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European Journal of Heart Failure 1999 1(4):327-336; doi:10.1016/S1388-9842(99)00057-4
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© 1999 European Society of Cardiology

Disorders of left ventricular structure and function in chronic uremia: how often, why and what to do with it?

O.I. Dyadyka,*, A.E. Bagriyb and N.F. Yarovayac

a Teatralniy Prospect 24, 18 Donetsk 340050, Ukraine
b Member of the European Working Group on Heart Failure Universitetskaya Street, 100a, 41 Donetsk 340114, Ukraine
c Sportivnaja Street 12, 2 Donetsk 340061, Ukraine

* Corresponding author. Fax: +38-0622-574074


   Abstract
Top
 Abstract
1. Introduction
 2. Left ventricular hypertrophy
 3. Pathophysiological mechanisms
 4. Unfavourable consequences of...
 5. Regression of LV...
 6. Conclusions
 References
 
Left ventricular (LV) structure and function abnormalities are frequent in individuals with chronic uraemia; these disorders are at increased risk of cardiovascular and overall morbidity and mortality in the pre-dialyzed population, during dialysis treatment and in renal transplant recipients. This review will attempt to summarize current knowledge of the prevalence, pathophysiological mechanisms of LV disease in chronic uraemia and to discuss useful medical strategies in this population.

Received June 10, 1999; Revised September 14, 1999; Accepted September 20, 1999


   1. Introduction
Top
 Abstract
 1. Introduction
2. Left ventricular hypertrophy
 3. Pathophysiological mechanisms
 4. Unfavourable consequences of...
 5. Regression of LV...
 6. Conclusions
 References
 
Cardiovascular disease is the leading cause of death in end-stage renal failure, representing 43–52% of overall mortality [1–3]. Following renal transplantation, cardiovascular disease is the most frequent cause of death with an incidence ranging from 14% to 50% [4,5]. The prevalence of coronary artery disease, left ventricular hypertrophy and dilatation, systolic and diastolic left ventricular dysfunction, persistent or recurrent heart failure and complex ventricular ectopy is high in the uremic population [4–14]. Indeed, cardiovascular mortality in patients on renal replacement therapy is 10–20 times more common than in the general population [4,8,13,15]. The current paradox of significant advances in renal replacement therapy is that patients with end-stage renal failure now die of cardiovascular disease rather than of uraemia [1–3,15]. Left ventricular (LV) dysfunction is a frequent occurrence in uremic patients and is an important adverse prognostic indicator [16,17]. Echocardiographically-proven LV hypertrophy, systolic dysfunction and dilatation are independent predictors of mortality in these individuals [13,16–18]. This review will attempt to summarize current knowledge of the prevalence, pathophysiological mechanisms of LV disease in chronic uraemia and to discuss useful medical strategies in this population.


   2. Left ventricular hypertrophy
Top
 Abstract
 1. Introduction
 2. Left ventricular hypertrophy
3. Pathophysiological mechanisms
 4. Unfavourable consequences of...
 5. Regression of LV...
 6. Conclusions
 References
 
Numerous studies show that LV hypertrophy is frequent in end-stage renal failure [15,17,19–23]. Echocardiographically-proven LV hypertrophy is detected in 60–75% of patients starting renal replacement therapy and in 60–90% of those on regular dialysis treatment [15,17,21,24]. LV hypertrophy is also frequently noted in patients with moderate to severe chronic renal failure not yet requiring dialysis. Greaves et al. [25] observed that of 38 undialyzed patients with chronic renal failure 63% had an abnormal echocardiogram, and left ventricular hypertrophy was the most common finding (24%). Tucker et al. [26] showed LV hypertrophy in 16% of patients with creatinine clearance >30 ml/min and in 38% of those with creatinine clearance <30 ml/min. A Canadian multi-center study determined LV hypertrophy to be more frequent in uremic patients with diabetes mellitus and in older patients. [16,21].

