Usefulness of Left Atrial Strain to Predict End Stage Renal Failure in Patients With Chronic Kidney Disease.

Left atrial (LA) enlargement predicts adverse cardiovascular events in patients with chronic kidney disease (CKD). The aim of our study was to evaluate the value of LA reservoir strain, a novel measure of LA function, as a prognostic marker for adverse renal outcomes. A total of 280 patients (65.8 ± 12.2years, 63% male) with stable Stage 3 and 4 CKD without prior cardiac history were evaluated with transthoracic echocardiography and prospectively followed for up to 5 years. The primary end point was progressive renal failure, which was the composite of death from renal cause, end-stage renal failure and/or doubling of serum creatinine. Over a mean follow up of 3.9 ± 2.7years, 56 patients reached the composite endpoint. By log rank test, older age, lower baseline eGFR, anemia, diabetes mellitus, higher urinary albumin/creatinine ratio, number of antihypertensive medications, higher indexed left ventricular mass, larger LA volumes, and impaired LA reservoir strain were significant predictors of the composite outcome (p <0.01 for all). Multi-variable Cox regression analysis found LA reservoir strain, eGFR, number of antihypertensive medications and urinary albumin/creatinine ratio were independent predictors for progressive renal failure (p <0.01 for all). Impaired LA reservoir strain was associated with a 2.5-fold higher risk of the composite outcome (HR 2.51, 95% CI 1.19 to 5.30, p = 0.02) and was the only echocardiographic parameter that predicted progressive renal failure independent of established clinical risk factors for end-stage renal failure. Its utility requires validation in high risk CKD patients with cardiac disease.

Left Atrial Reservoir Strain by Speckle Tracking Echocardiography: Association With Exercise Capacity in Chronic Kidney Disease.

Background Left atrial (LA) function plays a pivotal role in modulating left ventricular performance. The aim of our study was to evaluate the relationship between resting LA function by strain analysis and exercise capacity in patients with chronic kidney disease (CKD) and evaluate its utility compared with exercise E/e'. Methods and Results Consecutive patients with stage 3 and 4 CKD without prior cardiac history were prospectively recruited from outpatient nephrology clinics and underwent clinical evaluation and resting and exercise stress echocardiography. Resting echocardiographic parameters including E/e' and phasic LA strain (LA reservoir [LASr], conduit, and contractile strain) were measured and compared with exercise E/e'. A total of 218 (63.9±11.7 years, 64% men) patients with CKD were recruited. Independent clinical parameters associated with exercise capacity were age, estimated glomerular filtration rate, body mass index, and sex (P<0.01 for all), while independent resting echocardiographic parameters included E/e', LASr, and LA contractile strain (P<0.01 for all). Among resting echocardiographic parameters, LASr demonstrated the strongest positive correlation to metabolic equivalents achieved (r=0.70; P<0.01). Receiver operating characteristic curves demonstrated that LASr (area under the curve, 0.83) had similar diagnostic performance as exercise E/e' (area under the curve, 0.79; P=0.20 on DeLong test). A model combining LASr and clinical metrics showed robust association with metabolic equivalents achieved in patients with CKD. Conclusions LASr, a marker of decreased LA compliance is an independent correlate of exercise capacity in patients with stage 3 and 4 CKD, with similar diagnostic value to exercise E/e'. Thus, LASr may serve as a resting biomarker of functional capacity in this population.

