Immediate and mid-term results of repeat percutaneous mitral commissurotomy for restenosis following earlier percutaneous mitral commissurotomy.

AIMS: This study assessed the results of repeat percutaneous mitral commissurotomy for mitral restenosis following a first procedure. METHODS AND RESULTS: Repeat balloon commissurotomy was performed in 53 patients who had symptomatic restenosis a mean of 6+/-2 years (2-11) after a successful first procedure; seven patients had mildly calcified valves. All patients had restenosis with a fusion of both commissures as assessed by echocardiography. A double-balloon was used in one case and the Inoue technique in 52. Complications were stroke in one patient and severe mitral regurgitation (Sellers grade 3) in two. Valve area increased from 1.03+/-0.22 to 1.82+/-0.21 cm(2)(P<0.0001) as assessed by planimetry. Good immediate results, defined as valve area >/=1.5 cm(2)with no regurgitation >2/4, were obtained in 48 patients (91%). The 5-year survival rate without operation and in NYHA class I or II was 69+/-11% in the whole population, and 76+/-11% in the 48 patients who had had good immediate results. CONCLUSION: This study suggests that repeat balloon commissurotomy is a valid treatment for symptomatic restenosis after a first successful procedure. It gives good results in patients selected on the basis of favourable characteristics and the echocardiographic analysis of the mechanism of restenosis.

Late results of percutaneous mitral commissurotomy for calcific mitral stenosis.

The aim of this study was to assess late results of percutaneous mitral commissurotomy (PMC) in calcific mitral stenosis and to identify predictors to improve patient selection. We analyzed 422 patients who underwent PMC for calcific mitral stenosis. The extent of calcium was graded from 1 to 4 by fluoroscopy: 227 patients (53%) were graded 1, 125 (30%) graded 2, 55 graded 3 (13%), and 15 graded 4 (4%). The procedure failed in 15 patients, used a single balloon in 11, a double balloon in 126, and the Inoue balloon in 270. In-hospital mortality was 1.2%. Good immediate results (valve area >/=1.5 cm(2) without mitral regurgitation >2/4), were obtained in 321 patients (76%). Multivariate analysis identified 5 predictors of good immediate results: a younger age (p = 0.0004), a lesser degree of stenosis (p = 0.0005), a smaller extent of calcium (p = 0.04), the use of the Inoue balloon (p = 0.015), and a larger effective balloon dilating area (p = 0.006). Good functional results, defined as survival with no further intervention and in New York Heart Association class I or II, were 36 +/- 4% at 8 years. The predictors of good functional results after good immediate results were a younger age (p = 0.04), a lower pre-PMC New York Heart Association class (p <0.0001), sinus rhythm (p = 0.0006), a smaller extent of calcium (p = 0.02), and a lower gradient after PMC (p <0.0001). Despite a frequent deterioration on follow-up after PMC for calcific mitral stenosis, the predictive analysis suggests that PMC may be useful in deferring surgery in selected patients with mild to moderate calcific deposits, who have otherwise favorable characteristics.

Percutaneous mitral commissurotomy for restenosis after surgical commissurotomy: late efficacy and implications for patient selection.

OBJECTIVES: The results of percutaneous mitral commissurotomy were assessed in patients with restenosis after surgical commissurotomy. BACKGROUND: Balloon dilation is feasible in patients with restenosis after surgical commissurotomy, but little is known about its late efficacy. METHODS: We studied 232 patients who had undergone percutaneous mitral commissurotomy a mean of 16 +/- 8 years after surgical commissurotomy. Mean age was 47 +/- 14 years; 81 patients (35%) had valve calcification. All patients had restenosis with bilateral commissural fusion as assessed by echocardiography. Technical failure occurred in 9 patients and the procedure used a single balloon in 7 patients, a double balloon in 95, and the Inoue balloon in 121. RESULTS: Complications were death in 1 patient (0.4%) and mitral regurgitation >2/4 in 10 (4%); 191 patients (82%) had good immediate results (valve area > or =1.5 cm2 without regurgitation >2/4). Predictors of poor immediate results in multivariate analysis were older age (p < 0.001), lower initial valve area (p = 0.01) and the use of the double-balloon technique (p = 0.015). In the 175 patients who underwent follow-up, 8-year survival without operation and in New York Heart Association class I or II was 48 +/- 5%, and 58 +/- 6% after good immediate results. In this latter group, poor late functional results were predicted by higher cardiothoracic index (p < 0.0001), previous open-heart commissurotomy (p = 0.05) and lower final valve area (p < 0.0001) in a multivariate Cox model. CONCLUSIONS: Percutaneous mitral commissurotomy is safe and provides good immediate results in selected patients with restenosis after surgical commissurotomy. After good immediate results, the conditions of more than half of the patients remained improved at 8 years, enabling reoperation to be deferred.

