Structural and Functional Brain Changes in Acute Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome mimics an acute myocardial infarction, typically in the aftermath of mental or physical stress. OBJECTIVES: The mechanism by which emotional processing in the context of stress leads to significant cardiac injury is poorly understood, so a full exploration of brain structure and function in takotsubo syndrome patients merits investigation. METHODS: Twenty-five acute (<5 days) takotsubo patients and 25 control subjects were recruited into this observational cross-sectional study. Surface-based morphometry was carried out on magnetic resonance imaging (MRI) brain scans to extract cortical morphology based on volume, thickness, and surface area with the use of Freesurfer. Cortical morphology general linear models were corrected for age, sex, photoperiod, and total brain volume. Resting-state functional MRI and diffusion tensor tractography images were preprocessed and analyzed with the use of the Functional Magnetic Resonance Imaging of the Brain Diffusion Toolbox and Functional Connectivity Toolbox. RESULTS: There was significantly smaller total white matter and subcortical gray matter volumes in takotsubo (P < 0.001), with smaller total brain surface area but increased total cortical thickness (both P < 0.001). Individual gray matter regions (hippocampus and others) were significantly smaller in takotsubo (P < 0.001); only thalamus and insula were larger (P < 0.001). There was significant hyperfunctional and hypofunctional connectivity in multiple areas, including thalamus-amygdala-insula and basal ganglia (P < 0.05). All structural tractography connections were increased in takotsubo (P < 0.05). CONCLUSIONS: The authors showed smaller gray and white matter volumes driven by smaller cortical surface area, but increased cortical thickness and structural tractography connections with bidirectional changes in functional connectivity linked to emotion, language, reasoning, perception, and autonomic control. These are interventional targets in takotsubo patients' rehabilitation.

Smoking status and mortality outcomes following percutaneous coronary intervention.

OBJECTIVE: The aim of this study was to assess the impact of smoking on short (30-day) and intermediate (30-day to 6-month) mortality following percutaneous coronary intervention (PCI). BACKGROUND: The effect of smoking on mortality post-PCI is lacking in the modern PCI era. METHODS: This was a retrospective analysis of prospectively collected data comparing short- and intermediate-term mortality amongst smokers, ex-smokers and non-smokers. RESULTS: The study cohort consisted of 12,656 patients: never-smokers (n = 4288), ex-smokers (n = 4806) and current smokers (n = 3562). The mean age (±standard deviation) was 57 (±11) years in current smokers compared with 67 (±11) in ex-smokers and 67 (±12) in never-smokers; p < 0.0001. PCI was performed for acute coronary syndrome (ACS) in 84.1% of current smokers, 57% of ex-smokers and 62.9% in never-smokers; p < 0.0001. In a logistic regression model, the adjusted odds ratios (95% confidence intervals (CIs)) for 30-day mortality were 1.60 (1.10-2.32) in current smokers and 0.98 (0.70-1.38) in ex-smokers compared with never-smokers. In the Cox proportional hazard model, the adjusted hazard ratios (95% CI) for mortality between 30 days and 6 months were 1.03 (0.65-1.65) in current smokers and 1.19 (0.84-1.67) in ex-smokers compared with never-smokers. CONCLUSION: This large observational study of non-selected patients demonstrates that ex-smokers and never-smokers are of similar age at first presentation to PCI, and there is no short- or intermediate-term mortality difference between them following PCI. Current smokers undergo PCI at a younger age, more often for ACS, and have higher short-term mortality. These findings underscore the public message on the benefits of smoking cessation and the harmful effects of smoking.

