Pedro Mota

Age-Dependent Profile of Left-Sided Infective Endocarditis A 3-Center Experience

Background— The influence of age on the main epidemiological, clinical, echocardiographic, microbiological, and prognostic features of patients with infective endocarditis remains unknown. We present the series with the largest numbers and range of ages of subjects to date that analyzes the influence of age on the main characteristics of patients with isolated left-sided infective endocarditis. Furthermore, this series is the first one in which patients have been distributed according to age quartile. Methods and Results— A total of 600 episodes of left-sided endocarditis consecutively diagnosed in 3 tertiary centers were stratified into age-specific quartiles and 107 variables compared between the different groups. With increasing age, the percentage of women, previous heart disease, predisposing disease (diabetes mellitus and cancer), and infection by enterococci and Streptococcus bovis also increased. Valvular insufficiency and perforation and Staphylococcus aureus infection were more common in younger patients. The therapeutic approach differed depending on patient age because of the growing proportion of older patients who only received medical treatment. Clinical course and hospital prognosis were worse in the older patients because of increased surgical mortality among them. Conclusions— Increasing age is associated with less valvular impairment (insufficiency and perforation), a more favorable microbiological profile, and increased surgical mortality among adults with left-sided infective endocarditis.

Association between self-replicating calcifying nanoparticles and aortic stenosis: a possible link to valve calcification.

AIMS Among various hypotheses proposed for pathological tissue calcification, recent evidence supports the possibility that self-replicating calcifying nanoparticles (CNPs) can contribute to such calcification. These CNPs have been detected and isolated from calcified human tissues, including blood vessels and kidney stones, and are referred to as nanobacteria. We evaluated calcific aortic valves for the presence of CNP. METHODS AND RESULTS Calcific aortic valves were obtained from 75 patients undergoing surgical valve replacement. The control group was formed by eight aortic valves corresponding to patients with heart transplants. In the microbiology laboratory, valves were screened for CNP using a 4-6 weeks specific culture method. The culture for CNP was positive in 48 of the 75 valves with aortic stenosis (64.0%) in comparison with zero of eight (0%) for the control group (P = 0.0005). The observation of cultures by way of scanning electron microscopy highlighted the resemblance in size and morphology of CNP. CONCLUSION Self-replicating calcific nanometer-scale particles, similar to those described as CNP from other calcific human tissues, can be cultured and visualized from calcific human aortic valves. This finding raises the question as to whether CNP contribute to the pathogenesis of the disease or whether they are only innocent bystanders.

Rationale, design, and methods for the early surgery in infective endocarditis study (ENDOVAL 1): A multicenter, prospective, randomized trial comparing the state-of-the-art therapeutic strategy versus early surgery strategy in infective endocarditis

BACKGROUND The prognosis of infective endocarditis is poor and has remained steady over the last 4 decades. Several nonrandomized studies suggest that early surgery could improve prognosis. METHODS ENDOVAL 1 is a multicenter, prospective, randomized study designed to compare the state-of-the-art therapeutic strategy (advised by the international societies in their guidelines) with the early-surgery strategy in high-risk patients with infective endocarditis. Patients with infective endocarditis without indication for surgery will be included if they meet at least one of the following: (1) early-onset prosthetic endocarditis; (2) Staphylococcus aureus endocarditis; (3) periannular complications; (4) new-onset conduction abnormalities; (5) new-onset severe valvular dysfunction. A total of 216 patients will be randomized to either of the 2 strategies. Stratification will be done within 3 days of admission. In the early surgery arm, the surgical procedure will be performed within 48 hours of randomization. The only event to be considered will be death within 30 days. The study will be extended to 1 year. In the follow-up substudy, death and a new episode of endocarditis will be regarded as events. CONCLUSION ENDOVAL 1, the first randomized study on endocarditis, will provide crucial information regarding the putative benefit of early surgery over the state-of-the-art therapeutic approach in high-risk patients with infective endocarditis.

