Rodolfo Rivera

Left Ventricular Mass, Stroke Volume, and Ouabain-Like Factor in Essential Hypertension

Many patients with essential hypertension (EH) exhibit increased left ventricular mass. Similarly, elevated circulating levels of an endogenous ouabainlike factor (OLF) have been described in some but not all patients with EH. Moreover, ouabain has a hypertrophic influence on isolated cardiac myocytes. Accordingly, we investigated relationships among plasma OLF, left ventricular mass, and cardiac function in patients with EH. Plasma OLF was determined in 110 normotensive subjects and 128 patients with EH. Echocardiographic parameters and humoral determinants were measured in EH. Plasma OLF levels were increased (P<0.0001) in patients with EH (377+/-19 pmol/L) versus normotensive (253+/-53 pmol/L) subjects. The distribution of plasma OLF was unimodal in normotensives, whereas it was bimodal in EH. Twenty-four-hour diastolic ambulatory blood pressure was slighter higher in EH with high OLF compared with EH with normal OLF (93.2+/-1.14 versus 89.4+/-1.33 mm Hg, P=0.03). Left ventricular mass index and stroke volume in EH with high OLF were greater than in EH with normal OLF (101.9+/-3.3 versus 86.1+/-2.5 g/m(2), P=0.0003, and 57.10+/-1.48 versus 52.30+/-1.14 mL/m(2), P=0. 02, respectively), although heart rate was slower (74.2+/-1.3 versus 80.5+/-1.3 bpm, P=0.005). Multiple regression analysis that tested the influence of body mass index, age, gender, 24-hour blood pressure, and OLF on left ventricular mass revealed independent contributions of systolic (13.2%) and diastolic (12.4%) blood pressure and plasma OLF (11.6%) to left ventricular mass. We conclude that approximately 50% of patients with uncomplicated EH have elevated-high circulating OLF levels, higher diastolic blood pressure, greater left ventricular mass and stroke volume, and reduced heart rate. We propose that the OLF affects cardiovascular function and structure and should be considered as a factor that contributes to the risk of morbid events.

Endogenous ouabain and hemodynamic and left ventricular geometric patterns in essential hypertension

We sought to evaluate the relationships among circulating levels of an endogenous ouabain-like factor (EO) and systemic hemodynamics and left ventricular (LV) geometry in patients with recently diagnosed essential hypertension. We selected 92 never-treated patients with essential hypertension. Blood samples were drawn for estimation of plasma EO (radioimmunoassay) and subjects underwent echocardiographic examination to evaluate LV end-systolic and end-diastolic wall thickness and internal dimensions. LV volumes, stroke volume, cardiac output, total peripheral resistance, LV mass, and relative wall thickness were calculated, and all except the last parameter were indexed by body surface area. LV mass also was indexed by height. On the basis of the values of LV mass index (body surface area or height) and relative wall thickness, subjects were divided into groups with either normal geometry, concentric remodeling, concentric hypertrophy, or eccentric nondilated hypertrophy. In the study population as a whole, circulating EO levels were significantly and directly correlated with mean blood pressure (r = 0.21, P = .048), relative wall thickness (r = 0.34, P = .001), and total peripheral resistance index (r = 0.37, P = .0003). Plasma EO also was significantly and inversely correlated with LV end-diastolic volume index (r = -0.32, P = .002), stroke index (r = -0.34, P = .0009), and cardiac index (r = -0.35, P = .0007). In multiple regression analysis, plasma EO was an independent correlate of total peripheral resistance index, cardiac index, and relative wall thickness. Regardless of the indexation method used for LV mass, plasma EO was higher in patients with concentric remodeling than in those with either normal geometry or concentric hypertrophy. Plasma EO tended to be higher (indexation by body surface area) or was significantly higher (indexation by height) in subjects with concentric remodeling than in those with eccentric nondilated hypertrophy. Patients with concentric remodeling showed the highest total peripheral resistance index and the lowest cardiac index. Our data suggest that EO plays a role in regulating systemic hemodynamics and LV geometry in patients with essential hypertension.

Sudden cardiac death and chronic kidney disease: From pathophysiology to treatment strategies

Chronic kidney disease (CKD) patients demonstrate higher rates of cardiovascular mortality and morbidity; and increased incidence of sudden cardiac death (SCD) with declining kidney failure. Coronary artery disease (CAD) associated risk factors are the major determinants of SCD in the general population. However, current evidence suggests that in CKD patients, traditional cardiovascular risk factors may play a lesser role. Complex relationships between CKD-specific risk factors, structural heart disease, and ventricular arrhythmias (VA) contribute to the high risk of SCD. In dialysis patients, the occurrence of VA and SCD could be exacerbated by electrolyte shifts, divalent ion abnormalities, sympathetic overactivity, inflammation and iron toxicity. As outcomes in CKD patients after cardiac arrest are poor, primary and secondary prevention of SCD and cardiac arrest could reduce cardiovascular mortality in patients with CKD.

