Impact of New-Onset Right Bundle-Branch Block After Transcatheter Aortic Valve Replacement on Permanent Pacemaker Implantation.

BACKGROUND: A delayed and recurrent complete atrioventricular block (CAVB) is a life-threatening complication of transcatheter aortic valve replacement (TAVR). Post-TAVR evaluation may be important in predicting delayed and recurrent CAVB requiring permanent pacemaker implantation (PPI). The impact of new-onset right bundle-branch block (RBBB) after TAVR on PPI remains unknown. METHODS AND RESULTS: In total, 407 patients with aortic stenosis who underwent TAVR were included in this analysis. Intraprocedural CAVB was defined as CAVB that occurred during TAVR. A 12-lead ECG was evaluated at baseline, immediately after TAVR, on postoperative days 1 and 5, and according to the need to identify new-onset bundle-branch block (BBB) and CAVB after TAVR. Forty patients (9.8%) required PPI, 17 patients (4.2%) had persistent intraprocedural CAVB, and 23 (5.7%) had delayed or recurrent CAVB after TAVR. The rates of no new-onset BBB, new-onset left BBB, and new-onset RBBB were 65.1%, 26.8%, and 4.7%, respectively. Compared with patients without new-onset BBB and those with new-onset left BBB, the rate of PPI was higher in patients with new-onset RBBB (3.4% versus 5.6% versus 44.4%, P<0.0001). On post-TAVR evaluation in patients without persistent intraprocedural CAVB, the multivariate logistic regression analysis showed that new-onset RBBB was a statistically significant predictor of PPI compared with no new-onset BBB (odds ratio [OR], 18.0 [95% CI, 5.94-54.4]) in addition to the use of a self-expanding valve (OR, 2.97 [95% CI, 1.09-8.10]). CONCLUSIONS: Patients with new-onset RBBB after TAVR are at high risk for PPI.

Association between evolocumab use and slow progression of aortic valve stenosis.

No medications have been reported to inhibit the progression of aortic valve stenosis (AS). The present study aimed to investigate whether evolocumab use is related to the slow progression of AS evaluated by serial echocardiography. This was a retrospective observational study from 2017 to 2022 at Yokohama City University Medical Center. Patients aged ≥ 18 with moderate AS were included. Exclusion criteria were (1) mild AS; (2) severe AS defined by maximum aortic valve (AV) velocity ≥ 4.0 m/s; and/or (3) no data of annual follow-up echocardiography. The primary endpoint was the association between evolocumab use and annual changes in the maximum AV-velocity or peak AV-pressure gradient (PG). A total of 57 patients were enrolled: 9 patients treated with evolocumab (evolocumab group), and the other 48 patients assigned to a control group. During a median follow-up of 33 months, the cumulative incidence of AS events (a composite of all-cause death, AV intervention, or unplanned hospitalization for heart failure) was 11% in the evolocumab group and 58% in the control group (P = 0.012). Annual change of maximum AV-velocity or peak AV-PG from the baseline to the next year was 0.02 (- 0.18 to 0.22) m/s per year or 0.60 (- 4.20 to 6.44) mmHg per year in the evolocumab group, whereas it was 0.29 (0.04-0.59) m/s per year or 7.61 (1.46-16.48) mmHg per year in the control group (both P < 0.05). Evolocumab use was associated with slow progression of AS and a low incidence of AS events in patients with moderate AS.

Elevated Leukocyte Count and Platelet-Derived Thrombogenicity Measured Using the Total Thrombus-Formation Analysis System in Patients with ST-Segment Elevation Myocardial Infarction.

