Carotid intima layer thickness but not intima-media thickness is related to coronary artery calcification in type 2 diabetes individuals: Results from the Brazilian diabetes study.

BACKGROUND AND AIMS: Carotid intima-media thickness (cIMT) is inconsistent in predicting cardiovascular risk. This may stem from the variability of the media thickness (cM) outweighing the intimal thickness (cIT) as the sign of atherosclerosis. Thus, we evaluated in type 2 diabetes (T2D) individuals, the association between carotid measures and coronary artery calcification (CAC). METHODS AND RESULTS: Association between the presence of CAC and cIT, cM, and cIMT were examined on 224 individuals. Logistic binary regression was used to assess CAC predictors. The Akaike information criterion (AIC) and log-likelihood test (LLT) were used to assess differences among univariate models. The cIT (0.335 mm vs 0.363 mm; p = 0.001) and cIMT (0.715 vs 0.730; p = 0.019), but not cM (0.386 mm vs 0,393 mm; p = 0.089) were higher among individuals with CAC. In unadjusted analysis, cIT (273;-134; p = 0.001) showed greater relationship with CAC, when compared to cIMT (279;-137; p = 0.022) and cM (281;-139; p = 0.112) based on the AIC and LLT, respectively. In multivariate logistic regression, CAC was related to carotid plaque (OR): 1.91, 95% confidence interval (CI):1.08, 3.38; p = 0.027), and high-cIT (OR: 2.70, 95%CI:1.51, 4.84; p = 0.001), but not to high-cIMT (OR:1.70, 95%CI:0.96, 3.00; p = 0.067) nor high-cM (OR:1.33, 95%CI:0.76, 2.34; p = 0.322). CONCLUSION: In T2D individuals, cIT is a better predictor of CAC than cIMT; cM is not associated with CAC.

Prognostic role of renal replacement therapy among hospitalized patients with heart failure in the Brazilian national public health system.

Introduction: Data on patients hospitalized with acute heart failure in Brazil scarce. Methods: We performed a cross-sectional, retrospective, records-based study using data retrieved from a large public database of heart failure admissions to any hospital from the Brazilian National Public Health System (SUS) (SUS Hospital Information System [SIHSUS] registry) to determine the in-hospital all-cause mortality rate, in-hospital renal replacement therapy rate and its association with outcome. Results: In total, 910,128 hospitalizations due to heart failure were identified in the SIHSUS registry between April 2017 and August 2021, of which 106,383 (11.7%) resulted in in-hospital death. Renal replacement therapy (required by 8,179 non-survivors [7.7%] and 11,496 survivors [1.4%, p < 0.001]) was associated with a 56% increase in the risk of death in the univariate regression model (HR 1.56, 95% CI 1.52 -1.59), a more than threefold increase of the duration of hospitalization, and a 45% or greater increase of cost per day. All forms of renal replacement therapy remained independently associated with in-hospital mortality in multivariable analysis (intermittent hemodialysis: HR 1.64, 95% CI 1.60 -1.69; continuous hemodialysis: HR 1.52, 95% CI 1.42 -1.63; peritoneal dialysis: HR 1.47, 95% CI 1.20 -1.88). Discussion: The in-hospital mortality rate of 11.7% observed among patients with acute heart failure admitted to Brazilian public hospitals was alarmingly high, exceeding that of patients admitted to North American and European institutions. This is the first report to quantify the rate of renal replacement therapy in patients hospitalized with acute heart failure in Brazil.

Effectiveness of Oral Hydration in Preventing Contrast-Induced Nephropathy in Individuals Undergoing Elective Coronary Interventions. / Eficácia da Hidratação Oral na Prevenção da Nefropatia Induzida por Contraste em Indivíduos Submetidos a Intervenções Coronárias Eletivas.