Recurrent spontaneous coronary artery dissection in a middle-aged male athlete patient: a case report.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a rare condition, mainly affecting young women. Cases in male patients are rare, especially with recurrence. CASE SUMMARY: A 59-year-old male non-elite athlete presented as an ST-elevation myocardial infarction following a 5-km run. Urgent coronary angiogram was normal, but cardiac magnetic resonance showed a myocardial infarction. Four years later, he experienced similar chest pain with no ST-elevation on electrocardiogram and a mild troponin rise. Urgent coronary angiogram was initially thought normal but subsequent close inspection confirmed a Type 2b SCAD. Cardiac magnetic resonance showed a small additional myocardial infarction contained within an area of acute myocardial oedema. DISCUSSION: Spontaneous coronary artery dissection is more common in young women compared to men and recurrent dissection has been rarely reported in the literature. Cohort studies have shown the rate of recurrent dissection to be 13-16%, but most of the patients in these cohorts are female. Poor data exists on the best treatment of SCAD in men, but given the presence of intramural thrombus, dual antiplatelet therapy was discontinued on the presumption that it may exacerbate an intramural bleeding process.

Risk stratifying chest pain patients in the emergency department using HEART, GRACE and TIMI scores, with a single contemporary troponin result, to predict major adverse cardiac events.

BACKGROUND: The majority of patients presenting to the ED with cardiac sounding chest pain have a non-diagnostic ECG and the problem of differentiating those suffering an acute coronary syndrome from those without is familiar to all ED clinical staff. To stratify risk in these patients, specific scores have been developed. Recent work has focused on incorporating newer high-sensitivity cardiac troponin (hs-cTn) assays; however, issues regarding performance and availability of these assays remain. AIM: Prospectively compare HEART, Global Registry of Acute Coronary Events (GRACE) and Thrombolysis in Myocardial Infarction (TIMI) scores, using a single contemporary cTn at admission, to predict a major adverse cardiac event (MACE) at 30 days. METHOD: Prospective observational cohort study performed in a UK tertiary hospital in patients with suspected cardiac chest pain and no significant ST elevation on initial ECG. Data collection took place 2 December 2014 to 8 February 2016. The treating clinician recorded risk score data real time and a single contemporary cTn taken at presentation was used in score calculation. The primary endpoint was 30-day MACE. C-statistic was determined for each score and diagnostic characteristics of high-risk and low-risk cut-offs were calculated. RESULTS: 189/1000 patients in the study developed a 30-day MACE. The c-statistic of HEART for 30-day MACE (0.87 (95% CI 0.84 to 0.90)) was higher than TIMI (0.78 (95% CI 0.74 to 0.81)) and GRACE (0.74 (95% CI 0.70 to 0.78)).HEART score ≤3 identified low-risk patients with sensitivity 99.5% (95% CI 97.1% to 99.9%) and negative predictive value (NPV) 99.6% (95% CI 97.3% to 99.9%) exceeding TIMI 0 (sensitivity 97.4% (95% CI 93.9% to 99.1%) and NPV 97.8% (95% CI 94.8% to 99.1%)) and GRACE score 0-55 (sensitivity 95.2% (95% CI 91.1% to 97.8%) and NPV 95.8% (95% CI 92.2% to 97.7%)). CONCLUSION: HEART outperformed both TIMI and GRACE in overall discriminative capacity for 30-day MACE. Using a single contemporary cTn at presentation, a HEART score of ≤3 demonstrated sensitivity and NPV of ≥99.5% for 30-day MACE. These results reach the threshold for a safe discharge strategy but should be interpreted thoughtfully in light of other work.

Mortality after percutaneous coronary revascularization: Prior cardiovascular risk factor control and improved outcomes in patients with diabetes mellitus.

