Vascular endothelial cells (ECs) maintain circulatory system homeostasis by changing their functions in response to changes in hemodynamic forces, including shear stress and stretching. However, it is unclear how ECs sense changes in shear stress and stretching and transduce these changes into intracellular biochemical signals. The plasma membranes of ECs have recently been shown to respond to shear stress and stretching differently by rapidly changing their lipid order, fluidity, and cholesterol content. Such changes in the membranes’ physical properties trigger the activation of membrane receptors and cell responses specific to each type of force. Artificial lipid-bilayer membranes show similar changes in lipid order in response to shear stress and stretching, indicating that they are physical phenomena rather than biological reactions. These findings suggest that the plasma membranes of ECs act as mechanosensors; in response to mechanical forces, they first alter their physical properties, modifying the conformation and function of membrane proteins, which then activates downstream signaling pathways. This new appreciation of plasma membranes as mechanosensors could help to explain the distinctive features of mechanotransduction in ECs involving shear stress and stretching, which activate a variety of membrane proteins and multiple signal transduction pathways almost simultaneously.
Background: Mutation in the lamin A/C gene (LMNA) is associated with several cardiac phenotypes, such as cardiac conduction disorders (CCD), atrial arrhythmia (AA), malignant ventricular arrhythmia (MVA) and left ventricular dysfunction (LVD), leading to sudden cardiac death (SCD) and/or end-stage heart failure. We investigated how these phenotypes are associated with each other and which of them are most important for total mortality.
Methods and Results: A multicenter registry included 110 LMNA mutation carriers (age, 43±15 years, male: 62%) from 60 families. After genetic diagnosis of LMNA mutation (missense: 27%, non-missense: 73%), patients or subjects were followed to evaluate the manifestations of their phenotypes and the risk of total mortality; 90 patients could be followed (median: 5 [0–35] years). Prevalence of the 4 clinical phenotypes was significantly increased during follow-up. Among these phenotypes, AA was significantly associated with MVA. CCD was significantly associated with LVD. LVD, meanwhile, was significantly associated with CCD and MVA. Male sex was significantly associated with MVA. Furthermore, during follow-up, 17 patients died: 12 end-stage heart failure, 4 SCD and 1 stroke. LVD was the only independent predictor for all-cause death (OR: 41.7, 95% CI: 4.1–422.3; P=0.0016).
Conclusions: Several cardiac phenotypes were age-dependently increased in LMNA mutation carriers, suggesting that ICD or CRT-D could suppress SCD after middle age; however, LVD leading to end-stage heart failure was the only independent predictor for total mortality.
Background: In atrial fibrillation (AF) patients, the effect of direct oral anticoagulant (DOACs) therapy on the incidence of left atrial appendage thrombus (LAT) remains poorly investigated. This study examined the prevalence and risk factors of LAT in AF patients on DOACs undergoing catheter ablation, and sought an anticoagulation strategy for LAT.
Methods and Results: In 407 AF patients on DOACs, transesophageal echocardiography (TEE) was performed 1 day before ablation. If patients had LAT, initial DOACs were switched to dabigatran (300 mg) or warfarin based on their renal function; TEE was repeated after treatment for ≥4 weeks. LAT was detected in 18 patients (4.4%). The prevalence of persistent AF and low-dose treatment/inappropriate dose reduction of DOACs, CHADS2/CHA2DS2-VASc scores, serum N-terminal pro-brain natriuretic peptide levels, and LA dimension/LA volume index significantly increased in patients with LAT vs. those without LAT. AF rhythm on TEE and spontaneous echo contrast also increased in patients with LAT; LA appendage flow velocity decreased. In the multivariate analysis, persistent AF and inappropriately reduced DOAC dose were risk factors for LAT. On repeat TEE, LAT had disappeared in 13 of 16 patients treated with dabigatran and in 2 of 2 patients treated with warfarin.
Conclusions: DOACs still carry a finite risk of LAT in AF patients. Inappropriately reduced DOAC dose should be avoided to minimize the thromboembolic risk. Regular-dose dabigatran may have therapeutic efficacy against LAT.
Background: Key determinants for lesion formation in catheter ablation are contact force, radiofrequency (RF) power and time. The aim of this study was to evaluate the clinical applicability of ablation index (AI), a novel non-linear formula based on these components, and to compare AI with the conventional linear force-time interval (FTI) in pulmonary vein isolation (PVI).
