Five-Year Transcatheter Aortic Valve Replacement Outcomes in Chronic Hemodialysis vs. Non-Hemodialysis Patients Using Balloon-Expandable Devices.

BACKGROUND: Based on the results of a clinical trial in Japan, transcatheter aortic valve replacement (TAVR) for hemodialysis (HD) patients gained approval; however, mid-term TAVR outcomes and transcatheter aortic valve (TAV) durability in HD patients remain unexplored.Methods and Results: We analyzed background, procedural, in-hospital outcome, and follow-up data for 101 HD patients and 494 non-HD patients who underwent TAVR using balloon-expandable valves (SAPIEN XT or SAPIEN 3) retrieved from Osaka University Hospital TAVR database. Periprocedural mortality and TAVR-related complications were comparable between HD and non-HD patients. However, Kaplan-Meier analysis revealed that HD patients had significantly lower survival rates (log-rank test, P<0.001). In addition, HD patients had significantly higher rates of severe structural valve deterioration (SVD) than non-HD patients (Gray test, P=0.038). CONCLUSIONS: TAVR in HD patients had comparable periprocedural mortality but inferior mid-term survival and TAV durability than in non-HD patients. Indications for TAVR in younger HD patients should be carefully determined, considering the possibility of a TAV-in-TAV procedure when early SVD occurs.

Prognostic Impact of Echocardiographic Diastolic Dysfunction on Outcomes in Patients With Heart Failure With Preserved Ejection Fraction　- Insights From the PURSUIT-HFpEF Registry.

BACKGROUND: Although diastolic dysfunction is important pathophysiology in heart failure with preserved ejection fraction (HFpEF), its prognostic impact in HFpEF patients, including those with atrial fibrillation (AF), remains to be elucidated.Methods and Results:We included the data for 863 patients (321 patients with AF) registered in a prospective multicenter observational study of patients with HFpEF. Patients were divided into 3 groups according to the 2016 ASE/EACVI recommendations. The primary endpoint was a composite of all-cause death or HF rehospitalization. Median age was 83 years, and 55.5% were female. 196 (22.7%) were classified with normal diastolic function (ND), 253 (29.3%) with indeterminate (ID) and 414 (48.0%) with diastolic dysfunction (DD). The primary endpoint occurred more frequently in patients with DD than in those with ND or ID (log-rank P<0.001 for DD vs. ND, and log-rank P=0.007 for DD vs. ID, respectively). Taking ND as the reference, multivariable Cox regression analysis revealed that DD (hazard ratio (HR): 1.57, 95% confidence interval (CI):1.06-2.32, P=0.024) was independently associated with the composite endpoint, whereas ID (HR: 1.28, 95% CI: 0.84-1.95, P=0.255) was not. DD was associated with the composite endpoint in both patients with and without AF. CONCLUSIONS: HFpEF patients classified with DD using the 2016 ASE/EACVI recommendations had worse clinical outcomes than those with ND or ID. DD may be considered a prognostic marker in patients with HFpEF regardless of AF.

Evaluation of Need for Implantable Cardioverter-Defibrillator by Thallium-201 Scintigraphy Among Japanese Patients With Prior Myocardial Infarction.

BACKGROUND: Identifying who among current Japanese patients with prior myocardial infarction (MI) would benefit from an implantable cardioverter-defibrillator (ICD) is imperative. Accordingly, this study seeks to determine whether single-photon emission computed tomography (SPECT) can help identify such patients. Methods and Results: This retrospective study enrolled 60 consecutive patients with prior MI who underwent stress thallium-201 SPECT and ICD implantation from February 2000 to October 2014. Occurrence of arrhythmic death and/or or appropriate ICD therapy, defined as shock or antitachycardia pacing for ventricular fibrillation or tachycardia, was identified until November 2016. During the median follow-up interval of 6.6 years, 18 (30%) patients experienced arrhythmic death and/or appropriate ICD therapy. Multivariate Cox proportional hazard regression analysis revealed that the summed stress score (SSS) [hazard ratio (HR)=1.14; P=0.005] and left ventricular ejection fraction (LVEF) at rest (HR=0.92; P=0.038) were significantly associated with the occurrence of arrhythmic events. Patients with SSS ≥21 and LVEF ≤30%, which were determined to be the best cutoff points, had significantly higher incidence of the arrhythmic events than the other patients (64% vs. 11%; HR=7.18; log-rank P=0.001). CONCLUSIONS: SSS using stress thallium-201 SPECT in combination with LVEF can help determine the need for ICD therapy among current Japanese patients with prior MI.

