Cardiac Troponin Composition Characterization after Non ST-Elevation Myocardial Infarction: Relation with Culprit Artery, Ischemic Time Window, and Severity of Injury.

BACKGROUND: Troponin composition characterization has been implicated as a next step to differentiate among non-ST elevation myocardial infarction (NSTEMI) patients and improve distinction from other conditions with troponin release. We therefore studied coronary and peripheral troponin compositions in relation to clinical variables of NSTEMI patients. METHODS: Samples were obtained from the great cardiac vein (GCV), coronary sinus (CS), and peripheral circulation of 45 patients with NSTEMI. We measured total cTnI concentrations, and assessed both complex cTnI (binary cTnIC + all ternary cTnTIC forms), and large-size cTnTIC (full-size and partially truncated cTnTIC). Troponin compositions were studied in relation to culprit vessel localization (left anterior descending artery [LAD] or non-LAD), ischemic time window, and peak CK-MB value. RESULTS: Sampling occurred at a median of 25 hours after symptom onset. Of total peripheral cTnI, a median of 87[78-100]% consisted of complex cTnI; and 9[6-15]% was large-size cTnTIC. All concentrations (total, complex cTnI, and large-size cTnTIC) were significantly higher in the CS than in peripheral samples (P < 0.001). For LAD culprit patients, GCV concentrations were all significantly higher; in non-LAD culprit patients, CS concentrations were higher. Proportionally, more large-size cTnTIC was present in the earliest sampled patients and in those with the highest CK-MB peaks. CONCLUSIONS: In coronary veins draining the infarct area, concentrations of both full-size and degraded troponin were higher than in the peripheral circulation. This finding, and the observed associations of troponin composition with the ischemic time window and the extent of sustained injury may contribute to future characterization of different disease states among NSTEMI patients.

Sedentary behaviour in cardiovascular disease patients: Risk group identification and the impact of cardiac rehabilitation.

BACKGROUND: Sedentary behaviour (SB) is potentially an important target to improve cardiovascular health. This study 1) compared SB between cardiovascular disease (CVD) patients and age-matched controls, 2) identified characteristics associated with high SB levels, and 3) determined the impact of contemporary cardiac rehabilitation (CR) on SB. METHODS: For objective 1, we recruited 131 CVD patients and 117 controls. All participants were asked about their general characteristics and medical history. SB was assessed by an objective accelerometer (activPAL3 micro). For objective 2, 2584 CVD patients were asked to fill in a questionnaire about their general characteristics, lifestyle, medical history and their SB. For objective 3, 131 CVD patients were followed over time and measured, pre-, directly post- and 2 months post-CR. RESULTS: Objective 1. CVD patients spent 10.4 h/day (Q25 9.5; Q75 11.2) sedentary which was higher compared to healthy controls (9.4 h/day [Q25 8.4; Q75 10.29]). Objective 2. CVD patients being male, single or divorced, employed, physically inactive, reporting high alcohol consumption, living in an urban environment, having comorbidities and cardiac anxiety demonstrated a greater odds for large amounts of SB. Objective 3. The CR program significantly reduced sedentary time (-0.4 h/day [95%CI -0.7; -0.1]), which remained lower at 2-months post-CR (-0.3 h/day [95%CI -0.6; -0.03]). CONCLUSIONS: CVD patients had greater amounts of objectively measured sedentary time compared to healthy controls. Sedentarism was associated with personal- and lifestyle characteristics, and comorbidities. Participation in a contemporary CR program slightly reduced sedentary time, but tailored interventions are needed to target SB in CVD patients.

A multi-site coronary sampling study on CRP in non-STEMI: Novel insights into the inflammatory process in acute coronary syndromes.

