Impact of dynamic physical exercise on high-risk definite arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiomyopathy characterized by ventricular arrhythmias and heart failure. The variable phenotype suggesting that determined environmental factors may have an influence. The aim of our study was to discover the impact of the dynamic physical activity on patients with high-risk definite ARVC/D. METHODS AND RESULTS: Collection of data on physical activity at the time of diagnosis was conducted at an in-person clinical interview. The intensity of the activity was classified in accordance with the mean frequency of weekly physical exercise sessions in the 10 years before diagnosis and into the following three groups of dynamic activity: high/competitive (>3 h/wk), moderate (1 to 3 h) and minimal/inactive (<1 h). Seventeen patients practiced high dynamic physical activities. The intensity of dynamic activity was classified into three groups: 8 of high intensity, 9 moderate, and 19 inactive. The first major arrhythmic event and occurrence of severe right ventricular dysfunction were earlier in the high-intensity exercise group, followed by the moderate intensity group and at a later age in the low-intensity/inactive group. CONCLUSIONS: Dynamic exercise could be directly associated with the severity of the phenotype in relation to the precocity of major ventricular arrhythmic events and right ventricular systolic dysfunction in patients with high-risk definite ARVC/D.

Usefulness of Genetic Study by Next-generation Sequencing in High-risk Arrhythmogenic Cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium. This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC. METHODS: This was an observational, retrospective cohort study, which included 36 patients diagnosed with high-risk ARVC in our hospital between January 1998 and January 2015. Genetic analysis was performed using next-generation sequencing. RESULTS: Most patients were male (28 patients, 78%) with a mean age at diagnosis of 45 ± 18 years. A pathogenic or probably pathogenic desmosomal mutation was detected in 26 of the 35 index cases (74%): 5 nonsense, 14 frameshift, 1 splice, and 6 missense. Novel mutations were found in 15 patients (71%). The presence or absence of desmosomal mutations causing the disease and the type of mutation were not associated with specific electrocardiographic, clinical, arrhythmic, anatomic, or prognostic characteristics. CONCLUSIONS: The incidence of pathological or likely pathological desmosomal mutations in ARVC is very high, with most mutations causing truncation. The presence of desmosomal mutations was not associated with prognosis.

The importance of genotype-phenotype correlation in the clinical management of Marfan syndrome.

BACKGROUND: Marfan syndrome (MFS) is a disorder of autosomal dominant inheritance, in which aortic root dilation is the main cause of morbidity and mortality. Fibrillin-1 (FBN-1) gene mutations are found in more than 90% of MFS cases. The aim of our study was to summarise variants in FBN-1 and establish the genotype-phenotype correlation, with particular interest in the onset of aortic events, in a broad population of patients with an initial clinical suspicion of MFS. MATERIAL AND METHODS: This single centre prospective cohort study included all patients presenting variants in the FBN-1 gene who visited a Hereditary Aortopathy clinic between September 2010 and October 2016. RESULTS: The study included 90 patients with FBN-1 variants corresponding to 58 non-interrelated families. Of the 57 FBN-1 variants found, 25 (43.9%) had previously been described, 23 of which had been identified as associated with MFS, while the the remainder are described for the first time. For 84 patients (93.3%), it was possible to give a definite diagnosis of Marfan syndrome in accordance with Ghent criteria. 44 of them had missense mutations, 6 of whom had suffered an aortic event (with either prophylactic surgery for aneurysm or dissection), whereas 20 of the 35 patients with truncating mutations had suffered an event (13.6% vs. 57.1%, p < 0.001). These events tended to occur at earlier ages in patients with truncating compared to those with missense mutations, although not significantly (41.33 ± 3.77 vs. 37.5 ± 9.62 years, p = 0.162). CONCLUSIONS: Patients with MFS and truncating variants in FBN-1 presented a higher proportion of aortic events, compared to a more benign course in patients with missense mutations. Genetic findings could, therefore, have importance not only in the diagnosis, but also in risk stratification and clinical management of patients with suspected MFS.

Serum levels of interleukin-2 predict the recurrence of atrial fibrillation after pulmonary vein ablation.

