Impact of hyper-polypharmacy due to non-cardiovascular medications on long-term clinical outcomes following endovascular treatment for lower limb artery disease: A sub-analysis of the I-PAD Nagano registry.

BACKGROUND: Lower limb artery disease (LEAD) is accompanied by multiple comorbidities; however, the effect of hyperpolypharmacy on patients with LEAD has not been established. This study investigated the associations between hyperpolypharmacy, medication class, and adverse clinical outcomes in patients with LEAD. METHODS: This study used data from a prospective multicenter observational Japanese registry. A total of 366 patients who underwent endovascular treatment (EVT) for LEAD were enrolled in this study. The primary endpoints were major adverse cardiac events (MACE), including myocardial infarction, stroke, and all-cause death. RESULTS: Of 366 patients with LEAD, 12 with missing medication information were excluded. Of the 354 remaining patients, 166 had hyperpolypharmacy (≥10 medications, 46.9 %), 162 had polypharmacy (5-9 medications, 45.8 %), and 26 had nonpolypharmacy (<5 medications, 7.3 %). Over a 4.7-year median follow-up period, patients in the hyperpolypharmacy group showed worse outcomes than those in the other two groups (log-rank test, p < 0.001). Multivariate analysis revealed that the total number of medications was significantly associated with an increased risk of MACE (hazard ratio per medication increase 1.078, 95 % confidence interval 1.02-1.13 p = 0.012). Although an increased number of non-cardiovascular medications was associated with an elevated risk of MACE, the increase in cardiovascular medications was not statistically significant (log-rank test, p = 0.002 and 0.35, respectively). CONCLUSIONS: Hyperpolypharmacy due to non-cardiovascular medications was significantly associated with adverse outcomes in patients with LEAD who underwent EVT, suggesting the importance of medication reviews, including non-cardiovascular medications.

Association between complete revascularization of the coronary artery and clinical outcomes in peripheral artery disease: a sub-analysis of the I-PAD Nagano registry.

Peripheral artery disease (PAD) is commonly caused by atherosclerosis and has an unfavorable prognosis. Complete revascularization (CR) of the coronary artery reduces the risk of major adverse cardiovascular event (MACE) in patients with coronary artery disease (CAD). However, the impact of CR in patients with PAD has not been established to date. Therefore, we evaluated the impact of CR of CAD on the five-year clinical outcomes in patients with PAD. This study was based on a prospective, multicenter, observational registry in Japan. We enrolled 366 patients with PAD undergoing endovascular treatment. The primary endpoint was MACE, defined as a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke. After excluding ineligible patients, 96 and 68 patients received complete revascularization of the coronary artery (CR group) and incomplete revascularization of the coronary artery (ICR group), respectively. Freedom from MACE in the CR group was significantly higher than in the ICR group at 5 years (66.7% vs 46.0%, p < 0.01). Multivariate analysis revealed that CR emerged as an independent predictor of MACE (Hazard ratio: 0.56, 95% confidential interval: 0.34-0.94, p = 0.03). CR of CAD was significantly associated with improved clinical outcomes in patients with PAD undergoing endovascular treatment.

Validation and Comparison of the Prognosis Predicting Ability of Inflammation-Based Scores Following Endovascular Treatment for Peripheral Artery Disease.

We assessed the prognostic ability of several inflammation-based scores and compared their long-term outcomes in patients with peripheral artery disease (PAD) following endovascular treatment (EVT). We included 278 patients with PAD who underwent EVT and classified them according to their inflammation-based scores (Glasgow prognostic score [GPS], modified GPS [mGPS], platelet to lymphocyte ratio [PLR], prognostic index [PI], and prognostic nutritional index [PNI]). Major adverse cardiovascular events (MACE) at 5 years were examined, and C-statistics in each measure were calculated to compare their MACE predictive ability. During the follow-up period, 96 patients experienced MACE. Kaplan-Meier analysis showed that higher scores of all measures were associated with a higher MACE incidence. Multivariate Cox proportional hazard analysis showed that GPS 2, mGPS 2, PLR 1, and PNI 1, compared with GPS 0, mGPS 0, PLR 0, and PNI 0, were associated with an increased risk of MACE. C-statistics for MACE for PNI (.683) were greater than those for GPS (.635, P = .021), mGPS (.580, P = .019), PLR (.604, P = .024), and PI (.553, P < .001). PNI is associated with MACE risk and has a better prognosis-predicting ability than other inflammation-scoring models for patients with PAD following EVT.

