Pascal Leprince

Registry of transcatheter aortic-valve implantation in high-risk patients

BACKGROUND Transcatheter aortic-valve implantation (TAVI) is an emerging intervention for the treatment of high-risk patients with severe aortic stenosis and coexisting illnesses. We report the results of a prospective multicenter study of the French national transcatheter aortic-valve implantation registry, FRANCE 2. METHODS All TAVIs performed in France, as listed in the FRANCE 2 registry, were prospectively included in the study. The primary end point was death from any cause. RESULTS A total of 3195 patients were enrolled between January 2010 and October 2011 at 34 centers. The mean (±SD) age was 82.7±7.2 years; 49% of the patients were women. All patients were highly symptomatic and were at high surgical risk for aortic-valve replacement. Edwards SAPIEN and Medtronic CoreValve devices were implanted in 66.9% and 33.1% of patients, respectively. Approaches were either transarterial (transfemoral, 74.6%; subclavian, 5.8%; and other, 1.8%) or transapical (17.8%). The procedural success rate was 96.9%. Rates of death at 30 days and 1 year were 9.7% and 24.0%, respectively. At 1 year, the incidence of stroke was 4.1%, and the incidence of periprosthetic aortic regurgitation was 64.5%. In a multivariate model, a higher logistic risk score on the European System for Cardiac Operative Risk Evaluation (EuroSCORE), New York Heart Association functional class III or IV symptoms, the use of a transapical TAVI approach, and a higher amount of periprosthetic regurgitation were significantly associated with reduced survival. CONCLUSIONS This prospective registry study reflected real-life TAVI experience in high-risk elderly patients with aortic stenosis, in whom TAVI appeared to be a reasonable option. (Funded by Edwards Lifesciences and Medtronic.).

Pacemaker infective endocarditis

We identified 33 patients with definite pacemaker endocarditis--that is, with direct evidence of infective endocarditis, based on surgery or autopsy histologic findings of or bacteriologic findings (Gram stain or culture) of valvular vegetation or electrode-tip wire vegetation. Most of the patients (75%) were > or = 60 years of age (mean 66 +/- 3; range 21 to 86). Pouch hematoma or inflammation was common (58%), but other predisposing factors for endocarditis were rare. At the time that pacemaker endocarditis was found, the mean number of leads was 2.4 +/- 1.1 (range 1 to 7). The interval from the last procedure to diagnosis of endocarditis was 20 +/- 4 months (range 1 to 72). Endocarditis appeared after pacemaker implantation, early (< 3 months) in 10 patients and late (> or = 3 months) in 23 patients. Fever was the most common symptom, being isolated in 36%, associated with a poor general condition in 24%, and associated with septic shock in 9%. Transthoracic echocardiography showed vegetations in only 2 of 9 patients. Transesophageal echocardiography demonstrated the presence of lead vegetations (n = 20) or tricuspid vegetations (n = 3) in 23 of 24 patients (96%; p <0.0001 compared with transthoracic echocardiography). Pulmonary scintigraphy showed a typical pulmonary embolization in 7 of 17 patients (41%). Pathogens were mainly isolated from blood (82%) and lead (91%) cultures. The major pathogens causing pacemaker endocarditis were Staphylococcus epidermidis (n = 17) and S. aureus (n = 7). S. epidermidis was found more often in early than in late endocarditis (90% vs 50%; p = 0.05). All patients were treated with prolonged antibiotic regimens before and after electrode removal. Electrode removal was achieved by surgery (n = 29) or traction (n = 4). Associated procedures were performed in 9 patients. After the intensive care period, only 17 patients needed a new permanent pacemaker. Overall mortality was 24% after a mean follow-up period of 22 +/- 4 months (range 1 to 88). Eight patients who were significantly older (74 +/- 3 vs 63 +/- 3 years; p = 0.05) died < or = 2 months after electrode removal, whereas 25 were alive and asymptomatic.

