Intravenous enoxaparin versus unfractionated heparin in unselected patients undergoing percutaneous coronary interventions: the Zurich enoxaparin versus unfractionated heparin in PCI study (ZEUS).

AIMS: To evaluate the efficacy and safety of intravenous enoxaparin as an alternative to unfractionated heparin (UFH) as antithrombotic therapy in unselected patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: Eight hundred and seventy-six (876) consecutive eligible patients undergoing PCI were prospectively randomised to either intravenous enoxaparin 0.75 mg/kg or dose-adjusted UFH in this open-label study that was prematurely stopped due to slow recruitment. Randomisation was stratified on elective PCI or PCI for acute coronary syndrome (ACS). The primary endpoint was a combination of death, myocardial infarction, unplanned target vessel revascularisation and major bleeding at 30 days. Secondary endpoint was a composite of major and minor bleeding and thrombocytopenia < 50x109. The primary endpoint of intravenous enoxaparin did not differ from those of UFH (5.5% vs. 7.0%, p=ns) whereas safety endpoints were reduced with enoxaparin compared to UFH (9.9% vs. 20.0%, p<0.001). Among 229 (26%) patients presenting with ACS, the incidence of both, the primary and secondary endpoints, was lower with enoxaparin as compared to UFH (1.8% vs. 12.9% and 14.2% vs. 31%, p<0.001 and p=0.003, respectively). CONCLUSIONS: Due to the premature halting of the study and the low event rate, these data are observational only, and no definite conclusion could be made concerning efficacy and safety of intravenous enoxaparin as an alternative to UFH in unselected patients undergoing PCI.

Interaction of vitamin K antagonists with heparin affect monitoring by activated clotting times.

BACKGROUND: Unfractionated heparin is recommended during atrial fibrillation (AF) ablation to achieve activated clotting time (ACT) above 250-300 s to prevent clot. Many patients on therapeutic international normalised ratio (INR) undergo AF ablation procedures; however, it is unknown whether they require less heparin to achieve similar ACT levels. METHODS: During AF ablation, the ACT was measured before and 10 min after administration of i.v. unfractionated heparin in patients with and without anticoagulation. The association of INR, heparin, pre-procedure ACT and body weight with ACT after heparin administration was tested using multivariable linear regression models. RESULTS: The subjects of this study were 149 patients undergoing AF ablation, among them 40 (27%) with subtherapeutic INR < 2, 79 (53%) with an INR between 2 and 3, and 30 (20%) patients with INR > 3. Baseline ACT was associated with INR (r = 0.33, p < 0.001). After a mean of 8,685 +/- 2,015 U (range, 5,000-15,000 IU) unfractionated heparin, univariate predictors of ACT were baseline INR (p < 0.001), heparin dose (p = 0.012) and baseline ACT (p = 0.027). In the multivariable model, baseline INR (part r = 0.64, p < 0.001) and heparin dose (part r = 0.33, p < 0.001) strongly predicted post-heparin ACT. Estimated from the regression model, the heparin dose reductions by approximately one third in those with an INR of 2-3 and by at least two thirds in those with an INR above 3 may be favourable. Over the following 3 months, no thromboembolism and acute bleeding were observed. CONCLUSION: The INR was the strongest predictor of post-heparin ACT, even more important than the heparin dose itself. The reduction of heparin dose by one third if INR is between 2-3 and by two thirds if INR is above 3 may be favourable.

Long-term survival and functional outcome of unselected patients undergoing percutaneous coronary intervention for acute myocardial infarction.

BACKGROUND: Percutaneous coronary intervention (PCI) is the most effective reperfusion modality in patients with acute myocardial infarction (MI). Data concerning long-term survival and functional outcome are sparse. METHODS: One thousand consecutive patients treated by emergency PCI were systematically ana-lysed in a single-centre registry. Multivariate predictors of in-hospital mortality, post-discharge mortality and late functional capacity were identified. RESULTS: Follow-up was completed for 978 patients. The median clinical follow-up length was 3.2 years. In-hospital and post-discharge mortality were 7.6% and 7.3%, respectively. Annualised post-discharge mortality remained stable over time at 2% per year. Independent predictors of in-hospital death were cardiogenic shock, TIMI flow <3 after PCI, left ventricular ejection fraction <40%, age and time to patent artery >6 h. Independent predictors of post-discharge mortality were TIMI flow after PCI <3, prior MI, elevated glucose levels at admission, and increasing age. In contrast, cardiogenic shock, time to patent artery and left ventricular ejection fraction <40% were not independently associated with post-hospital death. At late follow-up, 47% of patients had normal functional capacity and 49.1% were in New York Heart Association functional class II. Predictors of impaired functional capacity at follow-up were age, gender, smoking habits and multivessel coronary disease. CONCLUSIONS: Post-discharge mortality after PCI for acute MI was 2% per year. Significant differences exist between predictors of in-hospital and post-discharge mortality. The functional capacity of surviving patients was remarkably good, even when presented in cardiogenic shock.