Impact of Frailty and Age on Clinical Outcomes in Patients Who Underwent Endovascular Therapy.

PURPOSE: Information on the relationship between frailty and the outcome of endovascular therapy (EVT) in elderly patients with lower extremity peripheral artery disease (PAD) is scarce. This study aimed to reveal the impact of frailty on the prognosis of super-elderly patients who underwent EVT. MATERIALS AND METHODS: From August 2015 to August 2016, 335 consecutive patients who underwent EVT were enrolled in the I-PAD registry from 7 institutes in Nagano prefecture. Among them, we categorized 323 patients into 4 groups according to age and the presence or absence of frailty as follows: elderly with frailty (age ≥ 75, Clinical Frailty Scale [CFS] ≥ 5), elderly without frailty (age ≥ 75, CFS ≤ 4), young with frailty (age < 75, CFS ≥ 5), and young without frailty (age < 75, CFS ≤ 4); we analyzed them accordingly. The primary endpoints were major adverse cardiovascular and limb events (MACLE), defined as a composite of cardiovascular death, myocardial infarction, stroke, admission for heart failure, major amputation, and revascularization. The secondary endpoint was cardiovascular death. RESULTS: The median follow-up period was 2.7 years. In the elderly with frailty, elderly without frailty, young with frailty, and young without frailty groups, the freedom rates from MACLE were 34.9%, 55.7%, 35.4%, and 63.0%, respectively (p<0.001) and from all-cause death were 43.5%, 73.4%, 50.7%, and 90.9%, respectively (p<0.001). The freedom rates from MACLE were significantly higher among elderly patients with frailty than among young patients without frailty (55.7% vs 35.4%, p=0.01). In multivariate analysis, frailty was independently associated with MACLE incidence. CONCLUSION: Frailty as defined by CFS might be a predictor of MACLE incidence in patients with PAD who underwent EVT. By considering treatment indications for patients with PAD by focusing on frailty rather than age, we may examine whether EVT policies are appropriate and manage patient and caregiver expectations for potential improvement in functional outcomes. Further studies are expected to investigate whether changes in frailty after EVT change prognosis.

Body composition and mortality in patients undergoing endovascular treatment for peripheral artery disease.

An inverse correlation between body mass index and mortality in patients with peripheral artery disease (PAD) has been reported. However, little information is available regarding the impact of body composition on the clinical outcomes in patients with PAD. This study evaluated the relationships between the lean body mass index (LBMI), body fat % (BF%), and mortality and major amputation rate in patients with PAD. We evaluated 320 patients with PAD after endovascular treatment (EVT) enrolled from August 2015 to July 2016 and divided them into low and high LBMI and BF% groups based on their median values (17.47 kg/m2 and 22.07%, respectively). We assessed 3-year mortality and major amputation for the following patient groups: Low LBMI/Low BF%, Low LBMI/High BF%, High LBMI/Low BF%, and High LBMI/High BF%. During the median 3.1-year follow-up period, 70 (21.9%) patients died and 9 (2.9%) patients experienced major amputation. The survival rate was lower in the Low LBMI than in the High LBMI group, and was not significantly different between the Low and High BF% groups. Survival rates were lowest in the Low LBMI/Low BF% group (57.5%) and highest in the High LBMI/High BF% group (94.4%). There were no significant differences in major amputation rate between the Low LBMI and High LBMI groups, and between the Low BF% and High BF% groups. The Low LBMI and Low BF% groups were associated with an increased risk of mortality after adjustment for age, sex, frailty and conventional risk factors [hazard ratio (HR): 4.02; 95% confidence interval (CI) 2.10-7.70; p < 0.001 and HR: 4.48; 95% CI 1.58-12.68, p = 0.005, respectively], for age, sex, hemodialysis, and prior cerebral cardiovascular disease (HR: 3.63; 95% CI 1.93-6.82; p < 0.001 and HR: 4.03; 95% CI 1.43-11.42, p = 0.009, respectively) and for age, sex, and laboratory date (HR: 3.97; 95% CI 1.88-8.37; p < 0.001 and HR: 3.31; 95% CI 1.15-9.53, p = 0.026, respectively). In conclusion, Low LBMI and Low BF% were associated with poor prognosis in patients undergoing EVT for PAD, and mortality was the lowest in the High LBMI/High BF% group compared with other body composition groups.