OBJECTIVES: To assess the mortality in patients with diabetes mellitus (DM) following percutaneous coronary intervention (PCI) according to their insulin requirement and PCI setting (elective, urgent, and emergency). BACKGROUND: DM is a major risk factor to develop coronary artery disease (CAD). It is unclear if meticulous glycemic control and aggressive risk factor management in patients with DM has improved outcomes following PCI. METHODS: Retrospective analysis of prospectively collected data on 9,224 patients treated with PCI at a regional tertiary center between 2008 and 2011. RESULTS: About 7,652 patients were nondiabetics (non-DM), 1,116 had non-insulin treated diabetes mellitus (NITDM) and 456 had ITDM. Multi-vessel coronary artery disease, renal impairment and non-coronary vascular disease were more prevalent in DM patients. Overall 30-day mortality rate was 2.4%. In a logistic regression model, the adjusted odds ratios (95% confidence intervals [CI]) for 30-day mortality were 1.28 (0.81-2.03, P = 0.34) in NITDM and 2.82 (1.61-4.94, P < 0.001) in ITDM compared with non-DM. During a median follow-up period of 641 days, longer-term post-30 day mortality rate was 5.3%. In the Cox's proportional hazard model, the hazard ratios (95% CI) for longer-term mortality were 1.15 (0.88-1.49, P = 0.31) in NITDM and 1.88 (1.38-2.55, P < 0.001) in ITDM compared with non-DM group. Similar result was observed in all three different PCI settings. CONCLUSION: In the modern era of aggressive cardiovascular risk factor control in diabetes, this study reveals higher mortality only in insulin-treated diabetic patients following PCI for stable coronary artery disease and acute coronary syndrome. Importantly, diabetic patients with good risk factor control and managed on diet or oral hypoglycemics have similar outcomes to the non-diabetic population. © 2016 The Authors Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.

Pneumonitis and pulmonary haemorrhage after acute myocardial infarction.

A 55-year-old man presented with acute ST-elevation myocardial infarction. He received rescue angioplasty with one drug eluting stent. He developed marked breathlessness and haemoptysis two days later. Investigations led to the diagnosis of pulmonary haemorrhage, possibly from pneumonitis caused by ticagrelor. He was successfully managed with high-dose steroids and ticagrelor was replaced with clopidogrel. On stopping the steroids a month later, mild haemoptysis recurred and this was managed conservatively. Pneumonitis and pulmonary haemorrhage is rarely reported with acute myocardial infarction, but poses serious challenge to the patient and the clinician. Diagnosis may be delayed as breathlessness can occur due to myriad causes after myocardial infarction. Interrupting dual anti-platelet therapy after angioplasty could lead to devastating stent thrombosis.

Shock-index as a novel predictor of long-term outcome following primary percutaneous coronary intervention.

UNLABELLED: Early identification of higher risk patients presenting with ST-elevation myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (PPCI) will allow a more aggressive strategy and approach. The aim of this study was to evaluate the shock index (ratio of heart rate/systolic blood pressure on admission) as a predictor of mortality post PPCI in addition to other parameters. METHODS: We analysed prospectively collected data on 3049 STEMI patients treated with PPCI in a large tertiary centre between March 2008-December 2011, out of which 2424 patients were aged up to 75 years (young) and 625 patients were older than 75 years (elderly). RESULTS: Compared to younger patients, in-hospital mortality rates were four-fold higher in the elderly (11.5% vs 2.8%, odds ratio (OR) 3.5, 95% confidence interval (CI) 2.0-5.9). Cardiogenic shock (OR 8.7 (5.1-14.6)), non-TIMI3 (Thrombosis In Myocardial Infarction) flow post percutaneous coronary intervention (PCI) (OR 5.0 (3.1-7.9)), age over 75 (OR 3.5 (2.3-5.3)) and a positive shock index pre PPCI (OR 3.5 (2.0-5.9)) were the strongest independent predictors of in-hospital mortality. For long-term outcome (median follow-up period 454 days) we excluded 141 (4.6%) patients that died during the initial hospital stay. Previous angina (hazard ratio (HR) 2.9), and previous cerebrovascular events (HR 3.7) were predictors of adverse outcome in the younger patients, while previous myocardial infarction (HR 2.0) and a positive shock index (HR 2.3) were predictors in the elderly. Cardiogenic shock prior to PPCI was not able to predict long-term outcome for in-hospital survivors. CONCLUSION: Mortality rates following PPCI were higher in elderly patients although remained acceptable. Invasively measured shock index before PPCI is the strongest independent predictor of long-term outcome in elderly patients. In addition, predictors of in-hospital mortality were similar across different age groups but differed significantly in relation to longer-term mortality.