AIMS: High platelet-derived thrombogenicity during the acute phase of ST-segment elevation myocardial infarction (STEMI) is associated with poor outcomes; however, the associated factors remain unclear. This study aimed to examine whether acute inflammatory response after STEMI affects platelet-derived thrombogenicity. METHODS: This retrospective observational single-center study included 150 patients with STEMI who were assessed for platelet-derived thrombogenicity during the acute phase. Platelet-derived thrombogenicity was assessed using the area under the flow-pressure curve for platelet chip (PL-AUC), which was measured using the total thrombus-formation analysis system (T-TAS). The peak leukocyte count was evaluated as an acute inflammatory response after STEMI. The patients were divided into two groups: the highest quartile of the peak leukocyte count and the other three quartiles combined. RESULTS: Patients with a high peak leukocyte count (＞15,222/mm3; n=37) had a higher PL-AUC upon admission (420 [386-457] vs. 385 [292-428], p=0.0018), higher PL-AUC during primary percutaneous coronary intervention (PPCI) (155 [76-229] vs. 96 [29-170], p=0.0065), a higher peak creatine kinase level (4200±2486 vs. 2373±1997, p＜0.0001), and higher PL-AUC 2 weeks after STEMI (119 [61-197] vs. 88 [46-122], p=0.048) than those with a low peak leukocyte count (≤ 15,222/mm3; n=113). The peak leukocyte count after STEMI positively correlated with PL-AUC during primary PPCI (r=0.37, p＜0.0001). A multivariable regression analysis showed the peak leukocyte count to be an independent factor for PL-AUC during PPCI (ß=0.26, p=0.0065). CONCLUSIONS: An elevated leukocyte count is associated with high T-TAS-based platelet-derived thrombogenicity during the acute phase of STEMI.

Coronary protection using a pressure wire during transcatheter aortic valve implantation.

Coronary obstruction is a rare but life-threatening complication of transcatheter aortic valve implantation (TAVI). This article describes the case of a patient with severe aortic valve stenosis treated with TAVI, during which preventive coronary wiring using a pressure wire was performed for coronary protection. After the deployment of the transcatheter heart valve (THV), the values of the fractional flow reserve (FFR) and resting full-cycle ratio (RFR) remarkably decreased, although the findings of transesophageal echocardiography and coronary angiography did not suggest coronary obstruction. Intravascular ultrasound revealed severe stenosis in the left main trunk due to the displacement of the calcified native leaflets. The decrease in the FFR and RFR values after THV deployment led to a diagnosis of partial coronary obstruction, and percutaneous coronary intervention was successfully performed. In patients at a high risk for coronary obstruction, coronary protection with a pressure wire is useful for the diagnosis and prevention of coronary flow deterioration during TAVI. Functional assessment using a pressure wire before and after TAVI may contribute to the accurate diagnosis of coronary obstruction. Learning objective: Accurate diagnosis of coronary obstruction during transcatheter aortic valve implantation (TAVI) is important for successful management. In patients at a high risk for coronary obstruction, coronary protection with a pressure wire is useful for the diagnosis and prevention of coronary flow deterioration during TAVI. The remarkable decrease in the fractional flow reserve and resting full-cycle ratio values after the deployment of the transcatheter heart valve may suggest coronary obstruction.

Influence of Obstructive Apnea Index on Persistent Left Ventricular Dysfunction in Patients with ST-Segment Elevation Myocardial Infarction.

Background: We retrospectively investigated the effects of the severity and classification of sleep-disordered breathing (SDB) on left ventricular (LV) function in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 115 patients with STEMIs underwent a sleep study using a multichannel frontopolar electroencephalography recording device (Sleep Profiler) one week after STEMI onset. We evaluated LV global longitudinal strain (LV-GLS) using two-dimensional echocardiography at one week and seven months. Patients were classified as no SDB (AHI < 5 events/h), obstructive SDB (over 50% of apnea events are obstructive), and central SDB (over 50% of apnea events are central). Due to the device's limitations in distinguishing obstructive from central hypopnea, SDB classification was based on apnea index percentages. Results: The obstructive apnea index (OAI) was significantly associated with LV-GLS at one week (r = 0.24, p = 0.027) and seven months (r = 0.21, p = 0.020). No such correlations were found for the central apnea index and SDB classification. Multivariable regression analysis showed that the OAI was independently associated with LV-GLS at one week (ß = 0.24, p = 0.002) and seven months (ß = 0.20, p = 0.008). Conclusions: OAI is associated with persistent LV dysfunction assessed by LV-GLS in STEMI.

