Pathological evaluation of predictors for delayed endothelial coverage after currently available drug-eluting stent implantation in coronary arteries: Impact of lesions with acute and chronic coronary syndromes.

BACKGROUND: The optimal duration of dual antiplatelet therapy after currently available drug-eluting stent (DES) implantation to prevent stent thrombosis (ST) remains controversial. Delayed healing is frequently identified as a leading cause of ST in the early phase. However, a thorough pathological investigation into strut coverage after currently available DES implantation is lacking-a gap addressed in the current study. METHODS: From our autopsy registry of 199 stented lesions, 4,713 struts from 66 currently available DES-stented lesions with an implant duration ≤370 days were histologically evaluated. Endothelial coverage was defined as the presence of luminal endothelial cells overlying struts and an underlying smooth muscle cell layer. The stented lesions were classified into acute coronary syndrome (ACS) (n = 40) and chronic coronary syndrome (CCS) (n = 26) groups and were compared. Endothelial coverage predictors were identified through logistic analysis. RESULTS: Although ACS and CCS lesions presented comparable clinical characteristics, including age, sex, and cause of death, the latter exhibited a significantly higher prevalence of chronic kidney disease and hemodialysis than the former (33.3% vs. 65.2%; P = .02, 7.7% vs. 30.4%; P = .02). The poststent implant median duration was significantly shorter in ACS lesions than in CCS lesions (13 [IQR 5-26 days] vs. 40 [IQR 16-233 days]; P < .01). The endothelial coverage percentage was 3.5% at 30 days and 27.7% at 90 days after currently available DES implantation. Multivariable logistic regression analysis implicated implant duration of ≤90 days (odds ratio [OR], 0.009; 95% confidence interval [CI], 0.006-0.012; P < .01), superficial calcification (OR, 0.11; 95% CI, 0.07-0.17; P < .01), ACS culprit site (OR, 0.29; 95% CI, 0.09-0.94; P = .039), and circumferentially durable polymer-coated DES (OR, 0.32; 95% CI, 0.24-0.41; P < .01) as delayed endothelial coverage predictors. CONCLUSIONS: Endothelial coverage was limited at 90 days after currently available DES implantation, and the ACS culprit site and circumferentially durable polymer-coated DES were identified as independent predictors of delayed endothelial coverage. Our findings suggest the importance of underlying plaque morphology and stent technology for vessel healing after such implantation.

Predictors of Optical Coherence Tomography-Defined Calcified Nodules in Patients With Acute Coronary Syndrome　- A Substudy From the TACTICS Registry.

BACKGROUND: Recent studies suggest that the presence of calcified nodules (CN) is associated with worse prognosis in patients with acute coronary syndrome (ACS). We investigated clinical predictors of optical coherence tomography (OCT)-defined CN in ACS patients in a prospective multicenter registry.Methods and Results: We investigated 695 patients enrolled in the TACTICS registry who underwent OCT assessment of the culprit lesion during primary percutaneous coronary intervention. OCT-CN was defined as calcific nodules erupting into the lumen with disruption of the fibrous cap and an underlying calcified plate. Compared with patients without OCT-CN, patients with OCT-CN (n=28) were older (mean [±SD] age 75.0±11.3 vs. 65.7±12.7 years; P<0.001), had a higher prevalence of diabetes (50.0% vs. 29.4%; P=0.034), hemodialysis (21.4% vs. 1.6%; P<0.001), and Killip Class III/IV heart failure (21.4% vs. 5.7%; P=0.003), and a higher preprocedural SYNTAX score (median [interquartile range] score 15 [11-25] vs. 11 [7-19]; P=0.003). On multivariable analysis, age (odds ratio [OR] 1.072; P<0.001), hemodialysis (OR 16.571; P<0.001), and Killip Class III/IV (OR 4.466; P=0.004) were significantly associated with the presence of OCT-CN. In non-dialysis patients (n=678), age (OR 1.081; P<0.001), diabetes (OR 3.046; P=0.014), and Killip Class III/IV (OR 4.414; P=0.009) were significantly associated with the presence of OCT-CN. CONCLUSIONS: The TACTICS registry shows that OCT-CN is associated with lesion severity and poor clinical background, which may worsen prognosis.