Clinical Influence and Predictors of Pacing-Induced Mechanical Asynchrony in Patients with Normal Cardiac Function with Ventricular Lead Placed in Non-Apical Position.

Right ventricular apical (RVA) pacing often causes left ventricular (LV) mechanical asynchrony, which is enhanced by impaired cardiac contraction and intrinsic conduction abnormality. However, data on patients with normal cardiac function and under RV non-apical (non-RVA) pacing are limited.We retrospectively investigated 97 consecutive patients with normal ejection fraction who received pacemaker implantation for atrioventricular block with the ventricular lead placed in a non-RVA position. We defined mechanical asynchrony as discoordinate contraction between opposing regions of the LV wall evaluated by echocardiography. Asynchrony was detected in 9 (9%) patients at baseline and in 38 (39%) under non-RVA pacing (P < 0.001). Asynchrony at baseline was significantly associated with complete left bundle branch block (CLBBB) [odds ratio (OR) = 20.8, P < 0.001]. Asynchrony under non-RVA pacing was significantly associated with left anterior fascicular block (LAFB) (OR = 7.14, P < 0.001) and CLBBB (OR = 13.3, P = 0.002) at baseline. New occurrence of asynchrony was significantly associated with LAFB at baseline (OR = 5.88, P = 0.001). During a median follow-up period of 4.8 years, the incidence of device-detected atrial fibrillation (AF) was more frequent in patients who developed asynchrony than in those who did not (53.3% versus 27.5%, hazard ratio = 2.17, 95% confidence interval = 1.02-4.61, P = 0.03).In patients with normal cardiac function, LAFB at baseline was significantly associated with new occurrence of mechanical asynchrony under non-RVA pacing. Abnormal contraction had a significant influence on the incidence of device-detected AF.

Angioplasty of the Occluded Persistent Sciatic Artery Using the Retrograde Approach from Superficial Femoral Artery.

Persistent sciatic artery is a rare developmental anomaly prone to atherosclerotic disease. We present a case of successful endovascular therapy for left persistent sciatic artery that was occluded at the distal site. The angioplasty was performed with both antegrade approach from contralateral common femoral artery and retrograde approach from ipsilateral superficial femoral artery. The guidewire was advanced via collateral channel and crossed through the lesion retrogradely. Rendez-vous technique was performed, and the lesion was successfully dilated by balloon inflation. Angioplasty of occluded sciatic artery can be performed successfully and effectively using the collateral channel.

Risk Factors for Progression of Degenerative Aortic Valve Disease in the Japanese- The Japanese Aortic Stenosis Study (JASS) Prospective Analysis.

BACKGROUND: Because of ethnic difference in the risk of degenerative aortic valve disease (DAVD), risk factors should be clarified in each race to establish prophylactic strategies for severe aortic valve stenosis (AS). METHODS AND RESULTS: This study prospectively followed 359 Japanese subjects with DAVD and age ≥50 years for 3 years. As both patients with peak aortic transvalvular flow velocity ≥2 m/s and <2 m/s were enrolled, subgroup analysis was also conducted. Most patients were under treatment for their comorbidities. The use of warfarin, but none of the traditional risk factors for atherosclerosis, was related to greater reduction in aortic valve area indexed to body surface area (iAVA). In patients with peak aortic transvalvular flow velocity <2 m/s, the use of an angiotensin-receptor blocker (ARB) was associated with less decrease in iAVA. In patients with peak velocity ≥2 m/s, changes in iAVA were not related to any baseline characteristics, but peak velocity was less increased under treatment with an angiotensin-converting enzyme inhibitor (ACEI). CONCLUSIONS: In Japanese, the use of warfarin may exacerbate DAVD, and augmented management of atherosclerotic risk factors beyond the recommendations in the current guidelines is unlikely to exert additional benefit. The prescription of ARB for DAVD patients before the development of AS or ACEI after the development of AS may be useful.

Endovascular aortic repair increases vascular stiffness and alters cardiac structure and function.