[The best of valvular heart disease in 1999]. / L'essentiel de 1999 dans les valvulopathies.

The year 1999 confirmed important changes in the clinical presentation, the methods of investigation and the treatment of valvular heart disease. The near disappearance of acute rheumatic fever in the developed world, associated with the increase in life expectancy has resulted in degenerative aetiologies becoming the most common causes of valvular heart disease with a dominance of aortic stenosis and mitral incompetence. The increase in average age of the operated patients explains the increasing role of comorbidity and the higher incidence of mixed (valvular and coronary artery) surgery. Doppler echocardiography is now the reference method of investigating valvular heart disease, both pre- and post-operatively (especially in mitral incompetence). The value of tri-dimensional echocardiography is beginning to be recognised. The technical advances in surgical techniques are also important, especially the extension of conservative methods both in mitral incompetence and parietal lesions of dystrophic aortic incompetence. The good long-term results of homograft aortic valves have been confirmed, especially in young patients and infectious endocarditis complicated by abscess. The Ross procedure is an interesting alternative in children and adolescents in the absence of available homografts. The persistence of good results in the long term has made percutaneous mitral commissurotomy the reference in mitral stenosis. The improvement in surgical and interventional methods has widened the operative indications which are now considered in patients who are pauci- or a-symptomatic.

Frequency and prognostic value of cardiac troponin I elevation after coronary stenting.

Mild myocardial injuries after coronary angioplasty are associated with adverse late outcomes. The incidence and prognostic value of this phenomenon when using cardiac troponin I (cTnI) after stent implantation is unknown. We studied cTnI and creatine kinase (CK) release in 109 patients after stenting. Clinical success was achieved in 103 patients (94%). In-hospital major adverse coronary events were: death in 1 patient, Q-wave myocardial infarction in 1 patient, and non-Q-wave myocardial infarction in 2 patients. Twenty-nine patients (27%) had postprocedural cTnI increase, 16 (15%) had CK elevation. No preprocedural variables predicted marker elevation. Marker release was related to the occurrence of in-lab complications (59% vs 29% [p = 0.004 for cTnI] and 69% vs 32% [p = 0.011 for CK]). In 34% no explanation was found for cTnI increase. Success was more frequent in patients without cTnI elevation (100% vs 86%, p <0.001). The negative predictive value of cTnI increase was 100% for in-hospital major adverse coronary events (MACE), whereas its positive predictive value was 14%. cTnI and CK concordant elevation was associated with more intra- and postprocedural adverse events. During a mean follow-up of 8+/-3 months, major adverse coronary events were: death in 2 patients, myocardial infarction in 2 patients, and repeat PTCA in 8 patients. cTnI elevation was not predictive of these late MACE. cTnI elevation is common after stenting, and is related to the occurrence of in-lab complications. Its isolated elevation is not a good predictor of MACE. Patients with concordant cTnI and CK elevation seem to be at higher risk of in-hospital MACE.

Results of IIb/IIIa receptor blockade in patients with unstable angina.

The efficacy of GPIIb/IIIa inhibitors has now been evaluated in over 20 000 patients with unstable angina and non-Q MI. These agents have shown great efficacy in patients undergoing percutaneous coronary intervention. They are also effective, even if to a lesser degree, as an addition to medical treatment. The safety profile is satisfactory. Several issues have to be investigated in the future: comparison of agents, use of oral inhibitors, associations with Heparin, consequences on management, and cost efficacy. As of now, it is clear that GPIIb/IIIa inhibitors represent a significant progress in the treatment of patients with acute coronary syndromes.

Late results of percutaneous mitral commissurotomy in a series of 1024 patients. Analysis of late clinical deterioration: frequency, anatomic findings, and predictive factors.