AIMS: Interleukin-2 has a significant antitumor activity in some types of cancer, and has been associated with the development of atrial fibrillation (AF). In addition, IL-2 serum levels in recent onset AF have been related with pharmaceutical cardioversion outcomes. We evaluated the hypothesis that a relationship exists between inflammation and the outcome of catheter ablation of AF. METHODS: We studied 44 patients with paroxysmal AF who underwent catheter ablation. Patients with structural heart disease, coronary artery or valve disease, active inflammatory disease, known or suspected neoplasm, endocrinopathies, or exposure to anti-inflammatory drugs were excluded. All study participants underwent evaluation with a standardized protocol, including echocardiography, and cytokine levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumour necrosis factor-alpha, and gamma-interferon determination before procedure. Clinical and electrocardiographic follow-up were performed with Holter-ECG at 3, 6 and 12months in order to know if sinus rhythm was maintained. RESULTS: After catheter ablation of the 44 patients included (53±10years, 27.3% female), all patients returned to sinus rhythm. During the first year of follow-up seven patients (15.9%) experienced recurrence of AF. The demographics, clinical and echocardiographic features, and pharmacological treatments of these patients were similar to those who maintained sinus rhythm. The only independent factor predictive of recurrence of AF was an elevated level of IL-2 (OR 1.18, 95% CI 1.12-1.38). CONCLUSIONS: High serum levels of interleukin-2, a pro-inflammatory non-vascular cytokine, are associated with the recurrence of AF in patients undergoing catheter ablation.

Short- and long-term outcomes of surgery for severe tricuspid regurgitation.

INTRODUCTION AND OBJECTIVES: There is little data available for Spain on the outcomes of surgical treatment for severe tricuspid regurgitation. The aim of this study was to analyze clinical and echocardiographic outcomes in a series of patients who received surgical treatment for severe tricuspid regurgitation and to compare outcomes according to the operative approach to valve repair or replacement. METHODS: Retrospective study in 119 consecutive patients with severe tricuspid regurgitation undergoing valve surgery between April 1996 and February 2010. RESULTS: A total of 61 ringless and 23 ring annuloplasties were performed and 11 bioprostheses and 24 mechanical prostheses were implanted. Perioperative mortality was 18.5% and was associated with age and cardiopulmonary bypass time. During clinical follow-up (median, 41 [interquartile range, 24-89] months), 2 reoperations were required in the ring annuloplasty and mechanical prosthesis groups; prosthetic thrombosis was diagnosed in 4 patients in the latter group. Total mortality after follow-up was 29.9% and was associated with age>70 years and extracorporeal circulation time. The emergence of new severe tricuspid regurgitation was associated with age and ringless annuloplasty (P=.04). CONCLUSIONS: Ringless repair was significantly associated with recurrence of severe tricuspid regurgitation. The use of mechanical prostheses was associated with a high rate of thrombosis. No significant differences in perioperative or total mortality were found between the different methods used for repair or valve replacement.

[Factors influencing mobilisation of endothelial progenitor cells and angiogenic cytokines after an extensive acute myocardial infarction]. / Factores que influyen en la liberación de células endoteliales progenitoras y citocinas angiogénicas tras un infarto de miocardio extenso.

BACKGROUND AND OBJECTIVES: Following an acute myocardial infarction (AMI), bone-marrow derived endothelial progenitor cells (EPC) are mobilised into the peripheral blood. Our aim was to examine the factors influencing this spontaneous cell mobilisation. PATIENTS AND METHODS: In this study we analysed 47 patients with extensive AMI (left ventricular ejection fraction [LVEF] <50% by echocardiography during the first week post-AMI); we studied the peripheral blood EPC populations expressing CD133(+), CD34(+), KDR(+), CXCR4(+), as well as the cytokines VEGF (vascular endothelial growth factor), SDF-1 (stromal cell-derived factor 1) and TSP-1 (thrombospondin 1), measured on day 5±2.5 after AMI. RESULTS: The extension of AMI (CPK peak) correlated with the number of CD133(+) mobilised cells: (r=0.40; P=.011). Patients who did not receive perfusion during the acute phase (34%) had more CD34(+)CXCR4(+) cells with a median (interquartile ranges) of 2,401 (498-7,004) vs. 999 (100-1,600), P=.048, and strong correlations between VEGF and CD133(+)CD34(+)KDR(+) (r=.84; P<.01) and SDF-1 and CD34(+)CXCR4(+) (r=.67; P<.01), and between these 2 cytokines (r=.57; P=.01). In the reperfused patients, the correlation between VEGF and CD133(+)CD34(+)KDR(+) was lower (r=.38; P=.03) and the correlation between SDF-1 and CD34(+)CXCR4(+) and VEGF disappeared. Multivariate analysis showed that a VEGF >7pg/mL (P<.01) predicted the mobilisation of CD133(+)CD34(+)KDR(+), whereas hypertension showed a trend (P=.055). Diabetes (P=.045) predicted the number of CD34(+)CXCR4(+), with reperfusion treatment showing a trend in this subpopulation (P=.054). CONCLUSIONS: Mobilisation of progenitor cells after AMI is influenced by factors such as diabetes and the cytokine VEGF. Hypertension and reperfusion therapy during the acute phase also tend to influence the cell response.

