Potential confounders of the obesity paradox in older patients following transcatheter aortic valve replacement.

PURPOSE: A higher body mass index (BMI) is associated with lower mortality in older patients following transcatheter aortic valve replacement (TAVR) for severe aortic valve stenosis. The current study aimed to investigate potential confounders of association between BMI and prognosis. METHODS: The retrospective single-center study included consecutive patients following TAVR and excluded those in whom subcutaneous fat accumulation (SFA), visceral fat accumulation (VFA), and major psoas muscle (MPM) volume were not assessed by computed tomography. Cachexia was defined as a combination of BMI < 20 kg/m2 and any biochemical abnormalities. RESULTS: After 2 patients were excluded, 234 (age, 86 ± 5 years; male, 77 [33%]; BMI, 22.4 ± 3.8 kg/m2; SFA, 109 (54-156) cm2; VFA, 71 (35-115) cm2; MPM, 202 (161-267) cm3; cachexia, 49 [21%]) were evaluated. SFA and VFA were strongly correlated with BMI (ρ = 0.734 and ρ = 0.712, respectively), whereas MPM was weakly correlated (ρ = 0.346). Two-year all-cause mortality was observed in 31 patients (13%). Higher BMI was associated with lower mortality (adjusted hazard ratio [aHR], 0.86; 95% confidence interval [CI], 0.77-0.95). A similar result was observed in the multivariate model including SFA (aHR in an increase of 20 cm2, 0.87; 95% CI, 0.77-0.98) instead of BMI, whereas VFA was not significant. Cachexia was a worse predictor (aHR, 2.51; 95% CI 1.11-5.65). CONCLUSIONS: Association of higher BMI with lower mortality may be confounded by SFA in older patients following TAVR. Cachexia might reflect higher mortality in patients with lower BMI.

Assessment of Residual Vasospasm in Patients with Plaque Rupture or Plaque Erosion using Optical Coherence Tomography.

AIMS: Coronary vasospasm is associated with acute coronary syndrome (ACS) and may persist during primary percutaneous coronary intervention (PCI). We aimed to elucidate the incidence, morphological characteristics, and prognostic impact of residual vasospasm in plaque rupture (PR) and plaque erosion (PE) lesions using optical coherence tomography (OCT). METHODS: We enrolled 142 patients with ACS who underwent OCT-guided primary PCI. All patients received intracoronary vasodilators before OCT examination. Residual vasospasm was identified as intimal gathering and categorised as polygonal- or wavy- patterned depending on the luminal shape. A wavy pattern was defined as a curved intimal surface line. A polygonal pattern was defined as a lumen with multiple angles. The incidence of major cardiovascular events, defined as death, non-fatal myocardial infarction, stroke, and any revascularization, within 1-year of PCI was identified. RESULTS: The prevalence of residual vasospasm in PR and PE was 15.1% (13 of 86) and 21.4% (12 of 56), respectively. Wavy pattern was the major shape of the residual vasospasm. Polygonal-patterned lumen was more frequently observed in PR than in PE (38.5 vs. 8.3 %). The polygonal-patterned lumens had significantly larger lipid arcs (257.9 vs. 78.0 °; P＜0.01), and significantly smaller areas (1.27 vs. 1.88 mm2; P=0.05) than wavy patterned lumens. Residual vasospasm had a prognostic impact on PR but not PE at 1-year of successful primary PCI. CONCLUSION: Considerable proportion of ACS including both PR and PE had residual vasospasm with variable morphological feature and different prognostic impact.

Association between Eicosapentaenoic Acid to Arachidonic Acid Ratio and Characteristics of Plaque Rupture.

AIMS: Eicosapentaenoic acid (EPA) has shown beneficial effects on coronary plaque stabilization. Based on our previous study, we speculated that EPA might be associated with the development of healed plaques and might limit thrombus size. This study aimed to elucidate the association between EPA and arachidonic acid (AA) ratios and various plaque characteristics in patients with plaque rupture. METHODS: A total of 95 patients with acute coronary syndrome (ACS) caused by plaque rupture who did not take lipid-lowering drugs and underwent percutaneous coronary intervention using optical coherence tomography (OCT) were included. Clinical characteristics, lipid profiles, and OCT findings were compared between patients with lower and higher EPA/AA ratios (0.41) according to the levels in the Japanese general population. RESULTS: In the high EPA/AA (n=29, 30.5%) and low EPA/AA (n=66, 69.5 %) groups, the high EPA/AA group was significantly older (76.1 vs. 66.1 years, P＜0.01) and had lower peak creatine kinase (556 vs. 1651 U/L, P=0.03) than those with low EPA/AA. Similarly, patients with high EPA/AA had higher prevalence of layered and calcified plaque (75.9 vs. 39.4 %, P＜0.01; 79.3 vs. 50.0 %, P＜0.01, respectively) than low EPA/AA group. Multivariate logistic regression analysis demonstrated that a high EPA/AA ratio was an independent factor in determining the development of layered and calcified plaques. CONCLUSION: A high EPA/AA ratio may be associated with the development of layered and calcified plaques in patients with plaque rupture.

