E/e' ratio and left atrial area are predictors of atrial fibrillation in patients with hypertrophic cardiomyopathy.

INTRODUCTION: Atrial fibrillation (AF) occurs in about 20%-25% of patients with hypertrophic cardiomyopathy and is associated with increased risk of cardioembolism and heart failure impacting on patients' morbidity and mortality. The aim of this study was to identify echocardiographic predictors of AF in a cohort of patients with hypertrophic cardiomyopathy (HCM). METHODS: Patients were recruited from 2 centers: Buenos Aires Cardiovascular Institute and the Hospital Vall d'Hebron of Barcelona which were analyzed together. Retrospective study using electronic charts. RESULTS: A total of 321 patients with HCM and no documented history of AF were included. Median follow-up was 3 years. Mean age was 54 ± 16 years. Obstructive HCM was present in 41% of the patients, and 94.2% had preserved systolic function. Thirty-eight patients developed AF during the follow-up period (11.8%). Univariate analysis showed that age, maximum myocardial thickness, atrial area, an E/e' ratio ≥ 17, and systolic pulmonary pressure estimated by echocardiography were associated with new-onset AF. Multivariate analysis showed that E/e' ≥ 17 ratio {HR 3.27 ([1.10-9.27] P = .033)} and atrial area {HR 1.06 ([1.01-1.13] P = .037)} remained predictors of AF. CONCLUSIONS: An E/e' ratio ≥ 17, as an expression of left ventricular filling pressures with impact on the left atrium, and left atrial area ≥28 cm2 are strong predictors of AF in patients with HCM.

[Diagnosis and treatment of familial hypercholesterolemia in Spain: consensus document]. / Diagnóstico y tratamiento de la hipercolesterolemia familiar en España: documento de consenso.

Familial hypercholesterolemia (FH) is a common genetic disorder, clinically manifested since birth, and associated with very high levels of plasma LDL-cholesterol (LDL-c), xanthomas, and premature coronary heart disease. Its early detection and treatment reduces coronary morbidity and mortality. Despite effective treatment being available, FH is under-diagnosed and under-treated. Identification of index cases and cascade screening using LDL-c levels and genetic testing are the most cost-effective strategies for detecting new cases and starting early treatment. Long-term treatment with statins has decreased the vascular risk to the levels of the general population. LDL-c targets are < 130 mg/dL for children and young adults, <100mg/dL for adults, and < 70 mg/dL for adults with known coronary heart disease or diabetes. Most patients do not to reach these goals, and combined treatments with ezetimibe or other drugs may be necessary. When the goals are not achieved with the maximum tolerated drug treatment, a reduction ≥ 50% in LDL-c levels can be acceptable. Lipoprotein apheresis can be useful in homozygous, and in treatment-resistant severe heterozygous, cases. This Consensus Paper gives recommendations on the diagnosis, screening, and treatment of FH in children and adults, and specific advice to specialists and general practitioners with the objective of improving the clinical management of these patients, in order to reduce the high burden of coronary heart disease.

FHL2 expression and variants in hypertrophic cardiomyopathy.

