Aldo Vladimir Ypanaque Prado - Academia.edu (original) (raw)

Papers by Aldo Vladimir Ypanaque Prado

Revista de la Federación Argentina de Cardiología, 2018

Journal of Cardiovascular Echography, 2020

Relapsing polychondritis (RP) is a rare multisystem disease characterized by inflammation in cart... more Relapsing polychondritis (RP) is a rare multisystem disease characterized by inflammation in cartilaginous structures and other connective tissues throughout the body, affecting the ears, nose, eyes, joints, respiratory tract, heart, and blood vessels. Cardiovascular involvement is the second most common cause of mortality after laryngotracheal involvement. [1] Here, we report a successful surgical case of RP in which the patient underwent aortic and mitral valve replacement and concomitant coronary artery bypass grafting.

Journal of the American Society of Echocardiography, 2021

BACKGROUND Echocardiography remains the most widely used modality to assess left ventricular (LV)... more BACKGROUND Echocardiography remains the most widely used modality to assess left ventricular (LV) chamber size and function. Currently this assessment is most frequently performed using 2D echocardiography (2DE). Yet, 3D echocardiography (3DE) has been shown to be more accurate and reproducible than 2DE. Current normative reference values for 3D LV analysis are predominantly based on data from North America and Europe. The World Alliance of Societies of Echocardiography (WASE) study was a designed to sample normal subjects from around the world to provide more universal global reference ranges. In this study we sought to assess the world-wide feasibility of LV 3DE and report on size and function measurements. METHODS 2262 healthy subjects were prospectively enrolled from 19 centers in 15 countries. 3D LV full-volume datasets were obtained and analyzed offline with vendor-neutral software. Measurements included end-diastolic and end-systolic volumes (EDV, ESV), ejection fraction (EF), global longitudinal and circumferential strain (GLS and GCS). Results were categorized by age (18-40, 41-65 and >65 years), sex and race. RESULTS 1589 subjects (feasibility 70%) had adequate LV datasets for analysis. Mean normal values for indexed EDV, ESV and EF in men and women were 70 ± 15 and 65 ± 12 mL, 28 ± 7 and 25 ± 6 mL and 60 ± 5, 62 ± 5% respectively. Men had larger LV volumes and lower EF than women. GLS and GCS were higher in magnitude in women. In both sexes, LV volumes were lower and EF tended to be higher with increasing age, especially considering the differences between the youngest and oldest age groups. While GLS was similar across age groups in men, in women, the youngest and middle-age cohorts revealed higher magnitudes of GLS when compared to the oldest age group. GCS was higher in magnitude at older age in both men and women. Finally, Asians had smaller chamber sizes and higher EF and absolute strain values than both blacks and whites. CONCLUSIONS Age, sex, and race should be considered when defining normal reference values for LV dimension and function parameters obtained by 3DE.

Journal of Cardiology & Current Research, 2020

The restrictive pathologies are a group of diseases of low prevalence. Cardiac amyloidosis is con... more The restrictive pathologies are a group of diseases of low prevalence. Cardiac amyloidosis is considered to be the prototype of the infiltrative form of restrictive cardiomyopathies. The myocardial involvement is frequent, even at the first appearance of the disease and it has a poor prognosis; and although pleural involvement is less frequent, its presence determines a much more torpid evolution than isolated cardiac presentations. The main problem that these pathologies concern is their late recognition and the consequences this implies in the patient evolution. Nowadays, cardiac images tools may facilitate the diagnosis, allowing an early detection. We share an unusual case of amyloidosis with pleural involvement, where the results of the echocardiogram and the cardiac magnetic resonance allowed an approach to an accurate diagnostic.