Methods and Results: Target AI ranges were defined for anatomical segments of the ipsilateral pulmonary veins. The operator was blinded to AI during PVI for the initial 11 patients (group A), and was unblinded for the remaining 23 patients (group B). We assessed (1) the clinical value of AI to avoid excessively high and low values with an operator blinded vs. non-blinded to AI; and (2) the relation of AI and FTI in predefined ranges. In group A, 235/564 lesions (41.7%) were in the predefined target range as compared with 1,171/1,412 lesions (82.9%) in group B (P<0.001). A given AI may correspond to a wide range of FTI, as reflected by a quartile coefficient of dispersion for AI of 0.11 vs. a quartile coefficient of dispersion for FTI of 0.36.
Conclusions: Incorporating RF current power, the non-linear AI provides more comprehensive information during PVI compared with FTI. Given that the FTI for a given AI varies widely, the value of FTI in clinical practice is questionable.
Background: Increased serum uric acid is associated with prevalence and incidence of atrial fibrillation (AF), but there is a lack of studies on the association between serum uric acid and risk of AF in the general population.
Methods and Results: We used the data from the Kangbuk Samsung Hospital health screening cohort recorded between 2002 and 2015. The primary outcome was incidence of AF diagnosed on 12-lead electrocardiography. We analyzed and compared the hazard ratios (HR) according to baseline serum uric acid quartiles. The present study involved 282,473 subjects without baseline AF. Mean follow-up was 5.4±3.6 years. During follow-up, AF was identified in 365 subjects (cumulative incidence, 0.13%). After multivariable adjustment, including that for C-reactive protein, the risk of AF was significantly higher in the upper 2 quartiles than in the lowest quartile in men (upper third quartile: adjusted HR, 1.53; 95% confidence interval [CI]: 1.11–2.89; highest quartile: HR, 1.60; 95% CI: 1.13–2.25). In women, even though AF incidence rate was very low (0.6 of 10,000 person-years), the risk of AF in the highest quartile was 6.93-fold that in the lowest quartile (95% CI: 1.53–31.29).
Conclusions: Serum uric acid is significantly and positively associated with incident AF in the Korean general population.
Background: We systematically reviewed the available literature on limb dysfunction after transradial access (TRA) or transfemoral access (TFA) cardiac catheterization.
Methods and Results: MEDLINE and EMBASE were searched for studies evaluating any transradial or transfemoral procedures and limb function outcomes. Data were extracted and results were narratively synthesized with similar treatment arms. The TRA group included 15 studies with 3,616 participants and of these 3 reported nerve damage with a combined incidence of 0.16% and 4 reported sensory loss, tingling and numbness with a pooled incidence of 1.61%. Pain after TRA was the most common form of limb dysfunction (7.77%) reported in 3 studies. The incidence of hand dysfunction defined as disability, grip strength change, power loss or neuropathy was low at 0.49%. Although radial artery occlusion (RAO) was not a primary endpoint for this review, it was observed in 3.57% of the participants in a total of 8 studies included. The TFA group included 4 studies with 15,903,894 participants; the rates of peripheral neuropathy were 0.004%, sensory neuropathy caused by local groin injury and retroperitoneal hematomas were 0.04% and 0.17%, respectively, and motor deficit caused by femoral and obturator nerve damage was 0.13%.
Conclusions: Limb dysfunction post cardiac catheterization is rare, but patients may have nonspecific sensory and motor complaints that resolve over a period of time.
Background: There are few data of clinical outcomes after drug-coated balloon (DCB) angioplasty according to neointimal characteristics. This study investigated long-term clinical outcomes according to timing of in-stent restenosis (ISR) and neointimal characteristics in patients with drug-eluting stent (DES) ISR after DCB angioplasty.
Methods and Results: In all, 122 patients (122 ISR lesions), treated with DCB under optical coherence tomography (OCT) examination before and after DCB, were categorized as early ISR (<12 months; E-ISR; n=21) and late ISR (≥12 months; L-ISR; n=101). Associations between OCT-based neointima characteristics and period of ISR, as well as clinical outcomes after DCB were evaluated. Major adverse cardiac events (MACE) were a composite of cardiac death, non-fatal myocardial infarction, or target lesion revascularization (TLR). Quantitative parameters of the neointima were similar, but qualitative characteristics showed significant differences between the E-ISR and L-ISR groups. The incidence of MACE (33.3% vs. 20.8%; P=0.069) and TLR (33.3% vs. 18.5%; P=0.040) was higher in the E-ISR group. In addition, the incidence of MACE was significantly higher for heterogeneous than non-heterogeneous neointima (43.7% vs. 19.6%; P=0.018), but was not significantly associated with neoatherosclerosis (33.4% vs. 18.4%; P=0.168).
Conclusions: DCB angioplasty is less effective for heterogeneous neointima in DES ISR. OCT-based neointimal evaluation may be helpful in guiding treatment of DES ISR.
