONS: The BI score at discharge was a significant risk factor for long-term mortality in the SAVR group, with a cut-off value of 60.0.

Impact of Helicopter Transport on Reperfusion Times and Long-Term Outcomes in Acute Myocardial Infarction Patients in Rural Areas: A Report From the Mie Acute Coronary Syndrome Registry.

OBJECTIVE: Helicopter emergency medical services (HEMS) are effective for time-sensitive conditions, such as stroke and trauma. However, prognostic data on helicopter transport for acute myocardial infarction (AMI) patients are insufficient. METHODS: We registered 2,681 AMI patients in the Mie Acute Coronary Syndrome Registry and enrolled 163 patients from rural areas to HEMS base hospitals with HEMS or ground emergency medical services (GEMS). They were categorized into 4 groups according to the transportation method for interhospital transfer (direct HEMS: n = 52, direct GEMS: n = 54, interhospital HEMS: n = 32, and interhospital GEMS: n = 25). The primary end point was the emergency medical services (EMS) call-to-balloon time. The secondary end point was 2-year major adverse cardiac and cerebrovascular events. RESULTS: The direct HEMS group was younger than the direct GEMS group (P = .029). The EMS call-to-balloon time was shorter in the direct HEMS and interhospital HEMS groups than in each GEMS group (P = .015 and P = .046). The incidence of 2-year major adverse cardiac and cerebrovascular events tended to be lower in both HEMS groups than in each GEMS group. CONCLUSION: Direct HEMS for AMI in rural areas shortens the time from the EMS call to reperfusion when the transport distance is expected to exceed 30 km, which may result in a better patient prognosis. In addition, prehospital diagnostic modalities, such as 12-lead electrocardiography and echocardiography, may shorten the duration from the EMS call to reperfusion.

Prognostic role of bronchial asthma in patients with heart failure.

There are few reports investigating the relationship between bronchial asthma (BA) and heart failure (HF). We hypothesized BA may have impact on prognosis in patients with HF. Among 323 consecutive outpatients with HF, 191 patients without chronic obstructive pulmonary disease were analyzed. Twenty patients had BA, most of whom (80.0%) had preserved left ventricular ejection fraction (LVEF ≥ 50%). The use of ß-blockers was less frequent (55.0% vs 83.0%. p = 0.01), systolic blood pressure (133 ± 22 vs 120 ± 17 mmHg, p = 0.003), and heart rate (83 ± 14 vs 74 ± 15 bpm, p = 0.02) were higher in patients with BA than those without BA. During median follow up of 24 months, 45 (23.6%) experienced primary outcome defined as a composite of all-cause death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unexpected hospitalization due to HF. Multivariate Cox regression analysis revealed that the presence of BA was independently associated with the occurrence of primary outcome (hazard ratio 3.08, 95% CI 1.42-6.71, p = 0.004). In the subgroup analysis of patients with preserved LVEF, patients with BA exhibited worse outcomes (p = 0.03 by log-rank). Patients with HF complicated by BA, most of whom had preserved LVEF, exhibited worse outcomes than those without BA.

Comparison of anti-inflammatory effects of rivaroxaban vs. dabigatran in patients with non-valvular atrial fibrillation (RIVAL-AF study): multicenter randomized study.

Some experimental studies have shown that direct oral anticoagulants (DOACs) have anti-inflammatory effects. However, the interval changes in inflammatory markers in patients with non-valvular atrial fibrillation (AF) who receive DOACs remain unknown. Between July 2013 and April 2014, a total of 187 AF patients randomly assigned to receive rivaroxaban (n = 91) or dabigatran (n = 96) were assessed for eligibility. The levels of the following inflammatory markers were serially evaluated: high-sensitivity C-reactive protein, pentraxin-3, interleukin (IL)-1ß, IL-6, IL-18, tumor necrosis factor-α, monocyte chemotactic protein-1, growth and differentiation factor-15, and soluble thrombomodulin (sTM). The aim in this study was to evaluate the anti-inflammatory effects of rivaroxaban and dabigatran in patients with AF, in addition to the impact of markers on bleeding events. Finally, 117 patients (rivaroxaban: n = 55, dabigatran: n = 62) were included in the analysis at 12 months. Although the interval changes in sTM levels tended to be greater in the dabigatran group [0.3 (0-0.7) vs. 0.5 (0-1.0) FU/ml, p = 0.061], there were no significant differences in the interval changes in any inflammatory marker between 2 groups. There were no significant differences in bleeding events between 2 groups. The interval changes in sTM levels were significantly greater in patients with bleeding compared with those without [0.8 (0.5-1.3) vs. 0.4 (- 0.1-0.8) FU/ml, p = 0.017]. There were no significant differences in the interval changes in any inflammatory marker between rivaroxaban and dabigatran treatments in patients with AF. The increased levels of sTM after DOACs treatment might be related to bleeding events.

