Sex Differences in Outcomes of Tetralogy of Fallot Patients With Implantable Cardioverter-Defibrillators.

BACKGROUND: Women with congenital heart disease at high risk for sudden cardiac death have been poorly studied thus far. OBJECTIVES: The aim of this study was to assess sex-related differences in patients with tetralogy of Fallot (TOF) and implantable cardioverter-defibrillators (ICDs). METHODS: Data were analyzed from the DAI-T4F (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator) cohort study, which has prospectively enrolled all patients with TOF with ICDs in France since 2010. Clinical events were centrally adjudicated by a blinded committee. RESULTS: A total of 165 patients (mean age 42.2 ± 13.3 years) were enrolled from 40 centers, including 49 women (29.7%). Among the 9,692 patients with TOF recorded in the national database, the proportion of women with ICDs was estimated to be 1.1% (95% CI: 0.8%-1.5%) vs 2.2% (95% CI: 1.8%-2.6%) in men (P < 0.001). The clinical profiles of patients at implantation, including the number of risk factors for ventricular arrhythmias, were similar between women and men. During a median follow-up period of 6.8 years (IQR: 2.5-11.4 years), 78 patients (47.3%) received at least 1 appropriate ICD therapy, without significant difference in annual incidences between women (12.1%) and men (9.9%) (HR: 1.22; 95% CI: 0.76-1.97; P = 0.40). The risk for overall ICD-related complications was similar in women and men (HR: 1.33; 95% CI: 0.81-2.19; P = 0.30), with 24 women (49.0%) experiencing at least 1 complication. CONCLUSIONS: Our findings suggest that women with TOF at high risk for sudden cardiac death have similar benefit/risk balance from ICD therapy compared with men. Whether ICD therapy is equally offered to at-risk women vs men warrants further evaluation in TOF as well as in other congenital heart disease populations. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574).

Impact of Pulmonary Valve Replacement on Ventricular Arrhythmias in Patients With Tetralogy of Fallot and Implantable Cardioverter-Defibrillator.

OBJECTIVES: This study aimed to assess the impact of pulmonary valve replacement (PVR) on ventricular arrhythmias burden in a population of tetralogy of Fallot (TOF) patients with continuous cardiac monitoring by implantable cardioverter-defibrillators (ICDs). BACKGROUND: Sudden cardiac death is a major cause of death in TOF, and right ventricular overload is commonly considered to be a potential trigger for ventricular arrhythmias. METHODS: Data were analyzed from a nationwide French ongoing study (DAI-T4F) including all TOF patients with an ICD since 2000. Survival data with recurrent events were used to compare the burden of appropriate ICD therapies before and after PVR in patients who underwent PVR over the study period. RESULTS: A total of 165 patients (mean age 42.2 ± 13.3 years, 70.1% male) were included from 40 centers. Over a median follow-up period of 6.8 (interquartile range: 2.5 to 11.4) years, 26 patients (15.8%) underwent PVR. Among those patients, 18 (69.2%) experienced at least 1 appropriate ICD therapy. When considering all ICD therapies delivered before (n = 62) and after (n = 16) PVR, the burden of appropriate ICD therapies was significantly lower after PVR (HR: 0.21; 95% confidence interval [CI]: 0.08 to 0.56; p = 0.002). Respective appropriate ICD therapies rates per 100 person-years were 44.0 (95% CI: 35.7 to 52.5) before and 13.2 (95% CI: 7.7 to 20.5) after PVR (p < 0.001). In the overall cohort, PVR before ICD implantation was also independently associated with a lower risk of appropriate ICD therapy in primary prevention patients (HR: 0.29 [95% CI: 0.10 to 0.89]; p = 0.031). CONCLUSIONS: In this cohort of high-risk TOF patients implanted with an ICD, the burden of appropriate ICD therapies was significantly reduced after PVR. While optimal indications and timing for PVR are debated, these findings suggest the importance of considering ventricular arrhythmias in the overall decision-making process. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574).

Quality of life of adult Fontan patients.

