Alfonso Castro-Beiras

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.

Humoral Heart Rejection (Severe Allograft Dysfunction with no Signs of Cellular Rejection or Ischemia): Incidence, Management, and the Value of C4d for Diagnosis

Severe allograft dysfunction after heart transplant (HT), without ischemia or evidence of cellular rejection upon endomyocardial biopsy (EMB), is a rare but potentially fatal condition that suggests humoral rejection (HR). Its incidence, and the methods of choice for its diagnosis and management, remain uncertain. We retrospectively studied 445 HT patients (April 1991–December 2003) to determine incidence of HR diagnosed by clinical and conventional histopathological criteria. We used immunofluorescence (IF) techniques to test archived frozen EMB issue for IgM, IgG, C1q, C3, fibrin and C4d. Twelve patients (2.7%) fulfilled the criteria for HR after a mean time post‐HT of 21.3 ± 24.7 months (range: 2–72 months). Patients were treated with high doses of steroids and plasmapheresis, with successful recovery in 11 cases. IF studies using classical markers were mainly negative for the six patients with enough EMB tissue for testing. All six patients showed positivity for C4d during the HR episode but not before or after. Humoral rejection was observed in less than 3% of HT patients. Plasmapheresis treatment was highly effective. Classical IF tests were not useful for diagnosis, but C4d appears to be useful both for confirmation of diagnosis and for monitoring response to treatment.

Prevalencia de angina y factores de riesgo cardiovascular en las diferentes comunidades autónomas de España: estudio PANES

Introduccion y objetivo En el estudio de la dimension del problema de las distintas formas de presentacion de la cardiopatia isquemica, la angina ha recibido escasa atencion. El objetivo de este estudio fue determinar la prevalencia de angina en la poblacion de 45 a 74 anos de las diferentes comunidades autonomas, asi como la prevalencia de factores de riesgo cardiovascular. Metodos Fueron seleccionados 10.248 individuos de 45 a 74 anos. El muestreo fue estratificado por sexos y por tres grupos de edad, y fue proporcional a la distribucion poblacional de las diferentes comunidades autonomas. Se realizo un muestreo polietapico; en primer lugar, se seleccionaron 200 municipios al azar, y posteriormente se eligieron tres ambientes socioeconomicos distintos y se utilizaron itinerarios. La unidad de muestreo fue la vivienda familiar. Se administro el cuestionario de angina de Rose y un cuestionario estructurado para recoger variables sociodemograficas y antecedentes de factores de riesgo. Resultados La prevalencia de angina en la poblacion espanola de 45 a 74 anos fue del 7,5%, siendo las comunidades autonomas con una prevalencia mayor y menor las Baleares (11,4%) y el Pais Vasco (3,1%), respectivamente. El coeficiente de correlacion entre la prevalencia de angina y la mortalidad por cardiopatia isquemica o por enfermedad cardiovascular en varones y mujeres fue 0,52 y 0,55 y 0,31 y 0,44, respectivamente. El 31,1% de los participantes declararon ser hipertensos, el 24,2% dislipemicos, el 14,3% diabeticos y el 34,6% fumadores. Conclusiones La prevalencia de angina varia significativamente entre comunidades autonomas y se asocia con la mortalidad por cardiopatia isquemica y por enfermedades cardiovasculares en las mismas, asi como con la prevalencia de factores de riesgo cardiovascular. La prevalencia de estos factores de riesgo varia significativamente entre comunidades autonomas.

Prevalence of angina pectoris in Spain

The frequency of coronary heart disease in a community is usually measured by myocardial infarction incidence and mortality rates. The measurement of the prevalence of angina pectoris may, however, become a convenient way of assessing coronary heart disease morbidity in the future. The aim of this study was to determine the prevalence of angina and validity of the Rose questionnaire in the Spanish population aged from 45 to 74 years. A cross-sectional study was conducted in 10,248 subjects (45–74 years), representative of the Spanish population. The WHO Rose questionnaire was used and a construct validation against regional mortality rates and cardiovascular risk factor prevalence was devised. The overall angina prevalence increased with age both in men and women, but was higher in the latter (7.3% and 7.7%, respectively). Angina prevalence also increased with the number of cardiovascular risk factors present and correlated with regional CHD mortality rates (r = 0.66). Sensitivity and specificity results of the Rose questionnaire were low when tested against exercise test (52.9% and 52.1%, respectively). As conclusions, Rose questionnaire is a reliable tool for assessing angina prevalence in the Spanish population which is similar to that of other industrialized countries with higher myocardial infarction morbidity and mortality.