Penetration rate of the placement of a drug-eluting stent for the treatment of superficial femoral artery lesions in Japan.

Stent placement for treating superficial femoral artery (SFA) lesions has been approved. The Zilver PTX stent, a drug-eluting stent (DES) for treating SFA lesions, has been available in Japan since 2012. However, the penetration rate of this DES has not yet been reported. This prospective multicenter registry study enrolled 314 patients (354 limbs) to be treated by stent placement in 2014 (UMIN000011551). The primary endpoint was the measurement of the penetration rate of the DES. The secondary endpoints were measuring the freedom from restenosis, freedom from target lesion revascularization (TLR), freedom from major adverse limb event (MALE), and the survival rate at 12 months postoperatively. Female patients comprised 28% participants. The mean age was 73.1 ± 9.2 years. A total of 56% patients had diabetes mellitus (DM), 36% patients were receiving hemodialysis, and 30% used cilostazol at baseline. The mean lesion length was 156 ± 101 mm, and the percentage of TASC II C/D lesions was 58%. Critical limb ischemia (CLI) was observed in 32% limbs. The penetration rates of the Zilver PTX stent were only 8%. The primary patency rate was similar between DES and bare-metal stents (BMS) at 12 months postoperatively (77 vs. 84%, p = 0.52). In this study, the rates of freedom from restenosis, freedom from TLR, freedom from MALE, and the survival rate at 12 months postoperatively were 83, 86, 85, and 89%, respectively. The penetration rate of a first-generation DES placement for treating SFA lesions is low in Japan. On the other hand, BMS is well utilized and its primary patency is acceptable.

Antibody against immunoglobulin E contained in blood components as causative factor for anaphylactic transfusion reactions.

BACKGROUND: Determining the mechanism underlying the development of transfusion reactions is important in transfusion therapy. Two bags of fresh-frozen plasma obtained from a donor (index donor) were implicated in two cases of anaphylactic transfusion reactions. STUDY DESIGN AND METHODS: The serum prepared from the index donor plasma transfused into the second patient (Patient 2) was evaluated using cord blood-derived mast cells (CBMCs) incubated with Patient 2 plasma. The component in the serum required for the degranulation was determined and quantified by chromatography in combination with degranulation assay, Western blot analysis, and enzyme-linked immunosorbent assay. The component in the plasma required for CBMC sensitization was determined using human immunoglobulin (Ig)E or normal plasma in place of Patient 2 plasma in the assay. Sera collected from the index donor between 2001 and 2008 were examined for the CBMC degranulation factor. RESULTS: The donor serum activated CBMCs incubated with Patient 2 plasma. The IgG fraction of the donor serum induced degranulation of CBMCs sensitized with IgE or plasma containing a normal IgE concentration. The IgG anti-IgE at a concentration higher than 2200 ng/mL, which showed CBMC degranulation activity, was detected in the donor sera for at least 7 years. CONCLUSION: Transfusion of a high concentration of the anti-IgE in the donor plasma was suggested to induce mast cell degranulation in the patients leading to the development of anaphylactic transfusion reactions. Antibodies existing in not only the patient circulation but also the transfused blood might cause transfusion-induced anaphylaxis.

Prognostic value of serum parathyroid hormone level in acute decompensated heart failure.