Left Atrial Strain Is the Best Predictor of Adverse Cardiovascular Outcomes in Patients with Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk of adverse cardiovascular events, which is underestimated by traditional risk stratification algorithms. We sought to determine clinical and echocardiographic predictors of adverse outcomes in CKD patients. METHODS: Two hundred forty-three prospectively recruited stage 3/4 CKD patients (male, 63%; mean age, 59.2 ± 14.4 years) without previous cardiac disease made up the study cohort. All participants underwent a transthoracic echocardiogram, with left ventricular (LV) and left atrial (LA) strain analysis. Participants were followed for 3.9 ± 2.7 years for the primary end point of cardiovascular death and major adverse cardiovascular event (MACE). The secondary end point was the composite of all-cause death and MACE. RESULTS: Fifty-four patients met the primary end point, and 65 the secondary end point. On log-rank tests, older age, diabetes mellitus, anemia, greater LV mass, reduced LV global longitudinal strain, larger indexed LA volume, higher E/e' ratio, and reduced LA reservoir strain (LASr; P < .01 for all) were independent predictors of cardiovascular death and MACE. On multivariable regression analysis of univariate predictors, LASr (P < .01) was the only independent predictor for the primary end point as well as for the secondary end point. Receiver operating characteristic curve analysis showed LASr was a stronger predictor of adverse events (area under the curve [AUC] = 0.84) compared to the Framingham (AUC = 0.58) and Atherosclerotic Cardiovascular Disease (AUC = 0.59) risk scores. CONCLUSIONS: LASr is an independent predictor of cardiovascular death and MACE in CKD patients, superior to clinical risk scores, LV parameters, and LA volume.

Exercise E/e' Is a Determinant of Exercise Capacity and Adverse Cardiovascular Outcomes in Chronic Kidney Disease.

OBJECTIVES: This study sought to assess the relationship between E/e' and exercise capacity in patients with chronic kidney disease (CKD) and evaluate its prognostic role. BACKGROUND: Patients with CKD have diastolic dysfunction, reduced physical fitness, and elevated risk of cardiovascular disease. METHODS: Patients with stage 3 and 4 CKD without previous cardiac disease underwent resting and exercise stress echocardiograms with assessment of exercise E/e'. Patients were compared to age-, sex-, and risk factor-matched control individuals and were followed annually for 5 years for cardiovascular death and major adverse cardiovascular event(s) (MACE). Exercise capacity was assessed as metabolic equivalents (METs), with reduced exercise capacity defined as METs of ≤7. Raised exercise E/e' was defined as >13. RESULTS: A total of 156 patients with CKD (age 62.8 ± 10.6 years; male: 62%) were compared to 156 matched control individuals. Patients with CKD were more likely to be anemic (p < 0.01) and had increased left ventricular mass (p < 0.01), larger left atrial volumes (p < 0.01), and higher resting (p < 0.01) and exercise E/e' (p < 0.01). Patients with CKD achieved lower exercise METs (p < 0.01), and more patients with CKD had METs of ≤7 (p < 0.01). Receiver-operating characteristic curves showed exercise E/e' (area under the curve [AUC]: 0.89; 95% CI: 0.84 to 0.95; p < 0.01) as the strongest predictor of reduced exercise capacity in patients with CKD. Over a follow-up period of 41.4 months, a raised exercise E/e' of >13 was an independent predictor of cardiovascular death and MACE on unadjusted and adjusted hazard models. CONCLUSION: E/e' is a strong predictor of exercise capacity and METs achieved by patients with CKD. Exercise capacity was reduced in patients with CKD, presumably consequent to diastolic dysfunction. Elevated exercise E/e' in patients with CKD is an independent predictor of cardiovascular death and MACE.

Validation of the RETRIEVE (REverse TRIage EVEnts) Criteria for Same Day Return of Non-ST Elevation Acute Coronary Syndrome Patients to Referring Non-PCI Centres.

BACKGROUND: There are continuing bed constraints in percutaneous coronary intervention centres (PCI) so efficient patient triage from referral hospitals is pivotal. To evaluate a strategy of PCI centre (PCIC) bed-sparing we examined return of patients to referral hospitals screened by the RETRIEVE (REverse TRIage EVEnts) criteria and validated its use as a tool for screening suitability for same day transfer of non-ST-elevation acute coronary syndrome (NSTEACS) patients post PCI to their referring non-PCI centre (NPCIC). METHODS: From May 2008 to May 2011, 433 NSTEACS patients were prospectively screened for suitability for same day transfer back to the referring hospital at the completion of PCI. Of these patients, 212 were excluded from same day transfer using the RETRIEVE criteria and 221 patients met the RETRIEVE criteria and were transferred back to their NPCIC. RESULTS: Over the study period, 218 patients (98.6%) had no major adverse events. The primary endpoint (death, arrhythmia, myocardial infarction, major bleeding event, cerebrovascular accident, major vascular site complication, or requirement for return to the PCIC) was seen in only three transferred patients (1.4%). CONCLUSIONS: The RETRIEVE criteria can be used successfully to identify NSTEACS patients suitable for transfer back to NPCIC following PCI. Same day transfer to a NPCIC using the RETRIEVE criteria was associated with very low rates of major complications or repeat transfer and appears to be as safe as routine overnight observation in a PCIC.