BACKGROUND: Progress in the management of complex congenital heart disease (CHD) led to an improvement in survival rates of adults with a Fontan-like circulation. The objective of this study was to assess the subjective health status and quality of life of this population. METHODS AND RESULTS: Patients aged more than 18 years at the time of the study, who underwent a Fontan-like procedure. Subjective health status was assessed by the SF-36 questionnaire and a linear analog scale was used to score patients' self-perception of their quality of life; cardiac and demographic parameters were collected. RESULTS: Among 65 eligible patients, 60 (23 females; mean ± SD age: 25.7 ± 7.2 years) answered the SF-36 questionnaire and 46 of these were interviewed to evaluate their perceived quality of life. Among them, 20 (33.3%) were working full-time and 21 (35%) experienced arrhythmias. The physical SF-36 scores were lower in patients than in the general population (p ≤ 0.05). The New York Hear Association (NYHA) class and occupation were correlated with SF-36 scores of physical activity (respectively, p = 0.0001 and p = 0.025). SF-36 scores of psychological status were associated with the number of drugs and occupation (respectively, p = 0.0001 and p = 0.02). The mean ± SD quality of life score measured using a linear analog scale was 7.02 ± 1.6 and was linked to education and occupation (p ≤ 0.05) but not with cardiac parameters. CONCLUSION: Adult Fontan patients perceive an impaired physical health but report a good overall quality of life. Education and occupation impacts significantly on Fontan patients' quality of life.

Long-Term Follow-Up of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator: The DAI-T4F Nationwide Registry.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the implantable cardioverter defibrillator (ICD) in this patient population remain scarce. METHODS: A Nationwide French Registry including all patients with tetralogy of Fallot with an ICD was initiated in 2010 by the French Institute of Health and Medical Research. The primary time to event end point was the time from ICD implantation to first appropriate ICD therapy. Secondary outcomes included ICD-related complications, heart transplantation, and death. Clinical events were centrally adjudicated by a blinded committee. RESULTS: A total of 165 patients (mean age, 42.2±13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (interquartile range) follow-up of 6.8 (2.5-11.4) years, 78 (47.3%) patients received at least 1 appropriate ICD therapy. The annual incidence of the primary outcome was 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively; P=0.03). Overall, 71 (43.0%) patients presented with at least 1 ICD complication, including inappropriate shocks in 42 (25.5%) patients and lead dysfunction in 36 (21.8%) patients. Among 61 (37.0%) patients in primary prevention, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with, respectively, 0, 1, 2, or ≥3 guidelines-recommended risk factors. QRS fragmentation was the only independent predictor of appropriate ICD therapies (hazard ratio, 3.47 [95% CI, 1.19-10.11]), and its integration in a model with current criteria increased the 5-year time-dependent area under the curve from 0.68 to 0.81 (P=0.006). Patients with congestive heart failure or reduced left ventricular ejection fraction had a higher risk of nonarrhythmic death or heart transplantation (hazard ratio, 11.01 [95% CI, 2.96-40.95]). CONCLUSIONS: Patients with tetralogy of Fallot and an ICD experience high rates of appropriate therapies, including those implanted in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria including QRS fragmentation might improve risk stratification. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03837574.

Outcome of adults with Eisenmenger syndrome treated with drugs specific to pulmonary arterial hypertension: A French multicentre study.

BACKGROUND: The relationship between pulmonary arterial hypertension-specific drug therapy (PAH-SDT) and mortality in Eisenmenger syndrome (ES) is controversial. AIMS: To investigate outcomes in patients with ES, and their relationship with PAH-SDT. METHODS: Retrospective, observational, nationwide, multicentre cohort study. RESULTS: We included 340 patients with ES: genetic syndrome (n=119; 35.3%); pretricuspid defect (n=75; 22.1%). Overall, 276 (81.2%) patients received PAH-SDT: monotherapy (endothelin receptor antagonist [ERA] or phosphodiesterase 5 inhibitor [PDE5I]) 46.7%; dual therapy (ERA+PDE5I) 40.9%; triple therapy (ERA+PDE5I+prostanoid) 9.1%. Median PAH-SDT duration was 5.5 years [3.0-9.1 years]. Events (death, lung or heart-lung transplantation) occurred in 95 (27.9%) patients at a median age of 40.5 years [29.4-47.6]. The cumulative occurrence of events was 16.7% [95% confidence interval 12.8-21.6%] and 46.4% [95% confidence interval 38.2-55.4%] at age 40 and 60 years, respectively. With age at evaluation or time since PAH diagnosis as time scales, cumulative occurrence of events was lower in patients taking one or two PAH-SDTs (P=0.0001 and P=0.004, respectively), with the largest differences in the post-tricuspid defect subgroup (P<0.001 and P<0.02, respectively) versus patients without PAH-SDT. By multivariable Cox analysis, with time since PAH diagnosis as time scale, New York Heart Association/World Health Organization functional class III/IV, lower peripheral arterial oxygen saturation and pretricuspid defect were associated with a higher risk of events (P=0.002, P=0.01 and P=0.04, respectively), and one or two PAH-SDTs with a lower risk of events (P=0.009). CONCLUSIONS: Outcomes are poor in ES, but seem better with PAH-SDT. ES with pretricuspid defects has worse outcomes despite the delayed disease onset.

