Rediscovery of the implication of albuminuria in heart failure: emerging classic index for cardiorenal interaction.

The development of new drugs and device therapies has led to remarkable advancements in heart failure (HF) treatment in the past couple of decades. However, it becomes increasingly evident that guideline-directed medical therapy cannot be one-size-fits-all across a wide range of ejection fractions (EFs) and various aetiologies. Therefore, classifications solely relying on EF and natriuretic peptide make optimization of treatment challenging, and there is a growing exploration of new indicators that enable efficient risk stratification of HF patients. Particularly when considering HF as a multi-organ interaction syndrome, the cardiorenal interaction plays a central role in its pathophysiology, and albuminuria has gained great prominence as its biomarker, independent from glomerular filtration rate. Albuminuria has been shown to exhibit a linear correlation with cardiovascular disease and HF prognosis in multiple epidemiological studies, ranging from normal (<30 mg/g) to high levels (>300 mg/g). However, on the other hand, it is only recently that the details of the pathological mechanisms that give rise to albuminuria have begun to be elucidated, including the efficient compaction/tightening of the glomerular basement membrane by podocytes and mesangial cells. Interestingly, renal disease, diabetes, and HF damage these components associated with albuminuria, and experimental models have demonstrated that recently developed HF drugs reduce albuminuria by ameliorating these pathological phenotypes. In this review, facing the rapid expansion of horizons in HF treatment, we aim to clarify the current understanding of the pathophysiology of albuminuria and explore the comprehensive understanding of albuminuria by examining the clinically established evidence to date, the pathophysiological mechanisms leading to its occurrence, and the outcomes of clinical studies utilizing various drug classes committed to specific pathological mechanisms to put albuminuria as a novel axis to depict the pathophysiology of HF.

Nocturnal Hypertension and Left Ventricular Diastolic Dysfunction in Patients With Diabetes With the Absence of Heart Failure: Prospective Cohort HSCAA Study.

BACKGROUND: Diabetes is an important risk factor for heart failure (HF) and is associated with left ventricular (LV) diastolic dysfunction. However, diabetic comorbid conditions, such as nocturnal hypertension, as predictors of diastolic dysfunction are not known in the absence of an HF period. The present study was conducted as the longitudinal examination of the predictive value of nocturnal hypertension profiles on the progression of LV diastolic dysfunction in patients with and without diabetes without HF. METHODS: The subjects (154 diabetes and 268 nondiabetes) in the absence of HF were followed for 36.8±18.2 months. The relationships among the patterns of nocturnal hypertension and the outcome of LV diastolic dysfunction, defined as an increase in E/e'>14, were investigated in the patients with and without diabetes. RESULTS: The interaction effect of the diabetes status and the patterns of nocturnal hypertension on the hazard rate of the occurrence of E/e'>14 was statistically significant (P=0.017). Kaplan-Meier analysis results revealed that patients with diabetes with nondipper (P=0.021 versus dipper) and riser (P=0.006 versus dipper) had a greater risk for a diastolic dysfunction event. Furthermore, multivariable Cox proportional hazards analysis revealed that nondipper (hazard ratio, 4.56 [95% CI, 1.49-13.96]; P=0.007) and riser (hazard ratio, 3.89 [95% CI, 1.31-11.57]; P=0.014) patterns were associated with elevated risk of the outcome of LV diastolic dysfunction. In contrast, no similar significant associations were found in patients without diabetes. CONCLUSIONS: During the absence of HF periods, nocturnal hypertension is an important predictor for the progression of LV diastolic dysfunction in patients with diabetes.

Hypoxia-inducible factor-prolyl hydroxylase inhibitor Roxadustat (FG-4592) reduces renal fibrosis in Dahl salt-sensitive rats.