BACKGROUND: Contrast-induced nephropathy (CIN) is defined as worsening renal function, represented by an increase in serum creatinine of ≥ 25% or ≥ 0.5 mg/dL up to 72 h after exposure to iodinated contrast medium (ICM). The most effective preventive measure to date is intravenous hydration (IVH). Little is known about the effectiveness of outpatient oral hydration (OH). OBJETIVE: To investigate whether outpatient OH with water is as effective as IVH with 0.9% saline solution in preventing CIN in elective coronary procedures. METHODS: In this retrospective observational study, we analyzed the medical records and laboratory data of individuals undergoing percutaneous coronary procedures with ICM. Data collected between 2012 and 2015 refer to individuals who underwent IVH and those collected between 2016 and 2020 (after implementation of an OH protocol) correspond to individuals who underwent OH at home before and after coronary procedures as instructed by the nursing team. Statistical significance was established at α = 0.05. RESULTS: In total, 116 patients were included in this study: 58 in the IVH group and 58 in the OH group. An incidence of CIN of 15% (9/58) was observed in the group that received IVH and an incidence of 12% (7/58) was seen in the group that received OH (p = 0.68). CONCLUSION: The OH protocol, performed by the patient, appears to be as effective as the in-hospital IVH protocol for the renal protection of individuals susceptible to CIN in elective coronary interventions. These findings should be put to test in larger trials.

FUNDAMENTO: A nefropatia induzida por contraste (NIC) é definida como deterioração da função renal, representada por um aumento da creatinina sérica ≥25% ou ≥0,5 mg/dL até 72 horas após a exposição ao meio de contraste iodado (MCI). A medida preventiva mais eficaz até o momento é a hidratação venosa (HV). Pouco se sabe sobre a eficácia da hidratação oral (HO) ambulatorial. OBJETIVO: Investigar se a HO ambulatorial com água é tão eficaz quanto a HV com solução salina a 0,9% na prevenção de NIC em procedimentos coronarianos eletivos. MÉTODOS: Neste estudo observacional retrospectivo, foram analisados prontuários médicos e dados laboratoriais para coletar dados de indivíduos submetidos a procedimentos coronarianos percutâneos com MCI. Os dados coletados entre 2012 e 2015 avaliaram indivíduos que foram submetidos à HV e entre 2016 e 2020 (após a implementação de um protocolo de HO), os indivíduos que foram submetidos à HO em casa antes e depois de procedimentos coronarianos, conforme orientação da equipe de enfermagem. A significância estatística adotada foi de α=0,05. RESULTADOS: No total, 116 pacientes foram incluídos neste estudo, 58 no grupo HV e 58 no grupo HO. Observou-se incidência de NIC de 15% (9/58) no grupo que recebeu HV e 12% (7/58) no grupo que recebeu HO (p=0,68). CONCLUSÃO: O protocolo de HO realizado pelo paciente parece ser tão eficaz quanto o protocolo de HV hospitalar na proteção renal de indivíduos suscetíveis a desenvolver NIC em intervenções coronarianas eletivas. Essas descobertas devem ser testadas em ensaios mais abrangentes.

Eficácia da Hidratação Oral na Prevenção da Nefropatia Induzida por Contraste em Indivíduos Submetidos a Intervenções Coronárias Eletivas / Effectiveness of Oral Hydration in Preventing Contrast-Induced Nephropathy in Individuals Undergoing Elective Coronary Interventions

Resumo Fundamento A nefropatia induzida por contraste (NIC) é definida como deterioração da função renal, representada por um aumento da creatinina sérica ≥25% ou ≥0,5 mg/dL até 72 horas após a exposição ao meio de contraste iodado (MCI). A medida preventiva mais eficaz até o momento é a hidratação venosa (HV). Pouco se sabe sobre a eficácia da hidratação oral (HO) ambulatorial. Objetivo Investigar se a HO ambulatorial com água é tão eficaz quanto a HV com solução salina a 0,9% na prevenção de NIC em procedimentos coronarianos eletivos. Métodos Neste estudo observacional retrospectivo, foram analisados prontuários médicos e dados laboratoriais para coletar dados de indivíduos submetidos a procedimentos coronarianos percutâneos com MCI. Os dados coletados entre 2012 e 2015 avaliaram indivíduos que foram submetidos à HV e entre 2016 e 2020 (após a implementação de um protocolo de HO), os indivíduos que foram submetidos à HO em casa antes e depois de procedimentos coronarianos, conforme orientação da equipe de enfermagem. A significância estatística adotada foi de α=0,05. Resultados No total, 116 pacientes foram incluídos neste estudo, 58 no grupo HV e 58 no grupo HO. Observou-se incidência de NIC de 15% (9/58) no grupo que recebeu HV e 12% (7/58) no grupo que recebeu HO (p=0,68). Conclusão O protocolo de HO realizado pelo paciente parece ser tão eficaz quanto o protocolo de HV hospitalar na proteção renal de indivíduos suscetíveis a desenvolver NIC em intervenções coronarianas eletivas. Essas descobertas devem ser testadas em ensaios mais abrangentes.

