Factors associated with coronary heart disease in COPD patients and controls.

BACKGROUND: COPD and coronary heart disease (CHD) frequently co-occur, yet which COPD phenotypes are most prone to CHD is poorly understood. The aim of this study was to see whether COPD patients did have a true higher risk for CHD than subjects without COPD, and to examine a range of potential factors associated with CHD in COPD patients and controls. METHODS: 347 COPD patients and 428 non-COPD controls, were invited for coronary computed tomography angiography (CCTA) and pulmonary CT. Arterial blood gas, bioelectrical impedance and lung function was measured, and a detailed medical history taken. The CCTA was evaluated for significant coronary stenosis and calcium score (CaSc), and emphysema defined as >10% of total area <-950 Hounsfield units. RESULTS: 12.6% of the COPD patients and 5.7% of the controls had coronary stenosis (p<0.01), whereas 55.9% of the COPD patients had a CaSc>100 compared to 31.6% of the controls (p<0.01). In a multivariable model adjusting for sex, age, body composition, pack-years, CRP, cholesterol/blood pressure lowering medication use and diabetes mellitus, the OR (95% CI) for having significant stenosis was 1.80 (0.86-3.78) in COPD patients compared with controls. In a similar model, the OR (95% CI) for having CaSc>100 was 1.68 (1.12-2.53) in COPD patients compared with controls. Examining the risk of significant stenosis and CaSc>100 among COPD patients, no variable was associated with significant stenosis, whereas male sex [OR 2.85 (1.56-5.21)], age [OR 3.74 (2.42-5.77)], statin use [OR 2.23 (1.23-4.50)] were associated with CaSc>100, after adjusting for body composition, pack-years, C-reactive protein, use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), diabetes, emphysema score, GOLD category, exacerbation frequency, eosinophilia, and hypoxemia. CONCLUSION: COPD patients were more likely to have CHD, but neither emphysema score, lung function, exacerbation frequency, nor hypoxemia predicted presence of either coronary stenosis or CaSc>100.

Frailty Status and Patient-Reported Outcomes in Octogenarians Following Transcatheter or Surgical Aortic Valve Replacement.

BACKGROUND: Frailty status and patient-reported outcomes are especially pertinent in octogenarians following transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) to guide treatment decisions and promote patient-centred care. AIM: We aimed to determine if frailty changed 6 months after aortic valve replacement (AVR) in octogenarians, and to describe changes in self-rated health according to frailty status in patients who underwent TAVI or SAVR. METHOD: In a prospective cohort study, frailty and self-rated health were measured one day prior to and 6 months after AVR. Frailty status was measured with the Study of Osteoporotic Fracture index. Self-rated health was measured comprehensively with the disease-specific Minnesota Living with Heart Failure Questionnaire, the generic Medical Outcomes Study Short Form-12 questionnaire (SF-12), and two global questions from The World Health Organization Quality of Life Instrument Abbreviated. RESULTS: Data were available for 143 consecutive patients (mean age 83±2.7 years, 57% women; 45% underwent TAVI). At baseline, 34% were robust, 27% prefrail, and 39% frail. Overall, there was no change in the distribution of frailty status 6 months after baseline (p=0.13). However, on an individual level 65 patients changed frailty status after AVR (40 patients improved and 25 declined). Improvement in frailty status was common in prefrail (33%; n=13) and frail patients (48%; n=27). Patients had improved self-rated health after AVR, with significant differences between frailty states both at baseline (SF-12 physical: 37.4 [robust], 33.1 [prefrail], 31.6 [frail], p=0.03); SF-12 mental: 51.9 [robust], 50.8 [prefrail], 44.5 [frail], p<0.001); and at the 6-month follow-up (SF-12 physical: 45.4 [robust], 38.3 [prefrail], 32.1 [frail], p<0.001); SF-12 mental: 54.9 [robust], 49.6 [prefrail], 46.8 [frail], p=0.002). CONCLUSIONS: Advanced treatment performed in a high-risk population allowed people to improve their self-rated health. Although frailty is associated with poor self-rated health, frailty status does not equal negative outcomes. The frail patients were those who improved most in self-rated physical and mental health. They had the lowest baseline self-rated health scores and had therefore the most to gain.

Indwelling urinary catheters, aortic valve treatment and delirium: a prospective cohort study.