OBJECTIVE: Although hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors have been developed for the treatment of renal anemia, their effects on cardiac and renal dysfunction remain unknown. We previously reported on Dahl salt-sensitive rats, in a rat model of salt-sensitive hypertension, that exhibited anemia and impaired expression of duodenal iron transporters after the development of hypertensive cardiac and renal dysfunction. Therefore, we investigated the effects of Roxadustat (FG-4592), an HIF-PH inhibitor, on anemia, iron regulation, and cardiac and renal dysfunction in Dahl salt-sensitive rats. METHODS: Six-week-old male Dahl salt-sensitive rats were fed a normal or high-salt diet for 8 weeks. A further subset of Dahl salt-sensitive rats, that were fed a high-salt diet, was administered Roxadustat for 8 weeks. RESULTS: Dahl salt-sensitive rats fed a high-salt diet developed hypertension, cardiac and renal dysfunction, and anemia after 8 weeks of feeding. Roxadustat increased hemoglobin and serum erythropoietin levels in Dahl salt-sensitive rats fed a high-salt diet. With regard to the iron-regulating system, Roxadustat lowered hepatic hepcidin gene expression and increased the gene expression of duodenal iron transporters, such as cytochrome b and divalent metal transporter 1 , in Dahl salt-sensitive rats fed a high-salt diet. Roxadustat did not affect the development of hypertension and cardiac hypertrophy in Dahl salt-sensitive rats with a high-salt diet; however, Roxadustat treatment attenuated renal fibrosis in these rats. CONCLUSIONS: Roxadustat ameliorated anemia with affecting the gene expression of the iron-regulating system, and did not affect cardiac hypertrophy but attenuated renal fibrosis in Dahl salt-sensitive rats fed a high-salt diet.

Proposal for a Display Method for Myocardial Single Photon Emission Computed Tomography Based on Left Ventricular Volume.

Bull's eye view for the display of myocardial single-photon emission computed tomography (SPECT) 3-D perfusion maps does not reflect left ventricular (LV) volume, an important parameter. We created and evaluated a myocardial SPECT display method that reflects the LV volume.Using Digital Imaging and Communications in Medicine data, short-axis slices from the apex to the base were reconstructed and interpolated into 0.5-mm thickness. We obtained the radial lengths at 1° intervals throughout 360°, and calculated the length of the LV long axis and half circumference (1/2 circ). Myocardial perfusion was displayed as 2 ellipsoidal developments that exhibited the left anterior descending coronary artery (LAD) and non-LAD regions. We created a system that can display these processes on a personal computer. Myocardial SPECT data from 526 individuals without heart disease were analyzed. The long axis and 1/2 circ were compared with the body size, LV end-diastolic diameter (LVDd) obtained by echocardiography, and the end-diastolic volume (EDV) obtained by electrocardiogram-gated SPECT analysis. The 1/2 circle correlated with the LVDd and EDV. The images obtained allowed a diagnosis comparable to that made using the conventional coordinate display system.The new myocardial display reflects ischemia and LV volume within a single image, which cannot be achieved with conventional SPECT image display. Additional studies of this display system are required to allow its application to patients with heart disease.

Mean pulmonary artery pressure estimated by echocardiogram rapidly exceeds 20 mmHg from the normal range in patients with connective tissue disease.

Earlier intervention for pulmonary hypertension (PH) has been reported to improve the prognosis of patients with connective tissue disease (CTD). However, it is not fully elucidated how rapidly PH develops in patients showing normal mean pulmonary arterial pressure (mPAP) at the index investigation. We evaluated 191 CTD patients with normal mPAP retrospectively. The mPAP was estimated by the formerly defined method employing echocardiography (mPAPecho). We investigated predictive factors that predict increasing mPAPecho at follow-up transthoracic echocardiography (TTE) using uni- and multi variable analysis. The mean age was 61.5 years old, and 160 patients were female. The percentage of patients in whom mPAPecho exceeded 20 mmHg at follow-up TTE was 38%. Multivariable analysis revealed that acceleration time/ejection time (AcT/ET) measured at the right ventricular outflow tract at initial TTE was independently associated with the consequent increase of mPAPecho at the follow-up TTE. When using 0.43 of best cutoff value in AcT/ET calculated by receiver operating characteristic analysis, the change in mPAPecho in patients with low AcT/ET was significantly higher than in those with high AcT/ET (3.05 mmHg in patients with AcT/ET < 0.43 and 1.00 mmHg in patients with AcT/ET ≥ 0.43, p < 0.001). Thirty-eight percent of CTD patients who show the normal estimated mPAP by TTE develop gradual elevation of mPAP to the level to consider early intervention within 2 years. AcT/ET at initial TTE can predict increasing mPAP at follow-up TTE.