Journal of the American Society of Echocardiography, 2021

BACKGROUND Assessment of cardiac output (CO) and stroke volume (SV) is essential to understand ca... more BACKGROUND Assessment of cardiac output (CO) and stroke volume (SV) is essential to understand cardiac function and hemodynamics. These parameters can be examined by three echocardiographic techniques (pulsed wave Doppler, 2D and 3D). Whether these methods can be used interchangeably is unclear. The influence of age, sex, and ethnicity on CO and SV has also not been examined in-depth. In this report from the World Alliance of Societies of Echocardiography (WASE) Normal Values study, we aim to compare CO and SV in healthy adults according to age, sex, ethnicity and measurement techniques. METHODS 1450 adult subjects (53% males) free from heart, lung and kidney disease were prospectively enrolled in 15 countries with even distribution among age groups and sex. Subjects were divided into three age groups: young (18-40), middle (41-65) and old (>65 years), and three main racial groups: whites, blacks, and Asians. CO and SV were indexed (CI and SVI, respectively) to body surface area (BSA) and height and measured using three echocardiographic methods: Doppler, 2D, and 3D. Images were analyzed in two core laboratories (one for each 2D and 3D). RESULTS CI and SVI were significantly lower by 2D compared to both Doppler and 3D methods in both sexes. SVI was significantly lower in females versus males by all 3 methods, while CI only differed by 2D. SVI decreased with aging by all three techniques, whereas CI declined only with 2D and 3D. CO and SV were smallest in Asians and largest in whites, and the differences persisted after normalization for BSA. CONCLUSION Our results provide normal reference values for CO and SV, which differ by age, sex and race. Further, CI and SVI measurements by the different echocardiographic techniques are not interchangeable. All these factors need to be taken into account when evaluating cardiac function and hemodynamics in individual patients.

Journal of the American Society of Echocardiography, 2021

BACKGROUND Left atrial (LA) evaluation includes volumetric and functional parameters with an abun... more BACKGROUND Left atrial (LA) evaluation includes volumetric and functional parameters with an abundance of diagnostic and prognostic implications. Solid normal reference ranges are compulsory for accurate interpretation in individual patients, but previous reports have yielded mixed conclusions regarding the effects of age, sex and/or race. The current report from the World Alliance Societies of Echocardiography (WASE) study focuses on 2D and 3D measures of LA structure and function, with subgroup analysis by age-, sex- and race. METHODS Transthoracic 2D and 3D echocardiographic images were obtained in 1,765 healthy individuals (901 males, 864 females) evenly distributed among age subgroups: 18-40 years (n=745), 41-65 years (n=618) and >65 years (n=402); 38.4% white, 39.9% Asian, 9.7% black. Images were analyzed using dedicated LA analysis software to measure LA volumes and phasic function from 3D volume and 2D strain curves. RESULTS 3D maximal and minimum LA volumes adjusted for BSA were nearly identical for men and women, but women demonstrated higher 3D total and passive EF. 2D reservoir strain was similar for both sexes. Age was associated with an incremental rise in LA volumes alongside characteristic shifts in functional indices. Total 2D EF, reservoir and conduit strain varied inversely with age, counteracted by higher booster strain, with a greater magnitude of effect in women. Active 3D EF was significantly higher, while total and passive EF decreased with age. Inter-racial differences were noted in LA volumes without substantial differences in functional indices. CONCLUSIONS While similar normal values for LA volumes and strain can be applied to both sexes, meaningful differences in LA size occur with aging. Indices of function also shift with age with a compensatory rise in booster function, which may serve to counteract observed lower total and passive EF. Defining age-associated normal values may help differentiate age-associated "healthy" LA aging from pathological processes.

