Subsequent Adverse Events Research Articles

The Adequateness of Methadone for Japanese Terminal Cancer Patients Can Be Determined Earlier than 7 Days: A Preliminary Retrospective Study.

Introduction: The Japanese packaging instructions for methadone prohibit dose escalation within 7 days of administration initiation as this may result in overdose and subsequent adverse events. However, for terminal cancer patients, evaluation of the effects of methadone may be desirable within 7 days because they have limited prognoses. We aimed to determine the possibility of estimating the adequateness of methadone earlier than the 7th day by investigating the onset timing of analgesic effects and adverse events of methadone in Japanese terminal cancer patients. Methods: Japanese terminal cancer patients who started taking methadone in Ashiya Municipal Hospital were enrolled from January 1, 2013 to February 28, 2019. Verbal rating scale (VRS) scores on pain and adverse events before and after methadone administration (on days 3, 5, and 7) were retrospectively investigated from medical records. Results: We enrolled 25 patients, of which 20 (80.0%) received methadone until day 7. The VRS score (mean ± standard deviation) on pain was significantly reduced to 0.90 ± 0.55 on day 3, compared with 1.65 ± 0.67 before the administration of methadone (p < 0.05). The mean VRS scores did not differ significantly on days 3, 5, and 7. Additionally, of the 23 patients who received methadone until day 3, 20 (87.0%) showed an analgesic effect on day 3 and 17 (85.0%) received methadone without experiencing serious adverse events until day 7. Conclusions: The adequateness of methadone in Japanese terminal cancer patients could be determined before day 7, considering the high analgesia incidence and few adverse events 3 days after the methadone administration under careful observation by a physician experienced in methadone administration. However, as this is a preliminary study, the relationship between pharmacokinetic parameters and analgesic effects was not evaluated. Further studies involving pharmacokinetics and multicenter prospective studies are required to support these findings.

Promena paradigme za stabilnu koronarnu bolest u hronični koronarni sindromi - novine u vodiču Evropskog udruženja kardiologa iz 2019. godine

Promena paradigme za stabilnu koronarnu bolest u hronični koronarni sindromi - novine u vodiču Evropskog udruženja kardiologa iz 2019. godine

Revascularization for Coronary Artery Disease: Principle and Challenges.

Coronary revascularization is the most important strategy for coronary artery disease. This review summarizes the current most prevalent approaches for coronary revascularization and discusses the evidence on the mechanisms, indications, techniques, and outcomes of these approaches. Targeting coronary thrombus, fibrinolysis is indicated for patients with diagnosed myocardial infarction and without high risk of severe hemorrhage. The development of fibrinolytic agents has improved the outcomes of ST-elevation myocardial infarction. Percutaneous coronary intervention has become the most frequently performed procedure for coronary artery disease. The evolution of stents plays an important role in the result of the procedure. Coronary artery bypass grafting is the most effective revascularization approach for stenotic coronary arteries. The choice of conduits and surgical techniques are important determinants of patient outcomes. Multidisciplinary decision-making should analyze current evidence, considering the clinical condition of patients, and determine the safety and necessity for coronary revascularization with either PCI or CABG. For coronary artery disease with more complex lesions like left main disease and multivessel disease, CABG results in more complete revascularization than PCI. Furthermore, comorbidities, such as heart failure and diabetes, are always correlated with adverse clinical events, and a routine invasive strategy should be recommended. For patients under revascularization, secondary prevention therapies are also of important value for the prevention of subsequent adverse events.

Sequential Pattern Mining of Longitudinal Adverse Events After Left Ventricular Assist Device Implant.

