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Anemia is prevalent in transthyretin amyloid cardiomyopathy (ATTR-CM), but its prognostic significance remains uncertain because of conflicting data mainly in patients not receiving disease-modifying therapy. Additionally, the effect of anemia on morbidity in this population has not been studied. This retrospective study included 270 patients diagnosed with ATTR-CM, receiving disease-modifying treatment (tafamidis), of which 30% (n = 80) were anemic (defined as a hemoglobin level <13 g/100 ml for males and <12 g/100 ml for females according to the World Health Organization). At baseline, patients with anemia were on average older (mean age 79 vs 77 years), more likely to be female (21% vs 12%), and exhibited higher symptom severity based on the New York Heart Association class (42% in class III vs 27%) compared with those without anemia. Additionally, they had a worse Columbia score (mean score 3 vs 5) and Columbia stage (12% in late-stage vs 7.1%) than those without anemia. Kaplan-Meier analysis indicates that anemia was associated with a higher likelihood of mortality, all-cause, and cardiovascular (CV) hospitalizations (p <0.05). However, in the Cox regression analysis, after adjusting for baseline age, ATTR genotype, and Columbia score, anemia was only associated with a higher risk of all-cause hospitalizations (hazard ratio 1.9 (1.3 to 2.7), p <0.001) and CV-related hospitalizations (hazard ratio 1.9 (1.2 to 2.9), p = 0.006). In conclusion, this study indicates that anemic patients with ATTR-CM have higher risks of CV and all-cause hospitalizations compared with nonanemic ATTR-CM patients. Further research is needed to understand how treating anemia may improve outcomes in this high-risk patient population.
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BACKGROUND: The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations study seeks to determine the prevalence of transthyretin cardiac amyloidosis (ATTR-CA) among older Black or Caribbean Hispanic individuals with heart failure and an increased wall thickness. We noticed varied recruitment percentages across the recruiting sites and sought to determine the factors associated with greater percentage enrollment of eligible participants. METHODS: The percentage of enrolled to eligible participants was calculated across study sites. Baseline demographic and clinical characteristics, health literacy, trust in providers, perceived discrimination, area deprivation index (ADI) and English proficiency were compared by site using Kruskal-Wallis's test or one-way ANOVA for continuous variables and the Chi-Square test or Fisher's exact test for categorical variables. Wilcoxon rank sum and Chi-Square tests, with multiple comparisons correction using the false discovery rate (FDR) method, were used as post-hoc analysis when results were statistically significant. RESULTS: Among the four recruiting sites, Boston Medical Center, Columbia University Irving Medical Center, Harlem Hospital and Yale University, which employed different recruitment approaches, the percentage of participants enrolled among eligible participants differed, with the highest rate at Harlem Hospital (n=149 of 310, 48%), followed by Yale University (n=27 of 67, 40%), Boston University (n=247 of 655, 38%), and Columbia University (n=137of 442, 32%), p <0.01. Direct recruitment by the primary cardiovascular care team providing clinical care was associated with higher percent enrolled across sites as were higher education levels and English proficiency. Enrollment differences across sites were not associated with the number of chronic diseases, physician trust, perceived discrimination, or health literacy. CONCLUSIONS: Recruitment of eligible under-represented minorities (URMs) in SCAN-MP was associated with approaches employed in recruitment, including direct initial contact by the primary cardiovascular care team providing the potential participant's clinical care. Such data may help improve approaches to more successful recruitment of URMs in clinical research.
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PURPOSE OF REVIEW: Tafamidis is currently the only approved disease-modifying treatment for ATTR-CM. However, there have been important developments in the treatment of ATTR-CM, as the results of two phase 3 trials were published and several other trials are in their final stages. In this review, we summarize current and future therapies for ATTR-CM. RECENT FINDINGS: Recently, acoramidis, a TTR stabilizer has been proven to be effective in reducing mortality and morbidity compared to placebo in the ATTRibute-CM trial. Additionally, patisiran, an RNA silencer, preserved functional capacity and quality of life compared to placebo in the APOLLO-B trial. However, the FDA declined to approve patisiran for ATTR-CM. The results of phase 1 trial of ALXN2220, an antiamyloid antibody raise hope for reversal of myocardial damage by amyloid depletion. Phase 3 trials evaluating the efficacy of different RNA silencers, gene editing with CRISPR-Cas9, and other anti-amyloid antibodies are ongoing. SUMMARY: Therapies targeting different mechanism in the pathophysiology of ATTR-CM provide new alternatives for treating patients with ATTR-CM. Future research should focus on comparing their effectiveness, the potential of combined treatment with agents from different classes and on identifying the patients who will benefit most from each class of medication.