BACKGROUND: Secondary hyperparathyroidism develops as a compensatory response to chronic heart failure (HF) and renal failure. The role of parathyroid hormone (PTH) level in acute decompensated HF remains unclear. The aim of this study was therefore to investigate the relationships among mortality, renal function, and serum PTH level in acute decompensated HF patients. METHODS AND RESULTS: A total of 266 consecutive patients admitted for acute decompensated HF without acute coronary syndrome (78±12 years; 48% male) were enrolled. Demographic, clinical, and laboratory characteristics were obtained on admission.During 1-year follow-up, 65 patients (24%) died. Serum PTH level on admission was within the normal range (10-65 pg/ml) in 108 patients (41%), of whom 39 (15%) had low-normal PTH (10-40 pg/ml). On Kaplan-Meier analysis all-cause mortality was significantly higher in patients with low-normal PTH than in those with high-normal (40-65 pg/ml) or high (>65 pg/ml) PTH (log-rank test). On univariate and multivariate Cox regression analysis, low-normal PTH was significantly associated with increased all-cause mortality (unadjusted HR, 2.88; 95% CI: 1.69-4.91; P<0.001; adjusted HR, 3.84; 95% CI: 1.54-9.57; P=0.004). CONCLUSIONS: In patients with acute decompensated HF resulting in hospitalization, low-normal PTH on admission is associated with increased all-cause mortality, regardless of renal function.

Left ventricular mass and valve performance after surgical and transcatheter aortic valve replacement: a single-center experience from Japan.

Background: There are few reports on the postoperative left ventricular mass (LVM), aortic valve area (AVA), and pressure gradient (PG) after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) in Japan. We aimed to compare the postoperative LVM, AVA, stroke volume (SV), PG, and long-term outcomes between patients undergoing SAVR and TAVR procedures from single center in Japan. Methods: This was a retrospective cohort study. We included 107 patients who underwent simple SAVR between January 2012 and May 2022 (SAVR group, n=107) and 274 who underwent TAVR between January 2016 and May 2022 (TAVR group, n=274). The overall mean follow-up periods was 28.8±25.9 months (median: 24 months; range, 0.03-117 months). Results: The aortic valve mean PG (mmHg) was significantly smaller in the TAVR group than in the SAVR group (P<0.001). The AVA index (cm2/m2) was significantly larger in the TAVR group than in the SAVR group (P<0.001). The SV index (mL/m2) was significantly smaller in the SAVR group than in the TAVR group (P=0.02). The LVM index (LVMI) (g/m2) was significantly smaller in the SAVR group than in the TAVR group (P<0.001). The incidence of mild or higher postoperative paravalvular leak (PVL) and pacemaker implantation were significantly higher in the TAVR group. The 5-year postoperative mortality, re-hospitalization, and major adverse cerebral and cardiovascular events (MACCEs) were significantly better in the SAVR group. Conclusions: The postoperative aortic valve PG, AVA, and SV were better in the TAVR group; however, LVM regression and postoperative outcomes were better in the SAVR group.

Cardiac Reversibility and Survival After Transcatheter Aortic Valve Implantation in Patients With Low-Gradient Aortic Stenosis.

Background Prognostic implications of transcatheter aortic valve implantation (TAVI) in low-gradient (LG) aortic stenosis (AS) remain controversial. The authors hypothesized that differences in cardiac functional recovery may solve this ongoing controversy. The aim was to evaluate clinical outcomes and the response of left ventricular (LV) function following TAVI in patients with LG AS. Methods and Results This multicenter retrospective study included 1742 patients with severe AS undergoing TAVI between January 2015 and March 2019. Patients were subdivided into low-flow (LF) LG, normal-flow (NF) LG, LF high-gradient, and NF high-gradient AS groups according to the mean gradient of the aortic valve (LG <40 mm Hg) and LV stroke volume index (LF <35 mL/m2). Outcomes and changes in echocardiographic parameters after TAVI were compared between the groups. A total of 227 patients (13%) had reduced ejection fraction, and 486 patients (28%) had LG AS (LF-LG 143 [8%]; NF-LG 343 [20%]). During a median follow-up period of 747 days, 301 patients experienced a composite end point of cardiovascular death and rehospitalization for cardiovascular events, which was higher in the LF-LG and NF-LG groups than in the high-gradient groups. LG AS was independently associated with the primary outcome (hazard ratio, 1.69; P<0.001). Among 1239 patients with follow-up echocardiography, LG AS showed less improvement in the LV mass index and LV end-diastolic volume compared with high-gradient AS after 1 year, while LV recovery was similar between the LF AS and NF AS groups. Conclusions LG AS was associated with poorer outcomes and LV recovery, regardless of flow status after TAVI. Careful evaluation of AS severity may be required in LG AS to provide TAVI within the appropriate time and advanced care afterward.