Background: Oxygen uptake (V̇O2) at peak workload and anaerobic threshold (AT) workload are often used for grading heart failure (HF) severity and predicting all-cause mortality. The clinical relevance of respiratory exchange ratio (RER) during exercise, however, is unknown.
Methods and Results: We retrospectively studied 295 HF patients (57±15 years, NYHA class I–III) who underwent cardiopulmonary exercise testing. RER was measured at rest; at AT workload; and at peak workload. Peak V̇O2 had an inverse correlation with RER at AT workload (r=−0.256), but not at rest (r=−0.084) or at peak workload (r=0.090). Using median RER at AT workload, we divided the patients into high RER (≥0.97) and low RER (<0.97) groups. Patients with high RER at AT workload were characterized by older age, lower body mass index, anemia, and advanced NYHA class. After propensity score matching, peak V̇O2 tended to be lower in the high-RER than in the low-RER group (14.9±4.5 vs. 16.1±5.0 mL/kg/min, P=0.06). On Kaplan-Meier analysis, HF patients with a high RER at AT workload had significantly worse clinical outcomes, including all-cause mortality and rate of readmission due to HF worsening over 3 years (29% vs. 15%, P=0.01).
Conclusions: High RER during submaximal exercise, particularly at AT workload, is associated with poor clinical outcome in HF patients.
Background: Surgical intervention is indicated in symptomatic hypertrophic cardiomyopathy (HCM) patients with a ventricular outflow pressure gradient more than 50 mmHg. The transmitral approach, along with the transapical and transaortic approaches, is routinely used for myectomy, but all are open procedures. We describe a robotic transmitral approach that can be used to resolve septal hypertrophied muscle and eliminate mitral regurgitation (MR) using 1 cardiac incision.
Methods and Results: We retrospectively analyzed 20 adult patients with obstructive HCM who exhibited concomitant severe MR and systolic anterior motion (SAM). The 2 groups comprised 12 standard full-sternotomy transaortic and 8 robotic transmitral approaches. The pre-intraventricular pressure gradient was 69±14.2 mmHg in the robotic transmitral group and 70.2±17.4 mmHg in the transaortic group (P=0.876). Both groups had a similar left ventricular ejection fraction (65±8% vs. 72±9%, P=0.901) and maximal ventricular wall thickness (22.3±4.5 and 21.7±6.0, P=0.835). Postoperative MR was reduced to less than grade II in all patients. In the robotic group, the postoperative pressure gradient was 1.5±2.6 mmHg, which was lower than that of the transaortic group at 10.6±10.8 mmHg (P=0.019). The cross-clamp time was 95.3±7.7 min in the robotic group and 104.7±20.8 min in the transaortic group (P=0.193). The operation time was 237.5±22.4 and 309.6±28.5 min (P<0.01) in the robotic transmitral and transaortic groups, respectively.
Conclusions: Using a robotic transmitral approach to treat with patients with HCM, SAM, and MR is feasible and reliable. Through 1 atrial incision, it is possible to resolve hypertrophy of the septum and eliminate both severe MR and SAM.
Background: The number of surgical aortic valve replacements using bioprosthetic valves is increasing, and newer bioprosthetic valves may offer clinical advantages in Japanese patients, who generally require smaller replacement valves than Western patients. In this study we retrospectively evaluated the Trifecta and Magna valves to compare clinical outcomes and hemodynamics in a group of Japanese patients.
Methods and Results: Data were retrospectively collected for 103 patients receiving a Trifecta valve and 356 patients receiving a Magna valve between June 2008 and 2017. Adverse events, outcomes, and valve hemodynamics were evaluated. There were no significant differences in early or late outcomes between the Trifecta and Magna groups. In the early postoperative period, mean (±SD) pressure gradient (9.0±3.1 vs. 13.8±4.8 mmHg; P<0.01) and effective orifice area (1.68±0.46 vs. 1.46±0.40 m2; P<0.01) were significantly better for Trifecta, but the differences decreased over time. In particular, the interaction between time and valve type (Trifecta or Magna) was significantly different for mean pressure gradient between the 2 groups (P<0.01). Left ventricular mass regressed substantially in both groups, with no significant difference between them. There were no significant differences for severe patient-prosthesis mismatch.
Conclusions: Postoperative outcomes were similar for both valves. An early hemodynamic advantage for the Trifecta valve lasted to approximately 1 year postoperatively but did not persist.
Background: Aortic artery disease (AAD), such as aortic dissection or aortic aneurysm rupture, is fatal, with an extremely high mortality. Because of its low incidence, the risk for the development of AAD has not yet been elucidated. Hypertension (HT) is an established risk factor for cardiovascular disease, but there has been no prospective study on the effect of HT on AAD-related mortality.