Impact of Low-Density Lipoprotein Cholesterol Levels at Acute Coronary Syndrome Admission on Long-Term Clinical Outcomes.

AIM: Low-density lipoprotein cholesterol (LDL-C) level reduction is highly effective in preventing the occurrence of a cardiovascular event. Contrariwise, an inverse association exists between LDL-C levels and prognosis in some patients with cardiovascular diseases-the so-called "cholesterol paradox." This study aimed to investigate whether the LDL-C level on admission affects the long-term prognosis in patients who develop acute coronary syndrome (ACS) and to examine factors associated with poor prognosis in patients with low LDL-C levels. METHODS: We enrolled 410 statin-naïve patients with ACS, whom we divided into low- and high-LDL-C groups based on an admission LDL-C cut-off (obtained from the Youden index) of 122 mg/dL. Endothelial function was assessed using the reactive hyperemia index 1 week after statin initiation. The primary composite endpoint included all-cause death, as well as myocardial infarction and ischemic stroke occurrences. RESULTS: During a median follow-up period of 6.1 years, 76 patients experienced the primary endpoint. Multivariate Cox regression analysis revealed that patients in the low LDL-C group had a 2.3-fold higher risk of experiencing the primary endpoint than those in the high LDL-C group (hazard ratio, 2.34; 95% confidence interval, 1.29-4.27; p=0.005). In the low LDL-C group, slow gait speed (frailty), elevated chronic-phase high-sensitivity C-reactive protein levels (chronic inflammation), and endothelial dysfunction were significantly associated with the primary endpoint. CONCLUSIONS: Patients with low LDL-C levels at admission due to ACS had a significantly worse long-term prognosis than those with high LDL-C levels; frailty, chronic inflammation, and endothelial dysfunction were poor prognostic factors.

Ratio of left ventricular outflow tract area to aortic annulus area and complete atrioventricular block after transcatheter aortic valve replacement for aortic stenosis.

BACKGROUND: Mechanical compression of cardiac conduction system by transcatheter heart valves leads to complete atrioventricular block (CAVB) after transcatheter aortic valve replacement (TAVR). Bulging of ventricular septum in the left ventricular outflow tract (LVOT) may be associated with greater compression of conduction system, leading to irreversible CAVB. OBJECTIVE: This study aimed to investigate the association of ventricular septal bulging with TAVR-related CAVB and permanent pacemaker implantation (PPI). METHODS: Among 294 consecutive patients with severe aortic stenosis who underwent TAVR between July 2017 and February 2023, 271 were included in the analysis. As a quantitative evaluation of bulging of the ventricular septum, the ratio of LVOT area to aortic annulus area (L/A ratio) was measured at the systolic phase of computed tomography images. RESULTS: TAVR-related CAVB occurred in 64 patients (23.6%). Twenty-eight patients (10.3%) required PPI. The optimal thresholds of L/A ratio for predicting TAVR-related CAVB and PPI were 1.0181 and 0.985, respectively. Patients with less than the cut-off values had higher rate of TAVR-related CAVB and PPI than those above (28.3% vs 13.1%, p = 0.0063; 14.7% vs 4.4%, p = 0.0077, respectively). A multivariate analysis showed that L/A ratio < 1.0181 was an independent predictor of TAVR-related CAVB (odds ratio [OR] 2.65, p = 0.011), in addition to prior right bundle branch block (OR 3.76, p = 0.0005), use of a self-expanding valve (OR 1.99, p = 0.030), and short membranous septum length (OR 0.96, p = 0.037). Only L/A ratio < 0.985 was independently associated with PPI (OR 3.70, p = 0.011). CONCLUSION: Low L/A ratio is a predictor of TAVR-related CAVB and PPI.