JAMA Cardiology, 2021

IMPORTANCE Inflammation promotes cardiovascular disease and anti-inflammatory treatment reduces c... more IMPORTANCE Inflammation promotes cardiovascular disease and anti-inflammatory treatment reduces cardiovascular events in patients with chronic coronary syndrome. Chronic kidney disease (CKD) is a risk factor for cardiovascular disease. It is unclear how inflammation mediated by interleukin 6 (IL-6) in patients with CKD is linked to cardiovascular disease. OBJECTIVE To investigate associations between IL-6 and cardiovascular outcomes in patients with chronic coronary syndrome in association with kidney function. DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study included patients enrolled at 663 centers in 39 countries with chronic coronary syndrome who were included in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial. Patients were enrolled between December 2008 and April 2010 and were followed up for a median length of 3.7 years. Analysis in this substudy began September 2020. EXPOSURES Exposures were IL-6 and creatinine estimated glomerular filtration rates (eGFR), which were collected at baseline. Associations between continuous and categorical levels (<2.0 ng/L vs Ն2.0 ng/L) of IL-6 and cardiovascular outcomes were tested in association with eGFR cutoffs (normal eGFR level [Ն90 mL/min/1.73 m 2 ], mildly decreased eGFR level [60-90 mL/min/1.73 m 2 ], and moderately to severely decreased eGFR level [<60 mL/min/1.73 m 2 ]). MAIN OUTCOMES AND MEASURES Main outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke. RESULTS This substudy of the STABILITY trial included 14 611 patients with available IL-6 levels at baseline. The median (interquartile range) age was 65 (59-71) years, and 2700 (18.5%) were female. During follow-up, MACE occurred in 1459 individuals (10.0%). Higher levels of IL-6 were in continuous models independently associated with risk of MACE (P < .001) in all CKD strata. Using predefined strata, elevated IL-6 level (Ն2.0 vs <2.0 ng/L) was associated with increased risk of MACE at normal kidney function (2.9% vs 1.9% events/y [hazard ratio, 1.35; 95% CI, 1.02-1.78]), mild CKD (3.3% vs 1.9% [hazard ratio, 1.57; 95% CI, 1.35-1.83]), and moderate to severe CKD (5.0% vs 2.9% [hazard ratio, 1.60; 95% CI, 1.28-1.99]). CONCLUSIONS AND RELEVANCE In patients with chronic coronary syndrome, elevated levels of IL-6 were associated with risk of MACE in all CKD strata. Thus, IL-6 and CKD stage may help when identifying patients with chronic coronary syndrome for anti-inflammatory treatment.

Journal of the American Society of Echocardiography, 2020

Background: The World Alliance Societies of Echocardiography (WASE) study was conducted to descri... more Background: The World Alliance Societies of Echocardiography (WASE) study was conducted to describe echocardiographic normal values in adults and to compare races and nationalities using a uniform acquisition and measurement protocol. This report focuses on left ventricular (LV) diastolic function. Methods: WASE is an international, cross-sectional study. Participants were enrolled with equal distribution according to age and gender. Echocardiograms were analyzed in a core laboratory based on the latest American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Left ventricular diastolic function was assessed by E, E/A, e' velocities, E/e', left atrial volume index (LAVI), and tricuspid regurgitation velocity. Determination of LV diastolic function was made using the algorithm proposed by the guidelines.

JACC: Heart Failure, 2020

Decreased systolic function is a central factor in HFrEF. Current and investigational inotropic c... more Decreased systolic function is a central factor in HFrEF. Current and investigational inotropic calcitropic drugs have uniformly resulted in signals of increased mortality. OM is a myotrope and a selective cardiac myosin activator that improves cardiac function. The GALACTIC-HF trial evaluates the effect of OM on outcomes in patients with chronic HF.

Journal of the American Society of Echocardiography, 2019

Background: The World Alliance Societies of Echocardiography (WASE) Normal Values Study evaluates... more Background: The World Alliance Societies of Echocardiography (WASE) Normal Values Study evaluates individuals from multiple countries and races with the aim of describing normative values that could be applied to the global community worldwide and to determine differences and similarities among people from different countries and races. The present report focuses specifically on two-dimensional (2D) left ventricular (LV) dimensions, volumes, and systolic function. Methods: The WASE Normal Values Study is a multicenter international, observational, prospective, crosssectional study of healthy adult individuals. Participants recruited in each country were evenly distributed among six predetermined subgroups according to age and gender. Comprehensive 2D transthoracic echocardiograms were acquired and analyzed following strict protocols based on recent American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines. Analysis was performed at the WASE 2D core laboratory and included 2D LV dimensions, LV volumes, and LV ejection fraction (LVEF) by the biplane Simpson method and global longitudinal strain (GLS). Results: Two thousand eight subjects were enrolled in 15 countries. The median age was 45 years (interquartile range, 32-65 years), 42.8% were white, 41.8% were Asian, and 9.7% were black. LV dimensions and volumes were larger in male subjects, while LVEF and GLS were higher in female subjects. Global

The Lancet, 2019

Patients with stable coronary artery disease and diabetes with previous percutaneous coronary int... more Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8-3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74-0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, pinteraction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78-1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75-1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48-2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36-3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74-1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75-0·95, p=0·005, in contrast to patients without PCI where it did not, pinteraction=0·012. Benefit was present irrespective of time from most recent PCI. In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk. AstraZeneca.

