Vicens Martí

Implantation of a drug-eluting stent with a different drug (switch strategy) in patients with drug-eluting stent restenosis. Results from a prospective multicenter study (RIBS III [Restenosis Intra-Stent: Balloon Angioplasty Versus Drug-Eluting Stent]).

OBJECTIVES This study sought to assess the effectiveness of a strategy of using drug-eluting stents (DES) with a different drug (switch) in patients with DES in-stent restenosis (ISR). BACKGROUND Treatment of patients with DES ISR remains a challenge. METHODS The RIBS-III (Restenosis Intra-Stent: Balloon Angioplasty Versus Drug-Eluting Stent) study was a prospective, multicenter study that aimed to assess results of coronary interventions in patients with DES ISR. The use of a different DES was the recommended strategy. The main angiographic endpoint was minimal lumen diameter at 9-month follow-up. The main clinical outcome measure was a composite of cardiac death, myocardial infarction, and target lesion revascularization. RESULTS This study included 363 consecutive patients with DES ISR from 12 Spanish sites. The different-DES strategy was used in 274 patients (75%) and alternative therapeutic modalities (no switch) in 89 patients (25%). Baseline characteristics were similar in the 2 groups, although lesion length was longer in the switch group. At late angiographic follow-up (77% of eligible patients, median: 278 days) minimal lumen diameter was larger (1.86 ± 0.7 mm vs. 1.40 ± 0.8 mm, p = 0.003) and recurrent restenosis rate lower (22% vs. 40%, p = 0.008) in the different-DES group. At the last clinical follow-up (99% of patients, median: 771 days), the combined clinical endpoint occurred less frequently (23% vs. 35%, p = 0.039) in the different-DES group. After adjustment using propensity score analyses, restenosis rate (relative risk: 0.41, 95% confidence interval [CI]: 0.21 to 0.80, p = 0.01), minimal lumen diameter (difference: 0.41 mm, 95% CI: 0.19 to 0.62, p = 0.001), and the event-free survival (hazard ratio: 0.56, 95% CI: 0.33 to 0.96, p = 0.038) remained significantly improved in the switch group. CONCLUSIONS In patients with DES ISR, the implantation of a different DES provides superior late clinical and angiographic results than do alternative interventional modalities.

Early postoperative reduction of monoclonal antimyosin antibody uptake is associated with absent rejection-related complications after heart transplantation.

BackgroundDetection and treatment for rejection after transplantation are based on the identification of myocyte damage upon endomyocardial biopsy. Noninvasive detection of such damage is possible with 111In-labeled monoclonal antimyosin antibodies (MAA). Although the presence and degree of MAA uptake parallels the rejection activity detected by biopsy, the relation between the degree of uptake and the occurrence of severe rejection-related complications has not been previously assessed. Methods and ResultsTwo hundred forty-seven MAA studies were performed coinciding with biopsies in 52 patients 1-71 months after transplantation. A heart-to-lung ratio (HLR) was used as a measure of relative MAA uptake, with an HLR of 1.55 discriminating normal from abnormal studies. Of the 247 antimyosin studies, 149 coincided with absent, 38 with mild, and 60 with moderate rejection at biopsy. HLR was 1.68±0.27, 1.79±0.22, and 1.91±0.33 in the three biopsy groups, respectively (p < 0.0001). Two hundred thirty-eight of 247 antimyosin studies coexisted with absent rejection-related complications; in nine of 247 patients, such complications were detected (five congestive heart failure episodes due to rejection and four episodes of vascular occlusion, which resulted in five deaths), and mean HLR was 1.74±0.3 and 2.1±0.16 in the two groups, respectively (p < 0.0001). No complications were noted in 193 studies of patients with HLR of less than 2.00, whereas in nine of 45 with HRL of 2.00 or greater, complications occurred (p < 0.0001). None of the 23 patients prospectively followed since surgery who had a gradual decrease in MAA uptake during the first 3 months showed rejection-related complications, whereas persistent uptake was associated with complications in five of nine patients (p < 0.001) ConclusionsNo rejection-related complications are seen coinciding with HLR of less than 2.00, whereas patients who have complications have an HLR of more than 2.00. The early 3-month pattern of decreasing MAA uptake is associated with a clinical course free of rejection-related complications, whereas a persistent pattern is a signal of the possibility of such complications.