OBJECTIVES: To determine whether an association exists between delirium and length of time indwelling urine catheters (IUC) are used in octogenarian patients treated with surgical aortic valve treatment (SAVR) or transcatheter aortic valve implantation (TAVI). DESIGN: Prospective cohort study. SETTING: Tertiary university hospital covering the western region of Norway. PARTICIPANTS: Octogenarian patients undergoing elective SAVR or TAVI and willing to participate in the study were eligible. Patients unable to speak Norwegian were excluded. Between 2011 and 2013, 143 consecutive patients were included, and data from 136 of them are presented. PRIMARY OUTCOME: Delirium. RESULTS: Logistic regression analysis shows that lower cognitive function was positively associated with delirium (OR 0.86, CI 0.74 to 0.99, p=0.047). Besides, the interaction term in the model shows that IUC use and delirium differed between SAVR and TAVI patients (p=0.04). The difference corresponded to a weaker association between hours of IUC use and delirium for SAVR (OR 1.01, CI: 0.99 to 1.03, p=0.54) compared with that for TAVI (OR 1.04, CI: 1.01 to 1.08, p=0.004). CONCLUSIONS: The association between IUC use and delirium is stronger for octogenarian patients treated with TAVI than for patients who received SAVR. Our results revealed a previously unknown association between the number of hours an IUC is used and postoperative delirium in octogenarian patients treated with TAVI.

"Eight Days of Nightmares " - Octogenarian Patients' Experiences of Postoperative Delirium after Transcatheter or Surgical Aortic Valve Replacement.

BACKGROUND: Surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) are increasingly performed in octogenarian patients with severe aortic stenosis (AS), including those with high surgical risk. Postoperative delirium (PD) is a common and serious complication in older patients, characterised by reduced awareness, change in consciousness, disturbance in logical thinking and hallucinations. METHODS: To explore how octogenarian patients experienced PD, a qualitative study was conducted including five women and five men between 81 and 88 years. The incidence of PD was assessed for five days using the Confusion Assessment Method. Cognitive function was assessed preoperatively and at a 6-month follow-up using the Mini-Mental State Examination. In-depth interviews were conducted 6-12 months post-discharge, transcribed, and analysed using Giorgi's phenomenological method. RESULTS: Postoperative delirium experiences were grouped into six themes: "Like dreaming while awake", "Disturbed experiences of time", "Existing in a twilight zone", "Trapped in medical tubes", "Moving between different surroundings" and "Meeting with death and the deceased". CONCLUSIONS: For the first time, we show that octogenarian patients who undergo SAVR or TAVI have strong and distressing memories of their delirious state that can persist for up to 12 months later. These findings provide valuable new information that will likely improve delivery of health services and enhance professional and empathic care of octogenarians after SAVR and TAVI.

Readmissions and mortality in delirious versus non-delirious octogenarian patients after aortic valve therapy: a prospective cohort study.

OBJECTIVES: To determine whether postoperative delirium predicts first-time readmissions and mortality in octogenarian patients within 180 days after aortic valve therapy with surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI), and to determine the most common diagnoses at readmission. DESIGN: Prospective cohort study of patients undergoing elective SAVR or TAVI. SETTING: Tertiary university hospital that performs all SAVRs and TAVIs in Western Norway. PARTICIPANTS: Patients 80+ years scheduled for SAVR or TAVI and willing to participate in the study were eligible. Those unable to speak Norwegian were excluded. Overall, 143 patients were included, and data from 136 are presented. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was a composite variable of time from discharge to first all-cause readmission or death. Secondary outcomes were all-cause first readmission alone and mortality within 180 days after discharge, and the primary diagnosis at discharge from first-time readmission. Delirium was assessed with the confusion assessment method. First-time readmissions, diagnoses and mortality were identified in hospital information registries. RESULTS: Delirium was identified in 56% of patients. The effect of delirium on readmissions and mortality was greatest during the first 2 months after discharge (adjusted HR 2.9 (95% CI 1.5 to 5.7)). Of 30 first-time readmissions occurring within 30 days, 24 (80%) were patients who experienced delirium. 1 patient (non-delirium group) died within 30 days after therapy. Delirious patients comprised 35 (64%) of 55 first-time readmissions occurring within 180 days. Circulatory system diseases and injuries were common causes of first-time readmissions within 180 days in delirious patients. 8 patients died 180 days after the procedure; 6 (75%) of them experienced delirium. CONCLUSIONS: Delirium in octogenarians after aortic valve therapy might be a serious risk factor for postoperative morbidity and mortality. Cardiovascular disorders and injuries were associated with first-time readmissions in these patients.

Delirium as a Predictor of Physical and Cognitive Function in Individuals Aged 80 and Older After Transcatheter Aortic Valve Implantation or Surgical Aortic Valve Replacement.

