Clinical outcomes of catheter ablation for atrial fibrillation, atrial flutter, and atrial tachycardia in wild-type transthyretin amyloid cardiomyopathy: a proposed treatment strategy for catheter ablation in each arrhythmia.

AIMS: Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is often accompanied by atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), which are difficult to control because beta-blockers and antiarrhythmic drugs can worsen heart failure (HF). This study aimed to investigate the outcomes of catheter ablation (CA) for AF/AFL/AT in patients with ATTRwt-CM and propose a treatment strategy for CA. METHODS AND RESULTS: A cohort study was conducted on 233 patients diagnosed with ATTRwt-CM, including 54 who underwent CA for AF/AFL/AT. The background of each arrhythmia and the details of the CA and its outcomes were investigated. The recurrence-free rate of AF/AFL/AT overall in ATTRwt-CM patients with multiple CA was 70.1% at 1-year, 57.6% at 2-year, and 44.0% at 5-year follow-up, but CA significantly reduced all-cause mortality [hazard ratio (HR): 0.342, 95% confidence interval (CI): 0.133-0.876, P = 0.025], cardiovascular mortality (HR: 0.378, 95% CI: 0.146-0.981, P = 0.045), and HF hospitalization (HR: 0.488, 95% CI: 0.269-0.889, P = 0.019) compared with those without CA. There was no recurrence of the cavotricuspid isthmus (CTI)-dependent AFL, non-CTI-dependent simple AFL terminated by one linear ablation, and focal AT originating from the atrioventricular (AV) annulus or crista terminalis eventually. Twelve of 13 patients with paroxysmal AF and 27 of 29 patients with persistent AF did not have recurrence as AF. However, all three patients with non-CTI-dependent complex AFL not terminated by a single linear ablation and 10 of 13 cases with focal AT or multiple focal ATs originating beyond the AV annulus or crista terminalis recurred even after multiple CA. CONCLUSION: The outcomes of CA for ATTRwt-CM were acceptable, except for multiple focal AT and complex AFL. Catheter ablation may be aggressively considered as a treatment strategy with the expectation of improving mortality and hospitalization for HF.

Coronary Stent Evaluation by CTA: Image Quality Comparison Between Super-Resolution Deep Learning Reconstruction and Other Reconstruction Algorithms.

BACKGROUND. A super-resolution deep learning reconstruction (SR-DLR) algorithm may provide better image sharpness than earlier reconstruction algorithms and thereby improve coronary stent assessment on coronary CTA. OBJECTIVE. The purpose of our study was to compare SR-DLR and other reconstruction algorithms in terms of image quality measures related to coronary stent evaluation in patients undergoing coronary CTA. METHODS. This retrospective study included patients with at least one coronary artery stent who underwent coronary CTA between January 2020 and December 2020. Examinations were performed using a 320-row normal-resolution scanner and were reconstructed with hybrid iterative reconstruction (HIR), model-based iterative reconstruction (MBIR), normal-resolution deep learning reconstruction (NR-DLR), and SR-DLR algorithms. Quantitative image quality measures were determined. Two radiologists independently reviewed images to rank the four reconstructions (4-point scale: 1 = worst reconstruction, 4 = best reconstruction) for qualitative measures and to score diagnostic confidence (5-point scale: score ≥ 3 indicating an assessable stent). The assessability rate was calculated for stents with a diameter of 3.0 mm or less. RESULTS. The sample included 24 patients (18 men, six women; mean age, 72.5 ± 9.8 [SD] years), with 51 stents. SR-DLR, in comparison with the other reconstructions, yielded lower stent-related blooming artifacts (median, 40.3 vs 53.4-58.2), stent-induced attenuation increase ratio (0.17 vs 0.27-0.31), and quantitative image noise (18.1 vs 20.9-30.4 HU) and higher in-stent lumen diameter (2.4 vs 1.7-1.9 mm), stent strut sharpness (327 vs 147-210 ΔHU/mm), and CNR (30.0 vs 16.0-25.6) (all p < .001). For both observers, all ranked measures (image sharpness; image noise; noise texture; delineation of stent strut, in-stent lumen, coronary artery wall, and calcified plaque surrounding the stent) and diagnostic confidence showed a higher score for SR-DLR (median, 4.0 for all features) than for the other reconstructions (range, 1.0-3.0) (all p < .001). The assessability rate for stents with a diameter of 3.0 mm or less (n = 37) was higher for SR-DLR (86.5% for observer 1 and 89.2% for observer 2) than for HIR (35.1% and 43.2%), MBIR (59.5% and 62.2%), and NR-DLR (62.2% and 64.9%) (all p < .05). CONCLUSION. SR-DLR yielded improved delineation of the stent strut and in-stent lumen, with better image sharpness and less image noise and blooming artifacts, in comparison with HIR, MBIR, and NR-DLR. CLINICAL IMPACT. SR-DLR may facilitate coronary stent assessment on a 320-row normal-resolution scanner, particularly for small-diameter stents.