Proinflammatory cytokines in acute myocardial infarction with and without cardiogenic shock.

BACKGROUND: Inflammatory response is an important feature of acute coronary syndromes and myocardial infarction (MI). The prognostic value of proinflammatory cytokines in patients with acute MI complicated by cardiogenic shock is unknown. METHODS AND RESULTS: In 41 patients admitted with acute MI (age 60 +/- 11 years, six females, 19 Killip class IV) serial plasma concentration of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and interleukin 1 receptor antagonist (IL-1Ra) were measured. Seven patients with cardiogenic shock (CS) developed a systemic inflammatory response syndrome (SIRS). Patients with CS-particularly those who developed SIRS-showed significantly higher cytokine levels than patients with uncomplicated MI. In patients with CS and SIRS peak levels of IL-1Ra were 223,973 pg/ml, IL-6 252.8 pg/ml and TNF-alpha 7.0 pg/ml. In CS without SIRS IL-1Ra levels were 19,988 pg/ml, IL-6 109.3 pg/ml and TNF-alpha 3.8 pg/ml. In uncomplicated MI peak IL-1Ra levels were 1,088 pg/ml, IL-6 34.1 pg/ml and TNF-alpha 2.6 pg/ml. CONCLUSIONS: The inflammation-associated cytokines TNF-alpha, IL-6 and IL-1Ra are significantly elevated in patients with MI complicated by CS when compared to patients with uncomplicated MI. Among shock-patients IL-1Ra levels are promising diagnostic markers for early identification of patients developing SIRS, heralding a poor outcome.

Atrium-driven mitral annulus motion velocity reflects global left ventricular function and pulmonary congestion during acute biventricular pacing.

BACKGROUND: The short-term effect of acute biventricular pacing on cardiac function in patients with chronic heart failure undergoing heart surgery is widely unknown. The present study was designed to determine whether mitral annular tissue Doppler imaging (TDI) is useful to predict acute changes in global systolic function determined by the continuous cardiac output method that was measured postoperatively during various pacing configurations in patients with depressed left ventricular (LV) function. METHODS: TDI peak velocities of systolic (Sm), early diastolic (Em), and late diastolic (Am) mitral annular motion waves were measured in 17 patients (age 67 +/- 8 years, 10 male) with depressed LV systolic function (LV ejection fraction < or = 35%) and QRS duration > 120 ms undergoing temporary epicardial biventricular pacing after aortocoronary bypass and valve surgery. TDI velocities, QRS duration on surface electrocardiogram, cardiac index (CI), right atrial pressure, pulmonary artery pressure, and pulmonary capillary wedge (PCW) pressure were measured simultaneously during various pacing configurations (right atrial-biventricular, right atrial-LV, right atrial-right ventricular, atrial inhibited, and no pacing). RESULTS: Univariate linear regression analysis showed a good correlation between Am and CI (r = 0.53, P = .0001) determined in all pacing modes, a weak correlation between Sm and CI (r = 0.31, P = .017), and no correlation between Em and CI (r = 0.21, P = .074). Am > 6 cm/s predicted a CI of 2.5 L/min/m(2) or more with a sensitivity of 95% and a specificity of 30%. All TDI values correlated negatively with PCW (r = -0.53, P = .0001 for Sm; r = -0.34, P = .01 for Em; r = -0.50, P = .0001 for Am). Am greater than 6 cm/s predicted a PCW of 16 mm Hg or less with a specificity of 100% and a sensitivity of 34%. Mean values of TDI velocities and hemodynamic parameters were not significantly different between each pacing configuration. CONCLUSIONS: Peak Am mitral annular velocity correlates well with CI and PCW, respectively, thus providing an easy means to assess LV systolic function and pulmonary congestion during cardiac pacing in chronic heart failure.

Acute biventricular pacing after cardiac surgery has no influence on regional and global left ventricular systolic function.