Long-Term Clinical Benefit of Sirolimus-Eluting Stents in Patients With In-Stent Restenosis: Results of the RIBS-II (Restenosis Intra-stent: Balloon angioplasty vs. elective sirolimus-eluting Stenting) Study

OBJECTIVES We sought to assess the long-term effectiveness and safety of sirolimus-eluting stents (SES) in patients with in-stent restenosis (ISR). BACKGROUND Treatment of patients with ISR remains a challenge. The long-term outcome of patients with ISR treated with SES remains unknown. METHODS The RIBS-II (Restenosis Intra-stent: Balloon angioplasty vs. elective sirolimus-eluting Stenting) study was a randomized trial conducted in 150 patients with ISR (76 SES, 74 balloon angioplasty [BA]). The long-term (>1 year) clinical outcome and pre-specified subgroup analyses were pre-defined secondary study end points. RESULTS At 1 year, the event-free survival (death, myocardial infarction, target vessel revascularization [TVR]) was better in the SES group (88% vs. 69%, p < 0.005). Additional long-term (>3 years) clinical follow-up was obtained in 97% of patients (median 3.3 years). After the first year, 3 patients died (1 SES, 2 BA), 5 suffered myocardial infarction (4 SES, 1 BA), and 7 required TVR (4 SES, 3 BA). At last follow-up, definitive/probable/possible stent thrombosis was similar in both groups (2/2/1 SES vs. 1/0/3 BA, p = NS). At 4 years, the event-free survival was 76% in the SES arm and 65% in the BA arm (p = 0.019). On multivariate analysis, SES implantation was an independent predictor of event-free survival. Subgroup analyses were consistent with the main outcome measure. CONCLUSIONS In patients with ISR, SES implantation remains effective and safe at very long-term clinical follow-up.

Efficacy of augmented immunosuppressive therapy for early vasculopathy in heart transplantation

OBJECTIVES The present study was undertaken to prospectively and comparatively evaluate the role of serial myocardial perfusion imaging and coronary angiography for the detection of early vasculopathy in a large patient population and also to determine the short- and long-term efficacy of augmented immunosuppressive therapy in the potential reversal of the early vasculopathy. BACKGROUND Allograft vasculopathy is the commonest cause of death after the first year of heart transplantation. Anecdotal studies have reported the efficacy of augmented immunosuppressive therapy after early detection of vascular involvement. However, no prospective study has evaluated the feasibility of early detection and treatment of allograft vasculopathy. METHODS In 76 cardiac allograft recipients, 230 coronary angiographic and 376 scintigraphic studies were performed in a follow-up period of 8 years. Angiography was performed at 1 month and every year after transplantation, and thallium-201 scintigraphy at 1, 3, 6 and 12 months after transplantation and twice a year thereafter. Prospective follow-up of 76 patients showed that 18 developed either angiographic or scintigraphic evidence of coronary vasculopathy. All episodes were treated with 3-day methylprednisolone pulse and antithymocyte globulin. RESULTS Twenty-two episodes of vasculopathy were diagnosed and treated in these 18 patients. Of these 22 episodes, two were detected only by angiography, seven by both angiography and scintigraphy, four by scintigraphy and histologic evidence of vasculitis and nine episodes only by thallium-201 scintigraphy studies. Angiographic and/or scintigraphic resolution was observed in 15 of the 22 episodes (68%) with augmented immunosuppression. The likelihood of regression was higher when treatment was instituted within the first year of transplantation (92%) than after the first year (40%) (p = 0.033). Eighty percent of patients who responded to follow-up. CONCLUSIONS The present study suggests that early detection of allograft coronary vasculopathy is feasible with surveillance myocardial perfusion or coronary angiographic studies. When identified early after transplantation, immunosuppressive treatment may result in regression of coronary disease.

Presence, evolving changes, and prognostic implications of myocardial damage detected in idiopathic and alcoholic dilated cardiomyopathy by 111In monoclonal antimyosin antibodies.