Clinical efficacy of tolvaptan in acute decompensated heart failure patients with severe aortic stenosis and atrial fibrillation: a sub-analysis from the LOHAS registry.

BACKGROUND: Severe aortic valve stenosis (AS) and atrial fibrillation (AF) are risk factors of hemodynamic instability in heart failure (HF) management due to low cardiac output, respectively. Therefore, the treatment of HF due to severe AS complicated with AF is anticipated to be difficult. Tolvaptan, a vasopressin V2 receptor inhibitor, is effective in controlling acute decompensated heart failure (ADHF) with hemodynamic stability. However, its clinical efficacy against ADHF caused by AS with AF remains to be determined. METHODS: Clinical information (from September 2014 to December 2017) of 59 patients diagnosed with ADHF due to severe AS (20 patients with AF; 39 patients with sinus rhythm [SR]) was obtained from the LOHAS registry. The registry collected data from seven hospitals and assessed the short-term effects of tolvaptan in patients hospitalized for ADHF with severe AS. We attempted to identify clinical differences from baseline up to 4 days, comparing patients with AF (AF group) versus those with SR (SR group). RESULTS: There were no significant differences between the groups in age (83.7 ± 4.5 vs. 85.8 ± 6.9 years, respectively; p = 0.11) and aortic valve area (0.60 [0.46-0.73] vs. 0.56 [0.37-0.70] cm2, respectively; p = 0.50). However, left atrial volume was larger (104 [85-126] vs. 87 [64-103] mL, respectively; p < 0.01), whereas stroke volume was lower (51.6 ± 14.8 vs. 59.0 ± 18.7 mL, respectively; p = 0.08) in the AF group versus the SR group. Body weight decreased daily from baseline up to day 4 in both groups (from 55.4 to 53.2 kg [p < 0.01] and from 53.5 to 51.0 kg [p < 0.01], respectively) without change in heart rate. Notably, the systolic blood pressure decreased slightly in the AF group after 2 days of treatment with tolvaptan. CONCLUSIONS: Short-term treatment with tolvaptan improved HF in patients hospitalized for severe AS, regardless of the presence of AF or SR. After achieving sufficient diuresis, a slight decrease in blood pressure was observed in the AF group, suggesting an appropriate timeframe for safe and effective use of tolvaptan.

Impact of tolvaptan on improvement of tricuspid regurgitation and right ventricular dimension in patients with right-sided heart failure.

Managing right-sided chronic heart failure (CHF) due to tricuspid regurgitation (TR) remains a clinical challenge. Tolvaptan (TLV), a vasopressin V2 receptor inhibitor, is effective in controlling decompensated HF. However, its effects on right-sided CHF caused by TR are unclear. We sought to clarify the effects of TLV in CHF patients complicated with TR. The cohort consisted of 33 CHF patients with moderate or severe TR and permanent atrial fibrillation, who required hospitalization for HF. We observed 19 patients treated with TLV plus conventional therapies (TLV group) and 14 patients with conventional therapies alone (conventional group). Clinical characteristics, echocardiographic parameters, and laboratory data were investigated. Baseline characteristics were similar between groups. In the TLV group, the severity of TR at admission was 73.7% moderate and 26.3% severe. In the conventional group, these percentages were 85.7% and 14.3%, respectively. During the follow-up, the severity of TR improved in the TLV group (trivial-mild: 52.6%; moderate: 36.8%; severe: 10.5%) (p < 0.01). However, it did not improve in the conventional group (trivial-mild: 21.4%; moderate: 50.0%; severe: 28.6%) (p = 0.08). The diameter of the tricuspid annulus (p < 0.01), basal (p = 0.02), and mid right ventricle (p = 0.04) was reduced at follow-up in the TLV group. Nevertheless, these parameters did not change in the conventional group. Serum creatinine levels were maintained (p = 0.74) in the TLV group, but deteriorated in the conventional group (p = 0.03). TLV reduced right ventricular dimensions and improved TR without deterioration of renal function. Thus, TLV may be a new drug for the treatment of CHF patients with TR.

Dose Comparison Study of Allogeneic Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy (The TRIDENT Study).