Nefropatía inducida por contraste y fracaso renal agudo tras cateterismo cardiaco urgente: incidencia, factores de riesgo y pronóstico

Introduction and objectives. The aim was to investigate the incidence and prognosis of, and predictive factors for, acute renal failure following urgent cardiac catheterization. Methods. The study involved 602 consecutive patients who underwent urgent cardiac catheterization. Acute renal failure (ARF) was defined as an increase in serum creatinine level ≥0.5 mg/dL within 72 hours following the procedure. Predictive factors for and the prognosis of ARF were evaluated in an initial cohort of 315 patients, and a risk score was derived. The risk score was validated in a second cohort of 287 patients. The median (interquartile) follow-up time was 1.3 years (0.8-2.0 years). Results. Seventy-two of the 602 patients (12.0%) developed ARF. In the initial cohort of 315 patients, the following factors were predictors of ARF: cardiogenic shock at admission (odds ratio [OR]= 4.56), diabetes mellitus (OR= 2.98), time to reperfusion >6 hours (OR= 3.18), anterior myocardial infarction (OR= 2.61), baseline serum creatinine level ≥1.5 mg/dL (OR= 3.51), and baseline serum urea level ≥50 mg/dL (OR= 3.00). A risk score based on these variables was constructed in which cardiogenic shock = 3 points and each of the remaining variables = 2 points. Patients in the validation cohort were divided into five risk categories: in those with 0 points, the incidence of ARF was 1.2%; with 2-3 points, 8.7%; with 4-5 points, 12.5%; with 6-7 points, 46.2%; and with ≥8 points, 66.7% (P<.0001). Cox regression analysis showed that ARF was a powerful predictor of total mortality (hazard ratio [HR]= 5.97, 95% confidence interval [CI], 2.54-14.03; P<.0001) and of a major cardiovascular event (HR= 3.29, 95% CI, 1.61-6.75; P=.001). Conclusions. The incidence of ARF after urgent cardiac catheterization is high. Cardiogenic shock,

Left atrial size and risk for all-cause mortality and ischemic stroke

Background: Limited data are available on the relation between left atrial size and outcome among patients referred for clinically indicated echocardiograms. Our aim was to assess the association of left atrial size with all-cause mortality and ischemic stroke in a large cohort of patients referred for echocardiography. Methods: Left atrial diameter was measured in 52 639 patients aged 18 years or older (mean age 61.8 [standard deviation (SD) 16.3] years; 52.9% men) who underwent a first transthoracic echocardiogram for clinical reasons at our institution between April 1990 and March 2008. The outcomes were all-cause mortality and nonfatal ischemic stroke. Results: Based on the criteria of the American Society of Echocardiography, 50.4% of the patients had no left atrial enlargement, whereas 24.5% had mild, 13.3% had moderate and 11.7% had severe left atrial enlargement. Over a mean follow-up period of 5.5 (SD 4.1) years, 12 527 patients died, and 2314 patients had a nonfatal ischemic stroke. Cumulative 10-year survival was 73.7% among patients with normal left atrial size, 62.5% among those with mild enlargement, 54.8% among those with moderate enlargement and 45% among those with severe enlargement (p < 0.001). After adjustment in multivariable Cox proportional hazard analysis, left atrial diameter remained a predictor of all-cause mortality in both sexes (hazard ratio [HR] per 1-cm increment in left atrial size 1.17, 95% confidence interval [CI] 1.12–1.22, p < 0.001 in women, and HR 1.09, 95% CI 1.05–1.13, p < 0.001 in men) and of ischemic stroke in women (HR 1.25, 95% CI 1.14–1.37, p < 0.001). Interpretation: Left atrial diameter has a graded and independent association with all-cause mortality in both sexes and with ischemic stroke in women.

Myocardin mRNA is augmented in the failing myocardium: expression profiling in the porcine model and human dilated cardiomyopathy

The implication of myocardin and homeodomain only protein (HOP) in combinatorial molecular pathways that guide heart development and cardio-specific gene expression has recently been reported. However, expression of these genes in the failing heart has not yet been investigated. This study was designed to elaborate a molecular profile of myocardin and HOP expression in the failing ventricular myocardium through the use of both explanted human heart samples and heart biopsies from neonatal piglets with doxorubicin-induced cardiomyopathy (Dox-CM). Myocardin and HOP mRNA levels were estimated by both northern blot hybridization and semiquantitative RT-PCR in human ventricular preparations in end-stage failure due to dilated cardiomyopathy (DCM), as well as in nonfailing donor hearts. Similar experiments were performed with ventricular samples from normal and Dox-treated neonatal piglets. The gene expression of brain natriuretic peptide (BNP) was used as a molecular marker of myocardial damage and failure. The study revealed the following novel findings: (1) myocardin transcripts are detected in neonatal human and pig hearts at lower levels than in mature cardiac tissues, (2) the myocardin transcript pool is significantly augmented in the failing human and porcine myocardium as compared to that in nonfailing heart samples, (3) in the failing human myocardium, increased levels of myocardin mRNA are associated with a diminished HOP transcript content, and (4) the inverse proportion in cardiac myocardin/HOP mRNA pools observed in explanted human hearts is also traceable in normal human heart and aorta. A possible dual consequence of increased myocardin and decreased HOP expression levels on serum response factor-dependent cardiac-specific expression in the normal heart and at heart failure is discussed. Therefore, increased abundance of the myocardin mRNA pool is judged to be a novel CM-related feature which, alone or in association with decreased HOP transcript levels, can be responsible for dysregulation of myocardin-mediated gene expression in failing myocardium.

