Version May 2024
INTRODUCTION — Valvular heart disease is common in patients undergoing maintenance dialysis. Abnormalities include valvular and annular thickening and calcification of any of the heart valves but commonly the aortic and mitral valves, with the subsequent development of valvular regurgitation and/or stenosis of the affected valve.
PREDISPOSING FACTORS — Many predisposing factors are associated with the development of valvular disease in dialysis patients, perhaps the most significant being the presence of secondary hyperparathyroidism [1-5]. Valvular calcification is also associated with vascular calcification, hypercalcemia, and hyperphosphatemia, all findings that can occur in patients with marked secondary hyperparathyroidism. (See "Refractory hyperparathyroidism and indications for parathyroidectomy in adult patients on dialysis".)
Valvular calcification may also be found in patients without secondary hyperparathyroidism, particularly among those with adynamic bone disease, older patients, and those who have undergone dialysis for a longer duration [6,7]. The association with adynamic bone disease may be related to the use of calcitriol and calcium-containing phosphate binders, with increased calcium deposition [8]. Progressive disease may be attenuated in part by substituting sevelamer for calcium-containing phosphate binders, as shown in a trial of 200 hemodialysis patients followed over a one-year period [9].
Additional factors that may enhance the development of valvular heart disease in this patient population include the presence of one or more of the following conditions [10]:
●Hypertension
●Diabetes mellitus
●Hyperlipidemia
●Left ventricular hypertrophy
●Malnutrition/inflammatory complex
●Uremic milieu
●Hypertrophic cardiomyopathy
●Mitral valve prolapse
●High cardiac output states
●Anemia
●Infective endocarditis (IE)
●Arteriovenous (AV) fistulae
The presence of valvular calcification is also a marker of generalized vascular calcification in patients with end-stage kidney (ESKD) disease [11]. Vascular calcification in this patient population is discussed in detail separately. (See "Vascular calcification in chronic kidney disease".)
PATHOGENESIS AND PATHOLOGY — Prior to discussing the different clinical valvular abnormalities in patients with end-stage kidney disease (ESKD), it is helpful to first review the pathogenesis and pathology of heart valve or annulus calcification, and of heart valve thickening. These processes underlie much of the valvular heart disease observed in patients with ESKD.
Valvular and annular calcification
Mitral annular calcification — Mitral annular calcification (MAC) is a chronic, degenerative process, which involves a slow, progressive calcification of the fibrous mitral annulus. MAC with or without degenerative mitral valve leaflet involvement is a significant and common cause of mitral regurgitation and nonrheumatic mitral stenosis [12,13].
The reported prevalence of MAC is approximately 8 to 15 percent, with significant increases commonly seen with advanced age, multiple cardiovascular risk factors, and chronic kidney disease [14]. MAC occurs in 10 to 50 percent of patients with ESKD [1,7,15,16]. As previously mentioned, it is associated with vascular calcification, hypercalcemia, and hyperphosphatemia.
MAC occurs earlier in patients with chronic kidney disease than those without kidney dysfunction due in part to the dialysis procedure alone [1]. In one study, MAC was more common in younger (less than 60 years of age) than older dialysis patients [7]. Since older dialysis patients are commonly dialyzed for fewer years because of a marked increase in mortality, MAC appears to occur more frequently in those dialyzed for a longer period of time. (See "Patient survival and maintenance dialysis".)
MAC is recognized echocardiographically as a uniform echodense rigid band, located posterior to the mitral leaflet and anterior to the left ventricular wall [3]. It can extend along the endocardium of the posterior basal wall and engulf and immobilize the posterior leaflet of the mitral valve. (See "Echocardiographic evaluation of the mitral valve", section on 'Mitral annular calcification'.)
Aortic valve calcification — Aortic valve calcification (AVC) is found in 25 to 55 percent of hemodialysis patients, occurring 10 to 20 years earlier than in the general population [2,6,7,15-20]. When adjusted for other cardiovascular risk factors, moderate chronic kidney disease is not significantly associated with AVC [21]. Furthermore, it has been shown that the prevalence and severity of AVC and coronary artery calcium (CAC) are increased among patients with atherosclerotic causes of kidney failure and do not vary with the severity of kidney disease [22].