BACKGROUND: Endovascular aortic repair (EVAR) is performed in patients with thoracic or abdominal aortic aneurysm because it is less invasive than conventional open repair. However, the effects of EVAR on vascular and cardiac function remain to be clarified. METHODS AND RESULTS: We studied the effects of EVAR on several outcome variables in 40 consecutive patients undergoing EVAR for abdominal and/or thoracic aneurysm with preserved ejection fraction. Echocardiography and brachial-ankle pulse wave velocity (baPWV) data were collected before, 1 week, and 1 year after EVAR. Although no changes in blood pressure were found, baPWV, left ventricular mass index (LVMI), and left atrial volume index were significantly elevated at both post-op time periods after EVAR compared with baseline data. The changes in LVMI correlated with those in baPWV (R=0.32, P<0.05). Among the 22 patients who were successfully followed up, 13 showed deterioration in exercise tolerance 1 year after EVAR. Diastolic wall strain, an index for LV distensibility, was lower at baseline in patients with worsening exercise tolerance than in those with unchanged tolerance. CONCLUSIONS: EVAR increased vascular stiffness and induced LV hypertrophy and diastolic dysfunction without a corresponding elevation of blood pressure in the acute and chronic phases. In addition, low LV distensibility at baseline was associated with the impairment of exercise tolerance. EVAR-induced stiffness of arteries leads to limited clinical symptoms.

Diverse distribution patterns of segmental longitudinal strain are associated with different clinical features and outcomes in dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) presents with diverse clinical courses, hardly predictable solely by the left ventricular (LV) ejection fraction (EF). Longitudinal strain (LS) offers distinct information from LVEF and exhibits various distribution patterns. This study aimed to evaluate the clinical significance of LS distribution patterns in DCM. METHODS: We studied 139 patients with DCM (LVEF ≤ 35%) who were admitted for heart failure (HF). LS distribution was assessed using a bull's eye map and the relative apical LS index (RapLSI), calculated by dividing apical LS by the sum of basal and mid-LS values. We evaluated the associations of LS distribution with cardiac events (cardiac death, LV assist device implantation, or HF hospitalization) and LV reverse remodeling (LVRR), as indicated by subsequent LVEF changes. RESULTS: Twenty six (19%) and 29 (21%) patients exhibited a pattern of relatively apical impaired or preserved LS (defined by RapLSI < 0.25 or > 0.75, signifying a 50% decrease or increase in apical LS compared to other segments), and the remaining patients exhibited a scattered/homogeneously impaired LS pattern. The proportion of new-onset heart failure and LVEF differed between the three groups. During the median 595-day follow-up, patients with relatively-impaired apical LS had a higher rate of cardiac events (both log-rank p < 0.05) and a lower incidence of LVRR (both p < 0.01) compared to patients with other patterns. RapLSI was significantly associated with cardiac event rates after adjusting for age, sex, and new-onset HF or global LS. CONCLUSION: DCM patients with reduced EF and distinct distribution patterns of impaired LS experienced different outcomes.

A novel heart failure mice model of hypertensive heart disease by angiotensin II infusion, nephrectomy, and salt loading.

Although the mouse heart failure (HF) model of hypertensive heart disease (HHD) is useful to investigate the pathophysiology and new therapeutic targets for HHD, the model using simple experimental procedures and stable phenotypes has not been established. This study aimed to develop a novel mouse HF model of HHD by combining salt loading and uninephrectomy with ANG II infusion. Eight-week-old C57BL/6 male mice were treated with ANG II infusion (AT), ANG II infusion and uninephrectomy (AN), ANG II infusion and salt loading (AS), or ANG II infusion, uninephrectomy, and salt loading (ANS). Systolic blood pressure was significantly elevated and left ventricular (LV) hypertrophy was found in AT, AN, AS, and ANS mice, and there were no significant differences in those parameters between the four groups. At 6 wk after the procedures, only ANS mice showed significant decreases in LV fractional shortening and increases in lung weight with a high incidence. This phenotype was reproducible, and there were few perioperative or early deaths in the experimental procedures. Severe LV fibrosis was found in ANS mice. Oxidative stress was enhanced and small GTPase Rac1 activity was upregulated in the hearts of ANS mice. After the addition of salt loading and uninephrectomy to the ANG II infusion mouse model, cardiac function was significantly impaired, and mice developed HF. This might be a novel and useful mouse HF model to study the transition from compensated LV hypertrophy to HF in HHD.

