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To investigate the effects of inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. Thirty patients with cardiogenic shock were included. Patients received dobutamine, enoximone, or norepinephrine. We performed hemodynamic measurements at baseline and after titration of the inotropic agent until cardiac index (CI) ≥ 2.5 L.min-1.m(-2) or mixed-venous oxygen saturation (SvO2) ≥ 70% (dobutamine or enoximone), and mean arterial pressure (MAP) ≥ 70 mmHg (norepinephrine). As parameters of tissue perfusion, we measured central-peripheral temperature gradient (delta-T) and sublingual perfused capillary density (PCD). All patients reached predefined therapeutic targets. The inotropes did not significantly change delta-T. Dobutamine did not change PCD. Enoximone increased PCD (9.1 [8.9-10.2] vs. 11.4 [8.4-13.9] mm.mm(-2); p<0.05), and norepinephrine tended to decrease PCD (9.8 [8.5-11.9] vs. 8.8 [8.2-9.6] mm.mm-2, p = 0.08). Fifteen patients (50%) died within 30 days after admission. Patients who had low final PCD (≤ 10.3 mm.mm-2; 64%) were more likely to die than patients who had preserved PCD (>10.3 mm.mm(-2); mortality 72% vs. 17%, p = 0.003). This study demonstrates the effects of commonly used inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. Despite hemodynamic optimization, tissue perfusion was not sufficiently restored in most patients. In these patients, mortality was high. Interventions directed at improving microcirculation may eventually help bridging the gap between improved hemodynamics and dismal patient outcome in cardiogenic shock.

ST2 is a member of the interleukin-1 receptor family that is up-regulated in conditions associated with increased myocardial strain. ST2 has been shown to be independently predictive of adverse outcome in heart failure and ST-segment elevation myocardial infarction, but its prognostic value in non–ST-elevation acute coronary syndrome (NSTE-ACS) has not been established. We measured ST2 at randomization and after 24, 48, and 72 hours in 403 NSTE-ACS patients from the GUSTO IV study, and studied its kinetics and its associations to clinical baseline factors and 1-year mortality. Median ST2 levels decreased from 28.4 U/mL at randomization to 21.8 U/mL at 72 hours (P < .001). Peak levels were noted 6 to 17 hours after symptom onset. Randomization ST2 levels were independently associated to N-terminal pro-B-type natriuretic peptide but otherwise exhibited only weak relations to cardiovascular risk factors and comorbidities, and biomarkers of myocardial necrosis or inflammation. ST2 was related to 1-year mortality independently of clinical risk indicators (odds ratio 2.3 [95% CI 1.1-4.6], P = .03) but lost its predictive value after additional adjustment for prognostic biomarkers, in particular N-terminal pro-B-type natriuretic peptide. ST2 levels are elevated early in NSTE-ACS and predict 1-year mortality. Our data indicate that ST2 represents an interesting novel pathophysiologic pathway in the setting of ischemia-related myocardial dysfunction. However, future prospective evaluations in larger populations are needed before the clinical utility of ST2 can be determined.

β-Blockers relieve angina/ischemia in stable coronary artery disease (CAD), and angiotensin-converting enzyme inhibitors prevent CAD outcomes. In EUROPA, the angiotensin-converting enzyme inhibitor perindopril reduced cardiovascular outcomes in low-risk stable CAD patients over 4.2 years. This post hoc analysis examined whether the addition of perindopril to β-blocker in EUROPA had additional benefits on outcomes compared with standard therapy including β-blocker. EUROPA was a multicenter, double-blind, placebo-controlled, randomized trial in patients with documented stable CAD. Randomized EUROPA patients who received β-blocker at baseline were identified, and the effect on cardiovascular outcomes of adding perindopril or placebo was analyzed. Endpoints were the same as those in EUROPA. At baseline, 62% (n = 7534 [3789 on perindopril and 3745 on placebo]) received β-blocker. Treatment with perindopril/β-blocker reduced the relative risk of the primary end point (cardiovascular death, nonfatal myocardial infarction, and resuscitated cardiac arrest) by 24% compared with placebo/β-blocker (HR, 0.76; 95% CI, 0.64-0.91; P = .002). Addition of perindopril also reduced fatal or nonfatal myocardial infarction by 28% (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and hospitalization for heart failure by 45% (HR, 0.55; 95% CI, 0.33-0.93; P = .025). Serious adverse drug reactions were rare in both groups, and cardiovascular death and hospitalizations occurred less often with perindopril/β-blocker. The addition of perindopril to β-blocker in stable CAD patients was safe and resulted in reductions in cardiovascular outcomes and mortality compared with standard therapy including β-blocker.