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Neuropatías Amiloides Familiares , Cardiomiopatías , Humanos , Neuropatías Amiloides Familiares/tratamiento farmacológico , Neuropatías Amiloides Familiares/terapia , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/terapia , Benzoxazoles/uso terapéutico , ARN Interferente PequeñoRESUMEN
AIMS: Despite their potential, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have not been well-studied in transthyretin amyloid cardiomyopathy (ATTR-CM) as randomized trials have excluded patients with this morbid disease. We performed a retrospective study assessing the short-term efficacy and safety of SGLT2i in ATTR-CM. METHODS AND RESULTS: We screened consecutive patients seen at a tertiary care centre and identified 87 ATTR-CM patients treated with SGLT2i and 95 untreated control patients. Endpoints included changes in weight, loop diuretic dose, and cardiac/renal biomarkers. The median age of the overall population was 79 (interquartile range [IQR] 11) years. Nearly 90% of patients were male, and 93% were on a transthyretin stabilizer. Control patients demonstrated generally less severe disease at baseline compared to SGLT2i-treated patients, with lower median Columbia risk score (p < 0.001). Median follow-up time was 5.6 (IQR 5.2) and 8.4 (IQR 2.1) months in the SGLT2i and control cohorts, respectively. Compared with controls, SGLT2i treatment was associated with significantly greater reductions from baseline in weight, loop diuretic dose, and uric acid during follow-up (p < 0.001). While no significant between-group differences were observed on cardiac biomarkers, estimated glomerular filtration rate was significantly reduced versus controls 1 month after SGLT2i initiation (p = 0.002), but no significant differences were observed at later timepoints. Results were similar in a propensity score-matched analysis (n = 42 per cohort). A total of 10 (11.5%) patients discontinued SGLT2i, most commonly due to genitourinary symptoms. CONCLUSION: Sodium-glucose cotransporter 2 inhibitors were well tolerated by most patients with ATTR-CM and appeared to improve volume status and combat diuretic resistance. Randomized studies are needed to confirm these findings.
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Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Masculino , Femenino , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Neuropatías Amiloides Familiares/tratamiento farmacológico , Cardiomiopatías/tratamiento farmacológico , Anciano de 80 o más AñosRESUMEN
AIMS: Complete haematologic response to treatment for light chain cardiac amyloidosis (AL-CA) may lead to improvement of myocardial function and better outcomes. We sought to evaluate the effect of response to treatment for AL-CA on echocardiographic indices of myocardial deformation and work and their prognostic significance. METHODS AND RESULTS: Sixty-one patients treated for AL were enrolled and underwent echocardiographic assessment at baseline and at 1 year. Patients were stratified according to haematologic response as complete or not complete responders. A significant reduction in median N-terminal pro-brain natriuretic peptide (NT-proBNP) (2771-1486 pg/mL; P < 0.001) and posterior wall thickness (13-12 mm; P = 0.002) and an increase in global work index (GWI) (1115-1356 mmHg%; P = 0.018) was observed at 1 year. Patients with complete response (CR) had a more pronounced decrease in intraventricular septum thickness (14.2-12.0 mm; P = 0.006), improved global longitudinal strain (GLS) (-11.6 to -13.1%; P for interaction = 0.045), increased global constructive work (1245-1436 mmHg%; P = 0.008), and GWI (926-1250 mmHg%, P = 0.002) compared with non-CR. Furthermore, deltaGLS (ρspearman = 0.35; P < 0.001) and deltaGWI (ρspearman = -0.32; P = 0.02) correlated with delta NT-proBNP. Importantly, patients with GLS and GWI response had a better prognosis (log-rank P = 0.048 and log-rank P = 0.007, respectively). After adjustment for Mayo stage, gender, and response status, deltaGLS [hazard ratio (HR) = 1.404, P = 0.046 per 1% increase] and deltaGWI (HR = 0.996, P = 0.042 per 1mmHg% increase) were independent predictors of survival. CONCLUSION: Complete haematologic response to treatment is associated with improved left ventricular myocardial work indices, and their change is associated with improved survival in AL-CA.
