Mitral annular calcification predicts mortality and coronary artery disease in end stage renal disease.

BACKGROUND: We sought to determine whether mitral annular calcification (MAC) predicts mortality and cardiac disease in a group of renal transplant candidates. METHODS: Hundred and forty patients were prospectively studied. All had echocardiography and coronary angiography. Significant coronary artery disease (CAD) was defined as luminal stenosis >70% by visual estimation in at least one coronary artery. RESULTS: There were 21 deaths over a follow-up period of 2.2+/-0.7 years. MAC occurred in 56 patients (40%) and was associated with higher mortality (p=0.04). Patients with MAC were older (p=or<0.001), had larger left ventricular (LV) end systolic (p=0.005) and LV end diastolic (p=0.04) diameter, larger left atrial diameter (p=0.001), lower LV fractional shortening (p=0.003), larger LV mass index (p=0.04) and higher mitral E/Ea ratio (p=0.03) compared to those without. Plasma calcium (p=0.002), phosphate (p=0.004), cardiac troponin T (p=0.03), N-terminal Pro-B-type natriuretic peptide (p=0.004) concentrations were higher in those with MAC but gender, total cholesterol, haemoglobin and creatinine were similar in the two groups. The proportion diabetic (p=0.03), on dialysis (p=0.05), with significant CAD (p=or<0.001), taking calcium containing phosphate binders (p=0.02) and Vitamin D3 (p=0.04) was significantly higher in those with MAC. Significant CAD (OR 12, 95% CI 3.25, p=0.001) was the only independent associate of MAC. CONCLUSIONS: MAC is associated with increased mortality and significant CAD in ESRD. These patients have increased LV cavity size, poorer LV systolic function, higher LV filling pressures compared to patients without MAC.

Evaluation of ischaemia-modified albumin as a marker of myocardial ischaemia in end-stage renal disease.

The early diagnosis of myocardial ischaemia is problematic in patients with ESRD (end-stage renal disease). The aim of the present study was to determine whether IMA (ischaemia-modified albumin) increases during dobutamine stress and detects myocardial ischaemia in patients with ESRD. A total of 114 renal transplant candidates were studied prospectively, and all received DSE (dobutamine stress echocardiography). IMA levels were taken at baseline and 1 h after cessation of DSE. A total of 35 patients (31%) had a positive DSE result. Baseline IMA levels were not significantly different in the DSE-positive and -negative groups. The increase in IMA was significantly higher in the DSE-positive group compared with those with no ischaemic response (26.5 +/- 19.1 compared with 8.2 +/- 9.6 kU/l respectively; P = 0.007; where kU is kilo-units). From ROC (receiver operator charactertistic) curve analysis, the optimal IMA increase to predict an ischaemic response was 20 kU/l, with a sensitivity of 81% and a specificity of 72% [area under the curve, 0.80 (95% confidence interval, 0.44-0.94); P = 0.03]. There were 18 deaths, ten of which were cardiac in nature over a follow up period of 2.25 +/- 0.71 years. An increase in IMA > or = 20 kU/l was associated with significantly worse survival (P = 0.02). In conclusion, IMA is a moderately accurate marker of myocardial ischaemia in ESRD. Patients with an increase in IMA > or = 20 kU/l during DSE had significantly worse survival.

Ischemia-modified albumin predicts mortality in ESRD.

BACKGROUND: The primary study aim is to determine whether ischemia-modified albumin (IMA) levels predict mortality in patients with end-stage renal disease (ESRD). The secondary aim is to determine characteristics of patients with elevated IMA levels. METHODS: A prospective observational study of 114 renal transplantation candidates was performed. All underwent coronary angiography and dobutamine stress echocardiography. The primary end point is total mortality. RESULTS: During a follow-up period of 2.25 +/- 0.71 years, there were 18 deaths; 10 were cardiac related. Diabetes, severe coronary artery disease, positive dobutamine stress echocardiography result, cardiac troponin T (cTnT) level, IMA level, left ventricular (LV) end-systolic diameter, LV ejection fraction, left atrial size, and mitral peak velocity of early filling (E)/early diastolic velocity (Ea) ratio all predicted mortality. The receiver operating characteristic area under the curve for mortality prediction was similar for IMA and cTnT levels. An IMA level of 95 KU/L or greater (n = 46) predicted mortality with a sensitivity of 76% and specificity of 74%. cTnT level of 0.06 ng/mL or greater (> or = 0.06 microg/L; n = 51) predicted mortality with a sensitivity of 75% and specificity of 72%. Thirty-eight patients (33%) had both IMA and cTnT levels elevated. With multivariate analysis, a positive dobutamine stress echocardiography result (P = 0.003), combined elevated IMA and cTnT levels (P = 0.005), and E/Ea ratio (P = 0.009) were independent prognostic factors. IMA and cTnT levels alone were not independent predictors of mortality. Patients with an elevated IMA level had a significantly larger LV size, decreased LV systolic function, and greater E/Ea ratio compared with those without an increased level. CONCLUSION: IMA level predicts mortality in patients with ESRD. Patients with elevated levels have larger LV size, decreased systolic function, and greater estimated LV filling pressures.