Methods and Results: We used a nationwide database of 276,197 subjects (aged 40–75 years) who participated in the annual “Specific Health Check and Guidance in Japan” from 2008 to 2010. There were 80 AAD-related deaths during the follow-up period of 1,049,549 person-years. On multivariate Cox proportional hazard regression, HT was an independent risk factor for AAD-related death in apparently healthy subjects. On receiver operating characteristics curve analysis for AAD-related death, abnormal systolic and diastolic blood pressure (SBP and DBP) were 130 mmHg and 82 mmHg, respectively. The prediction capacity was significantly improved by the addition of SBP to confounding risk factors. Notably, further improvement of the C index was observed by addition of DBP to the model with SBP.
Conclusions: This is the first report to prospectively show that HT is a risk factor for AAD-related death. Both SBP and DBP are of critical importance in the primary prevention of AAD-related death in apparently healthy subjects.
Background: This study is performed to explore the differential expression of long intergenic non-coding-p53 induced non-coding transcript, miR-208a-3p and JUN in acute myocardial infarction (AMI) and their potential mechanisms.
Methods and Results: Gene Expression Omnibus, R software, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis were used for analyzing the differentially expressed genes (DEGs) and pathways. The differential expressions of LINC-PINT and miR-208a-3p were examined by qRT-PCR. The expressions of JUN and the mitogen-activated protein kinase (MAPK) pathway-related proteins were analyzed by Western blot. The triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining methods were used to measure the myocardial infarction size and tissue apoptosis respectively. The targeted relationships between miR-208a-3p and LINC-PINT or JUN were confirmed using a dual luciferase reporter assay. DEGs were significantly enriched in the MAPK signaling pathway. LINC-PINT could sponge miR-208a-3p, which targeted and regulated JUN. LINC-PINT and JUN were confirmed to be overexpressed in AMI tissues. Silencing LINC-PINT and JUN could exert a protective influence against AMI. The expression of miR-208a-3p was significantly decreased in AMI tissues, and miR-208a-3p reduced myocardial ischemia-reperfusion injury and apoptosis. Downregulation of LINC-PINT facilitated miR-208a-3p expression and suppressed the protein level of JUN, contributing to the inactivation of the MAPK pathway in the AMI tissues and thus generating protective effects.
Conclusions: Knockdown of LINC-PINT inactivated the MAPK pathway by releasing miR-208a-3p and suppressing the JUN, protecting the injury during the process of AMI.
Background: Hospitalization for heart failure (HF) carries a risk of impairment in physical activity. We assessed the association between changes in Barthel index (BI) during hospitalization and prognosis in patients with acute HF.
Methods and Results: We evaluated the BI in 256 patients with acute HF at the time of hospital admission (pre-BI) and at discharge (post-BI). All patients were followed for 1 year after discharge. BI significantly decreased during hospitalization in enrolled patients. Patients with a post-BI <60 had longer hospital stays and higher rates of non-home discharge, and had a lower 1-year survival rate than those with a post-BI ≥60. Multivariate Cox regression analysis revealed that post-BI, not pre-BI or changes in BI, significantly correlated with all-cause death and the composite of all-cause death or rehospitalization for HF for 1 year after discharge. Patients with decreasing BI during hospitalization had significantly lower all-cause death- or HF readmission-free survival following acute HF than those having a pre-BI ≥60 and changes in BI ≥0.
Conclusions: Results demonstrate that low BI at discharge and decreased BI during hospitalization predicted poor outcomes in Japanese patients with acute HF. A comprehensive approach, beginning in the acute phase, aiming to maintain patients’ ability to perform activities of daily living could provide better management of HF.
Background: The aim of this study was to investigate long-term survival, clinical status, and echocardiographic findings of patients with severe functional mitral regurgitation (FMR) undergoing MitraClip (MC) treatment and to explore the role of baseline features on outcome.
Methods and Results: Randomized and observational studies of FMR patients undergoing MC treatment were collected to evaluate the overall survival, New York Heart Association (NYHA) class and echocardiographic changes after MC treatment. Baseline parameters associated with mortality and echocardiographic changes were also investigated. Across 23 studies enrolling 3,253 patients, the inhospital death rate was 2.31%, whereas the mortality rate was 5.37% at 1 month, 11.87% at 6 months, 18.47% at 1 year and 31.08% at 2 years. Mitral regurgitation Grade <3+ was observed in 92.76% patients at discharge and in 83.36% patients at follow-up. At follow-up, 76.63% of patients NYHA Class I–II and there were significant improvements in left ventricular (LV) volume, ejection fraction, and pulmonary pressure. Atrial fibrillation (AF) had a significant negative effect on 1-year survival (β=0.18±0.06; P=0.0047) and on the reduction in LV end-diastolic and end-systolic volumes (β=−1.05±0.47 [P=0.0248] and β=−2.60±0.53 [P=0.0024], respectively).