BACKGROUND: The optimal use of percutaneous mitral commissurotomy (PMC) in a wide range of patients requires accurate evaluation of late results and identification of their predictors. METHODS AND RESULTS: Late results of PMC were assessed in 1024 patients whose mean age was 49+/-14 years. Echocardiography showed that 141 patients (14%) had pliable valves and mild subvalvular disease, 569 (55%) had extensive subvalvular disease, and 314 (31%) had calcified valves. A single balloon was used in 26 patients, a double balloon in 390, and the Inoue Balloon in 608. Good immediate results were defined as valve area >/=1.5 cm2 without regurgitation >2/4 (Sellers' grade) and were obtained in 912 patients. Median duration of follow-up was 49 months. The 10-year actuarial rate of good functional results (survival with no cardiovascular death and no need for surgery or repeat dilatation and in New York Heart Association [NYHA] class I or II) was 56+/-4% in the entire population. Follow-up echocardiography was available in 90% of the patients who experienced poor functional results after good immediate results and showed restenosis in 97% of these. In multivariate analysis, the predictors of poor functional results were old age (P=0.0008), unfavorable valve anatomy (P=0.003), high NYHA class (P<0.0001), atrial fibrillation (P<0.0001), low valve area after PMC (P=0.001), high gradient after PMC (P<0.0001), and grade 2 mitral regurgitation after PMC (P=0.04). CONCLUSIONS: PMC can be performed with good late results in a variety of patient subsets. Prediction of late events is multifactorial. Knowledge of these predictors can improve patient selection and follow-up.

"Rescue" abciximab for complicated percutaneous transluminal coronary angioplasty.

We studied the in-hospital outcome of 138 consecutive patients who received abciximab as a "rescue" intervention for complicated coronary angioplasty in a high-risk clinical setting. "Rescue" treatment with abciximab was associated with clinical and angiographic success rates of 83% and 84%, respectively, whereas the risk of bleeding was higher in patients of low body weight.

Antegrade transseptal coronary angiography: an alternative technique in severe vascular disease.

We report the case of a patient with severe vascular disease in whom retrograde access to the aortic root was not possible because of aortoiliac and axillary vascular disease. Antegrade coronary angiography was performed through the transseptal approach using standard catheters, although several technical difficulties were encountered.

[5 years results of percutaneous mitral commissurotomy. Apropos of a series of 606 patients; late results after mitral dilatation]. / Résultats à 5 ans de la commissurotomie mitrale percutanée. A partir d'une série de 606 patients; résultats tardifs après dilatation mitrale.

The long-term results of percutaneous mitral commissurotomy were evaluated in 606 patients with a mean age of 48 +/- 14 years. One hundred and eleven patients (48%) had a history of surgical commissurotomy. At echocardiography, 91 patients (15%) had flexible leaflets and little subvalvular apparatus, and 180 (30%) have calcified valves. The procedure was performed with a single balloon in 21 patients, a double balloon in 402 patients and Inoue's balloon in 183 patients. A good immediate, result, defined as a mitral valve surface area > or = 1.5 cm2 without > 2/4 mitral regurgitation, was obtained in 528 patients (87%). Five hundred and eighty patients (96%) were followed up for an average of 30 +/- 18 months. The actuarial 5 year rates were: survival 94 +/- 4%; survival without surgery 74 +/- 6%; survival without surgery with a good functional result (NYHA Classe I and II) 66% +/- 6%. Factors predictive of a good functional result were the valvular anatomy (p = 0.01), the NYHA Class before the procedure (p = 0.02), the cardiothoracic ratio before the procedure (p = 0.005) and mitral valve surface area after the procedure (p = 0.007). The type of balloon had no influence on the result (p = 0.54). The authors conclude that the 5 year results of percutaneous mitral commissurotomy are good in a population of patients with varied characteristics. The persistence of good functional results depends on anatomical and functional data and the quality of the initial result, but not on variables related to the procedure.

[Modern "antiplatelet agents" in unstable angina]. / "Antiplaquettaires" modernes dans l'angor instable.

It has been established that platelet aggregation plays an important role in the physiopathology of unstable angina. Despite conventional therapy associating aspirin and heparin, the morbidity and mortality of unstable angina remain high with 8 to 10% of fatalities or infarcts in the weeks following the acute episode. Research for new antiplatelet agents has been concentrated on developing molecules which block the GPIIb/IIIa receptors which are the final step of platelet aggregation. Two main families of the GPIIb/IIIa receptor inhibitors may be distinguished: 1) non-specific inhibitors which are the best known and most widely studied, amongst which the c7E3, 2) specific antagonists such as cyclic peptides or "peptido-mimetic" agents. Most clinical experience has been obtained with c7E3 (ReoPro) which has been shown to be very effective in reducing the complications of coronary angioplasty in patients with unstable angina in the CAPTURE and EPIC trials. However, this agent increases the risk of bleeding, especially in cases of overdosage of heparin. The efficacy of specific inhibitors (integrelin, lamifiban, tirofiban) has been suggested in clinical trials but on limited numbers of patients. In conclusion, blockers of the GPIIb/IIIa receptors are an interesting therapeutic innovation in patients with unstable angina. The optimal mode of usage and precise indications of this new therapeutic class should become clear after several phase III trials under way at present.