Clinical, electrocardiographic, and echocardiographic parameters associated with the development of pacing and implantable cardioverter-defibrillator indication in patients with transthyretin amyloid cardiomyopathy.

AIMS: This study aimed to identify factors for attention leading to future pacing device implantation (PDI) and reveal the necessity of prophylactic PDI or implantable cardioverter-defibrillator (ICD) implantation in transthyretin amyloid cardiomyopathy (ATTR-CM) patients. METHODS AND RESULTS: This retrospective single-center observational study included consecutive 114 wild-type ATTR-CM (ATTRwt-CM) and 50 hereditary ATTR-CM (ATTRv-CM) patients, neither implanted with a pacing device nor fulfilling indications for PDI at diagnosis. As a study outcome, patient backgrounds were compared with and without future PDI, and the incidence of PDI in each conduction disturbance was examined. Furthermore, appropriate ICD therapies were investigated in all 19 patients with ICD implantation. PR-interval ≥220 msec, interventricular septum (IVS) thickness ≥16.9 mm, and bifascicular block were significantly associated with future PDI in ATTRwt-CM patients, and brain natriuretic peptide ≥35.7 pg/mL, IVS thickness ≥11.3 mm, and bifascicular block in ATTRv-CM patients. The incidence of subsequent PDI in patients with bifascicular block at diagnosis was significantly higher than that of normal atrioventricular (AV) conduction in both ATTRwt-CM [hazard ratio (HR): 13.70, P = 0.019] and ATTRv-CM (HR: 12.94, P = 0.002), whereas that of patients with first-degree AV block was neither (ATTRwt-CM: HR: 2.14, P = 0.511, ATTRv-CM: HR: 1.57, P = 0.701). Regarding ICD, only 2 of 16 ATTRwt-CM and 1 of 3 ATTRv-CM patients received appropriate anti-tachycardia pacing or shock therapy, under the number of intervals to detect for ventricular tachycardia of 16-32. CONCLUSIONS: According to our retrospective single-center observational study, prophylactic PDI did not require first-degree AV block in both ATTRwt-CM and ATTRv-CM patients, and prophylactic ICD implantation was also controversial in both ATTR-CM. Larger prospective, multi-center studies are necessary to confirm these results.

Prevalence of Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release With Amyloid Deposition.

BACKGROUND: Carpal tunnel syndrome (CTS) is considered an early sign of cardiac amyloidosis (CA) because amyloid deposition is often confirmed in the tenosynovium removed during carpal tunnel release (CTR); however, the prevalence of concomitant CA is unclear.Methods and Results: We prospectively examined 700 patients who underwent CTR and evaluated amyloid deposition after tenosynovium removal. Amyloid deposition was observed in 261 (37%) patients, who were significantly older and predominantly male (P<0.05). Of them, 120 agreed to cardiac screening. We performed 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy in 12 patients who met either of the following criteria: (1) interventricular septal diameter (IVSd) ≥14 mm or (2) 12 mm ≤ IVSd < 14 mm with above-normal limits in high-sensitivity cardiac troponin T (hs-cTnT). Six patients (50%) had positive findings on 99 mTc-PYP scintigraphy and were diagnosed with wild-type transthyretin CA. Concomitant CA was observed in 6/120 (5%) CTR patients with amyloid deposition and 50% (6/12) in patients with left ventricular hypertrophy (≥12 mm) with increased hs-cTnT levels. CONCLUSIONS: Amyloid deposition was frequently observed in the removed tenosynovium of elderly men with CTS. Cardiac screening may be useful for early diagnosis of CA in patients undergoing CTR with amyloid deposition.