Symptomatic and Asymptomatic Neurological Complications of Infective Endocarditis: Impact on Surgical Management and Prognosis.

OBJECTIVES: Symptomatic neurological complications (NC) are a major cause of mortality in infective endocarditis (IE) but the impact of asymptomatic complications is unknown. We aimed to assess the impact of asymptomatic NC (AsNC) on the management and prognosis of IE. METHODS: From the database of cases collected for a population-based study on IE, we selected 283 patients with definite left-sided IE who had undergone at least one neuroimaging procedure (cerebral CT scan and/or MRI) performed as part of initial evaluation. RESULTS: Among those 283 patients, 100 had symptomatic neurological complications (SNC) prior to the investigation, 35 had an asymptomatic neurological complications (AsNC), and 148 had a normal cerebral imaging (NoNC). The rate of valve surgery was 43% in the 100 patients with SNC, 77% in the 35 with AsNC, and 54% in the 148 with NoNC (p<0.001). In-hospital mortality was 42% in patients with SNC, 8.6% in patients with AsNC, and 16.9% in patients with NoNC (p<0.001). Among the 135 patients with NC, 95 had an indication for valve surgery (71%), which was performed in 70 of them (mortality 20%) and not performed in 25 (mortality 68%). In a multivariate adjusted analysis of the 135 patients with NC, age, renal failure, septic shock, and IE caused by S. aureus were independently associated with in-hospital and 1-year mortality. In addition SNC was an independent predictor of 1-year mortality. CONCLUSIONS: The presence of NC was associated with a poorer prognosis when symptomatic. Patients with AsNC had the highest rate of valve surgery and the lowest mortality rate, which suggests a protective role of surgery guided by systematic neuroimaging results.

Value of speckle tracking for the assessment of right ventricular function in patients operated on for tetralogy of fallot. Comparison with magnetic resonance imaging.

BACKGROUND: Right ventricular (RV) function is a major prognostic factor in patients (pts) with operated tetralogy of Fallot (TOF). We compared the results of RV speckle tracking (two-dimensional [2D] strain) with those of magnetic resonance imaging (MRI) in this setting. METHODS: At transthoracic echocardiogram (echo), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), velocity of S-wave at tricuspid annulus with tissue Doppler, and 2D strain (longitudinal maximal systolic strain) were recorded. Their results were compared to RV indexed end-diastolic volume (EDV), indexed end-systolic volume (ESV), and RV ejection fraction (EF) at MRI. RESULTS: Twenty-two pts (16 M) aged 11-62 years (mean 23.2 ± 10.8) were included. Parameters of RV systolic function were as follows: RVFAC = 40 ± 10%, TAPSE = 18 ± 4 mm, S-wave = 10 ± 0.2 cm/sec, and RV EF at MRI = 43 ± 11%. Global RV systolic strain was -15.5 ± 4.2%, free wall strain was -15.1 ± 6.3%, and septal strain was -15.8 ± 3.8% on average for the whole group. Echo indexed RV end-diastolic area correlated with EDV at MRI (r = 0.73), as well as echo indexed RV end-systolic area and ESV at MRI (r = 0.71). Global RV 2D strain correlated well with RV EF at MRI: r = 0.68; P < 0.05, and with ESV at MRI: r = 0.63. Feasibility, intra- and inter-observer reproducibility of 2D strain were adequate. CONCLUSIONS: Speckle tracking is a promising method to estimate RV systolic function in pts operated on for TOF.