Extracorporeal life support following out-of-hospital refractory cardiac arrest

IntroductionExtracorporeal life support (ECLS) has recently shown encouraging results in the resuscitation of in-hospital (IH) refractory cardiac arrest. We assessed the use of ECLS following out-of-hospital (OH) refractory cardiac arrest.MethodsWe evaluated 51 consecutive patients who experienced witnessed OH refractory cardiac arrest and received automated chest compression and ECLS upon arrival in the hospital. Patients with preexisting severe hypothermia who experienced IH cardiac arrest were excluded. A femorofemoral ECLS was set up on admission to the hospital by a mobile cardiothoracic surgical team.ResultsFifty-one patients were included (mean age, 42 ± 15 years). The median delays from cardiac arrest to cardiopulmonary resuscitation and ECLS were, respectively, 3 minutes (25th to 75th interquartile range, 1 to 7) and 120 minutes (25th to 75th interquartile range, 102-149). Initial rhythm was ventricular fibrillation in 32 patients (63%), asystole in 15 patients (29%) patients and pulseless rhythm in 4 patients (8%). ECLS failed in 9 patients (18%). Only two patients (4%) (95% confidence interval, 1% to 13%) were alive at day 28 with a favourable neurological outcome. There was a significant correlation (r = 0.36, P = 0.01) between blood lactate and delay between cardiac arrest and onset of ECLS, but not with arterial pH or blood potassium level. Deaths were the consequence of multiorgan failure (n = 43; 47%), brain death (n = 10; 20%) and refractory hemorrhagic shock (n = 7; 14%), and most patients (n = 46; 90%) died within 48 hours.ConclusionsThis poor outcome suggests that the use of ECLS should be more restricted following OH refractory cardiac arrest.

Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines

AIMS Recent studies have reported a relationship between the abundance of epicardial adipose tissue (EAT) and the risk of cardiovascular diseases including atrial fibrillation (AF). However, the underlying mechanisms are unknown. The aim of this study was to examine the effects of the secretome of human EAT on the histological properties of the myocardium. METHODS AND RESULTS Samples of EAT and subcutaneous adipose (SAT), obtained from 39 patients undergoing coronary bypass surgery, were analysed and tested in an organo-culture model of rat atria to evaluate the fibrotic properties of human fat depots. The EAT secretome induced global fibrosis (interstitial and peripheral) of rat atria in organo-culture conditions. Activin A was highly expressed in EAT compared with SAT and promoted atrial fibrosis, an effect blocked using neutralizing antibody. In addition, Activin A levels were enhanced in patients with low left-ventricular function. In sections of human atrial and ventricular myocardium, adipose and myocardial tissues were in close contact, together with fibrosis. CONCLUSION This study provides the first evidence that the secretome from EAT promotes myocardial fibrosis through the secretion of adipo-fibrokines such as Activin A.

Low Molecular Weight Heparin After Mechanical Heart Valve Replacement

BACKGROUND Patients with mechanical heart valves require life-long anticoagulation. We report here the first large and comparative series of consecutive patients anticoagulated with low molecular weight heparin (LMWH) after mechanical heart valve replacement. METHODS AND RESULTS In this comparative, nonrandomized study, 208 consecutive patients who underwent a single or double heart valve replacement with mechanical prostheses were anticoagulated subcutaneously with unfractionated heparin (UH) in the first period (n=106) and LMWH in the second phase (n=102) of the study. Baseline characteristics were similar in the 2 groups. The mean durations of UH and LMWH treatments were 13.6+/-0.5 and 14.1+/-0.6 days, respectively (not significant). On the second day of treatment, 87% of patients treated with LMWH had an anti-Xa activity within the range of efficacy (0.5 to 1 IU/mL), but only 9% of UH-treated patients had an activated partial-thromboplastin time value within the therapeutic range (1.5 to 2.5 times control, P<0.0001 between the 2 groups). On the last day of prescription, all LMWH-treated patients had anti-Xa activity above 0.5 IU/mL, but 19% were above 1 IU/mL. In the UH group, 27% of patients had an activated partial-thromboplastin time above 1.5 times control, but 62% were overanticoagulated. Two major bleedings occurred in each group, and one stroke occurred in the UH group. CONCLUSIONS In this first comparative study, anticoagulation with LMWHs after mechanical heart valve replacement appears feasible, provides adequate biological anticoagulation, and compares favorably with UH anticoagulation. Randomized studies are now needed to further evaluate this new therapeutic approach.