Isolated Right-Sided Valvular Endocarditis in Non-Intravenous Drug Users

INTRODUCTION AND OBJECTIVES Characteristics of isolated right-sided endocarditis in patients without a pacemaker and who are not intravenous drug users (IVDU) are poorly understood. The aim of this study was to investigate the current frequency of this entity and describe its clinical, microbiological, echocardiographic and prognostic profile. METHODS We have prospectively analyzed 17 consecutive cases of isolated right-sided endocarditis in non-IVDU who did not have a pacemaker, out of a total of 583 consecutive episodes of endocarditis (2.9%). RESULTS Mean age was 38+/-15 years; 11 of the 17 patients were men. Almost half of the patients had at least one predisposing disease. An intravascular catheter was the most frequent port of entry (35%). The most common signs and symptoms on admission were fever, dyspnea, septic pulmonary embolisms, pleural effusion and right-sided heart failure. The most frequent microorganism was Staphylococcus aureus (41%). In most cases (82%) the infection was located in the tricuspid valve. Recurrent pulmonary embolisms were the most frequent complication and the main cause for surgery, which was needed in 5 patients (29%). Two patients died during hospitalization (12%), both from septic shock. During follow-up one patient died of unknown causes 1 month after discharge, and other relapsed 3 months after discharge. CONCLUSIONS Isolated right-sided endocarditis should be included in the differential diagnosis of patients with febrile syndrome, respiratory symptoms and predisposing disease, even when they do not have a pacemaker and are not IVDU. The presence of intravascular catheters and Staphylococcus bacteriemia should heighten suspicion of endocarditis.

Endocarditis derecha aislada en pacientes no adictos a drogas por vía parenteral

Introduccion y objetivos La endocarditis derecha aislada es una entidad poco conocida cuando afecta a pacientes no portadores de marcapasos y no adictos a drogas por via parenteral (ADVP). Nuestro objetivo es estudiar la frecuencia actual de esta entidad y describir su perfil clinico, microbiologico, ecocardiografico y pronostico. Metodos Hemos analizado 17 casos de endocarditis derecha aislada en pacientes no ADVP y no portadores de marcapasos, de un total de 583 episodios consecutivamente diagnosticados de endocarditis infecciosa (3%). Resultados La media de edad fue 38 ± 15 anos y 11 pacientes eran varones. El 47% de los pacientes presentaban alguna enfermedad predisponente. El cateter intravascular fue la puerta de entrada mas frecuente (35%). Los sintomas y signos mas comunes al ingreso fueron fiebre, disnea, embolia pulmonar septica, derrame pleural e insuficiencia cardiaca derecha. El microorganismo mas frecuente fue Staphylococcus aureus (41%). La mayoria de los casos asentaron en la valvula tricuspide (82%). La embolia pulmonar recurrente fue la complicacion mas frecuente y la principal causa de cirugia, que fue precisa en 5 (29%) casos. Fallecieron 2 (12%) pacientes, ambos por shock septico. En el seguimiento, 1 paciente fallecio al mes del alta por causa desconocida y 1 presento una recaida al tercer mes. Conclusiones La endocarditis derecha aislada debe incluirse en el diagnostico diferencial de pacientes con sindrome febril, sintomas respiratorios y alguna enfermedad predisponente, aunque no sean portadores de marcapasos o ADVP. La presencia de cateteres intravasculares y la bacteriemia por estafilococos refuerzan la sospecha de endocarditis en estos pacientes.

Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial

Abstract Aims We aimed to determine whether treatment with sildenafil improves outcomes of patients with persistent pulmonary hypertension (PH) after correction of valvular heart disease (VHD). Methods and results The sildenafil for improving outcomes after valvular correction (SIOVAC) study was a multricentric, randomized, parallel, and placebo-controlled trial that enrolled stable adults with mean pulmonary artery pressure ≥ 30 mmHg who had undergone a successful valve replacement or repair procedure at least 1 year before inclusion. We assigned 200 patients to receive sildenafil (40 mg three times daily, n = 104) or placebo (n = 96) for 6 months. The primary endpoint was the composite clinical score combining death, hospital admission for heart failure (HF), change in functional class, and patient global self-assessment. Only 27 patients receiving sildenafil improved their composite clinical score, as compared with 44 patients receiving placebo; in contrast 33 patients in the sildenafil group worsened their composite score, as compared with 14 in the placebo group [odds ratio 0.39; 95% confidence interval (CI) 0.22–0.67; P < 0.001]. The Kaplan–Meier estimates for survival without admission due to HF were 0.76 and 0.86 in the sildenafil and placebo groups, respectively (hazard ratio 2.0, 95% CI = 1.0–4.0; log-rank P = 0.044). Changes in 6-min walk test distance, natriuretic peptides, and Doppler-derived systolic pulmonary pressure were similar in both groups. Conclusion Treatment with sildenafil in patients with persistent PH after successfully corrected VHD is associated to worse clinical outcomes than placebo. Off-label usage of sildenafil for treating this source of left heart disease PH should be avoided. The trial is registered with ClinicalTrials.gov, number NCT00862043.