Based on evidence that FHL2 (four and a half LIM domains protein 2) negatively regulates cardiac hypertrophy we tested whether FHL2 altered expression or variants could be associated with hypertrophic cardiomyopathy (HCM). HCM is a myocardial disease characterized by left ventricular hypertrophy, diastolic dysfunction and increased interstitial fibrosis and is mainly caused by mutations in genes coding for sarcomeric proteins. FHL2 mRNA level, FHL2 protein level and I-band-binding density were lower in HCM patients than control individuals. Screening of 121 HCM patients without mutations in established disease genes identified 2 novel (T171M, V187L) and 4 known (R177Q, N226N, D268D, P273P) FHL2 variants in unrelated HCM families. We assessed the structural and functional consequences of the nonsynonymous substitutions after adeno-associated viral-mediated gene transfer in cardiac myocytes and in 3D-engineered heart tissue (EHT). Overexpression of FHL2 wild type or nonsynonymous substitutions in cardiac myocytes markedly down-regulated α-skeletal actin and partially blunted hypertrophy induced by phenylephrine or endothelin-1. After gene transfer in EHTs, force and velocity of both contraction and relaxation were higher with T171M and V187L FHL2 variants than wild type under basal conditions. Finally, chronic phenylephrine stimulation depressed EHT function in all groups, but to a lower extent in T171M-transduced EHTs. These data suggest that (1) FHL2 is down-regulated in HCM, (2) both FHL2 wild type and variants partially protected phenylephrine- or endothelin-1-induced hypertrophy in cardiac myocytes, and (3) FHL2 T171M and V187L nonsynonymous variants induced altered EHT contractility. These findings provide evidence that the 2 novel FHL2 variants could increase cardiac function in HCM.

Factors associated with disease progression in patients with atrial fibrillation and heart failure anticoagulated with rivaroxaban.

BACKGROUND: Patients with atrial fibrillation (AF) and heart failure (HF) have a high risk of thromboembolism and other outcomes and anticoagulation is recommended. HYPOTHESIS: This study was aimed to explore the risk factors associated with HF worsening in patients with AF and HF taking rivaroxaban in Spain. METHODS: Multicenter, prospective, observational study that included adults with AF and chronic HF, receiving rivaroxaban ≥4 months before entering. HF worsening was defined as first hospitalization or emergency visit because of HF exacerbation. RESULTS: A total of 672 patients from 71 Spanish centers were recruited, of whom 658 (97.9%) were included in the safety analysis and 552 (82.1%) in the per protocol analysis. At baseline, mean age was 73.7 ± 10.9 years, 64.9% were male, CHA2 DS2 -VASc was 4.1 ± 1.5, HAS-BLED was 1.6 ± 0.9% and 51.3% had HF with preserved ejection fraction. After 24 months of follow-up, 24.9% of patients developed HF worsening, 11.6% died, 2.9% had a thromboembolic event, 3.1% a major bleeding, 0.5% an intracranial bleeding and no patient had a fatal hemorrhage. Older age, the history of chronic obstructive pulmonary disease, the previous use of vitamin K antagonists, and restrictive or infiltrative cardiomyopathies, were independently associated with HF worsening. Only 6.9% of patients permanently discontinued rivaroxaban treatment. CONCLUSIONS: Approximately one out of four patients with HF and AF treated with rivaroxaban developed a HF worsening episode after 2 years of follow-up. The identification of those factors that increase the risk of HF worsening could be helpful in the comprehensive management of this population.

Trends in clinical profile and medical treatments of atrial fibrillation patients over the last 10 years.

AIM: We sought to define trends in AF prevalence and its medical management using recent data based on data from two cross-sectional studies performed in a European country in 1999 and 2009. METHODS: CARDIOTENS 1999 and CARDIOTENS 2009 were two observational, cross-sectional, multicenter studies. Patients were recruited in from primary care and cardiology outpatient clinics. A total of 32 051 and 25 137 subjects were analyzed in the two studies, 1540 and 1524 of them, respectively, diagnosed with AF. RESULTS: Over the course of the study period there was an increase in the prevalence of AF (from 4.8% to 6.1%), mainly due to the higher prevalence of AF in patients aged over 70 years (24.7% vs. 37.1%). Furthermore, patients with AF had a higher prevalence of hypertension (64.9% vs. 87.0%), diabetes (19.0% vs. 37.4%), heart failure (30.8% vs. 34.8%), coronary artery disease (23.0% vs. 25.8%) and previous stroke (1.5% vs. 8.9%). An overall increase in prescription of antithrombotic/antiplatelet therapy was observed (33.0% vs. 62.7% and 31.0% vs. 38.2% respectively); the difference observed in 1999 between prescription of oral anticoagulation by general practitioners and cardiologists was not seen in the later study. Differences in prescription of angiotensin-converting enzyme inhibitors (28.0% vs. 40.7%), angiotensin receptor blockers (10.0% vs. 40.0%), beta-blockers (14.0% vs. 41.5%) and calcium channel blockers (21.0% vs. 34.9%) were also identified. CONCLUSIONS: The number of patients with AF and a higher risk for thromboembolic events increased over the last 10 years. More aggressive antithrombotic treatment has been observed, especially in older patients.