RATIONALE: Cell dose and concentration play crucial roles in phenotypic responses to cell-based therapy for heart failure. OBJECTIVE: To compare the safety and efficacy of 2 doses of allogeneic bone marrow-derived human mesenchymal stem cells identically delivered in patients with ischemic cardiomyopathy. METHODS AND RESULTS: Thirty patients with ischemic cardiomyopathy received in a blinded manner either 20 million (n=15) or 100 million (n=15) allogeneic human mesenchymal stem cells via transendocardial injection (0.5 cc per injection × 10 injections per patient). Patients were followed for 12 months for safety and efficacy end points. There were no treatment-emergent serious adverse events at 30 days or treatment-related serious adverse events at 12 months. The Major Adverse Cardiac Event rate was 20.0% (95% confidence interval [CI], 6.9% to 50.0%) in 20 million and 13.3% (95% CI, 3.5% to 43.6%) in 100 million (P=0.58). Worsening heart failure rehospitalization was 20.0% (95% CI, 6.9% to 50.0%) in 20 million and 7.1% (95% CI, 1.0% to 40.9%) in 100 million (P=0.27). Whereas scar size reduced to a similar degree in both groups: 20 million by -6.4 g (interquartile range, -13.5 to -3.4 g; P=0.001) and 100 million by -6.1 g (interquartile range, -8.1 to -4.6 g; P=0.0002), the ejection fraction improved only with 100 million by 3.7 U (interquartile range, 1.1 to 6.1; P=0.04). New York Heart Association class improved at 12 months in 35.7% (95% CI, 12.7% to 64.9%) in 20 million and 42.9% (95% CI, 17.7% to 71.1%) in 100 million. Importantly, proBNP (pro-brain natriuretic peptide) increased at 12 months in 20 million by 0.32 log pg/mL (95% CI, 0.02 to 0.62; P=0.039), but not in 100 million (-0.07 log pg/mL; 95% CI, -0.36 to 0.23; P=0.65; between group P=0.07). CONCLUSIONS: Although both cell doses reduced scar size, only the 100 million dose increased ejection fraction. This study highlights the crucial role of cell dose in the responses to cell therapy. Determining optimal dose and delivery is essential to advance the field, decipher mechanism(s) of action and enhance planning of pivotal Phase III trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02013674.

Simultaneous Intravascular Ultrasound Usage Overcomes Misinterpretation When Evaluating Lipid-Rich Plaques With Optical Frequency Domain Imaging--Ex Vivo Study.

BACKGROUND: The aim of this study was to investigate the accuracy of optical frequency domain imaging (OFDI) in lipid-rich plaque detection and determine the causes of "misinterpretation," and evaluate whether these limitations can be overcome with intravascular ultrasound (IVUS) using ex-vivo human coronaries. METHODS AND RESULTS: The OFDI images and corresponding 218 histological segments were evaluated. Segments with a poor signal and diffuse borders on OFDI, classified as lipid-rich plaques, were compared with the histological segments and IVUS images. Using histological images as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of OFDI for the detection of lipid-rich plaques were 93%, 93%, 85%, and 97%, respectively. The causes of false-positive diagnosis of lipid-rich plaque (11 segments) were superficial macrophage infiltration causing signal attenuation (8/11 segments, 73%) and tangential signal dropout of light (3/11 segments, 27%), whereas the cause of false-negative diagnosis was thickening of the fibrous cap (5 segments, 100%). Simultaneous IVUS helped to correct the misinterpretation of OFDI results and improved the diagnostic accuracy; the sensitivity, specificity, positive predictive value, and negative predictive value of OFDI with adjunct use of IVUS were 96%, 99%, 99%, and 98%, respectively. CONCLUSIONS: OFDI occasionally over- or underestimates the existence of lipid-rich plaques, which may be overcome with adjunctive usage of IVUS.

Coronary angiographic characteristics that influence fractional flow reserve.