Disappearance of Atypical Gastric Mucosal Bleeding due to Heyde's Syndrome after Transcatheter Aortic Valve Implantation.

An 82-year-old man was admitted to our hospital due to dyspnea on exertion. Blood tests showed iron deficiency anemia, and echocardiography revealed severe aortic stenosis (AS). Considering the possibility of Heyde's syndrome, esophagogastroduodenoscopy was performed to confirm the presence or absence of gastrointestinal angiodysplasia. Endoscopy revealed multiple sites of mucosal bleeding in the stomach without angiodysplasia or mucosal erosion. Although it was an atypical endoscopic finding, we diagnosed gastric mucosal bleeding associated with Heyde's syndrome. Since no atypical blood vessels could be found, endoscopic treatment was not performed, and only transcatheter aortic valve implantation (TAVI) for aortic valve stenosis was performed. TAVI immediately improved the dyspnea on exertion, and follow-up endoscopy 4 months after TAVI showed the disappearance of the multifocal mucosal bleeding in the stomach. Heyde's syndrome is characterized by AS, acquired deficiency or dysfunction of von Willebrand factor, and gastrointestinal angiodysplasia; however, the exact diagnostic criteria have not been established. This is a case of mucosal bleeding due to Heyde's syndrome, without the typical endoscopic image of angiodysplasia. Cardiologists and gastroenterologists need to consider the possibility of Heyde's syndrome in AS patients with atypical gastrointestinal bleeding on endoscopy.

Combining chronic kidney disease with 201thallium/123iodine beta methyliodophenyl pentadecanoic acid dual myocardial single-photon emission computed tomography findings is useful for the evaluation of cardiac event risk.

OBJECTIVE: Chronic kidney disease is a noteworthy pathophysiology as a risk factor of cardiovascular disease. We investigated the usefulness of combining glomerular filtration rate and 201thallium(201TI)/123iodine-beta-methyliodophenyl pentadecanoic acid (123I-BMIPP) dual myocardial scintigraphic findings for predicting cardiac events. METHODS: Seventy-five patients suspected of coronary artery disease underwent 201TI/123I-BMIPP dual myocardial scintigraphy. Clinical and nuclear variables were included in the multivariate analysis for predicting hard events (cardiac death and nonfatal myocardial infarction) and soft events (unstable angina, heart failure, and coronary revascularization). Glomerular filtration rate was estimated by the modification of diet in renal disease formula. Kaplan-Meier analysis was performed to investigate the incremental prognostic value of glomerular filtration rate. RESULTS: During the mean follow-up period of 425 days, eight patients had hard events and 20 patients had soft events. Multivariate analysis revealed that glomerular filtration rate and the sum of total defect score in 123I-BMIPP image were independent predictors of total cardiac events, whereas sex, diabetes, glomerular filtration rate, and the number of abnormal segments in 201TI image were those of hard events. Kaplan-Meier analysis revealed that greater risk stratification was achieved by adding a glomerular filtration rate of lesser than 60 ml/min/1.73 m2 to the sum of the total defect score > or = 5 in the 123I-BMIPP image. Greater risk stratification for hard events was also achieved by adding a glomerular filtration rate of lesser than 30 ml/min/1.73 m2 to the number of abnormal segments > or = 2 in 201TI image. CONCLUSION: Better risk stratification can be achieved by adding glomerular filtration rate to 201TI/123I-BMIPP dual myocardial scintigraphic findings.

Plaque Volume and Morphology are Associated with Fractional Flow Reserve Derived from Coronary Computed Tomography Angiography.