Impact of triglyceride-rich lipoproteins on early in-stent neoatherosclerosis formation in patients undergoing statin treatment.

BACKGROUND: Neoatherosclerosis (NA), which refers to neointimal atherosclerosis within a stent, is considered one of the underlying causes of late-phase stent failure following a newer generation drug-eluting stent (DES) placement procedure. Even contemporary guideline-directed medical therapy may be insufficient to prevent NA. OBJECTIVE: This study aimed to investigate how intricately lipid markers are associated with NA formation in the early phase of treatment with well-maintained low-density lipoprotein cholesterol (LDL-C) levels. METHODS: We enrolled 114 consecutive patients undergoing statin treatment and percutaneous coronary intervention (PCI) with current-generation DES for coronary artery disease. At a median 12 months after PCI, optical coherence tomography (OCT) was performed. Various lipid markers, including LDL-C, triglyceride (TG), triglyceride-rich lipoprotein cholesterol (TRL-C), non-high-density lipoprotein cholesterol (non-HDL-C), malondialdehyde-modified LDL (MDA-LDL), and several apolipoproteins, were also evaluated. RESULTS: NA was observed in 17 (14.9%) patients. The LDL-C level was equivalent in patients with or without NA (77.2 vs. 69.8 mg/dL; p=0.15). However, the levels of TG, apolipoprotein C3 (apoC3), TRL-C, non-HDL-C, and apolipoprotein B (apoB), and MDA-LDL were significantly higher in the patients with NA. Furthermore, multivariate logistic regression adjusting for HbA1c and stent duration revealed apoC3, TRL-C, non-HDL-C, apoB, and MDA-LDL levels as risk factors for NA. However, when apoB was included as a covariate, other factors became nonsignificant. CONCLUSIONS: Abnormal triglyceride-rich lipoprotein metabolism and high atherogenic apoB-containing lipoprotein particle numbers are associated with the formation of NA in patients undergoing statin treatment at a median 12 months post-PCI.

Insufficient adenosine-induced hyperemia is a major determinant of discordance between non-hyperemic pressure ratio and fractional flow reserve.

Adenosine occasionally overestimates fractional flow reserve (FFR) values (i.e., insufficient adenosine-induced hyperemia), leading to low non-hyperemic pressure ratios (NHPR)-high FFR discordance. We investigated the impact of insufficient adenosine-induced hyperemia on NHPR-FFR discordance and the reclassification of functional significance. We measured resting distal-to-aortic pressure ratio (Pd/Pa) and FFR by using adenosine (FFRADN) and papaverine (FFRPAP) in 326 patients (326 vessels). FFRADN overestimation was calculated as FFRADN - FFRPAP. We explored determinants of low Pd/Pa - high FFRADN discordance (Pd/Pa ≤ 0.92 and FFRADN > 0.80) versus high Pd/Pa - low FFRADN discordance (Pd/Pa > 0.92 and FFRADN ≤ 0.80). Reclassification of functional significance was defined as FFRADN > 0.80 and FFRPAP ≤ 0.80. Multivariable analysis identified FFRADN overestimation (p = 0.002) and heart rate at baseline (p = 0.048) as independent determinants of the low Pd/Pa-high FFRADN discordance. In the low Pd/Pa-high FFRADN group (n = 26), papaverine produced a further decline in the FFR value in 21 vessels (81%) compared with FFRADN, and the reclassification was observed in 17 vessels (65%). Insufficient adenosine-induced hyperemia is a major determinant of the low resting Pd/Pa-high FFR discordance. Physicians should bear in mind that the presence of low NHPR-high FFR discordance may indicate a false-negative FFR result.

Impact of overestimation of fractional flow reserve by adenosine on anatomical-functional mismatch.

