Dicer-2- and Piwi-mediated RNA interference in Rift Valley fever virus-infected mosquito cells.

Rift Valley fever virus (RVFV) is a Phlebovirus (Bunyaviridae family) transmitted by mosquitoes. It infects humans and ruminants, causing dramatic epidemics and epizootics in Africa, Yemen, and Saudi Arabia. While recent studies demonstrated the importance of the nonstructural protein NSs as a major component of virulence in vertebrates, little is known about infection of mosquito vectors. Here we studied RVFV infection in three different mosquito cell lines, Aag2 cells from Aedes aegypti and U4.4 and C6/36 cells from Aedes albopictus. In contrast with mammalian cells, where NSs forms nuclear filaments, U4.4 and Aag2 cells downregulated NSs expression such that NSs filaments were never formed in nuclei of U4.4 cells and disappeared at an early time postinfection in the case of Aag2 cells. On the contrary, in C6/36 cells, NSs nuclear filaments were visible during the entire time course of infection. Analysis of virus-derived small interfering RNAs (viRNAs) by deep sequencing indicated that production of viRNAs was very low in C6/36 cells, which are known to be Dicer-2 deficient but expressed some viRNAs presenting a Piwi signature. In contrast, Aag2 and U4.4 cells produced large amounts of viRNAs predominantly matching the S segment and displaying Dicer-2 and Piwi signatures. Whereas 21-nucleotide (nt) Dicer-2 viRNAs were prominent during early infection, the population of 24- to 27-nt Piwi RNAs (piRNAs) increased progressively and became predominant later during the acute infection and during persistence. In Aag2 and U4.4 cells, the combined actions of the Dicer-2 and Piwi pathways triggered an efficient antiviral response permitting, among other actions, suppression of NSs filament formation and allowing establishment of persistence. In C6/36 cells, Piwi-mediated RNA interference (RNAi) appeared to be sufficient to mount an antiviral response against a secondary infection with a superinfecting virus. This study provides new insights into the role of Dicer and Piwi in mosquito antiviral defense and the development of the antiviral response in mosquitoes.

Nonstructural NSs protein of rift valley fever virus interacts with pericentromeric DNA sequences of the host cell, inducing chromosome cohesion and segregation defects.

Rift Valley fever virus (RVFV) is an emerging, highly pathogenic virus; RVFV infection can lead to encephalitis, retinitis, or fatal hepatitis associated with hemorrhagic fever in humans, as well as death, abortions, and fetal deformities in animals. RVFV nonstructural NSs protein, a major factor of the virulence, forms filamentous structures in the nuclei of infected cells. In order to further understand RVFV pathology, we investigated, by chromatin immunoprecipitation, immunofluorescence, fluorescence in situ hybridization, and confocal microscopy, the capacity of NSs to interact with the host genome. Our results demonstrate that even though cellular DNA is predominantly excluded from NSs filaments, NSs interacts with some specific DNA regions of the host genome such as clusters of pericentromeric gamma-satellite sequence. Targeting of these sequences by NSs was correlated with the induction of chromosome cohesion and segregation defects in RVFV-infected murine, as well as sheep cells. Using recombinant nonpathogenic virus rZHDeltaNSs210-230, expressing a NSs protein deleted of its region of interaction with cellular factor SAP30, we showed that the NSs-SAP30 interaction was essential for NSs to target pericentromeric sequences, as well as for induction of chromosome segregation defects. The effect of RVFV upon the inheritance of genetic information is discussed with respect to the pathology associated with fetal deformities and abortions, highlighting the main role played by cellular cofactor SAP30 on the establishment of NSs interactions with host DNA sequences and RVFV pathogenesis.

Current status and needs for changes in critical care training: the voice of the young cardiologists.