AIM: Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) accurately diagnoses ischemic lesions of intermediate stenosis severity. However, significant determinants of FFRCT have not been fully evaluated. METHODS: This was a sub-analysis of the Treatment of Alogliptin on Coronary Atherosclerosis Evaluated by Computed Tomography-Based Fractional Flow Reserve trial. Thirty-nine diabetic patients (117 vessels) with intermediate coronary artery stenosis [percent diameter stenosis (%DS) ＜70%] in whom FFRCT was measured were included in this study. CCTA-defined, vessel-based volumetric and morphological characteristics of plaques were examined to determine their ability to predict FFRCT. RESULTS: Patient-based, multivariate linear regression analysis showed that hemoglobinA1c, triglycerides, and the estimated glomerular filtration rate were significant independent factors associated with FFRCT. Vessel-based, univariate linear regression analysis showed that the total atheroma volume (r=－0.233, p=0.01) and the percentage atheroma volume (PAV) (r=－0.284, p=0.002) as well as %DS (r=－0.316, p=0.006) were significant determinants of FFRCT. Among the plaque components, significant negative correlations were observed between FFRCT and low- (r=－0.248, p=0.007) or intermediate-attenuation plaque volume (r=－0.186, p=0.045), whereas calcified plaque volume was not associated with FFRCT. In the left anterior descending coronary artery (LAD), the plaque volume of each component was associated with FFRCT. CONCLUSIONS: Plaque volume, PAV, and %DS were significant determinants of FFRCT. Plaque morphology, particularly in LAD, was associated with FFRCT in diabetic patients with intermediate coronary artery stenosis.

Assessment of factors associated with measurability of fractional flow reserve derived from coronary computed tomography angiography in type 2 diabetic patients with intermediate coronary artery stenosis.

Recently, fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) (FFRCT) has been developed. However, FFRCT cannot be calculated for all patients from CCTA datasets. The purpose of the present study, therefore, was to evaluate the predictors that results in cases being inappropriate for FFRCT processing. This study was a sub-analysis of the TRACT trial, from which 50 patients were divided into 2 groups according to FFRCT measurability (measurable [group M] or not measurable [group N]) using CCTA examination at baseline. Thirty-nine (78%) patients comprised group M and 11 (22%) comprised group N. Heart rate at CCTA examination (72 beats/min vs. 63 beats/min; p = 0.007) and Agatston score (665 vs. 33; p = 0.002) in group N were significantly higher than those in group M. Multivariate logistic regression analyses revealed that heart rate at CCTA examination (OR 1.348 [95% CI 1.167-1.556]; p < 0.001) and Agatston score (OR 1.002 [95% CI 1.000-1.003]; p = 0.004) were significant, independent factors associated with non-measurability of FFRCT. The frequency of poor image quality was highest in patients with heart rate > 65 beats/min and Agatston score > 400 (p < 0.0001). In conclusions, high heart rate at the time of CCTA examination and higher Agatston score were associated with poor image quality that resulted in cases being inappropriate for FFRCT processing. Heart rate control at CCTA examination is necessary to acquire good-quality images required for computing FFRCT.

Role of radial strain and displacement imaging to quantify wall motion dyssynchrony in patients with left ventricular mechanical dyssynchrony and chronic right ventricular pressure overload.

Left ventricular (LV) deformation with ventricular septal shift is one of the most distinctive echocardiographic observations in patients with chronic right ventricular (RV) pressure overload (PO). However, little is known about the effects of RVPO on LV performance and regional synchrony. Accordingly, our objective was to test the hypothesis that chronic RVPO affects regional wall motion, synchronicity, and global LV function using a novel speckle-tracking approach to quantify and characterize regional LV wall motion dyssynchrony. Displacement and strain imaging echocardiographic studies were performed in 20 patients with RVPO from pulmonary arterial hypertension or pulmonic stenosis (mean age 53 +/- 16 years, New York Heart Association class 2.6 +/- 0.7, and peak RV systolic pressure 73 +/- 28 mm Hg) and 20 age-matched normal subjects (mean age 47 +/- 16 years). Segmental signals from 6 segments around the mid-LV short axis were defined as dyssynchronous if their changes were opposite to that of the global LV signal at each time frame, and overall LV dyssynchrony was calculated as the percentage of dyssynchrony in all 6 segments within the specified time interval from onset of QRS to the end of isovolumic relaxation. RVPO was associated with a large degree of regional dyssynchrony with paradoxical ventricular septal motion observed by displacement imaging (21 +/- 6%, p <0.05 vs control group), which was closely associated with LV eccentricity index (r = 0.79, p <0.05) and LV myocardial performance index with linear regression (r = 0.76, p <0.05). In contrast, strain imaging showed uniform segmental radial thickening in the RVPO group, which was similar to the control group, and suggests that there was no intrinsic LV contractile dyssynchrony. In conclusion, LV wall motion dyssynchrony assessed by displacement imaging, not intrinsic contractile dyssynchrony by strain imaging, coexists with LV chamber deformation with ventricular septal shift and is closely associated with impairment of LV performance.

