Silvio H. Barberato

Left Ventricular Mass in Chronic Kidney Disease and ESRD

Chronic kidney disease (CKD) and ESRD, treated with conventional hemo- or peritoneal dialysis are both associated with a high prevalence of an increase in left ventricular mass (left ventricular hypertrophy [LVH]), intermyocardial cell fibrosis, and capillary loss. Cardiac magnetic resonance imaging is the best way to detect and quantify these abnormalities, but M-Mode and 2-D echocardiography can also be used if one recognizes their pitfalls. The mechanisms underlying these abnormalities in CKD and ESRD are diverse but involve afterload (arterial pressure and compliance), preload (intravascular volume and anemia), and a wide variety of afterload/preload independent factors. The hemodynamic, metabolic, cellular, and molecular mediators of myocardial hypertrophy, fibrosis, apoptosis, and capillary degeneration are increasingly well understood. These abnormalities predispose to sudden cardiac death, most likely by promotion of electrical instability and re-entry arrhythmias and congestive heart failure. Current treatment modalities for CKD and ESRD, including thrice weekly conventional hemodialysis and peritoneal dialysis and metabolic and anemia management regimens, do not adequately prevent or correct these abnormalities. A new paradigm of therapy for CKD and ESRD that places prevention and reversal of LVH and cardiac fibrosis as a high priority is needed. This will require novel approaches to management and controlled interventional trials to provide evidence to fuel the transition from old to new treatment strategies. In the meantime, key management principles designed to ameliorate LVH and its complications should become a routine part of the care of the patients with CKD and ESRD.

Diastolic heart failure in dialysis patients: mechanisms, diagnostic approach, and treatment.

Heart failure (HF) is very common in the general population, and risk factors for HF, such as coronary artery disease, diabetes, obesity, and hypertension, are frequently present in patients with CKD. Therefore, HF is also an important cause of morbidity and mortality in this population. Diastolic heart failure (DHF), also called HF with preserved ejection fraction, refers to a clinical syndrome in which patients have symptoms and signs of HF, normal or near normal left ventricular (LV) systolic function, and evidence of diastolic dysfunction (e.g., abnormal LV filling and elevated filling pressure). Recent data suggest that HF with normal ejection fraction is even more common in patients than HF with low ejection fraction, including those on hemodialysis. Not surprisingly, DHF is a strong predictor of death in CKD patients. In this article, we review the information available on the mechanisms, clinical presentation, impact, and potential interventions in DHF based on evidence from CKD patients, as well as evidence from the general population potentially applicable to the CKD population.

Impact of Cholecalciferol Treatment on Biomarkers of Inflammation and Myocardial Structure in Hemodialysis Patients Without Hyperparathyroidism