High-potency statin and ezetimibe use and mortality in survivors of an acute myocardial infarction: a population-based study.

OBJECTIVE: To determine all-cause mortality in patients with a first myocardial infarct who were treated with simvastatin compared with high-potency statin and simvastatin/ezetimibe combination. BACKGROUND: Despite statin use, residual cardiovascular risk remains. Therapeutic options include more potent statins or addition of ezetimibe. There is no clinical outcome data on the use of ezetimibe in such patients. METHODS: Retrospective longitudinal study using the United Kingdom General Practice Research Database. Patients who had survived 30 days after their first acute myocardial infarct (AMI), had not received prior statin or ezetimibe therapy and were started on a statin within 30 days of AMI were included. Three groups were identified according to their follow-up: (i) simvastatin monotherapy; (ii) high-potency statin group (patients who started on simvastatin and switched to atorvastatin or rosuvastatin); and (iii) ezetimibe/statin combination group (patients who received ezetimibe in addition to statin). RESULTS: 9597 patients (57% male, mean age of 65 ± 13 years) matched study criteria: simvastatin (n=6990 (72.8%)); high-potency statin (n=1883, (19.6%)); and ezetimibe/statin combination (n=724 (7.5%)). During a mean follow-up of 3.2 years, there were 1134 (12%) deaths. In the multivariate proportional hazards model, the adjusted HR for high-potency statin and ezetimibe group were 0.72 (95% CI 0.59 to 0.88, p<0.001) and 0.96 (95% CI 0.64 to 1.43, p=0.85), respectively. A similar result was also obtained in the propensity score analysis that took into account covariates that predicted drug treatment groups. CONCLUSIONS: Patients switched to a high-potency statin had a significantly reduced mortality compared with simvastatin monotherapy. There was no observed mortality benefit in the ezetimibe group.

Antiplatelet therapy in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: a retrospective observational study of prasugrel and clopidogrel.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is a therapeutic success when supported by dual antiplatelet therapy. Prasugrel has been introduced as a potential alternative to clopidogrel alongside aspirin. We aimed to assess prasugrel versus clopidogrel mortality outcomes in patients admitted with STEMI undergoing PPCI. METHODS: Retrospective analysis of prospectively collected data of 1688 consecutive STEMI patients undergoing PPCI at a regional tertiary centre. Patients with age ≥75 years, weight<60 kg or history of cerebrovascular accident or TIA's, active bleeding or known hepatic impairment were excluded. All patients from March 2008 to 16 December 2009 belong to the Clopidogrel group and from 17 December 2009 to June 2011 belong to the Prasugrel group. RESULTS: A total of 866 patients were in the Clopidogrel group and 822 patients in the prasugrel group. In-hospital mortality was 1.7% in the Clopidogrel and 1.5% in Prasugrel group (P = 0.40). 30-day postdischarge mortality was 2.4% and 1.8% (P = 0.25) in the Clopidogrel and Prasugrel group, respectively. One-year mortality rate was recorded in 62 patients (3.7%): 39 (4.5%) in the Clopidogrel group and 23 (2.8%) in the prasugrel group. In the Cox proportional hazard model, the adjusted hazard ratio for all-cause mortality for the prasugrel group was 0.47 (95% CI: 0.253-0.881; P = 0.018). Independent predictors of one-year mortality postdischarge were age, admission creatinine and haemoglobin, admission heart rate, total ischaemic time, the presence of multivessel coronary artery disease, previous MI and post-PCI TIMI flow. CONCLUSION: In PPCI-treated STEMI patients, prasugrel is associated with a significant reduction in one-year mortality compared with clopidogrel.