Left ventricular stiffening as therapeutic target for heart failure with preserved ejection fraction.

The high prevalence of patients with heart failure (HF) with preserved ejection fraction (HFpEF) has highlighted the pivotal role of diastolic function in the development of HF. Abnormalities of diastolic function induce elevated left ventricular (LV) end-diastolic pressure, which leads to pulmonary edema and the symptoms of HF because the LV, left atrium and the pulmonary veins form 1 chamber while the mitral valve is opening. Thus, LV diastolic dysfunction results in the development of HF, in particular, HFpEF. LV stiffness mainly contributes to the transition to HFpEF, but noninvasive assessment and the therapeutic strategy for LV stiffness have not been fully established. This review will focus on the contribution of LV passive stiffness to the development of HFpEF and on the evaluation and treatment of LV stiffening based on insights gained from a hypertensive HFpEF animal model we have developed.

Early experiences of transcatheter aortic valve replacement in Japan.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a new alternative treatment with acceptable early results for patients with aortic valve stenosis considered to be inoperable. The first TAVR was performed in Japan in October 2009, and a total of 51 have been performed up to February 2012. METHODS AND RESULTS: Because it is not possible to disclose details for 36 patients at the time of writing due to ongoing clinical trials, the early and mid-term results of 15 patients are presented for the Edwards SAPIEN valves. Age was 83.4 ± 6.1 years. Mean pressure gradient and aortic valve area were 60.3 ± 21.1 mmHg and 0.64 ± 0.19 cm(2), respectively. Left ventricular ejection fraction was 55.5 ± 15.4%. The Logistic EuroSCORE, EuroSCORE II, and Society of Thoracic Surgeons score were 28.5 ± 21.5%, 11.1 ± 15.8%, and 10.0 ± 7.4%, respectively. All of the procedures were successful and did not require conversion to surgery. Perioperative stroke did not occur, although pacemakers were implanted in 2 patients (13.3%). At discharge, mean pressure gradient and aortic valve area were improved to 10.8 ± 4.4 mmHg and 1.77 ± 0.36 cm(2), respectively. Except for 1 patient who died of cancer 7 months after operation, all patients were alive at the time of writing (11-848 days after procedure; mean follow-up period, 184 days). CONCLUSIONS: Satisfactory early and mid-term results have been achieved with TAVR, indicating that this is a good alternative to treat aortic valve stenosis.

Impact of electrocardiogram-gated multi-slice computed tomography-based aortic annular measurement in the evaluation of paravalvular leakage following transcatheter aortic valve replacement: the efficacy of the OverSized AortiC Annular ratio (OSACA ratio) in TAVR.

BACKGROUND: Even mild paravalvular leakage (PVL) after transcatheter aortic valve replacement (TAVR) is associated with increased late mortality. Electrocardiogram-gated multi-slice computed tomography (MSCT) enables detailed aortic annulus assessment. We describe the impact of MSCT for PVL following TAVR. METHODS: Congruence between the prosthesis and annulus diameters affects PVL; therefore, we calculated the OverSized AortiC Annular ratio (OSACA ratio) and OSACA (transesophageal echocardiography, TEE) ratio as prosthesis diameter/annulus diameter on MSCT or TEE, respectively, and compared their relationship with PVL ≤ trace following TAVR. RESULTS: Of 36 consecutive patients undergoing TAVR (Group A), the occurrence of PVL ≤ trace (33.3%) was significantly related to the OSACA ratio (p = 0.00020). In receiver-operating characteristics analysis, the cutoff value of 1.03 for the OSACA ratio had the highest sum of sensitivity (75.0%) and specificity (91.7%; AUC = 0.87) with significantly higher discriminatory performance for PVL as compared to the OSACA (TEE) ratio (AUC = 0.69, p = 0.028). In nine consecutive patients (Group B) undergoing TAVR based on guidelines formulated from our experience with Group A, PVL ≤ trace was significantly more frequent (88.9%) than that in Group A (p = 0.0060). CONCLUSIONS: The OSACA ratio has a significantly higher discriminatory performance for PVL ≤ trace than the OSACA (TEE) ratio, and aortic annular measurement from MSCT is more accurate than that from TEE.