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Ecocardiografía , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Pronóstico , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/mortalidad , Péptido Natriurético Encefálico/sangre , Amiloidosis/diagnóstico por imagen , Amiloidosis/mortalidad , Resultado del Tratamiento , Fragmentos de Péptidos/sangre , Análisis de Supervivencia , Estudios de Cohortes , Medición de Riesgo , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/mortalidad , Disfunción Ventricular Izquierda/fisiopatología , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/mortalidad , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/diagnóstico por imagen , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Índice de Severidad de la Enfermedad , Tasa de SupervivenciaRESUMEN
Atrial fibrillation (AF) is the most common arrhythmia with a high burden of morbidity including impaired quality of life and increased risk of thromboembolism. Early detection and management of AF could prevent thromboembolic events. Artificial intelligence (AI)--based methods in healthcare are developing quickly and can be proved as valuable for the detection of atrial fibrillation. In this metanalysis, we aim to review the diagnostic accuracy of AI-based methods for the diagnosis of atrial fibrillation. A predetermined search strategy was applied on four databases, the PubMed on 31 August 2022, the Google Scholar and Cochrane Library on 3 September 2022, and the Embase on 15 October 2022. The identified studies were screened by two independent investigators. Studies assessing the diagnostic accuracy of AI-based devices for the detection of AF in adults against a gold standard were selected. Qualitative and quantitative synthesis to calculate the pooled sensitivity and specificity was performed, and the QUADAS-2 tool was used for the risk of bias and applicability assessment. We screened 14,770 studies, from which 31 were eligible and included. All were diagnostic accuracy studies with case-control or cohort design. The main technologies used were: (a) photoplethysmography (PPG) with pooled sensitivity 95.1% and specificity 96.2%, and (b) single-lead ECG with pooled sensitivity 92.3% and specificity 96.2%. In the PPG group, 0% to 43.2% of the tracings could not be classified using the AI algorithm as AF or not, and in the single-lead ECG group, this figure fluctuated between 0% and 38%. Our analysis showed that AI-based methods for the diagnosis of atrial fibrillation have high sensitivity and specificity for the detection of AF. Further studies should examine whether utilization of these methods could improve clinical outcomes.
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BACKGROUND: Clinical characteristics and outcomes of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) vary by region, necessitating the acquisition of country-specific evidence for proper management. METHODS: This is an observational study including sequential patients presenting in the Amyloidosis Reference Center of Greece, from 01/2014 to 12/2022. ATTR-CM was diagnosed by positive scintigraphy and exclusion of light-chain amyloidosis or positive biopsy typing. Genetic testing was performed in all cases. RESULTS: One-hundred and nine ATTR-CM patients were included (median age, 81 years) of which 15 carried TTR mutations (27% Val30Met). Most patients (82%) presented with heart failure and 59% with atrial fibrillation, while 10% had aortic stenosis. Importantly, 78 (71.6%) had clinically significant extracardiac manifestations (45% musculoskeletal disorder, 40% peripheral neuropathy and 33% gastrointestinal symptoms). Sixty-five (60%) received disease-specific treatment with tafamidis. Estimated median survival was 48 months; advanced NYHA class, National Amyloidosis Center stage, eGFR<45 ml/kg/1.73m2, NT-pro-BNP>5000 pg/mL were associated with worse survival, while tafamidis treatment was associated with improved survival in patients with IVS≥ 12 mm. DISCUSSION: These are the first data describing the characteristics, management, and outcomes of patients with ATTR-CM in Greece, which could influence local guidelines. SHORT TITLE: Transthyretin cardiomyopathy in Greece.