Echocardiographic abnormalities in patients on kidney transplant waiting list.

BACKGROUND: Echocardiographic abnormalities are well described in chronic kidney disease (CKD), and associated with increased cardiovascular events (CVEs) and mortality. Little is known regarding progression of these abnormalities in patients awaiting kidney transplantation. METHODS: We assessed the progression of echocardiographic variables in patients awaiting kidney transplantation and determined predictors of CVEs and mortality. The study included all patients awaiting kidney transplantation between 2004 and 2010 with repeat echocardiograms at least 1 year apart and at least 1 year after transplantation. RESULTS: We assessed 79 patients (57% male, mean age 55 ± 11 years; 27% with diabetes). Sixty-three patients remained on waiting list, and 16 had kidney transplants. Two deaths and 2 CVEs occurred in patients awaiting kidney transplantation. Repeat echocardiograms (31 ± 19 months from baseline) on patients who remained on waiting list showed significant increases in left ventricular mass index (LVMI) (55.3 ± 17.8 vs. 60.5 ± 21.9 g/m2.7, p=0.02) and in left atrium (LA) diameter (3.8 ± 0.6 vs. 4.1 ± 0.8 cm, p=0.02). There were no significant changes in LV fractional shortening (FS) or LV end-systolic and end-diastolic dimensions. Left atrium diameter (p=0.005), systolic dysfunction (p=0.007) and LVMI (p=0.01) were independent predictors of CVEs and mortality. CONCLUSIONS: Time on kidney transplant waiting list is associated with progressive increases in LA diameter and LVM, which are markers of adverse outcome.

The diagnostic and prognostic value of tissue Doppler imaging during dobutamine stress echocardiography in end-stage renal disease.

OBJECTIVE: To determine whether a quantitative measurement of peak systolic velocity (PSV) during dobutamine stress echocardiography (DSE) detects severe coronary artery disease (CAD) and predicts mortality in patients with end-stage renal disease. METHODS: One hundred and forty renal transplant candidates had DSE and coronary angiography. DSE analysis was performed using conventional visual wall motion assessment, longitudinal PSV, and combining the two modalities. Failure of PSV to rise by more than 50% predicted an ischemic response. Significant CAD was defined as luminal stenosis greater than 70%. RESULTS: The number of positive DSE studies according to conventional, PSV, and combined criteria was 41 (30%), 42 (31%), and 46 (34%) respectively. Forty patients (29%) had significant CAD at angiography. The sensitivity, specificity, positive and negative predictive values for conventional DSE analysis were 84, 91, 86, and 90% respectively. The same values for PSV analysis were 86, 92, 86, and 91%, respectively. The same values for the combination of visual and PSV analysis were 88, 94, 87, and 92% respectively. The differences between the three methods were not statistically significant. Sensitivity for single-vessel CAD (P=0.05) and circumflex artery disease (P=0.05) diagnosis was higher with PSV compared with conventional DSE analysis. Failure of PSV to rise by more than 50% during DSE was associated with significantly increased mortality (P=0.001). CONCLUSION: A quantitative interpretation of DSE, based on the percentage rise of PSV during stress, accurately detects CAD and predicts prognosis in end-stage renal disease.

Echocardiography-based score to predict outcome after renal transplantation.