Pulmonary Hypertension and Right Heart Failure in Chronic Kidney Disease: New Challenge for 21st-Century Cardionephrologists.

Pulmonary hypertension is defined as an increased systolic pulmonary pressure of >30 mm Hg, and it shows a 40% prevalence in hemodialysis patients due to vascular access (both central venous catheter and arteriovenous fistula). Secondary pulmonary hypertension in chronic kidney disease patients is strictly related to pulmonary circulation impairment together with chronic volume overload and increased levels of cytokines and growth factors, such as FGF, PDGF, and TGF-β, leading to fibrosis. Endothelial dysfunction, together with lower activation of NOS, increased levels of serum endothelin and fibrin storages, involves an extensive growth of endothelial cells leading to complete obliteration of pulmonary vessels. Pulmonary hypertension has no pathognomonic and distinctive symptoms and signs; standard transthoracic echocardiography allows easy assessment of compliance of the right heart chambers. The therapeutic approach is based on traditional drugs such as digitalis-derived drugs, vasodilatory agents (calcium channel blockers), and oral anticoagulants. New pharmacological agents are under investigation, such as prostaglandin analogues, endothelin receptor blockers, and phosphodiesterase-5 inhibitors.

Fibroblast growth factor 23 and parathyroid hormone predict extent of aortic valve calcifications in patients with mild to moderate chronic kidney disease

Background Cardiac valve calcifications are present in dialysis patients and regarded as dependent on a deranged mineral metabolism. Few data are available for patients with chronic kidney disease (CKD) not on dialysis. This study evaluates the potential association between the extent of cardiac valve calcification and levels of intact parathyroid hormone (i-PTH), phosphorus, calcium, 25-OH vitamin D, fibroblast growth factor 23 (FGF-23), Klotho and C-reactive protein (CRP) simultaneously measured in patients with mild to moderate CKD. Methods Consecutive non-hospitalized patients referring to five nephrology units were evaluated. Inclusion criteria were age >18 years, CKD Stages 3–4, and the presence of aortic and/or mitral valve calcification assessed by echocardiography as routinely clinical evaluation. Patients underwent clinical examination and routine biochemistry. Baseline i-PTH, phosphorus, calcium, 25-OH vitamin D, FGF-23, Klotho and CRP were simultaneously ascertained. Results Extent of aortic valve calcification (n = 100 patients) was moderate in 68 patients and mild in the remaining patients. Mitral valve calcification (n = 96 patients) score was 1, 2 and 3 in 61, 34 and 1 patients, respectively. In univariate analysis, no association was found between extent of mitral valve calcification and markers of mineral metabolism and CRP; aortic valve extent of calcification was positively associated with i-PTH (r2 = 0.212; P = 0.03) and FGF-23 (r2 = 0.272; P = 0.01), and negatively with Klotho (r2 = −0.208; P = 0.04). In multivariable analysis, extent of aortic valve calcification was associated with FGF-23 (P = 0.01) and PTH (P = 0.01) levels. Conclusions Extent of aortic valve calcification is associated to FGF-23 and PTH in naïve CKD patients with mild to moderate CKD. Further studies should examine whether FGF-23 assay should be included in routine clinical evaluation of CKD as part of cardiovascular risk stratification.

Ultrasonography: Ariadne's Thread in the Diagnosis of the Cardiorenal Syndrome

The term cardiorenal syndrome (CRS) describes a broad spectrum of clinical conditions with four combinations of acute and chronic heart and kidney failure. Based on the pathophysiological primum movens, the actual classification recognizes five CRS types: in type I and II CRS, the initiating event is heart failure (acute or chronic), while it is kidney failure in type III and IV CRS; type V is linked to systemic diseases. Ultrasound techniques (echocardiography and ultrasonography of the kidney, inferior vena cava and chest) can be extremely helpful in establishing a prompt diagnosis and a correct CRS classification. Basic echocardiography allows evaluation of ventricular diastolic and systolic functions, investigates pulmonary congestion and pericardial effusion, and describes volume overload. On the other hand, renal ultrasound helps clinicians to distinguish between acute and chronic renal failure, excludes urinary tract dilation or pathological bladder repletion, and provides crucial information regarding kidney volume or echogenicity. Applying basic knowledge of echocardiography and renal ultrasound, nephrologists may be in a better position for patient treatment and management, bearing in mind that doctors can properly use a stethoscope although not being a cardiologist.