INTRODUCTION Vitamin D (25-hydroxyvitamin D, 25(OH)D) deficiency, hypovitaminosis D, is highly prevalent in chronic kidney disease patients and is potentially involved with complications in the hemodialysis (HD) population. The aim of this study was to evaluate the impact of cholecalciferol supplementation on biomarkers of mineral metabolism, inflammation, and cardiac function in a group of HD patients presenting with hypovitaminosis D and low intact parathyroid hormone (iPTH) levels. MATERIAL AND METHODS HD patients with iPTH levels of <300 pg/mL, not receiving vitamin D therapy, and presenting with 25(OH)D levels of <30 ng/mL were enrolled in this prospective study. Oral cholecalciferol was prescribed once a week in the first 12 weeks (50,000 IU) and in the last 12 weeks (20,000 IU) of the study. High-sensitivity C-reactive protein, interleukin-6, and serum albumin were used as inflammatory markers. Echocardiograms were performed on a midweek interdialytic day at baseline and after 6 months of cholecalciferol supplementation. RESULTS In all, 30 patients were included in the final analysis. We observed a significant increase in serum 25(OH)D levels after 3 months (46.2 ± 14.4 ng/mL vs. 18.1 ± 6.6 ng/mL; P < .001) and after 6 months (40.4 ± 10.4 ng/mL vs. 18.1 ± 6.6 ng/mL; P < .001) of cholecalciferol supplementation. There were no significant changes in alkaline phosphatase, iPTH, phosphorus, and serum albumin levels, but there was a slight but significant increase in calcium levels after 6 months of cholecalciferol supplementation (9.4 ± 0.6 mg/dL vs. 9.0 ± 0.6 mg/dL; P = .02). Additionally, we observed a significant reduction in high-sensitivity C-reactive protein levels after 3 months (median: 0.62 [0.05 to 29.6] mg/L vs. 0.32 [0.02 to 3.13] mg/L; P = .02) and after 6 months (median: 0.62 [0.05 to 29.6] mg/L vs. 0.50 [0.02 to 5.66] mg/L; P = .04) of cholecalciferol supplementation, as well as a significant reduction in interleukin-6 levels (median: 6.44 pg/mL vs. 3.83 pg/mL; P = .018) after 6 months of supplementation. Left ventricular mass index was significantly reduced at the end of supplementation (159 ± 55 g/m(2) vs. 175 ± 63 g/m(2); P = .03). CONCLUSIONS Cholecalciferol supplementation in HD patients was found to be safe and efficient to correct hypovitaminosis D and established little impact on mineral metabolism markers. Additionally, we observed a reduction in important surrogate markers of cardiovascular risk, namely systemic inflammation and left ventricular hypertrophy, suggesting an anti-inflammatory action and possibly an improvement of cardiac dysfunction.

Impact of Residual Renal Function on Volume Status in Chronic Renal Failure

During the past few years, it has become increasingly evident that residual renal function (RRF) is an important and independent predictor of poor outcome in patients with chronic kidney disease (CKD). Although the causes of this observation are not fully understood, it appears that the loss of RRF impairs both fluid removal and clearance of solutes, which in turn leads to uremic toxicity and increased morbidity and mortality. There is increasing evidence that patients with CKD develop signs of fluid overload already in the early phases of the disease, and this may be a stimulus for inflammatory activation. Recently, an inflammatory component was identified in uremic atherosclerotic and non-atherosclerotic cardiovascular disease (CVD), which have been consistently associated with poor clinical outcome in patients with CKD. Signs of systemic inflammation occur in parallel to the impairment in renal function, and the pathophysiology is most likely multifactorial, including a decrease in cytokine clearance, advanced glycation end-product accumulation, oxidative stress, and principal fluid overload. Additionally, inflammation seems to be a predictor of accelerated loss of renal function. In this article, we discuss the evidence showing that patients with CKD generally have fluid overload, the mechanisms by which impaired renal function may lead to a chronic inflammatory state, and the available information linking fluid overload to accelerated loss of renal function and CVD through inflammation. Inflammation may lead to the development of complications of CKD, in particular CVD, but on the other hand may also lead to a faster progression of renal disease. Strategies aiming to reduce fluid overload may be useful to reduce cardiovascular morbidity and mortality, but also preserve RRF.

Echocardiography in Chronic Kidney Disease: Diagnostic and Prognostic Implications

Most of the recent advances in the understanding of chronic kidney disease (CKD)-related cardiovascular disease have focused on atherosclerosis and arteriosclerosis, and much less effort has been dedicated to unveil and evaluate the mechanisms and impact of interventions related to myocardial dysfunction. Hence, echocardiographic evaluation plays a pivotal role in establishing the diagnosis of myocardiopathy as well as in stratifying risk and defining the impact of interventions. The aim of this review is to examine the profile of myocardiopathy in CKD, and to identify how the echocardiogram can be useful in diagnostic and prognostic clinical approaches.