2.1. Prognostic significance
LV hypertrophy is a powerful risk factor for cardiovascular mortality in the general population [27] and is a frequent occurrence in patients with end-stage renal disease [7,25]. Foley et al. [13] found that LV hypertrophy independently predicted mortality in uremic patients. McGregor et al. [15] examined 141 patients by echocardiography with end-stage renal disease on the eve of renal transplantation and found that LV mass index was significantly increased (167 g/m2 vs. 134 g/m2) in those subjects who died during a follow-up period of 7.5 years after transplantation. Work by Silberberg et al. [18] in end-stage renal disease patients showed that LV hypertrophy is an independent predictor of cardiac death. Uremic patients with LV mass index >125 g/m2 had a 5-year mortality rate of 52%, significantly higher compared to 23% in patients with LV mass index <125 g/m2. Patients with concentric LV hypertrophy appear at greater risk of cardiovascular events compared to those with eccentric hypertrophy [17].

A Canadian multi-center study followed a cohort of 432 end-stage renal failure patients [9,28] prospectively. At initiation of end-stage renal disease therapy 41% had concentric LV hypertrophy and 28% LV dilatation. The median time to development of heart failure was 38 months in those with concentric LV hypertrophy and 38 months in those with LV dilatation. Median survival was 48 months in the group with concentric LV hypertrophy, 56 months in those with LV dilatation, and >66 months in those without cardiac dysfunction. Those with more severe cardiac dysfunction had a worse long-term outcome [9,28]


   3. Pathophysiological mechanisms
Top
 Abstract
 1. Introduction
 2. Left ventricular hypertrophy
 3. Pathophysiological mechanisms
4. Unfavourable consequences of...
 5. Regression of LV...
 6. Conclusions
 References
 
3.1. Patterns of LV hypertrophy in uremia
LV hypertrophy in uremia is multifactorial in origin, the main pathophysiological factors include LV pressure and/or volume overload and humoral mechanisms [20] which also determine the heterogeneity of geometric patterns of hypertrophy (Table 1) [17,29–31].


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  		Table 1 Patterns of LV hypertrophy in chronic uremia

 
Changes in LV geometry in uremic patients may be partly related to when the echocardiogram was performed in relation to hemodialysis. During or just after hemodialysis, ultrafiltration and blood volume depletion are accompanied by a decrease in the LV diameter, while wall thickness increases. Prior to haemodialysis the LV mass/volume ratio may be low for a given systolic blood pressure and may be considered ‘inadequate’ hypertrophy [17,30]. Indeed, haemodialysis sessions may transiently convert the inadequate eccentric LV hypertrophy into an adequate concentric LV hypertrophy [30,31]. Moreover, Harnett et al. [24] found that when echocardiograms were performed pre- and post-hemodialysis, calculated LV mass index varied by 25 g/m2 because of reduction in LV end-diastolic diameter.

3.2. LV pressure overload
Sustained arterial hypertension is a frequent occurrence in chronic renal failure [32,33] and is one of the most important causes of LV hypertrophy in uremic patients [20,23]. Greaves et al. [25] found, using multiple regression analysis, that in pre-dialysed patients and individuals on hemodialysis or continuous ambulatory peritoneal dialysis, LV wall thickness and hypertrophy was positively correlated with systolic blood pressure. Other investigators [16] identified arterial hypertension as a predictor of both concentric LV hypertrophy and LV dilatation.

However, some authors found that in uremic patients the correlation between cardiac mass and blood pressure often is weak or absent [17,31]. Hüting et al. [34] noted that LV hypertrophy in chronic uraemia increased over time both in normotensive individuals and in patients with well-controlled hypertension. In uremic rats LV hypertrophy can be dissociated from mean arterial blood pressure [35]. McGregor et al. [15] found no relationship between mean blood pressure and LV mass; they supposed that these findings may reflect the inadequacy of casual recordings and suggested 24-h ambulatory monitoring may be more informative. Indeed, in the study of Return et al. [22], ambulatory blood pressure monitoring, systolic blood pressure load and night-time systolic blood pressure level was better correlated to LV mass index and LV wall thickness than casual blood pressure measurements. Furthermore, LV hypertrophy was reported to be more common in patients with chronic renal failure who had blunted or absent nocturnal blood pressure drop (‘non-dipper’) [26,33,35]. Blunted circadian blood pressure rhythm variation may lead to an increase in mean night-time blood pressure levels and blood pressure loads [26,35]. In addition, several studies reported the crucial role of blood pressure lowering to the reduction of LV mass in end-stage renal disease [29,30] as well as in essential hypertension [37,38]. The disparity in the reported findings may be attributed to the different antihypertensive drugs used in these studies, and to inter-study differences in methods of blood pressure measurements (casual blood pressure or 24-h ambulatory blood pressure monitoring).