Left ventricular assist devices (LVADs) are an increasingly common therapy for patients with advanced heart failure. However, implantation of the LVAD increases the risk of stroke, infection, bleeding, and other serious adverse events (AEs). Most post-LVAD AEs studies have focused on individual AEs in isolation, neglecting the possible interrelation, or causality between AEs. This study is the first to conduct an exploratory analysis to discover common sequential chains of AEs following LVAD implantation that are correlated with important clinical outcomes. This analysis was derived from 58,575 recorded AEs for 13,192 patients in International Registry for Mechanical Circulatory Support (INTERMACS) who received a continuous-flow LVAD between 2006 and 2015. The pattern mining procedure involved three main steps: (1) creating a bank of AE sequences by converting the AEs for each patient into a single, chronologically sequenced record, (2) grouping patients with similar AE sequences using hierarchical clustering, and (3) extracting temporal chains of AEs for each group of patients using Markov modeling. The mined results indicate the existence of seven groups of sequential chains of AEs, characterized by common types of AEs that occurred in a unique order. The groups were identified as: GRP1: Recurrent bleeding, GRP2: Trajectory of device malfunction & explant, GRP3: Infection, GRP4: Trajectories to transplant, GRP5: Cardiac arrhythmia, GRP6: Trajectory of neurological dysfunction & death, and GRP7: Trajectory of respiratory failure, renal dysfunction & death. These patterns of sequential post-LVAD AEs disclose potential interdependence between AEs and may aid prediction, and prevention, of subsequent AEs in future studies.

Predictors and outcomes of atrial tachyarrhythmia among patients with implantable defibrillators

Atrial tachyarrhythmias (ATAs) are common among heart failure (HF) patients. The purpose of this study was to assess predictors for the development of new ATA and its components (atrial fibrillation/flutter [AF], supraventricular tachycardia [SVT]), and their association with subsequent clinical outcomes. We assessed predictors for first and recurrent ATA, AF, and SVT among 1500 patients in MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy). We also investigated the association of new ATA, AF, or SVT with subsequent ventricular arrhythmia (VA), adverse events (HF hospitalization, syncope, or death), or death by time-dependent analysis. During 17 months of follow-up, 286 patients (19%) developed new ATA, of whom 92 (6%) had AF and 194 (12%) had SVT. Younger age (≤65 years), diastolic blood pressure ≥72 mm Hg, heart rate ≥63 bpm, absence of diabetes, and prior atrial arrhythmia were independent predictors of ATA. Prior atrial arrhythmia was the only predictor of AF (hazard ratio 3.14; P <.001). New ATA was associated with significantly increased risk for subsequent VA (HR 2.12; P <.001), increased adverse events (HR 1.42; P <.001), and death (HR 1.85; P = .038). New AF and new SVT were both independently associated with >2-fold increased risk for the development of subsequent VA (HR 2.21; P= .012l and HR 2.15; P <.001, respectively) and adverse events. Among MADIT-RIT patients, younger age, absence of diabetes, higher blood pressure, higher heart rate, and prior atrial arrhythmia predicted device-detected ATA. Both AF and SVT were associated with increased risk for subsequent VA and adverse events. Aggressive management should be considered in HF patients who develop new-onset, device-detected ATA to improve clinical outcomes.

Longitudinal Trajectory of Frailty in Blood or Marrow Transplant (BMT) Survivors - a BMT Survivor Study (BMTSS)