A study including 1964 participants from the Chronic Renal Insufficiency Cohort Study revealed that decreased kidney function was associated in a dose-dependent manner with increased levels of AVC, independent of traditional risk factors [23].
AVC is associated with factors similar to those associated with MAC. AVC occurs more frequently in hemodialysis or peritoneal dialysis patients who are older, have received kidney replacement therapy for a longer period of time, and in those with elevated serum parathyroid hormone, calcium, and/or phosphorus levels [1-3,7,15,24-26]. Other factors that promote the development of AVC include increasing age, enhanced mechanical stress on the valve cusps, minor congenital cusp inequalities, hypertension, inflammation, malnutrition, diabetes, and dyslipidemia [2,5,21,27-29].
Combined valvular calcification — The co-occurrence of mitral valve and AVC has been reported in 15 to 29 percent of patients with ESKD [26,30,31]. In one study that included 243 hemodialysis patients, calcifications were present in either the mitral valve, aortic valve, or mitral annulus in 100 percent of patients [32]. Fewer than 2 percent of dialysis patients had one site that was free of calcification, and more than 50 percent of patients had at least mild calcification. Mild to moderate mitral valve calcification (MVC) and AVC were reported in 98.8 and 94.8 percent of patients, respectively, exceeding previously documented prevalences. Mild MAC was found in 68.7 percent of patients, and moderate to severe MAC was found in 31.3 percent of patients. Other findings in this study included a significantly increased prevalence of moderate to severe AVC in patients aged ≥65 years, males than females, and in White patients as compared with Black patients [32].
Tricuspid and pulmonic valve calcification — The occurrence of calcific deposits in the tricuspid and pulmonic valve annulus is rare.
Valvular thickening — Valvular thickening or sclerosis, which most commonly involves the aortic and mitral valves, is a frequent finding in hemodialysis patients. Among such patients, aortic and mitral valve sclerosis occur in 55 to 69 and 40 to 60 percent of individuals, respectively [2,7].
Although previously thought to be a nonspecific finding without clinical significance, valvular sclerosis is now recognized to be associated with progressive stenosis and increased cardiovascular mortality [33]. Prospective studies have found that valvular sclerosis may progress, usually gradually, but occasionally rapidly, to clinically significant stenosis [2,34]. In a Doppler echocardiographic study of 62 patients on hemodialysis, 34 had thickening of the aortic cusps; among these patients, eight had aortic stenosis, and eight had aortic regurgitation [2]. Twenty-five patients had thickening of the mitral annulus; among these patients, seven had mitral regurgitation, and three had mitral stenosis. (See "Aortic valve sclerosis and pathogenesis of calcific aortic stenosis".)
Histology — The thickening typically involves the chordae tendineae, valve cusps, and leaflets [35]. On gross examination, the chordae tendineae show irregular thickening and shortening. Histologically, the chordae tendineae appear as "concentric rings of loose connective tissue around a central dense core."
Pathogenesis — The pathogenesis of valvular thickening is unclear. However, the presence of abnormal annular tissue, hyperparathyroidism, uremia, and subclinical infection are possible mechanisms [2,36].
GENERAL ISSUES IN VALVULAR DISEASE — The principal valvular abnormalities of clinical consequence observed in dialysis patients are regurgitant and stenotic lesions. Infective endocarditis (IE), conduction abnormalities, and thromboembolism may also occur with these defects.
Clinical manifestations — The clinical features of patients with valvular disease are similar in those with and without kidney failure, but there are certain issues that are unique among dialysis patients. For example, valvular heart disease may be difficult to diagnose clinically via the physical examination because changing volume status makes the clinical assessment of murmurs difficult. Coexisting conditions, such as anemia and hypertension, also frequently exaggerate murmurs. In addition, valvular dysfunction may be associated with complications during hemodialysis [37]. (See "Auscultation of heart sounds" and "Auscultation of cardiac murmurs in adults" and "Intradialytic hypotension in an otherwise stable patient".)
