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Plaque rupture (PR), characterized by a disruption of the fibrous cap of lipid-rich plaques, is the major etiology of ST-segment elevation myocardial infarction (STEMI). Dyslipidemia is a well-known risk factor for PR. Nonetheless, the impact of detailed atherogenic lipid profiles, including small dense low-density lipoprotein cholesterol (sd-LDL-C) and triglyceride-rich lipoproteins (TRLs), on PR has not yet been investigated.To elucidate the impact of sd-LDL-C and TRL levels on PR in patients with STEMI using optical coherence tomography (OCT).A total of 106 consecutive statin-naive patients with STEMI were enrolled. The PR in culprit lesions was assessed on pre-intervention OCT images, and serum samples were collected immediately before coronary angiography. Sd-LDL-C was directly measured using a homogeneous assay. TRL-cholesterol (TRL-C) was estimated by subtracting the LDL-C level from the non-high-density lipoprotein cholesterol level. Clinical characteristics and lipid profiles were compared between the PR and intact fibrous cap (IFC).No difference in LDL-C levels was observed between the PR (n=64) and IFC (n=42) groups (120.0 mg/dL vs. 129.5 mg/dL, p=0.97); however, sd-LDL-C levels were significantly higher in the PR group (38.9 mg/dL vs. 32.4 mg/dL, p=0.04). Similarly, the PR group had higher TRL-C (24.0 mg/dL vs. 18.0 mg/dL, p=0.01) and triglyceride (130.0 mg/dL vs. 100.3 mg/dL, p=0.03) levels than the IFC group. Multivariate logistic regression analysis showed that sd-LDL-C was an independent factor determining PR (odds ratio, 1.53 per 10 mg/dL; p=0.04).Only sd-LDL-C levels were significantly associated with PR in culprit lesions in patients with STEMI.

The presence of cholesterol crystals (CCs) is recognized as a component of vulnerable atherosclerotic plaques at risk of rupture. The phagocytosis of atherogenic lipid factors by macrophages precedes and promotes the formation of vulnerable plaques, but it is not clear how these factors affect the formation of CC.This study aimed to evaluate the relationship between lipid biomarkers such as small dense low-density lipoprotein cholesterol (sd-LDL-c) and CC detected by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS).Serum samples were collected immediately before coronary angiography in consecutive 174 patients with ACS who did not take statins and underwent OCT imaging of the culprit lesion. The sd-LDL-c levels were measured using a direct homogenous assay. CC was defined as a thin linear structure with high reflectivity and low signal attenuation on the OCT images.CC was identified in 85 patients (48.9%). The prevalence of CC was significantly higher in lesions with ruptured plaques and greater macrophage grade. The sd-LDL-c levels were significantly higher in the patients with CC (41.6 vs. 31.2 mg/dL, p = 0.01) although there were no significant differences in the levels of LDL-c and apolipoprotein B. The CC group also had higher levels of apolipoprotein C3 and HbA1c levels. In multiple logistic regression analysis, sd-LDL-c was an independent risk factor of CC (odds ratio, 1.19 per 10 mg/dL; p = 0.03).sd-LDL may play an important role in the presence of CC in patients with ACS.

Background Caffeine intake from one cup of coffee one hour before adenosine stress tests, corresponding to serum caffeine levels of 3-4 mg/L, is thought to be acceptable for non-invasive imaging. Aims We aimed to elucidate whether serum caffeine is independently associated with adenosine-induced fractional flow reserve (FFR) overestimation and their concentration-response relationship. Methods FFR was measured using adenosine (FFRADN) and papaverine (FFRPAP) in 209 patients. FFRADN overestimation was defined as FFRADN - FFRPAP. The locally weighted scatterplot smoothing (LOWESS) approach was applied to evaluate the relationship between serum caffeine level and FFRADN overestimation. Multiple regression analysis was used to determine independent factors associated with FFRADN overestimation. Results Caffeine was ingested at l12 hours in 85 patients, at 12-24 hours in 35 patients, and at g24 hours in 89 patients. Multiple regression analysis identified serum caffeine level as the strongest factor associated with FFRADN overestimation (pl0.001). The LOWESS curve demonstrated that FFRADN overestimation started from just above the lower detection limit of serum caffeine and increased approximately 0.01 FFR unit per 1 mg/L increase in serum caffeine level with a linear relationship. The 90th percentile of serum caffeine levels for the ≤12-hour, the 12-24-hour, and the g24-hour groups corresponded to FFRADN overestimations by 0.06, 0.03, and 0.02, respectively. Conclusions Serum caffeine overestimates FFRADN values in a linear concentration-response manner. FFRADN overestimation occurs at much lower serum caffeine levels than those that were previously believed. Our results highlight that standardised caffeine control is required for reliable adenosine-induced FFR measurements.