The Lancet, 2019

Background Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascula... more Background Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A 1c (HbA 1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. Methods This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1•5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66•2 years [SD 6•5], median HbA 1c 7•2% [IQR 6•6-8•1], 4589 [46•3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5•4 years (IQR 5•1-5•9), the primary composite outcome occurred in 594 (12•0%) participants at an incidence rate of 2•4 per 100 person-years in the dulaglutide group and in 663 (13•4%) participants at an incidence rate of 2•7 per 100 person-years in the placebo group (hazard ratio [HR] 0•88, 95% CI 0•79-0•99; p=0•026). All-cause mortality did not differ between groups (536 [10•8%] in the dulaglutide group vs 592 [12•0%] in the placebo group; HR 0•90, 95% CI 0•80-1•01; p=0•067). 2347 (47•4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34•1%) participants assigned to placebo (p<0•0001). Interpretation Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with type 2 diabetes with either previous cardiovascular disease or cardiovascular risk factors. Funding Eli Lilly and Company.

The Lancet, 2019

BACKGROUND Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people... more BACKGROUND Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. METHODS REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the compos...

European Heart Journal - Cardiovascular Imaging, 2018

Aims Studies have demonstrated the ability of a new automated algorithm for volumetric analysis o... more Aims Studies have demonstrated the ability of a new automated algorithm for volumetric analysis of 3D echocardiographic (3DE) datasets to provide accurate and reproducible measurements of left ventricular and left atrial (LV, LA) volumes at end-systole and end-diastole. Recently, this methodology was expanded using a machine learning (ML) approach to automatically measure chamber volumes throughout the cardiac cycle, resulting in LV and LA volume–time curves. We aimed to validate ejection and filling parameters obtained from these curves by comparing them to independent well-validated reference techniques. Methods and results We studied 20 patients referred for cardiac magnetic resonance (CMR) examinations, who underwent 3DE imaging the same day. Volume–time curves were obtained for both LV and LA chambers using the ML algorithm (Philips HeartModel), and independently conventional 3DE volumetric analysis (TomTec), and CMR images (slice-by-slice, frame-by-frame manual tracing). Autom...

Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, Jan 23, 2017

Although left ventricular global longitudinal strain (GLS) is an index of systolic function recom... more Although left ventricular global longitudinal strain (GLS) is an index of systolic function recommended by the guidelines, poor image quality may hamper strain measurements. While contrast agents are commonly used to improve endocardial visualization, no commercial speckle-tracking software is able to measure strain in contrast-enhanced images. This study aimed to test the accuracy of speckle-tracking software when applied to contrast-enhanced images in patients with suboptimal image quality. We studied patients with a wide range of GLS values who underwent transthoracic echocardiography. Protocol 1 included 44 patients whose images justified use of contrast but still allowed noncontrast speckle-tracking echocardiography (STE), which was judged as accurate and used as a reference. Protocol 2 included 20 patients with poor image quality that precluded noncontrast STE; cardiac magnetic resonance- (CMR-) derived strain was used as the reference instead. Half the manufacturer recommende...

Journal of the American College of Cardiology, Jan 28, 2017

Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy wit... more Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers. The purpose of this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers. A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negativ...