BACKGROUND: Given the high cardiac mortality of renal transplant recipients, identification of high-risk patients is important to offer appropriate treatment before transplantation. AIM: To determine patients with high mortality after renal transplantation despite selection according to current criteria. METHODS: Preoperative parameters were collected from 203 renal transplant recipients over a follow-up time of 3.6 (1.9) years. The primary end point was all-cause mortality. RESULTS: 22 deaths (11%) and 12 cardiac failures (6%) were observed. Non-survivors were older (p< or =0.001), had larger left ventricular end-systolic diameter (LVSD) (p< or =0.001) and end-diastolic diameter (p = 0.002), and lower ejection fraction (p< or =0.001). Left ventricular mass index (p = 0.001), maximal wall thickness (p = 0.006) and the proportion with mitral annular calcification (p = 0.001) were significantly higher in the non-survivors. The risk factors for ischaemic heart disease and exercise test data were not significantly different between the two groups. Four independent predictors of mortality after renal transplantation were identified: age > or =50 years (p = 0.002), LVESD > or =3.5 cm (p = 0.002), maximal wall thickness > or =1.4 cm (p = 0.014) and mitral annular calcification (p = 0.036). The 5-year survival estimates for 0, 1, 2 and 3 prognostic factors were 96%, 86%, 69% and 38%, respectively. No patient had four prognostic factors. In patients > or =50 years, the 5-year survival estimates for 0, 1 and 2 additional prognostic factors were 73%, 45% and 18%, respectively. CONCLUSION: In addition to selection according to current guidelines, age and three conventional echocardiography parameters may further improve risk stratification before renal transplantation.

Pulse pressure and inhibition of renin-angiotensin system in chronic kidney disease.

BACKGROUND: Elevated pulse pressure (PP) is an indicator of poor outcome in hypertensives in the general population and on haemodialysis. The prognostic value of PP in pre-dialysis patients with chronic kidney disease (CKD) stages 4/5 and its interaction with renin-angiotensin system (RAS) inhibitors is unknown. METHODS: This retrospective study of 349 patients from the pre-dialysis clinic analysed the effect association of PP and RAS inhibition on adverse outcomes in CKD stages 4/5. Primary endpoints were a composite of death or dialysis. RESULTS: At baseline, 349 patients (63% males, 34% diabetics) were aged 60+/-0.8 years (mean+/-SEM) with systolic blood pressure (SBP) 149+/-1.3 mmHg, diastolic BP (DBP) 83+/-0.7 mmHg, PP 66+/- 1.0 mmHg, creatinine 442+/-16 micromol/l and haemoglobin 10.7+/-0.1 g/dl. Patients were followed up for 297+/-19 days and 93% took one to seven (2.45+/-0.07) antihypertensives. At presentation, the adverse outcome group had higher SBP (151+/-1.5 vs 145+/-2.4 mmHg; P<0.05), proportion of diabetes (39% vs 23%; P<0.05) and creatinine (478+/-22 vs 354+/-11 micromol/l; P<0.05), but lower haemoglobin (10.6+/-0.1 vs 11.2+/-0.2 g/dl; P<0.05). PP increased with age (r(2): 0.4; P<0.0001). PP >80 mmHg was associated with adverse outcome (Kaplan-Meier survival analysis, log-rank test P<0.05). In a model of proportional hazards regression, adjusted for age, baseline creatinine, diabetes and haemoglobin, elevated PP was associated with poorer outcome (hazards ratio: 1.09; 95% confidence interval: 1.01-1.18; P<0.05) and angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker use was beneficial (hazards ratio: 0.73; 95% confidence interval: 0.53-0.99; P<0.05). CONCLUSIONS: The study demonstrates that elevated PP indicates high risk of death or dialysis and the benefit of blockade of the RAS is independent of the baseline PP in patients with CKD stages 4/5.

Dynamic left ventricular obstruction: a potential cause of angina in end stage renal disease.