Evaluation of Serial High Sensitivity Troponin T Levels in Individuals Without Overt Coronary Heart Disease Following Exercise Stress Testing.

BACKGROUND: Detectable levels of high sensitivity (cardiac) troponin T (HsTnT), occur in the majority of patients with stable coronary heart disease (CHD), and often in 'healthy' individuals. Extreme physical activity may lead to marked elevations in creatine kinase MB and TnT levels. However, whether HsTnT elevations occur commonly after exercise stress testing (EST), and if so, whether this has clinical significance, needs clarification. METHODS: To determine whether HsTnT levels become elevated after EST (Bruce protocol) to ≥95% of predicted maximum heart rate in presumed healthy subjects without overt CHD, we assayed HsTnT levels for ∼5h post-EST in 105 subjects (median age 37 years). RESULTS: Pre-EST HsTnT levels <5 ng/L were present in 31/32 (97%) of females and 52/74 (70%) of males. Post-EST, 13 (12%) subjects developed HsTnT levels >14 ng/L, with troponin elevation occurring at least three hours post-EST. Additionally, a detectable ≥ 50% increase in HsTnT levels (4.9→9ng/L) occurred in 28 (27%) of subjects who during EST achieved ≥ 95% of their predicted target heart rate. The median age of the subjects with HsTnT elevations to > 14ng/L post-EST was higher than those without such elevation (42 and 36 years respectively; p=0.038). At a median follow-up of 13 months no adverse events were recorded. CONCLUSION: The current study demonstrates that detectable elevations occur in HsTnT post-EST in 'healthy' subjects without overt CHD. Future studies should evaluate the clinical significance of detectable elevations in post-EST HsTnT with long-term follow-up for adverse cardiac events.

Independent Echocardiographic Markers of Cardiovascular Involvement in Chronic Kidney Disease: The Value of Left Atrial Function and Volume.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular mortality and morbidity, particularly ischemic heart disease and cardiomyopathy. Newer echocardiographic techniques such as myocardial strain analysis provides the opportunity to detect early myocardial dysfunction. The aim of this study was to examine echocardiographic parameters, in particular left atrial (LA) function and volume, in patients with CKD. A further aim was to determine echocardiographic parameters that are sensitive to detect cardiovascular involvement in early CKD. METHODS: Seventy-six patients with stage 3 CKD (estimated glomerular filtration rate, 30-59 mL/min/1.73 m(2)) with hypertension and/or diabetes mellitus, without any previous cardiac illness, were prospectively recruited. These patients were compared with subjects matched for age, sex, and risk factors (hypertension and/or diabetes mellitus) with normal renal function and 76 healthy age-matched control subjects. Two-dimensional strain analyses of the left atrium and left ventricle were performed. Comprehensive echocardiographic examinations were performed in all participants, and traditional echocardiographic parameters including indexed LA volume (LAVI) and two-dimensional strain analysis of the left ventricle and left atrium were performed in all participants. Differences among the three groups on demographic, clinical, and echocardiographic parameters were examined. RESULTS: LA systolic strain (20.9 ± 6.3% vs 27.4 ± 7.9%, P < .0001) and systolic and late diastolic strain rates were altered in the CKD group, while early diastolic strain rate was similar to that in the risk factor-matched group. LAVI was significantly larger in the CKD group compared with the risk factor-matched group and healthy control subjects (38.5 ± 10 vs 31.2 ± 9 vs 22.3 ± 5 mL/m(2), P < .0001). LV strain as well as LV systolic and early diastolic strain rates were similar in the CKD and risk factor-matched groups. LV late diastolic strain rate, a surrogate measure of LA contractile function, was, however, reduced in the CKD group. Forward logistic regression analysis showed LA global strain to be the most sensitive predictor for the presence of CKD, followed by LAVI; though LV late diastolic strain rate was reduced in the CKD group, it was not an independent predictor. Furthermore, the addition of LA strain to traditional echocardiographic parameters significantly increased the predictive power to detect cardiovascular involvement (C statistic = 0.65 vs C statistic = 0.84, P < .0001). Increased LAVI, reduced left ventricular global strain, and the presence of CKD were independent predictors of LA strain, while left ventricular mass index, E/e' ratio, and the presence of CKD were predictors of LAVI. CONCLUSION: LA strain and LAVI are more sensitive parameters than traditional echocardiographic parameters as well as left ventricular strain in patients with early CKD. LA strain and LAVI may be useful to detect myocardial involvement in stage 3 CKD, and LA alterations may be consequent to increased activation of the renin-angiotensin-aldosterone pathway, causing myocardial fibrosis in CKD.