Early discharge after primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: To assess safety of early discharge following primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Retrospective analysis of prospectively collected data of 2448 STEMI patients treated with PPCI surviving to hospital discharge. Post-discharge all-cause mortality was reported at 1, 7, and 30 days and long-term follow up. A total of 1542 patients (63.0%) were discharged within 2 days of admission (early discharge group) and 906 patients (37.0%) after 2 days (late discharge group). In both groups, no deaths were recorded 1 day post discharge. The early and late discharge group mortality figures for 7 days were 0 and 4 patients (0.04%) and between 7 and 30 days were 11 (0.7%) and 11 patients (1.2%), respectively. During a mean follow up of 584 days, 178 patients (7.3%) died: 67 in the early discharge group (4.3%) and 111 in the late discharge group (12.3%). CONCLUSIONS: This exploratory, observational study demonstrates that discharging low-risk STEMI patients within 2 days following PPCI is safe. For providers of health care, early discharge can help to allay the cost of providing a 24-hour PPCI service and adds to the recognized benefits arising from PPCI.

Admission heart rate predicts mortality following primary percutaneous coronary intervention for ST-elevation myocardial infarction: an observational study.

BACKGROUND: The prognostic value of admission heart rate (HR) on long-term mortality in ST-elevation myocardial infarction (STEMI) remains uncertain in the modern era of primary percutaneous coronary intervention (PPCI). This study aimed to assess the predictive value of admission HR on long-term mortality following PPCI and the influence of beta-blockers on postdischarge survival. METHODS: Retrospective analysis of prospectively collected data on 2310 PPCI-treated STEMI patients at a regional tertiary center between March 2008 and June 2010. RESULTS: Patients were classified according to admission HR into either low (≤70 beat per minute [bpm], n = 1015) or high HR group (>70 bpm, n = 1295). At a median follow-up of 559 days, all-cause mortality was 7.0% in the low HR group compared to 12.7% in the high-HR group. In the Cox proportional hazard model, adjusted for several confounders, the hazard ratio (95% confidence interval) for all-cause mortality in the high HR group was 1.59 (1.15-2.20; P = 0.005). Every 10-bpm increase in admission HR was associated with 17% increase in all-cause mortality. Beta-blockers on discharge was associated with a reduction in postdischarge mortality only in the high HR group (adjusted hazard ratio, 0.49 [0.31-0.77; P = 0.002]), but not in the low HR group (adjusted hazard ratio, 0.74 [0.37-1.49; P = 0.33]). CONCLUSIONS: Elevated admission heart rate in PPCI-treated STEMI patients is associated with long-term all-cause mortality. Beta blocker therapy improved postdischarge survival in patients with elevated admission heart rate.

High-dose allopurinol reduces left ventricular mass in patients with ischemic heart disease.

OBJECTIVES: This study sought to ascertain if high-dose allopurinol regresses left ventricular mass (LVM) in patients with ischemic heart disease (IHD). BACKGROUND: LV hypertrophy (LVH) is common in patients with IHD including normotensive patients. Allopurinol, a xanthine oxidase inhibitor, has been shown to reduce LV afterload in IHD and may therefore also regress LVH. METHODS: A randomized, double-blind, placebo-controlled, parallel group study was conducted in 66 patients with IHD and LVH, comparing 600 mg/day allopurinol versus placebo therapy for 9 months. The primary outcome measure was change in LVM, assessed by cardiac magnetic resonance imaging (CMR). Secondary outcome measures were changes in LV volumes by CMR, changes in endothelial function by flow-mediated dilation (FMD), and arterial stiffness by applanation tonometry. RESULTS: Compared to placebo, allopurinol significantly reduced LVM (allopurinol -5.2 ± 5.8 g vs. placebo -1.3 ± 4.48 g; p = 0.007) and LVM index (LVMI) (allopurinol -2.2 ± 2.78 g/m(2) vs. placebo -0.53 ± 2.5 g/m(2); p = 0.023). The absolute mean difference between groups for change in LVM and LVMI was -3.89 g (95% confidence interval: -1.1 to -6.7) and -1.67 g/m(2) (95% confidence interval: -0.23 to -3.1), respectively. Allopurinol also reduced LV end-systolic volume (allopurinol -2.81 ± 7.8 mls vs. placebo +1.3 ± 7.22 mls; p = 0.047), improved FMD (allopurinol +0.82 ± 1.8% vs. placebo -0.69 ± 2.8%; p = 0.017) and augmentation index (allopurinol -2.8 ± 5.1% vs. placebo +0.9 ± 7%; p = 0.02). CONCLUSIONS: High-dose allopurinol regresses LVH, reduces LV end-systolic volume, and improves endothelial function in patients with IHD and LVH. This raises the possibility that allopurinol might reduce future cardiovascular events and mortality in these patients. (Does a Drug Allopurinol Reduce Heart Muscle Mass and Improve Blood Vessel Function in Patients With Normal Blood Pressure and Stable Angina?; ISRCTN73579730).