Recent clinical studies suggest that newer-generation drug-eluting stents that combine ultrathin struts and nanocoating (biodegradable polymer sirolimus-eluting stents, BP-SES) could improve long-term clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). However, the early vascular response to BP-SES in these patients has not been investigated so far.We examined this response in 20 patients with STEMI caused by plaque rupture using frequency-domain optical coherence tomography (OCT) to understand the underlying mechanisms. Plaque rupture was diagnosed by OCT before PCI with BP-SES implantation was performed. OCT was again performed before the final angiography (post-PCI) and after 2 weeks (2W-OCT).BP-SES placement caused protrusion of atherothrombotic material into the stent lumen and incomplete stent apposition in all patients. After 2 weeks, incomplete stent apposition was significantly reduced (% malapposed struts: post-PCI 4.7 ± 3.3%; 2W-OCT 0.9 ± 1.2%; P < 0.0001), and the percentage of uncovered struts also significantly decreased (% uncovered struts: post-PCI; 69.8 ± 18.3%: 2W-OCT; 29.6 ± 11.0%, P < 0.0001). The maximum protrusion area of the atherothrombotic burden was significantly reduced (post-PCI 1.36 ± 0.70 mm2; 2W-OCT 0.98 ± 0.55 mm2; P = 0.004).This study on the early vascular responses following BP-SES implantation showed rapid resolution of atherothrombotic material and progression of strut apposition and coverage. (UMIN000041324).

Background: The clinical frailty scale (CFS) predicts late mortality in patients undergoing transcatheter aortic valve replacement. We evaluated the CFS and other parameters associated with 1-year mortality after balloon aortic valvuloplasty (BAV). Methods and Results: Between January 2013 and May 2018, 148 patients with severe aortic stenosis (AS) who underwent BAV at the present hospital were enrolled. We recorded pre-procedural CFS grade, baseline characteristics, echocardiographic, and hemodynamic parameters. To investigate the potential risk to patients before BAV, we evaluated the Society of Thoracic Surgeons (STS) score. After patients who underwent surgical aortic valve replacement, transcatheter aortic valve replacement or repeat BAV were excluded, we investigated 1-year survival. Of 127 patients, 41 (32.3%) died ≤1 year after BAV, 8 of whom (19.5% of all-cause deaths) had cardiac deaths. Higher grade of CFS and STS score significantly correlated with 1-year mortality. Severe frailty and the high operative risk group (CFS ≥7 and STS score ≥8.7%) had an extremely poor prognosis (1-year mortality, 81.2%). Conclusions: In this BAV cohort, severe frailty was a predictor of 1-year mortality in elderly patients with severe AS.

A 58-year-old woman with pallor on her left hand due to chronic hemodialysis presented with a recent intractable skin ulcer on her left 3rd finger; the skin perfusion pressure (SPP) was 19 mmHg. Preoperative angiography revealed an occluded proximal left radial artery, no communication between the ulnar and superficial palmar arteries, several collaterals from the left ulnar to the radial artery, and no visualization of the finger arteries. Successful endovascular therapy to the occluded radial artery increased flow to the arteriovenous fistula (AVF), but not to the fingertips. Slightly compressing the AVF augmented the flow and wound blush at the wound sites on the 3rd fingertip, leading to a diagnosis of hemodialysis access-induced distal ischemia (HAIDI). Surgical AVF banding with intra-operative SPP monitoring improved the SPP to 34 mmHg, leading to complete wound healing over 1 month with a preserved AVF. We performed a bilateral temporal artery biopsy and diagnosed giant cell arteritis. As the angiographic wound blush at wound sites is reportedly an important factor for wound healing, angiography with AVF manual compression is essential to diagnose HAIDI and evaluate the blood flow for wound healing.

Aim: This study investigated whether the small dense low-density lipoprotein cholesterol (sd-LDL-c) level is associated with the rapid progression (RP) of non-culprit coronary artery lesions and cardiovascular events (CE) after acute coronary syndrome (ACS). Methods: In 142 consecutive patients with ACS who underwent primary percutaneous coronary intervention for the culprit lesion, the sd-LDL-c level was measured using a direct homogeneous assay on admission for ACS and at the 10-month follow-up coronary angiography. RP was defined as a progression of any pre-existing coronary stenosis and/or stenosis development in the initially normal coronary artery. CEs were defined as cardiac death, myocardial infarction, stroke, or coronary revascularization. Results: Patients were divided into two groups based on the presence ( n =29) or absence ( n =113) of RP after 10 months. The LDL-c and sd-LDL-c levels at baseline were equivalent in both the groups. However, the sd-LDL-c, triglyceride, remnant lipoprotein cholesterol (RL-c), and apoC3 levels at follow-up were significantly higher in the RP group than in the non-RP group. The optimal threshold values of sd-LDL-c, triglyceride, RL-c, and apoC3 for predicting RP according to receiver operating characteristics analysis were 20.9, 113, 5.5, and 9.7 mg/dL, respectively. Only the sd-LDL-c level (≥ 20.9 mg/dL) was significantly associated with incident CEs at 31±17 months (log-rank: 4.123, p =0.043). Conclusions: The sd-LDL-c level on treatment was significantly associated with RP of non-culprit lesions, resulting in CEs in ACS patients. On-treatment sd-LDL-c is a residual risk and aggressive reduction of sd-LDL-c might be needed to prevent CEs.