Specifics of technique in percutaneous mitral commissurotomy in a case of dextrocardia and situs inversus with mitral stenosis.

Percutaneous mitral commissurotomy (PMC) was successfully performed in a 48-year-old woman with dextrocardia and situs inversus and a severe mitral stenosis. After PMC, the valve area increased from 0.97 to 1.89 cm2, and no complication occurred. This case shows that PMC is practicable in a case of dextrocardia with situs inversus. The procedure appears to be safer and easier when carried out with the inoue balloon, image inversion on the screen, and under transesophageal echocardiographic monitoring.

[Indications of coronary angioplasty after thrombolysis]. / Indications de l'angioplastie coronaire après thrombolyse.

Thrombolysis is the most widely used method of coronary reperfusion in the acute phase of myocardial infarction. The indications of angioplasty after thrombolysis have been subject of considerable controversy over the last few years. Three randomised trials (TIMI 2, TAMI, ECSG) have shown that it is not desirable to perform systematic immediate angioplasty after intravenous thrombolysis with rt-PA. Angioplasty may be carried out as a "salvage" procedure in cases of failure of thrombolysis. The validity of this approach was confirmed recently by the "RESCUE" trial in anterior myocardial infarction. The practical application of its results is confronted by logistical problems inherent to the practice of angioplasty in the acute phase of myocardial infarction and to the inadequacy of non-invasive methods for the detection of coronary reperfusion after thrombolysis. Angioplasty may also be necessary in cases of left ventricular failure or cardiogenic shock. The efficacy of a rapid angioplasty in cases of recurrence of ischaemia after thrombolysis has been proved in reducing mortality and preserving left ventricular function. The results of TIMI IIB and SWIFT trials show that secondary angioplasty, several days after thrombolysis, is only usually indicated in patients with residual clinical ischaemia or positive stress tests. This attitude should however be modulated in the light of the "open artery" theory and the limitations of methods of evaluating myocardial viability. The present strategies will no doubt be modified with the introduction of new thrombolytic and/or antithrombotic agents and the use of coronary stents.

Pregnancy and prosthetic heart valves: a French cooperative retrospective study of 155 cases.

A French cooperative retrospective study analysed 155 pregnancies in 103 women with prosthetic heart valves: 95 mechanical prosthesis (MP) and 60 bioprostheses (BP). Among them 13 MP and 10 BP were bivalvular and four were mixed implants. In all, 182 (108 MP and 74 BP) prostheses were exposed to the risk of pregnancy. Among the 108 MP-bearing patients, 16 thromboembolic accidents (TEA) were recorded: 10 thromboses in 13 mitral, two aortic and one pulmonary MP. TEA were four times more frequent under oral anticoagulant therapy. Among the 74 BP, seven suffered premature valve failure. Ninety-nine infants were born to 50 MP-bearing women (53%) and 48 BP-bearing patients (80%) (P < 0.001). Twenty miscarriages were reported; they occurred more often under anticoagulant treatment (17%) than without it (4%) P < 0.02). Coumarin-induced embryopathies were rare (only one definitively identified). Because pregnancy with an MP under anticoagulant therapy is dangerous for the mother and may effect the fetus, the therapeutic indications for women of child-bearing age must be taken into consideration. In a women already with an MP at the time of conception, the duration of heparin therapy should be limited to the following two periods: from the 6th to the 12th week (coumarin-induced embryopathies) and during the last 2 weeks of gestation (haemorrhages during delivery and the neonatal period).

[Pregnancy in patients with heart valve prosthesis. A French retrospective cooperative study (155 cases)]. / Grossesses chez les porteuses de prothèses valvulaires. Etude coopérative rétrospective française (155 cas).