AIMS: The implementation of the 2013 European Society of Cardiology (ESC) Core Curriculum guidelines for acute cardiovascular care (acc) training among European countries is unknown. We aimed to evaluate the current status of acc training among cardiology trainees and young cardiologists (<40 years) from ESC countries. METHODS AND RESULTS: The survey (March-July 2019) asked about details of cardiology training, self-confidence in acc technical and non-technical skills, access to training opportunities, and needs for further training in the field. Overall 614 young doctors, 31 (26-43) years old, 55% males were surveyed. Place and duration of acc training differed between countries and between centres in the same country. Although the majority of the respondents (91%) had completed their acc training, the average self-confidence to perform invasive procedures and to manage acc clinical scenarios was low-44% (27.3-70.4). The opportunities for simulation-based learning were scarce-18% (5.8-51.3), as it was previous leadership training (32%) and knowledge about key teamwork principles was poor (48%). The need for further acc training was high-81% (61.9-94.3). Male gender, higher level of training centres, professional qualifications of respondents, longer duration of acc/intensive care training, debriefings, and previous leadership training as well as knowledge about teamwork were related to higher self-confidence in all investigated aspects. CONCLUSIONS: The current cardiology training program is burdened by deficits in acc technical/non-technical skills, substantial variability in programs across ESC countries, and a clear gender-related disparity in outcomes. The forthcoming ESC Core Curriculum for General Cardiology is expected to address these deficiencies.

Organization of intensive cardiac care units in Europe: Results of a multinational survey.

BACKGROUND: The present survey aims to describe the intensive cardiac care unit organization and admission policies in Europe. METHODS: A total of 228 hospitals (61% academic) from 27 countries participated in this survey. In addition to the organizational aspects of the intensive cardiac care units, including classification of the intensive cardiac care unit levels, data on the admission diagnoses were gathered from consecutive patients who were admitted during a two-day period. Admission policies were evaluated by comparing illness severity with the intensive cardiac care unit level. Gross national income was used to differentiate high-income countries (n=13) from middle-income countries (n=14). RESULTS: A total of 98% of the hospitals had an intensive cardiac care unit: 70% had a level 1 intensive cardiac care unit, 76% had a level 2 intensive cardiac care unit, 51% had a level 3 intensive cardiac care unit, and 60% of the hospitals had more than one intensive cardiac care unit level. High-income countries tended to have more level 3 intensive cardiac care units than middle-income countries (55% versus 41%, p=0.07). A total of 5159 admissions were scored on illness severity: 63% were low severity, 24% were intermediate severity, and 12% were high severity. Patients with low illness severity were predominantly admitted to level 1 intensive cardiac care units, whereas patients with high illness severity were predominantly admitted to level 2 and 3 intensive cardiac care units. A policy mismatch was observed in 12% of the patients; some patients with high illness severity were admitted to level 1 intensive cardiac care units, which occurred more often in middle-income countries, whereas some patients with low illness severity were admitted to level 3 intensive cardiac care units, which occurred more frequently in high-income countries. CONCLUSION: More than one-third of the admitted patients were considered intermediate or high risk. Although patients with higher illness severity were mostly admitted to high-level intensive cardiac care units, an admission policy mismatch was observed in 12% of the patients; this mismatch was partly related to insufficient logistic intensive cardiac care unit capacity.

Presence and extent of cardiac magnetic resonance microvascular obstruction in reperfused non-ST-elevated myocardial infarction and correlation with infarct size and myocardial enzyme release.