3.3. Increased arterial wall stiffness
Several publications by London et al. [39–41] described the pathophysiological role of increased arterial stiffness and reduced arterial dispensability in the development of LV hypertrophy in chronic renal failure. End-stage renal disease is characterized by a moderate increase in aortic diameter throughout the length of aorta [17,40]. A substantial increase in aortic stiffness and great arterial trunks with an increased pulse wave velocity in aorta has been demonstrated, accompanied by a fibrosis or fibroelastic thickening of the intima, calcification of the internal elastic lamina, proliferation with calcification of the medial connective tissue and a significant increase in calcium content of the vascular walls [42]. The main consequence of such a remodelling of conduit arteries and reduction in arterial dispensability in end-stage renal disease patients is an increase in arterial impedance and therefore LV load [40]. Obviously, increased arterial impedance and rigidity leads to an increase in systolic pressure and is responsible for the increase in the LV end-systolic wall stress [30,40,41]. Altered pulsatile arterial hemodynamics in uremic patients results in a deleterious effect on heart structure and provokes LV hypertrophy [23,30].

3.4. LV volume overload
Anaemia is a frequent finding in chronic renal failure and is associated with chronic LV volume overload due to (i) low peripheral resistance due to a decrease in blood viscosity and hypoxic vasodilatation, and (ii) an increase in heart rate and LV stroke volume [17]. The influence of anaemia on LV structure has been demonstrated by a variety of studies [17,43–45]. Some authors observed a positive correlation between LV mass and volume on the one hand and the degree of anaemia on the other hand [17,22,26]. The partial correction of anaemia with recombinant human erythropoietin is accompanied by a decrease of LV volume and a regression of LV hypertrophy [44–48].

A further pathophysiological factor of latent or overt intravascular fluid volume overload in chronic uraemia is sodium and water retention [15,20,49]. In hemodialysis patients, there is a correlation between LV volume and blood volume. Ultrafiltration during a dialysis session reduces LV size [15,49]. Huting et al. [36] have shown that it is possible to limit LV dilatation by prolonged maintenance of ‘dry’ weight.

An obvious factor that contributes to worsening of eccentric LV hypertrophy in the dialysed population is the derangement of the complex framework of the factors which regulate cardiac output in normal individuals [20]. In dialysed subjects, there is profound impairment of all the components controlling effective intravascular volume, including storage capacity of the interstitium, buffering capacity of the venous system, excretory renal function, and LV function.

An additional cause of sustained LV volume overload in hemodialysis patients is arteriovenous fistulae which constitute a circuit of low vascular resistance, resulting in a decrease in circulation transit time, an increase in venous return and therefore an increase in systolic volume and heart rate. Correction of abnormally high levels of blood flow through the fistula in hemodialysis patients is recommended to prevent excessive LV volume overload [17,23].

3.5. Humoral factors
Secondary hyperparathyroidism is an important condition associated with the development of an ‘inadequate’ LV hypertrophy in chronic renal failure [17,50]. Experimental studies have shown that parathyroid hormone (PTH) has direct deleterious effects on the myocardium. In cultures of myocardial cells incubated with PTH, it was noted that PTH increases cellular calcium entry [17,51]. In addition, in uremic animals, parathyroidectomy prevents accumulation of intramyocardial calcium, necrosis of myocardial cells, and their replacement by calcium deposits [50,51]. Recent studies showed that PTH is a permissive factor in activation and proliferation of cardiac interstitial cells and in the genesis of cardiac interstitial fibrosis [52]. Clinical studies confirm these experimental observations. Timio [51] showed a linear relationship between serum PTH levels and LV mass in dialysis patients. In hemodialysis patients it has been found that hyperparathyroidism is accompanied by an ‘inadequate’ LV hypertrophy and dilated cardiomyopathy [15]. Drueke et al. [53] demonstrated that high levels of PTH play a role in cardiac derangement of patients with end-stage renal failure. The reduction of excess PTH levels in uremic patients either by treatment with vitamin D or after parathyroidectomy improved LV systolic performance [53,54].

