Acetazolamide in Acute Decompensated Heart Failure with Volume Overload.

BACKGROUND: Whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload, is unclear. METHODS: In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro-B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). Randomization was stratified according to the left ventricular ejection fraction (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy. Secondary end points included a composite of death from any cause or rehospitalization for heart failure during 3 months of follow-up. Safety was also assessed. RESULTS: A total of 519 patients underwent randomization. Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P<0.001). Death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48). Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups. CONCLUSIONS: The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.).

Acetazolamide in Decompensated Heart Failure with Volume Overload trial (ADVOR): baseline characteristics.

AIMS: To describe the baseline characteristics of participants in the Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial and compare these with other contemporary diuretic trials in acute heart failure (AHF). METHODS AND RESULTS: ADVOR recruited 519 patients with AHF, clinically evident volume overload, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and maintenance loop diuretic therapy prior to admission. All participants received standardized loop diuretics and were randomized towards once daily intravenous acetazolamide (500 mg) versus placebo, stratified according to study centre and left ventricular ejection fraction (LVEF) (≤40% vs. >40%). The primary endpoint was successful decongestion assessed by a dedicated score indicating no more than trace oedema and no other signs of congestion after three consecutive days of treatment without need for escalating treatment. Mean age was 78 years, 63% were men, mean LVEF was 43%, and median NT-proBNP 6173 pg/ml. The median clinical congestion score was 4 with an EuroQol-5 dimensions health utility index of 0.6. Patients with LVEF ≤40% were more often male, had more ischaemic heart disease, higher levels of NT-proBNP and less atrial fibrillation. Compared with diuretic trials in AHF, patients enrolled in ADVOR were considerably older with higher NT-proBNP levels, reflecting the real-world clinical situation. CONCLUSION: ADVOR is the largest randomized diuretic trial in AHF, investigating acetazolamide to improve decongestion on top of standardized loop diuretics. The elderly enrolled population with poor quality of life provides a good representation of the real-world AHF population. The pragmatic design will provide novel insights in the diuretic treatment of patients with AHF.

Feasibility and cost of FH cascade screening in Belgium (BEL-CASCADE) including a novel rapid rule-out strategy.

BACKGROUND: Familial hypercholesterolaemia (FH) is underdiagnosed in most countries. We report our first experience from a national pilot project of cascade screening in relatives of FH patients. METHODOLOGY: Participating specialists recruited consecutive index patients (IP) with Dutch Lipid Clinic Network (DLCN) score ≥6. After informed consent, the relatives were visited by the nurses to collect relevant clinical data and perform blood sampling for lipid profile measurement. FH diagnosis in the relatives was based on the DLCN and/or MEDPED FH (Make-Early-Diagnosis-to-Prevent-Early-Deaths-in-FH) criteria. RESULTS: In a period of 18 months, a total of 127 IP (90 with definite FH and 37 with probable FH) were enrolled in 15 centres. Out of the 270 relatives visited by the nurses, 105 were suspected of having FH: 31 with DCLN score >8, 33 with DLCN score 5-8 and 41 with MEDPED FH criteria. In a post-hoc analysis, another set of MEDPED FH criteria established in the Netherlands and adapted to Belgium allowed to detect FH in 51 additional relatives. CONCLUSION: In a country with no national FH screening program, our pilot project demonstrated that implementing a simple phenotypical FH cascade screening strategy using the collaboration of motivated specialists and two nurses, allowed to diagnose FH in 127 index patients and an additional 105 of their relatives over the two-year period. Newly developed MEDPED FH cut-offs, easily applicable by a nurse with a single blood sample, might further improve the sensitivity of detecting FH within families.

A Belgian consensus strategy to identify familial hypercholesterolaemia in the coronary care unit and its subsequent cascade screening and treatment: BEL-FaHST (The BELgium Familial Hypercholesterolaemia STrategy).

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is an autosomal dominant lipoprotein disorder characterized by significant elevation of low-density lipoprotein cholesterol (LDL-C) and markedly increased risk of premature cardiovascular disease (CVD). Because of the very high coronary artery disease risk associated with this condition, the prevalence of FH among patients admitted for CVD outmatches many times the prevalence in the general population. Awareness of this disease is crucial for recognizing FH in the aftermath of a hospitalization of a patient with CVD, and also represents a unique opportunity to identify relatives of the index patient, who are unaware they have FH. This article aims to describe a feasible strategy to facilitate the detection and management of FH among patients hospitalized for CVD. METHODS: A multidisciplinary national panel of lipidologists, cardiologists, endocrinologists and cardio-geneticists developed a three-step diagnostic algorithm, each step including three key aspects of diagnosis, treatment and family care. RESULTS: A sequence of tasks was generated, starting with the process of suspecting FH amongst affected patients admitted for CVD, treating them to LDL-C target, finally culminating in extensive cascade-screening for FH in their family. Conceptually, the pathway is broken down into 3 phases to provide the treating physicians with a time-efficient chain of priorities. CONCLUSIONS: We emphasize the need for optimal collaboration between the various actors, starting with a "vigilant doctor" who actively develops the capability or framework to recognize potential FH patients, continuing with an "FH specialist", and finally involving the patient himself as "FH ambassador" to approach his/her family and facilitate cascade screening and subsequent treatment of relatives.

