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.

Epidemiology, microbiology, and diagnosis of infection in diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: A multicenter retrospective observational study.

AIMS: We investigated the characteristics of infection and the utility of inflammatory markers in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS). METHODS: A multicenter, retrospective observational study in 21 acute-care hospitals was conducted in Japan. This study included adult hospitalized patients with DKA and HHS. We analyzed the diagnostic accuracy of markers including C-reactive protein (CRP) and procalcitonin (PCT) for bacteremia. Multiple regression models were created for estimating bacteremia risk factors. RESULTS: A total of 771 patients, including 545 patients with DKA and 226 patients with HHS, were analyzed. The mean age was 58.2 (SD, 19.3) years. Of these, 70 tested positive for blood culture. The mortality rates of those with and without bacteremia were 14 % and 3.3 % (P-value < 0.001). The area under the curve (AUC) of CRP and PCT for diagnosis of bacteremia was 0.85 (95 %CI, 0.81-0.89) and 0.76 (95 %CI, 0.60-0.92), respectively. Logistic regression models identified older age, altered level of consciousness, hypotension, and higher CRP as risk factors for bacteremia. CONCLUSIONS: The mortality rate was higher in patients with bacteremia than patients without it. CRP, rather than PCT, may be valid for diagnosing bacteremia in hyperglycemic emergencies. TRIAL REGISTRATION: This study is registered in the UMIN clinical trial registration system (UMIN000025393, Registered December 23, 2016).

High versus low chloride load in adult hyperglycemic emergencies with acute kidney injury: a multicenter retrospective cohort study.

Hyperglycemic emergencies frequently lead to acute kidney injury (AKI) and require treatment with large amount of intravenous fluids. However, the effects of chloride loading on this population have not yet been investigated. We conducted a multicenter, retrospective, cohort study in 21 acute-care hospitals in Japan. The study included hospitalized adult patients with diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) who had AKI upon arrival. The patients were classified into high and low chloride groups based on the amount of chloride administered within the first 48 h of their arrival. The primary outcome was recovery from AKI; secondary outcome was major adverse kidney events within 30 days (MAKE30), including mortality and prolonged renal failure. A total of 390 patients with AKI, including 268 (69%) with DKA and 122 (31%) with HHS, were included in the study. Using the criteria of Kidney Disease Improving Global Outcomes, the severity of AKI in the patients was Stage 1 (n = 159, 41%), Stage 2 (n = 121, 31%), and Stage 3 (n = 110, 28%). The analysis showed no significant difference between the two groups in recovery from AKI (adjusted hazard ratio, 0.96; 95% CI 0.72-1.28; P = 0.78) and in MAKE30 (adjusted odds ratio, 0.91; 95% CI 0.45-1.76; P = 0.80). Chloride loading with fluid administration had no significant impact on recovery from AKI in patients with hyperglycemic emergencies.Trial Registration This study was registered in the UMIN clinical trial registration system (UMIN000025393, registered December 23, 2016).

Clinical profile of patients with diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome in Japan: a multicenter retrospective cohort study.

INTRODUCTION: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) are life-threatening complications of diabetes mellitus. Their clinical profiles have not been fully investigated. METHODS: A multicenter retrospective cohort study was conducted in 21 acute care hospitals in Japan. Patients included were adults aged 18 or older who had been hospitalized from January 1, 2012, to December 31, 2016 due to DKA or HHS. The data were extracted from patient medical records. A four-group comparison (mild DKA, moderate DKA, severe DKA, and HHS) was performed to evaluate outcomes. RESULTS: A total of 771 patients including 545 patients with DKA and 226 patients with HHS were identified during the study period. The major precipitating factors of disease episodes were poor medication compliance, infectious diseases, and excessive drinking of sugar-sweetened beverages. The median hospital stay was 16 days [IQR 10-26 days]. The intensive care unit (ICU) admission rate was 44.4% (mean) and the rate at each hospital ranged from 0 to 100%. The in-hospital mortality rate was 2.8% in patients with DKA and 7.1% in the HHS group. No significant difference in mortality was seen among the three DKA groups. CONCLUSIONS: The mortality rate of patients with DKA in Japan is similar to other studies, while that of HHS was lower. The ICU admission rate varied among institutions. There was no significant association between the severity of DKA and mortality in the study population. TRIAL REGISTRATION: This study is registered in the UMIN clinical Trial Registration System (UMIN000025393, Registered 23th December 2016).

Coronary microcirculatory dysfunction can be assessed by positive dicrotic wave and amplitude index on resting distal coronary pressure waveform, a newly developed index.

