Heart and Vessels最新文献

It remains to be elucidated whether Ca²⁺ antagonists induce pharmacological preconditioning to protect the heart against ischemia/reperfusion injury. The aim of this study was to determine whether and how pretreatment with a Ca²⁺ antagonist, azelnidipine, could protect cardiomyocytes against hypoxia/reoxygenation (H/R) injury in vitro. Using HL-1 cardiomyocytes, we studied effects of azelnidipine on NO synthase (NOS) expression, NO production, cell death and apoptosis during H/R. Action potential durations (APDs) were determined by the whole-cell patch-clamp technique. Azelnidipine enhanced endothelial NOS phosphorylation and NO production in HL-1 cells under normoxia, which was abolished by a heat shock protein 90 inhibitor, geldanamycin, and an antioxidant, N-acetylcysteine. Pretreatment with azelnidipine reduced cell death and shortened APDs during H/R. These effects of azelnidipine were diminished by a NOS inhibitor, L-NAME, but were influenced by neither a T-type Ca²⁺ channel inhibitor, NiCl₂, nor a N-type Ca²⁺ channel inhibitor, ω-conotoxin. The azelnidipine-induced reduction in cell death was not significantly enhanced by either additional azelnidipine treatment during H/R or increasing extracellular Ca²⁺ concentrations. RNA sequence (RNA-seq) data indicated that azelnidipine-induced attenuation of cell death, which depended on enhanced NO production, did not involve any significant modifications of gene expression responsible for the NO/cGMP/PKG pathway. We conclude that pretreatment with azelnidipine protects HL-1 cardiomyocytes against H/R injury via NO-dependent APD shortening and L-type Ca²⁺ channel blockade independently of effects on gene expression.

Awareness of transthyretin amyloid cardiomyopathy (ATTR-CM) has increased over the years due to diagnostic and therapeutic developments. Timely initiation of novel disease-modifying treatments improves both morbidity and mortality, which underlines the necessity for a prompt diagnosis. Nevertheless, early diagnosis of ATTR-CM remains challenging. This is a retrospective observational cohort study of patients diagnosed with ATTR-CM. Between 2016 and 2023, 87 patients were diagnosed with cardiac amyloidosis of which 65 (75%) patients with ATTR-CM and 22 (25%) patients with light chain amyloidosis. This study included 65 ATTR-CM patients (mean age 77 ± 7 years; 86% male) of whom 59 (91%) with wild-type ATTR-CM (ATTRwt) and six (9%) with variant ATTR-CM. We observed a surge in ATTR-CM diagnoses from 3 patients/year (2016-2020) to 16 patients/year (2021-2023), driven by ATTRwt. Nevertheless, the interval between the onset of heart failure symptoms and ATTR-CM diagnosis has not changed significantly (2016-2020 27.3 months [18.6-62.4]; 2021-2023 30.0 months [8.6-57.2]; p = 0.546), driven by time to referral. Red flags for ATTR-CM preceded diagnosis by several years: left ventricular hypertrophy (79%, 5.8 years [3.3-7.0]) and carpal tunnel syndrome (49%, 6.8 years [2.3-12.1]). Despite the presence of typical red flags, symptom-to-diagnosis duration has remained similar driven by time to referral. Improved recognition of red flags for ATTR-CM could reduce the time to diagnosis and improve overall recognition.

In pulmonary disease patients since oxygen desaturation during 6-min walk test (6MWT) affects walk distance (6MWD), some novel indices such as desaturation/distance ratio [DDR, oxygen desaturation area (DAO₂)/6MWD] and distance-saturation product [DSP, 6MWD × minimum peripheral oxygen saturation (SpO₂)] are evaluated. However, there has been no study examining these indices that consider exercise-induced desaturation (EID) in patients with cardiovascular disease. In 94 cardiovascular disease patients without pulmonary complications, 6MWT and echocardiography were performed at the entry of cardiac rehabilitation. SpO₂ was measured during 6MWT using a continuously monitorable pulse oximeter, and DSP and DDR were calculated using minimum SpO₂ and DAO₂ [sum of (100-SpO₂) per second during 6MWT], respectively. EID was defined as SpO₂ decrease of ≥ 4% or minimum SpO₂ of < 90% during 6MWT. DSP was slightly lower and DDR was markedly higher in patients with EID than in those without. When examining correlations of DSP and DDR with their components, DSP was correlated with 6MWD much closely than minimum SpO₂, while DDR was correlated as closely with DAO₂ as 6MWD. Furthermore, DAO₂, but not minimum SpO₂, had a direct correlation with 6MWD. As for associations with cardiac function, DSP was correlated with several cardiac parameters, but DDR was not correlated with any of these parameters. Our findings suggest that oxygen desaturation during 6MWT affects walking distance in cardiovascular disease patients even without pulmonary complications and that DDR is more appropriate than DSP as an index of walking performance that takes EID into consideration, independently of cardiac function.