Prognostic value of left atrial volume index in hemodialysis patients

OBJECTIVE To evaluate the prognostic value of left atrial volume index (LAVi) in the clinical course of hemodialysis (HD) patients, compared with previously established echocardiographic and clinical parameters. METHODS Echocardiograms were obtained from 118 hemodialysis patients, who were then followed for 19 +/- 8 months. Study endpoint was a composite of all-cause mortality and nonfatal cardiovascular events. Cox multivariate analysis was used do assess the independent prognostic value of LAVi. RESULTS On univariate analysis, LAVi and other clinical and echocardiographic parameters were predictive of prognosis. Multivariate analyses showed that LAVi was an independent predictor of prognosis (hazard ratio 1.03 per ml/m(2), 95% confidence interval: 1.01 to 1.05, p=0.014), and added incremental information to the model containing traditional predictors of cardiovascular risk, such as left ventricular mass, ejection fraction, and clinical variables (p=0.02). CONCLUSION LAVi is an independent predictor of prognosis in HD patients, providing incremental information to traditional clinical and Doppler echocardiographic data.

Influência da redução da pré-carga sobre o índice de desempenho miocárdico (índice de Tei) e outros parâmetros Doppler ecocardiográficos da função ventricular esquerda

OBJECTIVE To assess the influence of preload reduction by hemodialysis on Doppler Tei Index of myocardial performance and other parameters of cardiac function. METHODS The Tei index and left ventricular (LV) systolic and diastolic function parameters were estimated, before and after a single hemodialysis session. Only subjects who were in sinus rhythm, without history of coronary artery disease, and no evidence of cardiac valve disease and pericardial effusion were included in the study. RESULTS Fifteen patients (8 men, mean age 53 +/- 14 years) completed the study. After an ultrafiltration of 2.2 +/- 1.1 liters, peak mitral E velocity decreased (p < 0.05) and A velocity remained unchanged (p = ns), resulting in reduction of E/A ratio (p < 0.01). The Tei index increased (from 0.57 +/- 0.07 to 0.65 +/- 0.09, p < 0.01) because of significant prolongations in isovolumetric relaxation time (from 101 +/- 14 to 113 +/- 17 ms, p < 0.01) and ejection time (from 271 +/- 22 to 252 +/- 22, p < 0.05). The isovolumetric contraction time did not vary (p = ns). There was no change in diastolic tissue Doppler parameters, while systolic velocities increased (p < 0.05). CONCLUSION The Tei index was affected by hemodialysis-induced preload alterations, as well as other mitral inflow Doppler-derived parameters. The diastolic parameters of mitral annulus Doppler tissue were independent of preload, while systolic velocities suggested improved systolic function.

Hypovitaminosis D Is Associated with Systemic Inflammation and Concentric Myocardial Geometric Pattern in Hemodialysis Patients with Low iPTH Levels

Background: Vitamin D [25(OH)D] deficiency is a cardiovascular risk factor in the hemodialysis (HD) population. The aim of this study was to identify hypovitaminosis D in HD patients without signs of hyperparathyroidism and to analyze its association to inflammation and echocardiographic alterations. Methods: Patients on HD with iPTH <300 pg/ml not receiving vitamin D therapy were recruited. Hypovitaminosis D was defined as 25(OH)D <30 ng/ml. High-sensitivity C-reactive protein, interleukin-6 and serum albumin were used as inflammation markers. Echocardiograms were performed in an interdialytic mid-week day. Results: Sixty-one patients (mean age of 56 ± 15 years, 52% males, 93% Caucasians, 31% diabetic) were included, and 75% presented hypovitaminosis D. Inflammation was more prevalent among those with hypovitaminosis D, and these patients presented higher relative wall thickness (0.48 ± 0.11 vs. 0.42 ± 0.10 mm; p = 0.05) and lower left ventricular diastolic (49.8 ± 6.2 vs. 54.7 ± 5.8 mm; p = 0.013) and systolic (31.9 ± 5.7 vs. 36.8 ± 7.2 mm; p = 0.012) diameters. Conclusions: Hypovitaminosis D is associated with inflammation and concentric geometric pattern of the left ventricle, even in the absence of high iPTH levels. Vitamin D repletion (aiming to reduce cardiovascular complications) should also be considered in HD patients with normal or low iPTH levels.