Validation of the obesity paradox by body mass index and waist circumference in patients undergoing percutaneous coronary intervention.

BACKGROUND: The paradoxical association of obesity with mortality, named the "obesity paradox", has been inconsistent, possibly due to a difference between body mass index (BMI) and central obesity, estimated by waist circumference (WC) as patterns of adiposity. SUBJECTS/METHODS: We enrolled 8513 participants from the Kumamoto Intervention Conference Study, a multicenter registry that included consecutive patients undergoing percutaneous coronary intervention (PCI) at 18 centers between 2008 and 2017 in Japan. Patients were divided into quartiles in ascending order of the BMI or WC. The primary endpoints were all-cause mortality and cardiovascular death within a year. RESULTS: There were 186 deaths (case fatality rate, 22.1/1000 person-years) during the follow-up period. The lowest group (1st quartile) of BMI or WC had the worst prognosis among the quartiles (1st quartile, 4.2%; 2nd quartile, 1.9%; 3rd quartile, 1.5%; 4th quartile, 1.1%; P < 0.001 (χ2) and 1st quartile, 4.1%; 2nd quartile, 2.3%; 3rd quartile, 1.2%; 4th quartile, 1.5%; P < 0.001 (χ2), respectively). Similar results were obtained for cardiovascular death. In a multivariable analysis adjusted by nine conventional factors, the lowest group (1st quartile) of BMI (hazards ratio, 2.748; 95% confidence interval [CI], 1.712-4.411) and WC (hazards ratio, 2.340; 95% CI, 1.525-3.589) were independent prognostic factors for all-cause mortality. By dividing the participants into two groups according to either the BMI or WC based on the National Cholesterol Education Program Adult Treatment Panel III and World Health Organization classification, the highest mortality was observed in the lower group. However, the C-statistic after adding BMI (quartile) to conventional factors was found to be slightly higher than BMI (two categories) and WC (two categories) (0.735 vs. 0.734). CONCLUSIONS: The obesity paradox was observed in patients after PCI, and single-use of BMI (or WC) was sufficient to predict the prognosis of patients after PCI.

Malnutrition-associated high bleeding risk with low thrombogenicity in patients undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Although antithrombotic treatments are established for coronary artery disease (CAD), they increase the bleeding risk, especially in malnourished patients. The total thrombus-formation analysis system (T-TAS) is useful for the assessment of thrombogenicity in CAD patients. Here, we examined the relationships among malnutrition, thrombogenicity and 1-year bleeding events in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This was a retrospective analysis of 300 consecutive CAD patients undergoing PCI. Blood samples obtained on the day of PCI were used in the T-TAS to compute the thrombus formation area under the curve. We assigned patients to two groups based on the geriatric nutritional risk index (GNRI): 102 patients to the lower GNRI group (≤98), 198 patients to the higher GNRI group (98<). The primary endpoint was the incidence of 1-year bleeding events defined by Bleeding Academic Research Consortium criteria types 2, 3, or 5. The T-TAS levels were lower in the lower GNRI group than in the higher GNRI group. Kaplan-Meier analysis showed worse 1-year bleeding event-free survival in the lower GNRI group compared with the higher GNRI group. The combined model of the GNRI and the Academic Research Consortium for High Bleeding Risk (ARC-HBR) had good calibration and discrimination for bleeding risk prediction. In addition, having a lower GNRI and ARC-HBR positivity was associated with 1-year bleeding events. CONCLUSION: A lower GNRI could reflect low thrombogenicity evaluated by the T-TAS and determine bleeding risk in combination with ARC-HBR positivity.

Impact of cerebrovascular comorbidity on prognosis in Japanese patients undergoing PCI: 1-year data from Japanese multicenter registry (KICS).

Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data have been found about the impact of stroke with underlying cardiac disease. This study's objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across Japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15,979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age 73.5 ± 9.6, 69.7(± 11.5), respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p < 0.0001). During the 1-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p < 0.0001), cardiac death amounted for 2.2 and 1.2%, respectively (p < 0.0001), recurrent stroke for 3.1% and 1.2% (p < 0.0001), non-cardiac death for 3.6 and 1.54% (p < 0.0001), and finally, hemorrhagic complications with 2.6 and 1.3% (p < 0.0001). Kaplan-Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p < 0.0001). Cox hazard analysis also showed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR = 1.457, 95% CI 1.036-2.051, p = 0.031); hence, proving it to be a crucial predictor on cardiac prognosis. History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence. Thus, highlighting an urgent need for comprehensive prevention of cardiac and cerebrovascular diseases.

QRS duration is a risk indicator of adverse outcomes after MitraClip.

BACKGROUND: While QRS duration is a known marker of left ventricular (LV) function, little is known about its utility for predicting clinical prognosis after transcatheter mitral valve repair (TMVR). We investigated the association between QRS duration and one-year adverse events after TMVR with the MitraClip system. METHODS: From January 2011 through April 2019, we identified consecutive patients who underwent TMVR. Patients who had prior cardiac resynchronization therapy or a ventricular pacing rhythm were excluded. The patients were divided into two groups according to their QRS duration (<120 or ≥ 120 ms). Cox proportional hazard model was applied to determine the association between QRS duration and the composite outcome (all-cause mortality and re-hospitalization due to heart failure) within 1 year. RESULTS: A total of 348 patients were analyzed. Prolonged QRS duration (≥120 ms) was associated with an increased risk of the composite outcome (adjusted-HR 2.35, 95%CI 1.30-4.24, p = .005). There was a linear relationship between prolonged QRS duration and the increased risk of the composite outcomes. The observed association was consistent both in patients with left ventricular ejection fraction ≤35% and those with >35%. Furthermore, a QRS duration ≥120 ms was associated with lower improvement of LVEF at follow-up (adjusted-ß coefficient - 5.31%, 95%CI -8.17 to -2.46, p < .001). CONCLUSIONS: Prolonged QRS duration was associated with an increased risk of mortality and re-hospitalization and less improvement of LVEF following TMVR. QRS duration could be a useful marker to predict adverse outcomes and LV function after TMVR.

Association of heart failure duration with clinical outcomes after transcatheter mitral valve repair for functional mitral regurgitation.

BACKGROUND: Little is known about the association of heart failure (HF) chronicity with clinical outcomes after transcatheter mitral valve repair (TMVR) for functional mitral regurgitation (MR). METHODS: From January 2011 to March 2019, consecutive patients with functional MR who underwent a MitraClip procedure were analyzed. The patients were divided into two groups according to HF duration-those with duration ≤18 months and those with >18 months. The primary outcome measure was a composite of all-cause mortality and re-HF rehospitalization within 1 year after the procedure. These outcomes were also assessed separately. A Cox proportional hazard model was conducted for investigating the association of HF duration with the primary outcome. RESULTS: A total of 208 patients were analyzed. Patients with HF duration >18 months had a higher rate of the primary outcome compared to those with HF duration ≤18 months (38.1 vs. 19.0%, log-rank p = .003). A longer duration of HF was associated with an increased risk of the primary outcomes (adjusted-HR of >18 months, 2.12 95% CI, 1.14-4.19; p = .03; adjusted-HR (hazard ratios) for 1 year increase, 1.05; 95% CI, 1.02-1.09; p = .004). The association of HF duration with the primary outcomes showed a steep rise during the first 2 years of HF duration and progressive increase after 5 years. CONCLUSIONS: A longer HF duration before TMVR was associated with an increased risk of all-cause mortality or HF rehospitalization. HF duration can be used for the risk stratification marker in patients undergoing TMVR for functional MR.

The predictive value of intraprocedural mitral gradient for outcomes after MitraClip and its peri-interventional dynamics.