BACKGROUND The clinical relevance of myocardial cell damage in dilated cardiomyopathy is uncertain. Myocardial uptake of 111In monoclonal antimyosin antibodies (MAA) was used to study myocardial damage in patients with idiopathic (IDC) and alcoholic (ADC) dilated cardiomyopathy and to assess its prognostic implications. METHODS AND RESULTS MAA and echocardiographic studies were performed in 117 patients. Intensity of antibody uptake was measured by heart-to-lung ratio (HLR) (normal < 1.55). Studies were repeated in survivors and patients who did not receive a cardiac transplant. Follow-up extended up to 62 months (mean, 23 +/- 16 months). Eighty-eight patients with IDC showed a 77% prevalence of abnormal MAA. After acute-onset IDC, reduction of HLR (1.81 +/- 0.2 to 1.56 +/- 0.1) (P = .007) with improvement in ejection fraction (EF) (35 +/- 10% to 46 +/- 14%) (P = .018) was observed. No changes in HLR or EF were detected in patients with chronic stable IDC. Twenty-nine patients with ADC showed a lower prevalence (48%) of abnormal MAA studies than those with IDC (P = .003). HLR was higher in 13 active (1.78 +/- 0.3) than in 16 past consumers (1.49 +/- 0.2) (P = .019); in the former, HLR decreased to 1.44 +/- 0.2 (P = .012), and EF improved (35 +/- 14% to 53 +/- 18%) (P = .05) after abstention. Intensities of uptake HLR of > 1.87 were associated with increased risk of death or transplantation. CONCLUSIONS In patients with IDC, variations of MAA uptake are detected in patients who present acutely but not in those with chronic stable disease. In patients with ADC, MAA uptake mainly depends on alcohol consumption. In both situations, reduction of uptake correlates with improvement of ventricular function. Higher intensities of MAA uptake are associated with a worse outcome. The intensity of antibody uptake, along with other clinical and functional variables, may be helpful in risk stratification of patients with dilated cardiomyopathy.

Active myocardial damage without attending inflammatory response in dilated cardiomyopathy.

OBJECTIVES This study aimed to compare indium-111 (111In)-monoclonal antimyosin antibody uptake in patients with dilated cardiomyopathy before heart transplantation with the histologic findings in the explanted hearts. BACKGROUND A high prevalence of 111In-monoclonal antimyosin antibody uptake has been described in patients with dilated cardiomyopathy, suggesting the presence of active, ongoing myocyte damage; however, no correlation between monoclonal antimyosin antibodies and histologic findings is available in these patients. METHODS A consecutive series of 21 patients with dilated cardiomyopathy awaiting heart transplantation were studied with monoclonal antimyosin antibodies before the operation, and the results were compared with the histologic analysis of the explanted hearts. The interval between monoclonal antimyosin antibody studies and transplantation was 1 to 90 days (mean 58 +/- 31). RESULTS Using a semiquantitative method (heart/lung ratio), monoclonal antimyosin antibody uptake was present in 15 (71%) of 21 patients, but active myocarditis in the explanted hearts was detected in only 7. In 11 patients, intense monoclonal antimyosin antibody uptake coexisting with absent myocyte damage or cellular infiltration of explanted hearts was noted. One patient who showed preoperative monoclonal antimyosin antibody uptake underwent transplantation 11 h later, and ex vivo diffuse myocardial antimyosin uptake was detected, but active myocarditis was seen only at cardiectomy in only a small area of the heart; the rest of the myocardium showed no signs of myocyte damage. CONCLUSIONS In dilated cardiomyopathy, monoclonal antimyosin antibody uptake cannot be equated with the presence of an inflammatory response detected in the myocardium of the explanted heart.

Spectrum of Alcohol-Induced Myocardial Damage Detected by Indium-111–Labeled Monoclonal Antimyosin Antibodies