OBJECTIVE: Microvascular obstruction (MO) is a factor of adverse outcome in patients with ST-elevated myocardial infarction (STEMI). We assessed the presence and extent of MO and its relationship with infarct size and left ventricular (LV) functional parameters after acute non-ST-elevated myocardial infarction (NSTEMI). METHODS: Twenty-five patients with first acute NSTEMI underwent a cine and first-pass perfusion cardiac magnetic resonance (CMR) study, with late gadolinium enhancement imaging 72 h after myocardial infarction. RESULTS: MO was detected in 32% of patients, and its extent comprised 0.5-3.1% of the total LV mass (mean 1.9 +/- 1.2%). Patients with MO had a significantly larger infarct size than patients without (14.1 +/- 5.9 vs. 5.3 +/- 4.1% LV mass; p < 0.001). There was no significant difference between both groups for the LV functional parameters and LV ejection fraction (58.5 +/- 6.8 vs. 62.6 +/- 9.6%; p = 0.29). Patients with MO showed a higher troponin I release (570 +/- 364 vs. 148 +/- 103 IU; p = 0.003) and a higher creatine kinase release (29,887 +/- 18,263 vs. 10,287 +/- 5,283 IU; p = 0.007). CONCLUSIONS: In patients with acute NSTEMI, MO has a frequency similar to that observed in patients with STEMI and also correlates with the infarct extent. The prognostic significance on clinical outcome remains to be shown in this specific population.

Specific binding of high-mobility-group I (HMGI) protein and histone H1 to the upstream AT-rich region of the murine beta interferon promoter: HMGI protein acts as a potential antirepressor of the promoter.

The high-mobility-group I (HMGI) protein is a nonhistone component of active chromatin. In this work, we demonstrate that HMGI protein specifically binds to the AT-rich region of the murine beta interferon (IFN-beta) promoter localized upstream of the murine virus-responsive element (VRE). Contrary to what has been described for the human promoter, HMGI protein did not specifically bind to the VRE of the murine IFN-beta promoter. Stably transfected promoters carrying mutations on this HMGI binding site displayed delayed virus-induced kinetics of transcription. When integrated into chromatin, the mutated promoter remained repressed and never reached normal transcriptional activity. Such a phenomenon was not observed with transiently transfected promoters upon which chromatin was only partially reconstituted. Using UV footprinting, we show that the upstream AT-rich sequences of the murine IFN-beta promoter constitute a preferential binding region for histone H1. Transfection with a plasmid carrying scaffold attachment regions as well as incubation with distamycin led to the derepression of the IFN-beta promoter stably integrated into chromatin. In vitro, HMGI protein was able to displace histone H1 from the upstream AT-rich region of the wild-type promoter but not from the promoter carrying mutations on the upstream high-affinity HMGI binding site. Our results suggest that the binding of histone H1 to the upstream AT-rich region of the promoter might be partly responsible for the constitutive repression of the promoter. The displacement by HMGI protein of histone H1 could help to convert the IFN-beta promoter from a repressed to an active state.

WITHDRAWN: Primary angioplasty versus intravenous thrombolysis for acute myocardial infarction.

BACKGROUND: Intravenous thrombolytic therapy is the standard care for patients with acute myocardial infarction, based upon its widespread availability and ability to reduce patient mortality well demonstrated in randomised trials. Despite its proven efficacy, thrombolytic therapy has limitations. Many patients are ineligible for treatment with thrombolytics. Of those given thrombolytic therapy, 10 to 15 percent have persistent occlusion or reocclusion of the infarct-related artery. Consequently, primary angioplasty (primary PTCA) has been advocated as a better treatment of myocardial infarction. OBJECTIVES: To determine whether primary coronary angioplasty is superior to thrombolytic therapy for the treatment of patients with acute myocardial infarction. SEARCH STRATEGY: Electronic search of The Cochrane Library (1998; Issue 2). MEDLINE (to January 1998); references from reviews, trials and previously published meta-analyses; and experts. Date of most recent searches January 1998. SELECTION CRITERIA: All unconfounded, randomised controlled trials comparing primary angioplasty against intravenous thrombolysis in patients with acute myocardial infarction DATA COLLECTION AND ANALYSIS: At least two independent reviewers abstracted data on morbidity and mortality and trial characteristics. The following outcomes were assessed: total mortality at the end of the study, reinfarction, stroke of any type, composite endpoint of death and reinfarction, recurrent ischemia, severe bleeding and coronary artery bypass grafting. MAIN RESULTS: Ten trials including 2573 subjects were identified. Compared to thrombolytic therapy, primary angioplasty was associated with a significant reduction in short-term mortality at the end of the studies (relative reduction in risk RRR = 32% 95%CI = 5%;50%). Similar reductions were observed for the rate of reinfarction (RRR = 52%, 95%CI = 30%;67%), recurrent ischemia (RRR = 54%; 95%CI = 39%,66%) and for the combined criteria death or reinfarction (RRR = 46%; 95%CI=30%;58%). The frequency of strokes of any cause was significantly decreased by 66% (95%CI=28%;84%). No significant difference was observed for the incidence of major bleeding (relative risk RR =1.18, 95%CI = 0.73;1.90) but the confidence interval was large. The superiority of the primary angioplasty over thrombolysis in terms of the composite endpoint (mortality and reinfarction) was less with accelerated t-PA (RR=0.70, 95%CI=0.51;0.97) than with streptokinase (RR=0.30, 95%CI=0.17;0.53). The biggest and most recent trial, Gusto 2B (GUSTO-2B 97), which involved general as well as highly specialised centres, obtained less favorable results. AUTHORS' CONCLUSIONS: This meta-analysis suggests that angioplasty provides a short-term clinical advantage over thrombolysis which may not be sustained. Primary angioplasty when available promptly at experienced centres, may be considered the preferred strategy for myocardial reperfusion. In most situations, however, optimal thrombolytic therapy should still be regarded as an excellent reperfusion strategy.