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Cardiac amyloidosis (CA) is a rare but potentially life-threatening disease in which misfolded proteins accumulate in the cardiac wall tissue. Heart rhythm disorders in CA, including supraventricular arrhythmias, conduction system disturbances, or ventricular arrhythmias, play a major role in CA morbidity and mortality, and thus require supplementary management. Among them, AF is the most frequent arrhythmia during CA hospitalizations and is associated with significantly higher mortality, while ventricular arrhythmias are also common and are usually associated with poor prognosis. Early diagnosis of potential arrythmias could be performed through ECG, Holter monitoring, and/or electrophysiology study. Clinical management of these patients is quite significant, and it usually includes initiation of amiodarone and/or digoxin in patients with AF, potential electrical cardioversion, or ablation in specific patients with indication, as well as initiation of anticoagulants in all patients, independent of AF and CHADS-VASc score, for potential intracardiac thrombus. Moreover, identification of patients with conduction disorders that could benefit from prophylactic pacemaker implantation and/or CRT as well as identification of patients with life-threatening ventricular arrythmias that could benefit from ICD could both increase the survival rates of these patients and improve their quality of life.
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The appropriate diagnosis and subtyping of cardiac amyloidosis (CA) is frequently missed or delayed due to its vague presentation, clinical overlapping, and diagnostic pitfalls. Recent developments in both invasive and non-invasive diagnostic techniques have significantly changed the diagnostic approach of CA. With the present review, we aim to summarize the current diagnostic approach of CA and to underline the indications of tissue biopsy, either surrogate site or myocardial. The most important factor for timely diagnosis is increased clinical suspicion, especially in certain clinical scenarios. Appropriate imaging with echocardiography or cardiac magnetic resonance (CMR) can provide significant evidence for the diagnosis of CA. Importantly, all patients should undergo monoclonal proteins assessment, with these results significantly determining the steps to follow. A negative monoclonal protein assessment will lead to a non-invasive algorithm which, in combination with positive cardiac scintigraphy, can establish the diagnosis of ATTR-CA. The latter is the only clinical scenario in which the diagnosis can be established without the need of biopsy. However, if the imaging results are negative but the clinical suspicion remains high, a myocardial biopsy should be performed. In the case of the presence of monoclonal protein, an invasive algorithm follows, first by surrogate site sampling and then by myocardial biopsy if the results are inconclusive or prompt diagnosis is needed. The role of endomyocardial biopsy, even though limited by current advances in other techniques, is highly valuable in selected patients and is the only method to reliably establish a diagnosis in challenging cases.
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PURPOSE: Cardiovascular disease is commonly accompanied by renal dysfunction. Multimorbidity in hospitalized patients impacts unfavorably on prognosis and hospital stay. We aimed to illustrate the contemporary burden of cardiorenal morbidity across inpatient cardiology care in Greece. METHODS: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) used an electronic platform to collect demographic and clinically relevant information about all patients hospitalized on March 3, 2022, in Greece. The participating institutions covered all levels of inpatient cardiology care and most of the country's territories to collect a real-world, nation representative sample. RESULTS: A total of 923 patients (men 68.4%, median age 73 ± 14.8 years) were admitted to 55 different cardiology departments. 57.7% of the participants were aged >70 years. Hypertension was highly prevalent and present in 66% of the cases. History of chronic HF, diabetes mellitus, atrial fibrillation, and chronic kidney disease was present in 38%, 31.8%, 30%, and 26%, respectively. Furthermore, 64.1% of the sample exhibited at least one of these 4 entities. Accordingly, a combination of ≥2 of these morbid conditions was recorded in 38.7%, of ≥3 in 18.2%, whereas 4.3% of the sample combined all 4 in their medical history. The most common combination was the coexistence of heart failure-atrial fibrillation accounting for 20.6% of the sample. Nine of 10 nonelectively admitted patients were hospitalized due to acute HF (39.9%), acute coronary syndrome (33.5%), or tachyarrhythmias (13.2%). CONCLUSION: HECMOS participants carried a remarkable burden of cardio-reno-metabolic disease. HF in conjunction with atrial fibrillation was found to be the most prevalent combination among the studied cardiorenal nexus of morbidities in the whole study population.