A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy.

AIMS: Dilated cardiomyopathy (DCM) is a major cause of heart failure with a high familial recurrence risk. So far, the genetics of DCM remains largely unresolved. We conducted the first genome-wide association study (GWAS) to identify loci contributing to sporadic DCM. METHODS AND RESULTS: One thousand one hundred and seventy-nine DCM patients and 1108 controls contributed to the discovery phase. Pools of DNA stratified on disease status, population, age, and gender were constituted and used for testing association of DCM with 517 382 single nucleotide polymorphisms (SNPs). Three DCM-associated SNPs were confirmed by individual genotyping (P < 5.0 10(-7)), and two of them, rs10927875 and rs2234962, were replicated in independent samples (1165 DCM patients and 1302 controls), with P-values of 0.002 and 0.009, respectively. rs10927875 maps to a region on chromosome 1p36.13 which encompasses several genes among which HSPB7 has been formerly suggested to be implicated in DCM. The second identified locus involves rs2234962, a non-synonymous SNP (c.T757C, p. C151R) located within the sequence of BAG3 on chromosome 10q26. To assess whether coding mutations of BAG3 might cause monogenic forms of the disease, we sequenced BAG3 exons in 168 independent index cases diagnosed with familial DCM and identified four truncating and two missense mutations. Each mutation was heterozygous, present in all genotyped relatives affected by the disease and absent in a control group of 347 healthy individuals, strongly suggesting that these mutations are causing the disease. CONCLUSION: This GWAS identified two loci involved in sporadic DCM, one of them probably implicates BAG3. Our results show that rare mutations in BAG3 contribute to monogenic forms of the disease, while common variant(s) in the same gene are implicated in sporadic DCM.

Mid-regional proatrial natriuretic peptide for predicting prognosis in hypertrophic cardiomyopathy.

OBJECTIVES: N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM. METHODS: We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion. RESULTS: Of 357 patients enrolled, the median age was 52 (IQR: 36-65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10-4) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1-2 vs 3-4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001). CONCLUSIONS: MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM.

[Antialdosteronic agents: their role in heart failure]. / Fármacos antialdosterónicos: su papel en la insuficiencia cardíaca.

Antialdosteronic treatment is used again in heart failure. It pursues the neurohormonal blockage of the final effector of the renin-angiotensin axis. Employed agents include espironolactone and, more recently, eplerenone (which lacks the adverse effects of the former such as gynecomastia). They have beneficial effects both in advanced heart failure (NYHA class III or IV) and heart insufficiency appearing after myocardial infarction. It remains to be demonstrated if they are also effective in less advanced chronic heart insufficiency (NYHA class II) and diastolic cardiac failure, though several ongoing studies are testing this benefit. Trials with antialdosteronics have shown improvements in overall mortality, even when patients were already receiving full therapy including ACEIs and, lastly, beta-blockers. The limitation of antialdosteronics is hyperkaliemia, which occurs more frequently in the general population than in patients enrolled in clinical trials, since the former is an elderly population with greater comorbility and submitted to less controls. Therefore, antialdosteronic treatment cannot be administered in some cases (especially if there is a renal function impairment) and a careful monitoring of the serum ionnograme is mandatory.

Cardiac resynchronization therapy is associated with a reduction in ICD therapies as it improves ventricular function.