[Ictero-haemorrhagic leptospirosis with a cardiac presentation in a patient returning from an endemic zone]. / Leptospirose ictéro-hémorragique de presentation cardiaque chez une patiente de retour de zone d'endémie.

On returning from a tropical area, the occurrence of rapidly evolving cardiogenic shock in an infectious context should quickly suggest the diagnosis, for which specific treatment can affect the outcome. The dramatic case of a young female presenting with ictero-haemorrhagic leptospirosis diagnosed post-mortem, demonstrated this pathology with the unusual association of complete atrio-ventricular block and myocarditis in a haemorrhagic context.

Gated blood-pool SPECT evaluation of changes after radiofrequency catheter ablation of accessory pathways: evidence for persistent ventricular preexcitation despite successful therapy.

OBJECTIVES: This study was designed to prospectively evaluate the effects of radiofrequency ablation in Wolff-Parkinson-White (WPW) syndrome by scintigraphic analysis. BACKGROUND: The functional changes triggered by radiofrequency current ablation of atrioventricular accessory pathways are not fully known. METHODS: Forty-four patients with WPW syndrome were consecutively investigated before and 48 h after radiofrequency therapy. Fourteen patients had right sided atrioventricular pathways and 30 patients had left sided bypass-tracts. Planar gated imaging and gated blood pool tomography were performed in all of these patients. RESULTS: A significant increase in the left ventricular ejection fraction (LVEF) was demonstrated in patients with left preexcitation (62.2+/-7.9% before ablation against 64.4+/-6.3% after ablation, p = 0.02) but not for those with right sided anomalous pathway. Phase analysis only gave significant differences following ablation of right sided pathways (left-to-right phase difference = 14.4+/-13.8 degrees before ablation versus 7.5+/-7.2 degrees after ablation, p<0.05). Early abnormal ventricular contraction persisted in 12 patients with right accessory pathways and in 8 patients with left accessory pathways despite the complete disappearance of any abnormal conduction as proven electrophysiologically. CONCLUSIONS: Following catheter ablation of atrioventricular accessory pathways: 1) an improvement of left ventricular function may be seen, particularly in patients with left sided accessory pathways, and 2) unexpected persistence of local ventricular preexcitation at the site of successful ablation may be detected.

Arrhythmic cardiac arrest due to isolated coronary artery spasm: long-term outcome of seven resuscitated patients.