Another clinical issue related to volume status involves the presence of a diastolic murmur commonly heard in patients with end-stage kidney disease (ESKD). The exact origin of this murmur remains controversial. Although it was previously attributed to pericardial disease or aortic insufficiency, the murmur is now considered to arise from the pulmonic valve [38-40]. Typically, the murmur is described as a diastolic, decrescendo murmur that is blowing in quality and occurs immediately after the second heart sound. The maximal intensity is at the left sternal border or sometimes at the apex. It is best heard in the supine position, typically disappears after dialysis, and reappears when the patient becomes volume overloaded [38].
Evaluation — Echocardiography with Doppler flow analysis is an invaluable diagnostic screening tool for the presence of valvular heart disease; it is the modality of choice to detect and assess valvular dysfunction in patients with and without kidney failure. Echocardiography can also evaluate left ventricular function and pericardial disease. However, prior to performing echocardiography, the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend that the dry weight should be optimized [41]. (See "Echocardiographic evaluation of the mitral valve".)
Two-dimensional echocardiography permits a real-time evaluation of the anatomy of the valve, subvalvular structures, annulus, and other cardiac structures. Doppler flow analysis can also evaluate the degree of regurgitation/stenosis and flow dynamics. In patients with known valvular heart disease, serial echocardiograms are recommended to follow the progression of disease.
Although echocardiography most commonly provides an accurate assessment of disease severity, cardiac catheterization may be necessary in patients with aortic stenosis or regurgitation, settings in which hemodynamic severity can be difficult to assess noninvasively [42] (see "Hemodynamics of valvular disorders as measured by cardiac catheterization"). Coronary angiography is principally needed to evaluate for coronary artery disease in patients who may undergo valve replacement [42].
Treatment — Among dialysis patients, general therapeutic considerations for the treatment of valvular heart disease that are independent of the specific valvular defect should include the prevention and management of secondary hyperparathyroidism, hyperphosphatemia, hypercalcemia, and hypertension. Prevention is particularly important since there are limited data to show that management after onset is effective [9,43]. One trial found that in patients with ESKD and secondary hyperparathyroidism, treatment with the calcimimetic, cinacalcet, and low-dose vitamin D supplementation slowed the progression of valvular calcification [44,45].
Most investigators agree that the uremic milieu in association with other predisposing factors facilitate premature valvular heart disease and calcium deposition. (See "Management of hyperphosphatemia in adults with chronic kidney disease" and "Hypertension in patients on dialysis".)
Type of valve — Both bioprosthetic and mechanical valves, particularly in the dialysis patient, are at risk for endocarditis. Candidacy for long-term anticoagulation is also a factor in the clinical decision making in selecting a valve as it is required for all mechanical valves. However, accelerated dysfunction is common with bioprosthetic valves, while mechanical valves are associated with long-term function. (See "Mechanical prosthetic valve thrombosis or obstruction: Clinical manifestations and diagnosis".)
The optimal replacement valve (independent of the exact anatomic location) remains somewhat controversial in patients with ESKD. Many authors have traditionally favored a mechanical, not a bioprosthetic, valve. Features that support the use of a mechanical valve are the enhanced risks of accelerated dysfunction and calcification of a bioprosthetic valve due to the uremic milieu.
Bioprosthetic valves have been used in hemodialysis patients with relatively good short-term results (less than five years). This was illustrated in a retrospective study of nearly 6000 dialysis patients in which survival at two years was similar among those who underwent cardiac valve replacement with a mechanical or bioprosthetic valve (40 percent for both groups) [46].
Another comparative study of hemodialysis patients in China found equivalent rates of perioperative morbidity and mortality and late survival (47) after cardiac valve replacement with a bioprosthetic versus mechanical valve [47]. Benefits with bioprosthetic valves include a lower incidence of bleeding, thrombosis, and stroke (both early and late events) [48-50]. A meta-analysis that examined the heart valve prosthesis selection in patients with ESKD found no difference in survival between bioprosthetic and mechanical prosthetic valve types [51]. However, as demonstrated in earlier studies, valve replacement with bioprosthesis was associated with fewer valve-related complications compared with mechanical prostheses. A single-center, retrospective study of 202 patients with ESKD undergoing valve replacement over a 12-year period found no difference in 30-day mortality (19.9 percent) between bioprosthetic and mechanical valve replacements [52]. However, 10-year survival was poor at 18 percent and was not influenced by the valve type implanted.