Exaggerated hypertensive response to exercise in patients with diastolic heart failure.

Systolic load elevation during exercise prolongs left ventricular (LV) relaxation, compromises filling, and raises end-diastolic pressure, leading to reduced exercise tolerance. The aim of this study was to test the hypothesis that the hypertensive response to exercise is exaggerated in patients with diastolic heart failure (DHF). Echocardiograms and treadmill testing were performed in patients with DHF (n=20) and age-matched hypertension with LV hypertrophy (HTN; n=20). The Minnesota Living with Heart Failure Questionnaire was used to estimate quality of life (QOL). There were no differences in resting blood pressure or echocardiographic parameters between the groups. The maximum exercise time was significantly shorter in the DHF group than in the HTN group (6.0+/-3.0 vs. 12.5+/-2.5 min), and the peak systolic blood pressure during exercise was significantly higher in the DHF group (212+/-18 vs. 189+/-16 mmHg, p<0.05). After 4 weeks of treatment with candesartan, an angiotensin II receptor blocker (8 mg/d), peak systolic blood pressure during exercise decreased to 191+/-13 mmHg, maximum exercise time increased (10.4+/-3.0 min; p<0.05), and QOL improved in patients with DHF, while there was no change in patients with HTN, despite the similar resting blood pressure. In patients with DHF, systolic blood pressure markedly increased during exercise, and this was accompanied by impaired exercise tolerance and a decreased QOL, both of which were partly suppressed by blocking angiotensin II.

Hemodynamic characteristics of patients with diastolic heart failure and hypertension.

Diastolic heart failure (DHF) has different underlying pathophysiologic mechanisms. We sought to compare hemodynamic characteristics in DHF patients with or without hypertension. A conductance catheter with microtip-manometer was used to measure left ventricular (LV) function and hemodynamics in 28 DHF patients. After baseline measurements, nitroglycerin was infused to alter the loading condition and the measurements were repeated. At baseline, end-systolic pressure was higher and the time constant of LV relaxation (tau) was longer in hypertensive DHF patients. Patients in hypertensive DHF had lower LV-arterial coupling ratio than those in non-hypertensive DHF. The peak of loading sequence was in early systole in non-hypertensive DHF patients and in late systole in hypertensive DHF patients. Nitroglycerin decreased LV end-systolic pressure and end-diastolic volume in both groups. In non-hypertensive DHF, nitroglycerin significantly reduced stroke volume and shortened tau (59+/-11 vs. 54+/-10 ms, p<0.05) without any changes in the time to peak LV force, effective arterial elastance (E(a)), or LV-arterial coupling ratio. In contrast, in hypertensive DHF patients, nitroglycerin significantly reduced E(a) and shortened the time to peak LV force, resulting in an improved LV-arterial coupling ratio, preserved stroke volume and shortened tau (75+/-14 vs. 62+/-13 ms, p<0.05). In conclusion, LV relaxation was more prolonged in hypertensive DHF patients than non-hypertensive DHF patients, partly because of the different loading sequence. Changing the loading condition by nitroglycerin improved LV systolic and diastolic function in hypertensive DHF patients.

Patients with a hypertensive response to exercise have impaired left ventricular diastolic function.