Introduction: Frailty is a state of increased vulnerability resulting in a decline in reserve and function across multiple physiologic systems such that the ability to cope with every day or acute stressors is compromised. We previously reported that BMT recipients with frailty were at a 2.8-fold higher risk of subsequent mortality (JAMA Oncol. 2016;2:1277-86) when compared with non-frail survivors. However, longitudinal trends in frailty several years after BMT are not known, and could possibly help in identifying the vulnerable sub-populations at highest risk of subsequent adverse events. We used BMTSS to report transitions in the frailty state over time. Methods: We included 484 patients who were i) transplanted for a hematologic malignancy between 1974 and 1998 at 2 sites and had survived ≥2y post-BMT; ii) were ≥18y of age at study participation; and iii) were alive both at completion of the baseline survey (t1: median of 7.3 y after BMT) and at follow-up survey (t2: median of 20.6y after BMT); median interval between t1 and t2 was 13.2y. Frailty phenotype used the previous definition (JAMA Oncol. 2016;2:1277-86), and included the presence of ≥3 of the following indices: 1) clinically underweight (body mass index [BMI] &amp;lt;18.5); (2) exhaustion; (3) low energy expenditure; (4) slowness; and (5) weakness. Patients reporting the presence of 1-2 of the 5 indices were classified as pre-frail. We created the following categories of change in frailty status over time; A) Worsening of frailty status/ stable frail status : pre-frailty [t1] → frailty [t2]; no-frailty [t1] → pre-frailty/frailty [t2]; and frailty [t1] → frailty [t2]; B) Improvement of frailty status: frailty [t1] → pre-frailty [t2]; pre-frailty [t1] → no frailty [t2]; C) Stable non-frail/pre-frail status: non-frail [t1]→ non-frail [t2]; pre-frail [t1] → pre-frail [t2]. We used logistic regression to evaluate predictors of A) worsening of frailty status/stable frail status, and B) frailty at t2, controlling for age at questionnaire, sex, diagnosis, smoking status, socio-economic, and BMT related variables (conditioning, donor type, presence of cGvHD), grade 3-4 chronic health conditions, and pre-BMT treatments therapeutic exposures. Results: Median age (range) at t1 was 42.9y (18.5-67.4) and at t2 was 56.5y (31.0-80.0); 49.4% were females; 85.4% non-Hispanic whites; 15% had &amp;lt;high school education, and 50% had annual household income of &amp;lt;$60,000. Primary diagnoses included acute leukemia (31%), lymphoma (31%), and chronic myelogenous leukemia (25%); 57% had received an allogeneic BMT; 77% received TBI; 40.3% had cGvHD. Prevalence of frailty was 4.8% at t1 and 9.6% at t2, and that of pre-frailty was 13.9% at t1 and 16.1% at t2 (Figure). Worsening of frailty status was seen in 18.8% of the patients, improvement in 9.7%; 68.7% of the patients remained non-frail or pre-frail. Predictors of worsening of frailty status: Pre-BMT exposure to vincristine (OR=5.1, 95%CI: 2.3-11.4) and female sex (OR=1.5, 95%CI, 0.9-2.6, p=0.08) were associated with worsening. Predictors of frailty at t2: Pre-BMT exposure to vincristine (OR=4.6, 95%CI, 1.7-12.5, p=0.003), history of cGvHD at t1 (OR=2.3, 95%CI, 1.0-5.2, p=0.04) and grades 3-4 chronic health conditions at t1 (OR=2.1, 95%CI, 1.0-4.5, p=0.04) were associated with frailty at t2. Age was not a significant predictor in either analysis. Conclusions: In a cohort of patients followed longitudinally for a median of 20.6y from BMT, with measurement of frailty status 13.2y apart, we observed that the frailty status worsened for ~20% of the patients. Pre-transplant exposure to vincristine was associated with worsening of frailty status. Patients with cGvHD or morbidity at t1, as well as pre-BMT vincristine exposure placed BMT survivors at high risk for subsequent frailty, identifying sub-populations that could benefit from targeted interventions. Disclosures Weisdorf: Incyte: Research Funding; Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy.

Clinical significance of the presence of puff-chandelier ruptures detected by nonobstructive aortic angioscopy.

This study aimed to investigate the prevalence and prognostic significance of atherosclerotic aortic plaques (AAPs) or specific AAP types detected by nonobstructive angioscopy (NOA) in patients who underwent percutaneous coronary intervention (PCI). Although recent studies have reported the presence of various patterns of AAPs, identified by NOA, the clinical significance of the presence of AAPs remains elusive. In this retrospective, multicenter cohort study, a total of 167 patients who underwent PCI and intra-aortic scans with NOA were studied. The association between AAPs and the incidence of major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, stroke, and clinically driven unplanned revascularizations, was assessed. AAPs were detected in 126 patients (75%) who underwent NOA. MACEs occurred in 28 (17%) patients during the follow-up (median 2.9 years [range 2.1-3.8]). Among all types of AAPs, only puff-chandelier rupture (PCR) showed a significant difference in frequency between patients with and those without MACEs: 21 (75%) and 49 (35%), respectively (p < .001). Multivariable Cox proportional hazard analysis revealed that PCR (hazard ratio [HR] 3.73, 95% confidence interval [CI] 1.57-8.87, p = .004) and chronic kidney disease (HR 2.97, 95% CI 1.37-6.44, p = .010) were independent predictors of MACEs. Kaplan-Meier analysis revealed that PCR was significantly associated with more frequent MACEs. The detection of PCR in the aorta using NOA was significantly associated with an increased risk of subsequent adverse events after PCI.