Mortality outcome of out-of-hours primary percutaneous coronary intervention in the current era.

AIMS: To assess the impact of the time of primary percutaneous coronary intervention (PPCI) on in-hospital and long-term all-cause mortality in ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: The study retrospectively analyses the prospectively collected data on 2571 consecutive PPCI-treated STEMI patients between March 2008 and June 2011. Of these, 1036 patients (40.3%) underwent PPCI during a weekday between 08:00 and 18:00 (routine-hours group) and 1535 patients (59.7%) underwent PPCI on a weekday between 18:00 and 08:00 or a weekend (out-of-hours group). Compared with the routine-hours group, the out-of-hours group had a lower mean age, fewer patients with previous angina, longer call-to-hospital time, and fewer multivessel PCI. The overall in-hospital mortality rate was 4.5% with no significant difference [0.2%, 95% confidence interval (CI): -1.4 to 1.9%] between the routine-hours group (4.3%) and the out-of-hours group (4.6%) (adjusted odds ratio: 1.33, 95% CI: 0.73-2.40, P = 0.35). During a mean follow-up period of 560 days, 295 patients (11.5%) died, 12.2% in the routine-hours group and 11.0% in the out-of-hours group (difference of -0.1%, 95% CI: -0.4 to 0.2%). In the multiple Cox proportional hazards model, there was no difference in mortality between the two groups (adjusted hazard ratio: 1.09, 95% CI: 0.82-1.46, P = 0.57). Similarly, no increase in mortality was seen in patients who underwent PPCI later at night (22:00-06:00). CONCLUSION: This study of real-world, unselected STEMI patients demonstrates that in a large, well-staffed centre, PPCI outside routine-working hours is safe with no difference in outcome of in-hospital and long-term mortality compared with PPCI during routine-working hours.

Impact of thrombus aspiration during primary percutaneous coronary intervention on mortality in ST-segment elevation myocardial infarction.

AIMS: To assess the impact of thrombus aspiration during primary percutaneous coronary intervention (PPCI) on the mortality of patients with ST-elevation myocardial infarction (STEMI) patients. METHODS AND RESULTS: Retrospective analysis of prospectively collected data on 2567 consecutive PPCI-treated STEMI patients between 2008 and 2011. Cox proportional hazard models and multiple logistic regression analysis were used to adjust for known covariates. Thrombectomy was performed in 1095 patients (42.7%). Post-PPCI thrombolysis in myocardial infarction 3 flow was more frequently achieved in the thrombectomy group [adjusted odds ratio (OR); 1.92, 95% confidence interval (CI): 1.34-2.76, P = 0.0004]. Overall in-hospital and longer term (mean follow-up 9.9 months) mortality rates were 4.5 and 9.0%, respectively. Thrombectomy was associated with a significant reduction in in-hospital (adjusted OR: 0.51, 95% CI: 0.29-0.93, P = 0.027) and longer term mortality [adjusted hazard ratio (HR): 0.69, 95% CI: 0.48-0.96, P = 0.028]. With propensity weighting, the adjusted HR for longer term mortality for thrombectomy was 0.43 (95% CI: 0.19-0.97; P = 0.042). The association between thrombectomy and reduced longer term mortality was only significant in those with a total ischaemic time ≤180min (P = 0.001) but not in patients with a total ischaemic time >180min (P = 0.99). CONCLUSION: This study of real-world, unselected STEMI patients demonstrates that thrombus aspiration during PPCI is associated with a significant reduction in mortality, especially in those with a short total ischaemic time. These findings support the use of thrombectomy during PPCI in this group of patients.