OBJECTIVES We sought to determine the prevalence, intensity and evolving changes of myocardial damage detected by myocardial uptake of antimyosin antibodies in patients with alcohol-induced dilated cardiomyopathy, alcohol addicts attending a detoxification unit and healthy subjects with short-term alcohol consumption. BACKGROUND Evidence of alcohol-induced myocardial damage may be provided by myocardial uptake of indium-111-labeled monoclonal antimyosin antibodies. The spectrum of such damage in patients who are heavy drinkers (> 100 g for > 10 years), with or without cardiomyopathy, and the impact of short-term alcohol ingestion on antimyosin antibody uptake have not been adequately explored. METHODS One hundred twenty antimyosin studies were performed in 56 patients with dilated cardiomyopathy (group I), 15 alcohol addicts attending a detoxification unit (group II) and 6 volunteers for short-term alcohol ingestion (group III). Estimation of antibody uptake was calculated through a heart/lung ratio (HLR) (normal < 1.55). RESULTS The 56 patients in group I (54 men, 2 women; mean [+/-SD] age 46 +/- 11 years) had consumed 123 +/- 60 g/day of alcohol for 21 +/- 9 years, for a cumulative intake of 914 +/- 478 kg. Mean duration of symptoms was 46 +/- 49 months. Mean left ventricular end-diastolic diameter was 71 +/- 10 mm, and mean ejection fraction was 28 +/- 12%. No differences in New York Heart Association functional class, ventricular size or ejection fraction were noted between 28 active and 28 past consumers, except for the prevalence and intensity of antibody uptake (75% vs. 32%, p < 0.001) and HLR (1.75 +/- 0.26 vs. 1.49 +/- 0.17, p = 0.0001). In 19 patients in the active group restudied after alcohol withdrawal, antibody uptake decreased (from 1.76 +/- 0.17 to 1.55 +/- 0.19, p < 0.001), and ejection fraction improved (from 30 +/- 12% to 43 +/- 16%, (p < 0.001). No changes occurred in the 15 past consumers restudied. The 15 male patients in group II (mean age 36 +/- 4 years) had consumed 156 +/- 59 g/day for 17 +/- 5 years, for a cumulative alcohol intake of 978 +/- 537 kg, an amount similar to that in patients in group I, but antimyosin antibody uptake was detected in only 3 (20%) of 15 patients. None of six group III subjects developed antibody uptake after short-term ethanol ingestion. Despite the small sample size, the power to detect clinically relevant differences in most variables that did not reach statistical significance was amply sufficient. CONCLUSIONS In alcohol-induced dilated cardiomyopathy, alcohol withdrawal is associated with the reduction or disappearance of myocardial damage and improvement of function. The difference in prevalence of antimyosin antibody uptake in patients with and without cardiac disease who consume similar amounts of alcohol suggests the presence of those with different myocardial susceptibilities to alcohol. Short-term ethanol ingestion in healthy subjects does not induce detectable uptake of antimyosin antibodies.

Evaluation of Myocardial Cell Damage by In-111-Monoclonal Antimyosin Antibodies in Patients Under Chronic Tricyclic Antidepressant Drug Treatment

BACKGROUND The capability of chronic tricyclic antidepressant drug (TAD) treatment to elicit myocardial damage has been a subject of debate. Lack of an adequate noninvasive method to detect such damage has prevented an in-depth study. METHODS AND RESULTS A prospective study with In-111-monoclonal antimyosin antibodies was undertaken in a series of 21 young patients with major depression on TADs and a control group of 19 healthy subjects. A heart-to-lung ratio (HLR) of antimyosin uptake was used to discriminate normal from abnormal scans. HLR in healthy subjects was 1.39 +/- 0.08. Patients on imipramine (HLR, 1.41 +/- 0.09) or clomipramine (HLR, 1.44 +/- 0.06) showed normal studies. Those under amitriptyline had a higher HLR (1.58 +/- 0.12) compared with nonamitriptyline or normal groups (P < .05). None of the 15 patients on imipramine or clomipramine showed abnormal HLR, while 3 of 6 on amitriptyline did (P < .01). In these 3 patients, uptake decreased or disappeared after drug withdrawal. Ejection fraction was normal in every patient. CONCLUSIONS Monoclonal antimyosin antibody studies are normal in imipramine- and clomipramine-treated patients. Antibody uptake in those under amitriptyline treatment, which disappears after drug withdrawal, would suggest early evidence of myocardial toxicity.