BACKGROUND: The current data on the impact of the increased mitral gradient (MG) on outcomes are ambiguous, and intraprocedural assessment of MG can be challenging. Therefore, we aimed to evaluate (a) peri-interventional dynamics of MG, (b) the impact of intraprocedural MG on clinical outcomes, and (c) predictors for unfavorable MG values after MitraClip. METHODS: We prospectively included patients who underwent MitraClip. All patients underwent echocardiography at baseline, intraprocedurally, at discharge, and after 6 months. 12-month survival was documented. RESULTS: One hundred and seventy five patients (age 81.2 ± 8.2 years, 61.2% male) with severe mitral regurgitation (MR) were included. We divided our cohort into two groups according to intraprocedural MG with a threshold of 4.5 mm Hg, determined by a multivariate analysis of predictors for 12-month mortality (<4.5 mm Hg: Group 1, ≥4.5 mm Hg: Group 2). Intraprocedural MG ≥4.5 mm Hg was found to be the strongest independent predictor for 12-month mortality (HR: 2.33, P = .03, OR: 1.70, P = .05), and >3.9 mm Hg was associated with adverse functional outcomes (OR: 1.96, P = .04). The baseline leaflet-to-annulus index >1.1 was found to be the strongest independent predictor (OR: 9.74, P = .001) for unfavorable intraprocedural MG, followed by the number of implanted clips (P = .01), MG at baseline (P = .02), and central clip implantation (P = .05). CONCLUSION: An intraprocedural MG <3.9 mm Hg appears to be the best strategy for 1-year survival and favorable functional outcomes after edge-to-edge MV repair with MitraClip independently from MR etiology. Peri-interventional echocardiographic and procedural parameters are useful for the adequate assessment of intraprocedural MG.

Impact of combined baseline and postprocedural troponin values on clinical outcome following the MitraClip procedure.

OBJECTIVES: The purpose of this study was to investigate the impact of periprocedural troponin levels on clinical outcome following the MitraClip procedure. BACKGROUND: Cardiac troponin is known to be a predictive biomarker for various clinical outcomes; however, data about its predictive value in patients undergoing transcatheter mitral valve repair are limited. METHODS: Consecutive patients undergoing the MitraClip procedure were enrolled. Serum cardiac troponin I concentrations were measured before and after the procedure, and the maximal value recorded within 72 hr after the procedure was used for the postprocedural values. The clinical outcome was all-cause mortality within a 1-year follow-up. RESULTS: Out of 354 patients, 29 patients (8.2%) were deceased within 1 year. Patients who died had significantly higher baseline (0.05 [0.01-0.08] vs. 0.01 [0.01-0.03] ng/ml; p < .001) and postprocedural troponin I values (0.51 [0.30-1.42] vs. 0.20 [0.33-0.55] ng/ml; p = .005). A Kaplan-Meier analysis showed that patients with higher baseline troponin I values had a significantly worse prognosis than those with lower values (log-rank p < .001), and similarly, 1-year mortality was significantly higher in patients with higher postprocedural troponin I than those with lower levels (log-rank p = .021). Moreover, the highest mortality rate was observed in patients with both elevated baseline and postprocedural troponin I values (log-rank p = .001), which was found to be an independent predictor of mortality by multivariable analyses. CONCLUSIONS: The present study suggests that combined baseline and postprocedural troponin measurements are useful for risk stratification of 1-year mortality following the MitraClip procedure.

Usefulness of relative apical longitudinal strain index to predict positive 99m Tc-labeled pyrophosphate scintigraphy findings in advanced-age patients with suspected transthyretin amyloid cardiomyopathy.

BACKGROUND: We previously reported that a high score (2 or 3 points) according to the Kumamoto criteria, a combination of high-sensitivity cardiac troponin T (hs-cTnT) ≥0.308 ng/mL, the length of QRS ≥ 120 ms in electrocardiogram, and left ventricular (LV) posterior wall thickness ≥ 13.6 mm, increases the pretest probability of 99m Tc-labeled pyrophosphate (99m Tc-PYP) scintigraphy in patients with suspected transthyretin amyloid cardiomyopathy (ATTR-CM). However, some patients with a low score (0 or 1 point) show positive findings on 99m Tc-PYP scintigraphy. Therefore, we evaluated the usefulness of additional examinations, including echocardiographic assessment of myocardial strain, to raise the pretest probability of 99m Tc-PYP scintigraphy for these patients. METHODS AND RESULTS: We examined 109 consecutive patients aged ≥70 years with low scores according to the Kumamoto criteria who underwent 99m Tc-PYP scintigraphy. Nineteen patients (17%) had positive 99m Tc-PYP scintigraphy findings. The relative apical longitudinal strain (LS) index (apical LS/ basal LS + mid LS) (RapLSI) was significantly higher in patients with positive than negative 99m Tc-PYP scintigraphy findings (1.04 ± 0.37 vs 0.70 ± 0.28, P < .01). Multivariable logistic regression analysis revealed that a high RapLSI (≥1.04) was significantly associated with 99m Tc-PYP positivity (odds ratio, 14.14; 95% confidence interval, 3.36-59.47; P < .01). The sensitivity, specificity, and accuracy of the diagnostic model using the RapLSI for identification of 99m Tc-PYP positivity were 53%, 94%, and 87%, respectively. CONCLUSIONS: A high RapLSI can raise the pretest probability of 99m Tc-PYP scintigraphy in patients with a low score according to the Kumamoto criteria. The RapLSI can assist clinicians in determining strategies for these patients.