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Fibrilación Atrial , Cardiología , Insuficiencia Cardíaca , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Multimorbilidad , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , MorbilidadRESUMEN
BACKGROUND: Accumulating evidence suggests a substantial contribution of remnant cholesterol (RC) to residual risk for the development or relapse of atherosclerotic cardiovascular disease (ASCVD). We aimed to evaluate the association of RC levels with ASCVD risk by different risk categories and methods of RC assessment. We also assessed available evidence of the effects of lipid-lowering therapies (LLTs) on RC levels. METHODS: English-language searches of Medline, PubMed, and Embase (inception to 31 January 2023); ClinicalTrials.gov (October 2022); and reference lists of studies and reviews. Studies reporting on the risk of the composite endpoint [all-cause mortality, cardiovascular mortality, and major adverse cardiac events (MACE)] by RC levels were included. Moreover, we searched for studies reporting differences in RC levels after the administration of LLT(s). RESULTS: Among n = 29 studies with 257,387 participants, we found a pooled linear (pooled HR: 1.27 per 1-SD increase, 95% CI: 1.12-1.43, P < 0.001, I2 = 95%, n = 15 studies) and non-linear association (pooled HR: 1.59 per quartile increase, 95% CI: 1.35-1.85, P < 0.001, I2 = 87.9%, n = 15 studies) of RC levels and the risk of M ACE both in patients with and without established ASCVD. Interestingly, the risk of MACE was higher in studies with directly measured vs. calculated RC levels. In a limited number of studies and participants, LLTs reduced RC levels. CONCLUSION: RC levels are associated with ASCVD risk both in primary and secondary prevention. Directly measured RC levels are associated with ASCVD risk more evidently. Available LLTs tend to decrease RC levels, although the clinical relevance of RC decrease merits further investigation. PROSPERO REGISTRATION: CRD42022371346.
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Aterosclerosis , Enfermedades Cardiovasculares , Humanos , Colesterol , Aterosclerosis/epidemiología , Aterosclerosis/etiologíaRESUMEN
OBJECTIVE: Sex-specific data are limited regarding eligibility for hypolipidemic treatment. We aim to explore the sex-specific clinical utility of high-sensitivity C-reactive protein (hsCRP) and carotid ultrasound as risk modifiers for hypolipidemic treatment in primary prevention of atherosclerotic cardiovascular disease (ASCVD). METHODS: We aimed to explore these sex-specific trends in two pooled contemporary independent Greek cohorts (Athens Vascular Registry n = 698, 50.9% women and Menopause Clinic n = 373, 100% women) of individuals without overt ASCVD. Baseline ASCVD risk was estimated using the Systematic COronary Risk Evaluation-2 (SCORE2) tools. The presence of carotid plaque and hsCRP ≥2 mg/L were integrated as risk modifiers. RESULTS: Men had increased odds to achieve target LDL-C levels based on ASCVD risk (23.8% vs. 17.7%, OR: 1.45 95% CI: 1.05-2.00, p = 0.023, for men vs. women). Additionally, considering carotid plaque or high hsCRP levels did not change this association but reduced on-target LDL-C rate in both sexes. Women had decreased odds of being eligible for hypolipidemic treatment by ASCVD risk estimation (11.5% vs. 26.4%, p < 0.001) compared with men. The addition of carotid plaque presence or high hsCRP levels and their combination resulted in a higher relative increase in hypolipidemic treatment eligibility in women (from 11.5% to 70.9% vs. 26.4% to 61.4% for carotid plaque, from 11.5% to 38.5% vs. 26.4% to 50.8% for hsCRP and from 11.5% to 79.1% vs. 26.4% to 75% for their combination, all for women vs. men, pforinteraction < 0.001 for all) than men. CONCLUSIONS: Implementation of carotid plaque and hsCRP levels increases hypolipidemic treatment eligibility more prominently in women than in men. The impact on clinical outcomes in these untreated patients merits further investigation.