Prevalence and prognostic impact of diastolic dysfunction in patients with chronic kidney disease on hemodialysis

FUNDAMENTO: Disfuncao diastolica e frequente em pacientes de hemodialise, mas seu impacto na evolucao clinica e incerto. OBJETIVO: Avaliar a prevalencia e o impacto prognostico da disfuncao diastolica (DD) avancada (DDA) do ventriculo esquerdo (VE) em pacientes de hemodialise. METODOS: Ecocardiogramas foram realizados em pacientes no primeiro ano de hemodialise, em ritmo sinusal, sem doenca cardiovascular manifestada, excluindo-se aqueles com valvopatia significativa ou derrame pericardico. Pela avaliacao integrada dos dados ecodopplercardiograficos, a funcao diastolica foi classificada como: 1) normal, 2) DD discreta (alteracao do relaxamento) e 3) DDA (pseudonormalizacao e fluxo restritivo). Os desfechos pesquisados foram mortalidade geral e eventos cardiovasculares. RESULTADOS: Foram incluidos 129 pacientes (78 homens), com idade 52 ± 16 anos e prevalencia de DD de 73% (50% com DD discreta e 23% com DDA). No grupo com DDA, demonstrou-se maior idade (p < 0,01), pressao arterial sistolica (p < 0,01) e diastolica (p = 0,043), massa do VE (p < 0,01), indice do volume do atrio esquerdo (p < 0,01) e proporcao de diabeticos (p = 0,019), alem de menor fracao de ejecao (p < 0,01). Apos 17 ± 7 meses, a mortalidade geral foi significativamente maior naqueles com DDA, em comparacao aos normais e com DD discreta (p = 0,012, log rank test). Na analise multivariada de Cox, a DDA foi preditiva de eventos cardiovasculares (hazard ratio 2,2, intervalo de confianca 1,1-4,3, p = 0,021) apos ajuste para idade, genero, diabete, massa do VE e fracao de ejecao. CONCLUSAO: A DDA subclinica foi encontrada em aproximadamente um quarto dos pacientes de hemodialise e acarretou impacto prognostico, independente de outros dados clinicos e ecocardiograficos.BACKGROUND Diastolic dysfunction (DD) is frequent in patients on hemodialysis (HD), but its impact on the clinical evolution is yet to be established. OBJECTIVE To evaluate the prevalence and prognostic impact of left ventricular (LV) advanced diastolic dysfunction (ADD) in patients on hemodialysis. METHODS The echocardiograms were performed during the first year of HD therapy, in patients with sinus rhythm, with no evidence of cardiovascular disease, excluding those with significant valvopathy or pericardial effusion. The combined assessment of the Doppler echocardiographic data classified the diastolic dysfunction as: 1) normal diastolic function; 2) mild DD (relaxation alteration) and 3) ADD (pseudonormalization and restrictive flow pattern). The assessed outcomes were general mortality and cardiovascular events. RESULTS A total of 129 patients (78 males), aged 52 +/- 16 years, with a DD prevalence of 73% (50% with mild DD and 23% with ADD) were included in the study. The group with ADD was older (p < 0.01) and presented higher systolic (p < 0.01) and diastolic BP (p = 0.043), LV mass (p < 0.01), left atrial volume index (p < 0.01) and number of diabetic patients (p = 0.019), as well as lower ejection fraction (EF) (p < 0.01). After 17 +/- 7 months, the general mortality was significantly higher in individuals with ADD, when compared to those with normal function and mild DD (p = 0.012, log rank test). At Cox multivariate analysis, ADD was predictive of cardiovascular events (hazard ratio 2.2; confidence interval: 1.1-4.3; p = 0.021) after adjusted for age, gender, diabetes, LV mass and EF. CONCLUSION The subclinical ADD was identified in approximately 25% of the patients undergoing hemodialysis and had a prognostic impact, regardless of other clinical and echocardiographic data.

Aneurysm of the Right Atrial Appendage

Atrial aneurysms involving the free wall or atrial appendage are rare entities in cardiology practice and may be associated with atrial arrhythmias or embolic phenomena. We review the literature and report a case of aneurysm of the right atrial appendage in a young adult, whose diagnosis was established with echocardiography after an episode of paroxysmal atrial flutter.