Abstract Background Contrast-induced nephropathy (CIN) is defined as worsening renal function, represented by an increase in serum creatinine of ≥ 25% or ≥ 0.5 mg/dL up to 72 h after exposure to iodinated contrast medium (ICM). The most effective preventive measure to date is intravenous hydration (IVH). Little is known about the effectiveness of outpatient oral hydration (OH). Objetive To investigate whether outpatient OH with water is as effective as IVH with 0.9% saline solution in preventing CIN in elective coronary procedures. Methods In this retrospective observational study, we analyzed the medical records and laboratory data of individuals undergoing percutaneous coronary procedures with ICM. Data collected between 2012 and 2015 refer to individuals who underwent IVH and those collected between 2016 and 2020 (after implementation of an OH protocol) correspond to individuals who underwent OH at home before and after coronary procedures as instructed by the nursing team. Statistical significance was established at α = 0.05. Results In total, 116 patients were included in this study: 58 in the IVH group and 58 in the OH group. An incidence of CIN of 15% (9/58) was observed in the group that received IVH and an incidence of 12% (7/58) was seen in the group that received OH (p = 0.68). Conclusion The OH protocol, performed by the patient, appears to be as effective as the in-hospital IVH protocol for the renal protection of individuals susceptible to CIN in elective coronary interventions. These findings should be put to test in larger trials.

Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy.

There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310-517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = -0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.

Intrafamilial phenotypic heterogeneity related to a new DMD splice site variant.

Dystrophinopathies are a group of X-linked neuromuscular disorders that result from pathogenic variants in the DMD gene. Their pathophysiological substrate is the defective expression of dystrophin in many tissues. While patients from the same pedigree usually present similar dystrophin expression and clinical course, the extent of cardiac and skeletal muscle involvement may not correlate in the same individual. We identified a new splice site variant c.2803+5G>C (NM_004006) ClinVar VCV000803902, located in intron 22 of DMD in a Brazilian family that present a broad phenotypic and histological heterogeneity. One of the subjects had a typical Duchenne muscular dystrophy (DMD) phenotype, whereas the others had Becker muscular dystrophy (BMD). Cardiac involvement was remarkable in some of the BMD patients, but not in the DMD patient. Western blot analysis of skeletal muscle revealed much lower levels of calsequestrin in the most severely affected patient compared to his brother, whose phenotype is BMD, highlighting the potential role of proteins involved in skeletal muscle calcium homeostasis in differential degrees of dystrophinopathies.

Emerging Topics in Heart Failure: New Paradigms in Cardiac Amyloidosis. / Tópicos Emergentes em Insuficiência Cardíaca: Novos Paradigmas na Amiloidose Cardíaca.

Recent evidence suggests cardiac amyloidosis (CA) is a mostly underdiagnosed condition, particularly in the transthyretin-mediated form, and is a frequent cause of heart failure with preserved ejection fraction (HFpEF) in the elderly. New paradigms about CA also involve the development of disease-modifying specific therapies. This article summarizes these new concepts.