BACKGROUND: Percutaneous coronary intervention (PCI) guided with fractional flow reserve (FFR) has been shown to improve clinical outcome. Although coronary angiography is the standard method for PCI guidance, the visual severity of stenosis is not always correlated with functional severity, suggesting that there are additional angiographic factors that affect functional ischemia. METHODS AND RESULTS: To evaluate angiographic predictors of positive FFR in stenotic lesions, angiographic characteristics of 260 consecutive patients (362 lesions) who underwent FFR testing from April 2009 to September 2012 were analyzed. A scoring system (STABLED score) using these predictors was developed and compared with quantitative coronary angiography (QCA). %Diameter stenosis >50% (OR, 8.43; P<0.0001), tandem lesion (OR, 4.00; P<0.0001), true bifurcation (OR, 2.42; P=0.028), lesion length >20 mm (OR, 5.40; P=0.0002), and distance from ostium <20 mm (OR, 1.94; P=0.028) were determined as independent predictors of positive FFR. Area under the ROC curve for probability of positive FFR using the STABLED score (Stenosis 2 points, TAndem lesion 1 point, Bifurcation 1 point, LEsion length 1 point, Distance from ostium 1 point) was 0.85, higher than that for QCA stenosis alone (0.76). STABLED score ≥3 had 72.3% sensitivity and 83.6% specificity for predicting positive FFR, and PPV was 76.7%. CONCLUSIONS: Specific angiographic features are applicable for predicting functional ischemia. STABLED score correlates well with FFR.

Vericiguat and transcatheter edge-to-edge mitral valve repair for combined post- and pre-capillary pulmonary hypertension due to left ventricular low ejection fraction and functional mitral regurgitation.

A 66-year-old female was diagnosed with combined post- and pre-capillary pulmonary hypertension due to heart failure with reduced ejection fraction (47 %) and functional mitral regurgitation [mean pulmonary arterial wedge pressure: 27 mmHg; pulmonary arterial pressure: 91/30 (56) mmHg; pulmonary vascular resistance: 12.9 Wood units; and cardiac index: 1.77 L/min/m2]. Following treatment with vericiguat (a novel oral soluble guanylate cyclase stimulator), hemodynamics improved [mean pulmonary arterial wedge pressure: 27 mmHg; pulmonary arterial pressure: 54/26 (35) mmHg; pulmonary vascular resistance: 2.2 Wood units; and cardiac index: 2.80 L/min/m2]. Therefore, transcatheter edge-to-edge repair for functional mitral regurgitation was performed. One month later, further improvement in hemodynamics was confirmed. Learning objective: Vericiguat (a novel oral soluble guanylate cyclase stimulator) and transcatheter edge-to-edge mitral valve repair may improve combined post- and pre-capillary pulmonary hypertension due to low ejection fraction of the left ventricle and functional mitral regurgitation.

Left atrial diastasis strain slope is a marker of hemodynamic recovery in post-ST elevation myocardial infarction: the Laser Atherectomy for STemi, Pci Analysis with Scintigraphy Study (LAST-PASS).

Background: Left atrial (LA) mechanics are strongly linked with left ventricular (LV) filling. The LA diastasis strain slope (LADSS), which spans between the passive and active LA emptying phases, may be a key indicator of the LA-LV interplay during diastole. Aim: This study aimed to investigate the LA-LV interdependencies in post-ST elevation myocardial infarction (STEMI), with particular focus on the LADSS. Materials and methods: Patients with post-anterior STEMI who received primary percutaneous coronary intervention underwent contrast cardiac magnetic resonance imaging (MRI) during acute (5-9 days post-STEMI) and chronic (at 6 months) phases. The LADSS was categorized into three groups: Groups 1, 2, and 3 representing positive, flat, and negative slopes, respectively. Cross-sectional correlates of LADSS Group 2 or 3 compared to Group 1 were identified, adjusting for demographics, LA indices, and with or without LV indices. The associations of acute phase LADSS with the recovery of LV ejection fraction (LVEF) and scar amount were investigated. Results: Sixty-six acute phase (86.4% male, 63.1 ± 11.8 years) and 59 chronic phase cardiac MRI images were investigated. The distribution across LADSS Groups 1, 2, and 3 in the acute phase was 24.2%, 28.9%, and 47.0%, respectively, whereas in the chronic phase, it was 33.9%, 22.0%, and 44.1%, respectively. LADSS Group 3 demonstrated a higher heart rate than Group 1 in the acute phase (61.9 ± 8.7 vs. 73.5 ± 11.9 bpm, p < 0.01); lower LVEF (48.7 ± 8.6 vs. 41.8 ± 9.9%, p = 0.041) and weaker LA passive strain rate (SR) (-1.1 ± 0.4 vs. -0.7 [-1.2 to -0.6] s-1, p = 0.037) in the chronic phase. Chronic phase Group 3 exhibited weaker LA passive SR [relative risk ratio (RRR) = 8.8, p = 0.012] than Group 1 after adjusting for demographics and LA indices; lower LVEF (RRR = 0.85, p < 0.01), higher heart rate (RRR = 1.1, p = 0.070), and less likelihood of being male (RRR = 0.08, p = 0.058) after full adjustment. Acute phase LADSS Groups 2 and 3 predicted poor recovery of LVEF when adjusted for demographics and LA indices; LADSS Group 2 remained a predictor in the fully adjusted model (ß = -5.8, p = 0.013). Conclusion: The LADSS serves both as a marker of current LV hemodynamics and its recovery in post-anterior STEMI. The LADSS is an important index of LA-LV interdependency during diastole. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT03950310.

