José Alberto San Román

Experimental and Clinical Regenerative Capability of Human Bone Marrow Cells After Myocardial Infarction

Bone marrow mononuclear cells (BMCs) from 20 patients with extensive reperfused myocardial infarction (MI) were used to assess their myocardial regenerative capability “in vitro” and their effect on postinfarction left ventricular (LV) remodeling. Human BMCs were labeled, seeded on top of cryoinjured mice heart slices, and cultured. BMCs showed tropism for and ability to graft into the damaged mouse cardiac tissue and, after 1 week, acquired a cardiomyocyte phenotype and expressed cardiac proteins, including connexin43. In the clinical trial, autologous BMCs (78±41×106 per patient) were intracoronarily transplanted 13.5±5.5 days after MI. There were no adverse effects on microvascular function or myocardial injury. No major cardiac events occurred up to 11±5 months. At 6 months, magnetic resonance showed a decrease in the end-systolic volume, improvement of regional and global LV function, and increased thickness of the infarcted wall, whereas coronary restenosis was only 15%. No changes were found in a nonrandomized contemporary control group. Thus, BMCs are capable of nesting into the damaged myocardium and acquire a cardiac cell phenotype in vitro as well as safely benefiting ventricular remodeling in vivo. Large-scale randomized trials are needed now to assess the clinical efficacy of this treatment.

Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomised controlled trial

BACKGROUND In patients with ST-segment elevated myocardial infarction (STEMI), early post-thrombolysis routine angioplasty has been discouraged because of its association with high incidence of events. The GRACIA-1 trial was designed to reassess the benefits of an early post-thrombolysis interventional approach in the era of stents and new antiplatelet agents. METHODS 500 patients with thrombolysed STEMI (with recombinant tissue plasminogen activator) were randomly assigned to angiography and intervention if indicated within 24 h of thrombolysis, or to an ischaemia-guided conservative approach. The primary endpoint was the combined rate of death, reinfarction, or revascularisation at 12 months. Analysis was by intention to treat. FINDINGS Invasive treatment included stenting of the culprit artery in 80% (199 of 248) patients, bypass surgery in six (2%), non-culprit artery stenting in three, and no intervention in 40 (16%). Predischarge revascularisation was needed in 51 of 252 patients in the conservative group. By comparison with patients receiving conservative treatment, by 1 year, patients in the invasive group had lower frequency of primary endpoint (23 [9%] vs 51 [21%], risk ratio 0.44 [95% CI 0.28-0.70], p=0.0008), and they tended to have reduced rate of death or reinfarction (7% vs 12%, 0.59 [0.33-1.05], p=0.07). Index time in hospital was shorter in the invasive group, with no differences in major bleeding or vascular complications. At 30 days both groups had a similar incidence of cardiac events. In-hospital incidence of revascularisation induced by spontaneous recurrence of ischaemia was higher in patients in the conservative group than in those in the invasive group. INTERPRETATION In patients with STEMI, early post-thrombolysis catheterisation and appropriate intervention is safe and might be preferable to a conservative strategy since it reduces the need for unplanned in-hospital revascularisation, and improves 1-year clinical outcome.

Acute aortic syndrome

All variants of acute aortic pathology must be considered in the differential diagnosis of the patient presenting with an acute aortic syndrome. In addition to classic aortic dissection, this syndrome includes intramural aortic hematoma and penetrating aortic ulcer. The diagnosis of these two last lesions, which lack a mobile intimomedial flap and a double aortic lumen, is difficult. In this review, some anatomical and diagnostic aspects of the acute aortic pathology are discussed to help to better identify these patients.