Clinical Usefulness of Echocardiographic Measurement of Proximal Aortic Diameter in Early Differentiation Between Type A Acute Aortic Dissection and ST-Segment-Elevation Myocardial Infarction.

Background Contradictions between management modalities of type A acute aortic dissection (TAAAD) and ST-elevation-myocardial infarction (STEMI) may result in clinical catastrophe. Therefore, we aimed to explore which 2-dimensional echocardiography (2DE) findings are optimal for differentiating TAAAD from STEMI. Methods and Results This study included 340 patients with STEMI and 340 patients with TAAAD who underwent 2DE in the emergency department between 2012 and 2021. The proximal ascending aorta (PAA) diameter and other echocardiographic parameters were analyzed. PAA diameters were measured at 4 levels in the parasternal view: Valsalva, the sinotubular junction (STJ), the PAA at 1 cm above the STJ, and the PAA at 2 cm above the STJ. Receiver-operating characteristic curve analysis showed that Valsalva, STJ, PAA at 1 cm above the STJ, and PAA at 2 cm above the STJ were significant predictors of TAAAD (areas under the curve: 0.777, 0.924, 0.965, and 0.975, respectively; P<0.001) with the respective cutoff values of 39.4, 38.5, 39.8, and 41.2 mm. Multivariable analysis suggested that all 2DE parameters were significant predictors of TAAAD. Among the 2DE parameters examined, the incorporation of PAA at 2 cm above the STJ to clinical indicators exhibited the most significant diagnostic capability (C-statistics, 0.97; net reclassification improvement, 1.81; integrated discrimination improvement, 0.61). When only TAAAD with coronary malperfusion and STEMI were analyzed, the diagnostic utility of PAA at 1 cm above the STJ was evident (C-statistics, 0.99; net reclassification improvement, 1.79; integrated discrimination improvement, 0.67), with PAA at 2 cm above the STJ ranking second in diagnostic significance (C-statistics, 0.99; net reclassification improvement, 1.12; integrated discrimination improvement, 0.66). Conclusions PAA measurements were the most beneficial for diagnosing TAAAD in all 2DE findings and TAAAD from STEMI.

Prognostic importance of glycemic variability on left ventricular reverse remodeling after the first episode of ST-segment elevation myocardial infarction.

BACKGROUND: This study aimed to investigate the effect of glycemic variability (GV), determined using a continuous glucose monitoring system (CGMS), on left ventricular reverse remodeling (LVRR) after ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 201 consecutive patients with STEMI who underwent reperfusion therapy within 12 h of onset were enrolled. GV was measured using a CGMS and determined as the mean amplitude of glycemic excursion (MAGE). Left ventricular volumetric parameters were measured using cardiac magnetic resonance imaging (CMRI). LVRR was defined as an absolute decrease in the LV end-systolic volume index of > 10% from 1 week to 7 months after admission. Associations were also examined between GV and LVRR and between LVRR and the incidence of major adverse cardiovascular events (MACE; cardiovascular death, acute coronary syndrome recurrence, non-fatal stroke, and heart failure hospitalization). RESULTS: The prevalence of LVRR was 28% (n = 57). The MAGE was independent predictor of LVRR (odds ratio [OR] 0.98, p = 0.002). Twenty patients experienced MACE during the follow-up period (median, 65 months). The incidence of MACE was lower in patients with LVRR than in those without (2% vs. 13%, p = 0.016). CONCLUSION: Low GV, determined using a CGMS, was significantly associated with LVRR, which might lead to a good prognosis. Further studies are needed to validate the importance of GV in LVRR in patients with STEMI.

Biodegradable or durable polymer drug-eluting stents in patients with coronary artery disease: ten-year outcomes of the randomised NEXT Trial.