BACKGROUND AND AIMS: Inflammation has become a key element in cardiovascular disease, and recently, new anti-inflammatory interventions have shown promising results. In this context, CRP levels have been thoroughly studied in vitro and in animals, but studies in humans are scarce and insights into its release, site(s) of production and uptake are not uniform. METHODS: We performed a biomarker study with multi-site sampling in the coronary circulation, in non-ST elevation MI (NSTEMI) patients with coronary angiography and right-sided catheterisation. Trans-lesional gradients were obtained by sampling distal to the culprit lesion, in patients with a suitable anatomy. To asses trans-cardiac gradients, blood was sampled from the systemic circulation, coronary sinus (CS) and great cardiac vein. Concentrations of CRP were measured with a high-sensitivity assay. RESULTS: In 42 patients, a median systemic venous CRP concentration of 4.97 mg/L was observed. There was no evidence of a trans-lesional gradient (4.59 mg/L versus 4.56 mg/L, p = 0.278; n = 14). A significant decrease in CRP concentration was observed between systemic arterial and CS samples (4.88 mg/L versus 4.44 mg/L; p < 0.001; n = 42). This trans-cardiac gradient was irrespective of time of presentation, infarct size and culprit lesion location. The gradient was not only driven by blood that ran through the injured myocardium, but also by lower CRP concentrations in the coronary veins that drain non-infarcted myocardium. CONCLUSIONS: In the context of NSTEMI, we observed a trans-cardiac decrease in CRP, which may indicate the first human in vivo proof of a net CRP uptake by the myocardium, with a role for CRP both in the injured and adjacent myocardium.

Intracoronary infusion of mononuclear cells from bone marrow or peripheral blood compared with standard therapy in patients after acute myocardial infarction treated by primary percutaneous coronary intervention: results of the randomized controlled HEBE trial.

AIMS: Previous trials that investigated cell therapy as an adjunctive therapy after acute myocardial infarction (AMI) have shown conflicting results. We designed a randomized controlled trial to determine the effect of intracoronary infusion of mononuclear cells from bone marrow (BM) or peripheral blood in patients with AMI. METHODS AND RESULTS: In a multicentre trial, 200 patients with large first AMI treated with primary percutaneous coronary intervention were randomly assigned to either intracoronary infusion of mononuclear BM cells (n = 69), mononuclear peripheral blood cells (n = 66), or standard therapy (without placebo infusion) (n = 65). Mononuclear cells were delivered intracoronary between 3 and 8 days after AMI. Regional and global left ventricular myocardial function and volumes were assessed by magnetic resonance imaging before randomization and at 4 months, and clinical events were reported. The primary endpoint of the percentage of dysfunctional left ventricular segments that improved during follow-up did not differ significantly between either of the treatment groups and control: 38.6 ± 24.7% in the BM group, 36.8 ± 20.9% in the peripheral blood group, and 42.4 ± 18.7% in the control group (P = 0.33 and P = 0.14). Improvement of left ventricular ejection fraction was 3.8 ± 7.4% in the BM group, 4.2 ± 6.2% in the peripheral blood group when compared with 4.0 ± 5.8% in the control group (P = 0.94 and P = 0.90). Furthermore, the three groups did not differ significantly in changes in left ventricular volumes, mass, and infarct size and had similar rates of clinical events. CONCLUSION: Intracoronary infusion of mononuclear cells from BM or peripheral blood following AMI does not improve regional or global systolic myocardial function in the HEBE trial. REGISTRATION: The Netherlands Trial Register #NTR166 (www.trialregister.nl) and the International Standard Randomised Controlled Trial, #ISRCTN95796863 (http://isrctn.org).

Pre-hospital triage for primary angioplasty: direct referral to the intervention center versus interhospital transport.

OBJECTIVES: We sought to study the impact of direct referral to an intervention center after pre-hospital diagnosis of ST-segment elevation myocardial infarction (STEMI) on treatment intervals and outcome. BACKGROUND: Primary angioplasty has become the preferred reperfusion strategy in STEMI. Ambulance diagnosis and direct referral to an intervention center is an attractive treatment option that has not been studied extensively. METHODS: Consecutive pre-hospital patients with STEMI, who were referred to our intervention center for primary angioplasty between 2005 and 2007, were studied. After pre-hospital diagnosis, patients were either directly transported to our center or referred through a nonintervention center. The catheterization laboratory was activated before transport to the intervention center. RESULTS: Of the 581 patients referred, 454 (78%) came with direct transport and 127 (22%) through a nonintervention center. Direct transport was associated with a higher proportion of patients treated within the 90-min time window of the STEMI guidelines: 82% versus 23% (p < 0.01). Patients directly transported had a significantly shorter median symptom-to-balloon time of 149 min (Interquartile range: 118 to 197 min) versus 219 min (interquartile range: 178 to 315 min), p < 0.01, a higher post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 rate (92% vs. 84%; p = 0.03), and a lower 1-year mortality rate (7% vs. 13%; p = 0.03). Direct transport to the intervention center was independently associated with the symptom-to-balloon time, which in turn was an independent predictor of post-procedural TIMI flow grade 3, a strong prognosticator of outcome. CONCLUSIONS: After ambulance-based diagnosis of STEMI, direct transport to an intervention center with pre-hospital notification of the catheterization laboratory more than triples the proportion of patients treated within the time window of the guidelines. Time to balloon was an independent predictor of post-procedural TIMI flow grade 3, which underscores the need to reduce treatment delays.