OBJECTIVES: To determine how development of delirium after surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) could predict activity of daily living (ADL) and instrumental ADLs (IADL) disability, cognitive function, and self-reported health in individuals aged 80 and older. DESIGN: Prospective cohort study. SETTING: Tertiary university hospital. PARTICIPANTS: Individuals aged 80 and older undergoing elective SAVR or TAVI (N = 136). MEASUREMENTS: Delirium was assessed for 5 days using the Confusion Assessment Method. The Barthel Index, Nottingham Extended ADL Scale, and SF-12 were used to determine ADL and IADL ability and self-reported health at baseline and 1- and 6-month follow-up. Cognition was assessed using the Mini-Mental State Examination at baseline and 6-month follow-up. RESULTS: Participants had lower IADL scores 1 month after SAVR than at baseline (baseline 58, 1 month: delirium 42, no delirium 50, P ≤ .02), but scores had returned to baseline levels at 6 months. The Medical Outcomes Study 12-item Short-Form Health Survey (SF-12) Physical Component Summary (PCS) score was higher at 6-month follow-up (48) than at baseline (39), especially in participants who did not develop delirium (P < .001). No differences in other outcomes were found. Regression models suggest that delirium may help predict IADL disability 1 month after baseline (P ≤ .07) but does not predict large differences in ADL disability, cognitive function, or SF-12-scores. Individuals who underwent TAVI and developed delirium had lower ADL (baseline 19, 1-month 16, P < .001) and IADL (baseline 49, 1-month 40, P = .003) scores at 1-month follow-up. SF-12 PCS score (baseline 30) increased from baseline to 1- (35, P = .04) and 6- (35, P = .02) month follow-up in individuals who underwent TAVI and did not develop delirium. Delirium after TAVI predicted greater ADL and IADL disability at 1-month but not at 6-month follow-up. CONCLUSION: Individuals who develop delirium after SAVR and TAVI have poorer short-term IADL function but do not seem to have long-term reductions in physical, mental, or self-reported health.

Comparison of frequency, risk factors, and time course of postoperative delirium in octogenarians after transcatheter aortic valve implantation versus surgical aortic valve replacement.

Postoperative delirium (PD) after transcatheter aortic valve implantation (TAVI) remains to be explored. We sought to (1) determine the incidence of PD in octogenarians who underwent TAVI or surgical aortic valve replacement (SAVR), (2) identify its risk factors, and (3) describe possible differences in the onset and course of PD between treatment groups. A prospective cohort study of consecutive patients aged ≥80 years with severe aortic stenosis who underwent elective TAVI or SAVR (N = 143) was conducted. The incidence of PD was assessed for 5 days using the Confusion Assessment Method (CAM). Risk factors for PD were studied with logistic regression. Patients treated with TAVI were older (p ≤0.001), had lower cognitive scores (p = 0.007), and more co-morbidities (p = 0.003). Despite this, significantly fewer (p = 0.013) patients treated with TAVI (44%) experienced PD compared to patients treated with SAVR (66%). Undergoing SAVR (p = 0.02) and having lower cognitive function (p = 0.03) emerged as risk factors for PD, whereas gender, activities of daily living, frailty, atrial fibrillation, and postoperative use of opioids and anxiolytics did not. Patients treated with TAVI and without PD during the first 2 postoperative days were unlikely to experience PD on subsequent days. The onset of PD after SAVR could occur at any time during the postoperative evaluation. In conclusion, SAVR in octogenarian patients with aortic stenosis might be considered as a predisposing factor for PD. Our data also suggest that the onset of PD was more unpredictable after SAVR.

The Norwegian Stroke in the Young Study (NOR-SYS): rationale and design.

BACKGROUND: Ischemic stroke in young adults is a major health problem being associated with a higher vascular morbidity and mortality compared to controls, and a stroke recurrence rate of 25% during the first decade. The assumed cause of infarction and the detected risk factors determine the early- and long-term treatment. However, for many patients the cause of stroke remains unknown. Risk factor profile and etiology differ in young and elderly ischemic stroke patients, and atherosclerosis is the determined underlying condition in 10 to 15%. However, subclinical atherosclerosis is probably more prevalent and may go unrecognized. METHODS/DESIGN: NOR-SYS is a prospective long-term research program. Standardized methods are used for anamnestic, clinical, laboratory, imaging, and ultrasound data collection in ischemic stroke patients aged ≤60 years, their partners and joint adult offspring. The ultrasound protocol includes the assessment of intracranial, carotid and femoral arteries, abdominal aorta, and the estimation of VAT. To date, the study is a single centre study with approximately 400 patients, 250 partners and 350 adult offspring expected to be recruited at our site. DISCUSSION: NOR-SYS aims to increase our knowledge about heredity and the development of arterial vascular disease in young patients with ischemic stroke and their families. Moreover, optimization of diagnostics, prophylaxis and early intervention are major targets with the intention to reduce stroke recurrence and other clinical arterial events, physical disability, cognitive impairment and death.