Na+,K+,Cl− cotransport is a marker of distal tubular function in essential hypertension

Objective To analyze the natriuretic and diuretic response to frusemide in 33 male essential hypertensive patients as a function of basal renal sodium handling and erythrocyte transport system. Methods The natriuretic and diuretic response to an oral dose of frusemide (25 mg) was assessed with a simplified method. Urinary sodium and water excretion were measured in the basal state and every 30 min after the frusemide dose for 240 min. Basal 24h urinary sodium and water excretion, Na+, K+, Cl- cotransport and Li+–Na+ countertransport were measured 24 h before the test. Results There was a highly significant correlation between the natriuretic and diuretic response to frusemide and Na+, K+, Cl- cotransport and Li+–Na+ countertransport. After a multiple regression analysis the natriuretic and diuretic response to frusemide was not correlated with indices of proximal tubular function (Li+–Na+ countertransport, fractional uric acid excretion and the ratio of fractional sodium excretion to fractional uric acid excretion). Conclusion These results support the hypothesis that erythrocyte Na+, K+, Cl- cotransport is a marker of distal tubular function.

Coronary artery disease (CAD) in chronic kidney disease patients

There is a great deal of data demonstrating a close association between chronic kidney disease (CKD) and cardiovascular disease, particularly coronary artery disease (CAD). About one half of deaths in patients with end-stage renal disease (ESRD) are of cardiovascular causes. The association between CKD and ischemic heart disease can be explained in part because both conditions are related to the traditional risk factors for atherosclerotic vascular disease. However, CKD might also have a casual role in the development and progression of CAD, with several mechanisms potentially involved. Among CAD patients, those with CKD have systematically a worse prognosis than those without CKD irrespective of the clinical presentation or the treatments applied. Current therapy is based on small trials and observational data and on the extrapolation of the strategies that have been proved useful in the general population, although many treatments that have been shown to improve the prognosis of CAD patients are underused in those with renal impairment.

Left ventricul ar hypertrophy in patients with chronic kidney disease

Cardiovascular diseases such as coronary artery disease, congestive heart failure, arrhythmias, and sudden cardiac death represent main causes of morbidity and mortality in patients with chronic kidney disease (CKD). Their pathogenesis relates to the close linkage between heart and kidneys and involves both traditional and non-traditional risk factors. According to the well-established classification of cardio-renal syndrome, the cardiovascular involvement in chronic kidney disease is known as “type 4 cardiorenal syndrome” (chronic renocardiac syndrome). Uremic cardiopathy is mainly characterized by both left ventricular systolic and diastolic impairment, often associated to right heart dysfunction due to the presence of a vascular access for hemodialysis. The typical clinical picture is represented by left ventricular hypertrophy (LVH), the pathogenesis of which is multifactorial and closely linked to elevated blood pressure, vascular stiffness and atherosclerosis. The diagnosis is mainly made by ultrasound (2D and 3D echocardiography) and cardiac magnetic resonance imaging (CMRI), although echocardiography is most widely employed since it is non-invasive and cheaper than CMRI. The following chapter provides an overview of the epidemiology, pathophysiology, diagnosis, and treatment of left ventricular hypertrophy in CKD patients.

Dipyridamole stress echocardiography in diagnosis and prognosis of hemodialysis patients with asymptomatic coronary disease

The prevalence of coronary artery disease (CAD) is high in hemodialysis (HD) patients. The aim of the study was to assess the diagnostic and prognostic value of dipyridamole stress echocardiography (DSE) in nondiabetic HD patients without signs or symptoms of CAD. In 51 out of 158 evaluated HD patients (21 females, age 67 [33–85] years, HD duration 38 [9–271] months), resting echocardiography and DSE were performed. Exclusion criteria were known CAD, diabetes mellitus, and pulmonary and oncologic pathologies. Logistic regression analysis was carried out to identify predictors of abnormal DSE response, while Cox regression analysis was performed to determine variables associated with total and cardiovascular mortality, after 43.3 (11–60) months of follow‐up. Seven patients (14%) showed a positive response to DSE (DSE+). In 5/7, CAD was documented by angiography: All of them underwent coronary revascularization. DSE+ patients had significantly smaller body mass index than patients with a negative response (DSE‐): 21.7 ± 1.9 vs. 25.1 ± 3.4 kg/m2 (p = 0.018). During follow‐up, 16 (31%) patients died. Older age hazard ratio [HR = 1.07; confidence interval (CI) = 1.01–1.12; p = 0.02] and higher plasma phosphate levels (HR = 10.41; CI = 2.30–47.17; p < 0.01) were predictors of total mortality. Male gender (HR = 22.7; CI = 1.45–354.4; p = 0.03), older age (HR = 1.24; CI = 1.03–1.50; p = 0.02), longer HD duration (HR = 1.13; CI = 1.01–1.26; p = 0.04), and positive response to DSE (HR = 5.82; CI = 1.04–32.65; p = 0.04) were associated with cardiovascular mortality. Ten percent of asymptomatic HD patients had significant CAD, but timely diagnosis did not seem to improve their prognosis. Total survival was associated with age and higher levels of plasma phosphate, while male gender, older age, longer HD duration, and DSE+ were predictors of cardiovascular mortality.