BACKGROUND: There are no randomised trials reporting clinical outcomes of biodegradable polymer biolimus-eluting stents (BP-BES) and durable polymer everolimus-eluting stents (DP-EES) at 10 years. AIMS: We aimed to compare the 10-year clinical outcomes between BP-BES and DP-EES. METHODS: The randomised NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-eluting Stent Trial (NEXT) was originally designed to evaluate the non-inferiority of BP-BES relative to DP-EES with the primary efficacy endpoint of target lesion revascularisation (TLR) at 1 year and the primary safety endpoint of death or myocardial infarction (MI) at 3 years. In this extended follow-up study, clinical outcomes were compared from 1 year after stent implantation up to 10 years between patients with BP-BES and DP-EES. RESULTS: From May to October 2011, NEXT enrolled a total of 3,241 patients from 98 centres in Japan. The current study population consisted of 2,417 patients (1,204 patients with BP-BES and 1,213 with DP-EES) from 66 centres that agreed to participate in the extended study. Complete 10-year follow-up was achieved in 87.5% of patients. The cumulative 10-year incidence of death or MI was 34.0% in the BP-BES group and 33.1% in the DP-EES group (hazard ratio [HR] 1.04, 95% confidence interval [CI]: 0.90-1.20; p=0.58). TLR occurred in 15.9% of patients in the BP-BES group and in 14.1% of the DP-EES group (HR 1.12, 95% CI: 0.90-1.40; p=0.32). In a landmark analysis at 1 year, the cumulative incidences of death or MI and TLR were not significantly different between the 2 groups. CONCLUSIONS: The safety and efficacy outcomes for BP-BES were not significantly different from those for DP-EES at 1 year and up to 10 years after stent implantation.

Intravascular Ultrasound in Vulnerable Plaque and Acute Coronary Syndrome.

Vulnerable plaque plays a pivotal role in the pathogenesis of acute coronary syndrome (ACS), being responsible for most ACS. The concept of vulnerable plaque has evolved with advancements in basic and clinical investigations along with developments and rapid expansion of coronary imaging modalities. Intravascular ultrasound (IVUS) is the first widely applied clinical technology with sufficient tissue penetration and enables us to identify vulnerable plaque and comprehensively understand the pathophysiology of ACS. In this review, we summarize current clinical evidence established by IVUS and the recent advancements in our understanding of vulnerable plaque and its role in ACS management.

Impact of myocardial bridging on coronary artery plaque formation and long-term mortality after heart transplantation.

OBJECTIVES: This study aimed to explore the impact of myocardial bridging (MB) on early development of cardiac allograft vasculopathy and long-term graft survival after heart transplantation. BACKGROUND: MB has been reported to be associated with acceleration of proximal plaque development and endothelial dysfunction in native coronary atherosclerosis. However, its clinical significance in heart transplantation remains unclear. METHODS: In 103 heart-transplant recipients, serial (baseline and 1-year post-transplant) volumetric intravascular ultrasound (IVUS) analyses were performed in the first 50 mm of the left anterior descending (LAD) artery. Standard IVUS indices were evaluated in 3 equally divided LAD segments (proximal, middle, and distal segments). MB was defined by IVUS as an echolucent muscular band lying on top of the artery. The primary endpoint was death or re-transplantation, assessed for up to 12.2 years (median follow-up: 4.7 years). RESULTS: IVUS identified MB in 62% of the study population. At baseline, MB patients had smaller intimal volume in the distal LAD than non-MB patients (p = 0.002). During the first year, vessel volume decreased diffusely irrespective of the presence of MB. Intimal growth diffusely distributed in non-MB patients, whereas MB patients demonstrated significantly augmented intimal formation in the proximal LAD. Kaplan-Meier analysis revealed significantly lower event-free survival in patients with versus without MB (log-rank p = 0.02). In multivariate analysis, the presence of MB was independently associated with late adverse events [hazard ratio 5.1 (1.6-22.2)]. CONCLUSION: MB appears to relate to accelerated proximal intimal growth and reduced long-term survival in heart-transplant recipients.