Studies in Family Planning, 2011

Journal of the American College of Cardiology, 2013

Imaging fully auTomaTed QuanTificaTion of lefT venTricular and lefT aTrial volumes from TransThor... more Imaging fully auTomaTed QuanTificaTion of lefT venTricular and lefT aTrial volumes from TransThoracic 3d echocardiography: a validaTion sTudy Moderated Poster Contributions

Journal of the American College of Cardiology, 2002

Revista de la Federación Argentina de Cardiología, 2018

Journal of Cardiovascular Echography, 2020

Relapsing polychondritis (RP) is a rare multisystem disease characterized by inflammation in cart... more Relapsing polychondritis (RP) is a rare multisystem disease characterized by inflammation in cartilaginous structures and other connective tissues throughout the body, affecting the ears, nose, eyes, joints, respiratory tract, heart, and blood vessels. Cardiovascular involvement is the second most common cause of mortality after laryngotracheal involvement. [1] Here, we report a successful surgical case of RP in which the patient underwent aortic and mitral valve replacement and concomitant coronary artery bypass grafting.

Journal of the American Society of Echocardiography, 2021

BACKGROUND Echocardiography remains the most widely used modality to assess left ventricular (LV)... more BACKGROUND Echocardiography remains the most widely used modality to assess left ventricular (LV) chamber size and function. Currently this assessment is most frequently performed using 2D echocardiography (2DE). Yet, 3D echocardiography (3DE) has been shown to be more accurate and reproducible than 2DE. Current normative reference values for 3D LV analysis are predominantly based on data from North America and Europe. The World Alliance of Societies of Echocardiography (WASE) study was a designed to sample normal subjects from around the world to provide more universal global reference ranges. In this study we sought to assess the world-wide feasibility of LV 3DE and report on size and function measurements. METHODS 2262 healthy subjects were prospectively enrolled from 19 centers in 15 countries. 3D LV full-volume datasets were obtained and analyzed offline with vendor-neutral software. Measurements included end-diastolic and end-systolic volumes (EDV, ESV), ejection fraction (EF), global longitudinal and circumferential strain (GLS and GCS). Results were categorized by age (18-40, 41-65 and >65 years), sex and race. RESULTS 1589 subjects (feasibility 70%) had adequate LV datasets for analysis. Mean normal values for indexed EDV, ESV and EF in men and women were 70 ± 15 and 65 ± 12 mL, 28 ± 7 and 25 ± 6 mL and 60 ± 5, 62 ± 5% respectively. Men had larger LV volumes and lower EF than women. GLS and GCS were higher in magnitude in women. In both sexes, LV volumes were lower and EF tended to be higher with increasing age, especially considering the differences between the youngest and oldest age groups. While GLS was similar across age groups in men, in women, the youngest and middle-age cohorts revealed higher magnitudes of GLS when compared to the oldest age group. GCS was higher in magnitude at older age in both men and women. Finally, Asians had smaller chamber sizes and higher EF and absolute strain values than both blacks and whites. CONCLUSIONS Age, sex, and race should be considered when defining normal reference values for LV dimension and function parameters obtained by 3DE.

Journal of Cardiology & Current Research, 2020

The restrictive pathologies are a group of diseases of low prevalence. Cardiac amyloidosis is con... more The restrictive pathologies are a group of diseases of low prevalence. Cardiac amyloidosis is considered to be the prototype of the infiltrative form of restrictive cardiomyopathies. The myocardial involvement is frequent, even at the first appearance of the disease and it has a poor prognosis; and although pleural involvement is less frequent, its presence determines a much more torpid evolution than isolated cardiac presentations. The main problem that these pathologies concern is their late recognition and the consequences this implies in the patient evolution. Nowadays, cardiac images tools may facilitate the diagnosis, allowing an early detection. We share an unusual case of amyloidosis with pleural involvement, where the results of the echocardiogram and the cardiac magnetic resonance allowed an approach to an accurate diagnostic.