Resultados inmediatos y a largo plazo de la angioplastia con stent del tronco común

Introduccion y objetivos La cirugia de derivacion aortocoronaria ha sido considerada el tratamiento de eleccion de la estenosis del tronco comun. Diversos estudios multicentricos sugieren la posibilidad de la angioplastia con stent. El objetivo del presente estudio fue analizar los resultados inmediatos y a largo plazo de la angioplastia con stent en el tronco comun, asi como identificar los factores predictores de mortalidad. Pacientes y metodo Se incluyo a 38 pacientes no consecutivos de 69 ± 8 anos de edad con una lesion severa del tronco comun a los que se implanto un stent entre noviembre de 1997 y marzo del 2003. La indicacion de la angioplastia fue «electiva» en 27 pacientes y «urgente » en los 11 restantes. El tronco comun no estaba protegido en 23 pacientes (60,5%). En todos los pacientes se realizo el seguimiento clinico a los 25 ± 20 meses. Resultados En todos los pacientes, el procedimiento angiografico se realizo con exito. Un paciente presento una oclusion aguda 1 h despues. En 4 pacientes (10%) se produjo un infarto de miocardio no transmural. La mortalidad hospitalaria fue del 15,8%. En el grupo con indicacion urgente, 5 de 11 pacientes (45,4%) fallecieron por fallo cardiaco severo (clase Killip III-IV) en el contexto de un infarto agudo de miorcadio. En cambio, solo fallecio 1 de los 27 pacientes (3,7%) del grupo electivo (p = 0,007). Durante el seguimiento se produjeron eventos clinicos mayores en 5 pacientes (13%): 3 fallecieron y los 2 restantes presentaron recurrencia de la angina. Todos los pacientes que fallecieron tenian el tronco comun desprotegido. La probabilidad acumulada de supervivencia para el grupo electivo fue del 92 ± 0,5, 88 ± 0,6 y 86 ± 0,7% a los 6 meses, 1 y 3 anos, respectivamente. En cambio, para el grupo urgente fue del 54 ± 0,2% a partir del sexto mes (p Conclusiones La angioplastia con stent del tronco comun en pacientes seleccionados se asocia con una elevada tasa de exito inmediato. En la angioplastia electiva, la incidencia de eventos cardiacos durante el seguimiento es relativamente baja. La angioplastia urgente y la presencia de signos de disfuncion ventricular izquierda son los principales predictores de mortalidad.

Comparison of the Efficacy of Everolimus-Eluting Stents Versus Drug-Eluting Balloons in Patients With In-Stent Restenosis (from the RIBS IV and V Randomized Clinical Trials).

Treatment of patients with in-stent restenosis (ISR) remains a challenge. This study sought to compare the efficacy of everolimus-eluting stents (EESs) and drug-eluting balloons (DEBs) with paclitaxel in patients with ISR. A pooled analysis of the Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloon vs Everolimus-Eluting Stent (RIBS IV) and Restenosis Intra-Stent of Bare-Metal Stents: Drug-Eluting Balloon vs Everolimus-Eluting Stent (RIBS V) randomized trials was performed using patient-level data. In both trials, EESs were compared with DEBs in patients with ISR (RIBS V included 189 patients with bare-metal ISR; RIBS IV included 309 patients with drug-eluting ISR). Inclusion and exclusion criteria were identical in both trials. A total of 249 patients were allocated to EES and 249 to DEB. Clinical follow-up at 1 year was obtained in all (100%) patients and late angiography (median 249 days) in 91% of eligible patients. Compared with patients treated with DEBs, patients treated with EESs obtained better short-term results (postprocedural minimal lumen diameter 2.28 ± 0.5 vs 2.12 ± 0.4 mm, p <0.0001). At follow-up, patients treated with EESs had larger in-segment minimal lumen diameter (primary end point 2.16 ± 0.7 vs 1.88 ± 0.6 mm, p <0.0001; absolute mean difference 0.28 mm; 95% confidence interval [CI] 0.16 to 0.40) and net lumen gain (1.33 ± 0.6 vs 1.00 ± 0.7 mm, p <0.0001) and had lower %diameter stenosis (19 ± 21% vs 28 ± 22%, p <0.0001) and binary restenosis rate (8.7% vs 15.7%, p = 0.02). Consistent results were observed in the in-lesion analysis. No interactions were found between the underlying stent type and treatment effects. At 1-year clinical follow-up, the composite of cardiac death, myocardial infarction, and target vessel revascularization was significantly reduced in the EES arm (8.8% vs 14.5%, p = 0.03; hazard ratio 0.59, 95% CI 0.31 to 0.94) mainly driven by a lower need for target vessel revascularization (6% vs 12.4%, p = 0.01, hazard ratio 0.46, 95% CI 0.25 to 0.86). This pooled analysis of the RIBS IV and RIBS V randomized trials demonstrates the superiority of EES over DEB in the treatment of patients with ISR.