Endothelial dysfunction predicts bleeding and cardiovascular death in acute coronary syndrome.

BACKGROUNDS: Recently, there has been increasing awareness that bleeding may lead to adverse outcomes. Endothelial dysfunction is associated with increased risk of cardiovascular and bleeding events. This study aimed to investigate the association of endothelial dysfunction with major bleeding and specific causes of death in addition to major adverse cardiovascular events in patients with acute coronary syndrome. METHODS: This single-centre retrospective observational study was conducted at a tertiary-care hospital; patients with acute coronary syndrome were included between June 2010 and November 2014 (median follow-up, 6.1 years). The reactive hyperaemia index was assessed before their discharge; reactive hyperaemia index <1.67 was defined as endothelial dysfunction. The main outcomes were the incidence of major bleeding, all-cause death, cardiovascular death, non-cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. RESULTS: Among the included 674 patients with acute coronary syndrome, 264 (39.2%) had endothelial dysfunction. Multivariable Cox-hazard analyses revealed an independent predictive value of endothelial dysfunction for major bleeding (hazard ratio 2.29, 95% confidence interval 1.17-4.48, P = 0.016) and major adverse cardiovascular events (hazard ratio 2.04, 95% confidence interval 1.43-2.89, P < 0.001). The endothelial dysfunction group patients had a 2.5-fold greater risk of cardiovascular death; however, no association was found with non-cardiovascular death. CONCLUSION: Endothelial dysfunction assessed using reactive hyperaemia index predicted future major cardiovascular event as well as major bleeding and cardiovascular death in patients with acute coronary syndrome.

Clinical impact of left ventricular systolic dysfunction in patients undergoing dialysis access surgery.

BACKGROUND: An arteriovenous fistula (AVF) is the most frequently used dialysis access for haemodialysis. However, it can cause volume loading for the heart and may induce circulatory failure when performed in patients with low cardiac function. This study aimed to characterise patients with low cardiac function when initiating dialysis and determine how cardiac function changes after the dialysis access surgery. METHODS: We conducted a retrospective observational study at two centres incorporating 356 patients with end-stage kidney disease who underwent echocardiography before the dialysis access surgery. RESULTS: An AVF and a subcutaneously fixed superficial artery were selected in 70.4% and 23.5% of 81 patients with reduced/mildly reduced (< 50%) left ventricular ejection fraction (LVEF), respectively, and in 94.2% and 1.1% of 275 patients with preserved (≥ 50%) LVEF (p < 0.001), respectively. Follow-up echocardiography was performed in 70.4% and 38.2% of patients with reduced/mildly reduced and preserved LVEF, respectively, which showed a significant increase in LVEF (41 ± 9-44 ± 12%, p = 0.038) in patients with reduced/mildly reduced LVEF. LVEF remained unchanged in 12 patients with reduced/mildly reduced LVEF who underwent subcutaneously fixed superficial artery (30 ± 10-32 ± 15%, p = 0.527). Patients with reduced/mildly reduced LVEF had lower survival rates after surgery than those with preserved LVEF (p = 0.021 for log-rank). CONCLUSION: The LVEF subcategory was associated with dialysis access selection. After the dialysis access surgery, LVEF was increased in patients with reduced/mildly reduced LVEF. These results may help select dialysis access for patients initiating dialysis.

Prognostic impact of upper and lower extremity muscle mass in heart failure.