Overactivity of the tissue renin–angiotensin system may be another pathophysiological factor in the development of LV hypertrophy in chronic uraemia [20,55]. Although plasma renin activity is usually diminished in chronic renal failure, long-term treatment with ACE-inhibitors caused significant regression of LV hypertrophy in uremic patients and experimental animals [56–63]. In addition, some authors have suggested that LV hypertrophy in hemodialysis patients is due to sympathetic overactivity [17,20]. In chronic uraemia a significant correlation between increased plasma endothelin levels and increase in LV mass has also been documented [64]. However, the subtle impact of neurohumoral changes inherent in uraemia and the role of messenger systems, growth factors, and cytokines in LV structural and functional alterations in chronic renal failure remains to be fully evaluated.


   4. Unfavourable consequences of LV hypertrophy
Top
 Abstract
 1. Introduction
 2. Left ventricular hypertrophy
 3. Pathophysiological mechanisms
 4. Unfavourable consequences of...
5. Regression of LV...
 6. Conclusions
 References
 
In patients with chronic renal failure, as well as in non-uremic cardiac patients, LV hypertrophy, at least initially, is a beneficial compensatory process allowing the LV to produce additional force to increase the cardiac work and to maintain constant wall tension [15,23]. With sustained LV pressure and/or volume overload combined with prolonged neurohumoral activation, the deleterious effects of LV hypertrophy prevail and lead to altered coronary reserve, increased arrhythmogenicity and reduction of LV compliance (Fig. 1) [15–17].


Figure 1
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  		Fig. 1 Pathophysiologic mechanisms of LV hypertrophy in chronic uremia.

 
4.1. Ischemic heart disease
Ischaemic heart disease is one of the most important causes of death in uremic patients. According to international registries and recent publications, ischemic heart disease accounts for 30–63% of deaths in end-stage renal disease [1–3,10,11,65]. The increased incidence of ischemic heart disease in uremia is multifactorial. Risk factors for the development of atherosclerosis are frequently present in uremia including smoking, hypertension, hyperlipidemia and diabetes mellitus, as well as additional risk factors which may be associated with the development of chronic renal failure including uremic ‘toxic’ environment, elevated pro-coagulant activity, increased oxidant stress, hyperhomocysteinemia, accumulation of advanced glycation end products, and increased insulin resistance [12,50,66].

Non-atheromatous ischemic heart disease is also commonly seen in patients with chronic renal failure. It is important to note that 30–40% of uremic patients with suspected ischemic heart disease have patent coronary vessels by coronary angiography [11]. Uremic left ventricular hypertrophy is associated with a reduction in coronary vasodilator reserve and an increase in myocardial oxygen demands. Increased intramyocardial arterial wall thickness may partly account for a reduction in coronary reserve while diminished capillary length and density may increase the average oxygen diffusing distance [14,66,67]. The above problems may be compounded by anemia.

Uraemia is associated with a reduction of the gradient between diastolic aortic pressure and LV diastolic pressure (myocardial perfusion gradient), that results from the elevated LV end-diastolic pressure (by reduced LV compliance associated with LV hypertrophy) and/or low diastolic aortic pressure (because of reduced aortic compliance). Moreover, tachycardia and increased LV systolic pressure necessary for filling a more rigid aorta lead to further increase of myocardial oxygen demand [66,67].

4.2. Arrhythmias and conduction disturbances
Complex life-threatening arrhythmias and sudden cardiac death due to malignant arrhythmias are common in end-stage renal disease [23,68]. The genesis of cardiac arrhythmias in chronic uremia is complex: the main pathophysiological factors include disorders of fluid–electrolyte and acid–base balances, myocardial ischemia, LV hypertrophy and fibrosis, a high level of uremic waste products, and side effects of drug therapy [14,68]. The relationship between LV hypertrophy and ventricular ectopy in end-stage renal disease is not well documented [68,69]. However, two-thirds of patients with pronounced LV hypertrophy may have complex ventricular ectopy. Cardiac interstitial fibrosis associated with chronic uremia may play a role in the development of cardiac arrhythmias. Fibrotic bands in the myocardium could disrupt the propagation of action potentials through the LV causing fragmentation of the excitation front leading to re-entry arrhythmias [14].