Risk Factors and Prevalence of Deep Vein Thrombosis After the 2016 Kumamoto Earthquakes.

BACKGROUND: After previous earthquakes, a high prevalence of deep vein thrombosis (DVT) has been reported. We examined DVT prevalence and risk factors in evacuees of the Kumamoto earthquakes by performing mobile DVT screening at various evacuation centers around the epicenter. Methods and Results: For 1 month after the Kumamoto earthquake on 14 April 2016, mobile DVT screening using portable ultrasonography (US) was performed at 80 evacuation centers. Questionnaires, physical examination, and US of the lower limb were carried out, and simple D-dimer measurements were undertaken for DVT-positive examinees. The total number of examinees was 1,673, of whom 178 (10.6%) had DVT. The prevalence of DVT seemed to be gradually decreasing in the screening period, but age, use of sleep medication, prevalence of hypertension, dyslipidemia, leg edema, and lower leg varix were significantly higher in the DVT positive group than in the negative group. On multivariable logistic regression analysis, high age (≥70 years old), use of sleep medication, lower leg edema, and lower leg varix were significant predictors of DVT. In examinees with these 4 predictors, the DVT positive rate was 71.4%. CONCLUSIONS: In the first month after the Kumamoto earthquakes, DVT prevalence and severity, evaluated on D-dimer level, decreased with the passage of time. Mobile DVT screening indicated significant factors stratifying DVT risk in the evacuees.

Sex differences in the impact of CYP2C19 polymorphisms and low-grade inflammation on coronary microvascular disorder.

Categorization as a cytochrome P-450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. It is correlated with an increase in the circulating levels of high-sense C-reactive protein (hs-CRP) in women only, although its role in coronary microcirculation is unclear. We examined sex differences in the impact of the CYP2C19 genotype and low-grade inflammation on coronary microvascular disorder (CMVD). We examined CYP2C19 genotypes in patients with CMVD (n = 81) and in healthy subjects as control (n = 81). CMVD was defined as the absence of coronary artery stenosis and epicardial spasms, the presence of inverted lactic acid levels between the intracoronary and coronary sinuses, or an adenosine triphosphate-induced coronary flow reserve ratio < 2.5. CYP2C19 PMs have two loss-of-function (LOF) alleles (*2, *3). Extensive metabolizers have no LOF alleles, and intermediate metabolizers have one LOF allele. The ratio of CYP2C19 PM and hs-CRP levels in CMVD was significantly higher than that of controls, especially in women (40.9 vs. 13.8%, P = 0.013; 0.11 ± 0.06 vs. 0.07 ± 0.04 mg/dl, P = 0.001). Moreover, in each CYP2C19 genotype, hs-CRP levels in CMVD in CYP2C19 PMs were significantly higher than those of the controls, especially in women (0.15 ± 0.06 vs. 0.07 ± 0.03, P = 0.004). Multivariate analysis for CMVD indicated that the female sex, current smoking, and hypertension were predictive factors, and that high levels of hs-CRP and CYP2C19 PM were predictive factors in women only (odds ratio 3.5, 95% confidence interval 1.26-9.93, P = 0.033; odds ratio 4.1, 95% confidence interval 1.15-14.1, P = 0.038). CYP2C19 PM genotype may be a new candidate risk factor for CMVD via inflammation exclusively in the female population.