Tissue Doppler imaging in echocardiography: value and limitations.

Tissue Doppler imaging (TDI) is a useful echocardiographic technique to evaluate global and regional myocardial systolic as well as diastolic function. It can also be used to quantify right ventricular and left atrial function. Recent studies have demonstrated its utility as a diagnostic as well as prognostic tool in different cardiac conditions including coronary artery disease, heart failure (both systolic and diastolic), valvular heart disease, cardiomyopathies as well as constrictive pericarditis. TDI measurements are also helpful to identify patients who will benefit from cardiac resynchronisation therapy. Even though it is reproducible and relatively easy to obtain, it is underutilised in routine clinical practice. TDI is readily available on most commercially available echocardiographic systems, and we recommend that TDI be used for routine clinical echocardiographic evaluation of patients.

Chronic kidney disease is independently associated with alterations in left atrial function.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality; hence detection of early cardiovascular involvement in CKD is important to prevent future adverse cardiovascular events. Left atrial (LA) enlargement and dysfunction has been reported in end stage renal disease. However, there is a paucity of published data regarding the evaluation of LA function in CKD using noninvasive imaging parameters. In this study, we evaluated biplane LA volume as well as LA function (LA global systolic strain (GS) and strain rate [SR]) in stage 3 CKD patients (eGFR 30-59 mL/min per 1.73 m(2) ) to determine if LA function parameters are more significantly altered by the presence of CKD in addition to changes due to hypertension alone. METHODS: Thirty-three CKD patients (eGFR 30-59 mL/min per 1.73 m(2) ) with hypertension were compared to 33 normal controls and 34 hypertensive (HT) subjects with normal renal function; all participants underwent a detailed transthoracic echocardiogram. Indexed biplane LA volume (LAVI), LA segmental function, and GS and SR (systolic, early, and late diastole) derived from tissue Doppler imaging (TDI) were measured. Univariate predictors of LA strain were determined. Multiple logistic regression analysis was used to examine the effect of patient group (i.e. CKD) on GS and SR as well as LAVI. RESULTS: Left atrial volume indexed was significantly increased in both the HT and CKD with HT group compared to normal controls (28 ± 9 mL/m(2) vs. 28 ± 9 mL/m(2) vs. 23 ± 5 mL/m(2) , respectively, P = 0.02). However, LAVI was similar in the HT and CKD with HT group (28 ± 9 mL/m(2) vs. 28 ± 9 mL/m(2) ; P = NS). LA GS and SR were reduced in both the CKD with HT and HT group, compared to controls. However, a significantly lower LA GS was present in the CKD with HT group (Controls vs. HT vs. CKD with HT: 54.9 ± 14.5% vs. 34.5 ± 6.2% vs. 25.7 ± 9.3%, respectively; P = 0.001). To examine the effect of group, (i.e. presence of CKD) multiple logistic regression analysis was performed with univariate predictors including indexed left ventricular mass (LVMI), LV diastolic grade, LAVI, peak A-wave velocity, ß-blocker therapy, GS and SR; this demonstrated that CKD had an independent effect on LA GS and SR (systolic, early, and late diastole). GS demonstrated moderate correlation with systolic blood pressure (r = -0.5, P = 0.01), diastolic grade (r = -0.5, P = 0.01), E' velocity (r = 0.6, P = 0.0001), peak A velocity (r = -0.5, P = 0.004), and LAVI (r = -0.6, P = 0.002). CONCLUSIONS: Left atrial dysfunction is evident in stage 3 CKD with associated LA enlargement. This study demonstrates that LA GS and SR were reduced in the CKD group despite similar LAVI in the CKD with HT and HT group. Hence LA GS and SR may be a more sensitive noninvasive tool to detect cardiovascular involvement in CKD.