Prolonged anticoagulation therapy adjunctive to aspirin after successful fibrinolysis: from early reduction in reocclusion to improved long-term clinical outcome.

BACKGROUND: Long-term addition of antithrombotics (clopidogrel, anticoagulants) to aspirin has improved outcome after acute coronary syndromes. Data on the impact after fibrinolysis are scarce. In Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis-2 (APRICOT-2), adjunctive moderate-intensity coumarin (median international normalized ratio 2.6) conferred a marked reduction in 3-month reocclusion and ischemic events. Given the association between reocclusion and long-term outcome, we performed long-term clinical follow-up. METHODS: Patients with thrombolysis in myocardial infarction (TIMI) 3 flow <48 hours after fibrinolysis for ST-elevation myocardial infarction were randomized to aspirin plus coumarin, with prolonged heparinization until the target international normalized ratio (2-3) was reached, or aspirin with standard heparinization. Three-month follow-up angiography (reocclusion rates 15% vs 28%) and long-term clinical follow-up (median 7.3 years, interquartile range 5.9-8.6 years) were performed. RESULTS: Patients randomized to adjunctive anticoagulation (n = 123) received coumarin for a median of 280 days (113-387 days). Survival was 94% versus 88% in patients on aspirin alone (n = 128, P = .12). Infarct-free survival was 86% versus 71% (P = .01). Thrombolysis in myocardial infarction bleeding was 4% in both groups. Patients with reocclusion had impaired survival: 80% versus 94% (P < .01). In a multivariable model without reocclusion, combination therapy independently predicted survival (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.13-1.00) and infarct-free survival (HR 0.51, 95% CI 0.28-0.95). When adjusted for reocclusion, combination therapy did not predict outcome. Reocclusion independently predicted death (HR 2.56, 95% CI 1.02-6.43) and reinfarction. CONCLUSIONS: Moderate-intensity oral anticoagulation added to aspirin improved 8-year clinical outcome after successful fibrinolysis. The beneficial effect was largely attributed to a reduction in reocclusion, which independently predicted death and reinfarction. This study provides a mechanistic rationale for prolonged adjunctive anticoagulation after fibrinolysis.

The smoker's paradox after successful fibrinolysis: reduced risk of reocclusion but no improved long-term cardiac outcome.

BACKGROUND: In smokers treated with fibrinolysis for ST-elevation myocardial infarction (STEMI) a paradoxical beneficial short-term outcome has been reported. This was attributed to favorable clinical and angiographic baseline variables and a better response to fibrinolysis. During follow-up infarct artery reocclusion is an important prognosticator. We studied the effects of smoking on reocclusion and long-term cardiac outcome after successful fibrinolysis. METHODS: In the Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis trials (APRICOT-1 and -2) 499 STEMI patients with an open infarct artery <48 h after fibrinolysis received randomized antithrombotic treatment until 3-month follow-up angiography. Five-year clinical follow-up was complete. RESULTS: Current smokers (317 patients, 64%) had favorable clinical (age 54 vs. 60 years, P < 0.01) and angiographic (single vessel disease 61% vs. 49%, P = 0.02) baseline characteristics. Reocclusion rates were 21% (67/317) in smokers versus 32% (59/182) in non-smokers (P < 0.01). Five-year infarct-free cardiac survival did not differ: 82% vs. 85%. Reocclusion (HR 2.41, 95%CI 1.05-5.56, P = 0.04) independently predicted cardiac mortality. Smoking was independently associated with a reduced risk of reocclusion (OR 0.58, 95%CI 0.37-0.91, P = 0.02), but not with improved 5-year cardiac outcome (HR 1.34, 95%CI 0.79-2.25, P = ns). CONCLUSIONS: After successful fibrinolysis, smoking is independently associated with a more than 40% reduced risk of reocclusion, which is an independent predictor of adverse outcome. However, even with more favorable baseline characteristics smokers did not have improved 5-year cardiac outcome in this low-risk population.