BACKGROUND: Repeated implantable cardioverter-defibrillator (ICD) therapies cause myocardial damage and, thus, an increased risk of arrhythmias and mortality. HYPOTHESIS: Cardiac resynchronization therapy-defibrillator (CRT-D) reduces the number of appropriate therapies in patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] <50%). METHODS: The retrospective study involved 175 consecutive patients (mean age, 64.6 ±10.4 years; 86.9% males) with reduced LVEF of 27.9% ±7.6% treated with an ICD (56.6%) or CRT-D (43.4%), according to standard indications, between January 2009 and July 2014. Devices were placed for either primary (54.3%) or secondary prevention (45.7%). Mean follow-up was 2.5 ±1.5 years. Predictors of first appropriate therapy were assessed using Cox regression analysis. RESULTS: Forty-four (25.1%) patients received ≥1 appropriate therapy. Although patients treated with CRT-D had lower LVEF and poorer New York Heart Association class, CRT-D patients with LVEF improvement >35% at the end of follow-up had a significantly lower risk of receiving a first appropriate therapy relative to those with an ICD (adjusted hazard ratio: 0.24, 95% confidence interval: 0.07-0.83, P = 0.025), independently of ischemic cardiomyopathy, baseline LVEF, and secondary prevention. There were no differences in mortality between the ICD and the CRT-D groups. CONCLUSIONS: Although patients receiving CRT-D had a worse clinical profile, they received fewer device therapies in comparison with those receiving an ICD. This reduction is associated with a significant improvement in LVEF.

A risk score to predict the absence of left ventricular reverse remodeling: Implications for the timing of ICD implantation in primary prevention.

BACKGROUND: A prophylactic implantable cardioverter defibrillator (ICD) in patients with heart failure and reduced left ventricular ejection fraction (HFrEF) is only indicated when left ventricular ejection fraction (LVEF) reassessment remains ≤35% after 3-6 months on optimal pharmacological therapy. However, LVEF may not improve during this period and the patient may be exposed to an unnecessary risk of sudden cardiac death. This study aimed to determine the incidence and predictors of the absence of left ventricular reverse remodeling (LVRR) after pharmacological treatment optimization in patients with HFrEF to design a risk score of absence of LVRR. METHODS: Consecutive outpatients with LVEF ≤35% were included in this observational prospective study. Up-titration of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and ivabradine was performed in our Heart Failure (HF) Unit. The absence of LVRR was defined as the persistence of an LVEF ≤35% at the 6-month follow-up. RESULTS: One hundred and twenty patients were included. At the 6-month follow-up, 64%, 76%, 72%, and 7% of patients were at 100% of the target dose of ACE inhibitors/ARBs, beta-blockers, MRAs, and ivabradine, respectively. LVRR was observed in 48% of the patients. Ischemic cardiomyopathy, prolonged HF duration, and larger left ventricular end-diastolic diameter index (LVEDDI) were independent predictors of the absence of LVRR. The risk score based on these predictors showed a c-statistic value of 0.81. CONCLUSIONS: Pharmacological treatment optimization is associated with LVRR in approximately half of cases, reducing potential ICD indications in parallel. However, ischemic cardiomyopathy, prolonged HF duration, and larger LVEDDI predict the absence of LVRR and favor ICD implantation without delay. The risk score based on the former predictors may help the clinician with the timing of ICD implantation.

Consensus document for the use of the Polypill in the secondary prevention of cardiovascular disease. / Documento de consenso del uso clínico de la Polypill en la prevención secundaria del riesgo cardiovascular.