Lipid profile and risk factors for neoatherosclerosis after drug-eluting stent implantation in acute coronary syndrome.

BACKGROUND: Predictors of neoatherosclerosis in patients who received primary percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear. OBJECTIVE: The aim of this study is to investigate the frequency and risk factors of neoatherosclerosis 1-year after the onset of ACS. METHODS: This study investigated 83 patients who underwent PCI for ACS followed by 1-year follow-up optical coherence tomography. The patients were categorized into the neoatherosclerosis (n = 11) and non-neoatherosclerosis groups (n = 72). Baseline characteristics, PCI procedures, medical therapies, and blood tests at 1-year, including detailed lipid profiles, were compared between the two groups. RESULTS: Diabetes mellitus was more prominent in the neoatherosclerosis than in the non-neoatherosclerosis group (45% vs. 17 %, respectively, p = 0.03). Total cholesterol (171 ± 37 mg/dL vs. 145 ± 25 mg/dL, respectively, p < 0.01), non-high-density lipoprotein cholesterol (HDL-C) (124 ± 36 mg/dL vs. 94 ± 24 mg/dL, respectively, p < 0.01), low-density lipoprotein cholesterol (94 ± 36 mg/dL vs. 72 ± 19 mg/dL, respectively, p < 0.01), and lipoprotein (a) (Lp[a]) (70 [19-112] mg/dL vs. 10 [3-25] mg/dL, respectively, p = 0.03) at follow-up were significantly higher in the neoatherosclerosis group. Multivariate analysis revealed that neoatherosclerosis was associated with high serum non-HDL-C (odds ratio [OR]: 1.075; 95 % confidence interval [CI]: 1.011-1.144; p < 0.01) and high serum Lp(a) levels (>30 mg/dL) (OR: 11.0; 95 % CI: 1.492-81.02; p = 0.02). CONCLUSION: Poorly controlled non-HDL-C and Lp(a) would be risk factors of neoatherosclerosis in patients 1-year after ACS.

Optical frequency domain imaging-guided versus intravascular ultrasound-guided percutaneous coronary intervention for acute coronary syndromes: the OPINION ACS randomised trial.

BACKGROUND: The clinical benefits of optical frequency domain imaging (OFDI)-guided percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear. AIMS: We sought to compare intravascular ultrasound (IVUS)- and OFDI-guided PCI in patients with ACS. METHODS: OPINION ACS is a multicentre, prospective, randomised, non-inferiority trial that compared OFDI-guided PCI with IVUS-guided PCI using current-generation drug-eluting stents in ACS patients (n=158). The primary endpoint was in-stent minimum lumen area (MLA), assessed using 8-month follow-up OFDI. RESULTS: Patients presented with ST-segment elevation myocardial infarction (55%), non-ST-segment elevation myocardial infarction (29%), or unstable angina pectoris (16%). PCI procedural success was achieved in all patients, with comparably low periprocedural complications rates in both groups. Immediately after PCI, the minimum stent area (p=0.096) tended to be smaller for OFDI versus IVUS guidance. Proximal stent edge dissection (p=0.012) and irregular protrusion (p=0.03) were significantly less frequent in OFDI-guided procedures than in IVUS-guided procedures. Post-PCI coronary flow, assessed using corrected Thrombolysis in Myocardial Infarction frame counts, was significantly better in the OFDI-guided group than in the IVUS-guided group (p<0.001). The least squares mean (95% confidence interval [CI]) in-stent MLA at 8 months was 4.91 (95% CI: 4.53-5.30) mm2 and 4.76 (95% CI: 4.35-5.17) mm2 in the OFDI- and IVUS-guided groups, respectively, demonstrating the non-inferiority of OFDI guidance (pnon-inferiority<0.001). The average neointima area tended to be smaller in the OFDI-guided group. The frequency of major adverse cardiac events was similar. CONCLUSIONS: Among ACS patients, OFDI-guided PCI and IVUS-guided PCI were equally safe and feasible, with comparable in-stent MLA at 8 months. OFDI guidance may be a potential option in ACS patients. This study was registered in the Japan Registry of Clinical Trials (jrct.niph.go.jp: jRCTs052190093).