Adenosine occasionally results in overestimation of fractional flow reserve (FFR) values, compared with other hyperemic stimuli. We aimed to elucidate the association of overestimation of FFR by adenosine with anatomically significant but functionally non-significant lesions (anatomical-functional mismatch) and its influence on reclassification of functional significance. Distal-to-aortic pressure ratio (Pd/Pa) was measured using adenosine (Pd/PaADN) and papaverine (Pd/PaPAP) in 326 patients (326 vessels). The overestimation of FFR was calculated as Pd/PaADN-Pd/PaPAP. The anatomical-functional mismatch was defined as diameter stenosis > 50% and Pd/PaADN > 0.80. Reclassification was indicated by Pd/PaADN > 0.80 and Pd/PaPAP ≤ 0.80. The mismatch (n = 72) had a greater overestimation of FFR than the non-mismatch (n = 99): median 0.02 (interquartile range 0.01-0.05) versus 0.01 (0.00-0.04), p = 0.014. Multivariable analysis identified the overestimation of FFR (p = 0.003), minimal luminal diameter (p = 0.001), and non-left anterior descending artery (LAD) location (p < 0.001) as determinants of the mismatch. Reclassification was indicated in 29% of the mismatch and was more frequent in the LAD than in the non-LAD (52% vs. 20%, p = 0.005). The overestimation of FFR is an independent determinant of anatomical-functional mismatch. Anatomical-functional mismatch, specifically in the LAD, may suggest a false-negative result.

Impact of small dense low-density lipoprotein cholesterol and triglyceride-rich lipoproteins on plaque rupture with ST-segment elevation myocardial infarction.

BACKGROUND: 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. OBJECTIVE: To elucidate the impact of sd-LDL-C and TRL levels on PR in patients with STEMI using optical coherence tomography (OCT). METHODS: 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). RESULTS: 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). CONCLUSION: Only sd-LDL-C levels were significantly associated with PR in culprit lesions in patients with STEMI.

Clinical features and lipid profiles of plaque erosion over lipid-rich plaque versus fibrous plaque in patients with acute coronary syndrome.

BACKGROUND AND AIMS: Pathological reports have shown that plaque erosion (PE), a common cause of acute coronary syndrome (ACS), can form in both fibrous plaque and lipid-rich plaque (LRP). In plaque rupture (PR), which is the main cause of ACS, the underlying plaque is LRP with a thin fibrous cap. In this study, we aimed to investigate the clinical features and lipid profiles of PE with or without LRP in comparison with those of PR. METHODS: A total of 166 patients with ACS, who underwent percutaneous coronary intervention using optical coherence tomography (OCT) and met the criteria for PR or PE, were included. LRP was defined as plaque with a maximal lipid arc (>180°). Culprit lesions were categorized into PR and PE with/without LRP [PE(Lipid) or PE(Fibrous)]. RESULTS: The prevalence of PR, PE(Lipid), and PE(Fibrous) was 104 (62.7%), 43 (25.9%), and 19(11.4%), respectively. The patients with PR and PE(Lipid) had a significantly higher peak creatine kinase level (1338 and 1584U/L, respectively, p < 0.01) and prevalence of ST-elevation myocardial infarction (71.2% and 79.1%, respectively, p < 0.01) than those with PE(Fibrous) (214U/L and 21.1%, respectively). The various lipid profiles were mostly comparable between the patients with PE(Lipid) and PR, but different in those with PE(Fibrous). The levels of small dense low-density lipoprotein cholesterol were significantly higher in the patients with PR and PE(Lipid) than in those with PE(Fibrous) (39.0, 35.3, and 25.7 mg/dL, respectively, p = 0.02). CONCLUSIONS: The clinical features and lipid profiles are substantially different between PE(Lipid) and PE(Fibrous), but are somewhat similar between PE(Lipid) and PR.

Impact of small dense low-density lipoprotein cholesterol on cholesterol crystals in patients with acute coronary syndrome: An optical coherence tomography study.

BACKGROUND: 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. OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: sd-LDL may play an important role in the presence of CC in patients with ACS.

Coronary High-Intensity Plaques at T1-weighted MRI in Stable Coronary Artery Disease: Comparison with Near-Infrared Spectroscopy Intravascular US.

Background The histologic nature of coronary high-intensity plaques (HIPs) at T1-weighted MRI in patients with stable coronary artery disease remains to be fully understood. Coronary atherosclerosis T1-weighted characterization (CATCH) enables HIP detection by simultaneously acquiring dark-blood plaque and bright-blood anatomic reference images. Purpose To determine if intraplaque hemorrhage (IPH) or lipid is the predominant substrate of HIPs on T1-weighted images by comparing CATCH MRI scans with findings on near-infrared spectroscopy (NIRS) intravascular US (IVUS) images. Materials and Methods This study retrospectively included consecutive patients who underwent CATCH MRI before NIRS IVUS between December 2019 and February 2021 at two facilities. At MRI, HIP was defined as plaque-to-myocardium signal intensity ratio of at least 1.4. The presence of an echolucent zone at IVUS (reported to represent IPH) was recorded. NIRS was used to determine the lipid component of atherosclerotic plaque. Lipid core burden index (LCBI) was calculated as the fraction of pixels with a probability of lipid-core plaque greater than 0.6 within a region of interest. Plaque with maximum LCBI within any 4-mm-long segment (maxLCBI4 mm) greater than 400 was regarded as lipid rich. Multivariable analysis was performed to evaluate NIRS IVUS-derived parameters associated with HIPs. Results There were 205 plaques analyzed in 95 patients (median age, 74 years; interquartile range [IQR], 67-78 years; 75 men). HIPs (n = 42) at MRI were predominantly associated with an echolucent zone at IVUS (79% [33 of 42] vs 8.0% [13 of 163], respectively; P < .001) and a higher maxLCBI4 mm at NIRS (477 [IQR, 258-738] vs 232 [IQR, 59-422], respectively; P < .001) than non-HIPs. In the multivariable model, HIPs were independently associated with an echolucent zone (odds ratio, 24.5; 95% CI: 9.3, 64.7; P < .001), but not with lipid-rich plaque (odds ratio, 2.0; 95% CI: 0.7, 5.4; P = .20). Conclusion The predominant substrate of T1-weighed MRI-defined high-intensity plaques in stable coronary artery disease was intraplaque hemorrhage, not lipid. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Stuber in this issue.

