PRADOC: a trial on the efficiency of a transition care management plan for hospitalized patients with heart failure in France.

AIMS: Transition care programmes are designed to improve coordination of care between hospital and home. For heart failure patients, meta-analyses show a high efficacy but with moderate evidence level. Moreover, difficulties for implementation of such programmes limit their extrapolation. METHODS AND RESULTS: We designed a mixed-method study to assess the implementation of the PRADO-IC, a nationwide transition programme that aims to be offered to every patient with heart failure in France. This programme consists essentially in an administrative assistance to schedule follow-up visits and in a nurse follow-up during 2 to 6 months and aims to reduce the annual heart failure readmission rate by 30%. This study assessed three quantitative aims: the cost to avoid a readmission for heart failure within 1 year (primary aim, intended sample size 404 patients), clinical care pathways, and system economic outcomes; and two qualitative aims: perceived problems and benefits of the PRADO-IC. All analyses will be gathered at the end of study for a joint interpretation. Strengths of this study design are the randomized controlled design, the population included in six centres with low motivation bias, the primary efficiency analysis, the secondary efficacy analyses on care pathway and clinical outcomes, and the joint qualitative analysis. Limits are the heterogeneity of centres and of intervention in a control group and parallel development of other new therapeutic interventions in this field. CONCLUSIONS: The results of this study may help decision-makers to support an administratively managed transition programme.

Long-term outcome of heart transplantation performed after ventricular assist device compared with standard heart transplantation.

BACKGROUND: Data on the long-term outcome of heart transplantation in patients with a ventricular assist device (VAD) are scarce. AIM: To evaluate long-term outcome after heart transplantation in patients with a VAD compared with no mechanical circulatory support. METHODS: Consecutive all-comers who underwent heart transplantation were included at a single high-volume centre from January 2005 until December 2012, with 5 years of follow-up. Clinical and biological characteristics, operative results, outcomes and survival were recorded. Regression analyses were performed to determine predictors of 1-year and 5-year mortality. RESULTS: Fifty-two patients with bridge to transplantation by VAD (VAD group) and 289 patients transplanted without a VAD (standard group) were enrolled. The mean age was 46±11 years in the VAD group compared with 51±13 years in the standard group (P=0.01); 17% of the VAD group and 25% of the standard group were women (P=0.21). Ischaemic time was longer in the VAD group (207±54 vs 169±60minutes; P<0.01). There was no difference in primary graft failure (33% vs 25%; P=0.22) or 1-year mortality (17% vs 28%; P=0.12). In the multivariable analysis, preoperative VAD was an independent protective factor for 1-year mortality (odds ratio 0.40, 95% confidence interval 0.17-0.97; P=0.04). Independent risk factors for 1-year mortality were recipient age>60 years, recipient creatinine, body surface area mismatch and ischaemic time. The VAD and standard groups had similar long-term survival, with 5-year mortality rates of 35% and 40%, respectively (P=0.72). CONCLUSIONS: Bridge to transplantation by VAD was associated with a reduction in 1-year mortality, leading critically ill patients to similar long-term survival compared with patients who underwent standard heart transplantation. This alternative strategy may benefit carefully selected patients.

Low level exercise echocardiography helps diagnose early stage heart failure with preserved ejection fraction: a study of echocardiography versus catheterization.

BACKGROUND: Increased left ventricular end-diastolic pressure (LVEDP) with exercise is an early sign of heart failure with preserved left ventricular ejection fraction (LVEF). The abnormal exercise increase in LVEDP is nonlinear, with most change occurring at low-level exercise. Data on non-invasive approach of this condition are scarce. Our objective was assessing E/e' to estimate low level exercise LVEDP using a direct invasive measurement as the reference method. METHODS AND RESULTS: Sixty patients with LVEF >50 % prospectively underwent both exercise cardiac catheterization and echocardiography. E/e' was measured at rest and during low-level exercise. Abnormal LVEDP was defined as >16 mmHg. Patients with a history of coronary artery disease and/or abnormal LV morphology were classified as having apparent cardiac disease (CD). Thirty-four (57 %) patients had elevated LVEDP only during exercise. Most of the change in LVEDP occurred since the first exercise level (25 W). There was a correlation between LVEDP and septal E/e' at rest and during exercise. Lateral E/e' and E/average e' ratio had worse correlations with LVEDP. In the whole population, exercise septal E/e' at 25 W had the best accuracy for abnormal exercise LVEDP, area under curve (AUC) = 0.79. However, while low-level exercise septal E/e' had a high accuracy in CD patients (n = 26, AUC = 0.96), E/e' was not linked to LVEDP in patients without CD (n = 34). CONCLUSION: Low-level exercise septal E/e' is valuable for predicting abnormal exercise LVEDP in patients with preserved LVEF and apparent CD. However, this new diagnosis approach appears not reliable in patients with normal LV morphology and without coronary artery disease. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov . Unique identifier: NCT01714752.