Evidências recentes sugerem que a amiloidose cardíaca é uma doença amplamente subdiagnosticada, particularmente na sua forma ligada à transtirretina, podendo ser uma causa comum de insuficiência cardíaca com fração de ejeção preservada (ICFEP) no idoso. Os novos paradigmas sobre a doença incluem o desenvolvimento de novas terapias específicas que modificam a história natural da doença. Este artigo traz uma síntese destes novos conceitos.

Tópicos Emergentes em Insuficiência Cardíaca: Novos Paradigmas na Amiloidose Cardíaca / Emerging Topics in Heart Failure: New Paradigms in Cardiac Amyloidosis

Resumo Evidências recentes sugerem que a amiloidose cardíaca é uma doença amplamente subdiagnosticada, particularmente na sua forma ligada à transtirretina, podendo ser uma causa comum de insuficiência cardíaca com fração de ejeção preservada (ICFEP) no idoso. Os novos paradigmas sobre a doença incluem o desenvolvimento de novas terapias específicas que modificam a história natural da doença. Este artigo traz uma síntese destes novos conceitos.

Abstract Recent evidence suggests cardiac amyloidosis (CA) is a mostly underdiagnosed condition, particularly in the transthyretin-mediated form, and is a frequent cause of heart failure with preserved ejection fraction (HFpEF) in the elderly. New paradigms about CA also involve the development of disease-modifying specific therapies. This article summarizes these new concepts.

Advances in the Treatment of Cardiac Amyloidosis.

OPINION STATEMENT: Cardiac amyloidosis is associated with a high mortality rate, a long delay between the first signs and the diagnosis but a short interval between diagnosis and death. This scenario has changed recently due to improved disease awareness among doctors and significant progress in diagnosis thanks to multimodal imaging and a multidisciplinary approach. Therefore, during the last few years, we have had access to specific therapies for those patients. Those therapies are quite different depending on the type of amyloidosis, but there has been real progress. Systemic light chain amyloidosis (AL) with cardiac involvement is the most common form of cardiac amyloidosis. The severity of heart disease dictates the prognosis in AL amyloidosis. Advances in chemotherapy and immunotherapy that suppress light chain production have improved the outcomes. These recent improvements in survival rates have enabled therapies such as implanted cardiac defibrillators and heart transplantation that were usually not indicated for patients with advanced light chain amyloid cardiomyopathy to now be applied in selected patients. For transthyretin amyloidosis (ATTR), the second most common form of amyloidosis with cardiac involvement, there is also significant progress in treatment. Until recently, we had no specific therapy for ATTR cardiomyopathy (ATTR-CM), though now disease-modifying therapies are available. Therapies that stabilize transthyretin, such as tafamidis, have been shown to improve outcomes for patients with ATTR-CM. Modern treatments that stop the synthesis of TTR through gene silencing, such as patisiran and inotersen, have shown positive results for patients with TTR amyloidosis. Significant progress has been made in the treatment of amyloid cardiomyopathy, and hopefully, we will see even more progress with the spread of those treatments. We now can be optimistic about patients with this disease.

Lower bone mass is associated with subclinical atherosclerosis, endothelial dysfunction and carotid thickness in the very elderly.

BACKGROUND AND AIMS: Osteoporosis and coronary heart disease (CHD) are very common conditions among elderly people, and both represent a public health concern due to their prognostic consequences. Osteoporosis and CHD share many risk factors and pathophysiological mechanisms, such as calcification pathways. Clinical evidence associates lower bone mass with cardiovascular diseases and endothelial dysfunction. Hence, this study aims to investigate whether bone mass density is associated with subclinical atherosclerosis and/or endothelial dysfunction in the very elderly. METHODS: We performed a cross-sectional study of cohort enrolled individuals, ages 80 years or older (n = 208), who had never manifested cardiovascular diseases. Medical evaluation, blood tests, flow-mediated dilation (FMD), carotid intimal-media thickness (IMT), Dual Energy X-ray Absorptiometry (DEXA) and Coronary Calcium Score (CCS) were obtained. Odds Ratio (OR) was calculated by multivariate logistic regression models using CCS, FMD and IMT categories. Adjustments for covariates were done. RESULTS: Overall bone mass was independently and inversely associated with CCS categories [OR:1.68(1.16-8.85); p = 0.024] and IMT categories [OR:2.97(1.11-7.90); p = 0.030]. Conversely, overall bone mass was independent and directly associated with FMD categories [OR:2.73(1.36-70.39); p = 0.023]. CONCLUSIONS: This study indicates that overall bone mass is independently and inversely associated with subclinical atherosclerosis, endothelial dysfunction and thickness of carotid in the very elderly.