Association of CYP2C19 variants and epoxyeicosatrienoic acids on patients with microvascular angina.

Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the association of CYP2C19 polymorphisms and EETs on microvascular angina (MVA) caused by coronary microvascular dysfunction. We examined CYP2C19 genotypes in patients with MVA (n = 71) and healthy subjects as control (n = 71). MVA was defined as the absence of coronary artery stenosis and epicardial spasms and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphosphate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of-functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite. MVA group showed significantly higher CYP2C19 PM incidence (35% vs. 16%; P = 0.007) and high sense C-reactive protein (hs-CRP) levels (0.127 ± 0.142 vs. 0.086 ± 0.097 mg/dl; P = 0.043) than those of controls. Moreover, in MVA group, hs-CRP levels in CYP2C19 PM were significantly higher than that of non-PM (0.180 ± 0.107 vs. 0.106 ± 0.149 mg/dl, P = 0.045). Multivariate analysis indicated that smoking, hypertension, high hs-CRP, and CYP2C19 PM are predictive factors for MVA. In MVA group, DHET levels for CYP2C19 PM were significantly lower than that of non-PM [10.9 ± 1.64 vs. 14.2 ± 5.39 ng/ml, P = 0.019 (11,12-DHET); 15.2 ± 4.39 vs. 17.9 ± 4.73 ng/ml, P = 0.025 (14,15-DHET)]. CYP2C19 variants are associated with MVA. The decline of EET-based defensive mechanisms owing to CYP2C19 variants may affect coronary microvascular dysfunction.

Differential impact of peripheral endothelial dysfunction on subsequent cardiovascular events following percutaneous coronary intervention between chronic kidney disease (CKD) and non-CKD patients.

Chronic kidney disease (CKD) status might modify the predictive effect of peripheral endothelial dysfunction on cardiovascular events after percutaneous coronary intervention (PCI). The aim of this study was to examine the differential effect of peripheral endothelial dysfunction on clinical outcome after PCI between CKD and non-CKD patients. We conducted a cohort study of 435 patients following PCI. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2). Peripheral endothelial dysfunction was examined using reactive hyperemia-peripheral arterial tonometry index (RHI), and we divided patients into low- and high-natural logarithmic RHI (Ln-RHI) group. The endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, ischemic stroke, hospitalization due to unstable angina pectoris, and coronary revascularization. A total of 56 patients had a cardiovascular event. Patients who suffered a cardiovascular event had significantly lower Ln-RHI than other patients in the non-CKD group (0.46 ± 0.18 versus 0.60 ± 0.25; P = 0.002). Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in low Ln-RHI patients in the non-CKD group (log-rank test: P = 0.003). Multivariate Cox proportional hazards analysis identified Ln-RHI as an independent and significant predictor of future cardiovascular events in the non-CKD group (HR: 0.096; 95 % CI 0.02-0.47; P = 0.004) but not in the CKD group. There was a differential effect of peripheral endothelial dysfunction on clinical outcome after PCI between CKD and non-CKD patients, and peripheral endothelial dysfunction significantly correlates with subsequent cardiovascular events after PCI in non-CKD patients.

Clinical characteristics and intravascular ultrasound findings of culprit lesions in elderly patients with acute coronary syndrome.