Conclusions: MC results in durable reductions in mitral regurgitation associated with significant clinical and echocardiographic improvements in heart failure patients. AF negatively affects LV reverse remodeling and 1-year survival after MC treatment.
Background: There is a scarcity of reports on the clinical characteristics and management practice in contemporary all-comer patients with acute decompensated heart failure (ADHF).
Methods and Results: The Kyoto Congestive Heart Failure (KCHF) registry is a prospective observational cohort study enrolling 4,056 consecutive patients who had hospital admission due to ADHF without any exclusion criteria between October 2014 and March 2016 in the 19 participating hospitals in Japan. Baseline characteristics, clinical presentations, management, and in-hospital outcomes were compared between heart failure (HF) with reduced left ventricular ejection fraction (LVEF; HFrEF, LVEF <40%), HF with mid-range LVEF (HFmrEF, LVEF 40–49%), and HF with preserved LVEF (HFpEF, LVEF ≥50%). Of the 4,041 patients with documented LVEF, 1,744 (43%) had HFpEF; 746 (19%), HFmrEF; and 1,551 (38%), HFrEF. The median age was 80 years (IQR, 72–86 years) in the entire population, and was higher with increasing LVEF (P<0.001). The in-hospital mortality rate was higher in the HFrEF than in the HFmrEF and HFpEF groups (9.2%, 4.8%, and 5.1%, respectively, P<0.001).
Conclusions: This registry elucidated the clinical features and clinically relevant in-hospital outcomes in contemporary consecutive patients with ADHF in real-world clinical practice in Japan. When classified by LVEF, significant differences in characteristics and in-hospital outcomes existed between patients with HFrEF, HFmrEF, and HFpEF.
Background: Little is known of the relationship between optical coherence tomography (OCT) findings and recurrent restenosis after paclitaxel-coated balloon (PCB) angioplasty for drug-eluting stent in-stent restenosis (DES-ISR). To identify the predictors of recurrent restenosis after PCB angioplasty, we investigated quantitative and qualitative OCT findings during PCB angioplasty for DES-ISR.
Methods and Results: In all, 222 DES-ISR lesions treated by PCB angioplasty with OCT assessment and followed-up angiographically at 6 months were divided into restenotic and non-restenotic lesions on the basis of the presence or absence of restenosis at follow-up. There was a significantly higher proportion of the heterogeneous tissue pattern in restenotic than non-restenotic lesions (26.5% vs. 11.0%, respectively; P=0.02). The OCT-derived post-procedural minimal lumen and stent areas were significantly smaller in restenotic lesions, but the intima area was similar in both groups. Post-procedural stent underexpansion, defined as a stent diameter : size of the previous stent ratio <1.0, was more frequently observed in restenotic than non-restenotic lesions (33.3% vs. 17.4%, respectively; P=0.02). Multivariate analysis identified a heterogeneous tissue pattern (odds ratio [OR] 2.92; 95% confidence interval [CI] 1.32–6.47; P=0.006) and post-procedural stent underexpansion (OR 2.36; 95% CI 1.15–4.85; P=0.04) as independent predictors of recurrent restenosis.
Conclusions: The heterogeneous tissue pattern and insufficient post-procedural minimal lumen area, caused primarily by stent underexpansion, may be associated with restenosis after PCB angioplasty for DES-ISR.
Background: In addition to the airway-relaxing effects, β2 adrenergic receptor (β2AR) agonists are also found to have broad anti-inflammatory effects. The current study was conducted to define the role of β2AR agonists in limiting myocardial ischemia/reperfusion injury (IRI).
Methods and Results: Adult male wild-type (WT) and interleukin (IL)-10 knockout (KO) mice underwent a 40-min left coronary artery ligation and 60-min reperfusion. A selective β2AR agonist, Clenbuterol, at doses of 0.1 μg or 1 μg/g weight i.v. 5 min before reperfusion, significantly reduced myocardial infarct size (IS) by 28% and 39% (vs. control, P<0.05) in WT mice respectively, but had no protective effect in IL-10 KO mice. Inhalational therapy with nebulized Clenbuterol, Albuterol, Salmeterol or Arformoterol immediately before ischemia significantly reduced IS (P<0.05) in WT mice. Splenectomy similarly reduced IS as Clenbuterol-treated mice, but intravenous Clenbuterol did not further reduce IS in splenectomized mice. In splenectomized WT mice, acute transfer of isolated splenocytes, not the Clenbuterol-pretreated splenocytes, restored the myocardial IS to the level of intact mice. Intravenous Clenbuterol significantly increased splenic protein levels of β2AR, phosphorylated Akt and IL-10 and plasma IL-10, and inhibited the expression of pro-inflammatory mRNAs.