Patent foramen ovale closure versus medical therapy for cryptogenic stroke: An updated systematic review and meta-analysis

ObjectivesThe objective of this study was to compare safety and efficacy of patent foramen ovale (PFO) closure compared with medical therapy in patients with cryptogenic stroke (CS). BackgroundThe role of PFO closure in preventing recurrent stroke in patients with prior CS has been controversial. MethodsWe searched PubMed, EMBASE, the Cochrane Central Register of Controlled trials, and the clinical trial registry maintained at clinicaltrials.gov for randomized control trials that compared device closure with medical management and reported on subsequent stroke and adverse events. Event rates were compared using a forest plot of relative risk using a random-effects model assuming interstudy heterogeneity. ResultsA total of 6 studies (n = 3747) were included in the final analysis. Mean follow-up ranged from 2 to 5.9 years. Pooled analysis revealed that device closure compared to medical management was associated with a significant reduction in stroke (risk ratio [RR] = 0.41, 95% CI = 0.20–0.83, I2 = 51%, P = 0.01). There was, however, a significant increase in atrial fibrillation with device therapy (RR = 5.29, 95% CI = 2.32–12.06, I2 = 38%, P < 0.0001). No effect was observed on major bleeding (P = 0.50) or mortality (P = 0.42) with device therapy. Subgroup analyses showed that device closure significantly reduced the incidence of the composite primary end point among patients who had large shunt sizes (RR = 0.35, 95% CI = 0.18–0.68, I2 = 27%, P = 0.002). The presence/absence of atrial septal aneurysm (P = 0.52) had no effect on the outcome. ConclusionPFO closure is associated with a significant reduction in the risk of stroke compared to medical management. However, it causes an increased risk of atrial fibrillation.

Prognostic Value of QFR Measured Immediately After Successful Stent Implantation: The International Multicenter Prospective HAWKEYE Study

ObjectivesThe aim of this study was to investigate the potential role of post–percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) measurements to predict clinical outcomes in patients with successful PCI. BackgroundThe prognostic value of QFR measured immediately after PCI has not been prospectively investigated. MethodsPatients undergoing complete revascularization with successful PCI and stent implantation were eligible for acquisition of projections for QFR computation. At the end of the procedure, 2 angiographic projections for each vessel treated with PCI were acquired. Computation of QFR was performed offline by an independent core laboratory. The primary outcome was the vessel-oriented composite endpoint, defined as vessel-related cardiovascular death, vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. ResultsSeven hundred fifty-one vessels in 602 patients were analyzed. The median value of post-PCI QFR was 0.97 (interquartile range: 0.92 to 0.99). Lesion location in the left anterior descending coronary artery, baseline SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score, lesion length, and post-PCI diameter stenosis were found to be predictors of lower post-PCI QFR. Altogether, 77 events were detected in 53 treated vessels (7%). Post-PCI QFR was significantly lower in vessels with the vessel-oriented composite endpoint during follow-up, compared with those without it (0.88 [interquartile range: 0.81 to 0.99] vs. 0.97 [interquartile range: 0.93 to 0.99], respectively; p < 0.001). Receiver-operating characteristic curve analysis identified a post-PCI QFR best cutoff of ≤0.89 (area under the curve 0.77; 95% confidence interval: 0.74 to 0.80; p < 0.001). After correction for potential confounding factors, post-PCI QFR ≤0.89 was associated with a 3-fold increase in risk for the vessel-oriented composite endpoint (hazard ratio: 2.91; 95% confidence interval: 1.63 to 5.19; p < 0.001). ConclusionsLower values of QFR after complete and successful revascularization predict subsequent adverse events (Angio-Based Fractional Flow Reserve to Predict Adverse Events After Stent Implantation [HAWKEYE]; NCT02811796)

TCT-162 Impact of Thrombocytopenia on Subsequent 1-Year Major Adverse Cardiovascular Event (MACE) in Non–ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS)

The relationship of thrombocytopenia to subsequent major adverse cardiovascular events (MACE) in non–ST-segment elevation acute coronary syndrome (NSTE-ACS) is unclear. A total of 1,510 consecutive patients with NSTE-ACS presenting to a teaching hospital in Hong Kong in 2014 to 2018 were analyzed

Analysis of anticholinergic and sedative medicine effects on physical function, cognitive function, appetite and frailty: a cross-sectional study in Australia

ObjectiveTo test the association between use of medicines with anticholinergic or sedative properties and physical function, cognitive function, appetite and frailty.Design, setting and participantsThis cross-sectional study analysed baseline data collected...