Insights into genotype–phenotype correlation in hypertrophic cardiomyopathy. Findings from 18 Spanish families with a single mutation in MYBPC3

Background Mutations in the cardiac myosin-binding protein C (MYBPC3) gene are frequently found as a cause of hypertrophic cardiomyopathy (HCM). However, only a few studies have analysed genotype–phenotype correlations in small series of patients. The present study sought to determine the clinical characteristics, penetrance and prognosis of HCM with an identical mutation in MYBPC3. Methods 154 non-related patients with HCM (aged 55±16 years, 100 (64.9%) males) were studied. 18 (11.7%) were found to have an identical mutation in the MYBPC3 gene (IVS23+1G→A). Pedigree analysis, including both clinical evaluation and genotyping, was performed. Results 152 individuals (mean age 37±18 years, 53.3% males) from 18 families were evaluated. 65 carriers of the IVS23+1G→A mutation were identified, 61.5% of whom met HCM diagnostic criteria. Penetrance of the disease increased with age, with 50% affected at 46 years of age. Males tended to develop the disease earlier than females. 7 (15.6%) had systolic dysfunction. Compared with the rest of the HCM cohort, probands with the mutation had more hypertrophy and were younger at diagnosis. There was a trend towards a reduced survival free from sudden death (SD) (HR 1.71; 95% CI 0.98 to 2.98, p=0.059). There were 17 SD cases in 12 families with the mutation. Conclusions The MYBPC3 IVS23+1G→A mutation is associated with middle-age onset disease and poor outcome, with a significant proportion of patients developing systolic impairment and a high SD risk profile.

Prognostic Value of Exercise Echocardiography in Patients with Hypertrophic Cardiomyopathy

BACKGROUND Although exercise echocardiography may assess left ventricular (LV) function and LV outflow tract (LVOT) gradients during exercise in patients with hypertrophic cardiomyopathy (HCM), its value for predicting outcomes has not been studied. The aim of this study was to determine whether exercise echocardiography predicts outcomes in patients with HCM. METHODS LV function and LVOT gradients were evaluated during exercise echocardiography in 239 patients with HCM. RESULTS Sixty patients (25.1%) had LVOT obstruction at rest, and 43 (18%) developed exercise-induced LVOT obstruction. The mean resting LV ejection fraction was 69 ± 9%, and the mean resting wall motion score index was 1.00 ± 0.06. Wall motion abnormalities during exercise were seen in 19 patients (7.9%). During follow-up of 4.1 ± 2.6 years, 19 patients had hard events (cardiac death, cardiac transplantation, appropriate discharge of a defibrillator, stroke, myocardial infarction, or hospitalization for heart failure), and 41 patients had composite end points of hard or soft events (including atrial fibrillation and syncope). Exercise wall motion abnormalities occurred in 31.5% of patients with hard events compared with 5.9% of patients without hard events (P < .001). After adjustment, LV wall thickness (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.05-1.21; P = .002), resting wall motion score index (HR, 21.59; 95% CI, 2.38-196.1, P = .006), and metabolic equivalents (HR, 0.74; 95% CI, 0.63-0.88; P = .001) remained independent predictors of hard events. Change in wall motion score index was also independently associated with hard events (HR, 52.30; 95% CI, 3.81-718.5; P = .003) and with the composite end point (HR, 39.51; 95% CI, 3.79-412.4; P = .002). LVOT obstruction was not associated with either end point. CONCLUSIONS Assessment of exercise capacity and LV systolic function during exercise echocardiography may have a role in risk stratification of patients with HCM.

Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN –42 C>G mutation

Phospholamban is an endogenous sarcoplasmic reticulum calcium ATPase inhibitor with a regulatory effect on cardiac contraction/relaxation coupling. Mutations in the phospholamban gene (PLN) have been associated with primary cardiomyopathies.