Various surgical approaches address complex heart disease with arch anomalies. Bilateral pulmonary artery banding (bPAB) is a strategy for critically ill patients with complex arch anomalies. Some reports argued the potential effect of bPAB on the growth of the left ventricular outflow tract (LVOT) during inter-stage after bPAB. This study aimed to analyze the LVOT growth for biventricular repair candidates with arch anomaly and systemic ventricular outflow tract (SVOT) for univentricular repair candidates with arch anomaly. This retrospective study analyzed 17 patients undergoing initial bPAB followed by arch repair. The Z-scores of LVOT and SVOT were compared between pre-bPAB and pre-arch repair. Patient characteristics, transthoracic echocardiogram data, and PAB circumferences were reviewed. The diameter of the minimum LVOT for biventricular repair (BVR) candidates, the pulmonary valve (neo-aortic valve, neo-AoV) and the pulmonary trunk (the neo-ascending aorta, neo-AAo) for univentricular repair (UVR) candidates, and the degree of aortic or neo-aortic insufficiency in each candidate was statistically analyzed. 17 patients were divided into the UVR candidates (group U) with 9 patients and the BVR candidates (group B) with 8 patients. In group B, the median value of the Z-score of the minimum LVOT increased from -3.2 (range: - 4.1 ~ - 1.0) at pre-PAB to -2.8 (range: - 3.6 ~ - 0.3) at pre-arch repair with a significant difference (p = 0.012). In group U, the median value of the Z-score of the neo-AoV increased from 0.5 (range: - 1.0 ~ 1.7) at pre-bPAB to 1.2 (range: 0.2 ~ 1.9) at pre-arch repair with a significant difference (p < 0.01). The median value of the Z-score of the neo-AAo was also increased from 3.1 (range: 1.5 ~ 4.6) to 4.3 (range: 3.1 ~ 5.9) with a significant difference (p = 0.028). The growth of the LVOT for BVR candidates and SVOT for UVR candidates during the inter-stage between bPAB and arch repair was observed. These results suggest the potential advantage of bPAB in surgical strategies. Further research is needed to validate these findings and refine surgical approaches.

MicroRNA(miR)-143 and miR-145 are mainly expressed in vascular smooth muscle cells. However, the relationship between plasma miR-143 or miR-145 levels and the left ventricular (LV) function in patients with heart diseases remains unclear. Blood samples were taken from the antecubital vein in patients with heart diseases (n = 52), such as coronary artery disease, old myocardial infarction, cardiomyopathy, and valvular heart disease, and controls without heart diseases (n = 22). We measured plasma miR-143 and -145 levels by quantitative RT-PCR using TaqMan MicroRNA Assays and THUNDERBIRD Probe qPCR Mix. Plasma BNP levels were also measured. Echocardiography was performed to measure the LV ejection fraction (LVEF) and LV dilation. Plasma miR-143 and miR-145 levels were significantly higher in patients with heart diseases than in controls, respectively. Plasma miR-143 and miR-145 levels were significantly higher in patients with LVEF < 50% than in those with LVEF ≧ 50%, respectively. Plasma miR-143 and miR-145 levels were inversely correlated with LVEF, respectively. Plasma miR-143 and miR-145 levels were positively correlated with LV end-systolic dimension, respectively. Plasma miR-143 and -145 levels were positively correlated with plasma BNP levels, respectively. Plasma BNP levels were inversely correlated with LVEF. Plasma miR-143 and miR-145 levels are elevated in patients with LV dysfunction and may counteract LV dysfunction.