Timing, Predictive Factors, and Prognostic Value of Cerebrovascular Events in a Large Cohort of Patients Undergoing Transcatheter Aortic Valve Implantation

Background— The objective of this study was to evaluate the timing, predictive factors, and prognostic value of cerebrovascular events (CVEs) after transcatheter aortic valve implantation. Methods and Results— The study included 1061 consecutive patients who underwent transcatheter aortic valve implantation with a balloon-expandable (64%) or self-expandable (36%) valve. CVEs were classified as acute (⩽24 hours), subacute (1–30 days), or late (>30 days). CVEs occurred in 54 patients (5.1%; stroke, 4.2%) within 30 days after transcatheter aortic valve implantation (acute in 54% of cases). The predictors of acute CVEs were balloon postdilation of the valve prosthesis (odds ratio, 2.46; 95% confidence interval,1.07–5.67) and valve dislodgment/embolization (odds ratio, 4.36; 95% CI, 1.21–15.69); new-onset atrial fibrillation (odds ratio, 2.76; 95% CI, 1.11–6.83) was a predictor of subacute CVEs. Late CVEs occurred in 35 patients (3.3%; stroke, 2.1%) at a median follow-up of 12 months (3–23 months). The predictors of late CVEs were chronic atrial fibrillation (2.84; 95% CI, 1.46–5.53), peripheral vascular disease (hazard ratio, 2.02; 95% CI, 1.02–3.97), and prior cerebrovascular disease (hazard ratio, 2.04; 95% CI, 1.01–4.15). Major stroke was associated with 30-day (odds ratio, 7.43; 95% CI, 2.45–22.53) and late (hazard ratio, 1.75; 95% CI, 1.01–3.04) mortality. Conclusions— In a large cohort of patients undergoing transcatheter aortic valve implantation, the rates of acute and subacute CVEs were 2.7% and 2.4%, respectively. While balloon postdilation and valve dislodgment/embolization were the predictors of acute CVEs, new-onset atrial fibrillation determined a higher risk for subacute events. Late events were determined mainly by a history of chronic atrial fibrillation and peripheral and cerebrovascular disease. The occurrence of major stroke was associated with increased early and late mortality. These results provide important insights for the implementation of preventive measures for CVEs after transcatheter aortic valve implantation.

Natural history and serial morphology of aortic intramural hematoma: A novel variant of aortic dissection

BACKGROUND Acute aortic dissection is a cardiovascular emergency that requires prompt diagnosis and treatment. Transesophageal echocardiography is the current standard diagnostic imaging modality in many medical centers. Aortic intramural hematoma is a variant of aortic dissection whose natural history and prognosis have not been well studied. We performed transesophageal echocardiography in patients with aortic intramural hematoma to determine the echocardiographic characteristics and echocardiographic evolution of this lesion, impact on patient management, and patient outcome. METHODS AND RESULTS Twenty-one consecutive patients with aortic intramural hematoma confirmed anatomically (four patients) or with an additional diagnostic imaging technique (17 patients) underwent a transesophageal echocardiographic examination. Fifteen patients with longstanding hypertension had chest or back pain, and the intramural hematoma was visualized in the ascending aorta (n = 4), along the whole aorta (n = 4), in the descending aorta (n = 6), or in the aortic arch (n = 1). The thickening of the aortic wall was crescentic. Patients with ascending aortic intramural hematoma had the following results: two patients died suddenly, three patients underwent surgery because of increased aortic wall thickening (one patient) or secondary intimal tear (two patients), and the remaining three patients had regression of the hematoma. Patients with hematoma confined to the descending aorta and the patient with aortic arch involvement (n = 7) had a different result: one patient died from aortic rupture and the remaining six patients did well. Six patients had a traumatic aortic injury, and the intramural hematoma was located along the descending thoracic aorta. The thickening of the aortic wall was circular in five patients and crescentic in one. Three of these patients had normalized thickness of the aortic wall on follow-up transesophageal echocardiographic studies. The other three patients died from multiorgan system failure. Aortography showed a reduction of the diameter of the aortic lumen in four patients; diameter in the remaining 17 patients was normal. CONCLUSIONS Aortic intramural hematoma can be detected and monitored by transesophageal echocardiography but not by aortography. Two types of aortic intramural hematoma can be distinguished: (1) traumatic of good prognosis and (2) nontraumatic, which can be an early stage of the classic aortic dissection, with bad prognosis in cases involving the ascending aorta.