Ambulation after femoral sheath removal in percutaneous coronary intervention: a prospective comparison of early vs. late ambulation.

AIM AND OBJECTIVES: To investigate if ambulation four hours after sheath removal can replace ambulation 10 hours or more after sheath removal with regard to puncture site complications after percutaneous coronary interventions and to examine patient comfort in both groups. BACKGROUND: Early ambulation after percutaneous coronary intervention may facilitate earlier hospital discharge. Whether this approach is safe, is unknown. DESIGN: A non-randomised comparative study. METHODS: Percutaneous coronary intervention was performed by femoral approach. Registered nurses of the ward removed the sheath and haemostasis was achieved by manual compression. After bed rest with a compression bandage for four hours, the patients in the early ambulation group were ambulated. The patients in the control group stayed in bed till the next morning. Primary study endpoint was the composition of puncture site complications: haematoma, bleeding, false aneurysm and arteriovenous fistula. Secondary endpoints were occurrence of vasovagal collapse after mobilisation, back pain and problems with voiding. RESULTS: In the early ambulation group (n = 329) the total number of complications was nine (2.7%), vs. six (3.0%) in the control group (n = 202). The complication rate in the early ambulation group is not increased compared to the control group (test for non-inferiority p = 0.002). Hence non-inferiority is accepted and practical equivalence shown. There were no statistically significant differences concerning patient comfort between the groups. CONCLUSIONS: Early ambulation four hours after femoral sheath removal is feasible and safe. The incidence of puncture site complications in the early ambulation group is not increased in comparison with the group with prolonged bed rest. RELEVANCE TO CLINICAL PRACTICE: Patients could possibly be discharged earlier after percutaneous coronary intervention, allowing percutaneous coronary intervention in an ambulant setting. Further research should confirm these findings and extend the research to the effect of various closure devices in early ambulation and on patients' well-being.

Intracoronary infusion of autologous mononuclear bone marrow cells in patients with acute myocardial infarction treated with primary PCI: Pilot study of the multicenter HEBE trial.

OBJECTIVE: This study was a pilot trial to determine safety and feasibility of intracoronary infusion of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction (MI). BACKGROUND: Studies reporting the effect of MBMC therapy on improvement of left ventricular (LV) function have shown variable results. The HEBE trial is a large multicenter, randomized trial that currently enrolls patients. Prior to this trial we performed a pilot study. METHODS: Twenty-six patients with a first acute MI were prospectively enrolled in eight centers. Bone marrow aspiration was performed at a median of 6 days after primary PCI (interquartile range, 5-7 days). MBMC were isolated by gradient centrifugation and were infused intracoronary the same day. All patients underwent magnetic resonance imaging before cell infusion and after 4 months. Clinical events were assessed up to 12 months. RESULTS: Within 10 hr after bone marrow aspiration, 246 +/- 133 x 10(6) MBMC were infused, of which 3.9 +/- 2.3 x 10(6) cells were CD34(+). In one patient, this procedure was complicated by local dissection. LV ejection fraction significantly increased from 45.0 +/- 6.3% to 47.2 +/- 6.5% (P = 0.03). Systolic wall thickening in dysfunctional segments at baseline improved with 0.9 +/- 0.7 mm (P < 0.001). Infarct size decreased 37% from 17.8 +/- 8.2 to 11.2 +/- 4.2 gram (P < 0.001). During 12-month follow-up, 3 additional revascularizations were performed and an ICD was implanted in one patient, 3 weeks after PCI. CONCLUSION: In patients with acute MI, intracoronary infusion of MBMC is safe in a multicenter setting. At 4-month follow-up, a modest increase in global and regional LV function was observed, with a concomitant decrease in infarct size.

Transport for abciximab facilitated primary angioplasty versus on-site thrombolysis with a liberal rescue policy: the randomised Holland Infarction Study (HIS).