OBJECTIVES: Our aim was to look at the clinical features and long-term follow-up of seven patients without coronary artery disease, who had a history of life-threatening ventricular arrhythmias due to coronary spasm. BACKGROUND: Arrhythmic cardiac arrest due to isolated coronary spasm is rare, and there is limited information on the patients affected by this entity alone. METHODS: The seven patients were recruited retrospectively from a cohort of survivors of cardiac arrest. None had a history of angina pectoris, structural heart disease or significantly narrowed coronary segments. All had a positive ergonovine provocation test result. RESULTS: The patients' mean age was 44 years; three were male and four female. All were habitual cigarette smokers. No arrhythmias were induced on programmed ventricular stimulation; corrected QT interval (QTc) and corrected JT interval (JTc) dispersion were within normal ranges. After the ergonovine provocation test, treatment with calcium channel blocking agents (diltiazem, verapamil, nifedipine or amlodipine) was initiated at a dose determined by titration until a negative test result was obtained. At a mean follow-up interval of 58 months for the total group, six patients remained free of symptoms, whereas the one patient who did not stop smoking had a new cardiac arrest despite treatment for coronary spasm. CONCLUSIONS: A favorable long-term outcome may be expected in survivors of cardiac arrest due to coronary spasm, in the absence of significant coronary artery disease. Calcium channel blockers are the most appropriate therapy in these patients. These observations provide further evidence for the role of silent ischemia in cardiovascular death.

DNA-binding parameters of the HU protein of Escherichia coli to cruciform DNA.

We have previously studied the binding characteristics of the HU protein of Escherichia coli to different linear DNAs. In this work, using gel-retardation and footprint analysis, we studied the specific binding of HU protein to a synthetic cruciform DNA. We have quantified our results in order to precisely define the binding and cooperativity constants of HU protein towards cruciform DNA and compare them to those obtained with linear DNA. We used stringent high-salt conditions versus non-stringent low-salt conditions in order to differentiate the non-specific-protein HU-DNA complexes from the specific, high-salt-resistant complexes. We observe that HU-protein dimers bind specifically to the cruciform DNA with a binding constant K = 2.0 x 10(8) M-1 and a value for the cooperativity constant omega = 1 corresponding to a non-cooperative phenomenon. For the first time we observe a footprint pattern of HU protein bound to DNA using the hydroxyl-radical-footprinting technique on HU-protein-cruciform-DNA complexes. The residues protected by HU protein are localized at and near the junction point but interestingly they are mainly present in two of the four oligonucleotides which constitute the cruciform DNA. These two oligonucleotides are unpaired and opposite each other. These results support a model where two HU-protein dimers specifically bind to two equivalent angles present opposite each other in the four-way-junction-DNA structure with almost no dimer-dimer interactions.

[Levosimendan, a revolution in the world of inotropic agents?]. / Le levosimendan, une revolution dans le monde des inotropes?

Levosimendan is the first available drug of a new class of agents called calcium sensitizers. It increases cardiac contractility without increasing myocardial oxygen consumption. This new molecule has no proarrhythmic effects and has anti-ischemic properties. Levosimendan is infused over a 24-hour period and its hemodynamic effects, similar or superior to those of catecholamines, persist during one week. In a selected group of advanced heart failure patients levosimendan was associated with a mortality reduction at 14 days and at 6 months in comparison with dobutamine. In spite of its cost, this new inotropic agent appears very promising and it is expected that it will be widely used.

[Fatal surgical extraction of cardiac resynchronisation therapy defibrillator leads in a context of endocarditis due to methicillin-resistant Staphylococcus epidermidis. A case report and review of literature]. / Extraction chirurgicale fatale de sondes de défibrillateur cardiaque triple chambre dans un contexte d'endocardite à Staphylococcus epidermidis méthicilline-résistant. À propos d'un cas et revue de la littérature.