116. Comparison of imputation methods for evaluating long-term clinical outcomes following lumbar total disc replacement

BACKGROUND CONTEXT The problem of missing data is common in clinical trials, and it can have a significant impact on the conclusions that can be drawn from the data. Long-term results are particularly susceptible as the lost to follow-up (LTFU) rates increase over the course of a trial. Imputation methods are often used to account for missing data points, but some may either under or overestimate the true treatment effect. PURPOSE In this post-hoc analysis of a randomized clinical trial, we evaluated the clinical success of three motion preserving artificial discs up to 7 years following lumbar total disc replacement (TDR) using different imputation methods. STUDY DESIGN/SETTING Randomized, controlled, multicenter clinical IDE trial. PATIENT SAMPLE A total of 324 subjects with single level degenerative disc disease and discogenic pain. OUTCOME MEASURES Radigraphic range of motion on flexion-extension, Oswestry Disability Index (ODI), neurologic exam, adverse events, subsequent surgery. METHODS Subjects were randomized to receive either a semi-constrained mobile core disc (n=218) or a control device (n=106) which was either a constrained (n=65) or unconstrained (n=41) core disc. Several imputation methods were used to calculate clinical success, including: missing values=failure, missing values=success, last observation carried forward (LOCF), complete case, best case and worst case scenarios. Clinical success scores were compared between the treatment (semi-constrained) and control (constrained or unconstrained) groups.Clinical outcomes were collected from baseline through to 7 years following single level (L4-L5 or L5-S1) TDR. Clinical success was defined as a ≥15 point improvement in ODI from baseline, maintenance or improvement in ROM and neurological evaluation (motor and sensory), the absence of index-level subsequent surgical interventions (SSI) and serious device-related adverse events (SDAE). RESULTS By imputing missing values as failures, individual success scores decreased at 5 and 7 years compared to 2 years postop for both groups. Only ROM success at 2 years was significantly greater in the treatment compared to control group (58.7% vs 42.5%, p=0.0065). The overall success score, which is a composite of the individual success scores, also decreased over time, but it was significantly greater in the treatment group at 2 years (42.2% vs 28.3%, p=0.0020). Using complete case data, clinical success at 5 and 7 years was maintained close to 2-year values for overall and individual success scores, except for SDAE success which decreased at 7 years from 2 years for both the treatment (86.1% to 67.1%) and control groups (78.7% to 63.2%). Similarly, LOCF clinical outcomes were the same between 5 and 7 years postop for both groups. By imputing missing values as successes, the results were comparable to scores yielded by complete case and LOCF imputation methods. CONCLUSIONS The missing=failure imputation method is most susceptible to LFTU and may underestimate the treatment effect if there is a large LTFU rate, which is inherent in most long-term clinical studies. Complete case and LOCF imputation methods may be more accurate estimates of long-term clinical outcomes for clinical studies with a large patient enrollment. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

HsCRP Level and the Risk of Death or Recurrent Cardiovascular Events in Patients With Myocardial Infarction: a Healthcare-Based Study.

BackgroundBeyond the controlled setting of trials, scarce information exists on the burden, predictors, and outcomes associated with elevated hsCRP (high‐sensitivity C‐reactive protein) in “real‐world” patients with myocardial infarction (MI).Methods and ResultsWe included all‐coming MI survivors undergoing hsCRP testing >30 days after an MI during routine health care in Stockholm, Sweden (2006–2011). hsCRP tests measured during hospitalization/emergency department visits, followed by antibiotics or indicative of acute illness, were excluded, together with patients with ongoing/recent cancer, chronic infections, or immunosuppression. Inflammation was defined over a 3‐month baseline window and associated with subsequent death and major adverse cardiovascular events (composite of MI, ischemic stroke, or cardiovascular death). Included were 17 464 patients (63% men; mean age, 72.6 years) with a median hsCRP level of 2.2 (interquartile range, 1.0–6.0) mg/L and a median of 2.2 (interquartile range, 0.8–4.9) years since their MI. Most (66%) had hsCRP ≥2 mg/L, and 40% had hsCRP >3 mg/L. Lower hemoglobin, lower estimated glomerular filtration rate, and comorbidities (eg, heart failure, peripheral vascular disease, stroke, atrial fibrillation, diabetes mellitus, and rheumatoid diseases) were associated with higher odds of hsCRP ≥2 mg/L. Conversely, previous percutaneous coronary intervention, ongoing renin‐angiotensin blockade, and statins were associated with lower hsCRP ≥2 mg/L odds. Patients with hsCRP ≥2 mg/L were at higher risk of major adverse cardiovascular events (n=3900; adjusted hazard ratio, 1.28; 95% CI, 1.18–1.38) and death (n=4138; adjusted hazard ratio, 1.42; 95% CI, 1.31–1.53). Results were robust across subgroups of patients and after exclusion of events occurring during the first 6 to 12 months. On a continuous scale, the association between hsCRP and outcomes was linear until hsCRP >5 mg/L, plateauing thereafter.ConclusionsMost patients with MI exhibit elevated hsCRP levels. Besides identifying populations at high‐inflammatory risk, this study extends the prognostic validity of this biomarker from trial evidence to real‐world healthcare settings.