Influence of preinfarction angina on the release kinetics of endothelial progenitor cells and cytokines during the week after infarction.

BACKGROUND: Preinfarction angina, a possible form of ischaemic preconditioning, improves the prognosis in patients who experience a major ischaemic event; though the associated pathophysiology is not yet fully understood. The aim of this study was to determine the possible involvement of endothelial progenitor cells (EPC), the vascular endothelial growth factor (VEGF) and the hepatocyte growth factor (HGF) in the development of preinfarction angina. METHODS AND RESULTS: We studied 41 patients (60·5 ± 12 years; 34% women) and 14 healthy controls; 43·9% of the patients had preinfarction angina. No differences were found in the baseline characteristics of the two groups. Although the EPC, VEGF and HGF were raised as compared with the control group, no significant differences were found according to the presence or absence of preinfarction angina in the levels of EPC (baseline, P = 0·25; day 3, P = 0·11; day 7, P = 0·32), VEGF (baseline, P = 0·96; day 3, P = 0·06; day 7, P = 0·57) or HGF (baseline, P = 0·18; day 3, P = 1; day 7, P = 0·86). An association was seen in the patients who had preinfarction angina between the EPC levels at baseline and on days 3 and 7 and the HGF on admission with the time from the angina to the STEMI (ß = -0·070; ß = -0·066; ß = -0·081; ß = -80·16; P < 0·05), showing a reduction in the level of EPC cells for each hour passed since the event. CONCLUSIONS: No differences were found in the release kinetics of EPC, VEGF or HGF after a first infarction according to whether the patients had angina during the week before the infarction.

Long-term predictors of mortality and functional recovery after aortic valve replacement for severe aortic stenosis with left ventricular dysfunction.

INTRODUCTION AND OBJECTIVES: At present, surgery is the only recommended effective treatment for severe aortic stenosis. However, the surgical risk is increased when left ventricular dysfunction is present. The aim of this study was to identify predictors of postoperative and long-term mortality and functional improvement after valve replacement in patients with severe aortic stenosis and left ventricular dysfunction. METHODS: Between 1996 and 2008, 635 consecutive patients with severe aortic stenosis underwent surgery. Early postoperative mortality in the 82 with an ejection fraction <40% was 19.5%. The following independent predictors of early postoperative mortality were identified: female sex (odds ratio [OR]=2.60; 95% confidence interval [CI], 2.20-89.0; P=.004), mild mitral regurgitation (OR=2.38; 95% CI, 1.40-80.0; P=.020) and coronary artery disease (OR=2.09; 95% CI, 1.26-51.0; P=.027). RESULTS: During the mean follow-up period of 42.59+/-40.83 months, overall mortality was 18.8% and cardiovascular mortality was 11.3%. The only factor associated with increased mortality during follow-up was a low postoperative cardiac output (OR=4.40; 95% CI, 1.20-15.5; P=.02). In total, 70.5% showed early improvement in ventricular function, the predictors of which were: no improvement following a previous myocardial infarction (P=.04), no revascularized coronary lesions (P=.04), and a low aortic valve pressure gradient (P=.02). Functional class improved significantly during follow-up in 93.4% of patients. CONCLUSIONS: Despite considerable early postoperative mortality in patients with aortic stenosis and left ventricular dysfunction, over the long term there was evidence of better survival coupled to improved ventricular function and functional class.

[Influence of sex on perioperative outcomes in patients undergoing valve replacement for severe aortic stenosis]. / Influencia del sexo en el pronóstico perioperatorio de pacientes sometidos a sustitución valvular por estenosis aórtica severa.

INTRODUCTION AND OBJECTIVES: The influence of sex on the prognosis of patients undergoing aortic valve replacement for severe stenosis is unclear. Nevertheless, a number of studies have regarded sex as an independent risk factor. The aim of this study was to evaluate the influence of sex on perioperative outcomes in patients undergoing valve replacement for severe aortic stenosis. METHODS: This retrospective study involved 577 consecutive patients who underwent aortic valve replacement surgery for severe aortic stenosis between 1996 and April 2007. RESULTS: Women (44% of patients) were older than men (70.3+/-7.9 years vs. 66.8+/-9.8 years; P< .001), had a smaller body surface area (1.68+/-0.15 m(2) vs. 1.83+/-0.16 m(2); P< .001), more often had arterial hypertension (73% vs. 49%; P< .001), diabetes mellitus (33.5% vs. 24.5%; P=.001) and ventricular hypertrophy (89.1% vs. 83.1%; P< .001), and less often had coronary artery disease (19.1% vs. 31.8%; P< .001) and severe ventricular dysfunction (7.9% vs. 17.4%; P< .001). Nevertheless, women more often suffered acute myocardial infarction perioperatively (3.9% vs. 0.9%; P=.016), had a low cardiac output in the postoperative period (30.3% vs. 22.3%; P=.016) and experienced greater perioperative mortality (13% vs. 7.4%; P=.019) than men. However, after adjustment for various confounding factors, female sex was not a significant independent risk factor for mortality (odds ratio = 2.40; 95% confidence interval, 0.79-7.26; P=.119). CONCLUSIONS: Perioperative mortality in women with severe aortic stenosis who underwent valve replacement was high. However, after adjustment for potential confounding factors, particularly body surface area, female sex was not an independent risk factor for mortality.