Journal of the American Society of Echocardiography, 2021

BACKGROUND Assessment of cardiac output (CO) and stroke volume (SV) is essential to understand ca... more BACKGROUND Assessment of cardiac output (CO) and stroke volume (SV) is essential to understand cardiac function and hemodynamics. These parameters can be examined by three echocardiographic techniques (pulsed wave Doppler, 2D and 3D). Whether these methods can be used interchangeably is unclear. The influence of age, sex, and ethnicity on CO and SV has also not been examined in-depth. In this report from the World Alliance of Societies of Echocardiography (WASE) Normal Values study, we aim to compare CO and SV in healthy adults according to age, sex, ethnicity and measurement techniques. METHODS 1450 adult subjects (53% males) free from heart, lung and kidney disease were prospectively enrolled in 15 countries with even distribution among age groups and sex. Subjects were divided into three age groups: young (18-40), middle (41-65) and old (>65 years), and three main racial groups: whites, blacks, and Asians. CO and SV were indexed (CI and SVI, respectively) to body surface area (BSA) and height and measured using three echocardiographic methods: Doppler, 2D, and 3D. Images were analyzed in two core laboratories (one for each 2D and 3D). RESULTS CI and SVI were significantly lower by 2D compared to both Doppler and 3D methods in both sexes. SVI was significantly lower in females versus males by all 3 methods, while CI only differed by 2D. SVI decreased with aging by all three techniques, whereas CI declined only with 2D and 3D. CO and SV were smallest in Asians and largest in whites, and the differences persisted after normalization for BSA. CONCLUSION Our results provide normal reference values for CO and SV, which differ by age, sex and race. Further, CI and SVI measurements by the different echocardiographic techniques are not interchangeable. All these factors need to be taken into account when evaluating cardiac function and hemodynamics in individual patients.

Journal of the American Society of Echocardiography, 2021

BACKGROUND Left atrial (LA) evaluation includes volumetric and functional parameters with an abun... more BACKGROUND Left atrial (LA) evaluation includes volumetric and functional parameters with an abundance of diagnostic and prognostic implications. Solid normal reference ranges are compulsory for accurate interpretation in individual patients, but previous reports have yielded mixed conclusions regarding the effects of age, sex and/or race. The current report from the World Alliance Societies of Echocardiography (WASE) study focuses on 2D and 3D measures of LA structure and function, with subgroup analysis by age-, sex- and race. METHODS Transthoracic 2D and 3D echocardiographic images were obtained in 1,765 healthy individuals (901 males, 864 females) evenly distributed among age subgroups: 18-40 years (n=745), 41-65 years (n=618) and >65 years (n=402); 38.4% white, 39.9% Asian, 9.7% black. Images were analyzed using dedicated LA analysis software to measure LA volumes and phasic function from 3D volume and 2D strain curves. RESULTS 3D maximal and minimum LA volumes adjusted for BSA were nearly identical for men and women, but women demonstrated higher 3D total and passive EF. 2D reservoir strain was similar for both sexes. Age was associated with an incremental rise in LA volumes alongside characteristic shifts in functional indices. Total 2D EF, reservoir and conduit strain varied inversely with age, counteracted by higher booster strain, with a greater magnitude of effect in women. Active 3D EF was significantly higher, while total and passive EF decreased with age. Inter-racial differences were noted in LA volumes without substantial differences in functional indices. CONCLUSIONS While similar normal values for LA volumes and strain can be applied to both sexes, meaningful differences in LA size occur with aging. Indices of function also shift with age with a compensatory rise in booster function, which may serve to counteract observed lower total and passive EF. Defining age-associated normal values may help differentiate age-associated "healthy" LA aging from pathological processes.