Ca2+ entry mode of Na+/Ca2+ exchanger as a new therapeutic target for heart failure with preserved ejection fraction.

AIMS: Left ventricular (LV) fibrosis and stiffening play crucial roles in the development of heart failure with preserved ejection fraction (HFPEF). Plasma level of digitalis-like factors (DLFs) is increased in patients with hypertension, a principal underlying cardiovascular disease of HFPEF. Digitalis-like factors inhibit ion-pumping function of Na(+)/K(+)-ATPase and activate the Ca(2+) entry mode of Na(+)/Ca(2+) exchanger (NCX). Digitalis-like factors are known to promote collagen production in fibroblasts. The aim of this study was to explore whether the pharmacological inhibition of the NCX entry mode is effective in the prevention of LV fibrosis and in the development of HFPEF. METHODS AND RESULTS: (i) Dahl salt-sensitive rats fed 8% NaCl diet from age 6 weeks served as hypertensive HFPEF model. In this model, 24 h urine excretion of DLFs was greater than that in the age-matched control at compensatory hypertrophic and heart failure stages. (ii) Continuous administration of ouabain for 14 weeks developed LV fibrosis without affecting blood pressure in Sprague-Dawley rats. (iii) Ouabain elevated intracellular Ca(2+) concentration through the entry of extracellular Ca(2+), increased the phosphorylation level of p42/44 mitogen-activated protein kinases, and enhanced (3)H-proline incorporation in cardiac fibroblast; and SEA0400, the inhibitor of the NCX entry mode, suppressed these effects. (iv) In the HFPEF model, administration of SEA0400 at subdepressor dose improved the survival rate in association with the attenuation of LV fibrosis and stiffening. CONCLUSION: Digitalis-like factors and the subsequently activated NCX entry mode may play an important role in the development of hypertensive HFPEF, and the blockade of the NCX entry mode may be a new therapeutic strategy for this phenotype of heart failure.

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.

Left ventricular mechanics following restrictive mitral annuloplasty for functional mitral regurgitation: two-dimensional speckle tracking echocardiographic study.

BACKGROUND: Restrictive mitral annuloplasty (RMA) is widely employed for patients with functional mitral regurgitation (MR). Its improvement of left ventricular (LV) function has been demonstrated by only a gradual increase in LV ejection fraction (EF) in the chronic phase. However, the detailed evaluation of changes in LV function has not been fully elucidated in functional MR patients before and after RMA. Therefore, we performed two-dimensional speckle tracking echocardiography (2D-STE), which enables accurate evaluation of myocardial deformation and rotation that are undetectable by conventional echocardiography. METHODS: We studied 13 patients (mean age 61 ± 10 years) with functional MR associated with cardiomyopathy undergoing RMA. In addition to conventional echocardiographic measurements, 2D-STE was performed to measure peak systolic radial (RS), circumferential (CS), and longitudinal (LS) strains and twist before and 4 ± 2 weeks after surgery. LV twist was defined as the difference between the apical and basal rotations. RESULTS: After RMA, EF and LS remained unchanged, but RS and CS were significantly improved at the mid-LV (RS, 20.6 ± 10.8 vs 24.5 ± 11.6%; CS, -9.6 ± 5.2 vs -12.8 ± 5.6%) and at the apex (RS, 15.0 ± 12.2 vs 18.7 ± 8.6%; CS, -4.4 ± 3.0 vs -7.8 ± 4.8%). RS and CS were unchanged at the base. The apical and basal rotations changed significantly, from 3.5°± 0.7° to 9.2°± 2.1°, and -2.1°± 0.7° to -3.8°± 1.0°, respectively. Consequently, the LV twist increased significantly, from 5.6°± 1.0° to 13.0°± 1.9°. CONCLUSIONS: Radial and circumferential strains and LV twist increased significantly in the early postoperative period in functional MR patients after RMA and concomitant procedures.

A Risk Model for 1-Year Mortality After Transcatheter Aortic Valve Replacement From the J-TVT Registry.