Short-term recurrence of takotsubo syndrome with phenotypic variation: a case report.

Background: Takotsubo syndrome (TTS) is an acute and usually reversible heart failure syndrome characterized as an uncommon left ventricular (LV) cardiomyopathy. Recurrence of TTS is rare, estimated to be 1-6%. We report a rare case of TTS that occurred three times in 2 months but manifested various phenotypes. Case summary: A 68-year-old woman was admitted to our hospital with acute-onset chest pain and hypertension. The coronary angiography findings were normal, although left ventriculography revealed inferior wall hypokinesis, leading to a mid-ventricular TTS diagnosis. She was discharged on Day 3 after her symptoms improved and vitals stabilized. The patient's condition remained uneventful until 2-week post-discharge, when acute chest pain and hypertension recurred. She was admitted again with the same diagnosis. However, LV morphology revealed an apical ballooning pattern, with inferior LV wall hypokinesis. She was discharged on Day 7 after her symptoms and electrocardiography findings improved but was readmitted again 2 weeks later after acute chest pain and hypertension recurred. Left ventriculography performed a third time demonstrated mid-ventricular TTS. The patient was prescribed additional medications and discharged on Day 12. Her electrocardiography findings normalized, and the patient remained asymptomatic without recurrence 4 months after the initial presentation. Discussion: Recurrence and phenotypic change of TTS are rare. Some cases have been reported but occurring months to years after initial diagnosis. Combined treatment with ß-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists may be more effective to prevent the recurrence than monotherapies.

Pathological Analysis of Medial and Intimal Calcification in Lower Extremity Artery Disease: Impact of Hemodialysis.

Background: The prevalence and degree of lower extremity artery disease in hemodialysis (HD) patients is higher than in the general population. However, the pathological features have not yet been evaluated. Objectives: The aim of the study was: 1) to compare lesion characteristics of lower extremity artery disease in HD vs non-HD patients; and 2) to determine factors associated with severe medial calcification. Methods: Seventy-seven lower limb arteries were assessed from 36 patients (median age 77 years; 23 men; 21 HD and 15 non-HD) who underwent autopsy or lower limb amputation. Arteries were serially cut at 3- to 4-mm intervals creating 2,319 histological sections. Morphometric analysis and calcification measurements were performed using ZEN software. Calcification with a circumferential angle (arc) ≥180° was defined as severe calcification. Multivariable logistic regression was used to identify risk factors for severe medial calcification. Results: The degree of the medial calcification arc was significantly higher in the HD group compared to the non-HD group (P < 0.0001). In the multivariable analysis, HD was associated with severe medial calcification in below-the-knee lesions (OR: 17.1; P = 0.02). The degree of intimal calcification in above-the-knee lesions was also significantly higher in HD patients with a higher prevalence of advanced atherosclerotic plaque (P = 0.02). The prevalence of severe bone formation was more common in the HD patients (P = 0.01). Conclusions: Hemodialysis patients demonstrated a higher degree of medial and intimal calcification compared with non-HD patients. The difference was more prominent in the medial calcification of below-the-knee lesions.

Diagnosis and Prognostic Value of the Underlying Cause of Acute Coronary Syndrome in Optical Coherence Tomography-Guided Emergency Percutaneous Coronary Intervention.