Background Recent clinical study suggests newer-generation drug-eluting stents (DES) that combine ultrathin strut and nano-coating with biodegradable polymers sirolimus-eluting stent (BP-SES) could improve long-term clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) over current generation DES. However, safety profiles in very early phase have not been systematically addressed. Objective and method We exploratory investigate early vascular response following BP-SES implantation in patients with STEMI to reveal mechanism of the favorable clinical outcomes in recent studies using frequency domain-optical coherence tomography (FD-OCT). Consecutive twenty patients with STEMI who underwent FD-OCT immediately after primary PCI and were eligible for follow-up FD-OCT at 2 weeks after implantation were enrolled between June 2018 and November 2019. Results Twenty patients (age 62.7±11.3 years, male 85.0%) were enrolled with frequencies of hypertension (45.0%), diabetes mellitus (35.0%), dyslipidemia (55.0%) and smoking (80.0%). Aspiration catheter were used in all patients, and 1.13±0.34 stents were used. Only one patient (5.0%) received chronic antiplatelet therapy with aspirin prior to the onset of STEMI. All patients started to receive prasugrel as thienopyridine from this event and continued dual antiplatelet therapy for 2 weeks. The percentage of uncovered struts significantly decreased from post-procedure to 2W follow-up (69±18% post-procedure versus 30±11% at 2W follow up, p Conclusion(s) This study firstly elucidated very early vascular responses following ultrathin strut BP-SES implantation in STEMI patients, showing early progression of strut coverage and resolution of athero-thrombotic materials. This technology may have a potential to overcome the current generation DESs in this clinical setting. Thrombus, uncovered and malapposed struts Funding Acknowledgement Type of funding source: None

Background Adenosine and adenosine triphosphate (ATP) are widely used to induce hyperemia for fractional flow reserve (FFR) measurements. Caffeine attenuates their hyperemic effects, but not those of nicorandil and papaverine. No studies have systematically compared the hyperemic efficacies of nicorandil, papaverine, and ATP with and without caffeine abstention. Methods FFRs were measured using nicorandil 2 mg (FFRNC2), nicorandil 4 mg (FFRNC4), and papaverine (FFRPAP) in 40 patients (group 1), and using nicorandil 2 mg, ATP (FFRATP), ATP plus nicorandil (FFRATP+NC2), and papaverine in 20 patients with (group 2) and in 20 patients without caffeine abstention (group 3). Results In group 1, FFRNC2 and FFRNC4 did not differ (p = 0.321) and were higher than FFRPAP (p Conclusions Nicorandil 2 mg is a safe and practical alternative for patients who consume caffeine-containing products before the test or have contraindications for adenosine/ATP. Increasing the nicorandil dose to 4 mg or administering adjunctive nicorandil during ATP infusions does not offer any clinical advantages compared with administering nicorandil 2 mg alone.

Background Balloon aortic valvuloplasty (BAV) offers an alternative to conventional aortic valve replacement in elderly and frail patients with severe aortic stenosis (AS) for whom there are no other effective options. We aimed to investigate the mid-term effect of BAV on mitral regurgitation (MR) in patients with severe AS. Methods Our analysis was based on the data from 83 patients with severe AS (mean age, 86 ± 5 years; female, 68) treated using BAV. Echocardiography was performed before the procedure and at 1 and 3 months after. MR was quantified by measuring the MR jet area, with more-than-moderate MR being clinically significant. Results Forty patients were classified in this group (MR group). Significant reduction of MR was observed in the MR group at 1 month and 3 months after procedure, with no improvement in patients in the non-MR group. At 3 months, 15 of the 40 patients in the MR group still had significant MR, with the change at 1 month in the left ventricular end-systolic dimension (OR: 1.36; 95% CI: 1.05–1.76; P = 0.022) and MR jet area (OR: 1.95; 95% CI: 1.16–3.29; P = 0.012) being predictive of persisting significant MR at 3 months after BAV. The prevalence of New York Heart Association functional class III or IV decreased at 1 and 3 months after BAV in both groups. Conclusions BAV provides a useful therapeutic strategy for elderly patients with severe AS who are not candidates for surgical or transcatheter aortic valve replacement, especially in those with significant MR.