Acute coronary syndrome (ACS) is one of the main causes of cardiovascular death. According to rapid aging of society, the peak age of ACS onset has grown older globally. Despite growing recognition of the necessity to build the ACS prevention strategy in the elderly, patients background and culprit lesion morphology of these elderly ACS patients have not been well studied. We sought to assess the clinical characteristics and intravascular ultrasound (IVUS) findings of the culprit lesions in elderly ACS patients. One-hundred and fifty-eight consecutive ACS patients whose culprit lesions imaged by pre-intervention IVUS were divided into two groups based on the age of onset: elderly [E] group (≥75 years, n = 65) and non-elderly [NE] group (<75 years, n = 93). As compared with NE group, hemoglobin (12.7 ± 2.0 g/dL vs. 13.7 ± 1.6 g/dL, p = 0.001), estimated glomerular filtration rate (62.5 ± 22.5 mL/min/1.73 m(2) vs. 75.5 ± 20.5 mL/min/1.73 m(2), p = 0.0001), and body mass index (22.9 ± 3.4 kg/m(2) vs. 24.5 ± 3.4 kg/m(2), p = 0.003) were significantly lower, and comorbid malignancy was more common (20.0 vs 6.5 %, p = 0.01) in E group. Although whole culprit segment was not positively remodeled (mean vessel area was 15.2 ± 5.6 mm(3)/mm vs. 16.2 ± 5.1 mm(3)/mm, p = 0.16) in E group, at maximum external elastic membrane site of the culprit lesion, lumen area was smaller (5.5 ± 3.2 mm(2) vs. 6.7 ± 3.5 mm(2), p = 0.04), and plaque burden tended to be more abundant (70 ± 13 vs. 66 ± 13 %, p = 0.08). Interestingly, echo attenuation arc of culprit attenuated plaque was significantly greater in E group than in NE group (157 ± 83° vs. 118 ± 60°, p = 0.01). In conclusion, extracardiac comorbidity was more common in elderly ACS patients, and their culprit coronary lesions were still rupture prone, and "vulnerable."

Single-wire pressure and flow velocity measurement for quantifying microvascular dysfunction in patients with coronary vasospastic angina.

Endothelial and vascular smooth muscle dysfunction of epicardial coronary arteries play a pivotal role in the pathogenesis of vasospastic angina (VSA). However, coronary microvascular (MV) function in patients with VSA is not fully understood. In the present study, subjects without coronary obstruction were divided into two groups according to the acetylcholine provocation test: VSA group (n = 29) and non-VSA group (n = 21). Hyperemic MV resistance (hMR) was measured using a dual-sensor (Doppler velocity and pressure)-equipped guidewire, and guidewire-derived hemodynamic parameters were compared. There were no between-group differences in clinical demographics, including potential factors affecting MV function (e.g., diabetes). Although coronary flow velocity reserve was similar between the two groups [2.4 ± 1.0 (VSA group) vs. 2.4 ± 0.9 (non-VSA group); P = 0.8], coronary vessel resistance and hMR were significantly elevated in the VSA group compared with the non-VSA group (2.6 ± 3.1 vs. 1.2 ± 0.8, P = 0.04; 1.9 ± 0.6 vs. 1.6 ± 0.5, P = 0.03, respectively). Coronary vasospasm, older age, E/e', and estimated glomerular filtration rate were significantly associated with MV dysfunction [defined as ≥ median value of hMR (1.6)] in univariate analysis. Coronary vasospasm most strongly predicted higher hMR in multivariate logistic regression analysis (odds ratio, 4.61; 95% confidence interval, 0.98-21.60; P = 0.053). In conclusion, coronary MV resistance is impaired in patients with VSA compared with non-VSA patients, whereas coronary flow velocity reserve is maintained at normal levels in both groups. In vivo assessment of hMR might be a promising index of coronary MV dysfunction in patients with VSA.

Gender differences in impact of CYP2C19 polymorphism on development of coronary artery disease.

The aim was to clarify whether CYP2C19 polymorphism is associated with the development of coronary artery disease (CAD). This study enrolled 723 patients with CAD (men 71%, 70 years) and healthy subjects undergoing a medical checkup (n = 453) as controls (men 69%, 53 years). We analyzed the incidence of CYP2C19 polymorphism and its association with the development of CAD in the absence of diabetes, dyslipidemia, and chronic kidney disease to minimize the influence of conventional coronary risk factors. In the analysis without risk factors, there was no difference in the incidence of the CYP2C19 genotype between CAD (n = 115) and control (n = 194) groups [extensive metabolizer, intermediate metabolizer, poor metabolizer (PM) in non-risk CAD: 33%, 46%, 21%, respectively; in non-risk control: 31%, 52%, 17%, respectively]. Analysis between CAD and control groups by the χ test showed that there was significant difference in distribution of CYP2C19 genotype in women alone (P = 0.025) but not in total subjects (P = 0.471) or men (P = 0.678), respectively. CYP2C19 PM was an independent predictor of CAD risk in women alone (odds ratio, 10.717; 95% confidence interval, 1.753-65.505; P = 0.010) but not in men. CYP2C19 PM status might be associated with the development of CAD as a disease susceptibility gene, especially in women.