Plasma renin activity variation following admission predicts patient outcome in acute decompensated heart failure with reduced and mildly reduced ejection fraction.

Plasma renin activity (PRA) level at admission is reported to be a prognostic predictor of acute decompensated heart failure (ADHF) patients. Although PRA is affected during hospitalization by several factors including fluid volume and drug titration, whether the changes in PRA levels during hospitalization (ΔPRA) are associated with prognosis of ADHF patients are largely unknown. PURPOSE: Investigate the predictive impact of ΔPRA on the prognosis of ADHF patients with reduced ejection fraction (HFrEF) and mildly reduced ejection fraction (HFmrEF). METHODS: Retrospectively analyzed consecutive 116 HFrEF and HFmrEF patients admitted for ADHF. PRA measurements were acquired at admission and at discharge. The primary outcome was a composite of cardiovascular death and HF re-hospitalization. RESULTS: Out of 116 patients, 85 had PRA measurements both at admission and at discharge. Compared to admission, PRA level was significantly higher at discharge (0.8 (IQR 0.3-2.2) to 2.8 (IQR 1.0-7.2), p < 0.001). Tertiary groups ranked by PRA level on admission showed trend of poor prognosis in order of high, mid, and low PRA level (p = 0.07). On the contrary, PRA level at discharge significantly differentiated the prognosis and was poor in order of high, low, and mid (p = 0.026). Next, when the participants were divided into tertiary groups ranked by ΔPRA, prognosis worsened in the order of "minimal", "decreasing", and the "increasing" tier. Cubic splines analysis also indicate a similar tendency. CONCLUSIONS: In ADHF patients with HFrEF and HFmrEF, patients with minimal ΔPRA showed the better prognosis over the those with either increasing or decreasing.

Shorter door-to-balloon time, better long-term clinical outcomes in ST-segment elevation myocardial infarction patients: J-MINUET substudy.

BACKGROUND: The impact of shorter door-to-balloon (DTB time on long-term outcomes in ST-segment elevation myocardial infarction (STEMI treated with primary percutaneous coronary intervention (PPCI has not been fully elucidated. METHODS: We investigated 3283 consecutive patients with acute myocardial infarction selected from a prospective, nationwide, multicenter registry (J-MINUET database comprising 28 institutions in Japan between July 2012 and March 2014. Among the study population, we analyzed 1639 STEMI patients who had PPCI within 12 h of onset. Patients were stratified into four groups (DTB time < 45 min, 45-60 min, 61-90 min, >90 min. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. We performed landmark analysis for incidence of the primary endpoint from 31 days to 3 years among the four groups. RESULTS: The primary endpoint rate from 31 days to 3 years increased significantly and time-dependently with DTB time (10.2 % vs. 15.3 % vs. 16.2 % vs. 19.3 %, respectively; log-rank p = 0.0129. Higher logarithm-transformed DTB time was associated with greater risk of a primary endpoint from 31 days to 3 years, and the increased number of adverse long-term clinical outcomes persisted even after adjusting for other independent variables. CONCLUSION: Shorter DTB time was associated with better long-term clinical outcomes in STEMI patients treated with PPCI in contemporary clinical practice. Further efforts to shorten DTB time are recommended to improve long-term clinical outcomes in STEMI patients. TRIAL REGISTRATION: UMIN Unique trial Number: UMIN000010037.