To quantify the impact of the implementation of treatment modalities into clinical practice since 1985, on outcome of patients with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI). All consecutive patients admitted for STEMI or NSTEMI at the Thoraxcenter between 1985 and 2008 were included. Baseline characteristics, pharmacological and invasive treatment modalities, and survival status were collected. The study population was categorised in three groups of patients: those hospitalised between 1985-1990, 1990-2000, and 2000-2008. We identified 14,434 patients hospitalised for myocardial infarction (MI). Both STEMI and NSTEMI patients were increasingly treated with the current guideline based therapy. In STEMI, at 30 days following admission, cumulative mortality rate decreased from 17% in 1985-1990 to 13% in 1990-2000, and to 6% in 2000-2008. Adjusted 30-day and three-year mortality in the last period was 80% and 68% lower than in 1985, respectively. In NSTEMI, at 30 days following admission, cumulative mortality rate decreased from 6% in 1985-1990 to 4% in 1990-2000, and to 2% in 2000-2008. Adjusted 30-day and three-year mortality in the last period was 78% and 49% lower than in 1985, respectively. For patients admitted between 2000 and 2008, 3 year survival of STEMI and NSTEMI patients was 87% and 88%, respectively. Our results indicate substantial improvements in acute- and long-term survival in patients hospitalised for MI, related to improved acute- as well as long-term treatment. Early medical evaluation in suspected MI and intensive early hospital treatment both remain warranted in the future.

In a phase 2 trial, patients with mechanical heart valves were randomly assigned to receive either dabigatran or warfarin for anticoagulation. Dabigatran was associated with higher rates of ischemic stroke (5%, vs. 0% with warfarin) and major bleeding (4% vs. 2%). Prosthetic heart-valve replacement is recommended for many patients with severe valvular heart disease and is performed in several hundred thousand patients worldwide each year. 1 Mechanical valves are more durable than bioprosthetic valves 2 but typically require lifelong anticoagulant therapy. The use of vitamin K antagonists provides excellent protection against thromboembolic complications in patients with mechanical heart valves 3 but requires restrictions on food, alcohol, and drugs and lifelong coagulation monitoring. Because of the limitations of vitamin K antagonists, many patients opt for a bioprosthesis rather than a mechanical valve, despite the higher risk of premature valve failure requiring repeat valve-replacement surgery with . . .

There is conclusive evidence from clinical trials that reduction of mortality by fibrinolytic therapy in acute myocardial infarction is related to the time elapsing between onset of symptoms and commencement of treatment. However, the exact pattern of this relation continues to be debated. This paper discusses whether or not appreciable additional gain can be achieved with very early treatment. The relation between treatment delay and short-term mortality (up to 35 days) was evaluated using tabulated data from all randomised trials of at least 100 patients (n=22; 50 246 patients) that compared fibrinolytic therapy with placebo or control, reported between 1983 and 1993. Benefit of fibrinolytic therapy was 65 (SD 14), 37 (9), 26 (6) and 29 (5) lives saved per 1000 treated patients in the 0-1, 1-2, 2-3, and 3-6 h intervals, respectively. Proportional mortality reduction was significantly higher in patients treated within 2 h compared to those treated later (44% [95% CI 32, 53] vs 20% [15, 25]; p=0·001). The relation between treatment delay and mortality reduction per 1000 treated patients was expressed significantly better by a non-linear (19-4-0-6x+29-3x −1) than a linear (34 7-1·6x) regression equation (p=0·03). The beneficial effect of fibrinolytic therapy is substantially higher in patients presenting within 2 h after symptom onset compared to those presenting later.