AIMS: Reduced skeletal muscle mass is a major component of sarcopenia, associated with impaired exercise capacity and poor prognosis in patients with heart failure (HF). Measurement of skeletal muscle mass by dual-energy X-ray absorptiometry may be affected by fluid retention, typically in the patients' lower extremities. The aim of the present study was to elucidate the association between upper and lower extremity skeletal muscle mass (USM and LSM) and all-cause mortality in hospitalized patients with HF, after discharge. METHODS: This was a single-centre observational cohort study of 418 patients (59% were men) admitted with a diagnosis of HF (71 ± 13 years), with a left ventricular ejection fraction of 39 ± 16%. USM and LSM were measured by dual-energy X-ray absorptiometry with patients in a stable state after decongestion therapy. RESULTS: The USM and LSM were 5.29 ± 1.18 and 13.78 ± 3.20 kg for men and 3.37 ± 0.68 and 9.19 ± 1.80 kg for women. A positive correlation was obtained between USM and LSM with mid-upper arm circumference (r = 0.684, P < 0.001) and calf circumference (r = 0.822, P < 0.001), respectively. During a median follow-up of 37 months, 92 (22.0%) of the 418 patients died. A Kaplan-Meier analysis revealed that sex-specific quartiles of USM/height2 and LSM/height2 were associated with all-cause mortality (both P < 0.001 by the log-rank test). In Cox models adjusted by age, sex, creatinine, haemoglobin, NYHA class, and height2 , the hazard ratio with 95% confidence intervals for all-cause mortality was 0.557 [0.393-0.783] (P < 0.001) for USM per 1 kg, and 0.783 [0.689-0.891] (P < 0.001) for LSM per 1 kg. The receiver-operator-characteristic curve analysis showed a comparable area under the curve between the USM/height2 and LSM/height2 (0.557 vs. 0.568, P = 0.562) in predicting all-cause mortality. The ratio of USM to LSM was significantly lower in 37 patients with residual leg oedema than in the 360 patients without oedema (36.1% vs. 38.1%, P = 0.004), suggesting the influence of oedema on measured LSM. CONCLUSIONS: Both USM and LSM had a prognostic implication on mortality after discharge in HF, even though LSM may have been affected by leg oedema. These findings indicate that clinicians should not ignore a patient's USM or LSM in the prognostication of patients with HF.

Heterogeneous vascular response after implantation of bare nitinol self-expanding stents in the swine femoropopliteal artery.

BACKGROUND: Mechanism of femoropopliteal in-stent restenosis has been underappreciated. AIM: The aim of this animal study was to elucidate vascular response after femoropopliteal bare nitinol self-expanding stents (SESs) implantation. METHODS: Misago, Smart Flex, or Innova stent was randomly implanted in 36 swine femoropopliteal arteries. At week 4, quantitative vessel analysis (QVA) was performed on 36 legs, of which 18 underwent histological evaluation after angiography. The remaining 18 legs underwent QVA and histological evaluation at week 13. RESULTS: Fibrin deposition was excessive at week 4. Internal elastic lamina (IEL) progressively enlarged over time, and vessel injury developed from mild level at week 4 to moderate level at week 13. Vessel inflammatory reaction was mild to moderate at week 4, and was moderate to severe at week 13. Increased fibrin deposition was an early-acting, IEL enlargement and increased vessel inflammation were long-acting, and increased vessel injury and giant cells infiltration were late-acting contributors to neointimal hyperplasia (NIH). Stent type altered time-dependent process of vessel injury, vessel inflammation, eosinophils and giant cells infiltration. Misago had less fibrin deposition and vessel enlargement, and less progressive vessel injury, vessel inflammation, and eosinophils and giant cells infiltration. Net lumen as assessed by percent diameter stenosis or minimum lumen diameter was preserved with Misago, but was not preserved with the other stents. CONCLUSIONS: In the context of bare nitinol SES platform with less progressive mechanical stress and inflammatory reaction, the advantage of less NIH outweighed the disadvantage of less vessel enlargement, leading to net lumen preservation.