To improve specific patient survival, decrease morbidity, and reduce symptoms, the type of valve chosen should be individualized, with the decision based upon the age and clinical and functional status of the patient. Mechanical valves, particularly for the mitral valve, should be considered in younger and healthier patients; however, these individuals may be at a higher risk for bleeding and thrombotic complications. Careful consideration should be given in older patients, weighing such variables as the risk for bleeding, stroke, and the presence of hypercalcemia and/or hyperphosphatemia.
In general, both mechanical and bioprosthetic valves can be used in dialysis patients, as recommended in the 2005 KDOQI guidelines [41].
Type of procedure — Among patients with ESKD, the choice of the procedure for valve replacement needs to be individualized. Due to lack of prospective studies, the risks and benefits of surgical valve replacement compared with transcatheter valve implantation (TAVI) are not well established in this population [53,54]. Given the significantly reduced survival of patients with valvular heart disease and ESKD, the type of procedure is especially important because the median survival of >2 years is considered the threshold for cost-effectiveness of TAVI in the general population [55]. Detailed evaluations regarding choice of procedures in the general population are discussed at length elsewhere:
●(See "Choice of intervention for severe calcific aortic stenosis", section on 'TAVI versus SAVR'.)
●(See "Surgical procedures for severe chronic mitral regurgitation".)
●(See "Surgical and investigational approaches to management of mitral stenosis".)
●(See "Tricuspid stenosis", section on 'Intervention'.)
Delivery of dialysis — Whether the delivery of intensive doses of dialysis prior to or during surgery improves outcomes is unknown. In general, dialysis should at least be provided the day before surgery. (See "Medical management of the dialysis patient undergoing surgery".)
Prognosis — The survival of dialysis patients requiring valve replacement(s) (with or without coronary artery revascularization) is approximately 36 to 55 percent at five years, which is comparable to dialysis patients without valvular disease [6,50]. Many patients report clinical symptomatic improvement, as well as improvement in New York Heart Association (NYHA) classification [6,50].
The presence of cardiac valvular calcification has been an important negative prognostic factor in some studies [56-58]. Among nearly 200 peritoneal dialysis patients, valve calcification as detected by echocardiography at baseline was associated with a 2.5- and 5.4-fold increased risk of all-cause and cardiovascular death, respectively, at follow-up at 1.5 years [59]. Almost all patients (90 percent) with both valvular calcification and atherosclerotic vascular disease had died by one year, with death occurring in 21 and 23 percent of those with either abnormality alone and 13 percent of those with neither complication. A study of 144 adult hemodialysis patients found an increase in mortality for patients with valvular calcification of the mitral and aortic valve [58]. However, after adjustments for age, sex, race, diabetes mellitus, history of atherosclerotic disease, and pulse pressure, only mitral valve calcification (MVC) remained independently associated with all-cause mortality. Patients with calcification of both valves had a twofold increased risk of death compared with those without valvular calcification. Coronary and valvular calcification measured on chest computed tomography (CT) was also associated with all-cause mortality.
By contrast, in an Italian study of hemodialysis patients, the presence of calcifications was not an independent prognostic factor [60]. After adjustment for other cardiovascular risk factors, left ventricular mass index, and additional clinical characteristics, calcification failed to provide further independent predictive power.
VALVULAR STENOSIS — Stenosis of the aortic valve is the most common obstructive abnormality among hemodialysis patients, with the next most frequent lesion being mitral stenosis. By comparison, tricuspid and pulmonic stenoses are rare.
Etiology — Stenotic heart valves in patients undergoing maintenance dialysis occur most commonly in association with annular calcification, which (as previously mentioned) is frequently due to hyperparathyroidism and elevated serum levels of calcium and phosphorous. Thus, aortic and mitral stenoses are observed in association with aortic valve calcification (AVC) and mitral valve calcification (MVC), respectively [2]. Similar considerations apply to pulmonic and tricuspid stenosis [61].