A French cooperative study of 155 pregnancies in 103 women with valvular prosthesis (95 mechanical, 60 bioprostheses including 27 bivalvular prostheses) is reported. Therefore, a total of 182 prostheses (108 mechanical and 74 bioprostheses) were exposed to the risk of pregnancy. The maternal outcome in the group of 108 mechanical prostheses was complicated by 16 thromboembolic events (TE) including 10 prosthetic valve thromboses which required emergency valve replacement in 4 cases, 6 systemic TE in 13 mitral, 2 aortic and 1 pulmonary mechanical prostheses. The TE were four times more frequent in patients on heparin than in those on oral anticoagulants. There were 4 deaths, 3 among the 10 prosthetic valve thromboses (one reoperation, two sudden deaths). Seven of the 74 bioprostheses were reoperated for degeneration on average 5.9 years after the initial operation but there were no deaths or TE. The outcome of pregnancy was 99 children (63%), 49 of which were born to mothers with mechanical prostheses (53%) and 50 to mothers with bioprostheses (80%) (p < 0.001). Seven of the children were born prematurely, all mothers being on anticoagulant therapy. The birth weight was over 400 grams heavier (3 kg versus 2.6 kg) in the bioprosthesis group (p < 0.05). The 20 spontaneous abortions (13%) were more common in patients on anticoagulants (17%) than in those without (2%) (p < 0.02). Congenital defects due to oral anticoagulants were rare (one certain case). There was one case of phocomelia, an abnormality which has never been described in this context. The 36 remaining pregnancies were still deaths (N = 5), abortion due to maternal death (N = 4), maternal complications (N = 8), therapeutic (N = 9) or voluntary abortions (N = 10) (28 mechanical and 8 bioprostheses).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition by glucagon of the cGMP-inhibited low-Km cAMP phosphodiesterase in heart is mediated by a pertussis toxin-sensitive G-protein.

We have recently reported that glucagon activated the L-type Ca2+ channel current in frog ventricular myocytes and showed that this was linked to the inhibition of a membrane-bound low-Km cAMP phosphodiesterase (PDE) (Méry, P. F., Brechler, V., Pavoine, C., Pecker, F., and Fischmeister, R. (1990) Nature 345, 158-161). We show here that the inhibition of membrane-bound PDE activity by glucagon depends on guanine nucleotides, a reproducible inhibition of 40% being obtained with 0.1 microM glucagon in the presence of 10 microM GTP, with GTP greater than GTP gamma S, while GDP and ATP gamma S were without effect. Glucagon had no effect on the cytosolic low-Km cAMP PDE, assayed with or without 10 microM GTP. Glucagon inhibition of membrane-bound PDE activity was not affected by pretreatment of the ventricle particulate fraction with cholera toxin. However, it was abolished after pertussis toxin pretreatment. Mastoparan, a wasp venom peptide known to activate G(i)/G(o) proteins directly, mimicked the effect of glucagon. PDE inhibition by glucagon was additive with the inhibition induced by Ro 20-1724, but was prevented by milrinone. This was correlated with an increase by glucagon of cAMP levels in frog ventricular cells which was not additive with the increase in cAMP due to milrinone. We conclude that glucagon specifically inhibits the cGMP-inhibited, milrinone-sensitive PDE (CGI-PDE). Insensitivity of adenylylcyclase to glucagon and inhibition by the peptide of a low-Km cAMP PDE were not restricted to frog heart, but also occurred in mouse and guinea pig heart. These results confirm that two mechanisms mediate the action of glucagon in heart: one is the activation of adenylylcyclase through Gs, and the other relies on the inhibition of the membrane-bound low-Km CGI-PDE, via a pertussis toxin-sensitive G-protein.

Activation of Na+/Ca2+ exchange by adenosine in ewe heart sarcolemma is mediated by a pertussis toxin-sensitive G protein.

We studied the effect of adenosine on Na+/Ca2+ exchange activity in ewe heart ventricular sarcolemmal vesicles. Adenosine was found to stimulate Na+/Ca2+ exchange activity in a dose-dependent manner from 0.1 nM to 10 microM, with maximal stimulation (40%) at 0.1 microM adenosine. The Vmax of Na+/Ca2+ exchange was increased, but the Km for Ca2+ was not altered. The effect of adenosine was specific since 1 microM adenine, inosine, and guanosine led to less than 15% stimulation, and adenosine diphosphate had no effect. Caffeine antagonized the activation of Na+/Ca2+ exchange by adenosine, and the order of potency of adenosine analogs was N6-(L-2-phenylisopropyl)adenosine = N6-cyclohexyladenosine = 5'-(N- ethylcarboxamido)adenosine much greater than N6-(D-2-phenylisopropyl)adenosine, indicating the involvement of A1 subclass receptors. The effect of adenosine was mimicked by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and blocked by pertussis toxin treatment. Taken together, these results suggest that A1 subclass receptors coupled to a pertussis toxin-sensitive G protein mediate the activation of Na+/Ca2+ exchange activity by adenosine. We conclude that the negative inotropic effect of adenosine in ventricular muscle, antagonistic toward cyclic AMP, may involve activation of Na+/Ca2+ exchange.