Impact of lipoprotein(a) levels on primary patency after endovascular therapy for femoropopliteal lesions.

Lipoprotein(a) [Lp(a)] is a risk factor for peripheral artery disease (PAD). However, the relationship between Lp(a) levels and clinical events after endovascular therapy (EVT) for the femoropopliteal artery in PAD patients remains unclear. Thus, this study aimed to assess the impact of Lp(a) levels on primary patency after EVT for de novo femoropopliteal lesions in PAD patients. A retrospective analysis was conducted on 109 patients who underwent EVT for de novo femoropopliteal lesions, and Lp(a) levels were measured before EVT between June 2016 and December 2019. Patients were divided into low Lp(a) [Lp(a) < 30 mg/dL; 78 patients] and high Lp(a) [Lp(a) ≥ 30 mg/dL; 31 patients] groups. The main outcome was primary patency following EVT. Loss of primary patency was defined as a peak systolic velocity ratio > 2.4 on a duplex scan or > 50% stenosis on angiography. Cox proportional hazards analysis was performed to determine whether high Lp(a) levels were independently associated with loss of primary patency. The mean follow-up duration was 28 months. The rates of primary patency were 83 and 76% at 1 year and 75 and 58% at 2 years in the low and high Lp(a) groups, respectively (P = 0.02). After multivariate analysis, High Lp(a)[Lp(a) ≥ 30 mg/dL] (hazard ratio 2.44; 95% CI 1.10-5.44; P = 0.03) and female sex (hazard ratio 2.65; 95% CI 1.27-5.51; P < 0.01) were independent predictors of loss of primary patency. Lp(a) levels might be associated with primary patency after EVT for de novo femoropopliteal lesions.

The differences between conventional lead, thin lead, and leadless pacemakers regarding effects on tricuspid regurgitation in the early phase.

PURPOSE: Trans-venous pacemaker leads are associated with worsening of tricuspid regurgitation (TR) after pacemaker implantation (PMI) in some cases. Recently, leadless pacemakers and thin ventricular pacemaker leads without a stylet lumen have become popular. However, the differences in the effects of these leads on TR are unclear. We investigated differences in the changes in TR in the early phase after PMI in patients with conventional leads, thin leads, and leadless pacemakers. METHODS: We enrolled 65 patients who underwent PMI (32 males, 79 ± 8 years), including 48 with trans-venous PMI (29 with conventional 6.0-Fr leads and 19 with 4.1-Fr thin leads) and 17 with leadless pacemakers. Transthoracic echocardiography was performed before and 1 month after PMI for assessment of conventional echocardiographic parameters and severity of TR by quantitative assessment. RESULTS: Atrial fibrillation was the most frequent indication for PMI in patients with leadless pacemakers (p = 0.015). In the before and 1 month after PMI comparison, left ventricular ejection fraction decreased after PMI only in the conventional lead group (p = 0.022). The TR effective regurgitant orifice area (EROA) decreased post PMI in the leadless (p = 0.002) and thin lead groups (p = 0.001), but not in the conventional lead group (p = 0.596). The change in TR EROA was greater in the leadless and thin lead groups as compared with the conventional lead group (p < 0.05). CONCLUSION: The decrease in TR EROA in the early phase after PMI differed according to the type of pacemaker lead. The thin lead might be beneficial for reduction of TR after PMI.

Clinical impact of beta-blockers at discharge on long-term clinical outcomes in patients with non-reduced ejection fraction after acute myocardial infarction.