JAMA Cardiology, 2021

IMPORTANCE Inflammation promotes cardiovascular disease and anti-inflammatory treatment reduces c... more IMPORTANCE Inflammation promotes cardiovascular disease and anti-inflammatory treatment reduces cardiovascular events in patients with chronic coronary syndrome. Chronic kidney disease (CKD) is a risk factor for cardiovascular disease. It is unclear how inflammation mediated by interleukin 6 (IL-6) in patients with CKD is linked to cardiovascular disease. OBJECTIVE To investigate associations between IL-6 and cardiovascular outcomes in patients with chronic coronary syndrome in association with kidney function. DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study included patients enrolled at 663 centers in 39 countries with chronic coronary syndrome who were included in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial. Patients were enrolled between December 2008 and April 2010 and were followed up for a median length of 3.7 years. Analysis in this substudy began September 2020. EXPOSURES Exposures were IL-6 and creatinine estimated glomerular filtration rates (eGFR), which were collected at baseline. Associations between continuous and categorical levels (<2.0 ng/L vs Ն2.0 ng/L) of IL-6 and cardiovascular outcomes were tested in association with eGFR cutoffs (normal eGFR level [Ն90 mL/min/1.73 m 2 ], mildly decreased eGFR level [60-90 mL/min/1.73 m 2 ], and moderately to severely decreased eGFR level [<60 mL/min/1.73 m 2 ]). MAIN OUTCOMES AND MEASURES Main outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke. RESULTS This substudy of the STABILITY trial included 14 611 patients with available IL-6 levels at baseline. The median (interquartile range) age was 65 (59-71) years, and 2700 (18.5%) were female. During follow-up, MACE occurred in 1459 individuals (10.0%). Higher levels of IL-6 were in continuous models independently associated with risk of MACE (P < .001) in all CKD strata. Using predefined strata, elevated IL-6 level (Ն2.0 vs <2.0 ng/L) was associated with increased risk of MACE at normal kidney function (2.9% vs 1.9% events/y [hazard ratio, 1.35; 95% CI, 1.02-1.78]), mild CKD (3.3% vs 1.9% [hazard ratio, 1.57; 95% CI, 1.35-1.83]), and moderate to severe CKD (5.0% vs 2.9% [hazard ratio, 1.60; 95% CI, 1.28-1.99]). CONCLUSIONS AND RELEVANCE In patients with chronic coronary syndrome, elevated levels of IL-6 were associated with risk of MACE in all CKD strata. Thus, IL-6 and CKD stage may help when identifying patients with chronic coronary syndrome for anti-inflammatory treatment.

Journal of the American Society of Echocardiography, 2020

Background: The World Alliance Societies of Echocardiography (WASE) study was conducted to descri... more Background: The World Alliance Societies of Echocardiography (WASE) study was conducted to describe echocardiographic normal values in adults and to compare races and nationalities using a uniform acquisition and measurement protocol. This report focuses on left ventricular (LV) diastolic function. Methods: WASE is an international, cross-sectional study. Participants were enrolled with equal distribution according to age and gender. Echocardiograms were analyzed in a core laboratory based on the latest American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Left ventricular diastolic function was assessed by E, E/A, e' velocities, E/e', left atrial volume index (LAVI), and tricuspid regurgitation velocity. Determination of LV diastolic function was made using the algorithm proposed by the guidelines.

JACC: Heart Failure, 2020

Decreased systolic function is a central factor in HFrEF. Current and investigational inotropic c... more Decreased systolic function is a central factor in HFrEF. Current and investigational inotropic calcitropic drugs have uniformly resulted in signals of increased mortality. OM is a myotrope and a selective cardiac myosin activator that improves cardiac function. The GALACTIC-HF trial evaluates the effect of OM on outcomes in patients with chronic HF.

Journal of the American Society of Echocardiography, 2019

Background: The World Alliance Societies of Echocardiography (WASE) Normal Values Study evaluates... more Background: The World Alliance Societies of Echocardiography (WASE) Normal Values Study evaluates individuals from multiple countries and races with the aim of describing normative values that could be applied to the global community worldwide and to determine differences and similarities among people from different countries and races. The present report focuses specifically on two-dimensional (2D) left ventricular (LV) dimensions, volumes, and systolic function. Methods: The WASE Normal Values Study is a multicenter international, observational, prospective, crosssectional study of healthy adult individuals. Participants recruited in each country were evenly distributed among six predetermined subgroups according to age and gender. Comprehensive 2D transthoracic echocardiograms were acquired and analyzed following strict protocols based on recent American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines. Analysis was performed at the WASE 2D core laboratory and included 2D LV dimensions, LV volumes, and LV ejection fraction (LVEF) by the biplane Simpson method and global longitudinal strain (GLS). Results: Two thousand eight subjects were enrolled in 15 countries. The median age was 45 years (interquartile range, 32-65 years), 42.8% were white, 41.8% were Asian, and 9.7% were black. LV dimensions and volumes were larger in male subjects, while LVEF and GLS were higher in female subjects. Global

The Lancet, 2019

Patients with stable coronary artery disease and diabetes with previous percutaneous coronary int... more Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8-3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74-0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, pinteraction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78-1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75-1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48-2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36-3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74-1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75-0·95, p=0·005, in contrast to patients without PCI where it did not, pinteraction=0·012. Benefit was present irrespective of time from most recent PCI. In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk. AstraZeneca.