Noninvasive imaging assessment of rehabilitation therapy in heart failure with preserved and reduced left ventricular ejection fraction (IMAGING-REHAB-HF): design and rationale.

BACKGROUND: Studies have shown significant benefits of exercise therapy in heart failure (HF) with a reduced ejection fraction (HFrEF) and HF with a preserved ejection fraction (HFpEF). The mechanisms responsible for the beneficial effect of exercise in HFrEF and HFpEF are still unclear. We hypothesized that the effect of exercise on myocardial remodeling may explain its beneficial effect. METHODS: IMAGING-REHAB-HF is a single-center, randomized, controlled clinical trial using cardiac magnetic resonance imaging, vasomotor endothelial function, cardiac sympathetic activity imaging and serum biomarkers to compare the effect of exercise therapy in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%). Subjects will be assessed at baseline and after 4 months. The exercise program will consist of three 60-min exercise sessions/week. The primary endpoints are the effect of exercise on myocardial extracellular volume (ECV), left ventricular (LV) systolic function, LV mass, LV mass-to-volume and LV cardiomyocyte volume. Secondary endpoints include the effect of exercise on vasomotor endothelial function, cardiac sympathetic activity and plasmatic biomarkers. Patients will be allocated in a 2:1 fashion to supervised exercise program or usual care. A total sample size of 90 patients, divided into two groups according to LVEF:HFpEF group (45 patients:30 in the intervention arm and 15 in the control arm) and HFrEF group (45 patients:30 in the intervention arm and 15 in the control arm) - will be necessary to achieve adequate power. CONCLUSION: This will be the first study to evaluate the benefits of a rehabilitation program on cardiac remodeling in HF patients. The unique design of our study may provide unique data to further elucidate the mechanisms involved in reverse cardiac remodeling after exercise in HFpEF and HFrEF patients.

Adverse interaction between HDL and the mass of myocardial infarction.

BACKGROUND AND AIMS: Coronary reperfusion with HDL from healthy volunteers attenuates ischemia and reperfusion injury in animal models. In myocardial infarction (MI) patients, such an interaction is unclear. Hence, our first objective was to verify if there is interaction between HDL-C and MI mass in patients and the role of coronary reperfusion in the interaction. Furthermore, we investigated whether the effect in MI size of reperfusion with HDL obtained from healthy participants or MI patients could differ. METHODS: HDL-C was measured the first day after MI and MI mass was quantified by cardiac magnetic resonance (n = 94) and peak CKMB (n = 393). In an ex vivo rat heart model, we compared MI area and dP/dt max after coronary reperfusion with HDL from MI patients or healthy volunteers. RESULTS: HDL-C above the median (35 mg/dL) was associated with higher peak CKMB [255 (145-415) vs. 136 (84-287) UI/L; p = 0.02], higher MI mass [17 (9-21) vs. 10 (6-14) g; p < 0.01] and lower left ventricular ejection fraction [47 (34-53) vs. 51 (43-59); p = 0.02] than their counterparts. In restricted cubic spline and multivariate linear regression, HDL-C was directly associated with peak CKMB (p < 0.01) and MI mass (p < 0.01) only in reperfused patients with time to reperfusion <4 h. Reperfusion with healthy HDL, but not from MI patients, reduced MI mass (p < 0.01) and improved dP/dt max (p = 0.02). CONCLUSIONS: In MI patients undergoing early coronary reperfusion, HDL-C levels at admission are directly associated with MI size. In contrast to healthy HDL, reperfusion with HDL from MI patients do not reduce MI area in an ex vivo animal model.