Conclusions: Both intravenous and inhalational β2AR agonists exert a cardioprotective effect against IRI by activating the anti-inflammatory β2AR-IL-10 pathway.
Background: This study compared the diagnostic value of myocardial perfusion imaging (MPI) between the rest-stress 99 mTc-tetrofosmin protocol (Tc/Tc protocol) and simultaneous acquisition rest 99 mTc-tetrofosmin/stress 201Tl dual-isotope protocol (SDI protocol) with a semiconductor camera.
Methods and Results: We retrospectively studied 147 patients who underwent stress MPI using a cadmium-zinc-telluride camera and invasive coronary angiography within a 3-month interval. The Tc/Tc and SDI protocols were used in 59 and 88 patients, respectively. The sensitivity, specificity, and accuracy of the summed difference score in per-patient analysis were 56%, 85%, and 69%, respectively, for the Tc/Tc protocol and 89%, 82%, and 85%, respectively, for the SDI protocol. The area under the receiver operating characteristic curve was significantly better for the SDI than Tc/Tc protocol for the left anterior descending artery (0.836 vs. 0.674; P=0.0380), the left circumflex artery (0.754 vs. 0.599; P=0.0441), and in per-patient analysis (0.875 vs. 0.707; P=0.0135). There was no significant difference in the diagnostic accuracy of the summed stress score for any vessel or in per-patient analysis between the 2 protocols.
Conclusions: The SDI protocol had a higher diagnostic accuracy for the detection of coronary ischemia than the Tc/Tc protocol.
Background: The appropriate number of board-certified cardiologists (BCC) for the treatment of acute myocardial infarction (AMI) has not been thoroughly examined in Japan. This study investigated whether the number of BCC/50 cardiovascular beds affects acute outcome in AMI treatment.
Methods and Results: Data on 751 board-certified teaching hospitals and 63,603 patients with AMI were obtained from the Japanese Registry Of All cardiac and vascular Diseases (JROAD) and JROAD Diagnosis Procedure Combination (JROAD-DPC) databases between 1 April 2012 and 31 March 2014. The hospitals were categorized into 3 groups based on the median number of BCC/50 cardiovascular beds: first tertile, 5.0 (IQR, 4.0–5.7); second, 8.3 (IQR, 7.4–9.8); third, 15.3 (IQR, 12.5–22.7), and the patients with AMI admitted to the categorized hospitals were compared (first tertile, 12,002 patients; second, 23,930; third, 27,671). On hierarchical logistic modeling, the adjusted OR for 30-day mortality were 0.86 (95% CI: 0.74–1.00) for the second tertile and 0.75 (95% CI: 0.65–0.88) for the third tertile.
Conclusions: Patients with AMI admitted to hospitals with a large number of BCC/50 cardiovascular beds had a lower 30-day mortality rate. This tendency was independent of patient and hospital characteristics. This is the first study to provide new information on the association between the number of BCC and in-hospital AMI-related mortality in Japan.
Background: Obstructive sleep apnea syndrome (OSAS) is associated with augmented sympathetic nerve activity and cardiovascular diseases. However, the interaction between coronary artery plaque characteristics and sympathetic nerve activity remains unclear. The purpose of this study was to clarify the relationships between coronary artery plaque characteristics, sleep parameters and single- and multi-unit muscle sympathetic nerve activity (MSNA) in OSAS patients.
Methods and Results: A total of 32 OSAS patients who underwent full-polysomnography participated in this study. The coronary plaque volume was calculated with 320-slice coronary computed tomography (CT). Single- and multi-unit MSNA were obtained during the daytime within 1 week from full-polysomnography. Patients were divided into 2 groups according to their apnea-hypopnea index (AHI) score (mild-moderate group, AHI <30; and severe group, AHI ≥30). There were no group differences in risk factors for atherosclerosis; however, severe AHI patients showed significantly high single-unit MSNA, and low- and intermediate-attenuation plaque volumes. In regression analysis, the plaque volume of any CT value was not associated with single- or multi-unit MSNA; only AHI significantly correlated with low-attenuation plaque volume (R=0.52, P<0.05).
Conclusions: Our findings provided the evidence that AHI is an independent predictor for low-attenuated, vulnerable plaque volume, but not daytime MSNA, in patients with OSAS.
Background: Lipoprotein lipase (LPL) plays an important role in triglyceride metabolism. It is translocated across endothelial cells to reach the luminal surface of capillaries by glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1), where it hydrolyzes triglycerides in lipoproteins. MicroRNA 377 (miR-377) is highly associated with lipid levels. However, how miR-377 regulates triglyceride metabolism and whether it is involved in the development of atherosclerosis remain largely unexplored.