BACKGROUND: Beta-blockers are associated with several clinical benefits in patients with reduced left ventricular ejection fraction (REF) after acute myocardial infarction (AMI), such as lower rates of mortality, recurrence of myocardial infarction, and heart failure. However, the long-term prognosis of beta-blockers has rarely been investigated in patients with non-REF after AMI. This study aimed to investigate the clinical benefits of beta-blockers in these patients. METHODS: A total of 3281 consecutive patients who were hospitalized within 48 h after AMI were registered in the J-MINUET study. Patients who underwent primary percutaneous coronary intervention (PCI) and had a left ventricular ejection fraction ≥40 % were enrolled, and patients who died during admission were excluded. Included patients were divided into two groups according to the prescription of beta-blockers at discharge. Their characteristics and clinical outcomes were compared. RESULTS: The number of AMI patients treated with beta-blockers was 1353 (70.4 %). Patients who received beta-blockers were younger and had a higher incidence of hypertension, dyslipidemia, and ST-segment elevation myocardial infarction than those who did not receive beta-blockers. The peak creatine kinase level after primary PCI was significantly higher in patients who received beta-blockers. These patients also had a lower incidence of a composite of all-cause death, myocardial infarction, and stroke compared to those that did not receive beta-blockers (7.3 % vs. 11.9 %, p = 0.001). Multivariate analysis showed that beta-blocker use was an independent factor for better clinical outcomes. CONCLUSIONS: The J-MINUET study revealed the clinical benefit of beta-blockers in AMI patients with non-REF after primary PCI.

Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors on Outcomes After Catheter Ablation for Atrial Fibrillation.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently been a significant focus of attention because of their multiple pleiotropic effects. However, the impact of SGLT2i on atrial fibrillation (AF) remains unclear. OBJECTIVES: The goal of this study was to examine the effects of SGLT2i on AF after catheter ablation (CA). METHODS: This prospective, randomized controlled study compared the suppressive effect of SGLT2i vs dipeptidyl peptidase-4 inhibitors on AF recurrence after CA. Eighty AF patients with type 2 diabetes mellitus were randomized (by a computer-generated random sequence) to the tofogliflozin group (20 mg/d) or the anagliptin group (200 mg/d) stratified according to left atrial diameter and AF type (paroxysmal AF [PAF] or non-paroxysmal atrial fibrillation [PAF]) at screening. The primary outcome was AF recurrence at 12 months after CA. RESULTS: Seventy patients were analyzed (mean age 70.3 ± 8.1 years; 48 male; 30 with paroxysmal AF; 38 tofogliflozin treated). Recurrent AF was detected in 24 (34.3%) of 70 patients, and the AF recurrence ratio was higher in the anagliptin group than in the tofogliflozin group (15 of 32 patients [47%] vs 9 of 38 patients [24%]; P = 0.0417). Moreover, univariate analysis revealed that compared with the nonrecurrence group (n = 46), the recurrence group (n = 24) had a higher prevalence rate of non-PAF, elevated brain natriuretic peptide, higher urinary albumin-creatinine ratio, lower rate of SGLT2i use, larger left atrial diameter, elevated E wave, lower left ventricular ejection fraction, and lower rate of cryoballoon pulmonary vein isolation. CONCLUSIONS: Compared with anagliptin, tofogliflozin achieved greater suppression of AF recurrence after CA in patients with type 2 diabetes mellitus.

Potential of optical frequency domain imaging for differentiation between early and advanced coronary atherosclerosis.

PURPOSE: This study evaluated whether optical frequency domain imaging (OFDI) accurately distinguish between fibroatheroma (FA) and pathological intimal thickening (PIT) compared with histopathology. METHODS: A total of 631 histological cross-sections from 14 autopsy hearts were analyzed for the comparison between OFDI and histological images. Of those, 190 (30%) sections were diagnosed with PIT and 120 (19%) with FA. The OFDI signal attenuation rate was calculated from an exponential. The lipid length was measured longitudinally by detection of sequential OFDI frames within a plaque segment containing lipids. The lipid arc was measured with a protractor centered in the center of the lumen. The fibrous cap thickness was defined as the minimum thickness of the signal rich band overlying PIT and FA. RESULTS: There was no significant difference in the OFDI signal attenuation rate between FA and PIT (3.09 ± 1.04 versus 2.79 ± 1.20, p = 0.13). However, the lipid length was significantly longer, the maximum lipid arc was significantly larger, and the fibrous cap thickness was significantly thinner in FA than in PIT (7.5 [4.3-10.3] mm versus 4.3 [2.7-5.8] mm, p < 0.0001, 125 [101-174]° versus 96 [74-131]°, p < 0.0001, and 220 [167-280] µm versus 260 [190-332] µm, p = 0.019). CONCLUSIONS: This study revealed OFDI may have the potential capability for discriminating FA from PIT based on the longitudinal and circumferential extent of lipid plaque, although the OFDI signal attenuation rate was similar between FA and PIT.