Right ventricular pacing impairs endothelial function in man.

AIMS: Clinical trial data show that right ventricular pacing worsens cardiovascular outcomes. The underlying pathophysiology of this is undetermined. We studied the effects of right ventricular pacing on cardiac measures of vascular health (endothelial function), ventricular wall stress (B-type natriuretic peptide), and cardiac reserve (cardiac output response to exercise) in subjects with pacemakers. METHODS AND RESULTS: Twenty-two subjects [mean age 68.4 ± 8.8 (SD) years] with dual-chamber pacemakers implanted for sino-atrial disease were studied in a randomized crossover study comparing minimal right ventricular pacing [RVP-min; pacing with long atrioventricular delay (AVD)] to maximal right ventricular pacing (RVP-max; pacing with short AVD). Endothelial function was measured with reactive hyperaemia peripheral arterial tonometry. Cardiac output at rest and during exercise was determined using an inert gas rebreathing method. Right ventricular pacing was significantly higher in RVP-max when compared with RVP-min (90 ± 16 vs. 15 ± 20%, P < 0.001). Reactive hyperaemia peripheral arterial tonometry index was significantly lower after RVP-max vs. RVP-min (1.73 ± 0.33 vs. 1.96 ± 0.37, P < 0.05). B-type natriuretic peptide was not significantly different between pacing modes (113 ± 80 vs. 104 ± 108 pg/mL, P = NS). Cardiac output at peak exercise was significantly lower during RVP-max (7.65 ± 3.15 vs. 7.05 ± 2.61 L/min, P < 0.05). CONCLUSION: Right ventricular pacing is associated with worsened endothelial function and cardiac reserve.

Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial.

BACKGROUND: Experimental evidence suggests that xanthine oxidase inhibitors can reduce myocardial oxygen consumption for a particular stroke volume. If such an effect also occurs in man, this class of inhibitors could become a new treatment for ischaemia in patients with angina pectoris. We ascertained whether high-dose allopurinol prolongs exercise capability in patients with chronic stable angina. METHODS: 65 patients (aged 18-85 years) with angiographically documented coronary artery disease, a positive exercise tolerance test, and stable chronic angina pectoris (for at least 2 months) were recruited into a double-blind, randomised, placebo-controlled, crossover study in a hospital and two infirmaries in the UK. We used computer-generated randomisation to assign patients to allopurinol (600 mg per day) or placebo for 6 weeks before crossover. Our primary endpoint was the time to ST depression, and the secondary endpoints were total exercise time and time to chest pain. We did a completed case analysis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 82040078. FINDINGS: In the first treatment period, 31 patients were allocated to allopurinol and 28 were analysed, and 34 were allocated to placebo and 32 were analysed. In the second period, all 60 patients were analysed. Allopurinol increased the median time to ST depression to 298 s (IQR 211-408) from a baseline of 232 s (182-380), and placebo increased it to 249 s (200-375; p=0.0002). The point estimate (absolute difference between allopurinol and placebo) was 43 s (95% CI 31-58). Allopurinol increased median total exercise time to 393 s (IQR 280-519) from a baseline of 301 s (251-447), and placebo increased it to 307 s (232-430; p=0.0003); the point estimate was 58 s (95% CI 45-77). Allopurinol increased the time to chest pain from a baseline of 234 s (IQR 189-382) to 304 s (222-421), and placebo increased it to 272 s (200-380; p=0.001); the point estimate was 38 s (95% CI 17-55). No adverse effects of treatment were reported. INTERPRETATION: Allopurinol seems to be a useful, inexpensive, well tolerated, and safe anti-ischaemic drug for patients with angina. FUNDING: British Heart Foundation.