Guías de práctica clínica de la Sociedad Española de Cardiología en pruebas de esfuerzo

La mayor parte de las pruebas de esfuerzo se realizan a pacientes adultos con cardiopatia isquemica en estudio o ya conocida. En los ultimos anos se ha producido la incorporacion de las tecnicas de imagen en este campo, mejorando asi la informacion aportada por la prueba de esfuerzo convencional. Pero cada vez existen mas situaciones que escapan a esta norma general, tanto en sujetos sanos (asintomaticos, atletas, discapacitados, etc.) como en pacientes con cardiopatias diferentes de la isquemica (insuficiencia cardiaca congestiva avanzada, hipertension, trastornos del ritmo, cardiopatias congenitas etc.). Todos estos aspectos justifican un documento de consenso en Espana, necesariamente multidisciplinario. Este documento revisa en profundidad la metodologia de las pruebas de esfuerzo convencionales, sin olvidar las realizadas con determinacion de consumo de oxigeno. El papel de esta exploracion en el manejo de la cardiopatia isquemica, asi como las aplicaciones de las tecnicas de imagen al campo del estres, ocupan un lugar fundamental en esta revision. Por ultimo, se analiza la utilidad de las pruebas de esfuerzo en diversas cardiopatias no isquemicas y en diferentes poblaciones de sujetos sanos.

Acute Coronary Syndrome in Infective Endocarditis

INTRODUCTION AND OBJECTIVES To describe the clinical, microbiologic, echocardiographic characteristics, and disease progression in patients who experience an acute coronary syndrome during an episode of endocarditis. METHODS The study included 586 consecutive patients who were diagnosed of infective endocarditis (481 left-sided) at one of five hospitals between 1995 and 2005. RESULTS Overall, 14 patients (2.9%) had an acute coronary syndrome. Their mean age was 50 (17) years, and 50% had a prosthetic valve. For 11 episodes of endocarditis, laboratory cultures tested positive, with Staphylococcus aureus being the most frequently isolated microorganism. Vegetations were detected by transesophageal echography in 12 cases. The infection was located in the aortic valve in 12 cases. In the 14 patients, periannular complications were found more frequently (11 [78.6%] vs 172 [36.8%]; P=.03), and their size was greater than in other patients. Thirteen had moderate-to-severe valvular regurgitation. In most patients, acute coronary syndrome was an early complication of endocarditis. Myocardial ischemia was due to an embolism in three cases and to coronary artery compression in eight. During follow-up, patients with acute coronary syndrome had higher incidences of heart failure (6 [42.85%] vs 77 [16.48%]; P=.021), cardiogenic shock (5 [35.7%] vs 71 [15.2%]; P=.038), complete atrioventricular block (4 [28.57%] vs 43 [9.2%]; P=.039), and mortality (9 [64.29%] vs 151 [32.33%]; P=.019). CONCLUSIONS Acute coronary syndrome is usually an early complication of infective endocarditis. It is associated with virulent microorganisms, aortic valve infection, severe valvular regurgitation, extensive periannular complications, and increased mortality. The most frequent cause of myocardial ischemia was coronary artery compression secondary to periannular complications.

Clinical, Anatomic, and Echocardiographic Characteristics of Aneurysms of the Mitral Valve

This study describes the clinical, anatomic, echocardiographic, and Doppler features of 13 patients with mitral valve aneurysms. Eleven patients had definitive criteria for infective endocarditis. Transesophageal echocardiography was superior to conventional echocardiography in detecting and assessing aneurysms. Patients with heart failure required surgery. Echocardiographic detection of this lesion should not be, by itself, an immediate surgical indication.

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.