Absence of accelerated atherosclerotic disease progression after intracoronary infusion of bone marrow derived mononuclear cells in patients with acute myocardial infarction--angiographic and intravascular ultrasound--results from the TErapia Celular Aplicada al Miocardio Pilot study.

BACKGROUND We tried to evaluate a putative negative effect on coronary atherosclerosis in patients receiving intracoronary infusion of unfractionated bone marrow mononuclear cells (BMMC) following an acute ST-elevation myocardial infarction. Peripheral blood mononuclear cells or enriched CD133(+) BMMC have been associated with accelerated atherosclerosis of the distal segment of the infarct related artery (IRA). METHODS Thirty-seven patients with ST-elevation myocardial infarction from the TECAM pilot study underwent intracoronary infusion of autologous BMMC 9 +/- 3.1 days after onset of symptoms. We compared angiographic changes from baseline to 9 months of follow-up in the distal non-stented segment of the IRA, as well as in the contralateral coronary artery, with a matched control group. A subgroup of 15 treated patients underwent additional IVUS within the distal segment of the IRA. RESULTS No difference between stem cell and control group were found regarding changes in minimum lumen diameter (0.006 +/- 0.42 vs 0.06 +/- 0.41 mm, P = ns) and the percentage of stenosis (-2.68 +/- 12.33% vs -1.78 +/- 8.75%, P = ns) at follow-up. Likewise, no differences were seen regarding changes in the contralateral artery (minimum lumen diameter -0.004 +/- 0.54 mm vs -0.06 +/- 0.35 mm, P = ns). In the intravascular ultrasound substudy, no changes were demonstrated comparing baseline versus follow-up in maximum area stenosis and plaque volume. CONCLUSIONS In this pilot study, analysis of a subgroup of patients found that intracoronary injection of unfractionated BMMC in patients with acute ST-elevation myocardial infarction was not associated with accelerated atherosclerosis progression at mid term. Prospective, randomised studies in large cohorts with long-term angiographic and intravascular ultrasound follow-up are necessary to determine the safety of this therapy.

Comparison of Neointimal Hyperplasia With Drug-Eluting Stents Versus Bare Metal Stents in Patients Undergoing Intracoronary Bone-Marrow Mononuclear Cell Transplantation Following Acute Myocardial Infarction

The aims of this study were to assess the safety of drug-eluting stent (DES) use and to compare the incidence of in-stent restenosis (ISR) and neointimal hyperplasia formation according to the type of stent implanted (DES vs bare-metal stents [BMS]) in patients who underwent intracoronary bone marrow mononuclear cell transplantation after acute ST elevation myocardial infarction. Fifty-nine patients with successfully revascularized ST elevation myocardial infarction (37 using BMS and 22 using DES) underwent paired angiographic examinations at baseline and 6 to 9 months after the intracoronary injection of 91 million +/- 56 million autologous bone marrow mononuclear cells. A subgroup of 30 patients also underwent serial intravascular ultrasound examinations. Off-line angiographic assessment showed 4 cases of binary ISR, primarily in BMS (3 cases), and no major adverse cardiac events were associated with stent type (mean follow-up period 41 +/- 10 months). At follow-up, angiographic late luminal loss was significantly lower in patients with DES than in those patients with BMS (0.35 +/- 0.66 vs 0.71 +/- 0.38 mm, p = 0.011). Multivariate analysis identified the use of DES (beta = -0.32, 95% confidence interval [CI] -0.57 to -0.26, p = 0.03) and a smaller baseline reference vessel diameter (beta = 0.29, 95% CI 0.04 to 0.54, p = 0.02) as independent predictors of lower late loss. Moreover, intravascular ultrasound showed a significant reduction of in-stent neointimal hyperplasia formation related to DES use compared with BMS use (Delta neointimal hyperplasia volume 5.4 mm(3) [95% CI 2.7 to 28.1] vs 35.9 mm(3) [95% CI 22.0 to 43.6], p = 0.035). In conclusion, these findings suggest that the use of DES is safe and may prevent ISR and neointimal hyperplasia formation in patients who undergo intracoronary bone marrow mononuclear cell transplantation after a successfully revascularized ST elevation myocardial infarction.