AIMS: As of to date, the only large transportation trial comparing on-site fibrin-specific thrombolysis with transfer for primary angioplasty in patients presenting in a referral centre is the DANAMI-2 trial, with only 3% rescue angioplasty. The Holland Infarction Study (HIS) compared abciximab facilitated primary angioplasty (FP) with on-site fibrin-specific thrombolytic therapy (TT) with a liberal protocol-driven rescue angioplasty (transport to intervention centre in case < 50% ST resolution at 60 min). METHODS AND RESULTS: Patients in a referral centre without shock and < 4.5 h of chest pain presenting with ST-elevation having > or = 12 mm ST-segment shift were randomised to either strategy. Of the originally planned 900 patients only 48 were included due to suspension of financial funding. Death, recurrent MI and stroke at one year was 8% for the FP-group and 22% for the TT-group (p = 0.2). Two hours after randomisation the rates of complete ST-segment resolution (> or =70%) were 52% and 35%, respectively (p = 0.2). CONCLUSION: This prematurely discontinued randomised transportation trial shows favorable trends with respect to long-term clinical outcome and early ST-resolution for abciximab facilitated primary angioplasty. In view of the real world delays associated with interhospital transport for primary angioplasty, treatment strategies focusing on early fibrin-specific lysis with a liberal selective rescue policy are warranted.

Detection of elevated pulmonary capillary wedge pressure in elderly patients with various cardiac disorders by the Valsalva manoeuvre.

In the present study, we assessed whether elevated (> or =15 mmHg) PCWP (pulmonary capillary wedge pressure) can be detected using the blood pressure response to the Valsalva manoeuvre in a group of elderly patients with various cardiac disorders, including atrial fibrillation and valvular heart disease, and healthy elderly controls. The Valsalva manoeuvre was performed in 93 patients (71+/-4 years) and 28 healthy controls (70+/-4 years) undergoing right-sided cardiac catheterization. Blood pressure was measured non-invasively with Finapres. PPR (pulse pressure ratio), the ratio of minimum pulse pressure during phase 2 and maximum pulse pressure during phase 1 of the Valsalva manoeuvre, was correlated with PCWP (r=0.63, P<0.001). The area under the receiver operator characteristic curve of PPR with elevated PCWP was 0.85 (P<0.001). For PPR=0.62, sensitivity for elevated PCWP was 80%, specificity was 79%, positive predictive value was 76% and negative predictive value was 83%. Correlation of PPR with PCWP and the ability of PPR to detect elevated PCWP was present in atrial fibrillation, heart failure and valvular heart disease. In conclusion, PPR is a sensitive and specific instrument to diagnose elevated PCWP non-invasively in a large group of elderly patients with various cardiac disorders. This makes the Valsalva manoeuvre a useful non-invasive tool for diagnosing heart failure, applicable in elderly patients with common cardiac disorders, such as atrial fibrillation and valvular heart disease.

Normal values of pulmonary capillary wedge pressure and the blood pressure response to the Valsalva manoeuvre in healthy elderly subjects.

The blood pressure response to the Valsalva manoeuvre is related to pulmonary capillary wedge pressure (PCWP) and can be used to diagnose heart failure. However, this has never been studied specifically in the elderly, in whom the prevalence of heart failure is highest. Furthermore, normal values of the Valsalva manoeuvre are lacking. We aimed to obtain normal values of PCWP and the blood pressure response to the Valsalva manoeuvre in elderly subjects. Therefore, 28 healthy subjects, aged 70 +/- 4 years, performed Valsalva manoeuvres before and after anti-G garment inflation, which was used for temporary increase of PCWP. Before inflation, PCWP was 9.8 +/- 1.9 mmHg in supine and 8.9 +/- 2.1 in semi-recumbent position. From the blood pressure response, measured with Finapres, the systolic blood pressure ratio (SBPR), pulse pressure ratio (PPR), stroke volume ratio (SVR) and heart rate ratio (HRR) were calculated. In supine position, SBPR was 0.76 +/- 0.11, PPR 0.51 +/- 0.16, SVR 0.42 +/- 0.11, and HRR 1.17 +/- 0.12. Semi-recumbently, SBPR was 0.74 +/- 0.10, PPR 0.46 +/- 0.14, SVR 0.41 +/- 0.10, and HRR 1.24 +/- 0.23. After inflation of the anti-G garment, the areas under the Receiver Operator Characteristics curves of SBPR, PPR and SVR for elevated (> or = 15 mmHg) PCWP were >0.85 in supine position. In conclusion, this is the first study to obtain normal values of the blood pressure response to the Valsalva manoeuvre and PCWP in healthy elderly subjects, which is essential for the interpretation of patient data. The Valsalva manoeuvre showed significant discriminatory power in the detection of elevated PCWP, which underscores its potential in the non-invasive diagnosis of heart failure.

Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease.

1. Methylenetetrahydrofolate reductase (MTHFR) is a regulating enzyme in folate-dependant homocysteine remethylation, because it catalyses the reduction of 5,10 methylenetetrahydrofolate to 5-methyltetrahydrofolate (5-MTHF). 2. Subjects homozygous for the 677C --> T mutation in the MTHFR enzyme suffer from an increased cardiovascular risk. It can be speculated that the direct administration of 5-MTHF instead of folic acid can facilitate the remethylation of homocysteine in methionine. 3. The aim of this study was to determine the pharmacokinetic properties of orally administered 6[R,S] 5-MTHF versus folic acid in cardiovascular patients with homozygosity for 677C --> T MTHFR. 4. This is an open-controlled, two-way, two-period randomised crossover study. Patients received a single oral dose of either 5 mg folic acid or 5 mg 5-MTHF in each period. The concentrations of the 6[S] 5-MTHF and 6[R] 5-MTHF diastereoisomers were determined in venous blood samples. 5. All pharmacokinetic parameters demonstrate that the bioavailability of 5-MTHF is higher compared to folic acid. The peak concentration of both isomers following the administration of 6[R,S] 5-MTHF is almost seven times higher compared to folic acid, irrespective of the patient's genotype. However, at 1 week after the administration of a single dosage 6[R,S] 5-MTHF, we detected 6[R] 5-MTHF following the administration of folic acid, indicating storage of this isomer in the body. 6. Our results demonstrate that oral 5-MTHF has a different pharmacokinetic profile with a higher bioavailability compared to folic acid, irrespective of the patient's genotype. Detrimental effects of the storage of high levels of the non-natural isomer 6[R] 5-MTHF cannot be excluded.

Coronary endothelial function in hyperhomocysteinemia: improvement after treatment with folic acid and cobalamin in patients with coronary artery disease.

OBJECTIVES: We evaluated the effect of therapy with folic acid and cobalamin on coronary endothelial function, expressed as a change in volumetric coronary blood flow (CBF), in hyperhomocysteinemic patients with coronary artery disease (CAD). BACKGROUND: Hyperhomocysteinemia is an independent risk factor for CAD. The mechanism responsible for this increased risk is unclear, but it is generally assumed that hyperhomocysteinemia causes endothelial dysfunction. It is unknown whether lowering plasma homocysteine levels with folic acid and cobalamin improves coronary endothelial function in patients with hyperhomocysteinemia and symptomatic CAD. METHODS: Fifteen patients scheduled for elective percutaneous transluminal coronary angioplasty (PTCA) with plasma homocysteine levels of >or=16 micromol/l were randomized for six months of treatment with folic acid 5 mg and cobalamin 400 microg daily or placebo. Coronary endothelial function was evaluated in a non-PTCA vessel using acetylcholine infusion in dosages of 10(-8) M, 10(-7) M, and 10(-6) M. Endothelium- dependent CBF is determined using intracoronary Doppler velocity and quantitative coronary angiography at baseline and after six months. RESULTS: In the folic acid/cobalamin treated group, CBF increased after acetylcholine infusion with 96% (standard deviation 54; 95% confidence interval [CI]: 44% to 154%) compared with a decrease of 16% (standard deviation 35; 95% CI: -20% to +30%) of the CBF in the placebo-treated group (p < 0.005). CONCLUSIONS: This is the first prospective randomized placebo-controlled intervention study evaluating coronary endothelial function in hyperhomocysteinemic patients with CAD. Our results suggest that coronary endothelial function improves after treatment with folic acid and cobalamin.

Finapres arterial pulse wave analysis with Modelflow is not a reliable non-invasive method for assessment of cardiac output.