Effect of ex vivo extracorporeal membrane oxygenation flow dynamics on immune response.

Extracorporeal membrane oxygenation is a life-saving support for heart and/or lung failure patients. Despite technological advancement, abnormal physiology persists and has been associated with subsequent adverse events. These include thrombosis, bleeding, systemic inflammatory response syndrome and infection. However, the underlying mechanisms are yet to be elucidated. We aimed to investigate whether the different flow dynamics of extracorporeal membrane oxygenation would alter immune responses, specifically the overall inflammatory response, leukocyte numbers and activation/adhesion surface antigen expression. An ex vivo model was used with human whole blood circulating at 37°C for 6 hours at high (4 L/minute) or low (1.5 L/minute) flow dynamics, with serial blood samples taken for analysis. During high flow, production of interleukin-1β (p < 0.0001), interleukin-6 (p = 0.0075), tumour necrosis factor-α (p = 0.0013), myeloperoxidase (p < 0.0001) and neutrophil elastase (p < 0.0001) were significantly elevated over time compared to low flow, in particular at 6 hours. While the remaining assessments exhibited minute changes between flow dynamics, a consistent trend of modulation in leukocyte subset numbers and phenotype was observed at 6 hours. We conclude that prolonged circulation at high flow triggers a prominent pro-inflammatory cytokine response and activates neutrophil granule release, but further research is needed to better characterize the effect of flow during extracorporeal membrane oxygenation.

Sequential Chains of Adverse Events Post LVAD Implantation

Purpose Most post-LVAD Adverse Events (AEs) studies have focused on individual AEs in isolation, neglecting the possible interrelation, or causality between AEs. This study for the first time conducted a novel exploratory analysis to discover sequential chains of AEs following LVAD implantation. Methods This analysis was derived from 58,575 recorded AEs for 13,192 patients in INTERMACS who received a continuous-flow LVAD between 2006 and 2015. The data mining procedure involved three main steps: (1) create a bank of AE sequences, (2) group patients with similar AE sequences using hierarchical clustering, and (3) extract temporal chains of AEs for each group of patients using Markov modeling. Results The mined results indicate the existence of seven groups of sequential chains of AEs, characterized by common types of AEs that occurred in a unique order. A portion of the pattern analysis in this study is shown in Fig.1. The groups were identified as: GRP1(Recurrent bleeding) 862 patients with a minimum of 2 bleeding AEs, GRP2(Trajectory of device malfunction & explant) 1,591 patients who had device malfunction preceded by infection and bleeding, and then commonly had their LVADs removed, GRP3(Infection) 3,438 patients who suffered from recurrent infection or infection accompanied with bleeding , GRP4(Trajectories to transplant) 3,302 patients who received a heart transplant and commonly experienced bleeding, infection, and cardiac arrhythmia , GRP5(Cardiac arrhythmia) 1,275 patients who experienced one or recurrent cardiac arrhythmia commonly accompanied with infection and bleeding, GRP6(Trajectory of neurological dysfunction & death) 1,616 patients, and GRP7(Trajectory of respiratory failure, renal dysfunction & death) 1,108 patients who died with an average of 3 and 5 AEs, respectively, and median time to death of 6 and 3 post-LVAD months, respectively. Conclusion These chains of AEs disclose potential interdependence between post-LVAD AEs and may aid prediction, and prevention, of subsequent AEs - which is the topic of ongoing work.