Effects of local delivery of tetradecylthioacetic acid within the injured coronary vessel wall.

OBJECTIVES: Inflammation is involved in cell proliferation and collagen deposition causing vessel wall remodeling and restenosis after plain balloon angioplasty. Local drug delivery of bioactive agents that reduce the incidence of adverse wall remodeling is of considerable interest concerning treatment strategies for coronary vessel disease and could alter the need of repeated revascularization. DESIGN: In this study, 34 domestic pigs undergoing coronary balloon injury were randomly assigned to Tetradecylthioacetic acid (TTA) or placebo delivered locally. After four weeks, vessel wall collagen density, inflammatory markers and lipid fractions were assessed as well as cell proliferation. RESULTS: Collagen particle count was lower after TTA compared to placebo, 177 ± 11 n/area versus 225 ± 13 n/area (p = 0.007). Interleukin-2 (IL-2) concentration was reduced, 1.6 ± 0.02 pg/ml versus 2.6 ± 0.5 pg/ml, (p = 0.01). The anti-inflammatory index was increased after TTA, 46.28 ± 12.1 versus 34.66 ± 4.5, (p = 0.025). There were no differences between TTA and placebo with regard to cell proliferation. CONCLUSIONS: Local delivery of TTA reduced the local inflammatory response and collagen accumulation. Local balloon delivery of TTA into the vessel wall may represent an alternative antiproliferative strategy for preventing restenosis, in particular for vessels with obstructive disease not available for stent implantation.

Dose-dependent coronary artery intimal thickening after local delivery of the anti-oxidant tetradecylthioacetic acid from stents.

OBJECTIVE: To examine the in vitro uptake and elution of the anti-oxidant tetradecylthioacetic acid (TTA) from phosphorylcholine (PC)-coated stents, and the in vivo uptake, retention, inflammatory response and histomorphometric changes after overstretch injury of the porcine coronary artery. METHODS: PC-coated stents were loaded in one of three different concentrations of TTA (87, 174 and 347 mmol/L, i.e. 25, 50 and 100 mg/mL) and randomized versus PC-coated stents to the right coronary or left circumflex artery (18 pigs). Uptake of TTA into the coronary wall from the 347 mmol/L concentration was measured after 3 h and 24 h, 7 days, 14 days and 28 days (two pigs at each time point). RESULTS: In vitro, TTA was successfully loaded onto the stents and elution was nearly complete after 48 h. In vivo, TTA could be demonstrated in the vessel wall for up to 4 weeks. Percent area stenosis was significantly higher in the TTA group, 35.2+/-20.9% versus 27.5+/-17.0% (p=0.03). Dose-related comparison showed increased intimal thickness, 0.66+/-0.53 mm versus 0.29+/-0.26 mm (p=0.008) and intimal area, 2.83+/-1.61 mm2 versus 1.58+/-0.91 mm2 (p=0.004) for the 347 mmol/L TTA versus controls. There was a significantly positive relationship between the TTA-loading dose and both intimal area (B=0.69, p=0.01) and maximal intimal thickness (B=0.17, p=0.02). The pro-inflammatory precursor arachidonic acid increased four-fold in the arterial wall of the TTA group, while the anti-inflammatory fatty acid index, calculated as (docosapentaenoic acid+docosahexaenoic acid+dihomo-linolenic acid)/arachidonic acid, was suppressed to 0.65+/-0.27 compared to 1.13+/-0.23 in control vessels (p<0.001). CONCLUSION: TTA caused a dose-dependent intimal thickening and reduced anti-inflammatory fatty acid index. Contrary to expectations, TTA seems unsuitable as stent coating.

Implementing a best-treatment strategy with intracoronary brachytherapy for in-stent restenosis in patients at high risk for recurrence.