Cardiovascular disease is a chronic disorder which is usually already at an advanced stage when the first symptoms develop. The fact that the initial clinical presentation can be lethal or highly incapacitating emphasizes the need for primary and secondary prevention. It is estimated that the ratio of patients with good adherence to secondary prevention of cardiovascular disease is low and also decreases gradually over time. The Polypill for secondary prevention of cardiovascular disease is the first fixed-dose combination therapy of salicylic acid, atorvastatin and ramipril approved in Spain. The purpose of this consensus document was to define and recommend, through the evidence available in the literature and clinical expert opinion, the impact of treatment adherence in the secondary prevention of cardiovascular disease and the use of the Polypill in daily clinical practice as part of a global strategy including adjustments in patient lifestyle. A RAND/UCLA methodology based on scientific evidence, as well as the collective judgment and clinical expertise of an expert panel was used for this assessment. As a result, a final report of recommendations on the impact of the lack of adherence to treatment of secondary prevention of cardiovascular disease and the effect of using a Polypill in adherence of patients was produced. The recommendations included in this document have been addressed to all those specialists, cardiologists, internists and primary care physicians with competence in prescribing and monitoring patients with high and very high cardiovascular risks.

[Consensus on objectives and action guidelines on low density lipoproteins-cholesterol control in very high risk cardiovascular patients]. / Consenso sobre los objetivos y pautas de actuación en el control del colesterol ligado a lipoproteínas de baja densidad en pacientes de muy alto riesgo cardiovascular.

INTRODUCTION: Cardiovascular disease is the leading cause of death in developed countries. Among cardiovascular disease risk factors one of the most relevant is low-density lipoprotein-associated cholesterol (LDL-c), but there is controversy about the methods used to control it. The aim was to obtain an expert opinion to clarify the most relevant issues regarding the control of dyslipidemia in very high cardiovascular risk patients. MATERIALS AND METHODS: A survey with 55 items, stratified into 4 blocks: LDL-c as a therapeutic target, therapeutic goals, causes of the failure to achieve LDL-c goals, and recommendations to optimize their achievement, was addressed to 41 specialists (Cardiology and Internal Medicine) using the Delphi method to achieve professional consensus criteria. RESULTS: A high consensus was reached among all items, in line with the European recommendations. The panelists considered that the goal of 70mg/dl for LDL-c for high cardiovascular disease risk (mainly vascular disease, diabetes mellitus, and renal failure), using combined treatment when necessary. Lack of adherence and therapeutic inertia were considered the main reasons for treatment failure. CONCLUSION: The Spanish experts show an elevated consensus with the European recommendations, confirming the LDL-c control target of <70mg/dl. The simplification of the guidelines and the combined treatment may favor an improvement the achievement of lipid target goals.

Degree of Lipid Control in Patients With Coronary Heart Disease and Measures Adopted by Physicians. REPAR Study.

INTRODUCTION AND OBJECTIVES: Lipid control is insufficient in patients with coronary heart disease but this situation may be improving with the implementation of the latest clinical practice guidelines. The aim of this study was to analyze whether target values of low-density lipoprotein cholesterol are achieved and to identify associated factors and physicians' attitudes to deficient control. METHODS: We conducted a national, multicenter, prospective, observational study of 1103 patients with stable coronary heart disease, analyzing lipid values and a broad set of clinical variables. The statistical analysis involved a binary logistic regression model using backward stepwise elimination. RESULTS: Low-density lipoprotein cholesterol was < 70 mg/dL in only 26% of patients, even though 95.3% were receiving cholesterol-lowering agents, 45% of which were high-intensity therapies. Independent predictors of low-density lipoprotein cholesterol < 70 mg/dL were diabetes mellitus, wholegrain bread, shorter history of dyslipidemia, and, especially, high-intensity cholesterol-lowering therapies. Physicians increased therapy in only 26% of poorly controlled patients. The main predictor of increased therapy was low-intensity baseline therapy (odds ratio=5.05; 95% confidence interval, 3.3-9.2). A more proactive approach was observed in older physicians (P=.019) and longer physician practice (P=.02). CONCLUSIONS: Despite the new guidelines, only 26% of patients with coronary heart disease have adequate lipid control. In 70% of patients, physicians continue the same therapy, even though high-intensity cholesterol-lowering therapies are a key factor in good control.

Trends in Risk Factors and Treatments in Patients With Stable Ischemic Heart Disease Seen at Cardiology Clinics Between 2006 and 2014.