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Aterosclerosis , Enfermedades Cardiovasculares , Placa Aterosclerótica , Masculino , Humanos , Femenino , Proteína C-Reactiva/análisis , Factores de Riesgo , LDL-Colesterol , Aterosclerosis/prevención & control , Arterias Carótidas , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/tratamiento farmacológicoRESUMEN
BACKGROUND: The effect of SARS-CoV-2 infection in blood lipids of homozygous familial hypercholesterolemia (HoFH) has not been explored. CASE SUMMARY: We report a case of a 43-year-old male patient with -/-LDLR HoFH with previous history of premature coronary artery disease, coronary artery bypass graft (CABG) and surgical repair of aortic valve stenosis. He presented with an abrupt decrease of his blood lipid levels during acute infection with SARS-CoV2 and subsequently a rebound increase above pre-infection levels, refractory to treatment including LDL-apheresis, statin, ezetimibe and lomitapide up-titration to maximum tolerated doses. Markers of liver stiffness were closely monitored, increased at 9 months and decreased at 18 months after the infection. Potential interactions of hypolipidemic treatment with the viral replication process during the acute phase, as well as therapeutic dilemmas occurring in the post infection period are discussed.
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Anticolesterolemiantes , COVID-19 , Hipercolesterolemia Familiar Homocigótica , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Adulto , Humanos , Masculino , Anticolesterolemiantes/uso terapéutico , Homocigoto , Hipercolesterolemia/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/genética , Lípidos , ARN Viral/uso terapéutico , SARS-CoV-2RESUMEN
The causative associations between glycemia and early alterations in renal and vascular function remain unclear. To examine the interplay among glycemia, renal function, and markers of subclinical atherosclerosis in apparently healthy subjects. Nondiabetic (30-60 years old) individuals (n = 205) without chronic kidney disease or cardiovascular disease were consecutively recruited from a cardiovascular prevention clinic. All subjects underwent arterial stiffness assessment by measuring the carotid-femoral pulse wave velocity (cfPWV). Glomerular filtration rate (GFR) was estimated by CKD-EPI equation. Study procedures were identical in the two visits (median follow-up 66 months). We employed structural equation modeling (SEM) analysis to investigate the directionality of associations. Baseline fasting plasma glucose (FPG) was independently and inversely associated with GFR (p = 0.008). GFR was significantly associated with cfPWV (p < 0.001) at baseline. By SEM analysis decreasing baseline GFR directly correlated with increasing cfPWV (p = 0.003) whereas FPG correlated with cfPWV indirectly through GFR (mediation) (P = 0.032). FPG did not mediate the effect of GFR on cfPWV (P = 0.768). SEM analysis of longitudinal data revealed bidirectional correlations between changes in FPG and GFR (P < 0.001). Alterations in GFR were directly related to changes in cfPWV (p < 0.001) whereas FPG only indirectly correlated with cfPWV through GFR changes (P = 0.002). In apparently healthy nondiabetic subjects, the association between baseline or longitudinal glycemia levels and arterial stiffening was indirect, consistently mediated by renal function status. These findings provide the first clinical evidence supporting the directionality between kidney function and glycemia in nondiabetic subjects leading to vascular dysfunction. In apparently healthy nondiabetic subjects, without cardiovascular disease or chronic kidney disease, the association between baseline or longitudinal glycemia levels and arterial stiffening was indirect, consistently mediated by renal function status.
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Aterosclerosis , Enfermedades Cardiovasculares , Insuficiencia Renal Crónica , Rigidez Vascular , Humanos , Adulto , Persona de Mediana Edad , Enfermedades Cardiovasculares/etiología , Análisis de la Onda del Pulso/métodos , Análisis de Mediación , Riñón/fisiología , Insuficiencia Renal Crónica/complicaciones , Factores de Riesgo , Presión SanguíneaRESUMEN
BACKGROUND: Despite hypertrophic cardiomyopathy (HCM) being the most common inherited heart disease and conferring increased risk for heart failure (HF) and sudden cardiac death (SCD), risk assessment in HCM patients is still largely unresolved. OBJECTIVES: This study aims to synthesize and compare the prognostic impact of demographic, clinical, biochemical, and imaging findings in patients with HCM. METHODS: The authors searched PubMed, Embase, and Cochrane Library for studies published from 1955 to November 2020, and the endpoints were: 1) all-cause death; 2) an arrhythmic endpoint including SCD, sustained ventricular tachycardia, ventricular fibrillation, or aborted SCD; and 3) a composite endpoint including (1) or (2) plus hospitalization for HF or cardiac transplantation. The authors performed a pairwise meta-analysis obtaining the pooled estimate separately for the association between baseline variables and study endpoints. A random-effects network meta-analysis was subsequently used to comparatively assess the prognostic value of outcome associates. RESULTS: A total of 112 studies with 58,732 HCM patients were included. Among others, increased brain natriuretic peptide/N-terminal pro-B-type natriuretic peptide, late gadolinium enhancement (LGE), positive genotype, impaired global longitudinal strain, and presence of apical aneurysm conferred increased risk for the composite endpoint. At network meta-analysis, LGE showed the highest prognostic value for all endpoints and was superior to all other associates except New York Heart Association functional class >class II. A multiparametric imaging-based model was superior in predicting the composite endpoint compared to a prespecified model based on conventional risk factors. CONCLUSIONS: This network meta-analysis supports the development of multiparametric risk prediction algorithms, including advanced imaging markers additively to conventional risk factors, for refined risk stratification in HCM. (Long-term prognosis of hypertrophic cardiomyopathy according to genetic, clinical, biochemical and imaging findings: a systemic review and meta-analysis; CRD42020185219).