Background The prognostic impact of optical coherence tomography-diagnosed culprit lesion morphology in acute coronary syndrome (ACS) has not been systematically examined in real-world settings. Methods and Results This investigator-initiated, prospective, multicenter, observational study was conducted at 22 Japanese hospitals to identify the prevalence of underlying ACS causes (plaque rupture [PR], plaque erosion [PE], and calcified nodules [CN]) and their impact on clinical outcomes. Patients with ACS diagnosed within 24 hours of symptom onset undergoing emergency percutaneous coronary intervention were enrolled. Optical coherence tomography-guided percutaneous coronary intervention recipients were assessed for underlying ACS causes and followed up for major adverse cardiac events (cardiovascular death, myocardial infarction, heart failure, or ischemia-driven revascularization) at 1 year. Of 1702 patients with ACS, 702 (40.7%) underwent optical coherence tomography-guided percutaneous coronary intervention for analysis. PR, PE, and CN prevalence was 59.1%, 25.6%, and 4.0%, respectively. One-year major adverse cardiac events occurred most frequently in patients with CN (32.1%), followed by PR (12.4%) and PE (6.2%) (log-rank P<0.0001), primarily driven by increased cardiovascular death (CN, 25.0%; PR, 0.7%; PE, 1.1%; log-rank P<0.0001) and heart failure trend (CN, 7.1%; PR, 6.8%; PE, 2.2%; log-rank P<0.075). On multivariate Cox regression analysis, the underlying ACS cause was associated with 1-year major adverse cardiac events (CN [hazard ratio (HR), 4.49 [95% CI, 1.35-14.89], P=0.014]; PR (HR, 2.18 [95% CI, 1.05-4.53], P=0.036]; PE as reference). Conclusions Despite being the least common, CN was a clinically significant underlying ACS cause, associated with the highest future major adverse cardiac events risk, followed by PR and PE. Future studies should evaluate the possibility of ACS underlying cause-based optical coherence tomography-guided optimization.

Allogeneic Cell Combination Therapy Ameliorates Chronic Kidney Disease-Induced Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Left ventricular hypertrophy and heart failure with preserved ejection fraction (HFpEF) are primary manifestations of the cardiorenal syndrome in patients with chronic kidney disease (CKD). Therapies that improve morbidity and mortality in HFpEF are lacking. Cell-based therapies promote cardiac repair in ischemic and non-ischemic cardiomyopathies. We hypothesized that cell-based therapy ameliorates CKD-induced HFpEF. METHODS AND RESULTS: Yorkshire pigs (n = 26) underwent 5/6 embolization-mediated nephrectomy. CKD was confirmed by increased creatinine and decreased glomerular filtration rate (GFR). Mean arterial pressure (MAP) was not different between groups from baseline to 4 weeks. HFpEF was evident at 4 weeks by increased LV mass, relative wall thickening, end-diastolic pressure, and end-diastolic pressure-volume relationship, with no change in ejection fraction (EF). Four weeks post-embolization, allogeneic (allo) bone marrow-derived mesenchymal stem cells (MSC; 1 × 107 cells), allo-kidney-derived stem cells (KSC; 1 × 107 cells), allo-cell combination therapy (ACCT; MSC + KSC; 1:1 ratio; total = 1 × 107 cells), or placebo (Plasma-Lyte) was delivered via intra-renal artery. Eight weeks post-treatment, there was a significant increase in MAP in the placebo group (21.89 ± 6.05 mmHg) compared to the ACCT group. GFR significantly improved in the ACCT group. EF, relative wall thickness, and LV mass did not differ between groups at 12 weeks. EDPVR improved in the ACCT group, indicating decreased ventricular stiffness. CONCLUSIONS: Intra-renal artery allogeneic cell therapy was safe in a CKD swine model manifesting the characteristics of HFpEF. The beneficial effect on renal function and ventricular compliance in the ACCT group supports further research of cell therapy for cardiorenal syndrome.

Rationale and design of the TACTICS registry: Optical coherence tomography guided primary percutaneous coronary intervention for patients with acute coronary syndrome.