A 82-year-old man equipped with a cardiac resynchronisation therapy defibrillator for dilated cardiomyopathy with normal coronary arteries, in complete atrioventricular block, develops six months after a change of the generator-pocket a severe endocarditis due to a methicillin-resistant Staphylococcus epidermidis with a large lead vegetation. After 4 days of adapted antimicrobial therapy, a surgical device removal is realised with unfortunately a fatal end during extraction. This observation points out the severity of cardiovascular device infections in old and weak population, as well as the difficulty of treatment choices because of both infectious and rhythmic constraints. The lead extraction is a strong recommendation but the modality and timing of extraction are not consensual, especially in cardioverter defibrillator-dependent patients. Surgical removal remains an alternative to percutaneous lead extraction but with a higher operative risk.

Non-B-DNA structures on the interferon-beta promoter?

The high mobility group (HMG) I protein intervenes as an essential factor during the virus induced expression of the interferon-beta (IFN-beta) gene. It is a non-histone chromatine associated protein that has the dual capacity of binding to a non-B-DNA structure such as cruciform-DNA as well as to AT rich B-DNA sequences. In this work we compare the binding affinity of HMGI for a synthetic cruciform-DNA to its binding affinity for the HMGI-binding-site present in the positive regulatory domain II (PRDII) of the IFN-beta promoter. Using gel retardation experiments, we show that HMGI protein binds with at least ten times more affinity to the synthetic cruciform-DNA structure than to the PRDII B-DNA sequence. DNA hairpin sequences are present in both the human and the murine PRDII-DNAs. We discuss in this work the presence of, yet putative, non-B-DNA structures in the IFN-beta promoter.

HU and IHF: similarities and differences. In Escherichia coli, the lack of HU is not compensated for by IHF.

HU is one of the most abundant DNA binding proteins in Escherichia coli. Like the histones, HU is able to condense DNA in vitro and to introduce negative super-coiling in covalently closed circular, relaxed DNA molecules in the presence of topoisomerase I. HU is well conserved in all prokaryotes but surprisingly, it is also homologous to another E. coli DNA-binding protein, IHF. Contrary to HU, IHF shows sequence specificity and is much less abundant that HU. Both are heterodimers and all four polypeptide chains probably arose from a common ancestor. The question we raised was whether IHF could supply the main functions of HU in its absence. The answer seems to be negative for the following reasons. We did not observe any significant regulation of expression of the genes coding for HU by IHF, or vice-versa. The structures that these two proteins form with double-stranded or single-stranded DNA are completely different. Finally, overexpression of IHF does not relieve the growth defects observed in HU-less mutants. However, it can be speculated from our results that even if the two proteins are not equivalent and cannot replace one another, both could stimulate (or inhibit) some specific protein-DNA interactions or affect the DNA-binding properties of one another.

Cardiac troponin I does not increase after cardioversion.

BACKGROUND: Serum total creatine kinase (total CK) level increases in the patients following electrical cardioversion. The same has been observed with CK-MB, an isoenzyme of the total CK with some cardiospecificity. Cardiac troponin I (cTnI), a new specific cardiac biological marker, is highly effective to discriminate myocardial and muscular injuries after noncardiac surgery. METHODS: To assess cardiac damage after cardioversion, we measured serum cTnI, myoglobin, total CK, CK-MB mass, 1, 2, 3, 4, 8, 12, and 24 h after elective cardioversion of supraventricular tachycardia in 28 patients (eight women, 20 men; mean age, 64 +/- 10 years). Cumulative energy was below 370 J in 17 patients, between 370 and 900 J in eight patients, and 1,020 J in three patients. Serum cTnI was measured using a sandwich immunoenzymologic assay. The detection limit of the assay was 0.35 microgram/L and normal values range from 0.35 to 1.3 micrograms/L. RESULTS: In all but three patients, cTnI remained below 0.35 microgram/L. In these three patients, cTnI ranged between 0.35 and 0.9 microgram/L. There was no correlation between cTnI and the number or the energy of cardioversion. Myoglobin and total CK increased to abnormal concentrations in 11 patients (myoglobin, 630 +/- 190 micrograms/L, and total CK, 2,584 +/- 780 U/L) and reached myocardial infarction-like values in five patients. Modest increases of CK-MB were then also observed. A strong correlation was observed between the total energy of direct current cardioversion and the increase of either myoglobin (r = 0.87; p < 001) or total CK (r = 0.81; p < 001). CONCLUSION: Cardioversion in a clinical setting does not induce elevation of cTnI. Increase in total CK, CK-MB, and myoglobin may be due solely to muscular lesions and is closely related to the cumulative energy delivered.