An exaggerated increase in systolic blood pressure prolongs myocardial relaxation and increases left ventricular (LV) chamber stiffness, resulting in an increase in LV filling pressure. We hypothesize that patients with a marked hypertensive response to exercise (HRE) have LV diastolic dysfunction leading to exercise intolerance, even in the absence of resting hypertension. We recruited 129 subjects (age 63+/-9 years, 64% male) with a preserved ejection fraction and a negative stress test. HRE was evaluated at the end of a 6-min exercise test using the modified Bruce protocol. Patients were categorized into three groups: a group without HRE and without resting hypertension (control group; n=30), a group with HRE but without resting hypertension (HRE group; n=25), and a group with both HRE and resting hypertension (HTN group; n=74). Conventional Doppler and tissue Doppler imaging were performed at rest. After 6-min exercise tests, systolic blood pressure increased in the HRE and HTN groups, compared with the control group (226+/-17 mmHg, 226+/-17 mmHg, and 180+/-15 mmHg, respectively, p<0.001). There were no significant differences in LV ejection fraction, LV end-diastolic diameter, and early mitral inflow velocity among the three groups. However, early diastolic mitral annular velocity (E') was significantly lower and the ratio of early diastolic mitral inflow velocity (E) to E' (E/E') was significantly higher in patients of the HRE and HTN groups compared to controls (E': 5.9+/-1.6 cm/s, 5.9+/-1.7 cm/s, 8.0+/-1.9 cm/s, respectively, p<0.05). In conclusion, irrespective of the presence of resting hypertension, patients with hypertensive response to exercise had impaired LV longitudinal diastolic function and exercise intolerance.

Changes in coronary atherosclerosis, composition, and fractional flow reserve evaluated by coronary computed tomography angiography in patients with type 2 diabetes.

BACKGROUND: The use of coronary computed tomography angiography (CCTA) for noninvasive anatomic detection of coronary artery disease is increasing. Recently, fractional flow reserve (FFR) assessment using routinely acquired CCTA datasets (FFRCT) has been developed. However, there are no reports about changes in coronary atherosclerosis, composition, and FFRCT in patients with type 2 diabetes. METHODS: This prospective, multicenter, observational trial evaluated changes in coronary atherosclerosis after alogliptin therapy in patients with type 2 diabetes. Fifty-one patients with type 2 diabetes who underwent CCTA examination and having intermediate coronary artery stenosis were treated with 25 mg of alogliptin. After 48 weeks, CCTA examination was repeated. The primary endpoint was changes in FFRCT, and the secondary endpoint was changes in total atheroma volume (TAV) from the baseline to the 48-week follow-up. RESULTS: The FFRCT decreased from the baseline to follow-up, but not significantly. A significant increase in TAV (from 658.5 mm3 to 668.9 mm3, p = 0.048) was observed. Vessel volume tended to increase, whereas percentage atheroma volume and lumen volume did not change. A significant negative correlation was observed between percentage change in TAV and change in FFRCT (r = -0.185, p = 0.048). A significant increase in calcified plaques (p = 0.01) and a decrease in intermediate-attenuation plaques (p = 0.006) was observed. CONCLUSIONS: In Japanese patients with diabetes and intermediate coronary artery stenosis, alogliptin could not improve FFRCT or reduce atheroma volume, whereas the plaque composition changed. A progression of atheroma volume was associated with a reduction in FFRCT.

Effects of alogliptin on fractional flow reserve evaluated by coronary computed tomography angiography in patients with type 2 diabetes: Rationale and design of the TRACT study.

BACKGROUND: Patients with type 2 diabetes are at high risk for developing coronary artery disease (CAD). Noninvasive anatomic assessment by coronary computed tomography angiography (CCTA) is being increasingly used for detecting or excluding CAD. Recently, fractional flow reserve (FFR) using routinely acquired CCTA datasets (FFRCT) has been developed. Although intensive glycemic control can reduce the risk of microvascular complications, intensive glucose control does not seem to be beneficial in preventing major cardiovascular events when compared with standard therapy. However, it has been reported that dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherogenic effects in an animal model. In addition, DPP-4 inhibitors attenuate the progression of carotid intima-media thickness in patients with type 2 diabetes. Therefore, this study will be performed to evaluate the effects of alogliptin, a DPP-4 inhibitor, on coronary atherosclerosis using FFRCT in patients with type 2 diabetes. METHODS AND DESIGN: This study will be a prospective, non-randomized, multicenter trial performed in Japan. Patients with type 2 diabetes who have intermediate coronary artery stenosis (diameter stenosis <70%) as evaluated by CCTA will be treated with 25mg/day of alogliptin. After 48 weeks' treatment, CCTA will be repeated. The primary endpoint will be changes in FFRCT, and the secondary endpoint will be the change in plaque volume from baseline to the 48-week follow-up. CONCLUSION: This study will be the first multicenter trial to evaluate the effects of alogliptin on coronary atherosclerosis using the newly developed FFRCT as the primary endpoint, and the findings will clarify the anti-atherogenic effects of alogliptin.