BACKGROUND: Cardiac resynchronization therapy has been shown to improve systolic function in patients with advanced chronic heart failure and electromechanical delay (QRS width > 120 ms). However, the effect of acute biventricular (BiV) pacing on perioperative haemodynamic changes is not well defined. In the present study, acute changes in regional left ventricular (LV) systolic function determined by tissue Doppler imaging (TDI) and global LV systolic function determined by the continuous cardiac output method were measured during various pacing configurations in patients with depressed LV systolic function undergoing heart surgery. METHODS: Twenty-six patients (age 68 +/- 8 years, 15 males) with depressed systolic LV function (LV ejection fraction 120 ms undergoing temporary epicardial BiV pacing after aortocoronary bypass and valve surgery were included. QRS duration on surface electrocardiogram (ECG), TDI (systolic velocities of septal and lateral mitral annulus), cardiac index (CI), right atrial pressure, pulmonary artery pressure (PAP), and pulmonary capillary wedge pressure (PCW) were measured during various pacing configurations [no pacing (intrinsic rhythm), right atrial-biventricular (RA-BiV pacing), right atrial-left ventricular (RA-LV), right atrial-right ventricular (RA-RV), and AAI pacing]. RESULTS: There were no differences in QRS duration during intrinsic rhythm, RA-BiV pacing, and AAI pacing. However, RA-LV and RA-RV stimulations showed a longer QRS duration (P < 0.01 vs. intrinsic rhythm, RA-BiV pacing, and AAI, respectively). Tissue Doppler velocities of the septal and lateral mitral annulus were comparable in all pacing modes. Neither CI nor PAP or PCW showed significant differences during the various pacing configurations. There was a positive correlation between regional (TDI) and global (CI) parameters of LV systolic function. Conclusions Biventricular pacing after heart surgery does not improve parameters of regional and global LV systolic function acutely in patients with heart failure and intraventricular conduction delay and, thus, may not reflect changes observed with chronic BiV pacing.

Single-chamber ventricular pacing increases markers of left ventricular dysfunction compared with dual-chamber pacing.

AIMS: Large randomized trials comparing DDD with VVI pacing have shown no differences in mortality, but conflicting evidence exists in regard to heart failure endpoints. Here we evaluated the effect of pacing mode on serum levels of brain natriuretic peptide (BNP) and amino-terminal-proBNP (NT-proBNP). Methods Forty-one patients (age 73 +/- 10 years) with dual-chamber pacemakers were included in a prospective, single-blind, randomized crossover study evaluating the impact of DDD(R)/VDD versus VVI(R) mode on objective and functional parameters. Data were collected after a 2-week run-in phase and after 2 weeks each of VVI(R) and DDD(R)/VDD pacing or vice versa. Results BNP and NT-proBNP levels during DDD(R)/VDD stimulation (151 +/- 131 and 547 +/- 598 pg/mL) showed no change compared with baseline (154 +/- 130 and 565 +/- 555 pg/mL), but a significant 2.4-fold increase was observed during VVI(R) mode [360 +/- 221 and 1298 +/- 1032 pg/mL; P < 0.001 compared with DDD(R)/VDD]. The assessment of functional class, the presence of pacemaker syndrome [49% in VVI(R) mode] and the patients' preferred pacing mode showed significant differences in favour of DDD(R)/VDD pacing. CONCLUSION: Patients can differentiate between DDD(R)/VDD and VVI(R) pacing, and prefer the former. Compared with DDD(R)/VDD pacing, VVI(R) stimulation induces a two- to three-fold increase in serum BNP and NT-proBNP levels.

Admission glucose concentrations independently predict early and late mortality in patients with acute myocardial infarction treated by primary or rescue percutaneous coronary intervention.

BACKGROUND: In patients with acute myocardial infarction (MI), increased plasma glucose levels at hospital admission are associated with worse outcome. We aimed to assess the predictive value of admission glucose concentrations on short- and long-term mortality in patients with acute MI undergoing primary or rescue percutaneous coronary intervention (PCI). METHODS: We analyzed the 30-day and long-term (mean follow-up 3.7 years) outcome of 978 patients prospectively included in a single-center registry of patients with acute MI treated with PCI within 24 hours after onset of symptoms. Patients were classified according to plasma glucose levels at admission: < 7.8 mmol/L (group I, n = 322), 7.8 to 11 mmol/L (group II, n = 348), and > 11.0 mmol/L (group III, n = 308). RESULTS: Mortality at 30 days was 1.2% in group I, 6.3% in group II, and 16.6% in group III (P < .001). After multivariate adjustment for age, the presence of cardiogenic shock, and TIMI 3 flow after PCI, the association of mortality with glucose classification remained significant (P value for trend = .003). The relative risk of death at 30 days for group III versus group I was 3.9 (95% CI 1.2-13.2). During long-term follow-up, mortality was similar in groups I and II. However, in group III adjusted mortality remained significantly increased compared with group I (relative risk 1.76, CI 1.01-3.08). CONCLUSIONS: In patients undergoing emergency PCI for acute MI, glucose levels at hospital admission are predictive for short- and long-term survival. Knowledge of admission glucose levels may improve initial bedside risk stratification.

Ibutilide in persistent atrial fibrillation refractory to conventional cardioversion methods.