Weight change is associated with increased all-cause mortality and non-cardiac mortality among patients with type 2 diabetes mellitus.

It is unclear whether changes in weight affect subsequent adverse events in patients with type 2 diabetes mellitus (T2DM) already at high risk of cardiovascular disease (CVD). This is a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study data to examine the relationship between changes in weight and adverse events. Patients were divided into groups based on changes in body mass index (BMI): stable weight, gain or loss of BMI ≤1.5 kg/m2; moderate weight gain, BMI gain of 1.5-5 kg/m2; pronounced weight gain, BMI gain >5 kg/m2; moderate weight loss, BMI loss of 1.5-5 kg/m2; and pronounced weight loss, BMI loss >5 kg/m2. The primary endpoint of the present study was all-cause mortality. Secondary endpoints were cardiac death, non-fatal myocardial infarction (MI), and non-cardiac mortality. A total of 9372 T2DM patients with a mean follow-up of 8.08 ± 3.00 years were included for analysis. The average change in weight across the entire study population was 1.80 ± 9.00%, representing ~0.448 ± 2.98 kg/m2. Patients with pronounced weight loss had the highest risk of all-cause mortality (hazard ratio (HR) 2.07, 95% confidence interval (CI): 1.68-2.55), followed by patients with pronounced weight gain (HR 1.23, 95% CI: 1.02-1.56); patients with stable weight had the lowest risk. An asymmetric V-shaped relationship was observed between changes in BMI and all-cause mortality and non-cardiac mortality. Although no statistical significance was observed in terms of cardiac death and non-fatal MI, a flat V-shaped relationship may exist. Weight was stable in most T2DM patients with high risk of CVD. Weight loss and gain is associated with increased all-cause mortality and non-cardiac mortality. Pronounced weight loss and weight gain is associated with a slight increase in cardiac death and non-fatal MI incidence, which does not reach statistical significance.

Reasons for hospitalization and risk of mortality in patients with atrial fibrillation treated with dabigatran or warfarin in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial.

Hospitalizations are common among patients with atrial fibrillation. This article aimed to analyse the causes and consequences of hospitalizations occurring during the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial. The RE-LY database was used to evaluate predictors of hospitalization using multivariate regression modelling. The relationship between hospitalization and subsequent major adverse cardiac events was evaluated in a time dependent Cox proportional-hazard modelling. Of the 18 113 patients in RE-LY, 7200 (39.8%) were hospitalized at least once during a mean follow-up of 2 years. First hospitalization rates were 2312 (39.5%) for dabigatran etexilate (DE) 110, 2430 (41.6%) for DE 150, and 42.6% (N = 2458) for warfarin. Hospitalization was associated with post-discharge death [absolute event rate 9.1% vs. 2.2%; adjusted hazard ratio (HR) 3.6, 95% confidence interval (CI) 3.2-4.0, P < 0.0001], vascular death (adjusted HR 2.9, 95% CI 2.5-3.3, P < 0.0001), and sudden cardiac death (adjusted HR 2.3; 95% CI 1.8-2.9, P < 0.0001). Cardiovascular hospitalization was also associated with an increased risk of post-discharge death (adjusted HR 2.8, 95% CI 2.5-3.2, P < 0.0001), vascular death (adjusted HR 2.8, 95% CI 2.4-3.2, P < 0.0001), and sudden cardiac death (adjusted HR 2.1, 95% CI 1.6-2.7, P < 0.0001) compared with patients not hospitalized for any cardiovascular reason. Hospitalizations are associated an increased risk of with death and cardiovascular death in patients with atrial fibrillation.

Baroreceptor Sensitivity Predicts Functional Outcome and Complications after Acute Ischemic Stroke.