Linear concentration-response relationship of serum caffeine with adenosine-induced fractional flow reserve overestimation: a comparison with papaverine.

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 <12 hours in 85 patients, at 12-24 hours in 35 patients, and at >24 hours in 89 patients. Multiple regression analysis identified serum caffeine level as the strongest factor associated with FFRADN overestimation (p<0.001). 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 >24-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.

Early Vascular Healing Following Bioresorbable-Polymer Sirolimus-Eluting Stent Placement Compared to That with Durable-Polymer Everolimus-Eluting Stent.

A recent thinner strut drug-eluting stent might facilitate early strut coverage after its placement. We aimed to investigate early vascular healing responses after the placement of an ultrathin-strut bioresorbable-polymer sirolimus-eluting stent (BP-SES) compared to those with a durable-polymer everolimus-eluting stent (DP-EES) using optical coherence tomography (OCT) imaging.This study included 40 patients with chronic coronary syndrome (CCS) who underwent OCT-guided percutaneous coronary intervention (PCI). Twenty patients each received either BP-SES or DP-EES implantation. OCT was performed immediately after stent placement (baseline) and at 1-month follow-up.At one month, the percentage of uncovered struts reduced significantly in both the BP-SES (80.9 ± 10.3% to 2.9 ± 1.7%; P < 0.001) and DP-EES (81.9 ± 13.0% to 5.7 ± 1.8%; P < 0.001) groups, and the percentage was lower in the BP-SES group than in the DP-EES group (P < 0.001). In the BP-SES group, the percentage of malapposed struts also decreased significantly at 1 month (4.9 ± 3.7% to 2.6 ± 3.0%; P = 0.025), which was comparable to that of the DP-EES group (2.5 ± 2.2%; P = 0.860). The optimal cut-off value of the distance between the strut and vessel surface immediately after the placement to predict resolved malapposed struts was ≤ 160 µm for BP-SES and ≤ 190 µm for DP-EES.Compared to DP-EES, ultrathin-strut BP-SES demonstrated favorable vascular responses at one month, with a lower rate of uncovered struts and a comparable rate of malapposed struts.

Small Dense Low-Density Lipoprotein Cholesterol: A Residual Risk for Rapid Progression of Non-Culprit Coronary Lesion in Patients with Acute Coronary Syndrome.

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.

Early Vascular Response to Ultrathin Biodegradable Polymer Sirolimus-Eluting Stents for the Treatment of ST-Elevation Myocardial Infarction After Plaque Rupture.

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).

Feasibility of intracoronary nicorandil for inducing hyperemia on fractional flow reserve measurement: Comparison with intracoronary papaverine.

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 < 0.001 and p = 0.0026). Likewise, FFRNC2 was higher than FFRPAP in groups 2 (p = 0.049) and 3 (p < 0.010). In the whole group, Bland-Altman analysis showed a modest mean difference (0.015, p < 0.001) and narrow 95% limits of agreement (-0.025 and 0.056). FFRNC2 and FFRPAP strongly correlated (r = 0.975, p < 0.001). Compared with FFRPAP, FFRATP and FFRATP+NC2 did not differ in group 2 (p = 1.0 and p = 0.780), but they were higher (p = 0.002 and p = 0.02) in group 3. Adjunctive nicorandil did not decline FFR further in groups 2 (p = 0.942) and 3 (p = 0.294). 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.

Mid-term effect of balloon aortic valvuloplasty on mitral regurgitation in aortic stenosis.

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.

Prognostic Impact of the Clinical Frailty Scale After Balloon Aortic Valvuloplasty.

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.

Skin ulcer due to hemodialysis access-induced distal ischemia treated with arteriovenous fistula banding and endovascular therapy.

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. .