Troponin I, troponin T, or creatine kinase-MB to detect perioperative myocardial damage after coronary artery bypass surgery.

STUDY OBJECTIVES: To compare cardiac troponin I (cTnI), cardiac troponin T (cTnT), and creatine kinase MB (CKMB mass) in patients with and without new Q wave on the ECG following coronary artery bypass graft (CABG) surgery. PATIENTS: After ethic committee's approval and informed consent, 82 patients, mean age 63+/-10 years, scheduled for CABG were included. INTERVENTIONS: Arterial blood samples were drawn during cardiopulmonary bypass, before, and 6, 12, 24, and 48 h after aortic cross-clamp release. cTnI, cTnT, and CKMB mass were measured. The appearance of new Q wave on the ECG performed preoperatively and 24 h postoperatively was used to assess myocardial lesion independently of biological markers. RESULTS: There were 69 patients without new Q wave on the ECG (group 1) and 13 with (group 2). In group 1, cTnI reached a peak of 2.1 microg/L (median, interquartile range [IQ]=2.4) at 12 h, cTnT increased progressively with a peak of 0.22 microg/L (IQ=0.2) at 48 h, and CKMB presented an earlier peak of 10 microg/L (IQ=6.2) at 6 h. Starting with the same median value, group 2 patients presented significantly higher peaks: cTnI: 17 microg/L (IQ=16) at 12 h; cTnT: 1.4 microg/L (IQ=2.3) at 12 h; and CKMB mass: 74 microg/L (IQ=61) at 6 h. Receiver operating characteristic (ROC) curves were constructed. The area under the curve was 0.90 for cTnI, 0.84 for CKMB, and 0.81 for cTnT (not significant). The best cutoff values to discriminate between group 1 and group 2 patients were determined with the ROC curves: cTnI=5 microg/L; CKMB mass=20 microg/L; cTnT=0.3 microg/L. Sensitivity, specificity, and positive and negative values for cTnI (5 microg/L) were 91%, 82%, 53%, and 98%, respectively. CONCLUSIONS: There was little differences among cTnI, cTnT, and CKMB after CABG to diagnose myocardial damage as assessed by new Q wave on the ECG. There was a trend of cTnI to be a better discriminator than cTnT, but it did not reach statistical significance.

Safety and tolerability of intravenous cibenzoline for acute termination of spontaneous sustained ventricular tachycardia. Cibenzoline and spontaneous VT.

STUDY OBJECTIVES: To evaluate prospectively, the tolerability and safety of intravenous cibenzoline therapy, for the cardioversion of spontaneous monomorphic ventricular tachycardia (VT). SETTING AND PATIENTS: Between February 1990 and December 1996, fifty-eight patients aged 59+/-10 years old (fifty-three males, five females), with spontaneous VT not causing cardiac arrest, received intravenous cibenzoline. Their underlying heart conditions were: ischemic heart disease [35], dilated cardiomyopathy [14], right ventricular dysplasia [3], hypertrophic cardiomyopathy [1], valvulopathy [2], Fallot's Tetralogy [1] and primary arrhythmogenic disease [2]. The left ventricular ejection fraction was 42+/-13% (range 20%-76%). RESULTS: The mean dose of cibenzoline was 70+/-12 mg. The tachycardia stopped within 6+/-3 min in 47 (81%) patients. Side effects from cibenzoline occurred in two patients. The hemodynamic complications were limited to hypotension, that required vasopressor therapy in one patient. The only apparent proarrhythmic effect consisted of an isolated change in the morphology of the VT, that resolved spontaneously on withdrawal of the drug. No mortality occurred at the hospital. CONCLUSION: With appropriate rules for its administration, intravenous cibenzoline has the potential to become one of the first-line antiarrhythmic drugs, to be used for cardioversion of patients with spontaneous VT.