Prognostic ability of mid-term worsening renal function after percutaneous coronary intervention: findings from the SHINANO registry.

Chronic kidney disease is a prognostic factor for cardiovascular disease. Worsening renal function (WRF), specifically, is an important predictor of mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI). We evaluate the prognostic impact of mid-term WRF after PCI on future cardiovascular events. We examined the renal function data of 1086 patients in the first year after PCI using the SHINANO 5-year registry. Patients were divided into two groups, mid-term WRF and non-mid-term WRF, and primary outcomes were major adverse cardiovascular events (MACE) and death. Mid-term WRF was defined as an increase in creatinine (≥ 0.3 mg/dL) in the first year after PCI. Mid-term WRF was found in 101 patients (9.3%), and compared to non-mid-term WRF, it significantly increased the incidence of MACE (p < 0.001), and all-cause death (p < 0.001), myocardial infarction (p = 0.001). Furthermore, mid-term WRF patients had higher incidence of future heart failure (p < 0.001) and new-onset atrial fibrillation (p = 0.01). Patients with both mid-term WRF and chronic kidney disease had increased MACE compared to patients with either condition alone (p < 0.001). Similarly, patients with mid-term WRF and acute kidney injury had increased MACE compared to patients with either condition alone (p < 0.001). Multivariate Cox regression analysis revealed mid-term WRF as a strong predictor of MACE (hazard ratio: 2.50, 95% confidence interval 1.57-3.98, p < 0.001). Mid-term WRF after PCI negatively affects MACE, as well as future admission due to heart failure and new-onset atrial fibrillation, chronic kidney disease, and acute kidney injury.

Association of the Prognosis of Ankle-brachial Index Improvement One Year Following Endovascular Therapy in Patients with Peripheral Artery Disease: Data from the I-PAD NAGANO Registry.

Objective Despite reports on the effects of ankle-brachial index (ABI) improvement following endovascular therapy (EVT) on the limb prognosis, studies evaluating cardiovascular events are limited. We investigated whether or not ABI improvement 1 year following EVT was associated with cardiovascular events. Methods The I-PAD NAGANO registry is an observational multicenter cohort study that enrolled 337 patients with peripheral artery disease (PAD) who underwent EVT between August 2015 and July 2016. From this cohort, we identified 232 patients whose ABI data 1 year following EVT were available, after excluding patients with critical limb ischemia. We divided the patients into two groups according to the degree of ABI improvement 1 year following EVT (ΔABI) - the ΔABI <0.15 group and the ΔABI ≥0.15 group - and compared the outcomes. The primary endpoint was major adverse cardiovascular events (MACEs), including all - cause death, myocardial infarction (MI), and stroke. The secondary endpoints were major adverse limb events (MALEs), defined as a composite of target lesion revascularization and major amputation, all - cause death, MI, and stroke. The median follow-up period was 3.3 years. Results The incidence of MACEs was significantly higher in the ΔABI <0.15 group than in the ΔABI ≥0.15 group (ΔABI <0.15 vs. ΔABI ≥0.15, 25.8% vs. 11.9%, log-rank p=0.036), as was the incidence of stroke (14.1% vs. 2.2%, log-rank p=0.016). A Cox regression analysis revealed that ΔABI ≥0.15 was significantly associated with fewer MACEs (hazard ratio 0.38, 95% confidence interval 0.17-0.83, p=0.016). Conclusion An increase in ABI ≥0.15 at 1 year following EVT was a predictor of reduced MACEs.

Inter-observer differences in interpretation of coronary pressure-wire pullback data by non-expert interventional cardiologists.