Effects of the P-Selectin Antagonist Inclacumab on Myocardial Damage After Percutaneous Coronary Intervention According to Timing of Infusion: Insights From the SELECT-ACS Trial.

BACKGROUND: The Effects of the P-Selectin Antagonist Inclacumab on Myocardial Damage After Percutaneous Coronary Intervention for Non-ST-Segment Elevation Myocardial Infarction (SELECT-ACS) trial suggested beneficial effects of inclacumab, a monoclonal antibody directed against P-selectin, on periprocedural myocardial damage. This study evaluated the effect of inclacumab on myocardial damage according to varying time intervals between study drug infusion and percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients (n=544) enrolled in the SELECT-ACS trial and randomized to receive 1 infusion of placebo or inclacumab (5 or 20 mg/kg, administered between 1 and 24 hours before PCI) were divided according to the time interval between study drug infusion and PCI. The primary end point was the change in troponin I from baseline at 16 and 24 hours after PCI. In patients receiving inclacumab 20 mg/kg with a short (less than median) time interval between infusion and PCI, placebo-adjusted geometric mean percent changes in troponin I, creatine kinase-myocardial band, and peak troponin I at 24 hours were -45.6% (P=0.005), -30.7% (P=0.01), and -37.3% (P=0.02), respectively. No significant changes were observed in patients with a long (greater than median) time interval between infusion and PCI. Placebo-adjusted geometric mean percent changes in troponin I and creatine kinase-myocardial band were -43.5% (P=0.02) and -26.0% (P=0.07), respectively, when inclacumab 20 mg/kg was administered between 1 and 3 hours before PCI, whereas the drug had no effect with longer intervals. CONCLUSIONS: Inclacumab 20 mg/kg significantly reduces myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction, and benefits are larger when the infusion is administered <3 hours before PCI. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01327183.

Primary percutaneous coronary intervention for ST elevation myocardial infarction in nonagenarians.

OBJECTIVE: To assess outcomes following primary percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction (STEMI) in nonagenarian patients. METHODS: We conducted a multicentre retrospective study between 2006 and 2013 in five international high-volume centres and included consecutive all-comer nonagenarians treated with primary PCI for STEMI. There were no exclusion criteria. We enrolled 145 patients and collected demographic, clinical and procedural data. Severe clinical events and mortality at 6 months and 1 year were assessed. RESULTS: Cardiogenic shock was present at admission in 21%. Median (IQR) delay between symptom onset and balloon was 3.7 (2.4-5.6) hours and 60% of procedures were performed through the transradial approach. Successful revascularisation of the culprit vessel was obtained in 86% of the cases (thrombolysis in myocardial infarction flow of 2 or 3). Major or clinically relevant bleeding was observed in 4% of patients. Median left ventricular ejection fraction post PCI was 41.5% (32.0-50.0). The in-hospital mortality was 24%, with 6 months and 1-year survival rates of 61% and 53%, respectively. CONCLUSIONS: In our study, primary PCI in nonagenarians with STEMI was achieved and feasible through a transradial approach. It is associated with a high rate of reperfusion of the infarct-related artery and 53% survival at 1 year. These results suggest that primary PCI may be offered in selected nonagenarians with acute myocardial infarction.

Sex-related differences after contemporary primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