Among an increasingly older dialysis population, enhanced age alone is also a contributing factor to the development of aortic stenosis. Furthermore, aortic stenosis resulting from a bicuspid valve or rheumatic fever occurs at an earlier age among dialysis patients than those without kidney failure because of factors associated with the uremic milieu, particularly calcium and phosphorous abnormalities.
Clinical manifestations, evaluation, and treatment — Although the clinical manifestations and treatment of aortic, mitral, pulmonary, and tricuspid stenosis are similar in patients with and without kidney failure, certain features are relatively unique among patients undergoing maintenance dialysis.
Aortic stenosis — Approximately 15 to 20 percent of dialysis patients have aortic stenosis, with hemodynamically significant stenosis developing in 3 to 9 percent [6,17,20,62]. In one study of hemodialysis patients, the estimated incidence of symptomatic aortic stenosis was 3.3 percent per year [20].
The degree of aortic stenosis is related to the degree of calcification [24,28], with the rate of decrease in valve area significantly higher among dialysis patients than those without kidney failure (mean decrease of 0.23 versus 0.05 to 0.1 cm2 per year for uremic and nonuremic patients, respectively) [17,20,62] (see "Aortic valve area in aortic stenosis in adults"). Aortic stenosis progresses more quickly in end-stage kidney disease (ESKD) patients, with higher metabolic and hemodynamic loads on the aortic valve compared with individuals with normal kidney function [63].
Patients with aortic stenosis are commonly asymptomatic for a prolonged period of time. Angina, syncope, and dyspnea eventually develop, followed by symptoms and signs of heart failure (see "Natural history, epidemiology, and prognosis of aortic stenosis"). Progression is significantly more frequent in men than women [17,20,62], with rapid progression to symptomatic aortic stenosis being associated with a significant decrease in survival.
Among hemodialysis patients with aortic stenosis and left ventricular hypertrophy, aggressive ultrafiltration may lead to episodes of intradialytic hypotension [6]. Excessive reduction of end-diastolic filling pressure may reduce cardiac output and coronary perfusion and result in myocardial ischemia and impaired oxygen delivery [6]. Clinically, this may result in chest pain, dyspnea, syncope, cardiac arrhythmias, and myocardial infarction during dialysis. Thus, the use of controlled ultrafiltration and careful attention to dry weight assessment is essential in the management of these patients.
The principal sign of aortic stenosis is the characteristic systolic murmur, which is described as a systolic "ejection" murmur. It is typically heard best at the base of the heart where it has a harsh quality. The murmur is transmitted well and equally to the carotid arteries. (See "Auscultation of cardiac murmurs in adults".)
Among dialysis patients, systolic murmurs that are unrelated to aortic stenosis are common, resulting in diagnostic difficulties. Such murmurs include those due to a thickened aortic valve (but without hemodynamic compromise), MVC, and increased blood flow (resulting from hypervolemia) [64].
The modality of choice in the evaluation of aortic stenosis (as well as all other valvular abnormalities) is echocardiography and Doppler flow analysis. To promote the use of clinically accessible noninvasive imaging, the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend annual Doppler echocardiograms in the following patients [41] (see "Clinical manifestations and diagnosis of aortic stenosis in adults"):
●Asymptomatic waitlist patients with aortic valve area ≤1.0 cm2
●Other dialysis patients who are suitable candidates for aortic valve replacement based on overall clinical status
Cardiac catheterization may be necessary in some patients [42]. In addition, among patients in whom valve replacement is possible, coronary angiography is required to evaluate for coronary artery disease.
The timing of valve replacement is similar in patients with or without kidney failure. However, given that even mild disease with noncritical stenosis may result in significant cardiovascular morbidity among dialysis patients, early referral for valve replacement may be indicated. (See "Indications for valve replacement for high gradient aortic stenosis in adults".)