4.3. LV diastolic dysfunction
LV diastolic dysfunction has been frequently found by echocardiographic examinations in uremic patients including populations with chronic renal insufficiency, in the pre-dialysis phase, in subjects receiving dialysis treatment, and those after renal transplantation [17,23,70]. LV diastolic dysfunction is reported in 50–60% of patients [17]. The main factors responsible for the development of LV diastolic disorders in chronic renal failure include LV hypertrophy, myocardial fibrosis (by alteration of the strain–stress relationship), and myocardial ischemia (by heterogeneity and prolongation of LV relaxation and by increased myocardial rigidity due to post-ischemic scarring) [23,70].

Numerous studies have shown strong correlations between LV hypertrophy and disturbances in LV filling dynamics in chronic renal failure [17,70–72], with few exceptions [15,17,70]. However, Mc Gregor et al. [15] observed that median E/A ratio in uremic patients was 0.84 and suggested that diastolic dysfunction is not of major importance in studied population, but the range of E/A ratio varied widely (0.37–5.07), hence, among studied patients there were persons with impaired LV relaxation.

Increased LV wall stiffness and disturbances in LV filling result in abnormally high LV end-diastolic pressures. Hemodialysis patients had mean end-diastolic pressure at rest approximately double that of healthy persons, and the relationship between LV volume and LV pressure is abnormally steep [71]. Several investigators [30,31] have indicated that for dialysis patients this is a very important factor because of marked changes in LV volume between dialyses. Slight hypervolemia can thus cause pulmonary congestion and pulmonary oedema. On the other hand, volume depletion during rapid ultrafiltration can induce a fall in LV filling pressure results in dialysis-related hypotension and shock [72].

4.4. LV systolic dysfunction
LV systolic dysfunction is often observed in patients with chronic uremia and is of great importance as an unfavorable prognostic indicator [15,16]. Parfrey et al. [16] noted decreased LV systolic function in 16% of subjects starting renal replacement therapy; in this study median time to development of heart failure was 19 months in these individuals compared to 66 months in patients with normal echocardiograms. The relative risks of heart failure in the group with LV systolic dysfunction was significantly worse than in the normal group, after adjusting for age, diabetes and ischemic heart disease. The median survival in patients with LV systolic dysfunction was 38 months and significantly worse than those with a normal echocardiogram.

Similarly, McGregor et al. [15] found reduced LV systolic dysfunction in 28% of patients and this was an independent predictor of outcome in multivariate analysis.

The main factors responsible for the development of LV systolic dysfunction in end-stage renal disease include pre-existing ischemic heart disease, anemia, hyperparathyroidism, an increased serum calciumxphosphate product, uremic ‘toxic’ milieu, malnutrition, sustained and marked hemodynamic LV overload. Prospective follow-up showed that concentric LV hypertrophy and LV dilatation was usually present prior to the development of LV systolic dysfunction [15,16,73].

4.5. Heart failure
Heart failure may be present in 31% of patients at the beginning of renal replacement therapy [9,73]. Moreover, during dialysis therapy 7% of patients develop heart failure de novo each year [73]. Heart failure is an important risk factor of cardiovascular and overall mortality in the uremic population. In the Canadian multi-center prospective study median survival in the uremic group with heart failure was 32 months compared to 62 months in individuals without heart failure [73]. The main pathophysiological risk factors of heart failure in chronic uremia include diabetes mellitus, age and coronary heart disease; additional risk factors include anemia, hypoalbuminemia and arterial hypertension [20,23,73]. In half of the patients heart failure is predominantly due to systolic LV dysfunction often in association with LV dilatation and in the other half of patients it is mainly due to LV diastolic dysfunction [15,16,70,73].