BACKGROUND: The deployment of drug-eluting stents (DES) to treat bare-metal stent restenosis [in-stent restenosis (ISR)] has become routine practice, with a consequential decline in the use of intracoronary brachytherapy (ICBT). However, there are concerns as to the long-term safety profile of DES, particularly in terms of late stent thrombosis. In addition, an appropriate treatment strategy for stenosis within DES has not been developed. The aim of this study was to examine the efficacy of best treatment with ICBT for ISR in patients at high risk for future recurrence. METHODS: Forty-seven consecutive patients with symptomatic ISR with at least one or more increased risk criteria for recurrence were treated with beta-radiation. The patients received best treatment based on avoidance of previously reported procedural risk factors for recurrence (incomplete stent apposition, dissection, geographical miss, and damage to the noninjured vessel segment), deferring ICBT when provisional stenting was performed. A beta-radiation dose of 20 Gy was used, and clopidogrel was prescribed for at least 6 months. RESULTS: Treatment was successful for all patients without in-hospital complications. ICBT increased the total intervention procedure time by 15+/-10 min. ISR length was 25.4+/-11.5 mm. The angiographic minimal luminal diameter (MLD) was 2.24+/-0.43 mm after ICBT versus 0.75+/-0.58 mm at baseline (P<.05). On 9-month follow-up, the MLD was 1.93+/-0.48 mm (P<.05 vs. baseline). Binary restenosis was detected in six (13%) patients. At 29.7+/-9.3 months of follow-up, target lesion revascularization or target vessel (nonlesion) revascularization was performed in 17 (36%) patients. Only one patient suffered a myocardial infarction, and no deaths were observed. CONCLUSION: The adoption of a best-practice protocol for the use of ICBT to treat ISR can result in a safe and effective clinical and angiographic outcome. Under these circumstances and with appropriate patient selection, ICBT may continue to be of value despite the popular use of DES.

Nonemergent coronary angioplasty without on-site surgical backup: a randomized study evaluating outcomes in low-risk patients.

BACKGROUND: Percutaneous coronary intervention (PCI) in nonemergent patients with coronary artery disease in hospitals without on-site cardiac surgery backup is still controversial. To prospectively evaluate a set of low procedural risk criteria for PCI, patients with stable or unstable angina were randomized to treatment in either a community hospital, which had all supportive services except for on-site cardiac surgery, or a regional surgical hospital 213 km away. METHODS AND RESULTS: During a 4-year period, 609 (57%) of 1064 consecutive patients with stable or unstable angina who underwent coronary angiography at a teaching community hospital in Norway fulfilled the predefined low-risk criteria for PCI. The patients were randomized to treatment at either the community hospital (n = 305) or at the regional hospital (n = 304). The angiographic success rate (96% at both hospitals) and number of major periprocedural complications (overall 0.3%) were equal at the 2 hospitals. In particular, there were no deaths or need for urgent transfer to cardiac surgery. At 6 months of clinical follow-up, there was a significant higher major adverse cardiac event rate rate at the community hospital, compared with the regional hospital (6.9% vs 2.3%, respectively, P = .03) because of more repeat target vessel revascularizations. Improvement in angina functional class and exercise capacity was similar in both groups. The excluded high-risk PCI patients had higher 6-month major adverse cardiac event compared with all low-risk patients (8.4% vs 4.3%, respectively, P = .01). CONCLUSION: Selected nonemergent patients can, based on angiography, safely undergo PCI at hospitals without cardiac surgery backup. The angiographic selection criteria identified high-risk patients, which had worsened outcome at 6 months of follow-up.

Release of cardiac troponin I after temporally graded acute coronary ischaemia with electrocardiographic ST depression.

BACKGROUND: Elevation of cardiac biochemical markers and ST segment depression in the electrocardiogram have important roles in the risk stratification of unstable coronary syndromes. We assessed graded duration of acute coronary ischaemia with ST depression versus release of cardiac troponin I (cTnI) and conventional cardiac markers in 15 ischaemic pigs and 11 controls. METHODS: Coronary ischaemia was induced via percutaneous technique by semiinflating an angioplasty balloon in the left circumflex artery. Blood velocity monitored by Doppler was reduced until ST depression > or =0.1 mV was obtained. Among 26 pigs, six controls had jugular vein sheath introduced only, five controls jugular vein and bilateral femoral sheaths, and 15 pigs were divided into three equal groups (n=5) in which ischaemia was maintained for 10, 20 and 30 min, respectively. RESULTS: Mean blood flow velocity (cm/s) at baseline was 16.3+/-6.5 and was reduced to 4.1+/-3.2 (25% of normal, range 20-29%) during ischaemia. cTnI (microg/l) did not increase in controls but increased from 0.05 to 0.52 (P<0.05) and 0.76 (P<0.05) with 10 and 20 min of ischaemia, and to 30.77 (P<0.05) with 30 min of ischaemia. A rise of myoglobin and conventional cardiac enzymes did not distinguish controls with arterial cut-down from the ischaemia groups. CONCLUSION: Release of cTnI depends on the duration of ST depression ischaemia. The critical time for a major release seems to be between 20 and 30 min. Thus, very early intervention in patients with prolonged ST depression ischemia should be focused on in future clinical trials.