INTRODUCTION AND OBJECTIVES: Chronic ischemic heart disease is the most prevalent of all cardiovascular diseases. Patients are at high risk of complications. In recent decades, changes may have occurred in the clinical characteristics of the disease, its treatment and control of risk factors. METHODS: A direct comparison of 2 national registries of patients with chronic ischemic heart disease carried out in 2006 (n=1583) and 2014 (n=1110). RESULTS: We observed statistically significant differences between the 2 registries, with a higher percentage of men and smokers in the 2014 registry, but a lower prevalence of diabetes mellitus and hypertension. Heart failure and stroke were more prevalent in the 2006 registry. Patients in the 2014 registry had better results for lipid profile, blood glucose, creatinine, and glomerular filtration rate. We observed higher use of recommended drugs for secondary prevention and an increased percentage of patients receiving optimal medical therapy, from 32.5% to 49.5% (P<.01). Use of high-intensity statin doses also increased from 10.5% to 42.8% (P<.01). We found better control of some risk factors (improved dyslipidemia, heart rate, and blood glucose in patients with diabetes) but worse blood pressure control. CONCLUSIONS: The clinical profile of patients with chronic ischemic heart disease is similar in the 2 registries. There has been an improvement in patients' medical therapy and dyslipidemia control, blood glucose, and heart rate, but there is still much room for improvement in the control of other cardiovascular risk factors.

Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens.

AIMS: To assess the tolerability of initiating/uptitrating sacubitril/valsartan (LCZ696) from 50 to 200 mg twice daily (target dose) over 3 and 6 weeks in heart failure (HF) patients (ejection fraction ≤35%). METHODS AND RESULTS: A 5-day open-label run-in (sacubitril/valsartan 50 mg twice daily) preceded an 11-week, double-blind, randomization period [100 mg twice daily for 2 weeks followed by 200 mg twice daily ('condensed' regimen) vs. 50 mg twice daily for 2 weeks, 100 mg twice daily for 3 weeks, followed by 200 mg twice daily ('conservative' regimen)]. Patients were stratified by pre-study dose of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACEI/ARB; low-dose stratum included ACEI/ARB-naïve patients). Of 540 patients entering run-in, 498 (92%) were randomized and 429 (86.1% of randomized) completed the study. Pre-defined tolerability criteria were hypotension, renal dysfunction and hyperkalaemia; and adjudicated angioedema, which occurred in ('condensed' vs. 'conservative') 9.7% vs. 8.4% (P = 0.570), 7.3% vs. 7.6% (P = 0.990), 7.7% vs. 4.4% (P = 0.114), and 0.0% vs. 0.8% of patients, respectively. Corresponding proportions for pre-defined systolic blood pressure <95 mmHg, serum potassium >5.5 mmol/L, and serum creatinine >3.0 mg/dL were 8.9% vs. 5.2% (P = 0.102), 7.3% vs. 4.0% (P = 0.097), and 0.4% vs. 0%, respectively. In total, 378 (76%) patients achieved and maintained sacubitril/valsartan 200 mg twice daily without dose interruption/down-titration over 12 weeks (77.8% vs. 84.3% for 'condensed' vs. 'conservative'; P = 0.078). Rates by ACEI/ARB pre-study dose stratification were 82.6% vs. 83.8% (P = 0.783) for high-dose/'condensed' vs. high-dose/'conservative' and 84.9% vs. 73.6% (P = 0.030) for low-dose/'conservative' vs. low-dose/'condensed'. CONCLUSIONS: Initiation/uptitration of sacubitril/valsartan from 50 to 200 mg twice daily over 3 or 6 weeks had a tolerability profile in line with other HF treatments. More gradual initiation/uptitration maximized attainment of target dose in the low-dose ACEI/ARB group.

Clinical and neurohumoral consequences of diuretic withdrawal in patients with chronic, stabilized heart failure and systolic dysfunction.