Appropriate risk stratification of patients with established, stable coronary artery disease could contribute to the prevention of recurrent cardiovascular events. The purpose of the present study was to develop and validate risk prediction models for various cardiovascular end points in the EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) database, consisting of 12,218 patients with established coronary artery disease, with a median follow-up of 4.1 years. Cox proportional hazards models were used for model development. The end points examined were cardiovascular mortality, noncardiovascular mortality, nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, resuscitated cardiac arrest, and combinations of these end points. The performance measures included Nagelkerke's R2, time-dependent area under the receiver operating characteristic curves, and calibration plots. Backward selection resulted in a prediction model for cardiovascular mortality (464 events) containing age, current smoking, diabetes mellitus, total cholesterol, body mass index, previous myocardial infarction, history of congestive heart failure, peripheral vessel disease, previous revascularization, and previous stroke. The model performance was adequate for this end point, with a Nagelkerke R2 of 12%, and an area under the receiver operating characteristic curve of 0.73. However, the performance of models constructed for nonfatal and combined end points was considerably worse, with an area under the receiver operating characteristic curve of about 0.6. In conclusion, in patients with established coronary artery disease, the risk of cardiovascular mortality during longer term follow-up can be adequately predicted using the clinical characteristics available at baseline. However, the prediction of nonfatal outcomes, both separately and combined with fatal outcomes, poses major challenges for clinicians and model developers.

Noncompaction cardiomyopathy (NCC) is a primary cardiomyopathy characterized by an excessively prominent trabecular meshwork and deep intertrabecular recesses of the left ventricular walls. Most cases are inherited, with a dominant inheritance pattern. The aim of the present study was to determine the prevalence and clinical characteristics of cardiomyopathies in the close relatives of patients with NCC. We evaluated 156, mostly first-degree, family members of 44 adult patients with NCC who agreed to familial screening. A family history of cardiac disease was reported by 16 (36%) of the 44 patients, including premature sudden death in 8 families (18%). NCC (n = 32) or dilated cardiomyopathy (n = 9) was diagnosed in 41 relatives (26%) by echocardiography (n = 25), contrast echocardiography (n = 6), or magnetic resonance imaging (n = 10). Of these family members, 13 already had known cardiac symptoms and signs, but most (28 of 41) were asymptomatic. Most subjects with NCC had mild to moderate left ventricular dysfunction (n = 29, 71%). After a median follow-up of 55 months (interquartile range 43 to 93), most remained asymptomatic. Four family members were treated with prophylactic implantable cardioverter-defibrillator placement and 23 of those with NCC were treated with drugs, including angiotensin-converting enzyme inhibitors (41%), β blockers (34%), and anticoagulants (17%). In conclusion, there is a high prevalence, mostly asymptomatic, of cardiac disease (26%) among first- and second-degree family members of patients with NCC. This warrants screening and offers an opportunity for early intervention.

The purposes of the study were to determine the effects of addition of perindopril to long-term continuous treatment with calcium-channel blocker (CCB) on cardiac outcomes in the stable coronary artery disease (CAD) population of EUROPA and to explore the presence of synergy between perindopril and CCB in secondary prevention. We identified participants receiving CCB at every visit during the 4.2-year follow-up and analyzed the effect of addition of perindopril (n = 1,022 perindopril/CCB vs n = 1,100 placebo/CCB). Addition of perindopril to CCB significantly reduced total mortality by 46% (P < .01 vs placebo) and primary end point (a composite of cardiovascular mortality, nonfatal myocardial infarction, and resuscitated cardiac arrest) by 35% (P < .05 vs placebo). There were 41%, 54%, and 28% reductions in cardiovascular mortality, hospitalization for heart failure, and myocardial infarction, respectively. Comparison of hazard ratios suggests the presence of a clinical synergy between perindopril and CCB, with a greater effect than addition of individual effects. Addition of perindopril to CCB in stable CAD patients had a significant supplementary impact on cardiac outcomes and mortality.