Many authors feel that the replacement valve should be a mechanical rather than a bioprosthetic valve. However, the decision should be made on an individual basis since equivalent results have been noted with the two types of valves [46,49,50]. Complications of the various valves include difficulty in maintaining anticoagulation in patients with a mechanical valve and accelerated valve calcification with a tissue prosthesis.
Neither the 2020 American College of Cardiology/American Heart Association (ACC/AHA) guidelines nor the older European Society of Cardiology guidelines on the management of valvular heart disease made specific recommendations on the choice of valve in patients with aortic stenosis who have ESKD [65,66]. (See "Choice of prosthetic heart valve for surgical aortic or mitral valve replacement".)
Mitral stenosis — Among dialysis patients, mitral stenosis is most commonly due to mitral annular calcification (MAC) rather than rheumatic fever [2,67]. Data on prevalence are limited, but a review of 62 hemodialysis patients found mitral stenosis in three patients receiving dialysis [2].
Mitral stenosis can be associated with a variety of symptoms and signs that are primarily related to the severity of the valvular stenosis as reflected by the cardiac output, pulmonary pressures, and pulmonary vascular resistance (see "Rheumatic mitral stenosis: Clinical manifestations and diagnosis"). Hemodialysis may improve clinical symptoms by reducing preload; however, treatment requires careful assessment of dry weight and prevention of excessive ultrafiltration, which can reduce ventricular filling across the stenotic mitral valve. Antibiotic prophylaxis should also be considered in appropriate settings. (See 'Infective endocarditis' below.)
Rate control is important in patients with mitral stenosis who develop atrial tachyarrhythmias since a rapid heart rate can further impair ventricular filling. (See "Rheumatic mitral stenosis: Overview of management".)
Percutaneous mitral balloon valvotomy generally provides relief of symptoms in patients with mitral stenosis if the valve morphology is favorable. However, the use of this technique is generally contraindicated in patients with significant valvular and subvalvular calcification, mitral regurgitation, and left atrial or left atrial appendage clot. In such cases, open commissurotomy, valve reconstruction, or mitral valve replacement is preferable [42]. (See "Percutaneous mitral balloon commissurotomy in adults" and "Surgical and investigational approaches to management of mitral stenosis".)
Pulmonic stenosis — Calcific pulmonic deposits, when present, are often associated with pulmonic valve stenosis in dialysis patients [68]. This is usually accompanied by increased right ventricular systolic pressure and, eventually, right ventricular hypertrophy [69]. (See "Clinical manifestations and diagnosis of pulmonic stenosis in adults" and "Pulmonic valve stenosis in adults: Management".)
VALVULAR REGURGITATION — A high prevalence of mitral, tricuspid, and aortic regurgitation is observed in dialysis patients [2,7]. Mitral regurgitation is most common [7,70]. In a series of 75 patients with a mean age of 59 years, valvular regurgitation of the mitral, tricuspid, and aortic valves occurred in 95, 65, and 38 percent of patients, respectively [7]. Additional findings included:
●Moderate and severe regurgitation of the mitral valve occurred in 27 and 13 percent of patients, respectively.
●Moderate and severe regurgitation of the tricuspid valve occurred in 13 and 5 percent of patients, respectively.
●Moderate aortic regurgitation was present in 4 percent of patients, while the incidence of severe aortic regurgitation was not reported.
The prevalence and degree of regurgitation varies with volume status, degree of left ventricular function, and medications administered (particularly antihypertensive agents), with changes in volume status being the most significant. One study of 21 hemodialysis patients with both mitral and tricuspid valve regurgitation assessed whether valvular insufficiency disappeared with aggressive ultrafiltration [71]. After intensified sessions resulting in a decrease in body weight of approximately 5.4 kg, mitral and tricuspid regurgitation vanished in 13 and 14 patients, respectively. Among those with persistent abnormalities, the degree of regurgitation was much less severe.
Etiology — The disappearance of regurgitant lesions with aggressive volume and blood pressure control suggests that most valvular insufficiency in dialysis patients is "functional" in origin. Valvular calcification appears to be responsible for most other cases, while infective endocarditis (IE) may also result in a regurgitant lesion (see 'Infective endocarditis' below). In addition, mitral and aortic regurgitation may be more common in polycystic kidney disease, the former due in part to a possibly enhanced incidence of mitral valve prolapse [72]. (See "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations".)