Detection and quantification of myocardial scars by contrast-enhanced 3D echocardiography.

BACKGROUND: Myocardial infarct scars are usually imaged by delayed-enhanced cardiac magnetic resonance (DE-cMR). In this study, we tested the hypothesis that the detection and quantification of myocardial scars can be evaluated by 3D echocardiography (3D-echo). METHODS AND RESULTS: Fifty patients with a healed myocardial infarction (>3 months) and 10 controls underwent 3D echo and DE-cMR within 2 weeks. 3D-echo images were acquired with different settings, with or without contrast. The highest contrast-to-noise ratio was obtained with second-harmonic imaging (1.6/3.2 MHz), at a mechanical index of 0.5, in the presence of contrast. Using this modality, we calculated the sensitivity and specificity of the 3D-echo detection of cMR scars on a segmental basis to be 78% and 99%, respectively. On a per-patient basis, they were 96% and 90%, respectively. Good correlation and limits of agreement were found between the assessment of scar mass by 3D echo and DE-cMR (r=0.93, P<0.001; bias, 1.4+/-3.6 g), and the concordance between both techniques for the assessment of scar transmurality was good. Intraobserver, interobserver, and day-to-day reproducibility was comparable between 3D echo and DE-cMR for both the detection and quantification of scars. CONCLUSIONS: Contrast-enhanced 3D echo is a promising new tool for the detection and quantification of myocardial infarct scars.

Evaluation of anatomic valve opening and leaflet morphology in aortic valve bioprosthesis by using multidetector CT: comparison with transthoracic echocardiography.

PURPOSE: To prospectively determine whether cardiac-gated multidetector computed tomography (CT) allows visualization of aortic valve leaflets after bioprosthetic aortic valve replacement (AVR), to provide an accurate method for measuring the aortic valve opening, and to provide morphologic and functional information regarding the mechanism underlying poor function of the bioprosthetic valve. MATERIALS AND METHODS: The institutional review board approved the study protocol; informed consent was given. Fifty-four patients (27 men; mean age, 75 years + or - 8 [standard deviation]) with bioprosthetic AVR implanted 2 years + or - 3 earlier underwent 64-section CT and transthoracic echocardiography (TTE). Two blinded observers manually planimetered the aortic valve area (AVA) by using a computer workstation on end-systolic short-axis CT images and measured opening angles (OAs) between the bioprosthesis annulus base and the free margin on long-axis images. These measurements were compared with those of the effective orifice area (EOA) of the valve at Doppler continuity-equation TTE by using regression and Bland-Altman methods. Morphology and mobility of leaflets in normally functioning (EOA indexed to body surface area [EOA(i)] > 0.65 cm(2)/m(2)) and dysfunctional (EOA(i)< 0.65 cm(2)/m(2)) AVRs were compared. RESULTS: AVA at CT correlated highly to EOA at TTE (r = 0.93, P < .001) but was significantly larger (1.2 cm(2) + or - 0.4 vs 1.1 cm(2) + or - 0.3, P < .001) than EOA at TTE. In dysfunctional bioprostheses (n = 34), CT results showed a variety of morphologic abnormalities, such as leaflet thickening (n = 9), presumed thrombotic material (n = 6), and leaflet calcification (n = 1). Multidetector CT results demonstrated restriction of leaflet motion indicated by lower OA (64 degrees + or - 5 vs 79 degrees + or - 3, P < .0001) in dysfunctional AVRs than in normally functioning AVRs (n = 11). CONCLUSION: Sixty-four-section CT can help accurately measure AVA in bioprosthetic AVR compared with EOA at TTE. It can also show morphologic abnormalities and reduced leaflet motion in a dysfunctional bioprosthesis, thereby potentially unraveling the mechanism of dysfunction.

Long-term survival in asymptomatic patients with severe degenerative mitral regurgitation: a propensity score-based comparison between an early surgical strategy and a conservative treatment approach.