Characteristics, Antithrombotic Patterns, and Prognostic Outcomes in Claudication and Critical Limb-Threatening Ischemia Undergoing Endovascular Therapy.

PURPOSE: The underlying difference between intermittent claudication (IC) and critical limb-threatening ischemia (CLTI) still remains unclear. This prospective multicenter observational study aimed to clarify differences in clinical features and prognostic outcomes between IC and CLTI, and prognostic factors in patients undergoing endovascular therapy (EVT). MATERIALS AND METHODS: A total of 692 patients with 808 limbs were enrolled from 20 institutions in Japan. The primary measurements were the 3-year rates of major adverse cardiovascular event (MACE) and reintervention. RESULTS: Among patients, 79.0% had IC and 21.0% had CLTI. Patients with CLTI were more frequently women and more likely to have impaired functional status, undernutrition, comorbidities, hypercoagulation, hyperinflammation, distal artery disease, short single antiplatelet and long anticoagulation therapies, and late cilostazol than patients with IC. Aortoiliac and femoropopliteal diseases were dominant in patients with IC and infrapopliteal disease was dominant in patients with CLTI. Patients with CLTI underwent less frequently aortoiliac intervention and more frequently infrapopliteal intervention than patients with IC. Longitudinal change of ankle-brachial index (ABI) exhibited different patterns between IC and CLTI (pinteraction=0.002), but ABI improved after EVT both in IC and in CLTI (p<0.001), which was sustained over time. Dorsal and plantar skin perfusion pressure in CLTI showed a similar improvement pattern (pinteraction=0.181). Distribution of Rutherford category improved both in IC and in CLTI (each p<0.001). Three-year MACE rates were 20.4% and 42.3% and 3-year reintervention rates were 22.1% and 46.8% for patients with IC and CLTI, respectively (log-rank p<0.001). Elevated D-dimer (p=0.001), age (p=0.043), impaired functional status (p=0.018), and end-stage renal disease (p=0.019) were independently associated with MACE. After considering competing risks of death and major amputation for reintervention, elevated erythrocyte sedimentation rate (p=0.003) and infrainguinal intervention (p=0.002) were independently associated with reintervention. Patients with CLTI merely showed borderline significance for MACE (adjusted hazard ratio 1.700, 95% confidence interval 0.950-3.042, p=0.074) and reintervention (adjusted hazard ratio 1.976, 95% confidence interval 0.999-3.909, p=0.05). CONCLUSIONS: The CLTI is characterized not only by more systemic comorbidities and distal disease but also by more inflammatory coagulation disorder compared with IC. Also, CLTI has approximately twice MACE and reintervention rates than IC, and the underlying inflammatory coagulation disorder per se is associated with these outcomes. CLINICAL IMPACT: The underlying difference between intermittent claudication (IC) and critical limb-threatening ischemia (CLTI) still remains unclear. This prospective multicenter observational study, JPASSION study found that CLTI was characterized not only by more systemic comorbidities and distal disease but also by more inflammatory coagulation disorder compared to IC. Also, CLTI had approximately twice major adverse cardiovascular event (MACE) and reintervention rates than IC. Intriguingly, the underlying inflammatory coagulation disorder per se was independently associated with MACE and reintervention. Further studies to clarify the role of anticoagulation and anti-inflammatory therapies will contribute to the development of post-interventional therapeutics in the context of peripheral artery disease.