BACKGROUND: Patients with end stage renal disease (ESRD) often have angina which cannot be explained by coronary artery disease (CAD) alone. Symptoms are often attributed to systolic and diastolic dysfunction, arrhythmia or microvascular disease. This study proposes another potential cause for angina in renal failure, namely dynamic left ventricular obstruction (LVO). METHODS: 125 renal transplant candidates underwent dobutamine stress echocardiography and coronary angiography. LVO was defined as a peak LV outflow tract gradient >50 mm Hg. RESULTS: None of the patients had LVO at rest. 15 (12%) developed obstruction with dobutamine. The mechanism was systolic anterior motion of the mitral valve in 13 and mid cavity obstruction in 2. Of 53 patients with angina, 26% had dynamic LVO compared to only 1% in those without angina (p=0.004). The proportion with severe CAD, parameters of systolic and diastolic function and haemoglobin levels were similar in patients with and without angina. Significantly more patients with obstruction had angina (93% vs 28%, p<0.001). LV end-systolic (p=0.03) and LV end-diastolic (LVEDD, p=0.03) diameter were reduced and LV fractional shortening (LVFS) increased (p= or <0.001) in those with LVO. Haemoglobin levels, septal wall thickness, estimated LV filling pressure, the proportion with a positive DSE and severe CAD were similar in the 2 groups. LVFS was independently associated with the development of significant obstruction (OR 1.12, 95% CI [1.002, 1.244] p=0.04). CONCLUSIONS: Dynamic LVO occurs in 26% of ESRD patients with angina. In these patients, the angina could not be explained by severe CAD, impaired systolic or diastolic function. Such patients have smaller LV cavity size and increased LVFS.

Mitral peak Doppler E-wave to peak mitral annulus velocity ratio is an accurate estimate of left ventricular filling pressure and predicts mortality in end-stage renal disease.

OBJECTIVE: The study aimed to assess whether the mitral peak Doppler E-wave to peak mitral annulus velocity ratio (E/Ea) estimates left ventricular (LV) filling pressure (LVFP) and predicts mortality in end-stage renal disease. METHODS: In all, 125 candidates for renal transplant were prospectively studied. LV end-diastolic pressure of 15 mm Hg or greater at cardiac catheterization was defined as elevated LVFP. RESULTS: Severe coronary artery disease, N- terminal pro-B-type natriuretic peptide level, left atrial size, flow propagation velocity, mitral E/Ea ratio, pulmonary atrial reversal velocity, and pulmonary-mitral atrial wave duration predicted an increased LVFP. However, the mitral E/Ea ratio (odds ratio 8.1, 95% confidence interval 5.1-9.6, P = .003) was the only independent predictor. An E/Ea of 15 or more, seen in 31 (25%) patients, predicted increased LVFP with sensitivity of 82% and specificity of 88%, and was associated with increased mortality (P = .005). CONCLUSIONS: In end-stage renal disease, mitral E/Ea ratio 15 or higher accurately predicts increased LVFP and mortality.

Dobutamine stress echocardiography and the resting but not exercise electrocardiograph predict severe coronary artery disease in renal transplant candidates.

BACKGROUND: After renal transplantation half of all deaths are cardiac, so prior detection and treatment of severe coronary artery disease (CAD) is advocated. The aim of this study was to identify non-invasive predictors of severe CAD in a group of renal transplant candidates. METHODS: One hundred and twenty-five renal transplant candidates (mean age 52+/-12 years, 80 male, mean creatinine 608+/-272 micromol/l) were studied. All had coronary angiography, dobutamine stress echocardiography, and resting and exercise electrocardiograph (ECG). Severe CAD was defined as luminal stenosis >70% by visual estimation in at least one epicardial artery. The resting ECG was recorded as abnormal if there was evidence of pathological Q waves, left ventricular hypertrophy, ST depression or elevation > or=1 mm, T wave inversion or bundle branch block. Total exercise time, maximal ST segment change, maximal heart rate and systolic blood pressure, limiting symptoms and Duke score were calculated during the exercise ECG test. RESULTS: Of the patients, 36 (29%) had severe CAD, 55% were on dialysis and 39% were diabetic. Patients with severe CAD were significantly older (P<0.001), had higher total cholesterol (P = 0.05), higher CRP level (P = 0.05), larger left ventricular (LV), end systolic and end diastolic diameter (P = 0.007 for each), and lower LV ejection fraction (P = 0.01). A significantly higher percentage were diabetic (P = 0.05), had previous graft failure (P = 0.05), mitral annular calcification (P = 0.04), an abnormal resting ECG (P = 0.001) and positive stress echo result (P<0.001). Cardiac symptoms and exercise ECG parameters were not significantly different in the two groups. Stepwise logistic regression identified an abnormal resting ECG (OR 7, 95% CI 2, 34, P = 0.013) and positive stress echo result (OR 23, 95% CI 6, 88, P<0.001) as independent predictors of severe CAD. CONCLUSIONS: In selecting which potential renal transplant candidates should undergo coronary angiography, resting ECG and dobutamine stress echocardiography are the best predictors of severe CAD.