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Cardiomiopatía Hipertrófica , Insuficiencia Cardíaca , Humanos , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/complicaciones , Medios de Contraste , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Demografía , Gadolinio , Insuficiencia Cardíaca/complicaciones , Metaanálisis en Red , Pronóstico , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
AIM: Ubiquitin-Proteasome System (UPS) is of paramount importance regarding the function of the myocardial cell. Consistently, inhibition of this system has been found to affect myocardium in experimental models; yet, the clinical impact of UPS inhibition on cardiac function has not been comprehensively examined. Our aim was to gain insight into the effect of proteasome inhibition on myocardial mechanics in humans. METHODS AND RESULTS: We prospectively evaluated 48 patients with multiple myeloma and an indication to receive carfilzomib, an irreversible proteasome inhibitor. All patients were initially evaluated and underwent echocardiography with speckle tracking analysis. Carfilzomib was administered according to Kd treatment protocol. Follow-up echocardiography was performed at the 3rd and 6th month. Proteasome activity (PrA) was measured in peripheral blood mononuclear cells.At 3 months after treatment, we observed early left ventricular (LV) segmental dysfunction and deterioration of left atrial (LA) remodelling, which was sustained and more pronounced than that observed in a cardiotoxicity control group. At 6 months, LV and right ventricular functions were additionally attenuated (P < 0.05 for all). These changes were independent of blood pressure, endothelial function, inflammation, and cardiac injury levels. Changes in PrA were associated with changes in global longitudinal strain (GLS), segmental LV strain, and LA markers (P < 0.05 for all). Finally, baseline GLS < -18% or LA strain rate > 1.71 were associated with null hypertension events. CONCLUSION: Inhibition of the UPS induced global deterioration of cardiac function.
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Complejo de la Endopetidasa Proteasomal , Disfunción Ventricular Izquierda , Humanos , Estudios Prospectivos , Complejo de la Endopetidasa Proteasomal/farmacología , Leucocitos Mononucleares , Corazón , Función Ventricular Izquierda/fisiologíaRESUMEN
PURPOSE: The increase in cardiovascular risk after the menopausal transition remains partly explained until today. Further research is needed to identify risk factors potentially modifiable by primary prevention practices. This cross-sectional study, part of a larger prospective project, aims to investigate possible associations between dietary patterns and indices of vascular structure and function among healthy postmenopausal women. METHODS: Postmenopausal women (n = 310) without clinically overt cardiovascular disease were recruited consecutively from a University Menopause Clinic over three years. Dietary intake was assessed by a validated food frequency questionnaire and the MedDietScore. In addition, we assessed anthropometric/biochemical parameters, including the Triglyceride-glucose index (TyG-Index), body fat distribution [triceps skinfold (TSF), mid-upper arm circumference (MUAC)] and physical activity. The vascular assessment included carotid-femoral pulse wave velocity (PWV), carotid and femoral-artery intima-media thickness (IMT) and atheromatous plaques presence. RESULTS: Consumption of non-refined cereals was associated with carotid-bulb IMT (R2 = 5.5% b-coefficient = -0.142; p = 0.011), adjusting for age, physical activity, lipids, systolic blood pressure, smoking, body mass index, insulin resistance, and daily energy intake. PWV was associated with the intake of total dairy products (R2 = 27.3%, b-coefficient = -0.117; p = 0.017). Higher red meat consumption was related to a greater TyG-index (Model 1, R2 = 14.3%, b-coefficient=0.121; p = 0.048), an association mediated by total daily energy intake. Higher consumption of alcohol, as well as the MedDietScore, were inversely associated with TSF measurements, significant after Bonferroni correction. CONCLUSION: Dietary patterns are associated with metabolic indices and subclinical atherosclerosis in postmenopausal women independently of traditional cardiovascular risk factors, total energy intake or physical activity.