Methods and Results: The clinical examination displayed that miR-377 expression was markedly lower in plasma from patients with hypertriglyceridemia compared with non-hypertriglyceridemic subjects. Bioinformatics analyses and a luciferase reporter assay showed that DNA methyltransferase 1 (DNMT1) was a target gene of miR-377. Moreover, miR-377 increased LPL binding to GPIHBP1 by directly targeting DNMT1 in human umbilical vein endothelial cells (HUVECs) and apolipoprotein E (ApoE)-knockout (KO) mice aorta endothelial cells (MAECs). In vivo, hematoxylin-eosin (H&E), Oil Red O and Masson’s trichrome staining showed that ApoE-KO mice treated with miR-377 developed less atherosclerotic plaques, accompanied by reduced plasma triglyceride levels.
Conclusions: It is concluded that miR-377 upregulates GPIHBP1 expression, increases the LPL binding to GPIHBP1, and reduces plasma triglyceride levels, likely through targeting DNMT1, inhibiting atherosclerosis in ApoE-KO mice.
Background: Measuring anti-Xa activity (AXA) has been reported as useful for predicting future risk of hemorrhagic and ischemic events in stroke patients taking direct factor Xa inhibitors. We evaluated AXA levels of rivaroxaban or apixaban in acute stroke patients with non-valvular atrial fibrillation.
Methods and Results: This was a single-center, prospective, observational study. Consecutive patients with acute ischemic stroke or transient ischemic attack who were admitted within 7 days of onset and started taking rivaroxaban or apixaban for NVAF between January 2012 and April 2017 were enrolled. AXA was measured at 2 time points: just before (AXAtrough) and 4 h after (AXApeak) taking rivaroxaban or apixaban on the 2nd day or later of administration. Of 156 patients taking rivaroxaban, hemorrhagic events occurred in 13. Patients with hemorrhagic events had higher AXApeak than those without [median (interquartile range): 1.93 (1.11–3.75) vs. 1.35 (0.80–2.00) IU/mL; P<0.01]. Multivariable-adjusted Cox models showed that AXApeak was independently related to the incidence of hemorrhagic events. Of 169 patients taking apixaban, hemorrhagic events occurred in 11. Patients with hemorrhagic events had higher AXAtrough [2.78 (1.90–3.53) vs. 1.42 (0.93–2.08) IU/mL, P<0.01] and AXApeak [4.05 (3.44–4.72) vs. 2.43 (1.79–3.35) IU/mL, P<0.01] than those without. Both AXAtrough and AXApeak were independently related to the incidence of hemorrhagic events.
Conclusions: In these patients who started rivaroxaban or apixaban early after stroke, AXA levels in the early period were related to future hemorrhagic events.
Background:Prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) remains an important issue. The aim of this study was to assess the value of a new discongruence index, to predict PPM after TAVR.
Methods and Results: A total of 185 patients with severe aortic stenosis who underwent TAVR with the Edwards Sapien prosthesis or CoreValve Revalving system were included (Edwards valve, n=119; Core Valve Revalving system, n=66). Discongruence index was calculated pre-procedurally as the ratio of selected transcatheter valve size (mm) to body surface area (cm2). PPM was defined as effective orifice area (EOA) ≤0.85 cm2/m2 on transthoracic echocardiography before hospital discharge. Mean age was 82±5 years and 72 patients (38.9%) were men. The overall incidence of post-TAVR PPM was 35.1% (n=65). Discongruence index correlated with post-TAVR indexed EOA (y=0.18+0.057x; P<0.001). On multivariate logistic regression analysis, discongruence index was the only independent predictor of post-TAVR PPM (OR, 0.15; 95% CI: 0.03–0.66; P=0.012), and the area under the receiver operating characteristic curve was 0.62 (95% CI: 0.54–0.70, P=0.003), with an optimal cut-off point of 15.02 (sensitivity, 86.2%; specificity, 72.5%; positive predictive value, 74.3%; negative predictive value, 83.4%).
Conclusions:The new discongruence index may be useful tool to predict PPM after TAVR.
Background: Basal interventricular septum (IVS) hypertrophy (BSH) with reduced basal IVS contraction and IVS-aorta angle is frequently associated with aortic stenosis (AS). BSH shape suggests compression by the longitudinally elongated ascending aorta, causing basal IVS thickening and contractile dysfunction, further suggesting the possibility of aortic wall shortening to improve the BSH. Surgical aortic valve replacement (SAVR), as opposed to transcatheter AVR (TAVR), includes aortic wall shortening by incision and stitching on the wall and may potentially improve BSH. We hypothesized that BSH configuration and its contraction improves after SAVR in patients with AS.