Autonomic dysfunctions including impaired baroreflex sensitivity (BRS) can develop after acute ischemic stroke (AIS) and may predispose patients to subsequent cardiovascular adverse events and serve as potential indicators of long-term mortality. This study aimed to determine the potential short-term prognostic significance of BRS after AIS. All patients admitted to Kaohsiung Veterans General Hospital within 72 h after onset of first-ever AIS between April 2008 and December 2012 were enrolled. Autonomic evaluation with continuous 10-minute monitoring of beat-to-beat hemodynamic and intracranial parameters was performed within 1 week after stroke by using the Task Force Monitor and transcranial Doppler. The 176 enrolled AIS patients were divided into high-BRS and low-BRS groups. All but two enrolled patients (who died within 3 months after stroke) attended scheduled follow-ups. The high-BRS group had significantly lower National Institutes of Health Stroke Scale (NIHSS) scores at 1 and 2 weeks after stroke and at discharge; lower modified Rankin scale (mRS) scores 1, 3, 6, and 12 months after stroke; and lower rates of complications and stroke recurrence compared to the low-BRS group. This study provides novel evidence of the utility of BRS to independently predict outcomes after AIS. Furthermore, modifying BRS may hold potential in future applications as a novel therapeutic strategy for acute stroke.

Impact of the Temporal Distribution of Coronary Artery Disease Progression on Subsequent Consequences in Patients with Acute Coronary Syndrome.

The late consequences of acute coronary syndrome (ACS) have been underestimated. We hypothesized that the temporal distribution of the clinically silent coronary artery disease progression (CP) is associated with the subsequent consequences of ACS.We studied 243 patients (202 men, 64 ± 10 years) with ACS undergoing percutaneous coronary intervention (PCI) during initial hospitalization. All patients underwent serial coronary angiograms (CAGs) immediately before PCI and at 7 ± 3 and 60 ± 10 months after presentation. CP was defined as an increase ≥ 15% in stenosis severity of the lesion between 2 serial CAGs. The impact of CP between each 2 serial CAGs on subsequent major adverse cardiovascular and cerebrovascular events (MACCEs) after the final CAG was examined using multivariate Cox and propensity-matched analyses.During the median follow-up duration after the final CAG of 67 months, 76 MACCEs (31.3%) were observed. Multivariate Cox proportional hazards analysis revealed that CP between the first and second CAGs (hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.32-3.94; P = 0.003) and CP between the second and final CAGs (HR, 1.96; 95% CI, 1.20-3.21; P = 0.008) were independently associated with a higher rate of MACCEs beyond the final CAG. Consistent results were obtained in the propensity score-matched analyses.CP in both the early (0-7 months) and late phases (7-60 months) were independently associated with subsequent clinical events. This may indicate the prognostic significance of persistent widespread coronary disease activity following presentation in patients with ACS undergoing PCI.

Complication Rates and Downstream Medical Costs Associated With Invasive Diagnostic Procedures for Lung Abnormalities in the Community Setting

The Centers for Medicare & Medicaid Services added lung cancer screening with low-dose computed tomography (LDCT) as a Medicare preventive service benefit in 2015 following findings from the National Lung Screening Trial (NLST) that showed a 16% reduction in lung cancer mortality associated with LDCT. A challenge in developing and promoting a national lung cancer screening program is the high false-positive rate of LDCT because abnormal findings from thoracic imaging often trigger subsequent invasive diagnostic procedures and could lead to postprocedural complications. To determine the complication rates and downstream medical costs associated with invasive diagnostic procedures performed for identification of lung abnormalities in the community setting. A retrospective cohort study of non-protocol-driven community practices captured in MarketScan Commercial Claims & Encounters and Medicare supplemental databases was conducted. A nationally representative sample of 344 510 patients aged 55 to 77 years who underwent invasive diagnostic procedures between 2008 and 2013 was included. One-year complication rates were calculated for 4 groups of invasive diagnostic procedures. The complication rates and costs were further stratified by age group. Of the 344 510 individuals aged 55 to 77 years included in the study, 174 702 comprised the study group (109 363 [62.6%] women) and 169 808 served as the control group (106 007 [62.4%] women). The estimated complication rate was 22.2% (95% CI, 21.7%-22.7%) for individuals in the young age group and 23.8% (95% CI, 23.0%-24.6%) for those in the Medicare group; the rates were approximately twice as high as those reported in the NLST (9.8% and 8.5%, respectively). The mean incremental complication costs were $6320 (95% CI, $5863-$6777) for minor complications to $56 845 (95% CI, $47 953-$65 737) for major complications. The rates of complications after invasive diagnostic procedures were higher than the rates reported in clinical trials. Physicians and patients should be aware of the potential risks of subsequent adverse events and their high downstream costs in the shared decision-making process.