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Enfermedades de las Arterias Carótidas , Rigidez Vascular , Femenino , Humanos , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Estudios Transversales , Posmenopausia , Estudios Prospectivos , Análisis de la Onda del Pulso , Factores de Riesgo , Rigidez Vascular/fisiologíaRESUMEN
BACKGROUND: Accumulating evidence suggests that endothelial dysfunction is implicated in the pathogenesis and severity of coronavirus disease 2019 (COVID-19). In this context, vascular impairment in COVID-19 might be associated with clinical manifestations and could refine risk stratification in these patients. METHODS: This systematic review aims to synthesize current evidence on the frequency and the prognostic value of vascular dysfunction during acute and post-recovery COVID-19. After systematically searching the MEDLINE, clinicaltrials.gov and the Cochrane Library from 1 December 2019 until 05 March 2022, we identified 24 eligible studies with laboratory confirmed COVID-19 and a thorough examination of vascular function. Flow-mediated dilation (FMD) was assessed in 5 and 12 studies in acute and post-recovery phase respectively; pulse wave velocity (PWV) was the marker of interest in three studies in the acute and four studies in the post-recovery phase. RESULTS: All studies except for one in the acute and in the post-recovery phase showed positive association between vascular dysfunction and COVID-19 infection. Endothelial dysfunction in two studies and increased arterial stiffness in three studies were related to inferior survival in COVID-19. DISCUSSION: Overall, a detrimental effect of COVID-19 on markers of endothelial function and arterial stiffness that could persist even for months after the resolution of the infection and provide prognostic value was congruent across published studies. Further research is warranted to elucidate clinical implications of this association.
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COVID-19 , Rigidez Vascular , Arteria Braquial , COVID-19/complicaciones , Endotelio , Endotelio Vascular , Humanos , Análisis de la Onda del PulsoRESUMEN
BACKGROUND: The noncoding antisense transcript for ß-secretase-1 (BACE1-AS) is a long noncoding RNA with a pivotal role in the regulation of amyloid-ß (Aß). We aimed to explore the clinical value of BACE1-AS expression in atherosclerotic cardiovascular disease (ASCVD). METHODS: Expression of BACE1-AS and its target, ß-secretase 1 (BACE1) mRNA, was measured in peripheral blood mononuclear cells derived from 434 individuals (259 without established ASCVD [non-CVD], 90 with stable coronary artery disease [CAD], and 85 with acute coronary syndrome). Intima-media thickness and atheromatous plaques evaluated by ultrasonography, as well as arterial wave reflections and pulse wave velocity, were measured as markers of subclinical ASCVD. Patients were followed for a median of 52 months for major adverse cardiovascular events (MACE). RESULTS: In the cross-sectional arm, BACE1-AS expression correlated with BACE1 expression (r = 0.396, p < 0.001) and marginally with Aß1-40 levels in plasma (r = 0.141, p = 0.008). Higher BACE1-AS was associated with higher estimated CVD risk assessed by HeartScore for non-CVD subjects and by European Society of Cardiology clinical criteria for the total population (p < 0.05 for both). BACE1-AS was associated with higher prevalence of CAD (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.37-2.5), multivessel CAD (OR = 1.36, 95% CI: 1.06-1.75), and with higher number of diseased vascular beds (OR = 1.31, 95% CI: 1.07-1.61, for multiple diseased vascular beds) after multivariable adjustment for traditional cardiovascular risk factors. In the prospective arm, BACE1-AS was an independent predictor of MACE in high cardiovascular risk patients (adjusted hazard ratio = 1.86 per ascending tertile, 95% CI: 1.011-3.43, p = 0.046). CONCLUSION: BACE1-AS is associated with the incidence and severity of ASCVD.