Emergency circulatory support in refractory cardiogenic shock patients in remote institutions: a pilot study (the cardiac-RESCUE program)

AIMS Temporary circulatory support with extracorporeal membrane oxygenation (ECMO) is often the only alternative for supporting patients with refractory cardiogenic shock (RCS). In practice, this strategy is limited to a small minority of patients hospitalized in tertiary-care centres with ECMO programs. The cardiac-RESCUE program was designed to test the feasibility of providing circulatory support distant from specialized ECMO centres, for RCS patients in remote locations. METHODS AND RESULTS From January 2005 to December 2009, hospitals without ECMO facilities throughout the Greater Paris area were invited to participate. One hundred and four RCS cases were assessed and 87 consecutively eligible patients (mean age 46 ± 15 years, 41% following cardiac arrest) had ECMO support instituted locally and were enrolled into the program. Local initiation of ECMO support allowed successful transfer to the tertiary-care centre in 75 patients. Of these, 32 patients survived to hospital discharge [overall survival rate 36.8%, 95% confidence interval (CI) 27.4-46.2]. Independent predictors for in-hospital mortality included initiation of ECMO during cardiopulmonary resuscitation [hazard ratio (HR) = 4.81, 95% CI 2.25-10.30, P < 0.001] and oligo-anuria (HR = 2.48, 95% CI 1.29-4.76, P = 0.006). After adjusting for other confounding factors, in-hospital mortality was not statistically different from that of 123 consecutive patients who received ECMO at our institution during the same period (odds ratio 1.48, 95% CI 0.72-3.00, P = 0.29). CONCLUSION Offering local ECMO support appears feasible in a majority of RCS patients hospitalized in remote hospitals. In this otherwise lethal situation, our pilot experience suggests that over one-third of such patients can survive to hospital discharge.

Early Percutaneous Tracheotomy Versus Prolonged Intubation of Mechanically Ventilated Patients After Cardiac Surgery: A Randomized Trial

BACKGROUND Whether early percutaneous tracheotomy in patients who require prolonged mechanical ventilation can shorten mechanical ventilation duration and lower mortality remains controversial. OBJECTIVE To compare the outcomes of severely ill patients who require prolonged mechanical ventilation randomly assigned to early percutaneous tracheotomy or prolonged intubation. DESIGN Prospective, randomized, controlled, single-center trial (ClinicalTrials.gov registration number: NCT00347321). SETTING Academic center. PATIENTS 216 adults requiring mechanical ventilation 4 or more days after cardiac surgery. INTERVENTION Immediate early percutaneous tracheotomy or prolonged intubation with tracheotomy 15 days after randomization. MEASUREMENTS The primary end point was the number of ventilator-free days during the first 60 days after randomization. Secondary outcomes included 28-, 60-, or 90-day mortality rates; durations of mechanical ventilation, intensive care unit stay, and hospitalization; sedative, analgesic, and neuroleptic use; ventilator-associated pneumonia rate; unscheduled extubations; comfort and ease of care; and long-term health-related quality of life (HRQoL) and psychosocial evaluations. RESULTS There was no difference in ventilator-free days during the first 60 days after randomization between early percutaneous tracheotomy and prolonged intubation groups (mean, 30.4 days [SD, 22.4] vs. 28.3 days [SD, 23.7], respectively; absolute difference, 2.1 days [95% CI, -4.1 to 8.3 days]) nor in 28-, 60-, or 90-day mortality rates (16% vs. 21%, 26% vs. 28%, and 30% vs. 30%, respectively). The durations of mechanical ventilation and hospitalization, as well as frequencies of ventilator-associated pneumonia and other severe infections, were also similar. However, early percutaneous tracheotomy was associated with less intravenous sedation; less time of heavy sedation; less haloperidol use for agitation, delirium, or both; fewer unscheduled extubations; better comfort and ease of care; and earlier resumption of oral nutrition. After a median follow-up of 873 days, between-group survival, psychosocial evaluations, and HRQoL were similar. LIMITATION The prolonged intubation group had more ventilator-free days during days 1 to 60 than what was hypothesized (mean, 23.0 days [SD, 17.0]). CONCLUSION Early tracheotomy provided no benefit in terms of mechanical ventilation and length of hospital stay, rates of mortality or infectious complications, and long-term HRQoL for patients who require prolonged mechanical ventilation after cardiac surgery. However, the well-tolerated procedure was associated with less sedation, better comfort, and earlier resumption of autonomy. PRIMARY FUNDING SOURCE French Ministry of Health.