AIMS: The management of asymptomatic severe mitral regurgitation remains controversial. The aim of the study was to assess the long-term survival, incidence of cardiac complications, factors that predict outcome, and effect of mitral surgery on the long-term prognosis of patients with asymptomatic severe mitral regurgitation amenable to valve repair. METHODS: One hundred ninety-two asymptomatic patients (mean age, 63 +/- 13 years) with severe degenerative mitral regurgitation diagnosed by 2-dimensional echocardiography between 1990 and 2001 were prospectively followed for a median of 8.5 years. RESULTS: Overall, cardiovascular, and event-free survival was evaluated in 2 groups of patients: a "conservative approach" group (n = 67) and an "early surgery" group (n = 125). Outcomes were also analyzed among patients with atrial fibrillation, pulmonary hypertension, or both, as well as in patients free of any mitral regurgitation complications. In the whole population, 10-year overall survival was significantly lower with the conservative approach than early surgery (50% +/- 7% vs 86% +/- 4%, log-rank < 0.0001). Similar results were obtained in the subgroups with atrial fibrillation and/or pulmonary hypertension. The 10-year propensity-matched score-adjusted hazards ratio for overall mortality, cardiac mortality, and cardiovascular events for the conservative treatment were 5.21, 4.83, and 4.40, respectively. CONCLUSION: Our results show that the outcome of asymptomatic patients with severe degenerative mitral regurgitation is better with an early surgical approach rather than a more conservative treatment strategy.

Long-term clinical outcome of mitral valve repair in asymptomatic severe mitral regurgitation.

OBJECTIVE: To assess the long-term survival, the incidence of cardiac complications and the factors that predict outcome in asymptomatic patients with severe degenerative mitral regurgitation (MR) undergoing mitral valve repair. METHODS: Up to 143 asymptomatic patients (mean age 63+/-12 years) with severe degenerative MR who underwent mitral valve repair between 1990 and 2001 were subsequently followed up for a median of 8 years. The study population was subdivided into three subgroups: patients with left ventricular (LV) dysfunction and/or dilatation (n=18), patients with atrial fibrillation and/or pulmonary hypertension (n=44) and patients without MR-related complications (n=81). RESULTS: For the patients, 10-year overall and cardiovascular survival was 82+/-4% and 90+/-3%. At 10 years, patients without preoperative MR-related complications had significantly better overall survival than patients with preoperative LV dysfunction and/or dilatation (89+/-4% vs 57+/-13%, log rank p=0.001). Patients without preoperative MR-related complications also tended to have a better 10-year overall and cardiovascular survival than patients with atrial fibrillation and/or pulmonary hypertension (overall survival of 79+/-8%), although this did not reach statistical significance (log rank p=0.17). Cox regression analysis identified the baseline left ventricular ejection fraction and age as the sole independent predictors of outcome. CONCLUSION: Our data indicate that in asymptomatic patients with severe degenerative MR, mitral valve repair is associated with an excellent long-term prognosis. Nonetheless, the presence of preoperative MR-related complications, in particular LV dysfunction and/or dilatation, greatly attenuates the benefits of surgery. This suggests that mitral valve repair should be performed early, before any MR-related complications ensue.

Assessment of subendocardial vs. subepicardial left ventricular rotation and twist using two-dimensional speckle tracking echocardiography: comparison with tagged cardiac magnetic resonance.

AIMS: The aim of this article is to evaluate the accuracy and reproducibility of two-dimensional speckle tracking echocardiography (2D-STE) for the estimation of left ventricular (LV) twist, using tagged cardiac magnetic resonance (cMR) as the reference standard, and to assess how much 2D-STE rotational parameters are affected by the level at which measurements are made within the LV. METHODS AND RESULTS: Forty-three patients with various heart diseases and 10 healthy volunteers underwent cMR and 2D-STE on the same day. With both methods, basal and apical time-rotation curves were generated at endocardial, midwall, and epicardial levels. By using the most apical cMR short-axis cross-section as a comparator, apical rotation was significantly underestimated by 2D-STE. When 2D-STE and cMR short-axis cross-sections were matched for their internal dimensions, measurements of endocardial, midwall, and epicardial twists no longer differ between cMR and 2D-STE (12.6 +/- 5.9 vs. 12.5 +/- 5.7 degrees , 10.5 +/- 4.6 vs. 9.7 +/- 4.1 degrees , and 8.9 +/- 4.0 vs. 8.4 +/- 3.7 degrees , respectively, all P = ns). CONCLUSION: Compared with tagged cMR, 2D-STE underestimates apical rotation and LV twist. This is related to the inability of 2D-STE to image the real LV apex in most of the patients. However, when 2D-STE and cMR data are compared at similar acquisition levels, both techniques provide similar values.