BACKGROUND: Recent retrospective investigations have suggested that optical coherence tomography (OCT) enables the diagnosis of underlying acute coronary syndrome (ACS) causes such as plaque rupture, plaque erosion, and calcified nodule. The relationships of these etiologies with clinical outcomes, and the clinical utility of OCT-guided primary percutaneous coronary intervention (PCI) are not systematically studied in real-world ACS treatment settings. METHODS: The TACTICS registry is an investigator-initiated, prospective, multicenter, observational study to be conducted at 21 hospitals in Japan. A total of 700 patients with ACS (symptom onset within 24 h) undergoing OCT-guided primary PCI will be enrolled. The primary endpoint of the study is to identify the underlying causes of ACS using OCT-defined morphological assessment of the culprit lesion. The key secondary clinical endpoints are hazard ratios of the composite of cardiovascular death, non-fatal myocardial infarction, heart failure, or ischemia-driven revascularization in patients with underlying etiologies at the 12- and 24-month follow-ups. The feasibility of OCT-guided primary PCI for ACS will be assessed by the achievement rates of optimal post-procedural results and safety endpoints. CONCLUSION: The TACTICS registry will provide an overview of the underlying causes of ACS using OCT, and will reveal any difference in clinical outcomes depending on the underlying causes. The registry will also inform on the feasibility of OCT-guided primary PCI for patients with ACS.

First Reported Use of a Visualization Device for the Radial Artery With Near-Infrared Rays Through the Transradial Approach.

OBJECTIVES: The transradial approach (TRA) is recommended in coronary catheterization due to the lower rate of bleeding complications compared with the transfemoral approach. However, a disadvantage of TRA is difficulty in puncturing under palpation of the radial pulse alone without arterial visibility. To overcome this limitation, a vessel visualization device using near-infrared rays, Art View (Forte Grow Medical Company), was used in the puncture of the radial artery (RA). METHODS: Patients who underwent coronary angiography via the right RA with Art View were retrospectively surveyed. According to the quality of RA visibility, the performance of the Art View was rated as follows: 5 = excellent; 4 = good; 3 = fair; 2 = not good; and 1 = poor. The primary endpoint was the procedural success of TRA using the Art View device. The secondary endpoints were procedural time (from injection of local anesthesia to successful crossing of the guidewire attached to the sheath), number of RA punctures, and change of puncture method or approach site. RESULTS: The Art View device was used in 38 patients (mean age, 71 ± 11 years). Puncturing of the visualized RA was successful in 30 patients (79.0%). Among successful cases, the mean procedural time was 142 ± 87 seconds. The success rates of each visualization evaluation were 100%, 100%, 84.6%, 33.3%, and 0% from grades 5 to 1, respectively (P<.01). The mean procedural times were 92 ± 18 seconds, 102 ± 58 seconds, 180 ± 75 seconds, 306 ± 80 seconds, and not available from grades 5 to 1, respectively (P<.01). CONCLUSION: The Art View RA visualization device is useful for RA puncture.

Clinical and procedure characteristics in patients treated with polytetrafluoroethylene-covered stents after coronary perforation: a CIRC-8U multicenter registry and literature review.

This study aimed at identifying the clinical characteristics and in-hospital outcomes of patients treated with polytetrafluorethylene (PTFE)-covered stents after coronary interventions in a multicenter registry. Subjects with coronary artery perforation were selected from 31,262 consecutive patients who underwent coronary interventions in the hospital registries. Subjects were divided into two groups: those with a PTFE-covered stent implantation and those without a PTFE-covered stent implantation. Clinical characteristics and in-hospital outcomes were compared between the two groups. Data for 82 consecutive coronary perforations (15 PTFE-covered stents and 67 non-PTFE-covered stents) were extracted from each hospital registry. The PTFE-covered stent group had a higher prevalence of perforations due to pre-dilatation before stenting or post-dilatation after stenting (80% vs. 10.4%; p < 0.001), more Ellis classification III perforations (66.6% vs. 28.4%; p = 0.019), longer perforation to hemostasis time (74 min vs. 10 min; p < 0.001), lower hemostatic success rates (73.3% vs. 94.0%; p = 0.015), and higher in-hospital mortality (26.7% vs. 6.0%; p = 0.015) than the non-PTFE-covered stent group. Although the prevalence of intravascular ultrasound (IVUS) usage was high during coronary interventions (86.7%), IVUS was performed in less than half the cases just before coronary perforations (47%) in the PTFE-covered stent group. Patients requiring PTFE-covered stents are more likely to be observed after balloon dilatation before or after stenting and have a poor prognosis. Careful coronary intervention is needed when IVUS image acquisition is not achieved in addition to proper evaluation of IVUS. Furthermore, if coronary artery perforation occurs, it is important to determine the need for a prompt PTFE-covered stent.