Report from a consensus conference on primary graft dysfunction after cardiac transplantation

Although primary graft dysfunction (PGD) is fairly common early after cardiac transplant, standardized schemes for diagnosis and treatment remain contentious. Most major cardiac transplant centers use different definitions and parameters of cardiac function. Thus, there is difficulty comparing published reports and no agreed protocol for management. A consensus conference was organized to better define, diagnose, and manage PGD. There were 71 participants (transplant cardiologists, surgeons, immunologists and pathologists), with vast clinical and published experience in PGD, representing 42 heart transplant centers worldwide. State-of-the-art PGD presentations occurred with subsequent breakout sessions planned in an attempt to reach consensus on various issues. Graft dysfunction will be classified into primary graft dysfunction (PGD) or secondary graft dysfunction where there is a discernible cause such as hyperacute rejection, pulmonary hypertension, or surgical complications. PGD must be diagnosed within 24 hours of completion of surgery. PGD is divided into PGD-left ventricle and PGD-right ventricle. PGD-left ventricle is categorized into mild, moderate, or severe grades depending on the level of cardiac function and the extent of inotrope and mechanical support required. Agreed risk factors for PGD include donor, recipient, and surgical procedural factors. Recommended management involves minimization of risk factors, gradual increase of inotropes, and use of mechanical circulatory support as needed. Retransplantation may be indicated if risk factors are minimal. With a standardized definition of PGD, there will be more consistent recognition of this phenomenon and treatment modalities will be more comparable. This should lead to better understanding of PGD and prevention/minimization of its adverse outcomes.

Postprocedural Aortic Regurgitation in Balloon-Expandable and Self-Expandable Transcatheter Aortic Valve Replacement Procedures Analysis of Predictors and Impact on Long-Term Mortality: Insights From the FRANCE2 Registry

Background— Significant postprocedural aortic regurgitation (AR) is observed in 10% to 20% of cases after transcatheter aortic valve replacement (TAVR). The prognostic value and the predictors of such a complication in balloon-expandable (BE) and self-expandable (SE) TAVR remain unclear. Methods and Results— TAVR was performed in 3195 consecutive patients at 34 hospitals. Postprocedural transthoracic echocardiography was performed in 2769 (92%) patients of the eligible population, and these patients constituted the study group. Median follow-up was 306 days (Q1–Q3=178–490). BE and SE devices were implanted in 67.6% (n=1872) and 32.4% (n=897). Delivery was femoral (75.3%) or nonfemoral (24.7%). A postprocedural AR≥grade 2 was observed in 15.8% and was more frequent in SE (21.5%) than in BE-TAVR (13.0%, P=0.0001). Extensive multivariable analysis confirmed that the use of a SE device was one of the most powerful independent predictors of postprocedural AR≥grade 2. For BE-TAVR, 8 independent predictors of postprocedural AR≥grade 2 were identified including femoral delivery (P=0.04), larger aortic annulus (P=0.0004), and smaller prosthesis diameter (P=0.0001). For SE-TAVR, 2 independent predictors were identified including femoral delivery(P=0.0001). Aortic annulus and prosthesis diameter were not predictors of postprocedural AR for SE-TAVR. A postprocedural AR≥grade 2, but not a postprocedural AR=grade 1, was a strong independent predictor of 1-year mortality for BE (hazard ratio=2.50; P=0.0001) and SE-TAVR (hazard ratio=2.11; P=0.0001). Although postprocedural AR≥grade 2 was well tolerated in patients with AR≥grade 2 at baseline (1-year mortality=7%), it was associated with a very high mortality in other subgroups: renal failure (43%), AR<grade 2 at baseline (31%), low transaortic gradient (35%), or nonfemoral delivery (45%). Conclusions— Postprocedural AR≥grade 2 was observed in 15.8% of successful TAVR and was the strongest independent predictor of 1-year mortality. The use of the SE device was a powerful independent predictor of postprocedural AR≥grade 2.Background— Significant postprocedural aortic regurgitation (AR) is observed in 10% to 20% of cases after transcatheter aortic valve replacement (TAVR). The prognostic value and the predictors of such a complication in balloon-expandable (BE) and self-expandable (SE) TAVR remain unclear. Methods and Results— TAVR was performed in 3195 consecutive patients at 34 hospitals. Postprocedural transthoracic echocardiography was performed in 2769 (92%) patients of the eligible population, and these patients constituted the study group. Median follow-up was 306 days (Q1–Q3=178–490). BE and SE devices were implanted in 67.6% (n=1872) and 32.4% (n=897). Delivery was femoral (75.3%) or nonfemoral (24.7%). A postprocedural AR≥grade 2 was observed in 15.8% and was more frequent in SE (21.5%) than in BE-TAVR (13.0%, P =0.0001). Extensive multivariable analysis confirmed that the use of a SE device was one of the most powerful independent predictors of postprocedural AR≥grade 2. For BE-TAVR, 8 independent predictors of postprocedural AR≥grade 2 were identified including femoral delivery ( P =0.04), larger aortic annulus ( P =0.0004), and smaller prosthesis diameter ( P =0.0001). For SE-TAVR, 2 independent predictors were identified including femoral delivery( P =0.0001). Aortic annulus and prosthesis diameter were not predictors of postprocedural AR for SE-TAVR. A postprocedural AR≥grade 2, but not a postprocedural AR=grade 1, was a strong independent predictor of 1-year mortality for BE (hazard ratio=2.50; P =0.0001) and SE-TAVR (hazard ratio=2.11; P =0.0001). Although postprocedural AR≥grade 2 was well tolerated in patients with AR≥grade 2 at baseline (1-year mortality=7%), it was associated with a very high mortality in other subgroups: renal failure (43%), AR<grade 2 at baseline (31%), low transaortic gradient (35%), or nonfemoral delivery (45%). Conclusions— Postprocedural AR≥grade 2 was observed in 15.8% of successful TAVR and was the strongest independent predictor of 1-year mortality. The use of the SE device was a powerful independent predictor of postprocedural AR≥grade 2. # CLINICAL PERSPECTIVE {#article-title-26}