The Lancet, 2019

Background Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascula... more Background Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A 1c (HbA 1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. Methods This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1•5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66•2 years [SD 6•5], median HbA 1c 7•2% [IQR 6•6-8•1], 4589 [46•3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5•4 years (IQR 5•1-5•9), the primary composite outcome occurred in 594 (12•0%) participants at an incidence rate of 2•4 per 100 person-years in the dulaglutide group and in 663 (13•4%) participants at an incidence rate of 2•7 per 100 person-years in the placebo group (hazard ratio [HR] 0•88, 95% CI 0•79-0•99; p=0•026). All-cause mortality did not differ between groups (536 [10•8%] in the dulaglutide group vs 592 [12•0%] in the placebo group; HR 0•90, 95% CI 0•80-1•01; p=0•067). 2347 (47•4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34•1%) participants assigned to placebo (p<0•0001). Interpretation Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with type 2 diabetes with either previous cardiovascular disease or cardiovascular risk factors. Funding Eli Lilly and Company.

The Lancet, 2019

BACKGROUND Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people... more BACKGROUND Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. METHODS REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the compos...

European Heart Journal - Cardiovascular Imaging, 2018

Aims Studies have demonstrated the ability of a new automated algorithm for volumetric analysis o... more Aims Studies have demonstrated the ability of a new automated algorithm for volumetric analysis of 3D echocardiographic (3DE) datasets to provide accurate and reproducible measurements of left ventricular and left atrial (LV, LA) volumes at end-systole and end-diastole. Recently, this methodology was expanded using a machine learning (ML) approach to automatically measure chamber volumes throughout the cardiac cycle, resulting in LV and LA volume–time curves. We aimed to validate ejection and filling parameters obtained from these curves by comparing them to independent well-validated reference techniques. Methods and results We studied 20 patients referred for cardiac magnetic resonance (CMR) examinations, who underwent 3DE imaging the same day. Volume–time curves were obtained for both LV and LA chambers using the ML algorithm (Philips HeartModel), and independently conventional 3DE volumetric analysis (TomTec), and CMR images (slice-by-slice, frame-by-frame manual tracing). Autom...

Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, Jan 23, 2017

Although left ventricular global longitudinal strain (GLS) is an index of systolic function recom... more Although left ventricular global longitudinal strain (GLS) is an index of systolic function recommended by the guidelines, poor image quality may hamper strain measurements. While contrast agents are commonly used to improve endocardial visualization, no commercial speckle-tracking software is able to measure strain in contrast-enhanced images. This study aimed to test the accuracy of speckle-tracking software when applied to contrast-enhanced images in patients with suboptimal image quality. We studied patients with a wide range of GLS values who underwent transthoracic echocardiography. Protocol 1 included 44 patients whose images justified use of contrast but still allowed noncontrast speckle-tracking echocardiography (STE), which was judged as accurate and used as a reference. Protocol 2 included 20 patients with poor image quality that precluded noncontrast STE; cardiac magnetic resonance- (CMR-) derived strain was used as the reference instead. Half the manufacturer recommende...

Journal of the American College of Cardiology, Jan 28, 2017

Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy wit... more Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers. The purpose of this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers. A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negativ...

Studies in Family Planning, 2011

Journal of the American College of Cardiology, 2013

Imaging fully auTomaTed QuanTificaTion of lefT venTricular and lefT aTrial volumes from TransThor... more Imaging fully auTomaTed QuanTificaTion of lefT venTricular and lefT aTrial volumes from TransThoracic 3d echocardiography: a validaTion sTudy Moderated Poster Contributions

Journal of the American College of Cardiology, 2002