Outcomes of coronary revascularization (percutaneous or bypass) in patients with diabetes mellitus and multivessel coronary disease.

Clinical outcomes in patients with diabetes mellitus and multivessel disease (MVD) undergoing coronary revascularization have not been extensively evaluated, we sought to examine outcomes in a diabetic cohort of 195 consecutive patients with MVD characterized by SYNTAX scores (SSs) undergoing nonrandomized revascularization, 102 (52%) by percutaneous intervention (PCI) and 93 (48%) by coronary artery bypass grafting (CABG) at Liverpool Hospital (Sydney, Australia) from June 2006 to March 2010. Clinical outcomes were assessed at a median term of 14 months. The overall median SS was 44, with significantly higher SSs in CABG- than PCI-treated patients (48 vs 39, p <0.0001). There was a similar incidence of all-cause death, nonfatal myocardial infarction and stroke in PCI- and CABG-treated patients (6.1% vs 8.3%, p = 0.383; 12% vs 4.9%, p = 0.152; 3.1% vs 3.5%, p = 0.680 respectively). However, the rates of target vessel revascularization and major adverse coronary and cerebral event were significantly higher in PCI-treated patients than in those undergoing CABG (20% vs 1.2%, p <0.0001; 29% vs 15%, p = 0.034). Despite a much higher SS, patients who underwent PCI achieved comparable outcomes at 1 year to those with diabetes mellitus and a SS ≥ 33 as reported in the SYNTAX trial. In conclusion, in this single-center nonrandomized observational study, coronary revascularization by PCI is associated with increased major adverse coronary and cerebral events at 1-year follow-up, predominantly driven by a high rate of target vessel revascularization. Thus, CABG should remain the revascularization procedure of choice for diabetic patients with MVD and high SSs.

Prognostic implications of left atrial volume index in patients in sinus rhythm.

The maximum left atrial volume index (LAVI) has been shown to be of prognostic values, but previous studies have largely been limited to older patients with specific cardiovascular conditions. We examined the independent prognostic values of LAVI in a large unselected series of predominantly younger patients in sinus rhythm followed up for a long period. We evaluated 483 consecutive patients (mean age 47.3 years) using transthoracic echocardiography. The median LAVI was 24 ml/m(2). A primary combined end point of cardiovascular death, stroke, heart failure, myocardial infarction, and atrial fibrillation was sought. We had complete follow-up data for 97.3% of the 483 patients. During a median follow-up of 6.8 years, 86 patients (18.3%) reached the primary end point. Older age, male gender, diabetes, hypertension, hypercholesterolemia, chronic renal failure, a history of myocardial infarction or stroke, a mitral E deceleration time of /=24 ml/m(2) were univariate predictors of the primary end point. Event-free survival was significantly lower for patients with a LAVI of >/=24 ml/m(2). Age, a history of stroke, hypertension, chronic renal failure, and male gender were independent clinical predictors. A LAVI of >/=24 ml/m(2) was the only independent echocardiographic predictor (hazard ratio 1.72, 95% confidence interval 1.34 to 2.13, p = 0.018), with the chi-square of the Cox model increased significantly with the addition of the LAVI (p <0.001). The LAVI independently predicted an increased risk of cardiovascular death, heart failure, atrial fibrillation, stroke, or myocardial infarction during a median follow-up of 6.8 years. In conclusion, the prognostic values were incremental to the clinical risks and were valid in a younger, general patient population.