Long-term prognostic value of residual pulmonary vascular obstruction at discharge in patients with intermediate- to high-risk pulmonary embolism.

BACKGROUND: We evaluated prognostic value at 6 months of residual pulmonary vascular obstruction (RPVO) measured before discharge in patients with intermediate- or high-risk pulmonary embolism (PE). METHODS AND RESULTS: Prospective registry including 416 consecutive patients with intermediate- or high-risk PE who survived the acute phase. Patients with previous cardiopulmonary disease were excluded. Perfusion lung scans were performed within 6-8 days after the onset of treatment. Residual pulmonary vascular obstruction was graded as the proportion of the lung not perfused. Primary objective was a combined endpoint at 6 months, including death, recurrent PE, and appearance of signs of heart failure. At 6 months, 32 patients (7.7%) had at least one adverse event: 12 deaths (2.9%), 12 recurrent PE (2.9%), and 14 (3.4%) heart failure. Independent predictors of combined endpoint were: cancer [odds ratio (OR) 3.07 (1.22-7.85)]; renal insufficiency at admission [OR: 2.53 (1.17-5.8)]; persistent signs of right ventricular dysfunction at 48 h echography [OR: 3.99 (1.36-11.3)]. The severity of RPVO at discharge was significantly associated with an unfavourable outcome [OR: 2.66 (1.58-3.93)]. The incremental prognostic value of RPVO information was confirmed by significantly improved goodness-of-fit. Threshold RPVO for predicting adverse events was estimated at 35% [area under the curve = 0.76 (0.73-0.82)]. Patients with RPVO greater than threshold at discharge had a significantly higher risk of death at 6 months (P = 0.01). CONCLUSIONS: Residual pulmonary vascular obstruction evaluated before hospital discharge in patients with intermediate- to high-risk PE is a powerful prognostic factor for a 6-month outcome. RPVO ≥35% is associated with an increased risk of adverse events at 6 months.

Comparison of right ventricular systolic function in patients with low risk and intermediate-to-high risk pulmonary embolism: a two-dimensional strain imaging study.

AIM: Right ventricular (RV) dysfunction is key for risk stratification in pulmonary embolism (PE). The goal of this study was to compare RV strain values between low and intermediate-to-high risk PE patients assessed by two-dimensional (2D) strain imaging. METHODS: The inclusion criterion was a diagnosis of PE confirmed by thoracic computed tomography scan with contrast medium, or by scintigraphy perfusion lung scan. Risk stratification of PE was defined as high when there was hemodynamic instability; intermediate when there were signs of RV dysfunction on echocardiography; and/or elevated troponin I and/or brain natriuretic peptide and low when none of these criteria were present. All patients underwent echocardiography at admission. Apical four-chamber images were analyzed off line using both conventional and 2D strain imaging. RESULTS: Sixty-two patients (mean age 66 years) were prospectively recruited: 33 with low risk PE, 29 with intermediate-to-high risk PE. Global 2D RV strain differed significantly between groups (-13.1% vs. -18.7%, P < 0.01), as did free wall (-12.7% vs. -20.2%, P < 0.016) and septal wall (-13.5% vs. -17.2%, P < 0.01). When the RV was divided into segments, we observed a similar reduction in absolute strain value in the mid and apical free wall segments and in the apical septal wall (-20.3 ± -7.6 vs. -11.8 ± 8.9%; P < 0.01 and -19.6 ± 6.9 vs. -7.4 ± 9.1%; P < 0.01, and -17.7 ± 7.0 vs. 9.9 ± 8.0; P < 0.01, respectively). 2D strain and tricuspid annular plane systolic excursion were significantly related (r(2)  = 0.35, P < 0.01). CONCLUSIONS: Peak RV longitudinal 2D strain is reduced in patients with intermediate-to-high risk PE, especially in the apical and mid segments of the free wall. Global and regional RV longitudinal 2D strain is altered in patients with intermediate-to-high risk PE as compared with low risk PE.

Clinical and microbiologic features of multivalvular endocarditis.