BACKGROUND: Whether outcomes differ for women and men after percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) remains controversial. AIM: To compare 1-year outcomes after primary PCI in women and men with STEMI, matched for age and diabetes. METHODS: Consecutive women with STEMI of<24 hours' duration referred (August 2007 to January 2011) for primary PCI were compared with men matched for age and diabetes. Rates of all-cause mortality, target vessel revascularization (TVR) and major cardiovascular and cerebrovascular events (MACCE) (death/myocardial infarction/stroke) were assessed at 1 year. RESULTS: Among 775 consecutive patients, 182 (23.5%) women were compared with 182 matched men. Mean age was 69±15 years, 18% had diabetes. Patient characteristics were similar, except for lower creatinine clearance (73±41 vs 82±38 µmol/L; P=0.041), more cardiogenic shock (14.8% vs 6.6%; P=0.017) and less radial PCI (81.3% vs 90.1%; P=0.024) in women. Rates of 1-year death (22.7% vs 18.1%), TVR (8.3% vs 6.0%) and MACCE (24.3% vs 20.9%) were not statistically different in women (P>0.05 for all). After exclusion of patients with shock (10.7%) and out-of-hospital cardiac arrest (6.6%), death rates were even more similar (11.3% vs 11.8%; P=0.10). Female sex was not independently associated with death (odds ratio 1.01, 95% confidence interval 0.55-1.87; P=0.97). CONCLUSION: In our consecutive unselected patient population, women had similar 1-year outcomes to men matched for age and diabetes, after contemporary primary PCI for STEMI, despite having a higher risk profile at baseline.

Outcomes of primary percutaneous coronary interventions in nonagenarians with acute myocardial infarction.

BACKGROUND: Few data are available on primary percutaneous coronary intervention (pPCI) in nonagenarians. In a large prospective registry on pPCI for STEMI we compared the demographics, procedural and in-hospital outcomes between nonagenarians (age ≥ 90 years) and patients aged < 90 years. METHODS AND RESULTS: We included 26,157 consecutive patients with pPCI in the Greater Paris Area region between 2003 and 2011. Of these, 418 (1.6%) were ≥ 90 years old. Nonagenarians (versus patients < 90 years) were more likely to be female (62.3% versus 22.5%, p < 0.0001), nonsmokers (81.6% versus 36.7%, p < 0.0001), in cardiogenic shock (Killip IV) upon admission (10.5% versus 4.8%, p < 0.001), and had significant co-morbidities. Over two-thirds of patients underwent procedures via the radial artery (61% versus 72.1%, p = 0.007). Both groups had high and similar angiographic success rates (98.1% versus 98.7%, p = 0.33). Drug-eluting stents were used less often in nonagenarians (4.4% versus 16.7%, p < 0.0001). Hospital mortality was significantly much higher in patients over 90 years old (24.9% versus 5.1%, p < 0.001) in univariate analysis. After adjustment for sex, cardiogenic shock, diabetes, triple vessel disease, drug-eluting stent use and glycoprotein IIb/IIIa inhibitors use, mortality remains higher in nonagenarian patients (OR: 4.31; 95% CI: 3.26-5.71, p < 0.0001). CONCLUSIONS: In a real-world setting, we found important demographic differences in nonagenarian compared to younger patients. Despite achieving a high rate of reperfusion with pPCI using mainly radial access, similar to that achieved in younger patients, hospital mortality was higher in nonagenarians.

Intra-aortic balloon pump effects on macrocirculation and microcirculation in cardiogenic shock patients supported by venoarterial extracorporeal membrane oxygenation*.

OBJECTIVES: This study was designed to assess the effects on macrocirculation and microcirculation of adding an intra-aortic balloon pump to peripheral venoarterial extracorporeal membrane oxygenation in patients with severe cardiogenic shock and little/no residual left ventricular ejection. DESIGN: A prospective, single-center, observational study where macrocirculation and microcirculation were assessed with clinical-, Doppler echocardiography-, and pulmonary artery-derived hemodynamic variables and also cerebral and thenar eminence tissue oxygenation and side-stream dark-field imaging of sublingual microcirculation. SETTING: A 26-bed tertiary ICU in a university hospital. PATIENTS: We evaluated 12 consecutive patients before and 30 minutes after interrupting and restarting intra-aortic balloon pump. INTERVENTIONS: Measurements were performed before, and 30 minutes after interrupting and restarting intra-aortic balloon pump. MEASUREMENTS AND MAIN RESULTS: Stopping intra-aortic balloon pump was associated with higher pulmonary artery-occlusion pressure (19 ± 10 vs 15 ± 8 mm Hg, p = 0.01), increased left ventricular end-systolic (51 ± 13 vs 50 ± 14 mm, p = 0.05) and end-diastolic (55 ± 13 vs 52 ± 14 mm, p = 0.003) dimensions, and decreased pulse pressure (15 ± 13 vs 29 ± 22 mm Hg, p = 0.02). Maximum pulmonary artery-occlusion pressure reduction when the intra-aortic balloon pump was restarted was observed in the seven patients whose pulmonary artery-occlusion pressure was more than 15 mm Hg when intra-aortic balloon pump was off (-6.6 ± 4.3 vs -0.6 ± 3.4 mm Hg, respectively). Thenar eminence and brain tissue oxygenation and side-stream dark-field-assessed sublingual microcirculation were unchanged by stopping and restarting intra-aortic balloon pump. CONCLUSIONS: Restoring pulsatility and decreasing left ventricular afterload with intra-aortic balloon pump was associated with smaller left ventricular dimensions and lower pulmonary artery pressures but did not affect microcirculation variables in cardiogenic shock patients with little/no residual left ventricular ejection while on peripheral venoarterial extracorporeal membrane oxygenation.