Culprit Lesion Morphology of Rapidly Progressive and Extensive Anterior-Wall ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Rapidly progressive, extensive myocardial injury/infarction (RPEMI) beyond the concept of wave-front phenomenon can be observed even when achieving timely reperfusion; however, the pathogenesis of RPEMI remains unknown. This retrospective study investigated clinical and lesion characteristics of RPEMI, focusing on culprit-lesion morphology (CLM). METHODS: Among patients with extensive anterior-wall ST-segment elevation myocardial infarction due to proximal left anterior descending artery lesions who had reperfusion within 3 hours of symptom onset, 60 patients undergoing both intravascular ultrasound and cardiac magnetic resonance imaging were enrolled. Myocardial injury/infarction before reperfusion therapy was assessed by QRS scores at hospitalization electrocardiogram, and the extent of myocardial injury/infarction was evaluated by cardiac magnetic resonance imaging, which measured area at risk, infarct size, myocardial salvage index, microvascular obstruction, and left ventricular ejection fraction. RPEMI was defined as lower left ventricular ejection fraction (less median value) with microvascular obstruction. RESULTS: Despite comparable onset-to-door and onset-to-reperfusion times and area at risk, patients with RPEMI showed higher QRS scores at hospitalization (5 [4.3-6] versus 3 [2-4], P<0.001) and infarct size (26.5±9.1 versus 20.4±10.5%, P=0.04), and a tendency toward lower myocardial salvage index (0.27±0.14 versus 0.36±0.20, P=0.10) compared with those without. Patients with versus without RPEMI more frequently observed specific CLM on intravascular ultrasound, characterized by the combination of vulnerable plaques, plaque ruptures, and/or large thrombi. When stratified by CLM-score composed of these 3 criteria, higher CLM-scores were or tended to be associated with higher QRS scores and incidence of RPEMI. In multivariate analyses including no-reflow phenomenon and final coronary-flow deterioration, increased CLM-score (≥2) was independently associated with high QRS scores and RPEMI (odd ratio 11.25 [95% CI, 2.43-52.00]; P=0.002). CONCLUSIONS: Vulnerable CLM was a consistent determinant of advanced myocardial injury/infarction both before and after reperfusion therapy and may play a pivotal role in the development of RPEMI.

Impact of early intervention with alogliptin on coronary plaque regression and stabilization in patients with acute coronary syndromes.

BACKGROUND AND AIMS: Anti-atherosclerotic effects of early intervention with dipeptidyl peptidase-4 inhibitors remain poorly defined. METHODS: In a prospective, single-center, randomized trial, 66 patients with acute coronary syndrome (ACS) and mild dysglycemia (HbA1c 6.0 (5.7, 6.3)%, 58% of impaired glucose tolerance) were randomly assigned to receive alogliptin (n = 33) or placebo (n = 33) in addition to standard treatments. Serial intravascular ultrasound (IVUS) was performed at baseline and 10 months to evaluate changes in coronary percent plaque volumes (%PV) and plaque tissue components of non-culprit lesions (NCLs). RESULTS: Baseline clinical and IVUS characteristics, as well as decreases in HbA1c and lipid variables during 10 months, did not differ significantly between the 2 groups. In contrast, with respect to vascular responses, the alogliptin group showed significantly greater decreases in plaque volumes (-0.3 ± 0.6 vs. -0.04 ± 0.7 mm3/mm, p = 0.03) and %PV (-0.9 ± 2.8 vs. 1.2 ± 3.6%, p = 0.01), with a tendency toward smaller lumen loss (-0.1 ± 0.7 vs. -0.4 ± 0.8 mm3/mm, p = 0.07) compared with the placebo group. Significantly decreased percent necrotic volumes (%NV) (-1.9 ± 3.8 vs. 0.3 ± 3.7%, p = 0.03) and increased fibrotic volumes (2.5 ± 5.0 vs. -0.3 ± 5.3%, p = 0.05) were or tended to be seen in alogliptin versus placebo groups at 10 months. In multiple regression analysis, alogliptin use was a statistically significant determinant of changes in %PV (ß = -0.33, p = 0.004) and %NV (ß = -0.28, p = 0.03) at 10 months. CONCLUSIONS: Alogliptin treatment, independently of glycemic and lipid status, resulted in significant plaque regression and stabilization in NCLs in patients with ACS and mild dysglycemia, suggesting the potential utility of early intervention with incretin-based treatments for this patients' subset.