The physiological pattern of coronary artery disease as determined by pressure-wire (PW)-pullback is important for decision-making of revascularization and risk stratification of patients. However, it remains unclear whether inter-observer differences in interpreting PW-pullback data are subject to the expertise of physicians. This study sought to investigate the subjectivity of this assessment among non-experts. Expert interventional cardiologists classified 545 PW-pullback traces into physiologically focal or physiologically diffuse disease pattern. Defining expert-consensus as the reference standard, we evaluated ten non-expert doctors' classification performance. Observers were stratified equally by two ways: (i) years of experience as interventional cardiologists (middle-level vs. junior-level) and (ii) volume of institutions where they belonged to (high-volume center vs. low-volume center). When judged against the expert-consensus, the agreement of non-expert observers in assessing physiological pattern of disease (focal or diffuse) ranged from 69.1 to 85.0% (p for heterogeneity < 0.0001). There was no evidence for a moderating effect of years of experience; the pooled accuracy of middle-level doctors was 78.8% (95% confidential interval [CI] 72.8-84.7%) vs. 79.1% for junior-level doctors (95% CI 75.9-82.2%, p = 0.95 for difference). On the other hand, we observed a significant moderating effect of center volume. Accuracy across non-experts in high-volume centers was 82.7% (95% CI 80.3-85.1%) vs. 75.1% for low-volume centers (95% CI 71.9-78.3%, p = 0.0002 for difference). Interpretation of PW-pullback by non-expert interventional cardiologists was considerably subjective.

Per-Vessel Level Analysis of Fractional Flow Reserve and Instantaneous Wave-Free Ratio Discordance　- Insights From the AJIP Registry.

BACKGROUND: The per-vessel level impact of physiological pattern of disease on the discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) has not been clarified.Methods and Results:Using the AJIP registry, vessels with FFR/iFR discordance (133/671 [19.8%]) were analyzed. In the left anterior descending artery (LAD), physiologically diffuse disease, as assessed by pressure-wire pullback, was associated with FFR-/iFR+ (83.3% [40/48]), while physiologically focal disease was associated with FFR+/iFR- (57.4% [31/54]), significantly (P<0.0001). These differences were not significant in non-LAD (P=0.17). CONCLUSIONS: The impact of physiological pattern of disease on FFR/iFR discordance is more pronounced in the LAD.

Algorithmic Versus Expert Human Interpretation of Instantaneous Wave-Free Ratio Coronary Pressure-Wire Pull Back Data.

OBJECTIVES: The aim of this study was to investigate whether algorithmic interpretation (AI) of instantaneous wave-free ratio (iFR) pressure-wire pull back data would be noninferior to expert human interpretation. BACKGROUND: Interpretation of iFR pressure-wire pull back data can be complex and is subjective. METHODS: Fifteen human experts interpreted 1,008 iFR pull back traces (691 unique, 317 duplicate). For each trace, experts determined the hemodynamic appropriateness for percutaneous coronary intervention (PCI) and, in such cases, the optimal physiological strategy for PCI. The heart team (HT) interpretation was determined by consensus of the individual expert opinions. The same 1,008 pull back traces were also interpreted algorithmically. The coprimary hypotheses of this study were that AI would be noninferior to the interpretation of the median expert human in determining: 1) the hemodynamic appropriateness for PCI; and 2) the physiological strategy for PCI. RESULTS: Regarding the hemodynamic appropriateness for PCI, the median expert human demonstrated 89.3% agreement with the HT in comparison with 89.4% for AI (p < 0.01 for noninferiority). Across the 372 cases judged as hemodynamically appropriate for PCI according to the HT, the median expert human demonstrated 88.8% agreement with the HT in comparison with 89.7% for AI (p < 0.0001 for noninferiority). On reproducibility testing, the HT opinion itself changed 1 in 10 times for both the appropriateness for PCI and the physiological PCI strategy. In contrast, AI showed no change. CONCLUSIONS: AI of iFR pressure-wire pull back data was noninferior to expert human interpretation in determining both the hemodynamic appropriateness for PCI and the optimal physiological strategy for PCI.

Physiological Pattern of Disease Assessed by Pressure-Wire Pullback Has an Influence on Fractional Flow Reserve/Instantaneous Wave-Free Ratio Discordance.