Effects of the P-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention for non-ST-segment elevation myocardial infarction: results of the SELECT-ACS trial.

OBJECTIVES: The study aimed to evaluate inclacumab for the reduction of myocardial damage during a percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction. BACKGROUND: P-selectin is an adhesion molecule involved in interactions between endothelial cells, platelets, and leukocytes. Inclacumab is a recombinant monoclonal antibody against P-selectin, with potential anti-inflammatory, antithrombotic, and antiatherogenic properties. METHODS: Patients (N = 544) with non-ST-segment elevation myocardial infarction scheduled for coronary angiography and possible ad hoc PCI were randomized to receive 1 pre-procedural infusion of inclacumab 5 or 20 mg/kg or placebo. The primary endpoint, evaluated in patients who underwent PCI, received study medication, and had available efficacy data (n = 322), was the change in troponin I from baseline at 16 and 24 h after PCI. RESULTS: There was no effect of inclacumab 5 mg/kg. Placebo-adjusted geometric mean percent changes in troponin I with inclacumab 20 mg/kg were -24.4% at 24 h (p = 0.05) and -22.4% at 16 h (p = 0.07). Peak troponin I was reduced by 23.8% (p = 0.05) and area under the curve over 24 h by 33.9% (p = 0.08). Creatine kinase-myocardial band yielded similar results, with changes of -17.4% at 24 h (p = 0.06) and -16.3% at 16 h (p = 0.09). The incidence of creatine kinase-myocardial band increases >3 times the upper limit of normal within 24 h was 18.3% and 8.9% in the placebo and inclacumab 20-mg/kg groups, respectively (p = 0.05). Placebo-adjusted changes in soluble P-selectin level were -9.5% (p = 0.25) and -22.0% (p < 0.01) with inclacumab 5 and 20 mg/kg. There was no significant difference in adverse events between groups. CONCLUSIONS: Inclacumab appears to reduce myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction. (A Study of RO4905417 in Patients With Non ST-Elevation Myocardial Infarction [Non-STEMI] Undergoing Percutaneous Coronary Intervention; NCT01327183).

24-hour time-dependent aspirin efficacy in patients with stable coronary artery disease.

Aspirin-induced cyclooxygenase (COX)-1 acetylation is irreversible and it is assumed that the platelet thromboxane-A2 aggregation pathway is inhibited for at least 24 hours (h) after aspirin ingestion. However, time course of biological efficacy of daily low-dose aspirin has rarely been assessed in patients with coronary artery disease (CAD). We aimed to assess the 24-h biological efficacy of daily low-dose aspirin in CAD patients. The peak and trough (2 h-24 h) effect of a chronic treatment with once daily dose aspirin were studied in 150 consecutive stable CAD patients. The main outcome measure was light transmission aggregometry (LTA) triggered with 0.5 mg/ml arachidonic acid (AA). In the last 47 consecutive patients, additional tests were conducted at 6, 12, 16, 20 h after last aspirin administration. 4.7% of the patients had significant aggregation (>20% maximal intensity LTA-AA) 2 h after aspirin ingestion and 24.7% at 24 h (p<0.0001). The more precise assessments in the last 47 patients showed that significant platelet aggregation progressively reappeared with time after aspirin intake (2 h--4% of patients, 6 h-- 4%, 12 h--11%, 16 h--16%, 20 h--19% and 24 h--28%). Concordant results were observed using production of thromboxane-B2 and other techniques evaluating AA-induced platelet aggregation/activation. No significant differences were found between lower (75-100 mg/day) and higher (>100 mg/day) dose aspirin. Such aspirin «resistance¼ at 24 h after ingestion was related to biological inflammatory markers, current smoking and diabetes. In conclusion, once daily aspirin does not provide stable 24-h antiplatelet protection in a significant proportion of CAD patients. Any biological assessment of aspirin efficacy should take time since last aspirin intake into consideration.