Degradation of vascular extracellular matrix is important in atherosclerosis. Cysteine protease legumain is upregulated in atherosclerotic plaques. We recently reported that plasma legumain levels are high in patients with complex coronary lesions. This study investigated the association between legumain levels and cardiovascular events in 372 patients undergoing coronary angiography. Patients with acute coronary syndrome were excluded. Of the 372 patients, 225 had coronary artery disease (CAD). During a mean follow-up of 7.0 ± 4.3 years, cardiovascular events occured in 62 patients. Compared with 310 patients without events, 62 with events tended to have higher prevalence of complex lesions (15% vs. 10%). Notably, patients with events had higher legumain levels (median 5.51 vs. 4.90 ng/mL, P < 0.01) than those without events. A Kaplan-Meier analysis showed lower event-free survival in patients with legumain > 5.0 ng/mL than in those with ≤ 5.0 ng/mL (P < 0.01). In multivariate Cox regression analysis, legumain level was an independent predictor of cardiovascular events. The hazard ratio for legumain > 5.0 ng/mL for cardiovascular events was 2.18 (95%CI = 1.27-3.77, P < 0.01). Only among 225 patients with CAD, patients with events had higher legumain levels (5.49 vs. 4.73 ng/mL) than without events (P < 0.02). Legumain level was also a predictor of cardiovascular events in patients with CAD. Thus, high plasma legumain levels were associated with an increased risk of cardiovascular events in patients undergoing coronary angiography and those with stable CAD.

In drug-coated balloon (DCB) angioplasty for femoropopliteal lesions, there are adverse effects of drug embolization on downstream non-target organs following the slow-flow phenomenon. We devised a novel method, known as VaSodilator injection via the over-the-wire lumen during DCB dilatation to prevent the slow-flow phenomenon in treatment of femoropopliteal lesions (V.S.O.P.), and evaluated its efficacy and safety. This single-center, retrospective, observational study analyzed 196 femoropopliteal lesions treated with IN.PACT Admiral between April 2018 and July 2023. The IN.PACT Admiral is a DCB consisting of a 0.035-inch over-the-wire (OTW) lumen balloon coated with high-dose paclitaxel. Regarding the V.S.O.P. method, we injected vasodilators through the OTW lumen during DCB dilation of the lesions. The cohort was classified into two groups according to the use of the V.S.O.P. method (V.S.O.P. group: n = 53; non-V.S.O.P. group: n = 143). The V.S.O.P. group had lower rates of hemodialysis (21% vs. 43%, p = 0.01) and higher rates of critical limb-threatening ischemia (56% vs. 23%, p < 0.01) and severe calcification lesions (Peripheral Arterial Calcium Scoring Systems score 3/4) (53% vs. 34%, p = 0.01) than the non-V.S.O.P. group. The occurrence of the slow-flow phenomenon was significantly lower in the V.S.O.P. group than in the non-V.S.O.P. group. The V.S.O.P. method could be an effective method for preventing the slow-flow phenomenon after DCB angioplasty for femoropopliteal lesions.

Dobutamine stress echocardiography (DSE) is an effective noninvasive modality for evaluating coronary artery disease (CAD), with high accuracy. However, data on the prognostic value of DSE in patients with chronic kidney disease (CKD) are limited. This study aims to assess the prognostic significance of DSE in patients with CKD and known or suspected CAD. We included consecutive patients with CKD stage 3 or higher and known or suspected CAD who underwent clinically indicated DSE between 2007 and 2017. The primary endpoint was all-cause mortality at 5 years. Univariable and multivariable analyses were conducted to identify predictors of all-cause mortality, with a p value < 0.05 considered statistically significant. A total of 274 patients were included in the study. The mean age was 64.0 ± 13.1 years, with 54% being male and 13.1% having known CAD. Among the patients, 64.6% had advanced CKD (≥ stage 4). Abnormal DSE was observed in 62 patients (22.6%). During a follow-up period of 7.0 ± 3.5 years, 78 patients (28.5%) died. The mortality rate was significantly higher in patients with abnormal DSE compared to those with normal DSE (48.4% vs. 22.6%, p < 0.001). Multivariable analysis identified age (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.008-1.05, p = 0.005), New York Heart Association (NYHA) functional class (HR 1.60, 95% CI 1.05-2.43, p = 0.03), and chronotropic index < 0.73 (HR 2.61, 95% CI 1.60-4.25, p < 0.001) as independent predictors of mortality. Conversely, a normal DSE result was found to be a protective factor (HR 0.49, 95% CI 0.30-0.81, p = 0.005). In conclusion, DSE demonstrated significant prognostic value in patients with CKD and known or suspected CAD. Age, NYHA functional class, and a chronotropic index < 0.73 were identified as independent predictors of all-cause mortality.