Methods and Results: In 32 patients with SAVR and 36 with TAVR for AS, regional wall thickness and systolic contraction (longitudinal strain) of 18 left ventricular (LV) segments, and IVS-aorta angle were measured on echocardiography. After SAVR, basal IVS/average LV wall thickness ratio, basal IVS strain, and IVS-aorta angle significantly improved (1.11±0.24 to 1.06±0.17; −6.2±5.7 to −9.1±5.2%; 115±22 to 123±14°, P<0.001, respectively). Contractile improvement in basal IVS was correlated with pre-SAVR BSH (basal IVS/average LV wall thickness ratio or IVS-aorta angle: r=0.47 and 0.49, P<0.01, respectively). In contrast, BSH indices did not improve after TAVR.
Conclusions: In patients with AS, SAVR as opposed to TAVR improves associated BSH and its functional impairment.
Background: Early surgery for infective endocarditis (IE) with acute heart failure (AHF) is recommended, despite clinical results being unclear. We investigated the effect of initial treatment in such patients.
Methods and Results: Outcomes for 470 patients with active IE who underwent valvular surgery during 2009–2016 were reviewed. Of them, 177 had symptomatic AHF when diagnosed with IE (excluding those with cardiogenic shock or intubated for AHF). They were divided into 2 groups based on initial treatment: Group S (underwent valvular surgery immediately; n=74) and Group M (received initial medical treatment for infection and HF; n=103). The median (interquartile range) waiting period from diagnosis to surgery in Groups S and M was 1 (1–3) and 15 (8–33) days, respectively (P<0.001). The 5-year survival rate was higher in Group S than Group M (80% vs. 64%; P=0.108). Group M was divided into Group P (initial medical treatment was effective and elective surgery was performed; n=62) and Group E (emergency surgery was necessary during medical treatment; n=41); overall 5-year survival was significantly worse in Group E than Group P (42% vs. 79%; P<0.012). In Group M, multivariate analysis indicated that Staphylococcus aureus infection (odds ratio 3.82; 95% confidence interval 1.19–13.3; P=0.024) was a significant risk factor for conversion to emergency surgery.
Conclusions: Considering poor outcomes of emergency surgery for medically refractory HF, early surgery may be a reasonable option for IE patients, especially those with S. aureus infection.
Background: Resistance exercise has beneficial effects for patients with peripheral arterial diseases. The hypothesis that muscle growth promotes angiogenesis by interacting with neighboring cells in ischemic lesions was assessed.
Methods and Results: Skeletal muscle-specific inducible Akt1 transgenic (Akt1-TG) mice that induce growth of functional skeletal muscles as a model of resistance training were used. Proteomics analysis identified significant upregulation of heme oxigenase-1 (HO-1) in muscle tissue in Akt1-TG mice compared with control mice. Blood flow recovery after hindlimb ischemia was significantly increased in Akt1-TG mice compared with control mice. Enhanced blood flow and capillary density in Akt1-TG mice were completely abolished by the HO-1 inhibitor, Tin-mesoporphyrin. Immunohistochemistry showed that HO-1 expression was not increased in muscle cells, but it was increased in macrophages and endothelial cells. Consistent with these findings, blood flow recovery after hindlimb ischemia was similar between control mice and skeletal muscle-specific HO-1-knockout mice. Adenoviral-mediated overexpression of Akt1 did not increase HO-1 protein expression in C2C12 myotubes; however, the conditioned medium from Akt1-overexpressing C2C12 myotubes increased HO-1 expression in endothelial cells. Cytokine array demonstrated that a panel of cytokine secretion was upregulated in Akt1-overexpressing C2C12 cells, suggesting paracrine interaction between muscle cells and endothelial cells and macrophages.
Conclusions: Akt1-mediated muscle growth improves blood flow recovery after hindlimb ischemia by enhancing HO-1 expression in neighboring cells.
Background: Post-repair atrial septal defects (ASD) patients are frequently discharged from follow-up, but the extent of pulmonary symptoms long-term post-repair is unknown.
Methods and Results: The national CONgenital CORvitia registry was linked to the national Drug Registry to investigate all ambulatory-dispensed pulmonary inhalants for 2006–2014. ASD patients were compared with age- and sex-matched referents from the general population. A total of 1,959 adult patients (age 42±17 years; 66% female; 1,223 [62%] repaired) were included. Compared with the referents, ASD patients had more inhalant use, even at long-term post-repair follow-up (OR=1.81 [95% CI 1.62–2.03]; P<0.001).
Conclusions: ASD patients had 2-fold higher inhalant use compared with referents even at long-term post-repair follow-up, suggesting persistent pulmonary functional impairment.