Sleep Apnea and Physical Movement During Sleep, But Not Sleep Duration, Are Independently Associated With Progression of Left Ventricular Diastolic Dysfunction: Prospective Hyogo Sleep Cardio-Autonomic Atherosclerosis Cohort Study.

Background Although co-occurrence of sleep disorder with heart failure is known, it is not clear whether that condition is a cause or consequence of heart failure. The present study was conducted as a longitudinal examination of the predictive value of sleep parameters on progression of left ventricular diastolic dysfunction. Methods and Results Four-hundred fifty-two subjects were followed for a mean of 34.7 months. An outcome of diastolic dysfunction was defined as increase in early inflow velocity/early diastolic tissue velocity >14. Sleep apnea-hypopnea index, minimal oxygen saturation, sleep duration, and activity index (physical movement during sleep time, a potential parameter of poor sleep quality) were determined using apnomonitor and actigraphy findings, while heart rate variability was measured with a 24-hour active tracer device. Sixty-six of the patients developed diastolic dysfunction during the follow-up period, with a median time of 25 months. Kaplan-Meier analysis results revealed that those with sleep apnea classified as moderate (apnea-hypopnea index 15 to <30, P<0.01 versus none) or severe (apnea-hypopnea index ≥30, P<0.01 versus none), and with a high activity index (Q3 or Q4, P<0.01 versus Q1), but not short sleep duration (P=0.27) had a significantly greater risk for a diastolic dysfunction event. Results of multivariable Cox proportional hazards regression analysis indicated that moderate to severe sleep apnea after a follow-up period of 3 years (hazard ratio [HR], 9.26 [95% CI, 1.89-45.26], P<0.01) and high activity index (HR, 1.85 [95% CI, 1.01-3.39], P=0.04) were significantly and independently associated with future diastolic dysfunction. Moreover, significant association of high activity index with the outcome was not confounded by either minimal oxygen saturation or heart rate variability. Conclusions Sleep apnea and physical movement during sleep, but not sleep duration and autonomic nervous dysfunction, are independent important predictors for progression of left ventricular diastolic dysfunction.

Twelve-month safety and effectiveness of TCD-17187 drug-coated balloon for the treatment of atherosclerotic lesions in the superficial femoral and proximal popliteal artery.

PURPOSE: The aim of this preapproval trial was to evaluate the 12-month safety and effectiveness of the TCD-17187 drug-coated balloon (DCB) for the treatment of atherosclerotic lesions in the superficial femoral artery (SFA) and/or proximal popliteal artery (PA). METHODS: This was a prospective, multicenter, core laboratory adjudicated, single-arm trial. From October 2019 to November 2020, a total of 121 symptomatic peripheral artery disease patients with SFA and/or proximal PA lesions were enrolled. The primary effectiveness endpoint was 12-month primary patency defined as freedom from restenosis as determined by duplex ultrasonography in the absence of clinically driven target lesion revascularization (CD-TLR). The safety endpoint was the major adverse event (MAE) rate defined as freedom from a composite of device- and procedure-related death within 30 days, and index limb major amputation and/or CD-TLR through follow-up. RESULTS: Average age was 74.5 ± 7.3 years and the frequency of diabetes mellitus was 67.5%. Average lesion length and vessel diameter were 106.0 ± 52.6 and 5.2 ± 0.8 mm, respectively. The frequency of chronic total occlusion and bilateral calcification was 17.5% and 50.8% of patients, respectively. The 12-month primary patency rate calculated by Kaplan-Meier analysis was 81.1%, while 12-month freedom from CD-TLR was 95.8%. The MAE rate at 30 days was 1.7% and all events comprised CD-TLR. There were no instances of device- or procedure-related deaths, major amputations, or thrombosis throughout the 12-month evaluation period. CONCLUSION: This preapproval trial confirmed the safety and effectiveness of TCD-17187 DCB in the treatment of atherosclerotic lesions in the SFA and/or proximal PA.