Aims: Some lesions have high resting distal coronary pressure/aortic pressure (Pd/Pa) despite low fractional flow reserve (FFR). This study aimed to assess microcirculatory dysfunction as a possible basal mechanism. Methods and results: Patients were grouped into two according to coffee intake (caffeine 222 mg) before coronary angiography. Through an adenosine-induced Pd/Pa decrease, amplitude index was calculated by dividing the difference between the highest pressure after the inflection point and the minimal diastolic pressure by the pulse pressure on the Pd waveform. In 130 coronary lesions (caffeine group, n = 69; non-caffeine group, n = 61) from 113 patients, the amplitude index through the adenosine-induced Pd/Pa decrease in all lesions was 0.54 ± 0.11 at resting Pd/Pa and 0.44 ± 0.12 at FFR (P < 0.0001). The positive dicrotic wave distribution on a maximal hyperaemia (FFRnicr)-resting Pd/Pa graph was analysed. In lesions with FFRnicr <0.80 on the FFRnicr-resting Pd/Pa graph, the resting Pd/Pa was divided into three zones based on Pd/Pa values: high-remaining, intermediate, and low. The high-remaining zone had a higher amplitude index than the intermediate zone (0.60 ± 0.09 vs. 0.48 ± 0.12; P < 0.005); the low zone lesions had no inflection point (no amplitude index). The high-remaining zone correlated with a larger positive dicrotic wave than the intermediate zone (94 vs. 30%; P < 0.005). Most lesions in the high-remaining zone corresponded to the caffeine group. Conclusion: In severe coronary stenosis, a high-remaining resting Pd/Pa with a high amplitude index or a positive dicrotic wave on the resting Pd waveform suggests microcirculatory dysfunction, such as insufficient arteriolar dilation reactive to myocardial ischaemia. Registration: UMIN000046883.

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.

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.

An application of pacemaker respiratory monitoring system for the prediction of heart failure.

Sleep-disordered breathing (SDB) is one of the most common complications among heart failure (HF) patients. Changes of respiratory patterns during the various stages in patients with HF have not been fully investigated. In this case, the algorism using thoracic impedance sensor and minute ventilation (sleep apnea monitoring [SAM] algorithm) with implanted pacemaker (REPLY 200 SR or DR, Sorin CRM SAS, Clamart, France) was used to monitor respiration. Impedance data from the implanted pacemaker can be converted into respiratory data, which can be used to calculate the respiratory disturbance index (RDI) per unit of time. Using this algorithm, we observed a sudden appearance of abnormal breathing at the onset of HF, followed by gradual improvement of respiratory patterns during the recovery stage. The results from respiratory monitoring using the SAM algorithm were strongly correlated with those from the positive airway pressure device. This case report could imply that proper utilization of this sensor could facilitate the early detection and therapeutic control of HF.

Saline-induced Pd/Pa ratio predicts functional significance of coronary stenosis assessed using fractional flow reserve.

AIMS: Fractional flow reserve (FFR), assessed using distal coronary pressure/aortic pressure (Pd)/(Pa) ratio, functionally evaluates coronary stenosis. An assessment method without vasodilators would be helpful. A single intracoronary bolus of saline decreases Pd because of the speculated low-viscosity effect. We hypothesised that saline-induced Pd/Pa ratio (SPR) could functionally evaluate coronary stenosis. This study aimed to test the accuracy and utility of SPR for predicting FFR ≤0.80. METHODS AND RESULTS: In 137 coronary lesions with over 50% angiographic diameter stenosis, SPR was assessed using an intracoronary bolus of saline (2 mL/s) for five heartbeats (SPR-5) and three heartbeats (SPR-3). FFR was obtained after intravenous adenosine infusion (140 µg/kg/min). There was a strong correlation between FFR and SPR-5 or SPR-3 (R=0.941 and R=0.933, respectively). Receiver operating characteristic (ROC) curve analysis demonstrated good accuracy (86.3%) for SPR-5, with a cut-off of ≤0.84 for predicting FFR ≤0.80 (area under ROC curve 0.96, specificity 94.3, sensitivity 79.9). Thirty-three lesions (24%) were located in the "grey zone" (SPR 0.83-0.88). No complications were observed in 673 SPR measurements. CONCLUSIONS: SPR may accurately predict FFR and can limit adenosine use to one in four lesions. Further studies are needed to confirm the validity of SPR.

Eosinophilic Myocarditis due to Toxocariasis: Not a Rare Cause.

Myocarditis is a clinically important disease because of the high mortality. From the perspective of treatment strategy, eosinophilic myocarditis should be distinguished from other types of myocarditis. Toxocariasis, caused by Toxocara canis or Toxocara cati, is known as a cause of eosinophilic myocarditis but is considered rare. As it is an unpopular disease, eosinophilic myocarditis due to toxocariasis may be underdiagnosed. We experienced two cases of eosinophilic myocarditis due to toxocariasis from different geographical areas in quick succession between 2013 and 2014. Case 1 is 32-year-old man. Case 2 is 66-year-old woman. In both cases, diagnosis was done by endomyocardial biopsy and IgG-ELISA against Toxocara excretory-secretory antigen. Only a corticosteroid was used in Case 1, whereas a corticosteroid and albendazole were used in Case 2 as induction therapy. Both patients recovered. Albendazole was also used in Case 1 to prevent recurrence after induction therapy. Eosinophilic myocarditis by toxocariasis may in actuality not be a rare disease, and corticosteroid is an effective drug as induction therapy even before use of albendazole.