Multivalvular endocarditis accounts for 15% of all endocarditis. The mechanisms of spread of the infection differs whether endocarditis is only left-sided (involving both the mitral and aortic valves) or bilateral. In left-sided bivalvular endocarditis, it is often a secondary mitral lesion following a primary aortic endocarditis. Multivalvular endocarditis often results in severe and extensive cardiac lesions, well described at echocardiography and frequently responsible for severe heart failure. Patients often need surgery, which consists of radical debridement of all the infected tissue with reconstruction using different types of prostheses; therefore, the surgery may be very complex. The goal should be an early diagnosis of endocarditis to avoid spread of the infection to more than one valve, to improve the prognosis for those patients.

Immediate versus delayed angioplasty in infarct-related arteries with TIMI III flow and ST segment recovery: a matched comparison in acute myocardial infarction patients.

BACKGROUND: Early management of patients with patent infarct-related artery (IRA) and optimal ST resolution in ST elevation myocardial infarction (STEMI) has never been assessed. We compared immediate vs delayed PCI in these patients. METHODS: Matched comparison of immediate vs delayed (24 h) PCI in STEMI patients presenting with patent IRA, thrombus-containing lesion and ST resolution >or=70%. Patients were matched for duration of symptoms, intervention type, angiographic data, diabetes. Patients in immediate PCI group received standard therapy in the cathlab. Patients in delayed PCI group received dual antiplatelet therapy, antithrombins, and GPIIb-IIIa inhibitors until PCI. Primary endpoint was procedural success. Secondary endpoints were enzyme release and in-hospital adverse events. RESULTS: Seventy-eight patients were included: 39 per group. Average age 62 years, 75% males. There was a significantly higher procedural success rate in the delayed PCI group (95% success, Vs. 77% in the immediate group, P = 0.008). Initial thrombus burden score did not differ between immediate and delayed PCI groups, but improved significantly in the delayed group between baseline angiography and time of PCI (P = 0.039). There was no difference in major adverse events or bleeding complications between groups. Peak CK levels were significantly higher in the immediate versus delayed PCI group (P = 0.02), although there was no difference between groups in peak CK-MB, peak troponin, or peak CK-MB ratio. CONCLUSION: Our data suggest that in STEMI patients with patent IRA, optimal ST-segment resolution, and thrombus-containing lesion, deferred PCI when patients are given dual antiplatelet therapy, antithrombin agents, and GPIIb-IIIa inhibitors results in a higher procedural success rate, without an increased risk of MACE.

Prognostic value of albuminuria on 1-month mortality in acute myocardial infarction.

RATIONALE: An increase in albuminuria occurs in the early days after acute myocardial infarction. The aim of this study was to assess the relation between albuminuria and 30-day mortality, as well as its incremental predictive value, on top of established prognostic parameters. METHODS AND RESULTS: Demographic, clinical, and biological characteristics at admission, as well as in-hospital treatments and 1-month survival, were recorded in 1,211 consecutive patients admitted for acute myocardial infarction. Albuminuria was assessed from an 8-hour overnight urine collection within the first 2 days using immunonephelemetry. The population was categorized into 3 groups according to albuminuria levels (<20, 20-200, and >200 microg/min). Among survivors on day 2, 52% (625/1,211) of patients had an albuminuria level <20 microg/min, 39% (477) between 20 and 200 microg/min, and 9% (109) >200 microg/min. High levels of albuminuria were associated with older age, peripheral vessel disease, systolic blood pressure, glucose, creatinine, troponin, B-type natriuretic peptide, and high-sensitivity C reactive protein levels, as well as use of angiography, angiotensin-converting enzyme inhibitors, and beta blockers. At 1 month, there was a significantly higher mortality rate in groups with higher albuminuria. After adjustment for baseline characteristics, patients with albuminuria level of >20 microg/min had a 2.7-fold higher 30-day mortality, and those with >200 microg/min had an almost 4-fold higher 30-day mortality compared to those with albuminuria level of <20 microg/min. The addition of albuminuria information improved the discrimination capacity of the model and the global risk prediction. CONCLUSIONS: Albuminuria level, taken as a quantitative or categorical variable, is an independent and powerful predictor of mortality after acute myocardial infarction.

Safety and efficacy of fondaparinux as an adjunctive treatment to thrombolysis in patients with high and intermediate risk pulmonary embolism.