Long-term results of heart transplantation deteriorate more rapidly in patients over 60 years of age.

It is generally agreed that the upper age limit for heart transplantation is 60 years. However, an increasing number of elderly candidates are accepted for heart transplantation. We retrospectively analyzed our experience with a total of 204 consecutive transplantations, performed in 195 adult patients (9 retransplantations) between March 1987 and September 1993. There were 48 patients older than 60 years (mean 62.9 +/- 3), group I (gr I) and 156 patients between 20 and 59 years old (mean 47.5 +/- 8), group II (gr II). The two groups were matched for sex-ratio (female 10.4 vs 14.2%), indications (cardiomyopathy, ischemic, others), and hemodynamic parameters (pulmonary artery pressure, capillary wedge pressure, cardiac index). A ventricular assist device was used in 14 patients as bridge to transplantation in gr II vs 0 to gr I. There were seven early deaths in gr I (14.6%) vs 14 in gr II (8.97%, NS). A total of 183 survivors (41 vs 142) have been followed up for 1 month-6.3 years (mean follow-up 20.4 +/- 19.3 months in gr I, 35.4 +/- 23 in gr II). No patient was lost to follow-up. There were 11 late deaths in gr I vs 16 in gr II. The most common cause was malignancy (n = 4) in gr I and sudden death (n = 9) in gr II, with a significant difference. The actuarial survival was 68.8% in gr I vs 88.5% in gr II at 1 year 43.5% in gr I vs 76.4% in gr II at 5 years. In conclusion, transplanted patients over 60 years of age have a significantly poorer late survival than younger patients, despite similar good early results. Moreover, the causes of late deaths were different in the two groups. So, heart transplantation in patients over 60 years of age should be carefully considered.

Mechanical cardiac valve thrombosis in patients in critical hemodynamic compromise.

BACKGROUND: Valve obstruction is a life threatening complication of mechanical valve prosthesis. METHODS: From 1985 to 1993, 29 consecutive patients were hospitalized in our intensive care unit for mechanical prosthetic valve thrombosis (PVT). There were 12 men and 17 women aged 25-75 years (57 +/- 12). Prosthetic valve location was mitral in 14 patients, aortic in 6, aortic and mitral in 9. PVT occurred from 15 days to 174 months (67 +/- 52 months) after surgery. Delay from first symptoms to hospitalization ranged from 1 to 45 days (11 +/- 11). RESULTS: First clinical symptoms were progressive left heart failure in 17 patients, stroke in 6, and chest pain in 6. Furthermore, acute myocardial infarction was later documented in 3. Left heart failure NYHA III-IV was present in 26 patients (90%) on admission and 10 of those were in cardiogenic shock. Anticoagulation regimen was inadequate in 13 cases (45%). It has been recently stopped in 8 patients and incorrectly conducted in 5. Total hospital mortality was 41.3% (12). It was independent of type and position of the valve prosthesis. Diagnosis of PVT was only made at autopsy in 3 patients who died of recurrent myocardial infarction (2) or cardiogenic shock (1). Five further patients died before any surgery could be attempted (cardiac arrest: 2, cardiogenic shock: 3). Valve replacement could be done in 21 cases, 7 of whom were in cardiogenic shock and 9 had severe pulmonary edema. Four patients died after surgery, the operative mortality was 19%. CONCLUSION: PVT remains a serious complication of mechanical heart valve prostheses. Overall mortality rate is high, related to difficulty to diagnosis, delay to hospitalization and severe clinical condition at admission. In our study, operative risk remained acceptable even when the clinical presentation was severe.