Background: Although transcatheter aortic valve replacement (TAVR) has demonstrated favorable outcomes in randomized studies, there remains a sizable group of patients in whom TAVR may be futile. Characterizing the survival rate in a wide array of patients undergoing TAVR can help develop effective strategies for improving the allocation of medial resources. Objectives: The aim of this study was to develop a risk model to estimate 1-year mortality after TAVR from a representative nationwide registry in Japan. Methods: The J-TVT (Japan Transcatheter Valve Therapies) registry contains complete data, including 1-year outcomes, on patients undergoing TAVR in Japan. A total of 17,655 patients underwent TAVR between 2013 and 2018. They were randomly divided into 2 groups in a 7:3 ratio to form a derivation cohort of 12,316 patients and a validation cohort of 5,339 patients. A risk model was constructed for 1-year mortality in the derivation cohort, and its discrimination and calibration were assessed in the validation cohort. Results: The mean age of all registered patients was 84.4 years, and 68.8% were women. The mean body size area was 1.43 m2, and the mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 7.3%. The estimated 1-year survival was 91.8%; 202 and 1,316 deaths were observed at 30 days and 1 year, respectively; The estimated C index for the developed model was 0.733 (95% CI: 0.709-0.757) in the validation cohort, with good calibration. Conclusions: A prediction model for 1-year survival following TAVR derived from a national clinical database performed well and should aid physicians managing TAVR patients.

Pathophysiological evaluations of initial plaque development after heart transplantation via serial multimodality imaging and cytokine assessments.

BACKGROUND: Detailed morphological characteristics of de novo and donor-transmitted plaques and the association of serum T-lymphocyte cytokine levels with plaque progression of coronary allograft vasculopathy within 1 year after heart transplantation are unknown. METHODS: In this retrospective analysis of data in a prospectively maintained database, 40 heart transplant recipients were included. We performed serial 3 vessel optical coherence tomography and intravascular ultrasound analyses, at the 8 week (baseline) and 12 month post-transplantation follow-ups, and serum cytokine measurements (n = 23). The correlation between serum cytokines and Δplaque burden (between baseline and follow-up) was evaluated depending on plaque morphology. RESULTS: Thirteen de novo plaques (maximum intimal thickness ≥0.5 mm at the 12 month follow-up without plaques at baseline) were identified in 8 recipients, and 31 donor-transmitted plaques (maximum intimal thickness ≥0.5 mm at baseline) were detected in 17 recipients. Compared with donor-transmitted plaques, the Δplaque burden in the de novo plaques, with mainly fibrous morphology, was high (38.8% [29.6%-41.2%] vs 8.7% [1.33%-13.6%], p < 0.001). Stratification of the morphology of donor-transmitted plaques revealed that the Δplaque burden in fibrous plaques (10.6% [7.0%-18.0%]) was similar to that in fibroatheroma (10.3% [8.7%-23.8%]). Serum interleukin-31 levels at baseline correlated with fibrous plaque proliferation (r = 0.73, p = 0.007) even under immunosuppressive conditions, whereas other cytokines (interleukin-1ß, interleukin-17, and interferon-gamma) were mostly undetectable. CONCLUSIONS: Intimal fibrous proliferation contributed to the progression of donor-transmitted and de novo plaques. Serum interleukin-31 levels at baseline may contribute to intimal fibrous proliferation within 1 year after heart transplantation.

Diabetic retinopathy is associated with impaired left ventricular relaxation.

BACKGROUND: Diabetic retinopathy (DR) is an independent predictor of heart failure (HF) in patients with diabetes mellitus (DM). However, it is unclear how DR is related to the development of HF. We hypothesized that DR is associated with left ventricular (LV) diastolic dysfunction, which is well recognized to subsequently result in HF. METHODS AND RESULTS: Data were collected in 63 consecutive patients with DM and LV ejection fraction (EF) ≥50%. Patients were excluded if they had HF diagnosed according to the modified Framingham criteria. Doppler echocardiographic indices including peak early-diastolic mitral annular movement velocity (E') were obtained in each patient.We also assessed the diastolic index of echocardiographic color kinesis (CK-DI), which proportionally decreases with LV relaxation abnormality independently of LV filling pressure, as recently published. The DM patients were divided into groups without (DM-N; n = 30) and with (DM-DR; n = 33) DR. Age, gender, LV end-diastolic dimension, EF, E/A ratio of the transmitral flow velocity curves, E', and E/E' were not different between DM-N and DM-DR. However, CK-DI was significantly lower in DM-DR than DM-N. CONCLUSIONS: DR is associated with LV diastolic dysfunction, and this may at least in part explain the increased incidence of HF in DM patients with DR.