BACKGROUND: Loop diuretics are beneficial in heart failure in the short term because they eliminate fluid retention, but in the long-term, they could adversely influence prognosis due to activation of neurohumoral mechanisms. AIMS: To explore the changes induced by diuretic withdrawal in chronic nonadvanced heart failure. METHODS: Diuretics were withdrawn in 26 stabilized heart failure patients with systolic dysfunction (ejection fraction [EF]<45%). Clinical status was evaluated by physical exam, exercise capacity (corridor test) and New York Heart Association (NYHA) class. Biochemical and neurohumoral determinations were performed at baseline and at 3 months. RESULTS: At 3 months, 17 out of 26 patients (65%) were able to tolerate diuretic interruption without a deterioration in exercise capacity or New York Heart Association functional class. Renal function parameters improved (baseline urea 46.2+/-10.8 to 39.2+/-10.1 mg/dl at 3 months, p=0.014; creatinine 1.1+/-0.23 to 0.98+/-0.2 mg/dl, p=0.013). Glucose metabolism also improved (fasting glucose 151+/-91 to 122+/-14 mg/dl, p=0.035). Heart rate and systolic blood pressure did not significantly change, while diastolic blood pressure increased (from 80+/-10 to 87+/-13 mm Hg, p=0.006). Neurohumoral determinations showed a decrease in plasma renin activity (4.19+/-5.96 to 2.88+/-4.98 ng/ml, p=0.026), with no changes in aldosterone, arginine-vasopressin, endothelin-1 and norepinephrine. In contrast, atrial natriuretic peptide significantly increased (115+/-87 to 168+/-155 pg/ml, p=0.004). CONCLUSION: Diuretic withdrawal in stabilized heart failure with systolic dysfunction is associated with an improvement in renal function parameters, glucose metabolism and some neurohumoral parameters, such as plasma renin activity; however, atrial natriuretic peptide levels increased.

Assessment of the markers of platelet and coagulation activation following transcatheter closure of atrial septal defects.

BACKGROUND: Aspirin has been routinely prescribed following transcatheter closure of secundum atrial septal defects (ASDs) but its rationale has not been clinically or biologically evaluated; and despite aspirin, thrombotic complications occur following transcatheter ASD closure. We therefore evaluated the presence, degree and timing of the activation of the coagulation and platelet systems following transcatheter closure of ASDs. METHODS AND RESULTS: Fourteen consecutive patients (9 females, mean age 41+/-22 years) who underwent successful transcatheter closure of an ASD defect with the Amplatzer septal occluder were prospectively studied. Measurements of the prothrombin fragment 1+2 (F1+2) levels and the percentage of activated platelets (determined by P-selectin expression detected by flow cytometry) were taken at baseline just before the procedure, and at 1, 7, 30 and 90 days following device implantation. F1+2 levels increased from 0.85+/-0.29 nmol/l at baseline to a maximal value of 1.20+/-0.52 nmol/l at 7 days, gradually returning to the baseline levels at 90 days (0.79+/-0.54 nmol/l) (p<0.001). F1+2 levels at 7 days were also significantly higher than those obtained in a control group of 20 healthy subjects (p=0.016). A greater increase in coagulation activation was observed in cases of residual shunt following ASD closure (r=0.53, p=0.050). No significant variations in the percentage of platelets expressing P-selectin were detected at any time. CONCLUSIONS: Transcatheter closure of ASDs with the Amplatzer septal occluder was associated with a significant increase in F1+2 levels during the first week after device implantation, but there was no detectable effect on platelet system activation. These findings raise the question whether the optimal prophylactic approach following transcatheter ASD closure should be anticoagulant instead of antiplatelet therapy.

Implantable Cardioverter-defibrillator Therapy for Hypertrophic Cardiomyopathy: Usefulness in Primary and Secondary Prevention.