Clinical manifestations, evaluation, and treatment — The clinical features of regurgitant lesions are described in detail separately (see "Clinical manifestations and diagnosis of chronic mitral regurgitation" and "Clinical manifestations and diagnosis of surgical aortic and mitral prosthetic valve regurgitation" and "Clinical manifestations and diagnosis of chronic aortic regurgitation in adults" and "Natural history and management of chronic aortic regurgitation in adults"). However, there are issues that are unique to patients with end-stage kidney disease (ESKD). Compared with patients without kidney failure, the management of regurgitant lesions in dialysis patients, particularly mitral and tricuspid regurgitation, should focus upon volume and blood pressure control. Aortic regurgitation is also worsened in the setting of elevated systolic pressure and increased afterload conditions. Aggressive ultrafiltration to attain clinical dry weight and optimal blood pressure control (with antihypertensive medications, if necessary) should be therapeutic goals in these patients. The attainment of optimal intravascular volume may eliminate or severely reduce regurgitant valvular lesions, as well as diminish the clinical murmurs associated with these lesions [71].
However, more aggressive ultrafiltration does not always improve the clinical status of the patient. This finding may signal more advanced ventricular dysfunction.
INFECTIVE ENDOCARDITIS — Infective endocarditis (IE) occurs in approximately 3 percent of patients receiving hemodialysis and approximately 9 percent of those with an infected access [73]. Thus, the presence of a vascular access is a significant risk factor for the development of IE, including a primary arteriovenous (AV) fistula [74-76].
Most data related to IE in dialysis patients are derived from relatively small studies. The following are the two largest reports describing the clinical features of patients with end-stage kidney disease (ESKD) and IE:
●Among 40 dialysis patients with definite endocarditis, access types were an AV fistula, intravenous catheter, and polytetrafluoroethylene graft in 60, 30, and 18 percent, respectively [77]. The mitral valve, aortic valve, or both were infected in 53, 20, and 20 percent, respectively.
●In another series of 28 dialysis patients with 30 episodes of endocarditis, the source of sepsis was related to a tunnel catheter, AV fistula, polytetrafluoroethylene graft, and nontunneled catheter in 48, 32, 12, and 4 percent of patients, respectively [75]. Infection of the mitral valve, aortic valve, or both valves occurred in 41, 38, and 17 percent, respectively. Over one-half of affected patients had an abnormal valve, frequently calcified, prior to the valve infection.
IE is also a known complication of mitral annular calcification (MAC). In one report, IE occurred in approximately 4 percent of patients with this abnormality [78].
The short- and long-term survival of dialysis patients with IE is poor and has not improved over time. In a retrospective United States study of over 13,000 patients, the in-hospital mortality rate for those with IE was 24 percent [79]. In addition, among those hospitalized between 1977 and 1991, between 1992 and 1996, and between 1997 and 2000, the survival rates at one year were 46, 41, and 38 percent, respectively, while the three-year rates were 24, 21, and 18 percent, respectively. Similar poor outcomes were reported in an analysis from the Hemodialysis (HEMO) study [80].
A poor prognosis was also seen in patients on dialysis who required valve replacement after treatment for endocarditis, with a one-year mortality of approximately 50 percent [81].
The clinical manifestations and treatment of IE are discussed separately. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis" and "Antimicrobial therapy of left-sided native valve endocarditis".)
ADDITIONAL COMPLICATIONS — Dialysis patients with valvular heart abnormalities are at an increased risk of developing conduction disturbances and thromboembolism.
Arrhythmias and conduction abnormalities — Several arrhythmias and conduction system abnormalities, such as supraventricular arrhythmias, sinus node dysfunction, atrioventricular (AV) nodal, and intraventricular blocks, are common in patients with mitral annular calcification (MAC) and aortic valve calcification (AVC) with or without stenosis [43,78,82-86]. This may be in part hemodynamically mediated, but calcification within the conduction system is probably more important [43].