   5. Regression of LV hypertrophy
Top
 Abstract
 1. Introduction
 2. Left ventricular hypertrophy
 3. Pathophysiological mechanisms
 4. Unfavourable consequences of...
 5. Regression of LV...
6. Conclusions
 References
 
Since LV hypertrophy represents a powerful cardiovascular risk factor in both uremic and non-uremic populations, the prevention of hypertrophy, its early detection, and reduction of LV muscle mass index at early stages of chronic renal failure may reduce cardiovascular events [4,13,18,20,27,30]. The regression of LV hypertrophy in chronic renal failure is a complex process (Fig. 2). Recently several experimental and clinical studies have shown reversal of myocardial hypertrophy in end-stage renal disease during long-term vigorous pharmacological control of blood pressure [56,60–63]. The regression of LV hypertrophy in end-stage renal disease has been demonstrated after the treatment with recombinant human erythropoietin [44,45,74], after strict volume control by ultrafiltration [49] and after renal transplantation [75–77]. Since parathyroid hormone plays a role in the genesis of myocardial hypertrophy and fibrosis in uremia, careful control of hyperparathyroidism is indicated [19,51].


Figure 2
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  		Fig. 2 Treatment strategies in uremic patients with LV hypertrophy.

 
5.1. Antihypertensive treatment
In non-uremic hypertensive LV hypertrophy, prolonged restoration of normal loading conditions with most classes of antihypertensive drugs excluding direct vasodilators and diuretics leads to a significant decrease in LV muscle mass index and LV wall thickness and to improvement of LV systolic and diastolic properties [38,78,79]. In the last several years, a growing number of experimental and clinical reports have analysed the structural LV changes during antihypertensive treatment (predominantly, ACE-inhibition) in uraemia [56,60–63,80–84]. The results were controversial. Rambausek et al. [83] suggested that LV develops and progresses despite blood pressure normalization by ACE-inhibitors in uremic animals. These results are in accordance with findings of Roithinger et al. [84] who showed that the ACE-inhibitor lisinopril, at a dose which left the blood pressure unchanged throughout the study period, was not able to induce reduction of LV mass.

In contrast, several studies have demonstrated beneficial effects of ACE-inhibition on LV structure and function in uremic patients [56,60–63,80,81]. We recently published data from a randomized prospective longitudinal study [63,85] indicating that in patients with chronic renal failure and moderate arterial hypertension long-term treatment with ACE-inhibitors, captopril and enalapril, significantly lowered arterial pressure and reduced LV hypertrophy. In this study, LV mass index was reduced by 12% and 14% after 6 months of treatment with captopril and enalapril, respectively. These agents appeared equally effective.

In agreement with our results, London et al. [62] comparing ACE-inhibitors and calcium channel blockers in patients with LV hypertrophy and end-stage renal failure showed that, in spite of similar effects on blood pressure, only the ACE-inhibitor decreased LV mass and volume. Cannella et al. [61] reported the results of a long-term follow-up of a group of dialysed hypertensive uremic patients with LV hypertrophy who received combined antihypertensive therapy with ACE inhibitors, calcium channel blockers and beta-blockers over a period of 24 months. They showed that aggressive antihypertensive therapy significantly decreased 24-h monitored blood pressure levels and consistently reduced LV hypertrophy. Using multiple regression analysis the decrease in LV mass has been shown to be mainly related to the decrease of the 24-h blood pressure.

These results confirm that in patients with chronic renal failure regression of LV hypertrophy can occur with antihypertensive treatment with ACE-inhibitors. Whether this is due to a lowering of blood pressure or to a direct effect of the drugs on the myocardium in addition, is unclear. In our study [85] the decrement in LV hypertrophy was not correlated with the reduction in the systolic and diastolic blood pressure. In agreement with our findings, some clinical and experimental studies have shown that the LV mass correlated poorly with blood pressure level during both the development and the reversal of hypertensive LV hypertrophy [79]. In our study [85], the regression of LV hypertrophy during antihypertensive treatment of chronic renal failure patients with ACE-inhibitors was associated with significant improvement in the LV diastolic function. The reduction of LV mass index was shown to be achieved safely, without a demonstrable deterioration in LV systolic performance. In contrast with our findings, Roithinger et al. [84] were unable to show improvement in diastolic filling in patients with chronic renal failure receiving ACE-inhibitor.