No data are available on the efficacy and safety of a combination of fondaparinux and thrombolysis in the setting of high to intermediate risk pulmonary embolism (PE). Patients submitted to thrombolysis and fondaparinux, presenting with > or =1 of the following criteria were included: (1) cardiogenic shock, (2) syncope, (3) > or =1 proximal thrombo-embolus at CT scan, (4) positive troponin test, (5) echocardiographic findings indicating right ventricular (RV) dysfunction. In-hospital results included death, recurrent PE, persistent RV dysfunction at 48 h echocardiography, bleeding complications. Twenty seven patients were included; 22 received a 2 h infusion of rt-PA and 5 received a 2 h infusion of streptokinase. Ten patients presented with cardiogenic shock (37%), 8 with syncope (30%), all had RV dysfunction. 82% of patients had an uneventful in-hospital course. One patient died during hospital stay from refractory shock. Thrombolysis failed in 2 patients (7%), requiring successful rescue surgical embolectomy. Bleeding events occurred in 2 patients (7%), of whom 1 required blood transfusion. Despite the small sample size, our data suggest that fondaparinux procures adequate tolerability compared to standard current therapy in combination with thrombolysis in high to intermediate risk PE.

Management of unsuccessful thrombolysis in acute massive pulmonary embolism.

BACKGROUND: The management of patients with acute massive pulmonary embolism (PE) who do not respond to fibrinolytic therapy remains unclear. We aimed to compare rescue surgical embolectomy and repeat thrombolysis in patients who did not respond to thrombolysis. METHODS: We conducted a prospective single-center registry of PE patients who underwent thrombolytic therapy. Lack of response to thrombolysis within the first 36 h was prospectively defined as both persistent clinical instability and residual echocardiographic right ventricular dysfunction. Patients underwent surgical embolectomy or repeat thrombolysis, at the discretion of the attending physician. The clinical end point was a combined end point including recurrent PE, bleeding complications, or PE-related death, which was defined as death from recurrent PE or cardiogenic shock. Long-term adverse outcomes included death, recurrent thromboembolic events, and congestive heart failure. RESULTS: From January 1995 to January 2005, 488 PE patients underwent thrombolysis, of whom 40 (8.2%) did not respond to thrombolysis. Fourteen patients were treated by rescue surgical embolectomy, and 26 were treated by repeat thrombolysis. There was no significant difference in baseline characteristics between the two groups. The in-hospital course was uneventful in 11 of the surgically treated patients (79%) and in 8 patients (31%) treated by repeat thrombolysis (p = 0.004). There was a trend for higher mortality in the medical group than in the surgical group (10 vs 1 deaths, respectively; p = 0.07). There were significantly more recurrent PEs (fatal and nonfatal) in the repeat-thrombolysis group (35% vs 0%, respectively; p = 0.015). While no significant difference was observed in number of major bleeding events, all bleeding events in the repeat-thrombolysis group were fatal. The rate of uneventful long-term evolution was the same in the two groups. CONCLUSION: Rescue surgical embolectomy led to a better in-hospital course when compared with repeat thrombolysis in patients with massive PE who have not responded to thrombolysis. The transfer of patients who have not responded to thrombolysis to tertiary cardiac surgery centers could be considered as an alternative option.

Cost Effectiveness of Cardioprotective Strategies in Patients with Aggressive Non-Hodgkin's Lymphoma.