BACKGROUND: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) disagree on the hemodynamic significance of a coronary lesion in ≈20% of cases. It is unknown whether the physiological pattern of disease is an influencing factor for this. This study assessed whether the physiological pattern of coronary artery disease influences discordance between FFR and iFR measurement. METHODS AND RESULTS: Three-hundred and sixty intermediate coronary lesions (345 patients; mean age, 64.4±10.3 years; 76% men) with combined FFR, iFR, and iFR pressure-wire pullback were included for analysis from an international multicenter registry. Cut points for hemodynamic significance were FFR ≤0.80 and iFR ≤0.89, respectively. Lesions were classified into FFR+/iFR+ (n=154; 42.7%), FFR-/iFR+ (n=38; 10.6%), FFR+/iFR- (n=41; 11.4%), and FFR-/iFR- (n=127; 35.3%) groups. The physiological pattern of disease was classified according to the iFR pullback recordings as predominantly physiologically focal (n=171; 47.5%) or predominantly physiologically diffuse (n=189; 52.5%). Median FFR and iFR were 0.80 (interquartile range, 0.75-0.85) and 0.89 (interquartile range, 0.86-0.92), respectively. FFR disagreed with iFR in 22% (79 of 360). The physiological pattern of disease was the only influencing factor relating to FFR/iFR discordance: predominantly physiologically focal was significantly associated with FFR+/iFR- (58.5% [24 of 41]), and predominantly physiologically diffuse was significantly associated with FFR-/iFR+ (81.6% [31 of 38]; P<0.001 for pattern of disease between FFR+/iFR- and FFR-/iFR+ groups). CONCLUSIONS: The physiological pattern of coronary artery disease was an important influencing factor for FFR/iFR discordance.

Impact of a combination of full coverage stenting and proximal optimization technique on long term outcome for unprotected distal left main disease.

BACKGROUND: There is no consensual opinion regarding the percutaneous coronary intervention (PCI) procedure for unprotected distal left main (UDLM) lesion. METHODS: Between April 2005 and August 2011, 586 consecutive patients with UDLM stenosis treated with drug-eluting stents were recruited for this study to clarify the impact of combination of full-coverage stenting and proximal optimization technique (POT) for UDLM lesion. An optimal strategy of full-coverage stenting and POT was performed in 353 patients and the other 233 patients were not optimally treated. Major adverse cardiovascular events (MACEs) were defined as all-cause death, myocardial infarction, or target lesion revascularization (TLR) during follow-up period. TLRs were also evaluated for main branch (MB) restenosis. RESULTS: At 1615days of follow-up, MACE occurred in 166 (28.3%) patients. The occurrence of MACE and TLR had a trend to being lower in the optimal strategy [propensity score-adjusted HR, 0.73 (95% CI, 0.53-1.01), p=0.05 and propensity score-adjusted HR, 0.69 (95% CI, 0.46-1.02), p=0.06, respectively]. TLR of the MB occurred significantly less frequently in the optimal strategy [propensity score-adjusted HR, 0.34 (95% CI, 0.15-0.76), p=0.008]. Cardiac death occurred in 28 (4.8%) patients. There was no significant difference in cardiac death between the two groups. These results were sustained after propensity-score matching. CONCLUSIONS: An optimal PCI strategy of full-coverage stenting and POT might be effective for UDLM lesion to reduce the occurrence of MACE, especially driven by TLR of the MB.

Impact of rotational atherectomy on heavily calcified, unprotected left main disease.

BACKGROUND: There is little data on percutaneous coronary intervention (PCI) using rotational atherectomy (Rota) for severely calcified unprotected left main (ULM) lesions. METHODS AND RESULTS: Between January 2005 and August 2011, 64 consecutive patients who underwent drug-eluting stent implantation using Rota were retrospectively evaluated. Of these, 54.7% and 20.3% patients had diabetes and were undergoing hemodialysis (HD), respectively. The mean EuroSCORE and SYNTAX score was 5.6 and 35.4, respectively. Procedural success, defined as residual stenosis <30%, was achieved in 95.3% of patients without fatal complications. Periprocedural myocardial infarction occurred in 7.8% patients. At the 1-year follow up, cardiac death was observed in 6.3% of patients, and target lesion revascularization (TLR) and TLR in the main branch (TLR-MB) were required in 18.8% and 10.9% patients, respectively. Optimal stent expansion was achieved in the majority of 33 patients with available intravascular ultrasound (IVUS) data. However, 5 of 9 HD patients who underwent IVUS required TLR-MB despite optimal stent expansion. The rate of TLR-MB was significantly lower in the non-HD patients than in the HD patients (2.1% vs. 46.2%; P=0.003). CONCLUSIONS: PCI using Rota for calcified ULM lesions might guarantee high procedural success and a low complication rate. Although acceptable results were obtained at the 1-year follow up for non-HD patients, the rate of TLR-MB was considerably high for HD patients despite optimal stent expansion.