Non-invasive continuous monitoring of cardiac output could be very useful in clinical care and in research settings, particularly in elderly subjects. We studied whether Finapres arterial pulse wave analysis with Modelflow is a reliable non-invasive method for the assessment of cardiac output in healthy elderly subjects. We compared Modelflow cardiac output (MFCO) with thermodilution cardiac output (TDCO) in 28 healthy subjects, aged 70+/-4 years (mean+/-S.D.). TDCO was measured during right-sided heart catheterization, while MFCO was calculated with Modelflow(R) software from non-invasive arterial Finapres blood pressure, which was measured simultaneously. The two methods were compared using a paired t-test, by Pearson correlation, and by Bland-Altman analysis. TDCO was 6.4+/-1.1 litres/min (mean+/-S.D.) and MFCO was 4.7+/-1.3 litres/min (P<0.001). There was no significant correlation between MFCO and TDCO (r=0.28, P=0.13). Mean difference (bias) was -1.7 litres/min (S.E.M. 0.27 litres/min), with an S.D. (precision) of 1.5 litres/min. The 95% limits of agreement were -4.6 to +1.1 litres/min. In conclusion, non-invasive MFCO values differed significantly from and showed no significant correlation with invasively determined TDCO values in the normal range. Although simple, non-invasive and patient-friendly, the Modelflow method is inaccurate for assessment of cardiac output without invasive calibration.

Aspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis (APRICOT)-2 Trial.

BACKGROUND: Despite the use of aspirin, reocclusion of the infarct-related artery occurs in approximately 30% of patients within the first year after successful fibrinolysis, with impaired clinical outcome. This study sought to assess the impact of a prolonged anticoagulation regimen as adjunctive to aspirin in the prevention of reocclusion and recurrent ischemic events after fibrinolysis for ST-elevation myocardial infarction. METHODS AND RESULTS: At coronary angiography <48 hours after fibrinolytic therapy, 308 patients receiving aspirin and intravenous heparin had a patent infarct-related artery (Thrombolysis In Myocardial Infarction [TIMI] grade 3 flow). They were randomly assigned to standard heparinization and continuation of aspirin alone or to a 3-month combination of aspirin with moderate-intensity coumarin, including continued heparinization until a target international normalized ratio (INR) of 2.0 to 3.0. Angiographic and clinical follow-up were assessed at 3 months. Median INR was 2.6 (25 to 75th percentiles 2.1 to 3.1). Reocclusion (< or =TIMI grade 2 flow) was observed in 15% of patients receiving aspirin and coumarin compared with 28% in those receiving aspirin alone (relative risk [RR], 0.55; 95% CI 0.33 to 0.90; P<0.02). TIMI grade 0 to 1 flow rates were 9% and 20%, respectively (RR, 0.46; 95% CI, 0.24 to 0.89; P<0.02). Survival rates free from reinfarction and revascularization were 86% and 66%, respectively (P<0.01). Bleeding (TIMI major and minor) was infrequent: 5% versus 3% (P=NS). CONCLUSIONS: As adjunctive to aspirin, a 3-month-regimen of moderate-intensity coumarin, including heparinization until the target INR is reached, markedly reduces reocclusion and recurrent events after successful fibrinolysis. This conceptual study provides a mechanistic rationale to further investigate the role of prolonged anticoagulation after fibrinolytic therapy.

Recruitment and coaching of healthy elderly subjects for invasive cardiovascular research with right-sided catheterisation.

BACKGROUND AND AIMS: Heart failure is primarily a disorder of the elderly. To investigate a non-invasive method to diagnose heart failure in the elderly, right-sided catheterisation was needed in healthy elderly subjects. We studied the feasibility of recruitment of healthy elderly subjects for this invasive investigation and aimed to identify the factors important for recruitment and for successful participation. METHODS: Healthy subjects, aged >/=65 years, were invited by advertisement in a local newspaper to participate in an invasive study, preceded by extensive medical examination. An experienced research nurse provided coaching and care on an individual basis. Motivation to participate, satisfaction and the expected and perceived burden were assessed with a questionnaire before and after catheterisation. RESULTS: From 180 subjects responding, 53 were invited for screening of whom 38 were included. Cardiovascular examination was the most important reason for participation. The questionnaire showed considerable satisfaction about the information and care given and about participating in the study in general. CONCLUSIONS: Recruitment of healthy elderly subjects for an invasive cardiovascular study is feasible. Individual coaching contributed to the satisfaction experienced. The appointment of an experienced research nurse appears important for successful recruitment and participation of healthy elderly subjects in an invasive cardiovascular study.