Atrial fibrillation is a particularly common finding [78]. In one study, for example, atrial fibrillation occurred in 29 percent of patients with MAC [78].
Thromboembolism — Thromboembolism is another significant complication of MAC and AVC, with numerous reports of calcific emboli occurring in those with calcified valves [78,87-89]. As with valvular infection, superimposed thrombus can form on the calcified annulus. The thrombotic or ulcerative changes that occur within heavily calcified valves when exposed to the intracardiac lumen can result in an erupted mass of calcium entering the systemic circulation [78]. Additional factors that contribute to calcific thromboemboli include the presence of cardiac arrhythmias and left atrial enlargement [78].
Thromboemboli in patients with MAC usually result in cerebral ischemia. By comparison, those with AVC experience relatively more episodes of retinal emboli, resulting in retinal artery occlusion and transient monocular blindness. This difference suggests that emboli in patients with AVC are relatively small in size [90].
Other potential sources for stroke often coexist with valvular calcification; these include dilated cardiomyopathy with left atrial enlargement, infective endocarditis (IE), intracardiac thrombosis, and cardiac arrhythmias [78,90,91]. Atrial fibrillation, for example, has been found in 50 percent of patients with MAC and cerebral infarction [90]. The treatment of these patients is reviewed separately. (See "Atrial fibrillation in adults: Use of oral anticoagulants".)
SUMMARY AND RECOMMENDATIONS
●Predisposing factors – Valvular heart disease is common in patients undergoing maintenance dialysis. Many predisposing factors are associated with the development of valvular disease in this population. These include secondary hyperparathyroidism, elevated serum levels of calcium and phosphorus, vascular calcification, uremic milieu, and a host of other factors. (See 'Predisposing factors' above.)
●Valvular and annular calcification – Among those with end-stage kidney disease (ESKD), mitral annular and aortic valve calcification (MAC and AVC) occur in 10 to 50 percent and 25 to 55 percent of patients, respectively. By comparison, the occurrence of tricuspid and pulmonic valvular calcification is rare. (See 'Valvular and annular calcification' above.)
●Valvular thickening – Valvular thickening or sclerosis of the aortic and mitral valve is a frequent occurrence in hemodialysis patients, occurring in 55 to 69 percent of individuals. Valvular sclerosis is associated with progressive stenosis and increased cardiovascular mortality. (See 'Valvular thickening' above.)
●General issues in valvular disease – The clinical diagnosis of valvular heart disease is difficult by physical exam secondary to the changing volume status of dialysis patients, presence of anemia, and hypertension. Thus, echocardiography with Doppler flow analysis is an invaluable diagnostic screening tool for the presence and extent of valvular heart disease. General therapeutic considerations that are independent of the specific valvular defect should encompass the prevention and management of secondary hyperparathyroidism, hyperphosphatemia, hypercalcemia, and hypertension. (See 'General issues in valvular disease' above.)
●Valvular stenosis – Stenosis of the aortic valve is the most common obstructive abnormality among hemodialysis patients, with the next most frequent lesion being mitral stenosis. By comparison, tricuspid and pulmonic stenoses are rare. Although the clinical manifestations and treatment of aortic, mitral, pulmonary, and tricuspid stenosis are similar in patients with and without kidney failure, certain features are relatively unique among patients undergoing maintenance dialysis. (See 'Valvular stenosis' above.)
●Valvular regurgitation – A high prevalence of mitral, tricuspid, and aortic regurgitation is observed in dialysis patients. The disappearance of regurgitant lesions with aggressive volume and blood pressure control suggests that most valvular insufficiency in dialysis patients is "functional" in origin, and aggressive ultrafiltration to attain clinical dry weight and optimal blood pressure control should be therapeutic goals in dialysis patients. (See 'Valvular regurgitation' above.)
●Complications – Infective endocarditis (IE), arrhythmias, conduction abnormalities, and thromboembolism are significant issues in dialysis patients with valvular abnormalities. (See 'Infective endocarditis' above and 'Additional complications' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William L Henrich, MD, MACP, who contributed to an earlier version of this topic review.
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