5.2. Treatment of anemia
Correction of anemia by administration of recombinant human erythropoietin (r-HuEPO) has been shown to decrease LV mass index in uremic subjects [45,46,86]. In several studies [44,45,87] over a treatment period of 6–12 months in dialysis patients LV dilatation diminished and LV mass index significantly decreased from 170–190 g/m2 to approximately 130 g/m2. Average percentage LV mass decrease during r-HuEPO treatment was 18% (4–34%) [44–48,87]. Vanrenterghem et al. [47] suggested that it would seem preferable to try to prevent LV hypertrophy by correcting anemia with r-HuEPO at the earlier stages of chronic renal failure, before starting renal replacement therapy. It is of note that correction of anemia with r-HuEPO should be gradual in order to prevent development or worsening of arterial hypertension. r-HuEPO-induced increase of blood pressure may abolish the beneficial effect of anemia correction on LV hypertrophy [46,47,86].

5.3. Dialysis modalities and arterio-venous shunts.
Adjustment of dialysis schedules and correction of high-flow arterio-venous shunts (more than 1 l/min) in order to prevent hypervolemia and to optimize LV loading conditions are useful tools in the management of uremic patients with eccentric LV hypertrophy [49,67,70]. In an earlier report, maintaining blood pressure at a strictly normal level by long hemodialysis sessions in the absence of antihypertensive treatment was found not to prevent LV hypertrophy [34]. In contrast, recently Özkahya et al. [49] in retrospective study have observed that in patients on hemodialysis good long-term blood pressure control and LV hypertrophy regression can be achieved by continuous efforts to control hypervolemia (by careful control of ultrafiltration and reduced salt intake). It is important to use dialysis regimen which prevents hypervolemia (more frequent dialysis schedule) as well as hypovolemia (longer duration of dialysis sessions) [67].

5.4. Transplantation
Renal transplantation improves disorders of LV structure and function. The regression of LV hypertrophy and improvement of LV diastolic dysfunction have been reported following renal transplantation [74,75]. It was concluded that, in the absence of underlying coronary heart disease, the existence of these abnormalities does not preclude renal transplantation [74–76]. It is of note, that systemic hypertension leading to aggravation of constant LV pressure overload, is extremely common in the post-transplant patients with a prevalence of approximately 50%. Mechanism of hypertension in such patients is complex, the main contributing factors include impaired renal function associated with chronic graft rejection, cyclosporine administration, donor-related factors and retained native kidneys. Cyclosporine-induced mechanisms of hypertension include both renal and systemic vasoconstriction (mainly due to increased sensitivity to vasoconstrictors and to altered endothelial and arteriolar smooth muscle function), and cyclosporine vasculopathy. Cyclosporine-mediated hypertension may be a serious factor attenuating the beneficial effects of renal transplantation on LV structure [74–76].


   6. Conclusions
Top
 Abstract
 1. Introduction
 2. Left ventricular hypertrophy
 3. Pathophysiological mechanisms
 4. Unfavourable consequences of...
 5. Regression of LV...
 6. Conclusions
References
 
Echocardiographically-determined disorders of LV structure and function are common features in chronic uremia; these abnormalities indicate an increased risk of cardiovascular and overall morbidity and mortality in a pre-dialyzed population, during dialysis treatment and in renal transplant recipients. Prolonged careful antihypertensive treatment, correction of anemia, optimization of the dialysis regimen, and control of hyperparathyroidism may represent important strategies to prevent progression and to achieve partial reduction of such LV abnormalities. Further larger-scale randomized studies of different antihypertensive agents, using 24-h blood pressure control, erythropoietin treatment, strict control of intravascular fluid volume overload, correction of secondary hyperparathyroidism are necessary in patients with chronic uremia including end-stage renal disease as well as earlier stages of chronic renal failure. In addition, long-term trials targeted at determining whether treatment-induced regression of LV hypertrophy results in a decrease in cardiovascular morbidity and mortality rates are also necessary. Obviously, the future development of other treatment modalities (for example, those aimed to correction of increased aortic wall stiffness or influence on molecular messenger and trigger systems of LV disease, etc.) may be of great importance.


   References
Top
 Abstract
 1. Introduction
 2. Left ventricular hypertrophy
 3. Pathophysiological mechanisms
 4. Unfavourable consequences of...
 5. Regression of LV...
 6. Conclusions
 References
 

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