INTRODUCTION AND OBJECTIVES: Hypertrophic cardiomyopathy is a frequent cause of sudden death. Clinical practice guidelines indicate defibrillator implantation for primary prevention in patients with 1 or more risk factors and for secondary prevention in patients with a history of aborted sudden death or sustained ventricular arrhythmias. The aim of the present study was to analyze the follow-up of patients who received an implantable defibrillator following the current guidelines in nonreferral centers for this disease. METHODS: This retrospective observational study included all patients who underwent defibrillator implantation between January 1996 and December 2012 in 3 centers in the province of Barcelona. RESULTS: The study included 69 patients (mean age [standard deviation], 44.8 [17] years; 79.3% men), 48 in primary prevention and 21 in secondary prevention. The mean number of risk factors per patient was 1.8 in the primary prevention group and 0.5 in the secondary prevention group (P=.029). The median follow-up duration was 40.5 months. The appropriate therapy rate was 32.7/100 patient-years in secondary prevention and 1.7/100 patient-years in primary prevention (P<.001). Overall mortality was 10.1%. Implant-related complications were experienced by 8.7% of patients, and 13% had inappropriate defibrillator discharges. CONCLUSIONS: In patients with a defibrillator for primary prevention, the appropriate therapy rate is extremely low, indicating the low predictive power of the current risk stratification criteria.

Update in cardiology: vascular risk and cardiac rehabilitation.

As in other fields, understanding of vascular risk and rehabilitation is constantly improving. The present review of recent epidemiological update shows how far we are from achieving good risk factor control: in diet and nutrition, where unhealthy and excessive societal consumption is clearly increasing the prevalence of obesity; in exercise, where it is difficult to find a balance between benefit and risk, despite systemization efforts; in smoking, where developments center on programs and policies, with the electronic cigarette seeming more like a problem than a solution; in lipids, where the transatlantic debate between guidelines is becoming a paradigm of the divergence of views in this extensively studied area; in hypertension, where a nonpharmacological alternative (renal denervation) has been undermined by the SYMPLICITY HTN-3 setback, forcing a deep reassessment; in diabetes mellitus, where the new dipeptidyl peptidase-4 and sodium-glucose cotransporter type 2 inhibitors and glucagon like peptide 1 analogues have contributed much new information and a glimpse of the future of diabetes treatment, and in cardiac rehabilitation, which continues to benefit from new information and communication technologies and where clinical benefit is not hindered by advanced diseases, such as heart failure. Our summary concludes with the update in elderly patients, whose treatment criteria are extrapolated from those of younger patients, with the present review clearly indicating that should not be the case.

[Diagnosis and treatment of familial hypercholesterolemia in Spain: Consensus document]. / Diagnóstico y tratamiento de la hipercolesterolemia familiar en España: documento de consenso.

Familial hypercholesterolemia (FH) is a common genetic disorder, clinically manifested since birth, and associated with very high levels of plasma LDL-cholesterol (LDL-c), xanthomas, and premature coronary heart disease. Its early detection and treatment reduces coronary morbidity and mortality. Despite effective treatment being available, FH is under-diagnosed and under-treated. Identification of index cases and cascade screening using LDL-c levels and genetic testing are the most cost-effective strategies for detecting new cases and starting early treatment. Long-term treatment with statins has decreased the vascular risk to the levels of the general population. LDL-c targets are <130mg/dL for children and young adults, <100mg/dL for adults, and <70mg/dL for adults with known coronary heart disease or diabetes. Most patients do not to reach these goals, and combined treatments with ezetimibe or other drugs may be necessary. When the goals are not achieved with the maximum tolerated drug treatment, a reduction ≥50% in LDL-c levels can be acceptable. Lipoprotein apheresis can be useful in homozygous, and in treatment-resistant severe heterozygous, cases. This Consensus Paper gives recommendations on the diagnosis, screening, and treatment of FH in children and adults, and specific advice to specialists and general practitioners with the objective of improving the clinical management of these patients, in order to reduce the high burden of coronary heart disease.