OBJECTIVE: The cardiotoxicity of anthracyclines remains a key problem in patients with aggressive non-Hodgkin's lymphoma (NHL). With regard to the actual long-term prognosis of aggressive NHL, the development of cardioprotective strategies is mandatory for these patients. A cost-effectiveness analysis was carried out to determine the potential economic profile of dexrazoxane or liposome-encapsulated doxorubicin in patients with aggressive NHL treated with a CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) as first-line therapy. METHODS: A decision-analysis model described clinical events and economic consequences for theoretical patients who were to receive eight consecutive cycles of a CHOP regimen containing 50 mg/m(2) of doxorubicin as first-line chemotherapy. The timeframe of the model was the patient's lifetime. The probabilities were related to the cumulative dose of doxorubicin and age. The study was carried out from the perspective of the French healthcare system. Patients entered the model at 'choose' node: no cardioprotection versus cardioprotection with dexrazoxane or liposome-encapsulated doxorubicin. The model was based on a retrospective epidemiological study and on published data. The clinical end-point was life expectancy. Direct medical costs related to the cardioprotection and the treatment of congestive heart failure were considered. Monetary values for French prices in the year 2002 were used. Several univariate sensitivity analyses were carried out with varying clinical and economic parameters. RESULTS: Per 100 patients, the two cardioprotective strategies provided similar benefits that were estimated as 24.5 and 13.4 life-years in 60- and 40-year-old patients, respectively. The cost per life-year saved with dexrazoxane was estimated as euro6931 and euro15 599 in 60- and 40-year-old patients, respectively, and euro22 940 and euro44 982, respectively, with liposome-encapsulated doxorubicin. Several sensitivity analyses showed the robustness of the model. CONCLUSION: The results suggest the potential clinical and economic usefulness of cardioprotective therapies in patients with aggressive NHL. Prospective studies are needed to confirm these findings.

Endocarditis in patients with a permanent pacemaker: a 1-year epidemiological survey on infective endocarditis due to valvular and/or pacemaker infection.

To describe characteristics of infective endocarditis (IE) in pacemaker (PM) recipients, including the annual incidence and exact localization of IE on PM leads, cardiac valves, or both, we prospectively analyzed 45 PM recipients from a group of 559 patients with definite IE who responded to a population-based survey conducted in France in 1999. Thirty-three patients had definite PM-lead IE (group I), and 12 had valvular IE without evidence of PM involvement (group II). The valvular structure was involved in almost two-thirds of IE cases among PM recipients. Of the 28 patients (62%) with valvular IE, 10 group I patients had tricuspid involvement, and 6 group I patients had left heart-valve involvement. The most frequent causative organisms in groups I and II were staphylococci (82%) and streptococci (50%), respectively. The incidence of age- and sex-standardized IE was 550 cases/million PM recipients per year. The incidence of IE with PM involvement is between that of valvular IE in the general population and prosthetic valve IE.

In-hospital and long-term outcome after sub-massive and massive pulmonary embolism submitted to thrombolytic therapy.

BACKGROUND: From a registry of 249 confirmed pulmonary embolism (PE) patients submitted to thrombolytic therapy (TT), we analysed predictors of in-hospital course and long-term mortality. METHODS AND RESULTS: The combined clinical end point of in-hospital course associated death, recurrent PE, repeat thrombolysis, surgical embolectomy or bleeding complications. The long-term follow-up included analysis of survival, and occurrence of PE-related events, defined as recurrent deep vein thrombosis, recurrent PE, occurrence of congestive heart failure or change of New York Heart Association functional class to class III or IV in patients who survived the acute phase.In-hospital clinical course was uneventful in 165 (66.3%) patients. Initial right ventricular (RV) dysfunction was reversible in 80% within 48 h following TT. Initial pulmonary vascular obstruction >70% (RR=5.3 [2.1; 13.6]); haemodynamic instability at presentation (RR=2.6 [1.1; 6]); persistence of septal paradoxical motion after TT (RR=5.9 [1.4; 25.9]); and insertion of intracaval filter (RR=3.7 [1.4; 9.4]) were independent predictors of poor in-hospital course. Mean follow-up was 5.3+/-2.6 years. Of the 227 patients alive after the hospital stay, the probability of survival was 92% at 1 year, 79% at 3 years and 56% at 10 years. Multivariate predictors of long-term mortality were age >75 years (RR=2.73 [2.18; 3.21]; P=0.0002), persistence of vascular pulmonary obstruction >30% after thrombolytic treatment (RR=2.22 [1.69; 2.74]; P=0.003), and cancer (RR=2.03 [1.40; 2.65]; P=0.04). CONCLUSION: The recovery of RV function should be considered as a marker of thrombolysis efficacy, while residual pulmonary vascular obstruction and cancer are independent predictors of long-term mortality. These results advocate the identification of high-risk patients by means of systematic lung-scan and echocardiography pre- and post-thrombolysis, and raise the question of the need for thromboendarterectomy in patients with residual pulmonary vascular obstruction.