BACKGROUND: Electrical cardioversion of atrial fibrillation seems to be enhanced by pretreatment with ibutilide, but only few is known about the effects of ibutilide in atrial fibrillation which failed to convert with class III antiarrhythmic agents and electrical cardioversion. The objectives of this study were to evaluate the efficacy and safety of ibutilide administration in patients with persistent atrial fibrillation refractory to long-term therapy with class III antiarrhythmic drugs and transthoracic cardioversion. METHODS: Prospective study in 22 patients (16 men and 6 women, mean age 63+/-9 years) with structural heart disease and persistent atrial fibrillation for a mean duration of 39+/-50 (range 1-145) months. All patients had failed to convert to sinus rhythm after transthoracic cardioversion while on treatment with class III antiarrhythmic drugs (amiodarone in 82%, sotalol in 18%). One milligram of ibutilide was administered in all patients and electrical cardioversion was performed again, if necessary. RESULTS: The total conversion rate to sinus rhythm was 95% (21 of 22 patients). Two patients (9%) were successfully converted after ibutilide alone and 19 patients (86%) when transthoracic cardioversion was repeated after ibutilide. The QTc intervals increased from 451+/-28 to 491+/-49 ms (p<0.001) after ibutilide. No adverse effects occurred. The rate of freedom from atrial fibrillation after 1 month of follow-up was 64%. CONCLUSIONS: The efficacy of concomitant use of ibutilide infusion and, if necessary, repeated transthoracic cardioversion for restoration of sinus rhythm in long-term persistent atrial fibrillation and previously failed antiarrhythmic and electrical cardioversion was 95%. There were no adverse effects associated with ibutilde administration. Our results suggest that this combined strategy may be safe and successful in patients with atrial fibrillation resistant to conventional cardioversion methods and may be an alternative to internal cardioversion.

Long-term outcome of acute myocarditis is independent of cardiac enzyme release.

BACKGROUND: There are few data concerning prognostic markers of acute myocarditis. The purpose of this study was to assess the prognostic value of initial measurements of creatine kinase (CK), cardiac troponin I (cTnI) and myoglobin as regards late recovery of the left ventricular ejection fraction on follow-up. METHODS: A total of 22 patients (53+/-15 years old, 11 female) with acute myocarditis were followed up in a prospective observational study. Of these, 11 (50%) showed a history of acute infection prior to hospitalisation and seven (32%) had pericardial effusion. The median ejection fraction during the acute phase was 47+/-17%; after a mean follow-up of 119+/-163 days it improved to 60+/-9% (P<0.001). Considering maximal CK-rise values of 641+/-961 U/l (P=0.38), cTnI-rise values of 3.7+/-8.6 microg/l (P=0.16) and myoglobin values of 7.4+/-12 nmol/l (P=0.69), there was no correlation between initial cardiac enzyme levels and the initial and late left ventricular ejection fraction. CONCLUSION: After acute myocarditis, there is late recovery of left ventricular ejection fraction, which is independent of the initial myocardial damage measured by cardiac enzyme release.

Long-term results after acute percutaneous transluminal coronary angioplasty in acute myocardial infarction and cardiogenic shock.

The aim of this study was to determine the long-term outcome in unselected, consecutive patients after acute percutaneous transluminal angioplasty (PTCA) for acute myocardial infarction (AMI) complicated by cardiogenic shock. This involved a follow-up study from a prospectively conducted patient registry in a tertiary referral center. A total of 59 patients (10 female/49 male; median age 62 years (32-91)) with percutaneous transluminal cardiac interventions in primary cardiogenic shock were identified between January 1995 and January 2000. Twenty-two patients (37%) had been resuscitated successfully before intervention. The in-hospital mortality of shock patients was 36% (n=21, median age 68 (47-84)). The median follow-up of survivors was 18.1 (7-57.3) months, during which three further patients died (8%; two because of sudden cardiac deaths, one because of acute reinfarction). Achievement of thrombolysis in myocardial infarction (TIMI) flow III after acute PTCA (84% in survivors vs. 38% in non-survivors; P<0.001) and the absence of the left main coronary artery (3% survivors vs. 29% non-survivors; P=0.003) as culprit lesion in patients with cardiogenic shock was strongly associated with an improved survival rate. A second cardiac intervention was performed in seven patients (18%). Overall functional capacity of shock survivors was good. At final follow-up, 80% of the survivors were completely asymptomatic. One patient had angina pectoris NYHA II, five patients dyspnoea NYHA class II. Exercise stress-test was performed in 24 of the 38 surviving patients, median exercise capacity was 100% (range 55-113%) of the age adjusted predicted value. In unselected patients with cardiogenic shock due to AMI, treatment with acute PTCA resulted in an in-hospital mortality of 36%, low late mortality and good functional capacity in long-term survivors. TIMI flow grade III after acute PTCA in patients with acute myocardial infarction complicated by cardiogenic shock was strongly associated with an improved survival rate whereas the left main coronary artery as culprit lesion was associated with worse outcome.