Venoarterial extracorporeal membrane oxygenation support for refractory cardiovascular dysfunction during severe bacterial septic shock.

Objectives:Profound myocardial depression can occur during severe septic shock. Although good outcomes of venoarterial extracorporeal membrane oxygenation–treated children with refractory septic shock have been reported, little is known about adults’ outcomes. This study was designed to assess the outcomes and long-term health-related quality-of-life of patients supported by venoarterial extracorporeal membrane oxygenation for refractory cardiac and hemodynamic failure during severe septic shock. Design:A retrospective, single-center, observational study and a cross-sectional survey to assess health-related quality of life by the Short Form-36 questionnaire and frequencies of anxiety, depression and posttraumatic stress disorder symptoms by the Hospital Anxiety and Depression Scale and the Impact of Event Scale, respectively. Setting:A 26-bed tertiary intensive care unit in a university hospital. Patients:We evaluated the outcomes of patients who received venoarterial extracorporeal membrane oxygenation rescue therapy for refractory cardiovascular failure during bacterial septic shock. Results are expressed as medians (range). Measurements and Main Results:From January 2008 to September 2011, 14 patients, 45 years old (28–66), seven males, none with a history of left ventricular dysfunction, received venoarterial extracorporeal membrane oxygenation for septic shock refractory to conventional treatment, 24 hours (3–108) after shock onset. All exhibited severe myocardial dysfunction at extracorporeal membrane oxygenation implantation. Left ventricular ejection fraction was 16% (10% to 30%), cardiac index was 1.3 L/min/m2 (0.7–2.2 ) and systemic resistance vascular index was 3162 (2047–7685). All were receiving high-dose catecholamines and had signs of multiple organ failure: pH 7.16 (6.68–7.39), blood lactate 9 (2–17) mmol/L, PaO2/FIO2 87 (28–364), Simplified Acute Physiology Score III 84 (75–106) and Sepsis-Related Organ Failure Assessment score 18 (8–21). Twelve patients (86%) could be weaned off venoarterial extracorporeal membrane oxygenation after 5.5 days (2–12) days of support and 10 patients (71%) were discharged to home and were alive after a median follow-up of 13 months (3–43). All 10 survivors had normal left ventricular ejection fraction and reported good health-related quality of life at long-term follow-up. Conclusions:Venoarterial extracorporeal membrane oxygenation rescued more than 70% of the patients who developed refractory cardiovascular dysfunction during severe bacterial septic shock. Survivors reported good long-term quality of life. Venoarterial extracorporeal membrane oxygenation might represent a valuable therapeutic option for adults in severe septic shock with refractory cardiac and hemodynamic failure.