Incidence, associated factors and evolution of non-severe functional mitral regurgitation in patients with severe aortic stenosis undergoing aortic valve replacement.

INTRODUCTION: In order to improve the prognosis, repair of severe mitral regurgitation should be undertaken at the same time as aortic valve replacement in patients with severe aortic valve stenosis. However, mitral regurgitation may be secondary to pressure overload or ventricular dysfunction and improve after surgery. AIM: To assess the incidence of non-severe functional mitral regurgitation before and after isolated aortic valve replacement and determine its influence on the postoperative course. METHODS: The clinical and surgical characteristics were compared in a cohort of 577 consecutive patients who underwent isolated aortic valve replacement. RESULTS: The mean age was 68.4+/-9.2 years (44% women). Non-severe functional mitral valve regurgitation was detected prior to surgery in 26.5% of the patients. These patients were older (p=0.009), more often had ventricular dysfunction (p=0.005) and pulmonary hypertension (0.002), and had been admitted more frequently for heart failure (0.002), with fewer of them conserving sinus rhythm (p<0.001). Additionally, the pre-surgery existence of mitral regurgitation was associated with greater morbidity and mortality (10.5% vs 5.6%; p=0.025). The mitral regurgitation disappeared or improved prior to hospital discharge in 56.2% and 15.6%, respectively. Independent factors predicting this improvement were the presence of coronary lesions (OR 3.7, p=0.038), and the absence of diabetes (OR 0.28, p=0.011) and pulmonary hypertension (0.33, p=0.046). CONCLUSIONS: The presence of intermediate degree mitral regurgitation in patients undergoing isolated aortic valve replacement increases morbidity and mortality. However, a high percentage of those who do survive experience disappearance or improvement of the mitral regurgitation.

[Heart failure in 2006]. / Insuficiencia cardiaca en el año 2006.

This article are summarizes the most relevant articles in the field of heart failure including epidemiology, diagnostic and therapeutic issues. Therapy includes drugs, cardiac resinchronization therapy, automatic implantable defibrillator, heart transplantation and cell therapy. Stem cell therapy is feasible and short term data indicates it is safe. However there are unresolved concerns on arrhythmias, restenosis and efficacy. At this point experts recommend that medium-sized randomized controlled trials, using surrogate endpoints, should be carried out to establish the efficacy and safety of this form of treatment.

[Transcatheter closure of aorto-left atrial fistula using an Amplatzer device]. / Cierre percutáneo de una fístula entre aorta y aurícula izquierda mediante dispositivo Amplatzer.

Aorto-left atrial fistulas are rare. We describe the case of a patient in whom transcatheter closure of an aorto-left atrial fistula was carried out using an Amplatzer septal occluder. The patient had previously undergone cardiac surgery twice because of a recurrent left atrial myxoma. Closure of this type of fistula using a transcatheter device should be considered when the location and size of the fistula are appropriate and there are no associated abnormalities. The risk of surgery must also be taken into account.

[Collagen synthesis and heart failure]. / Síntesis de colágeno e insuficiencia cardíaca.

Little is known about collagen metabolism in heart failure, with or without left ventricular systolic dysfunction. We studied serum concentrations of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type-I synthesis, and of the carboxy-terminal telopeptide of collagen type I (ICTP), a marker of collagen type-I degradation, in 70 patients admitted for heart failure (35 with depressed left ventricular systolic function and 35 with preserved left ventricular systolic function) and in 30 control subjects. Patients with kidney failure, liver disease, metabolic bone disease, rheumatic disease, recent (within 3 months) major trauma or surgery, or serious wounds were excluded. The concentration of the collagen synthesis marker, PIP, was higher in heart failure patients than control subjects, at 140+/-56.38 mg/L vs 113.66+/-36.6 microg/L, respectively (P=.01). However, there was no difference in the concentration of the collagen degradation marker, ICTP, between heart failure patients and control subjects, at 2.89+/-2.37 mg/L vs 2.26+/-1.7 microg/l, respectively. In heart failure patients, left ventricular systolic function had nonsignificant effect on the PIP or ICTP concentration.